Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 233 appraisals
Journal of critical care
Artificial intelligence and computerized decision support in adult intensive care: A systematic review of randomized controlled trials
BACKGROUND: Artificial intelligence (AI) and computerized clinical decision support systems (CDSS) are increasingly applied in intensive care, yet their clinical impact remains uncertain, as most studies focus on model development rather than prospective evaluation. OBJECTIVES: To identify randomized controlled trials (RCTs) evaluating AI-based or CDSS interventions intended to influence real-time decision-making in adult intensive care units (ICUs) and to assess their effects on process and patient-centered outcomes. METHODS: We conducted a systematic review of randomized controlled trials (RCTs). PubMed, Embase, Cochrane CENTRAL, ScienceDirect, and IEEE Xplore were searched from inception to November 2025. Eligible studies evaluated AI-based or CDSS interventions in adult ICU patients. Study quality was assessed using RoB 2 and CONSORT-AI criteria. RESULTS: Ten RCTs were included, enrolling approximately 100,000 adult ICU patients. Five trials evaluated AI-based interventions and five evaluated CDSS. Eight trials showed improvements in at least one process measure, including earlier recognition of deterioration, improved protocol adherence, and physiological stability. However, patient-centered benefits were uncommon. Two trials reported reductions in mortality (a sepsis prediction model and a machine-learning-based early-warning system), while most studies showed no consistent effects on clinical outcomes. Reporting of AI-specific elements-dataset provenance, algorithm versioning, and human-AI interaction-was frequently incomplete. CONCLUSIONS: AI and CDSS interventions in adult ICUs are associated with improvements in process-related outcomes but show limited and inconsistent effects on patient-centered endpoints. These findings highlight a persistent gap between algorithmic innovation and clinical validation and underscore the need for pragmatic randomized trials with improved reporting and integration into clinical workflows.
3 Aug 2026
Read appraisal →The Journal of rheumatology
Examining the Role of Wearables in Inflammatory Arthritis Care: A Narrative Literature Review
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis are types of inflammatory arthritis (IA) characterized by joint pain and stiffness that, despite therapeutic advances, remain difficult to treat. Changes in physical activity (PA) and sleep patterns may provide insights into IA disease course and activity. Wearable accelerometers have been validated as reliable, objective measures of PA and have provided insight into IA disease activity and progression through both PA and sleep metrics. Further, the granular nature of accelerometry data may provide the opportunity to identify early signals of treatment response or disease flares, leading to more effective and personalized therapeutic regimens in patients with IA. In this review, we summarize the current state of wearable technology in IA and explore the potential of wearables to bridge gaps in care.
3 Aug 2026
Read appraisal →European journal of radiology
A CT-based deep learning model to differentiate between benign and malignant adrenal lesions
OBJECTIVE: To develop a deep learning model to differentiate benign from malignant adrenal lesions. MATERIALS AND METHODS: A total of 380 patients with 385 pathologically confirmed adrenal lesions (101 malignant, 284 benign) were retrospectively included. Adrenal lesions were manually segmented on CT images and analyzed in a deep learning pipeline aimed at differentiating benign from malignant lesions. Four predictive models were developed that incorporated combinations of radiological data (tumor size, and spontaneous attenuation) and non-radiological data (i.e., medical history and laboratory results). Data of 267 patients were used as a training set and those of 113 patients for the test set. The diagnostic capabilities of the four models were estimated using sensitivity, specificity, accuracy, and areas under the receiver operating characteristic curves (AUC) using histopathological findings as the gold standard. The reproducibility of manual segmentation was estimated using the Dice similarity coefficient after blinded resegmentation of 40 adrenal lesions by an independent radiologist. RESULTS: Segmentation reproducibility achieved a mean Dice similarity coefficient of 0.92 ± 0.03 (range: 0.72-0.97). The most accurate model, which combined clinical, biological, and radiological data, achieved 84.2% accuracy (95% confidence interval: 79.9, 88.6) and an AUC of 0.93 (95% confidence interval: 89.9, 97.9) in the test set for diagnosis of malignant adrenal lesion. CONCLUSION: A deep learning model integrating preoperative clinical, biological, and radiological features demonstrates high capabilities in differentiating benign from malignant adrenal lesions on initial CT examination.
3 Aug 2026
Read appraisal →Rheumatic diseases clinics of North America
Demystifying Artificial Intelligence: Key Concepts with Examples in Rheumatology
Artificial intelligence (AI) refers to a broad class of computational methods to perform tasks that typically require human intelligence, such as learning patterns, reasoning, and problem solving. AI is increasingly applied across rheumatology research and clinical practice to analyze complex data and support clinical decision-making, yet its underlying concepts are often perceived as opaque or inaccessible. This aim of this article is to demystify foundational AI concepts by defining core terminology and describing major learning paradigms and analytical methods, highlighted through clinically relevant examples from rheumatology. We explain how modern AI models differ from traditional analytical approaches.
2 Aug 2026
Read appraisal →Current opinion in critical care
Smart feeding: the role of artificial intelligence and integrated nutrition platforms in the ICU
PURPOSE OF REVIEW: Tremendous improvement in the use of artificial intelligence has opened new opportunities to analyze the data obtained from electronic health records and imaging. New technologies have tried to overcome obstacles to implement guidelines and recommendations. This review aims to describe the recent progress in the use of machine learning and new technologies in the field of nutrition of the critically ill. RECENT FINDINGS: Increase in data availability, ability to extract these data and analyze them using machine learning has allowed data scientists together with ICU specialists to improve nutritional screening and assessment and to predict occurrence of obstacles like enteral feeding intolerance or refeeding hypophosphatemia. In addition, new technologies can ensure nasogastric tube positioning and enteral feeding efficacy. Integrated platforms can integrate nutritional needs with most adequate prescriptions and modulate the nutritional administration according to the patient's tolerance and requirements. Analysis of continuous recording of imaging obtained from ultrasound can also predict gastric intolerance. SUMMARY: Using machine learning, numerous algorithms and nomograms have been suggested to predict enteral feeding intolerance but validation of these predictions is still required. New technologies integrating energy requirements and delivery of the optimal enteral feeding are very promising.
2 Aug 2026
Read appraisal →Rheumatic diseases clinics of North America
Machine Learning-Enhanced Autoantibody Discovery and Diagnostics in Systemic Autoimmune Rheumatic Diseases
The growing implementation of machine learning (ML) has extended into autoantibody research for the study of systemic autoimmune rheumatic diseases (SARDs). ML methods offer a promising approach for efficiently handling and identifying important signals within the big data generated by modern autoantibody technologies. The novel biomarkers identified through advanced ML techniques show promise in outperforming current clinical tools, bringing us closer to the goal of precision medicine. In this article, we will provide an overview of ML approaches and how they have been applied in autoantibody research to improve the diagnosis and characterization of SARDs.
2 Aug 2026
Read appraisal →Rheumatic diseases clinics of North America
Artificial Intelligence Regulation in the United States: Current Landscape and Implications for Rheumatology
Artificial intelligence (AI) is increasingly embedded in clinical tools used in rheumatology, including imaging interpretation, longitudinal disease monitoring, and electronic health record-based decision support. AI has moved from the periphery of biomedical research to an operational component of clinical care, increasingly embedded in electronic health records, imaging platforms, and decision support systems. In rheumatology, where care is longitudinal, AI systems offer substantial promise-but also poses distinct risks. Together, these commitments-advancing humanity, ensuring equity, engaging impacted individuals, improving workforce well-being, monitoring performance, innovating and learning, and promoting sustainability-operationalize trustworthy AI systems across a patient's care trajectory.
2 Aug 2026
Read appraisal →Rheumatic diseases clinics of North America
Sources of Bias in Clinical Artificial Intelligence and Applications in Rheumatology
Rheumatology machine-learning models are limited by preexisting, technical, and emergent biases; the interaction of data constraints, design choices, and real-world clinical workflows, rather than from isolated technical errors. Across the model lifecycle, optimization objectives can encode patterns of care, access, and documentation, producing hidden subgroup failures that are obscured by aggregate performance metrics. Given the heterogeneity of rheumatic disease and current disparities in care delivery, addressing bias requires deliberate design choices before, during, and after a model is built, as well as a commitment to transparency, and sustained oversight.
2 Aug 2026
Read appraisal →Rheumatic diseases clinics of North America
Toward Artificial Intelligence-driven Clinical Decision Support Tools in Rheumatology
Clinical decision support systems (CDSS) have the potential to enhance rheumatology practice by assisting with differential diagnosis, treatment decisions, and predicting patient outcomes. Rheumatic conditions are complex diseases largely diagnosed clinically rather than with a predefined set of clinical, laboratory, or imaging findings. Newer artificial intelligence (AI)-driven CDSS, known as machine-learning-based systems, may be better suited for applications to rheumatic conditions compared to knowledge-based systems, which rely on a set of predefined rules. This report reviews existing studies on CDSS in rheumatology and highlights the potential benefits and pitfalls of incorporating AI-driven CDSS into rheumatology practice.
1 Aug 2026
Read appraisal →Clinical and experimental dermatology
Pemphigus vegetans: insights from a systematic review of the literature.
BACKGROUND: Pemphigus vegetans (PVg) is a rare variant of pemphigus vulgaris with distinct clinical and histological features, with fewer than 200 cases of patients with the condition reported. OBJECTIVES: To systematically review cases of patients with PVg and summarize clinical, histopathological, immunological features, treatment and outcomes. METHODS: Following PRISMA guidelines, PubMed, Embase and Web of Science were searched (1889 to January 2025) using 'pemphigus AND vegetans'. Eligible studies included case reports, series and observational studies. Data on demographics, subtypes, histopathology, immunopathology, treatment and outcomes were extracted. RESULTS: In total, 197 patients with the condition from 148 studies were identified. The mean age was 52.2 (SD 20.2) years with near-equal sex distribution. Oral mucosa was the commonest initial site (44.7%, 73/163); flexural areas such as the groin and axilla were frequently involved. Reported triggers included drugs, infections and vaccination. In 89 patients where clinical subtypes were reported, the Hallopeau variant was found in 47 (53%). When treatment outcomes were reported by subtype, patients with the Hallopeau variant demonstrated higher sustained remission rates (68%, 28/41) and lower mortality (2%, 1/41) compared with those with the Neumann variant [52% (16/31) sustained remission; 16% (5/31) mortality]. Key histological findings included suprabasal acantholysis (84.9%, 158/186) and eosinophilic microabscesses (65.1%, 121/186). Direct immunofluorescence showed intercellular IgG (92.4%, 121/131) and C3 (53.4%, 70/131). Oral corticosteroids (89.5%, 145/162) were the most used therapy. Relapse occurred in 23.0% (35/152) of patients achieving remission. CONCLUSIONS: This review highlights the need for standardized diagnostic criteria, improved immunological profiling and collaborative data collection to guide evidence-based management.
25 July 2026
Read appraisal →Food & function
Efficacy of different dietary fibers for chronic idiopathic constipation: a systematic review and network meta-analysis
This study aims to compare the efficacy and safety of different dietary fiber subtypes in treating patients with chronic idiopathic constipation (CIC) through network meta-analysis (NMA). PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to October 23, 2025. The risk of bias was evaluated using the Cochrane RoB 2.0 tool, and treatment rankings were calculated using the surface under the cumulative ranking curve (SUCRA). 17 randomized controlled trials (RCTs) involving 1423 adults with CIC were included. NMA suggested that viscous soluble fibers were associated with greater efficacy compared with placebo in relieving defecation difficulty (high certainty, class 1), and were also associated with improvements in stool consistency and stool frequency relative to placebo (moderate certainty, class 1). According to SUCRA rankings, viscous soluble fibers tended to have a higher probability of favorable performance compared with other dietary fiber subtypes in improving straining during defecation (moderate certainty), stool frequency (low certainty), and stool consistency (low certainty), and was associated with a relatively favorable tolerability profile (moderate certainty). Insoluble dietary fibers showed the highest ranking probability for improvement in overall constipation symptom scores; however, this finding was supported by very low certainty evidence. Overall, the findings suggest that viscous soluble fibers have a higher probability of improving stool consistency, stool frequency, and straining during defecation. In contrast, insoluble fibers showed a relatively higher ranking for improvement in overall constipation symptom scores. These results support a symptom-oriented and individualized approach to dietary fiber selection in the management of CIC.
21 July 2026
Read appraisal →The American journal of cardiology
Systematic Review of Coronary Computed Tomography Angiography Guidance for Chronic Total Occlusion Percutaneous Coronary Intervention
Coronary computed tomography angiography (CCTA) is emerging as a valuable adjunct for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), particularly for lesions in which angiography incompletely defines procedural anatomy. In this systematic review, the authors evaluated the role of CCTA in CTO diagnosis, lesion characterization, prediction of guidewire crossing and procedural success, and procedural guidance. CCTA provides a detailed assessment of key features that directly influence CTO PCI strategy and outcomes. Randomized and observational data suggest that preprocedural CCTA can improve procedural planning, increase technical success in complex lesions, and support safer and more efficient CTO PCI through fluoroscopic co-registration and other real-time guidance applications. These findings highlight the clinical value of CCTA as a tool that can enhance case selection, optimize crossing strategy, and improve procedural success in contemporary CTO PCI.
18 July 2026
Read appraisal →Acta odontologica Scandinavica
Obstructive sleep apnea and periodontitis: a systematic review with considerations on CPAP therapy
OBJECTIVE: To evaluate the association between obstructive sleep apnoea (OSA) and periodontitis and to assess the available evidence on the effects of continuous positive airway pressure (CPAP) therapy on periodontal status. MATERIALS AND METHODS: This review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guidelines. Comprehensive literature searches were performed in Cochrane, PubMed, Scopus, and Web of Science. Study selection and data extraction were carried out independently by two reviewers. A total of 20 original studies met the inclusion criteria. Methodological quality was assessed using the Joanna Briggs Institute critical appraisal tool. RESULTS: Fourteen of the 20 studies (70%) reported a significant association between OSA and periodontitis. However, only two studies fulfilled all methodological quality criteria, indicating an overall moderate to low quality of evidence. Data on the effects of CPAP therapy on periodontal outcomes were limited, and the available studies generally showed no significant impact. CONCLUSIONS: Current evidence supports an association between OSA and periodontitis, suggesting that OSA may contribute to periodontitis. Robust, well-designed studies with larger sample sizes and rigorous methodology are needed to clarify the nature of this relationship and to determine whether CPAP therapy influences periodontal health.
17 July 2026
Read appraisal →European journal of clinical pharmacology
Clomiphene citrate versus testosterone replacement therapy in male hypogonadism: a systematic review of literature and meta-analysis
INTRODUCTION: Male hypogonadism, including age-related and functional forms, is characterized by insufficient testosterone production often associated with obesity and metabolic comorbidities. Testosterone replacement therapy (TRT) increases serum testosterone but suppresses spermatogenesis and may cause adverse effects. Selective estrogen receptor modulators (SERMs), such as clomiphene citrate, have emerged as an alternative approach to restore endogenous testosterone while preserving fertility. This study aimed to compare the efficacy of clomiphene citrate versus testosterone replacement therapy (TRT) in increasing serum testosterone levels in men with hypogonadism. METHODS: We conducted a systematic review of the literature in PubMed, Embase, Scopus, The Cochrane Library, and Google Scholar to identify studies comparing clomiphene citrate and testosterone replacement therapy (TRT) in men with male hypogonadism'. The primary outcome was the change in serum testosterone levels before and after treatment. Secondary outcomes included variations in other hormonal parameters, and clinical symptom improvement assessed through standardized instruments. RESULTS: A total of 11 studies with 1512 patients were included (764 on clomiphene citrate; 748 on testosterone replacement therapy, TRT). For serum testosterone, the overall pooled effect showed no significant difference between clomiphene and TRT (MD = 6.64 ng/dL; 95% CI -35.35 to 48.63; I² = 80.6%). Subgroup analyses indicated injectable testosterone achieved higher levels than clomiphene (1 study, 62 patients; MD = -290.50; 95% CI -518.78 to -62.22), whereas gel-based TRT showed no difference (8 studies, 1012 patients; MD = 24.29; 95% CI -18.91 to 67.48; I² = 76.1%). For sexual function, three studies (199 patients; 85 on clomiphene; 114 on TRT) assessing post-treatment libido (ADAM 1-5) showed lower libido scores with clomiphene than TRT (MD = - 0.54; 95% CI - 0.87 to - 0.21; P = 0.009; I² = 18.8%). CONCLUSIONS: No statistically significant difference in serum testosterone levels was observed between clomiphene citrate and testosterone gel, although the evidence is limited by high heterogeneity and some concerns to high risk of bias. TRT was associated with greater improvements in libido. These findings should be interpreted as preliminary, and large-scale randomized trials incorporating clinical and fertility endpoints are needed.
13 July 2026
Read appraisal →Current diabetes reports
Digital Management of Early-Onset Type 2 Diabetes: Empowerment, Challenges, and Future Outlook
PURPOSE OF REVIEW: Early-onset type 2 diabetes (EOT2D), defined as a diabetes diagnosis before 40 years of age, is rising globally and associated with an aggressive disease course and early complications. This review examines the role of digital health technologies (DHT) in addressing the unique clinical and life-course challenges of EOT2D. RECENT FINDINGS: DHT, including continuous glucose monitoring, mobile health applications, digital therapeutics, telemedicine, remote patient monitoring, wearable devices, and artificial intelligence-based analytics, have demonstrated modest improvements in glycemic control, weight management, and patient engagement in people with type 2 diabetes. However, evidence in adults with EOT2D remains limited. Compared with usual-onset T2D, people with EOT2D may derive particular benefits due to higher digital literacy, greater lifestyle variability, and longer anticipated disease duration. Although DHT shows promise for improving empowerment and care integration in EOT2D, important gaps persist, including a lack of EOT2D-specific trials, digital divide-related inequities, interoperability challenges, and reimbursement barriers. Future research should prioritize tailored interventions and hybrid care models to optimize long-term outcomes in this high-risk population.
11 July 2026
Read appraisal →Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
AI-enhanced non-invasive diagnosis of chronic kidney disease using LIBS of fingernail biomarkers
Chronic kidney disease (CKD) is a systemic condition that leads to progressive renal failure and metabolic imbalances that may be detected in the keratinized bio-tissues of the body such as fingernails. Nevertheless, still its early detection is difficult due to the invasive nature of current clinical screening approaches. This research paper provides a precise, non-invasive, and AI-enhanced diagnostic model of CKD screening through the combination of Laser-Induced Breakdown Spectroscopy (LIBS) and the cutting-edge ensemble machine learning to determine the elemental patterns of fingernail biomarkers. In this study, 55 participants with chronic kidney disease and 45 healthy controls were taken as the subjects and their emission spectra were measured with a nanosecond LIBS spectrometer using a laser of a fundamental wavelength @ 1064 nm. To handle the high-dimensional spectral data, Principal Component Analysis (PCA) was used as a feature extraction approach, forming the basis for novel machine-learning models. A sophisticated ensemble learning algorithm specifically Extreme Gradient Boosting (XGBoost) was applied to examine the biochemical change between CKD and control samples and the predictive quality was tested by a relative comparison with a Support Vector Machine (SVM) algorithm. Using 10-fold cross-validation, the XGBoost model outperformed SVM, attaining 97% accuracy, 98% sensitivity, 96% precision and specificity, and a 97% F1-Score. Moreover, external validation on a separate dataset showed that the model is robust and generalizable with 95% accuracy, 97% sensitivity, and an F1-score of 95%. The results conclude that fingernail-based LIBS integrated with ensemble machine learning is a potential and non-invasive instrument for CKD classification.
6 July 2026
Read appraisal →JMIR medical informatics
Graph Network Feature Space Fusion for Predicting Irregularly Sampled Medical Time-Series Data: Deep Learning Model Development and Validation Study
BACKGROUND: Irregularly sampled data, as a common data structure in the medical field, is frequently observed in emergency clinical datasets. It poses problems such as unequal sampling time intervals and frequencies, making it difficult to align the data without losing information for input into models. Meanwhile, due to information loss in the dataset, it is also difficult for the model to effectively analyze the overall data variation and predict the complex and dynamic conditions of emergency patients in the future. OBJECTIVE: This study aimed to address the impact of issues such as missing values and irregularly sampled time intervals on prediction results. This paper proposes a method that converts time-series data into a graph network structure and develops a prediction model for graph data to better support complex tasks. METHODS: In this paper, feature channels and measurement times in time-series data are constructed as nodes, and feature measurements at time points are constructed as edge weights. The point feature space and edge weight space are extracted by a graph convolutional neural network and a gated convolutional attention mechanism network, respectively, and feature fusion is carried out under the action of the learnable head. RESULTS: The proposed method was tested on 4 datasets and compared with both irregularly sampled time-series predictors and state-of-the-art methods for complete data. In addition, a dedicated analysis was conducted leveraging data from 5 key clinical treatment phases. In single-target classification and single-target regression tasks, the method proposed in this study outperforms other comparative methods in most experiments (accuracy=0.74-0.88, area under the curve=0.70-0.87, and mean absolute error=0.038-0.061). Meanwhile, this study constructs clinical phenotypes during patients' hospitalization as multitarget prediction tasks, and the proposed model also outperforms comparative methods in multitarget classification tasks (mean accuracy=0.75-0.91 and mean area under the curve=0.70-0.75). Ablation experiments verify the effectiveness of fusion between the node feature space and the edge feature space. The interpretability analysis of time points identifies key features that require focused attention for patients across different target tasks and time periods. CONCLUSIONS: The proposed model can effectively analyze medical data with missing values and uneven sampling. It achieves high prediction accuracy in both regression prediction tasks and classification tasks. The graph network-based model structure endows the model with better interpretability, enabling effective exploration of factors that trigger changes.
5 July 2026
Read appraisal →International journal of medical informatics
Artificial intelligence in gastroenterology clinical practice: Scoping review of large language model applications.
BACKGROUND: Advances in artificial intelligence have brought renewed attention to tools that can work with the large amount of written information generated in clinical practice. Among these, large language models (LLMs) stand out for their ability to interpret and generate medical text in a flexible, context-aware way. Gastroenterology, like many specialties, produces a wide range of narrative and semi-structured data, and this has encouraged researchers to explore how LLMs might help clinicians manage everyday tasks. Recent studies have examined their potential contributions to patient education, communication between care teams and patients, decision support, and routine documentation, reflecting a growing interest in how these systems might fit into real-world clinical workflows. OBJECTIVE: This scoping review aimed to map current applications of LLMs in gastroenterology clinical practice, including subspecialty focus, study designs, model types, and reported outcomes. METHOD: Following PRISMA guidelines, a systematic search was conducted in PubMed, Scopus, and Web of Science for studies published between January 2022 and August 2025. Eligible studies included original research assessing LLM applications in gastroenterology clinical practice. Data were extracted on subspecialty, application domain, LLM type, data source, and outcomes. We employed thematic analysis to address our primary research question. RESULTS: 73 out of 2895 studies identified in the initial search met the inclusion criteria. Six subspecialties and six application domains emerged from our review. Hepatology (20/73 studies, 27.3%) and endoscopy (17/73 studies, 23.2%) were the most represented subspecialties. The most frequently investigated application domains were patient education and communication (38 studies) and decision support and clinical guidance (24 studies). Most studies were simulation-based or literature-based cases, although an increasing number have used real-world clinical data, particularly in recent years. The majority evaluated general-purpose models such as GPT-3.5 and GPT-4, with some incorporating retrieval augmentation or fine-tuning. Reported outcomes varied by application domain and included measures of accuracy, concordance, completeness, relevance, safety, reliability, usability, user satisfaction, efficiency, time savings, and educational value. Commonly described limitations included variable reliability, incomplete responses, and challenges in generalizing from simulated to clinical settings. CONCLUSIONS: Research on LLMs in gastroenterology has expanded across multiple subspecialties and application domains. Current evidence is primarily based on simulation studies, with limited but growing evaluation using real-world clinical data. Further work is needed to assess performance in prospective and applied clinical contexts.
2 July 2026
Read appraisal →Human genetics
AI in variant analysis: fast track to genetic diagnoses
While falling costs have expanded access to genomic sequencing, clinical utility is frequently hindered by the challenge of interpreting complex genetic data. Variant analysis for rare disease patients especially requires significant time and expertise, creating a bottleneck that delays diagnostics. Although advances in genetic variant classification have improved diagnostic precision, they have also increased the identification of variants of uncertain significance (VUSs), widening the interpretation gap between data generation and clinical actionability. The high prevalence of VUSs can lead to false reassurance or psychological distress by misinterpretting inconclusive results. We propose that artificial intelligence (AI) is a critical clinical decision-support tool for bridging this gap, offering a scalable framework to optimize variant interpretation and shorten the diagnostic odyssey. While reclassification ultimately requires biological evidence that AI cannot replace, these tools serve as essential aggregators and prioritizers, especially as guidelines transition toward the upcoming quantitative ACMG v4 framework. We advocate integrating AI throughout the genetic diagnostic workflow-from initial phenotyping to variant prioritization-to facilitate data-driven, personalized treatment. We outline current AI-assisted approaches and discuss anticipated challenges in this pursuit, such as privacy, training data bias and quality, model explainability, and the necessity of a total product life cycle for validation. To address these challenges, we provide recommendations for "human-in-the-loop" design and intuitive workflow integration to ensure AI tools meet the highest standards of precision, reproducibility, and transparency to maximize adoption. By standardizing AI across the variant analysis pipeline, we can fast-track the path to genetic diagnoses, effectively bridging the interpretation gap and enabling rapid delivery of personalized medical interventions.
28 June 2026
Read appraisal →Medicine
Efficacy and safety of traditional Chinese medicine decoctions as an adjuvant treatment for rheumatoid arthritis: A systematic review and meta-analysis
BACKGROUND: To assess the effectiveness and safety of traditional Chinese medicine (TCM) decoctions as an additional therapy for rheumatoid arthritis (RA) via a systematic review and meta-analysis. METHODS: Databases including PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang were searched up to June 2024. Randomized controlled trials (RCTs) on TCM decoctions as adjunctive RA treatment were included. Primary outcomes were efficacy and safety. Effect sizes were measured using standardized mean difference, risk ratio, and 95% confidence intervals. Sensitivity and subgroup analyses were conducted to test result robustness and identify heterogeneity sources. Data were analyzed using RevMan 5.4 and Stata 15. In addition, the quality of evidence was assessed using grading of recommendations assessment, development and evaluation grading. RESULTS: Thirty-six RCTs with 6934 participants showed that TCM decoctions significantly improved overall efficacy versus control (risk ratio = 1.25, 95% confidence interval [1.21-1.29], P < .00001). They also reduced erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, swollen joint count, Disease Activity Score, and morning stiffness duration compared to placebo. Subgroup analysis suggested treatment duration, disease duration, and age may affect efficacy. Among them, the quality of evidence was high for Visual Analog Scale, and moderate for overall efficacy, C-reactive protein, Disease Activity Score, Traditional Chinese Medicine Symptom Score, and interleukin-1. CONCLUSION: TCM decoctions as adjunctive RA treatment significantly enhance efficacy. However, due to study limitations, further large-scale, multicenter RCTs are needed to confirm these findings.
28 June 2026
Read appraisal →BMJ open
Effectiveness and safety of pharmacist prescribing: a systematic review
OBJECTIVE: To examine the effectiveness and safety of pharmacist prescribing across multiple healthcare settings. DESIGN: A systematic review of quantitative studies. ELIGIBILITY CRITERIA FOR THE SELECTION OF STUDIES: Quantitative studies assessing the effectiveness and safety of pharmacist prescribing compared with non-pharmacist prescribing in any healthcare setting and for any healthcare population. A clear statement of pharmacists' prescriptive authority was required for inclusion in this systematic review. DATA SOURCES: A systematic search was conducted using six electronic databases: Embase (Ovid), MEDLINE (EBSCO), SCiELO, Dimensions AI, Cochrane Library and Epistemonikos. Database searches were conducted from database inception to 29 January 2025. Additional grey literature searches were conducted using Google and DuckDuckGo. Both backward and forward citation chasing were conducted for all included studies. DATA EXTRACTION AND SYNTHESIS: Data were extracted using standardised bespoke data extraction forms. The revised Cochrane Risk of Bias 2 tool for randomised controlled trials and the Risk of Bias in Non-Randomised Studies of Interventions tool were used to assess risk of bias. A narrative synthesis approach was applied following the Synthesis Without Meta-analysis guideline. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the level of certainty of the evidence. RESULTS: Of the 39 included studies, 32 studies reported on effectiveness and 20 studies reported on safety across 15 health conditions. Healthcare settings included outpatient (n=14), primary care (n=10), community pharmacy (n=6), inpatient (n=5), emergency department (n=1) and long-term care (n=3). These studies were based in the USA (n=26), Canada (n=5), the UK (n=4), Australia (n=2) and Singapore (n=2). In total, there were 153 outcomes related to safety and effectiveness. For 74 outcomes, no significant difference was reported between pharmacist prescribing and non-pharmacist prescribing, while 46 outcomes were significantly improved with pharmacist prescribing. Four outcomes reported in favour of non-pharmacist prescribing. Inferential statistics were not reported for 29 outcomes, meaning we cannot comment on their statistical significance. The certainty of evidence was low or very low for all outcomes. CONCLUSIONS: The consistency of effectiveness and safety findings across studies, showing either no significant difference (indicating equivalence of care and outcomes) or significant improvement in pharmacist prescribing groups, suggests it is a potential policy option. Future research on implementation, public and patient preferences and cost-effectiveness would provide valuable insights into the potential benefits of pharmacist prescribing at a health system level.
28 June 2026
Read appraisal →Oral health & preventive dentistry
Association Between Ankylosing Spondylitis and Periodontitis: A Systematic Review
PURPOSE: This systematic review aimed to investigate a potential association between ankylosing spondylitis (AS) and periodontitis (PD), two chronic inflammatory diseases. METHODS AND MATERIALS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, searches were conducted in PubMed, The Cochrane Library, Scopus, and Web of Science. Keywords included 'spondyloarthritis', 'ankylosing spondylitis', 'periodontal diseases', and 'periodontitis'. Study selection was performed by independent authors, and quality was assessed using Scottish Intercollegiate Guidelines Network (SIGN) methodology and the STROBE-MR statement. RESULTS: Out of 255 initial studies, 18 eligible studies (3 cohort, 14 case-control, 1 Mendelian randomisation) were selected, all of acceptable to high quality. The prevalence of PD in AS patients showed conflicting results. Periodontal parameters like bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) didn't consistently show statistically significant differences but were frequently correlated with AS parameters (eg, MASES, BASDAI, BASFI, CRP, AS duration). AS treatment with anti-TNF-α agents was associated with a decrease in PPD and CAL. Other findings included an increase in Gingival Index in AS patients treated with anti-TNF-α and mixed results for the Decayed, Missing, and Filled Teeth Index. Microbiological studies showed inconsistent results for Porphyromonas gingivalis (Pg), but anti-Pg IgG levels correlated with AS parameters. PD appeared to significantly increase inflammatory markers (IL-6, TNF-α, CRP, ESR) in AS patients. Only one study investigated a genetic association, finding none. CONCLUSION: A definitive conclusion regarding an increased prevalence of PD in AS patients cannot be drawn with certainty from this review, possibly due to heterogeneous classification criteria. However, the correlation between PD and AS parameters, alongside the impact of AS therapy on periodontal health, is noteworthy. Screening and treating periodontal disease in AS patients might delay symptom progression and reduce drug dosage, though targeted clinical trials are necessary to confirm these findings.
26 June 2026
Read appraisal →Rheumatology international
Pruritus associated with systemic sclerosis: a systematic review of treatment-based clinical trials
This paper aims to examine the latest research on treatments for itch (pruritus) in people with systemic sclerosis (SSc), identify areas where information is lacking, and propose suggestions for future studies.A comprehensive literature search was performed in PubMed and Scopus in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies evaluating therapeutic interventions for pruritus in SSc. Eligible studies included randomized controlled trials, cohort studies, and case series comprising a minimum of three patients. Data extraction encompassed study design, patient demographics, pruritus assessment instruments including validated and non-validated measures, and clinical outcomes. Studies were excluded if they concerned localized scleroderma, irrelevant populations, case reports, systematic reviews, lacking relevant outcome data, or incomplete trials. Ten studies met criteria, evaluating immunomodulatory agents, mast cell stabilizers, opioid receptor antagonist, and lysophosphatidic acid receptor antagonists. Pruritus assessment varied and was often secondary to fibrosis outcomes. Oral lenabasum improved pruritus in a phase II trial; low-dose opioid receptor modulators and rituximab also showed qualitative improvement. Pruritus is a frequently overlooked yet clinically significant symptom in systemic sclerosis (SSc) that negatively impacts patients' quality of life. Existing evidence regarding effective therapeutic options remains limited. Future research should prioritize pruritus as a predefined outcome and utilize validated assessment instruments to inform treatment strategies and enhance patient quality of life.
23 June 2026
Read appraisal →Rheumatology international
Mortality and survival in patients with systemic lupus erythematosus in the Middle East and North Africa: a systematic review and meta-analysis
Systemic lupus erythematosus (SLE) is associated with increased mortality compared with the general population, with outcomes influenced by ethnicity and organ involvement. Data from the Middle East and North Africa (MENA) remain limited, particularly regarding long-term survival and mortality predictors. To estimate and compare all-cause mortality and survival rates among adult patients with SLE in the MENA region and identify predictors of mortality. A systematic review and meta-analysis of cohort studies reporting survival and mortality in patients with SLE in the MENA region was conducted. Eligible studies were identified through a comprehensive database search and screened according to PRISMA guidelines. Data on treatment exposures and clinical predictors of mortality were extracted. Twelve cohort studies, including 3,478 adults with SLE from five MENA countries (Türkiye, Iran, Egypt, Israel, and Tunisia), were analyzed. The pooled all-cause mortality rate was 9.9% (95% CI: 7.2%-14.0%; I² = 89.7%). Survival remained high at 5 years (93.9%) and 10 years (90.0%), but declined at 15 years (85.5%) and 20 years (71.7%), with long-term estimates highly sensitive to single-study exclusion. Leave-one-out analysis slightly increased survival estimates and reduced heterogeneity. Major mortality predictors included renal involvement, cardiovascular disease, infections, hypertension, diabetes, hematologic abnormalities, and male sex. Higher cumulative corticosteroid and cyclophosphamide exposure was linked to increased mortality, whereas hydroxychloroquine and azathioprine appeared protective. Infection was the leading cause of death, followed by active disease, renal failure, and cardiovascular complications. Patients with SLE in the MENA region show high short-term survival, but long-term outcomes remain variable. Mortality is mainly driven by renal, cardiovascular, and infectious complications, with treatment exposure contributing to risk. These findings highlight the need for multicenter registries, standardized reporting, and strategies to reduce infection burden and optimize nephritis care.
23 June 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Diabetes technology: an update.
Diabetes is one of the most prevalent chronic diseases worldwide, with rates that continue to increase. More than 30 years ago, the Diabetes Control and Complications Trial demonstrated that intensive glucose management decreased long-term vascular complications. Unfortunately, many people with diabetes still struggle to meet glycemic goals. In this mini-review, we highlight advances in diabetes technology that are associated with improvements in glycemic management. Continuous glucose monitoring (CGM) and automated insulin delivery systems are associated with significant improvements in glycated hemoglobin (HbA1c), time in range (70-180 mg/dL), and decreases in severe hypoglycemia and diabetic ketoacidosis in people with both type 1 and type 2 diabetes. Recent data show that these technologies improve outcomes early in the course of type 1 diabetes. CGM is also being explored as a tool to monitor progression through early-stage type 1 diabetes (2 antibodies positive) to identify individuals who may benefit from disease-modifying therapies as well as to prevent the onset of diabetic ketoacidosis at onset of stage 3 (insulin-requiring) type 1 diabetes. Adjunctive pharmacologic therapies and artificial intelligence may further expand and improve therapies, offering potential synergistic benefits. However, there continue to be significant disparities in access to diabetes technologies and access to insulin worldwide. This mini-review summarizes recently published data, highlights emerging applications, and underscores the need to pair technological innovation with strategies that promote equitable access and support for diabetes care to improve outcomes for all people with diabetes.
19 June 2026
Read appraisal →The American journal of cardiology
Efficacy and Safety of Olezarsen for the Management of Dyslipidemia: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
This updated systematic review and meta-analysis evaluated the efficacy and safety of olezarsen in patients with dyslipidemia. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched through September 2025 for randomized controlled trials comparing olezarsen with placebo. Seven trials (n = 2,121) were included. Olezarsen significantly reduced triglycerides (mean difference [MD] -59.20 mg/dL), very-low-density lipoprotein cholesterol (MD -52.68 mg/dL), apolipoprotein B (MD -10.74 mg/dL), non-HDL cholesterol (MD -17.06 mg/dL), and apolipoprotein C-III (MD -64.16 mg/dL), and increased HDL cholesterol (MD 30.97 mg/dL), with no significant effect on LDL cholesterol. Injection site reactions (risk ratio [RR] 3.93) and platelet counts <140,000/µL (RR 4.76) were increased, whereas serious adverse events and significant liver enzyme elevations were comparable to placebo. Certainty of evidence ranged from moderate to low. In conclusion, olezarsen produces substantial improvements in triglyceride-rich lipoproteins with an acceptable safety profile; long-term cardiovascular outcome trials are warranted.
16 June 2026
Read appraisal →European journal of pharmacology
Inhibition of the serotonin transporter and risk of heart valve disease: A systematic review and meta-analysis
BACKGROUND: The serotonin transporter (SERT) plays an essential role in regulating a wide range of physiological and psychological processes, including neurotransmitter homeostasis, circadian rhythm, sleep regulation, platelet function, immune modulation, mood and emotions. Although SERT was initially studied in the context of neurological and psychiatric disorders, growing evidence highlights how its off-target exogenous inhibition, and the resulting dysregulation of serotonin signaling, can promote valvular interstitial cell proliferation, extracellular matrix remodeling, and fibrosis, thereby contributing to the pathophysiology of heart valve disease (HVD). Despite the increasing interest in the role of SERT in valve biology, mechanistic studies remain limited, and a deeper understanding of the implications of commonly used SERT-targeting drugs in the progression of HVD is still needed. METHODS: In this review, we examine the impact of drug-induced SERT inhibition on HVD, integrating findings from cellular studies, animal models, and clinical data to better understand the risks associated with chronic use of SERT inhibitors. To strengthen the clinical relevance of our review, we also performed a meta-analysis of published clinical studies on SERT-modulating drugs, which revealed a significant association between the use of these medications and increased HVD risk (OR = 2.76). CONCLUSIONS: Our analysis supports the implementation of clinical screening for high-risk patients, such as those with diabetes, hypertension, or pre-existing valvular abnormalities, prior to serotonergic drug recommendations. Ultimately, a deeper understanding of the role of serotonin and SERT in valvular pathophysiology may guide safer prescribing practices and facilitate the development of novel therapeutics for managing or preventing the progression of HVD.
16 June 2026
Read appraisal →The American journal of cardiology
Sacubitril/Valsartan and Prevention of Chemotherapy-Induced Cardiac Dysfunction: Meta-analysis of Randomized Trials
Chemotherapy-related cardiac dysfunction (CTRCD) is a major limitation of cardiotoxic cancer therapies. Although global longitudinal strain (GLS) allows early detection of myocardial injury, preventive strategies remain scarce. Angiotensin receptor-neprilysin inhibitors (ARNIs) may offer cardioprotection, but current evidence is limited. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating Sacubitril/Valsartan versus control in patients undergoing chemotherapy. PubMed, Embase, and Cochrane databases were searched. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were computed for binary and continuous outcomes. Four randomized controlled trials comprising 412 participants were included; 42.7% received ARNI therapy, with follow-up ranging from 6 to 18 months. Compared with control, ARNI significantly preserved left ventricular systolic function (MD 1.47%, 95% CI 0.59-2.34) and attenuated GLS deterioration (MD -0.93%, 95% CI -1.49 to -0.38). However, ARNI did not significantly reduce the incidence of CTRCD (RR 0.40, 95% CI 0.08-1.97) or all-cause mortality (RR 0.63, 95% CI 0.08-5.01). ARNI increased the risk of hypotension but had no significant effects on NT-proBNP or dyspnea. In conclusion, ARNI therapy improves GLS and left ventricular ejection fraction during chemotherapy but has not yet demonstrated reductions in CTRCD or mortality. Hypotension remains a key safety consideration.
16 June 2026
Read appraisal →Life sciences
Intermittent fasting and cardiometabolic responses under cardiac stress: a systematic review of preclinical studies
Intermittent fasting (IF) has emerged as a dietary strategy with benefits that extend beyond weight management and glycemic control. Although growing evidence supports its favorable effects on cardiometabolic health, the impact of IF under conditions of cardiac stress remains poorly characterized. Since clinical trials cannot ethically expose patients to acute cardiac stress during IF protocols, preclinical models are essential to elucidate its potential cardioprotective mechanisms. This systematic review aimed to synthesize the preclinical evidence on the effects of IF in models of cardiac stress. Following a registered protocol (PROSPERO:#CRD42023466215), we searched databases for preclinical studies evaluating IF under cardiac stress. Models included atherosclerosis induction, diet modulation, hypercholesterolemic mice, doxorubicin-induced cardiotoxicity, pulmonary arterial hypertension, myocardial infarction, ischemia-reperfusion injury, among others. All IF regimens, encompassing variations in timing, frequency, and type, were considered. Clinical trials, observational studies, reviews, meta-analyses, updates, guidelines were excluded. Thirty-two studies involving 451 predominantly male animals were included. Approximately 80% reported that IF improved cardiovascular outcomes, reducing blood pressure, cardiac hypertrophy, fibrosis, and ischemic injury while enhancing vascular and metabolic function. Mechanistically, IF protects the heart under stress by downregulating NF-κB, IL-1β, and TNF, and activating SIRT3 and AMPK pathways, improving mitochondrial function, lipid metabolism, and cardiac energy homeostasis. Cardioprotective benefits were dependent on fasting duration and regimen, emphasizing the importance of metabolic context. In conclusion, IF appears to enhance cardiovascular resilience under stress through multiple metabolic and molecular pathways. These findings support further clinical investigation of IF as a potential adjunct strategy for cardiometabolic protection under stress.
15 June 2026
Read appraisal →Pulmonology
Hypnodensity sleep metrics from fingertip photoplethysmography are better associated with daytime sleepiness and fatigue than traditional metrics from polysomnography
BACKGROUND: Traditional sleep metrics from polysomnography are often limited by the hypnogram, in which each 30-s epoch is classified into one of the five sleep stages. This oversimplifies sleep stage continuity and fragmented sleep, typical in sleep-disordered breathing (SDB). Deep learning offers more dynamic sleep modelling with a higher temporal resolution by providing probabilities for each sleep stage, known as hypnodensities. RESEARCH QUESTION AND METHODS: We investigated whether high-frequency (1/s) hypnodensities captured from nocturnal fingertip photoplethysmography (PPG) recordings better correlate with patient-reported outcomes in SDB than traditional metrics. RESULTS: Among 2,280 patients (65% male, mean age 62 years, mean apnoea-hypopnoea index (AHI) 23.5/h), we found that several PPG-derived hypnodensity metrics correlate with self-reported daytime fatigue and sleepiness. The level of correlation was better or similar compared to traditional hypnogram-based sleep metrics derived from manually scored polysomnography. Specifically, PPG-based hypnodensities for N1 and N3 sleep showed a stronger association (p < 0.005) with fatigue and sleepiness than manually scored N1 and N3 sleep. Multivariable logistic regression (adjusted for age, sex, body mass index, AHI, and total sleep time below 90% blood oxygen saturation) revealed significant associations (p < 0.01) between multiple PPG-based hypnodensity metrics and daytime sleepiness. CONCLUSION: These findings suggest that PPG-based hypnodensities improve the characterisation of sleep quality and better predict patient-reported outcomes in SDB patients. Future uses may include tracking sleep quality with fingertip pulse oximeters outside of sleep centres, potentially over multiple nights due to their simplicity.
14 June 2026
Read appraisal →BMC cardiovascular disorders
Trends in cardiac implantable electronic device infections: 2015 to 2019
BACKGROUND: Cardiovascular implantable electronic devices (CIEDs) improve survival in patients with cardiac rhythm disorders but carry risks of complications, most notably major infections. Reported infection rates vary internationally, and contemporary large-scale data from Germany are scarce. We aimed to determine nationwide rates of CIED infection-related hospitalizations and associated mortality over a five-year period. METHODS: We analyzed administrative claims from Germany's largest statutory health insurer covering more than 27 million beneficiaries. All CIED procedures performed between January 2015 and December 2019 were identified, including initial implantations, upgrades or downgrades, generator replacements, early revisions, and device extractions. Major infections were detected using International Classification of Diseases (ICD-10-GM) and procedural codes, and stratified as generator pocket infections or lead-associated endocarditis. In-hospital mortality was determined from discharge records. RESULTS: Among 282,205 patients (57.7% male) undergoing CIED procedures, 6,577 individuals (2.33%) experienced 7,704 major infections within three months. Generator pocket infections occurred in 5,396 cases (1.91%), lead-associated endocarditis in 2,308 (0.82%), and combined infections in 1,127 patients (0.39%) within the acute 90-day observation period. CIED infections substantially increased healthcare utilization: Infected patients required substantially more procedures than non-infected patients, despite correct treatment. In-hospital mortality reached 8.36% for pocket infections and 15.0% for endocarditis. Extended follow-up in the 2015 cohort revealed a 4.33% infection-related procedure rate over five years. CONCLUSIONS: Nationwide German data reveal higher acute CIED infection rates than previously reported, with considerable mortality and procedural burden. These findings highlight an urgent need for improved prevention and management strategies.
14 June 2026
Read appraisal →BMJ open
Difficult intravenous access (DIVA) in the adult population: an umbrella review.
OBJECTIVES: To synthesise evidence from systematic reviews on difficult intravenous access (DIVA) in adults, focusing on definitions, diagnostic criteria, risk factors and clinical interventions to guide clinical practice and health policy. DESIGN: Umbrella review of systematic reviews and meta-analyses. SETTING: Any clinical setting involving adult patients requiring peripheral venous access (including hospital, emergency and outpatient care). DATA SOURCES: A systematic search was performed in PubMed, CINAHL, Cochrane, Scopus and Web of Science in July 2025. ELIGIBILITY CRITERIA: Systematic reviews and meta-analyses published from 2014 to 2025 that addressed DIVA in the adult population were included. Primary studies and protocols were excluded. DATA EXTRACTION AND SYNTHESIS: Methodological quality was assessed using the Risk Of Bias In Systematic Reviews tool. Data extraction followed the Joanna Briggs Institute methodology for overviews and the Preferred Reporting Items for Overviews of Reviews reporting guideline. RESULTS: Seven reviews (six systematic reviews and one meta-analysis) were included. Three analytical dimensions emerged: (1) the conceptual and operational definition of DIVA, identifying common elements such as ≥2 failed attempts, lack of visible or palpable veins and a documented history of difficult access; (2) risk factors and clinical assessment, highlighting obesity, chronic diseases, prior chemotherapy, venous invisibility or non-palpability and the limited validation of diagnostic tools and (3) interventions, including organisational strategies (escalation protocols, specialised teams), technological resources (ultrasound guidance) and clinical measures (pain management and technique optimisation). CONCLUSIONS: DIVA is a multifactorial challenge that requires a standardised definition to improve clinical identification. Effective management relies on a combination of specialised training, the use of ultrasound technology and the implementation of escalation protocols to ensure patient safety and efficiency. PROSPERO REGISTRATION NUMBER: CRD420251084947.
14 June 2026
Read appraisal →Annals of medicine
Predicting major adverse cardiovascular and cerebrovascular events in chronic heart failure: a machine learning study
BACKGROUND: Heart failure (HF) is a clinical syndrome characterized by impaired cardiac diastolic and systolic function due to structural or functional damage to the myocardium. HF represents the end-stage manifestation of many cardiac diseases. Therefore, early identification of high-risk patients is crucial. This study aims to utilize machine learning (ML) methods to develop and validate a model to predict major adverse cardiovascular and cerebrovascular events (MACCE) in patients with HF and identify its key predictive features. METHODS: This study is a retrospective cohort study. We enrolled a total of 271 patients, who were divided into training and testing sets. Baseline data, including cardiopulmonary exercise testing (CPET) parameters and laboratory tests, were collected for all participants. Based on the presence or absence of MACCE during follow-up, they were categorized into a No-event group and MACCE group. We developed seven ML models to predict the incidence of MACCE in patients with chronic heart failure (CHF) using CPET parameters. The predictive performance of these models was systematically compared, and model interpretability was evaluated using Shapley Additive exPlanations (SHAP). Subsequently, retaining only those with HF with preserved ejection fraction (HFpEF) for a sensitivity analysis. Additionally, a subgroup analysis was conducted between No-event group and Worsening HF (WHF) group. RESULTS: We used Boruta feature selection, four important predictive features were identified. Among the ML models constructed with these features, the Categorical Boosting (CatBoost) model demonstrated the best performance. SHAP analysis was applied to interpret the optimal model, revealing that lower values of heart rate recovery at 1 min (HRR1), as well as a higher carbon dioxide ventilation equivalent slope (VE/VCO2 slope), were associated with higher SHAP values-indicating greater importance in predicting adverse outcomes. CONCLUSION: HRR1 and VE/VCO2 slope can serve as independent predictors for the incidence of MACCE in patients with CHF. Both impaired HRR1 and an elevated VE/VCO2 slope serve as significant independent predictors of MACCE in the CHF population.HRR1 is an independent predictor of WHF in patients with CHF.
14 June 2026
Read appraisal →Scientific reports
AIDx: a locally deployable AI system for physician clinical decision support
The dynamic environment of medicine, particularly in settings such as the Emergency Department, challenges physicians with an influx of patient data and the need for swift diagnosis and treatment under high-pressure conditions. Numerous AI models have been developed for medical applications, yet their integration into hospital systems remains limited because they often do not align with existing clinical workflows. To address these challenges, I developed AIDx, an AI-powered system designed to help physicians streamline clinical decision making, improve diagnostic support, and provide an integrated platform for AI-assisted analysis. Unlike many standalone systems, AIDx is designed for interoperability with electronic health record (EHR) systems and can leverage supplementary tools such as updated medical knowledge bases and auxiliary AI models. At its core, AIDx includes AIDx-Copilot, a large language model fine-tuned on de-identified EHR data and optionally grounded using retrieval-augmented generation (RAG) from open medical references. This study is a text-only benchmark assessment. I evaluated AIDx-Copilot using the MultiMedQA benchmark suite under a unified, deterministic, single-pass protocol (temperature=0; no voting). Across nine MultiMedQA subsets (MedQA, PubMedQA, MedMCQA, and medically focused MMLU subjects), AIDx-Copilot achieves a mean accuracy of 83.61% (SD 7.37). I report per-dataset Wilson 95% confidence intervals to quantify uncertainty from finite test set sizes. To isolate component contributions, I conducted ablation experiments comparing the base model, the fine-tuned model without retrieval, and the fine-tuned model with RAG enabled. EHR-based fine-tuning accounts for the majority of the performance gain (+17.8 percentage points over the base model on average), while RAG provides a modest additional benefit (+0.4 points on average) that varies by dataset. A qualitative error analysis of 200 incorrectly answered items identifies knowledge gaps (41.0%) and reasoning errors (38.0%) as the dominant failure modes. Comparative numbers for larger proprietary systems are provided only as context in the supplementary material because they may use different prompts and inference settings. The deployment configuration (quantized weights and on-premises serving) supports fast inference and local deployment. Under the quantized configuration, the system achieves a median latency of 0.84 seconds per query and fits within 28.1 GB of VRAM across two commodity GPUs. The primary results are based on public benchmark evaluations without RAG; I did not perform clinical, user-study, or real-world validations. In addition, while AIDx is designed to support fully local operation, specific deployments may choose to use third-party embedding or vector-search services; this paper documents the data-flow boundary and a fully local configuration path.
14 June 2026
Read appraisal →Lancet (London, England)
Atrasentan in patients with IgA nephropathy (ALIGN): final 2·5-year results from a randomised, double-blind, placebo-controlled, phase 3 trial
BACKGROUND: Atrasentan, a selective endothelin A receptor antagonist, reduced proteinuria in the prespecified interim analysis (week 36) of the ALIGN trial in adults with IgA nephropathy. We assessed whether atrasentan slowed estimated glomerular filtration rate (eGFR) decline after 2·5 years' treatment. METHODS: We performed a randomised, double-blind, placebo-controlled, phase 3 trial (133 sites, 20 countries). Adults with biopsy-proven IgA nephropathy, eGFR of at least 30 mL/min per 1·73 m2, and urinary protein excretion of at least 1·0 g/day while receiving renin-angiotensin system inhibition were enrolled (main stratum). An exploratory stratum enrolled participants also receiving an SGLT2 inhibitor. Participants were randomly assigned (1:1) to oral atrasentan 0·75 mg once daily or placebo for 132 weeks, followed by a 4-week off-treatment follow-up. The key secondary endpoint was change from baseline to week 136 in eGFR in the main stratum, assessed in all randomised patients (excluding data after intercurrent events, defined as initiation of restricted or alternative IgA nephropathy medications or kidney replacement therapy). Safety was assessed in all randomised patients who received at least one dose of study treatment. ALIGN is registered with ClinicalTrials.gov, NCT04573478; the double-blind section is complete, and the open-label extension is ongoing. FINDINGS: Between March 15, 2021, and April 28, 2023, 404 participants were randomly assigned (main stratum: 340; SGLT2 inhibitor stratum: 64). In the main stratum, change from baseline in eGFR at week 136 was -7·5 mL/min per 1·73 m2 (95% CI -9·2 to -5·8) with atrasentan and -9·9 mL/min per 1·73 m2 (-11·7 to -8·1) with placebo (between-group difference 2·4 mL/min per 1·73 m2; 95% CI -0·1 to 4·8; p=0·057). The between-group difference in eGFR change from baseline at end of treatment (week 132) was 2·6 mL/min per 1·73 m2 (95% CI 0·1-5·0), and the difference in total eGFR slope (baseline to week 136) was 1·4 mL/min per 1·73 m2 per year (95% CI 0·5-2·3). In the SGLT2 inhibitor stratum, the difference in eGFR change from baseline at week 136 between atrasentan and placebo was 9·1 mL/min per 1·73 m2 (95% CI 3·0-15·2). Treatment-emergent adverse events were well balanced between atrasentan and placebo, with no new safety signals. In the main stratum, fluid retention adverse events occurred in 24 (14%) of 169 patients receiving atrasentan and 20 (12%) of 170 receiving placebo. INTERPRETATION: Atrasentan reduced proteinuria and preserved kidney function after 2·5 years. This effect was present with or without concomitant SGLT2 inhibitor use. Atrasentan was well tolerated. FUNDING: Novartis.
14 June 2026
Read appraisal →Lancet (London, England)
Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial
BACKGROUND: Retatrutide is a GIP, GLP-1, and glucagon triple hormone receptor agonist, under clinical development for type 2 diabetes, obesity, and related complications. We aimed to assess the efficacy and safety of retatrutide as a monotherapy in people with type 2 diabetes that is inadequately controlled by diet and exercise alone. METHODS: In this 40-week, phase 3, randomised, double-blind, placebo-controlled trial at 48 sites in the USA, Mexico, and India, we recruited adults (aged ≥18 years) with type 2 diabetes that is inadequately controlled by diet and exercise alone, glycated haemoglobin (HbA1c) between 7·0% and 9·5% (53-80 mmol/mol), and BMI of at least 23 kg/m2. Participants were randomly assigned (1:1:1:1) to receive retatrutide (4 mg, 9 mg, or 12 mg) or placebo by once-weekly subcutaneous injection. The primary endpoint was the change in HbA1c concentration from baseline to week 40. A key secondary endpoint was the percentage change in bodyweight from baseline to week 40. This trial is registered with ClinicalTrials.gov, NCT06354660, and is completed. FINDINGS: Between April 10, 2024, and April 21, 2025, 930 participants were screened and 537 (296 [55%] female and 241 [45%] male) were randomly assigned: 134 to retatrutide 4 mg, 133 to retatrutide 9 mg, 136 to retatrutide 12 mg, and 134 to placebo. Baseline mean age was 48·8 years (SD 12·1), mean HbA1c concentration was 7·9% (SD 1·1), mean duration of diabetes was 2·5 years (SD 4·4), and mean BMI was 35·8 kg/m2 (SD 7·0). 490 (91%) participants completed the treatment period on study drug and 504 (94%) completed the study. For the treatment regimen estimand, the mean change from baseline in HbA1c concentration was -1·69% (SE 0·11) with retatrutide 4 mg, -1·86% (0·10) with 9 mg, and -1·94% (0·08) with 12 mg, versus -0·81% (0·12) with placebo, resulting in estimated treatment differences versus placebo of -0·88% (95% CI -1·18 to -0·59) with retatrutide 4 mg, -1·04% (-1·32 to -0·76) with 9 mg, and -1·12% (-1·39 to -0·85) with 12 mg (all p<0·0001). The mean percentage change from baseline in bodyweight was -11·5% (SE 0·7) with retatrutide 4 mg, -13·9% (0·8) with 9 mg, and -15·3% (0·8) with 12 mg, versus -2·6% (0·5) with placebo. The most frequent adverse events with retatrutide were generally mild to moderate gastrointestinal events, which subsided over time. Study intervention discontinuations due to adverse events were 2-5% with retatrutide and 0% with placebo. No severe hypoglycaemia was reported. Two deaths occurred during the study, both in the retatrutide 4 mg group and unrelated to the study drug. INTERPRETATION: Retatrutide showed significant improvements in glycaemic control and bodyweight reduction as a monotherapy in adults with type 2 diabetes that is inadequately controlled with diet and exercise alone, with an adverse event profile consistent with molecules with GLP-1 agonist activity, supporting its potential as an effective treatment for type 2 diabetes. FUNDING: Eli Lilly and Company.
13 June 2026
Read appraisal →Blood
Fixed-duration VenO vs FCR/BR in fit patients with untreated CLL: primary analysis of the phase 3 CRISTALLO trial
The phase 3 CRISTALLO trial compared first-line fixed-duration venetoclax-obinutuzumab (VenO) vs fludarabine, cyclophosphamide, and rituximab (FCR)/bendamustine-rituximab (BR) in patients with chronic lymphocytic leukemia (CLL), using undetectable minimal residual disease (uMRD) as the sole primary end point. Previously untreated patients with a cumulative illness rating scale score ≤6 and creatinine clearance ≥70 mL/min without del(17p)/TP53 mutations were randomized 1:1 to VenO or FCR/BR. The primary end point was uMRD (<10-4) in peripheral blood (PB) using next-generation sequencing at month 15. Key secondary end points included uMRD (<10-4) in PB and bone marrow (BM) at end of treatment (EOT) and progression-free survival (PFS). uMRD at deeper cutoffs were explored. At data cutoff (19 March 2024), 80 patients received VenO, and 86 received FCR/BR. Baseline characteristics were generally balanced across arms. The primary end point was met: 81.3% (VenO) and 54.7% (FCR/BR) achieved uMRD (<10-4) in PB at month 15 (P = .0004). uMRD (<10-4) in PB and BM at EOT was also higher with VenO vs FCR/BR. Short follow-up precluded evaluation of PFS at the first planned interim analysis; however, fewer patients progressed/died with VenO vs FCR/BR (7 vs 13). At month 15, 65.0% (VenO) and 25.6% (FCR/BR) achieved uMRD (<10-6) in PB. The overall safety profile was consistent with the known safety profile of each drug. No patient in the VenO arm was deemed high risk for tumor lysis syndrome (TLS) after obinutuzumab debulking; no clinical TLS occurred. These results confirm and extend the findings from the GAIA-CLL13 trial, validating increased depth of response with VenO vs chemoimmunotherapies. This trial was registered at www.clinicaltrials.gov as NCT04285567.
13 June 2026
Read appraisal →BMJ open gastroenterology
Safety and efficacy of advanced combination therapies for treating inflammatory bowel disease in adults: a systematic review and meta-analysis
OBJECTIVES: To systematically synthesise available evidence on the safety of advanced combination therapy (ACT) in adults with inflammatory bowel disease (IBD), with secondary exploratory evaluation of efficacy outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Searches of Embase (via Ovid), MEDLINE and PubMed were initially undertaken on 9 May 2025 and updated on 8 April 2026. Additional studies were identified through hand-searching and reference list screening. Eligible publications were restricted to those published between 1 January 2015 and 31 March 2026. ELIGIBILITY CRITERIA: We included randomised controlled trials as well as observational and descriptive studies. Conference abstracts, reviews, editorials and commentaries were excluded. Inclusion was restricted to publications in English. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened studies, extracted data and assessed risk of bias using Joanna Briggs Institute tools and Cochrane RoB-1. Pooled proportions of total adverse events (TAEs), serious adverse events (SAEs) and treatment discontinuations were calculated using random-effects meta-analysis. Subgroup analyses were conducted by drug class. Where meta-analysis was not appropriate, findings were narratively synthesised. RESULTS: Fifty-two studies (n=2022 participants) were included. The most frequent combinations were anti-TNFa plus integrin inhibitors and interleukin (IL) 23 plus integrin inhibitors. Pooled analyses demonstrated low rates of SAEs (eg, anti-TNFa plus integrin inhibitors: 2.7%, 95% CI 0.22% to 6.86%) and discontinuations (6.38%, 95% CI 2.36% to 11.58%), although heterogeneity was substantial and certainty of evidence was very low, with some analyses based on small sample sizes. CONCLUSION: ACT may be associated with low rates of SAEs in selected patients with refractory IBD; however, the evidence is limited by small sample sizes, heterogeneity and predominantly observational designs. Robust conclusions regarding safety and efficacy cannot be made due to very low GRADE certainty. PROSPERO REGISTRATION NUMBER: CRD420251025883.
13 June 2026
Read appraisal →Blood advances
A phase 1/2 study of duvelisib plus venetoclax in patients with relapsed/refractory CLL/SLL or Richter transformation
In this phase 1/2 study we evaluated duvelisib plus venetoclax in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and Richter transformation (RT). Venetoclax was added after 1 week of duvelisib. After 1 year of therapy, patients with a complete response (CR) and undetectable minimal residual disease (uMRD) could discontinue therapy; patients with detectable MRD continued venetoclax monotherapy until 2 separate occasions of uMRD. Thirty five patients with CLL/SLL and 9 with RT enrolled. Among patients with CLL, 77% had unmutated immunoglobulin heavy chain variable region, 46% had TP53 aberrancy, and patients had a median of 2 prior therapies, including 60% with prior Bruton tyrosine kinase inhibitor. In phase 1 the maximum tolerated dose was not reached, and the recommended phase 2 dose was 25mg twice daily duvelisib plus 400mg daily venetoclax. 91% of patients experienced ≥grade 3 neutropenia, with febrile neutropenia in 6%. Common nonhematologic toxicities were diarrhea (63%, 14% ≥grade 3) and elevated aspartate aminotransferase (51%, 9% ≥grade 3). The best CR and overall response rates were 60% and 91%, respectively. At cycle 13, peripheral blood and bone marrow uMRD at 10-4 were 43% and 40%, respectively. The median progression-free survival (PFS) for patients with CLL/SLL was 46 months, and the 3-year PFS was 67% (95% confidence interval, 0.51-0.86). Four patients with RS achieved a response (3 CRs). Overall, duvelisib plus venetoclax was active in R/R CLL/SLL and RT, although serious adverse events occurred, including immune-mediated toxicities. This trial was registered at www.clinicaltrials.gov as NCT03534323.
9 June 2026
Read appraisal →Blood advances
Final phase 2 study results of acalabrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia
Acalabrutinib is a selective, covalent Bruton tyrosine kinase inhibitor approved for marketing in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). We report final, long-term phase 1/2 study results in 99 patients with treatment-naive (TN) and 134 with relapsed/refractory (R/R) CLL/SLL. At final data cutoff, 71% and 31% of patients in the TN and R/R cohorts, respectively, remained on acalabrutinib treatment (median follow-up of 73.7 and 52.6 months). Among the events of clinical interest (any grade) in the TN and R/R cohorts, atrial fibrillation was reported in 6.1% and 9.0%, hypertension in 29.3% and 23.1%, other malignancies (excluding nonmelanoma skin cancer) in 14.1% and 17.2%, and major bleeding in 8.1% and 8.2% of patients, respectively. The incidence of the most common adverse events decreased over time. Overall response rates were 97.0% and 94.8% in the TN and R/R cohorts, respectively, with similar response findings among patients with standard and high-risk genomic features. In the TN cohort, median progression-free survival (PFS) was not reached and the 72-month PFS rate was 86.7% (95% confidence interval [CI], 77.0-92.5). For the R/R cohort, median PFS was 66.1 months (range, 0.4-87.8) and the 72-month PFS rate was 45.1% (95% CI, 35.6-54.1). This final analysis extends the duration of benefit observed with acalabrutinib, demonstrates that no new safety signals are apparent with longer follow-up, and confirms the safety and tolerability of acalabrutinib monotherapy for patients with CLL/SLL. This trial was registered at www.clinicaltrials.gov as #NCT02029443.
9 June 2026
Read appraisal →Blood advances
Ropeginterferon alfa-2b for prefibrotic myelofibrosis and lower-risk myelofibrosis requiring cytoreduction
There is currently no consensus on the optimal treatment of early myelofibrosis (MF). Ropeginterferon alfa-2b (ropeg) is a next-generation monopegylated interferon alfa-2b developed specifically to treat myeloproliferative neoplasms. We conducted a phase 2 study in patients with prefibrotic primary MF (pre-PMF) and Dynamic International Prognostic Scoring System low-/intermediate-1-risk fibrotic PMF or secondary MF (SMF) who required cytoreduction. Ongoing treatment with hydroxyurea was substituted with ropeg (week 0, 250 μg; week 2, 350 μg; week 4 onward, 500 μg every 2 weeks). The primary end points were safety and clinicohematologic complete response (CHCR). Seventy-one patients (40 men and 31 women) with a median age of 60 years (range, 31-86) were enrolled and followed up for a median of 119 weeks (range, 10-131). At weeks 24, 48, and 104, CHCR was achieved in 63.8% (pre-PMF, 74%; fibrotic PMF, 20%; fibrotic SMF, 42.9%), 63.5% (pre-PMF, 69.6%; fibrotic PMF, 25%; SMF, 53.9%), and 70% of patients (pre-PMF, 78.4%; fibrotic PMF, 33.3%; SMF, 50%), respectively. Thrombo-hemorrhagic events were not observed after stopping hydroxyurea. At weeks 24, 48, and 104, reduction in JAK2V617F variant allele frequency (VAF) was observed in 53.1%, 70%, and 67.6% of patients, and reduction in CALR mutant VAF was observed in 52.6%, 42.9%, and 40% of patients, respectively. In 50 evaluable cases at week 104, 13 patients (26%) had reduced bone marrow reticulin fibrosis. There were 3 treatment discontinuations (4.2%) due to adverse events. In conclusion, ropeg was safe and induced CHCR associated with significant molecular responses in patients with early MF. This trial was registered at www.clinicaltrials.gov as NCT04988815.
9 June 2026
Read appraisal →Blood advances
Accurate identification of sickle cell disease cases in a large genotyped cohort using electronic health record data
The US Food and Drug Administration recently approved sickle cell disease (SCD) gene therapies that require a contemporaneous cohort to compare their outcomes with those of individuals who did not receive gene therapy. Previously, we developed an automated algorithm to create a contemporaneous cohort of children and adults with SCD using electronic health record data. We tested the hypothesis that the updated Vanderbilt University Medical Center (VUMC) algorithm can identify individuals with SCD with sensitivity and specificity of >95%. In the VUMC health care system, we identified a cohort of 33 141 adults and children of primarily African ancestry who underwent β-globin gene sequencing, with a 1.4% prevalence of SCD (473/33 141). For SCD, the performance of the VUMC algorithm using International Classification of Diseases (ICD) and laboratory data showed a sensitivity of 97.6% (462/473), specificity of 99.9% (32 663/32 668), positive predictive value of 98.9% (462/467), and negative predictive value of 99.9% (32 663/32 674). Three SCD phenotypes account for 98.5% of the individuals in the cohort. The cohort had sensitivities of 96.8% (272/281), 93.7% (136/145), and 85% (34/40) for hemoglobin SS (HbSS)/Hb Sβ0-thalassemia (HbSβ0), HbSC, and HbSβ+, respectively. The cohort had a specificity of 99.9% across all 3 phenotypes: HbSS/HbSβ0, HbSC, and HbSβ+, respectively. We have developed an updated algorithm using ICD and laboratory data that accurately identifies individuals with SCD within a large health care system, and distinguishes HbSS/HbSβ0, HbSC, and HbSβ+.
9 June 2026
Read appraisal →Neurology
Acute Kidney Injury and Risk of Adverse Neurocognitive Outcomes: A Systematic Review and Meta-Analysis
BACKGROUND AND OBJECTIVES: Chronic kidney disease is a recognized risk factor for adverse neurocognitive outcomes, but the effect of acute kidney injury (AKI) on brain health remains less well defined. We conducted a systematic review and meta-analysis to evaluate associations between AKI and subsequent risk of stroke, delirium, and dementia. METHODS: Eligible studies were identified by searching Ovid MEDLINE and Embase from inception (Ovid: January 1946; Embase: January 1970) until April 2025. Studies were included if they reported quantitative estimates with measures of precision for the association between AKI and delirium, stroke, or dementia in adult populations. Two reviewers independently screened and extracted data, and study quality was assessed using standardized criteria. Study characteristics, participant demographics, and adjusted effect estimates (hazard ratios [HRs] or odds ratios [ORs]) with 95% CIs were extracted. Pooled HRs and ORs with 95% CIs were calculated using random-effects models. Heterogeneity was evaluated with the χ2 test and I2 statistic, and sources of heterogeneity were explored through prespecified subgroup analyses and meta-regression. RESULTS: We identified 49 studies comprising 11,253,825 participants with 1,279,145 events. Individuals with AKI were at increased risk of stroke (pooled adjusted HR 1.35, 95% CI 1.20-1.52), delirium (pooled adjusted OR 1.76; 1.42-2.17), and dementia (pooled adjusted HR 1.64, 1.41-1.89). A gradient of risk across increasing AKI stages was demonstrated for stroke (stage 1: HR 1.11; 1.00-1.23; combined stages 2 and 3: HR 1.57; 1.35-1.81). AKI was also associated with higher in-hospital and 90-day mortality poststroke (pooled HR 2.13, 1.56-2.90, and 4.81, 2.55-9.08, respectively) and with 90-day disability (pooled adjusted OR 1.47, 1.22-1.76). Associations between AKI and all outcomes were directionally consistent across sensitivity analyses and pooled propensity score-matched studies. DISCUSSION: In this systematic review and meta-analysis, AKI was consistently associated with increased short-term and long-term neurocognitive risk, including stroke, delirium, and dementia. These findings suggest that AKI may identify individuals vulnerable to both acute and chronic brain injury. Further studies are needed to clarify mechanisms linking AKI to brain injury and to identify strategies to mitigate neurocognitive risk in this high-risk population.
9 June 2026
Read appraisal →Bioorganic chemistry
Multi-relational knowledge graph for drug-drug interaction prediction via dual aggregation and collaborative optimization
Identifying potential drug-drug interactions is crucial in clinical care and new drug development, as mutual interference between drugs can lead to adverse reactions. Recently, computational methods have been widely employed for predicting DDIs. However, these approaches often encounter high computational complexity during the process of node feature representation and frequently overlook the interactivity and polysemy of entities. Effectively handling heterogeneous information remains a significant challenge. To cope with these limitations, we propose a dual aggregation and collaborative optimization learning framework，named MRACO，for DDIs prediction based on a multi-relational knowledge graph. MRACO utilizes structural information from these graphs, efficiently learning interactivity information across various relationship types. Additionally, MRACO employs dual aggregation operations to explicitly encode and aggregate multi-type information, capturing diverse semantic relationships of drug nodes. Moreover, MRACO simplifies complex computational processes by utilizing the collaborative loss optimization function, eliminating redundant information and enhancing model robustness. By integrating deep-level interactive information, MRACO leverages rich contextual data from knowledge graphs, enhancing prediction stability. Experiments demonstrate the effective of MRACO feature extraction capabilities in multi-relational networks, highlighting its understanding of the underlying mechanisms of DDIs.
7 June 2026
Read appraisal →Medicine
Triple oral therapy combining metformin, SGLT-2 and DPP-4 inhibitors versus dual therapy in type 2 diabetes mellitus: A systematic review and meta-analysis
BACKGROUND: Triple oral therapy combining metformin, sodium-glucose cotransporter 2 inhibitor, and a dipeptidyl peptidase-4 inhibitor has been proposed as a synergistic approach to intensify glycemic control in patients with type 2 diabetes mellitus. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of triple therapy compared to dual therapy (metformin plus either sodium-glucose cotransporter 2 or dipeptidyl peptidase-4 inhibitor). METHODS: Following preferred reporting items for systematic review and meta-analysis guidelines, we searched PubMed, Embase, Scopus, and Web of Science through January 2026. Studies included randomized controlled trials comparing triple versus dual therapy in adults with type 2 diabetes mellitus. Outcomes included hemoglobin A1c (HbA1c), fasting plasma glucose, body weight, achievement of HbA1c < 7%, and adverse events (AEs). Pooled standardized mean differences (SMDs) and risk ratios (RRs) were calculated using random-effects models. RESULTS: Eight studies encompassing 2606 participants were included. Findings indicate triple therapy significantly reduced HbA1c levels compared to dual therapy, with a SMD of - 0.54 (95% confidence interval [CI]: -0.92 to -0.16; P = .005). Triple therapy resulted in greater reduction in fasting plasma glucose, with an SMD of -0.30 (95% CI: -0.62 to 0.01; P = .06). Patients on triple therapy were more likely to achieve HbA1c levels below 7% (RR: 2.02; 95% CI: 1.55-2.63; P < .0001). Weight reduction was modest, with an SMD: -0.14 (95% CI: -0.22 to -0.07; P = .0002). No significant differences were found in total AEs (RR = 0.97; P = .69) or hypoglycemia (RR = 1.32; P = .32), although there was higher discontinuation due to AEs (RR = 2.62; P = .03). CONCLUSION: Triple therapy offers superior glycemic control over dual therapy without major safety trade-offs, though tolerability may affect long-term adherence.
31 May 2026
Read appraisal →BMJ health & care informatics
Machine learning-based prediction of a high-risk kidney function trajectory class after acute kidney injury
OBJECTIVES: Monitoring kidney function after acute kidney injury (AKI) hospitalisation is essential for identifying patients at risk of rapid progression. This study developed a machine learning (ML) model to predict membership in a high-risk longitudinal estimated glomerular filtration rate (eGFR) trajectory associated with subsequent kidney replacement therapy (KRT) initiation. METHODS: We conducted a cohort study of 88 632 adults with ≥2 post-discharge eGFR measurements between 2010 and 2017. Joint latent class mixed models were used to identify dynamic eGFR trajectories from 665 499 measurements. Patient-level data splitting (80/20) was strictly enforced. Extreme gradient boosting (XGBoost) and random forest models were trained using clinical features within 3 months after discharge to predict membership in the highest-risk eGFR trajectory class. RESULTS: Three eGFR trajectories were identified: Steady Low (high-risk phenotype), Slow Decline and Recovery. The Steady Low group showed the strongest association with KRT. The 10-variable XGBoost model demonstrated excellent discrimination (AUROC 0.974, sensitivity 0.913, specificity 0.919). The eGFR slope from discharge to 3 months was the most influential predictor of high-risk progression. DISCUSSION: Although the study was limited to a single healthcare system, this ML framework identified patients at risk of rapid kidney function decline using routinely available clinical data. The model supports early risk stratification after AKI and may enable more timely kidney-protective interventions. External validation, calibration assessment and benchmarking against simpler eGFR-based rules remain important next steps. CONCLUSION: A 10-variable XGBoost model accurately identifies patients with deteriorative eGFR trajectories (Steady Low) early after discharge, providing a practical framework for personalised post-AKI kidney care.
29 May 2026
Read appraisal →BMJ open
Multicentre prospective cohort study to develop and validate a machine learning-based model for predicting 6-month all-cause mortality in elderly patients with advanced chronic obstructive pulmonary disease in China: study protocol
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) has an unpredictable clinical course, causing difficulties in short-term mortality prediction, overtreatment and delayed palliative care. Existing prediction models are limited and lack applicability to Chinese elderly patients with advanced COPD. Given the heavy disease burden and limited palliative care in China, we designed this multicentre cohort study to develop a 6-month mortality prediction model for elderly patients with advanced COPD to aid risk stratification, timely palliative care and efficient healthcare resource allocation. METHODS AND ANALYSIS: Patient recruitment has been ongoing since May 2024 and will be completed by December 2026, with a 12-month follow-up to be completed by December 2027. Eligible patients are being enrolled, and multidimensional baseline data including demographic characteristics, clinical indicators, laboratory results, comprehensive geriatric assessment and COPD-specific prognostic factors are being systematically collected. All participants will receive 12 months of standardised follow-up (monthly for the first 6 months and quarterly thereafter) to monitor 6-month all-cause mortality (primary outcome), as well as survival duration, end-of-life healthcare utilisation and do-not-resuscitate status (secondary outcomes). After completion of data collection, we will employ multiple machine learning algorithms to develop and internally validate a 6-month mortality prediction model with pre-specified centres reserved for external validation. Model performance will be evaluated by discrimination and calibration and head-to-head comparisons with the Body Mass Index, Airflow Obstruction, Dyspnoea and Exercise Capacity (BODE) and Age, Dyspnoea and Airflow Obstruction (ADO) indices will be conducted to verify its clinical value. The findings will provide a China-specific prediction tool for elderly patients with advanced COPD to guide clinical intervention, palliative care referral and healthcare resource allocation. ETHICS AND DISSEMINATION: This study was approved by the Biomedical Ethics Review Committee of West China Hospital, Sichuan University (No. 2024-2662) and registered at ChiCTR2500100351. Informed consent is being obtained from all participants. Results will be published in peer-reviewed journals and presented at academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2500100351.
29 May 2026
Read appraisal →Polish archives of internal medicine
Biologic and targeted synthetic treatment of SAPHO syndrome: systematic literature review
INTRODUCTION: SAPHO syndrome is a rare autoimmune / autoinflammatory disorder with no approved therapies or standardized management guidelines. Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are increasingly used off‑label. OBJECTIVES: This review aimed to systematically evaluate the evidence for the efficacy of b/tsDMARDs in SAPHO. PATIENTS AND METHODS: A PRISMA‑guided search of PubMed database was conducted through March 31, 2025. Studies of any design reporting outcomes of b/tsDMARDs in patients with SAPHO fulfilling the modified Kahn criteria were included. Exclusion criteria were non‑English language, inaccessible full text, and insufficient treatment details. Data on patient characteristics, drug class, follow‑up duration, and treatment response were extracted. As all the included studies were case reports or case series, the risk of bias was not assessed. Treatment responses were summarized using descriptive statistics. RESULTS: Of 1610 screened records, 106 studies comprising 385 instances of b/tsDMARD use met the inclusion criteria; no randomized controlled trials were identified. Tumor necrosis factor inhibitors (TNFis) were used in 203 patients, with complete skeletal and skin responses in 81% and 72%, respectively. The use of Janus kinase inhibitors (JAKis) in 77 patients was associated with complete response rates of 89% (skeletal) and 94% (skin). Other b/tsDMARD classes-including interleukin 17 (IL‑17), IL‑23, IL‑1, and IL‑6 inhibitors, as well as phosphodiesterase‑4 inhibitors-demonstrated variable and generally lower efficacy. CONCLUSIONS: Evidence for b/tsDMARD efficacy in SAPHO remains limited to low‑quality, uncontrolled studies with substantial heterogeneity and probable publication bias. TNFis and JAKis are among the most consistently effective therapies reported in the available literature, but high‑quality research, including randomized trials or prospective registries, is urgently needed to inform evidence‑based management.
29 May 2026
Read appraisal →JAMA
Fast Antimicrobial Susceptibility Testing for Gram-Negative Bacteremia: The FAST Randomized Clinical Trial
IMPORTANCE: Novel blood culture diagnostics provide rapid antimicrobial susceptibility testing (AST) results for bacteria causing bloodstream infections (BSIs) but have unclear clinical impact. OBJECTIVE: To evaluate clinical outcomes of blood culture testing using a rapid AST method compared with standard AST in patients with BSIs caused by gram-negative bacilli in regions with high prevalence of antimicrobial resistance. DESIGN, SETTING, AND PARTICIPANTS: Open-label randomized clinical trial that enrolled participants from December 2023 to May 2025 (final follow-up, June 18, 2025) at 7 medical centers in Greece (n = 2), India (n = 1), Israel (n = 3), and Spain (n = 1). Hospitalized patients (adults and children) with BSIs caused by gram-negative bacilli were eligible. Statistical analysis was conducted from August 2025 to January 2026. INTERVENTION: Patients were randomized to undergo blood culture evaluation using rapid, phenotypic AST directly from positive blood cultures plus standard susceptibility testing (n = 413) vs standard susceptibility testing alone (n = 437). Local antimicrobial stewardship teams reviewed all patients and provided treatment recommendations. MAIN OUTCOMES AND MEASURES: The primary outcome was a desirability of outcome ranking (DOOR) at day 30, with 3 categories (alive without deleterious events, alive with deleterious events, and death). The difference between rapid and standard testing was summarized as the probability that the DOOR outcomes were more desirable in the rapid testing group. Superiority was concluded if the lower limit of the 95% CI exceeded 50%. Secondary outcomes included 30-day mortality, length of hospitalization, intensive care unit admission, acquisition of hospital-acquired infections, time to effective antibiotic therapy within 3 days, and time to antibiotic escalation or deescalation within 3 days. RESULTS: Of the 899 patients randomized, 850 were included in the primary outcome analysis (median [IQR] age, 72 [21] years; 43% female). The probability that DOOR outcomes were more favorable in the rapid testing group was 48.8% (95% CI, 45.3%-52.4%). Median time to effective antibiotic therapy was not different between the groups in the as-randomized population. Median time to antibiotic escalation or deescalation was faster in the rapid testing group by 14 hours (95% CI, 6-22) in the as-randomized population. There were no differences between the groups in other secondary outcomes. In the prespecified subgroup with carbapenem-resistant infections, median time to effective therapy was 9.5 hours in the rapid testing group vs 28 hours in the standard testing group (difference, -18 hours [95% CI, -42 to 6]). CONCLUSIONS AND RELEVANCE: Among patients with gram-negative bacilli BSIs, rapid blood culture AST was not superior to standard testing by DOOR. When considered with other efficacy and safety outcomes, these findings may help inform the use of rapid susceptibility testing in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06174649.
29 May 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
Muscle sympathetic nerve activity in COPD: a systematic review and meta-analysis
BACKGROUND: Cardiovascular disease is a primary driver of mortality in COPD. Elevated sympathetic nerve activity is a key proposed mechanism, but the magnitude of this autonomic overactivity has not been quantified in a pooled analysis. OBJECTIVE: To determine if adults with COPD exhibit higher resting muscle sympathetic nerve activity (MSNA) than healthy controls, assess associated cardiorespiratory effects, and evaluate the short-term impact of COPD interventions on MSNA. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, eight databases were searched from inception to 15 May 2025 to inform this systematic review and meta-analysis (PROSPERO CRD420251044931). Eligible studies included adults with spirometry-defined COPD in whom MSNA was measured by microneurography at rest. Primary outcomes were MSNA burst frequency (bursts·min-1) and incidence (bursts per 100 heartbeats). Secondary outcomes included resting heart rate and blood pressure. RESULTS: A total of 11 studies (171 COPD participants, 105 controls) met inclusion criteria. Compared with controls, COPD was associated with markedly higher MSNA, burst frequency (+18.5, 95% CI 9.4-27.7 bursts·min-1) and burst incidence (+21.3, 95% CI 9.2-33.4 bursts per 100 heartbeats). Resting heart rate was also elevated (+10.7, 95% CI 6.1-15.3 beats·min-1), while blood pressure did not differ significantly. Three studies on noninvasive ventilation or inhaled β2-agonists found no significant pooled changes in MSNA. CONCLUSIONS: Resting MSNA is significantly elevated in patients with COPD despite normal blood pressure. This chronic sympathetic excitation likely contributes to COPD-related cardiovascular morbidity and exercise intolerance, highlighting the importance of developing therapies that reduce sympathetic nerve activity.
29 May 2026
Read appraisal →BMJ open
Does a protocolised oxygenation target impact clinical outcomes in mechanically ventilated patients in the intensive care unit across the 10 academic and community hospitals in the UCHealth system? Protocol and statistical analysis plan for an EHR-embedded pragmatic stepped-wedge randomised controlled trial.
INTRODUCTION: We designed the Optimising Care in Critically Ill at the UCHealth by Liberalising the Target O₂ in Mechanically ventilated intensive care unit (ICU) Patients to determine the effectiveness of a multimodal educational and electronic health record order panel intervention in limiting occult hypoxaemia and hyperoxaemia in patients receiving invasive mechanical ventilation by targeting a prespecified oxygen saturation (SpO₂ 90%-96%) range. METHODS AND ANALYSIS: This trial is a pragmatic electronic health record-embedded, multisite, cluster-randomised, stepped-wedge implementation of a multimodal educational and electronic health record order panel intervention aimed at achieving a standardised intermediate target range of SpO₂ (90%-96%) or partial pressure of oxygen (PaO₂ 60-100 mm Hg) in mechanically ventilated adult patients admitted to the ICU across a 10 hospital health system that includes a large academic centre and smaller community hospitals.The primary endpoint is ventilator-free days to day 30, defined as the number of days alive and not receiving support through invasive mechanical ventilation following the first initiation of invasive mechanical ventilation in a participating ICU during the hospitalisation. Secondary outcomes include a variety of clinical endpoints: hospital-free days to day 30, all-cause mortality to day 90, need for supplemental oxygen at discharge and incidence of occult hypoxaemia and hypoxaemia. We will analyse primary and secondary endpoints using a mixed effects modelling framework, with specific distributions chosen depending on the type of outcome (eg, binary, count, ordinal, time-to-event). ETHICS AND DISSEMINATION: Research is performed under a waiver of informed consent for minimal-risk research, as approved by Colorado Multiple Institutional Review Board (24-0065). Results will be disseminated in peer-reviewed publications and at national and international conferences. TRIAL REGISTRATION NUMBER: NCT06501118.
28 May 2026
Read appraisal →BMC nephrology
Roxadustat for CKD-related anemia in patients undergoing peritoneal dialysis: a systematic review and meta-analysis
BACKGROUND: CKD-related anemia remains a major complication in patients receiving peritoneal dialysis (PD), with limited treatment options beyond erythropoiesis-stimulating agents. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, has shown promise in correcting CKD-related anemia and modulating iron and metabolic parameters. However, its evidence in PD remains limited. METHODS: We conducted a systematic search of PubMed, Scopus, and Web of Science from inception to July 20, 2025. We included studies reporting the efficacy and safety of roxadustat in PD. Statistical analysis was performed using Review Manager (RevMan 5.4 for Windows) and R Studio. RESULTS: Eight studies were included in the meta-analysis (n = 607). Roxadustat significantly increased hemoglobin at all time points (MD 0.35 g/dL, 95% CI 0.28-0.41; p < 0.00001), serum iron (MD 0.95 µmol/L, 95% CI 0.02-1.89; p = 0.05), and total iron-binding capacity (MD 6.25 µmol/L, 95% CI 3.95-8.55; p < 0.00001), and reduced hepcidin (MD - 12.28 ng/mL, 95% CI - 21.06 to - 3.50; p = 0.006). No significant effects were observed for ferritin (p = 0.49), transferrin saturation (p = 0.45), cholesterol (p = 0.07), LDL (p = 0.14), HDL (p = 0.27), triglycerides (p = 0.26), CRP (p = 0.75), systolic blood pressure (p = 0.10), or diastolic blood pressure (p = 0.08). Heterogeneity was low to moderate for most outcomes. CONCLUSION: Roxadustat is effective in improving hemoglobin and iron metabolism in patients with PD, while exerting neutral effects on lipids, inflammation, and blood pressure. These findings support its role as a promising therapy for CKD-related anemia in PD. CLINICAL TRIAL NUMBER: Not applicable.
28 May 2026
Read appraisal →Autoimmunity
IgA Vasculitis with necrotizing arteritis: a multicenter retrospective study from the French Vasculitis Study Group and systematic review of the literature
IgA vasculitis (IgAV) primarily affects small vessels, but rare cases with necrotizing arteritis (NA) raise questions about overlap with polyarteritis nodosa (PAN). To characterize IgAV with necrotizing arteritis (IgAV-NA) and compare its phenotype with classical IgAV and PAN. We performed a multicenter retrospective study combined with a systematic literature review (1990-2025). Patients fulfilled EULAR/PRINTO/PRES IgAV criteria, had pathological or imaging evidence of NA in small or medium arteries, and were ANCA-negative. Thirty patients were included (7 from databases, 23 from the literature). NA was confirmed by biopsy (n = 16) or vascular imaging (n = 14). Clinical features, treatments, remission, and mortality were compared with 257 adult IgAV and 196 PAN patients. Median age was 54.5 years. IgAV-NA was characterized by severe manifestations, including gastrointestinal bleeding, perforation, surgical abdomen, neuropathy, pancreatitis, and livedo. Compared with classical IgAV, IgAV-NA showed significantly higher rates of multi-organ involvement and mortality. Compared with PAN, IgAV-NA shared vascular complications but had less fever and neuropathy. Despite arterial involvement, patients did not fulfil PAN criteria. IgAV-NA represents a rare, severe IgAV phenotype with life-threatening complications rather than an IgAV-PAN overlap. Severe or atypical IgAV presentations should prompt vascular imaging and intensified immunosuppression.
28 May 2026
Read appraisal →The Cochrane database of systematic reviews
Steroid avoidance or withdrawal for kidney transplant recipients.
RATIONALE: Steroid-sparing strategies aim to reduce the adverse effects associated with steroid use. The main concern has been a potential increase in the risk of rejection, as reported in previous systematic reviews. In recent years, improvements in immunosuppressive regimens and a significant decline in the incidence of acute rejection have renewed interest in steroid-sparing strategies. More contemporary trials suggest that reducing steroid exposure might be safe. This is an updated review, previously published in 2009 and 2016. OBJECTIVES: To evaluate the benefits and harms of steroid withdrawal or avoidance for kidney transplant recipients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register, CENTRAL, MEDLINE, Embase and two trials registers up to 29 April 2025. ELIGIBILITY CRITERIA: All randomised and quasi-randomised controlled trials that evaluated steroid avoidance or withdrawal after kidney transplantation. OUTCOMES: Critical outcomes were all-cause death, graft loss and biopsy-proven acute rejection. Important outcomes were post-transplant diabetes mellitus, cardiovascular events, infection, malignancy, and kidney function measures. RISK OF BIAS: Risk of bias was assessed with the Cochrane RoB 1 tool. SYNTHESIS METHODS: Assessment of risk of bias and data extraction were performed independently by at least two authors, and disagreements were resolved through discussion. Statistical analyses were performed using the random-effects model, and dichotomous outcomes were reported as risk ratios (RRs) and continuous outcomes as mean differences (MDs) with 95% confidence intervals (CIs). The certainty of the evidence was assessed using the GRADE approach. INCLUDED STUDIES: This updated review includes 53 studies (261 reports, 8317 randomised kidney transplant recipients). Of these, three studies were conducted in children (204 randomised participants). SYNTHESIS OF RESULTS: The overall certainty of the evidence of the included studies was low, ranging from moderate to very low. Factors downgraded on GRADE were primarily risk of bias and imprecision. Over 50% of the included studies did not adequately report random sequence generation or allocation concealment. Only five of 53 studies blinded participants and investigators. Incomplete outcome data was judged to be low in 26 studies, and 41 were free of selective reporting. Studies in adult kidney transplant recipients Steroid avoidance versus steroid maintenance The evidence is very uncertain about the effect of steroid avoidance on all-cause death up to one year (RR 0.84, 95% CI 0.51 to 1.39; 13 studies, 2126 participants; very-low-certainty evidence). Steroid avoidance may reduce death by one to five years (RR 0.61, 95% CI 0.39 to 0.96; 9 studies, 1607 participants; low-certainty evidence), and has little to no effect on graft loss censored for death up to one year (RR 0.95, 95% CI 0.62 to 1.46; moderate-certainty evidence). Steroid avoidance may increase the risk of biopsy-proven acute rejection up to one year (RR 1.58, 95% CI 1.11 to 2.25; 10 studies, 1845 participants; low-certainty evidence), although subgroup analysis showed no increase in risk when steroid avoidance was used in combination with tacrolimus, an antimetabolite and induction therapy. Steroid avoidance may reduce the risk of post-transplant diabetes mellitus up to five years (RR 0.70, 95% CI 0.59 to 0.84; 13 studies, 2390 participants; low-certainty evidence), but may have little to no effect on cardiovascular events (RR 0.73, 95% CI 0.46 to 1.18; 6 studies, 1417 participants; low-certainty evidence), infection (all) (RR 0.96, 95% CI 0.87 to 1.05; 11 studies, 2426 participants; low-certainty evidence), and probably has little to no effect on cytomegalovirus (CMV) infection (RR 1.01, 95% CI 0.80 to 1.27; 9 studies, 2155 participants; moderate-certainty evidence). Steroid withdrawal versus steroid maintenance Compared to steroid maintenance, steroid withdrawal may have little to no effect on all-cause death up to one year (RR 0.69, 95% CI 0.35 to 1.37; 9 studies, 1884 participants; low-certainty evidence) or one to five years (RR 1.17, 95% CI 0.67 to 2.03; 8 studies, 1189 participants; low-certainty evidence), and probably has little to no effect on graft loss censored for death up to one year (RR 1.19, 95% CI 0.72 to 1.96; 8 studies, 1854 participants; moderate-certainty evidence). Steroid withdrawal may have little to no effect on biopsy-proven acute rejection up to one year (RR 1.41, 95% CI 0.89 to 2.23; 5 studies, 1406 participants; low-certainty evidence). Steroid withdrawal probably has little to no effect on post-transplant diabetes mellitus up to five years (RR 0.82, 95% CI 0.55 to 1.21; 8 studies, 1647 participants; moderate-certainty evidence), and may have little to no effect on cardiovascular events up to five years (RR 0.91, 95% CI 0.42 to 1.97; 3 studies, 712 participants; low-certainty evidence) or infection (all) up to five years (RR 1.06, 95% CI 0.83 to 1.36; 6 studies, 1924 participants; low-certainty evidence). Steroid withdrawal probably has little to no effect on CMV infection up to five years (RR 1.10, 95% CI 0.85 to 1.43; 7 studies, 1956 participants; moderate-certainty evidence). Steroid avoidance versus steroid withdrawal The evidence is very uncertain regarding the effects of steroid avoidance compared with steroid withdrawal (4 studies, 466 randomised participants). Studies in paediatric kidney transplant recipients The evidence is very uncertain regarding the effects of steroid-sparing regimens in paediatric kidney transplant recipients (3 studies, 204 randomised participants). AUTHORS' CONCLUSIONS: There was no evidence to suggest a difference in patient death or graft loss up to one year after transplantation with steroid avoidance or withdrawal compared to maintenance, but steroid avoidance may reduce patient death at five years in adult kidney transplant recipients. Steroid avoidance may increase the risk of biopsy-proven acute rejection, but the risk may be similar when steroid avoidance is paired with tacrolimus, antimetabolite and induction therapy. The risk of biopsy-proven acute rejection in steroid withdrawal regimens may be similar to steroid maintenance regimens. We found no evidence to suggest differences in cardiovascular events or infection, but steroid avoidance compared to steroid maintenance may reduce the risk of post-transplant diabetes mellitus. FUNDING: LO is supported by a Río Hortega predoctoral fellowship from the Instituto de Salud Carlos III. REGISTRATION: Protocol and previous versions available via https://doi.org/10.1002/14651858.CD005632, https://doi.org/10.1002/14651858.CD005632.pub2, and https://doi.org/10.1002/14651858.CD005632.pub3.
27 May 2026
Read appraisal →Nature communications
Measuring multi-site pulse transit time with an AI-enabled mmWave radar
Pulse Transit Time (PTT) is a measure of arterial stiffness and a physiological marker associated with cardiovascular function, with an inverse relationship to diastolic blood pressure (DBP). We present an AI-enabled mmWave system for contactless multi-site PTT measurement using a single radar. By leveraging radar beamforming and deep learning algorithms our system simultaneously measures PTT and estimates diastolic blood pressure at multiple sites. The system was evaluated across three physiological pathways - heart-to-radial artery, heart-to-carotid artery, and mastoid area-to-radial artery - achieving correlation coefficients of 0.75-0.86 compared to contact-based reference sensors for measuring PTT. Furthermore, the system demonstrated correlation coefficients of 0.90-0.91 for estimating DBP, and achieved a mean error of -0.62-0.06 mmHg and standard deviation of 4.54-5.20 mmHg, meeting the FDA's AAMI guidelines for non-invasive blood pressure monitors. These results suggest that our proposed system has the potential to provide a non-invasive measure of cardiovascular health across multiple regions of the body.
27 May 2026
Read appraisal →Renal failure
Complication rates of 16- and 18-gauge needles for native kidney biopsies: a systematic review and proportional meta-analysis
This systematic review and meta-analysis evaluated complication rates and diagnostic yield reported in studies of adult native kidney biopsy using 16-gauge (16 G) or 18-gauge (18 G) needles. We included randomized trials and cohort studies of real-time ultrasound-guided biopsies, including case series. MEDLINE, Embase, and CENTRAL were searched through October 2024. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using Joanna Briggs Institute tools. Random-effects meta-analyses estimated pooled proportions with 95% confidence intervals (CI), and univariable random-effects meta-regression explored study-level associations with major complications, transfusion, or gross hematuria. We screened 4,499 titles and abstracts and reviewed 319 full-text articles; 62 studies comprising 68 biopsy series were included. The pooled major complication rate in studies using 16 G needles was 1.83% (95% CI: 1.20-2.79) and 1.29% (95% CI: 0.78-2.13) in studies using 18 G needles, with no statistically significant difference. Mean glomerular yield was 18.8 with 16 G and 17.5 with 18 G needles. In study-level meta-regression, studies with higher prevalence of acute kidney injury, lower mean estimated glomerular filtration rate, or lower mean hemoglobin reported higher pooled complication rates. Most studies were single-arm cohorts; between-needle differences therefore reflect indirect study-level contrasts. Interpretation is limited by retrospective design and heterogeneity across studies. Overall, studies using both needle sizes reported low complication rates and similar diagnostic yield, although definitions and reporting varied. Direct comparative studies are needed to determine whether meaningful differences exist. What was knownKidney biopsy is essential for diagnosing many medical kidney diseases and guiding treatment, requiring adequate tissue samples for subsequent analyses.Modern biopsy techniques use spring-loaded, ultrasound-guided devices with smaller gauge needles, but optimal needle size remains uncertain.While 14G needles are associated with higher complication risk, evidence on whether 16G or 18G needles differ in safety or diagnostic yield is conflicting.This study addsIn this systematic review and meta-analysis of 62 studies involving 22,208 adult native kidney biopsies, we found no statistically significant difference in major complication rates between studies using 16G and 18G needles.In study-level meta-regression analyses, studies with a higher prevalence of acute kidney injury, lower mean estimated glomerular filtration rate, and lower mean hemoglobin reported higher pooled major complication rates.Potential impactStudies using both 16G and 18G needles reported similarly low major complication rates, although comparisons are based on indirect evidence with substantial heterogeneity.Findings support the ethical feasibility and clinical relevance of a large, randomized controlled trial to definitively guide needle size selection in native kidney biopsies.
26 May 2026
Read appraisal →Blood advances
Selinexor plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: a multicenter, open-label, phase 1 study
The phase 1 portion of SENTRY/XPORT-MF-034 (NCT04562389) evaluated the exportin 1 inhibitor selinexor (40 mg/60 mg once weekly) plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis (n = 24). Primary end points were maximum tolerated selinexor dose, recommended clinical trial dose, and safety. No dose-limiting toxicities were reported. Common adverse events were nausea, fatigue, anemia, thrombocytopenia, constipation, vomiting, and headache. Nausea was transient, mainly grade 1, and managed by prophylactic antiemetics. Four deaths occurred, all unrelated to study treatment. Selinexor 60 mg in combination with ruxolitinib was identified as the recommended phase 3 dose based on safety, efficacy, and exposure-response analyses. Overall safety profiles and grades of clinically significant adverse events were similar and generally manageable regardless of selinexor dose. A greater proportion of patients achieved spleen volume reduction of ≥35% (SVR35) and total symptom score reduction of ≥50% (TSS50) at week 24 in the selinexor 60-mg group (79% and 58%) than the 40-mg group (38% and 25%). Among evaluable patients who received suboptimal ruxolitinib ≤5 mg twice daily in the selinexor 60-mg group, SVR35 was observed in 100% (6/6) and TSS50 in 75% (3/4) of patients. The trial was registered at ClinicalTrials.gov as NCT04562389.
26 May 2026
Read appraisal →Blood advances
Phase 2 study of the lysine-specific demethylase 1 inhibitor bomedemstat for essential thrombocythemia
Novel treatments that can improve outcomes of essential thrombocythemia (ET) are needed. In a phase 2 trial, participants with ET who required cytoreduction and had inadequate response to, or were intolerant of, ≥1 standard therapy received bomedemstat at a starting dose of 0.6 mg/kg per day, titrated to achieve a target platelet count (200 × 109/L to 400 × 109/L). Primary end points were safety and response, defined as a platelet count of ≤400 × 109/L without new thromboembolic events. Of 73 who received bomedemstat, at 24 weeks, 49 of 64 evaluable participants (77%) achieved a response. Durable reductions in platelet count (≤400 × 109/L for ≥12 weeks) were observed in 52 of 72 participants (72%). Durable reduction in white blood cell count (<10 × 109/L for ≥12 weeks) was observed in 61 of 72 participants (85%); of 10 participants with elevated white blood cell count at baseline, 9 had normal white blood cell count (<10 × 109/L) at week 24. Hemoglobin levels remained stable. After 24 weeks of treatment, a decrease in variant allele frequency of CALR, JAK2, or MPL was observed in 39 of 46 (85%) evaluable participants. By week 24, 2 of 73 participants (3%) had experienced ≥1 thrombotic event, and 15 of 73 (21%) experienced ≥1 hemorrhagic event. During overall treatment period, grade 3 or 4 adverse events (AEs) occurred in 34 of 73 participants (47%). AEs led to temporary treatment interruption in 29 participants (40%) and permanent discontinuation in 11 (15%). No participants died due to AEs. Bomedemstat had clinically relevant activity and manageable safety in participants with ET. This trial was registered at www.clinicaltrials.gov as #NCT04254978.
26 May 2026
Read appraisal →Circulation journal : official journal of the Japanese Circulation Society
High Human Epididymis Protein 4 Levels Are Associated With Lower Systolic Function and Poor Prognosis in Heart Failure With Reduced Ejection Fraction
BACKGROUND: Human epididymis protein 4 (HE4) is a novel fibrosis marker expressed in activated myofibroblasts. Although we previously demonstrated its prognostic value in dilated cardiomyopathy, its significance in general heart failure with reduced ejection fraction (HFrEF) remains unclear. METHODS AND RESULTS: Serum HE4 concentrations were measured in 140 patients with HFrEF (left ventricular ejection fraction <40%) and followed for up to 3 years to assess cardiovascular (CV) death and heart failure hospitalization. Kaplan-Meier analysis revealed significantly higher CV event rates in the high HE4 group (above the median) than in the low HE4 group (log-rank P<0.001). Multivariate Cox regression analysis identified HE4 (ln[HE4]) as an independent predictor of adverse outcomes (hazard ratio 3.99; 95% confidence interval [CI] 2.05-7.75; P<0.001). In multivariate linear regression, HE4 was significantly associated with age, serum creatinine, plasma B-type natriuretic peptide, E/e', and global longitudinal strain (GLS; β=-0.083; 95% CI -0.111, -0.054; P<0.001). Combining HE4 and GLS demonstrated that patients with high HE4 and low GLS had the highest CV event rate (log-rank P<0.001). CONCLUSIONS: HE4 is an independent prognostic biomarker in HFrEF, and its association with GLS may reflect underlying myocardial dysfunction and fibrotic remodeling leading to adverse outcomes.
26 May 2026
Read appraisal →Circulation journal : official journal of the Japanese Circulation Society
Association Between Ventricular-Arterial Coupling and C-Reactive Protein in Patients at Risk for Heart Failure
BACKGROUND: Although ventricular-arterial coupling (VAC) and C-reactive protein (CRP) are associated with the pathogenesis of heart failure (HF), their association in patients at risk of HF remains unclear. METHODS AND RESULTS: VAC was assessed by arterial elastance (Ea) to left ventricular endsystolic elastance (Ees) ratio (Ea/Ees) using the noninvasive single-beat method in 112 hypertensive patients. Log-transformed high-sensitivity CRP (hs-CRP) and categorical hs-CRP were associated with Ea/Ees on univariate analysis. Categorical hs-CRP was independently associated with Ea/Ees after adjusting for atherosclerotic risk factors, cardiac function and vascular function (β=0.27, P=0.003). CONCLUSIONS: hs-CRP was independently associated with VAC assessed by Ea/Ees in patients at risk of HF.
25 May 2026
Read appraisal →Rheumatology international
Diffuse splenic calcifications in systemic lupus erythematosus: a case-based review
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease with a wide spectrum of splenic manifestations. In recent literature, splenic calcifications have increasingly been recognized as a rare manifestation of SLE. We describe a patient presenting with fever in whom abdominal imaging revealed splenomegaly with diffuse splenic microcalcifications, prompting further diagnostic evaluation that ultimately led to the diagnosis of SLE. To contextualize this finding, we performed a systematic case-based literature review and identified 29 previously reported cases, resulting in a total of 30 cases including our own. Across reported cases, no distinct serological or clinical phenotype could be identified. However, a characteristic imaging pattern emerged, predominantly consisting of diffuse, small, round-to-rod-shaped splenic calcifications. When longitudinal data were available, calcifications were usually stable, although progression was reported in association with disease flares, sometimes evolving to functional autosplenectomy. This case illustrates that splenic calcifications may represent an early or presenting manifestation of SLE and that an incidental detection should prompt consideration of autoimmune disease in the broad differential diagnosis. By synthesizing previously scattered reports, this review provides an updated overview to support clinical interpretation and awareness.
25 May 2026
Read appraisal →Hepatology communications
Midodrine versus placebo in patients with acute-on-chronic liver failure with ascites-A randomized trial (MIDAS trial)
BACKGROUND: Ascites is common in patients with acute-on-chronic liver failure (ACLF) and can complicate the course of ACLF due to circulatory dysfunction and hemodynamic compromise. Oral midodrine has been variably reported to improve hemodynamics and reduce complications of ascites in patients with decompensated cirrhosis, but its role in patients with high MELD ACLF remains unknown, which we aimed to assess. METHODS: In this single-center, double-blind, randomized trial, patients with ACLF were assigned 1:1 to receive midodrine (5-7.5 mg tid) or a placebo for 30 days, alongside standard care. Transplant-free survival (TFS) at 1 month was the primary outcome, while secondary outcomes included TFS at 3 months, the proportion of patients achieving ascites control, changes in mean arterial pressure (MAP) and plasma renin activity at 1 month, the incidence of cirrhosis complications, and diuretic-related complications. RESULTS: One hundred thirty patients with ACLF were enrolled. Midodrine use was not associated with improvement in TFS at 1 (HR, 0.99 [95% CI: 0.37-2.65]) and 3 months (HR, 0.93 [95% CI: 0.48-1.8]). Ascites control at day 30 (placebo: 9.2% [95% CI: 3.5-19] vs. midodrine: 20% [95% CI: 12.3-33.5]; p=0.08) and 90 (placebo: 44.6% [95% CI: 32.2-57.5] vs. midodrine: 53.8% [95% CI: 41-66.3]; p=0.29) was comparable. Midodrine increased the MAP (1.9 vs. 6.9 mm Hg; p=0.003) with an insignificant reduction in plasma renin activity levels (delta change: 0.22±1.6 vs. -1.6±2.2; p=0.09). Cirrhosis-related and diuretic-related complications were similar in both groups. CONCLUSIONS: Midodrine increases MAP in patients with ACLF and high MELD scores without TFS benefit and does not reduce the rate of ascites-related complications.
25 May 2026
Read appraisal →Journal of medical systems
Machine Learning-Predicted Risk Trajectories for Incident Chronic Kidney Disease and Associations with Post-CKD Outcomes
Chronic kidney disease (CKD) is a progressive condition where risk accumulates before clinical onset. However, strategies for evaluating CKD risk remain limited, and the trajectories of risk over time are poorly understood. We enrolled 51,156 individuals without CKD in the University of California health system between 2012 and 2024. A debiased XGBoost model was developed to predict CKD risk, and the predicted probabilities from this model at each visit were used to derive risk trajectories through latent class growth mixture modeling. The model achieved a time-dependent area under the curve of 0.95 (95% confidence interval (CI), 0.94-0.96), a C-index of 0.93 (0.92-0.94), and a Brier score of 0.027 (0.026-0.028) for predicting 5-year CKD occurrence. Similar predictive performance was observed for 1 to 4 years. Longitudinal patterns of predicted CKD risk revealed three distinct trajectories: gradual (75.9%), progressive (10.1%), and rapid increase (14.0%). Compared to the gradual trajectory, the progressive trajectory was associated with a higher risk of estimated glomerular filtration rate (eGFR) decline of ≥ 25% (adjusted hazard ratio (HR) 1.31; 95% CI, 1.06-1.61) and ≥ 50% (HR 1.59; 95% CI, 1.09-2.31) following CKD onset. The progressive and rapid trajectory was linked to an increased risk of cardiovascular events (HR 1.84; 95% CI 1.18-2.91) and all-cause mortality (HR 2.36; 95% CI 1.49-3.73). Our machine learning model demonstrated strong predictive performance for incident CKD risk and identified three distinct risk trajectories that were associated with different post-CKD outcomes, highlighting the importance of early risk monitoring.
25 May 2026
Read appraisal →Lasers in medical science
Acute effect of photobiomodulation therapy in quadriceps strength, fatigue and pain of patients with chronic kidney failure: a randomized, double-blind, placebo controlled crossover clinical trial
Patients with chronic kidney failure (CKF) present changes in physical capacity and low exercise tolerance. Photobiomodulation therapy (PBMT) has shown an ergogenic effect on exercise in studies with different populations and may be an adjuvant treatment in rehabilitation programs for CKF patients. This study aimed to evaluate the acute effects of different doses of PBMT on quadriceps strength, fatigue and muscle pain in CKF patients. This study is a randomized, placebo-controlled, double-blind, crossover clinical trial. Adult patients with CKF received four PBMT applications with different energy doses (30J, 60J, 90J, or placebo), administered in a random order. A one-week interval was maintained between each dose, and an 830nm laser was applied to six points of the quadriceps muscle. Immediately after PBMT, maximal isometric quadriceps muscle strength was assessed by dynamometry. Before the intervention and after the assessment of muscle strength, muscle fatigue (Borg rating of perceived exertion scale and blood lactate) and pain perception in the lower limbs (visual analogue scale) were measured. Fifteen patients were randomized and fourteen completed the study. There was no significant difference between the doses tested for maximal isometric muscle strength in the right (p=0.053) and left (p=0.509) quadriceps. The perception of fatigue assessed by the modified Borg scale was not altered (p=0.703) nor were blood lactate levels, regardless of the PBMT dose and measurement time (t0: p=0.126; t3: p=0.667; t6: p=0.700). There was no change in pain perception after quadriceps irradiation for any of the PBMT doses tested (p=0.566). A single application of PBMT with a dose of 30J, 60J, or 90J did not alter maximal isometric quadriceps muscle strength, fatigue, or muscle pain perception in the lower limbs of CKF patients on HD.
24 May 2026
Read appraisal →Open heart
Predictors of high-grade atrioventricular block recovery in Takotsubo cardiomyopathy: a systematic review of case reports
BACKGROUND: Atrioventricular block (AVB) in Takotsubo cardiomyopathy (TCM) is a rarely reported complication. Due to its low incidence and lack of randomised trials, there remain significant gaps in the evidence regarding its underlying mechanisms, the probability of conduction recovery and the optimal timing for permanent pacemaker implantation. METHODS: A systematic review was conducted on published case reports on TCM associated with high-grade AVB, diagnosed simultaneously or within the same hospital admission. Cases with low-grade AVB, sole sinus node disease or TCM induced by pacemaker implantation were excluded. RESULTS: A total of 50 cases were included in the final analysis; stratified into two groups based on AVB recovery. Fifteen patients (30%) developed complete AVB recovery. Compared with persistent AVB, those who experienced recovery were younger (median (IQR): 66 (61-73) vs 77 (65-82), p=0.02), more frequently reported identifiable emotional or physical stressors (93% vs 49%, p=0.004) and demonstrated earlier recovery of left ventricular ejection fraction (LVEF) within 1 week (60% vs 24%, p=0.02). No significant differences were observed in terms of comorbidities (hypertension in 27% vs 47%, p=0.22), presenting symptoms (chest pain in 40% vs 14%, syncope or presyncope in 27% vs 46%, p=0.22), ST elevation (27% vs 14%, p=0.28) or regional wall motion abnormalities (apical akinesia in 47% vs 46%, p=0.93). On multivariate analysis, the presence of an identifiable stressor was an independent predictor of AVB recovery (HR 8.27; 95% CI 1.07 to 63.73, p=0.04). CONCLUSION: In patients with TCM and high-grade AVB, the absence of a clear stressor highlights the possibility of baseline conduction disorder, with a higher risk of persistent AVB. Earlier LVEF recovery and younger age may help to predict AVB recovery and guide patient selection for PPM implantation. PROSPERO REGISTRATION NUMBER: CRD420251173831.
24 May 2026
Read appraisal →The AAPS journal
A Mechanistic Framework Integrating Renal QSP-PK-PD and Machine Learning for Baseline-Informed Stratification of Diuretic Resistance
Diuretic resistance represents a major source of heterogeneity in loop diuretic response and remains a key barrier to effective decongestion in heart failure. A key clinical challenge is the early identification of patients at high risk of an inadequate response to standard-dose furosemide in order to inform timely treatment intensification or alternative decongestive strategies. However, current approaches remain reactive and rely on post-treatment response, limiting prospective risk stratification and treatment decision-making. To address this problem, we integrated a mechanistic renal quantitative systems pharmacology (QSP) model with furosemide pharmacokinetics and pharmacodynamics to enable baseline-informed risk stratification of diuretic resistance. The model was calibrated using published clinical pharmacokinetic and renal response data and applied to generate a physiologically constrained virtual patient population capturing heterogeneity in renal function, tubular sodium handling, and neurohormonal activation. Machine learning methods were incorporated as complementary analytical tools to identify and validate baseline physiological determinants that define risk categories of diuretic response within the mechanistic simulation framework. Model-based analyses indicated that diuretic resistance arises from the combined effects of reduced filtration capacity, enhanced tubular sodium avidity, diminished pharmacodynamic sensitivity and sustained neurohormonal activation. Across analytical approaches, baseline fractional excretion of sodium and glomerular filtration rate emerged as integrative biomarkers that stratify patients into distinct risk categories of diuretic response, reflecting a mechanism-informed reduction of underlying physiological variability. These findings provide a mechanistically grounded framework for baseline-informed risk stratification and may inform earlier identification of patients at risk of inadequate response, supporting model-informed evaluation of treatment intensification or alternative decongestive strategies.
24 May 2026
Read appraisal →Medicine
Nomogram and machine learning models for predicting the risk of delirium in ICU patients with NSTEMI
Delirium is a frequent and clinically consequential complication among patients admitted to the intensive care unit (ICU). Early risk stratification in patients with non-ST-segment elevation myocardial infarction (NSTEMI) remains challenging. We aimed to develop and validate prediction models for ICU delirium in NSTEMI patients using Boruta-based feature selection and machine learning (ML) approaches, and to compare ML performance with a nomogram model. We retrospectively identified adult ICU patients (≥ 18 years) diagnosed with NSTEMI in the Medical Information Mart for Intensive Care IV database, and included only those with no delirium within the first 24 hours of admission and no prior history of delirium. A total of 392 patients were included (mean age 72.2 ± 12.6 years; 64% male) and categorized into a delirium group (n = 201) and a non-delirium group (n = 191). Clinical characteristics and laboratory indices were extracted. Participants were randomly split into a training cohort (70%) and a validation cohort (30%). The Boruta algorithm was applied in the training cohort for feature selection and identification of relevant predictors. A nomogram was constructed using Boruta-selected variables. In parallel, the same features were incorporated into ML models; model discrimination and clinical utility were evaluated using receiver operating characteristic curves, calibration curves, and decision curve analysis. SHapley Additive exPlanations were used to quantify and visualize feature contributions for the best-performing model. Boruta identified 9 key variables: systolic blood pressure, serum calcium, pulse oximetry, serum sodium, creatinine, serum chloride, anion gap, blood urea nitrogen, and body temperature. In the validation cohort, CatBoost achieved the best discrimination among ML models, with an area under the receiver operating characteristic curve of 0.743 (95% CI = 0.653-0.833). The nomogram demonstrated lower discrimination (validation area under the curve = 0.61). SHapley Additive exPlanations analyses indicated that the Boruta-selected variables contributed differentially to delirium prediction, supporting model interpretability. In ICU patients with NSTEMI, a Boruta-informed CatBoost model showed moderate predictive performance and outperformed a nomogram constructed from the same predictors. This interpretable ML approach may facilitate early identification of patients at high risk of delirium and support timely preventive strategies.
24 May 2026
Read appraisal →Medicine
Efficacy of traditional Chinese medicine in treating severe pneumonia: A meta-analysis and systematic review
BACKGROUND: Severe pneumonia (SP) is a critical respiratory disease characterized by its severity and high mortality rate. Traditional Chinese medicine (TCM) has gradually been used as an adjunctive therapy in clinical treatment of SP, yet its efficacy and safety lack systematic evidence. This study aims to analyze, evaluate, and compare current research evidence on TCM adjunctive therapy for SP, providing a basis for clinical treatment of this condition. METHODS: A systematic search was conducted on both English and Chinese online databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP) to identify relevant papers published from inception to November 2023. High-quality randomized controlled tests (RCTs) were selected for analysis. Outcome measures related to SP were extracted from the literature. Statistical analysis was performed using RevMan 5.3 (Cochrane) software to assess heterogeneity among included studies, calculate mean differences, odds ratios, and their 95% confidence intervals, and detect publication bias. RESULTS: A total of 34 RCTs met the inclusion criteria. Comparative analysis revealed that integrating TCM with conventional treatment significantly improves the overall clinical effective rate(P < .05). Specifically, it markedly alleviates TCM symptoms (P < .05). Additionally, TCM adjunctive therapy reduces levels of inflammatory markers including white blood cells, C-reactive protein (P < .05), and decreases Clinical Pulmonary Infection Score and Acute Physiology and Chronic Health Evaluation II scores compared to conventional treatment alone (P < .05). Compared to conventional treatment alone, TCM adjunctive therapy also enhances arterial blood gas indices (PaO2) (P < .05) and pulmonary function (forced expiratory volume in 1 second) (P < .05). Complication rates and mortality are lower in the TCM adjunctive therapy group(P < .05). Moreover, TCM treatment significantly boosts immune function (cluster of differentiation 4+ T lymphocyte) (P < .05). CONCLUSION: Integrating TCM with conventional treatment shows advantages in the efficacy of SP treatment, clinical symptoms management, inflammatory markers, and severity grading. Compared to conventional treatment alone, TCM adjunctive therapy improves immune function, pulmonary function, complication rates. However, future research should focus on large-scale, high-quality RCTs to further validate the effectiveness and safety of TCM adjunctive therapy for SP.
24 May 2026
Read appraisal →Studies in health technology and informatics
Evaluating the Potential of Machine Learning for Discharge Management on Routine Health Insurance Data
Machine learning (ML) has great potential in healthcare, especially with large structured data. Routine health insurance claims (HIC) data are a valuable resource, comprising standardized longitudinal patient information. However, to fully leverage ML in HIC, challenges such as large data volumes, variability, data gaps, sparsity, and high dimensionality must be addressed. To overcome these barriers, our publicly funded KI-THRUST project accessed a large-scale dataset of 2 million anonymized routine insurance records from four German providers. Subsequently, a thorough performance evaluation of various linear and nonlinear ML models (logistic regression, AdaBoost, Random Forest, Neural Network) for their potential to predict clinical outcomes such as mortality and unplanned readmissions was conducted, and the results were interpreted using explainable AI methods (Integrated Gradients, Shapley values, LIME). In particular, we investigated the predictive value of feature sets comprising base demographics (M1) and ICD-10 codes for previous conditions and procedures (M2, M3). While AdaBoost achieved the best overall performance, the less complex logistic regression performed comparably. The additional diagnostic and procedural information in M2 led to a significant performance gain, whereas additional time-related information did not. Overall, our results show the potential of large-scale HIC data when combined with ML methods and XAI. Ultimately, paving the way for future applications like discharge management systems and other healthcare areas.
24 May 2026
Read appraisal →Studies in health technology and informatics
Assessing AI-Based Decision Support in Early Sepsis and AKI Recognition
Sepsis and acute kidney injury (AKI) remain among the most critical conditions in acute care, associated with high morbidity and mortality. Early risk recognition is essential but often hampered by nonspecific symptoms. Recent studies have demonstrated that AI- and ML-based Clinical Decision Support Systems (CDSS) can enhance the early detection of sepsis and AKI and support clinical decision-making [1-3]. In May 2025, the University Hospital Augsburg (UKA) integrated an externally developed AI-based CDSS to provide real-time risk predictions for sepsis and AKI. This study evaluates the effectiveness of the system in routine clinical practice using retrospective data from periods before and after its implementation. Primary endpoints include diagnostic accuracy. The results will indicate whether the CDSS contributes to improved early risk recognition and enhanced patient safety in a real-world hospital environment.
24 May 2026
Read appraisal →PloS one
A qualitative study to inform the design and implementation of AI-driven diagnosis: Challenges, barriers, and clinical insights of physicians
INTRODUCTION: Acute febrile illnesses are significant clinical challenge in tropical regions due to overlapping symptomatology among infections such as dengue, scrub typhus, and leptospirosis. This diagnostic dilemma leads to delays in appropriate treatment and negatively impacted patient outcome due to limited diagnostic tool availability. Recent advancement in artificial intelligence (AI) application in healthcare help in developing diagnostic aiding tool in such clinical dilemma. AIMS: Study aimed to explore physicians' perspectives on diagnostic challenges of tropical Acute-febrile-illnesses and assess perceived utility of AI as a supportive tool in clinical decision-making. METHODS: A qualitative interview was conducted using validated semi-structured interview guide using literature and expert opinion and validated by IPR method. To understand the physicians perspective on management infectious diseases in critical care, interview guide administered among ten physicians with 10-30 years of experience across different centres of India. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed using ATLAS.ti software. RESULTS: Four major themes emerged: clinical experience and practice, diagnostic-challenges, diagnostic-parameters and decision-making, and AI integration in clinical-practice. However, no statistical test can be performed since study mainly focused to understand perception of physicians with respect to managing illness and hence prevalence cannot be determined. Diseases such as dengue, scrub typhus, and leptospirosis were reported as most prevalent, particularly during monsoon seasons. Key diagnostic challenges included overlapping symptoms, diagnostic delays, limited sensitivity/specificity of available tests, and cost constraints. Physicians primarily relied on clinical judgment and laboratory findings, despite the limitations. Most of the participants expressed positive attitudes toward the potential of AI as supportive tool, citing its ability to enhance diagnostic accuracy and streamline clinical workflow with proper validation. CONCLUSIONS: Growing in clinical dilemma AI has significant role in diagnosis of tropical fever with integration of the clinical data & physician perspective can successfully able to incorporate in clinical application.
23 May 2026
Read appraisal →Lupus science & medicine
Can disease activity and treatment responses be captured by a core set of domains in SLE clinical trials? An analysis of phase III belimumab trial data.
OBJECTIVE: Outcome measures used in SLE randomised controlled trials (RCTs) have impeded trial success and drug approval. In an ongoing global project to develop a novel outcome measure for SLE RCTs, a 'core set' of domains with which to determine treatment response was chosen via consensus. We investigated the impact of restricting disease activity assessment to this core set on responder classification in RCTs. METHODS: Using pooled baseline and week 52 data from two phase III SLE RCTs (Belimumab in Subjects with Systemic Lupus Erythematosus (BLISS)-52, NCT00424476; BLISS-76, NCT00410384), we divided items from the British Isles Lupus Assessment Group (BILAG) disease activity index into core and non-core sets. The core set included 30 of 86 BILAG items across five domains: mucocutaneous (rash, alopecia, mucosal ulcers), haematological (thrombocytopenia, haemolytic anaemia), arthritis, serositis and nephritis. We analysed baseline disease activity and treatment response at week 52. RESULTS: We analysed 1526 patients. At baseline, the core set captured the majority of disease activity captured using the full BILAG (1426/1526 (93.5%) of patients). Cutaneous vasculitis, non-haemolytic anaemia, leucopenia, dyspnoea and fatigue were the most common non-core set manifestations present. At week 52, about 1278/1426 (89.5%) patients demonstrated concordant treatment responses measured with the core set only versus all BILAG items. Discordance was again driven by cutaneous vasculitis, non-haemolytic anaemia, leucopenia and fatigue. CONCLUSIONS: Limiting the classification of treatment response to a core set of domains has the potential to simplify SLE RCT endpoints without a significant negative impact on patient inclusion or responder classification.
23 May 2026
Read appraisal →Journal of medical economics
A systematic review of acute and long-term outcomes in patients with non-transvenous implantable cardioverter-defibrillators
BACKGROUND: Non-transvenous implantable cardioverter-defibrillator (ICD) systems have been developed to address limitations of transvenous ICDs. This systematic literature review aimed to summarize periprocedural and long-term outcomes of non-transvenous ICD systems in adult patients with guideline-based indications for ICD therapy. METHODS: A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420261327618). Eligible studies enrolled adults (≥18 years) receiving a non-transvenous ICD for primary or secondary prevention. Outcomes included periprocedural and long-term endpoints and were summarized descriptively. The Newcastle-Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) checklist for case series were used to assess risk of bias. RESULTS: Twenty-five publications representing 18 unique studies and 4,633 patients were included. Most studies were single-arm (n = 13), while 2 were randomized controlled trials and 3 were nonrandomized comparative studies. Procedural success ranged from 81%-100%, with rates ≥94% of patients in all but one early-phase study; defibrillation threshold testing success ranged from 89%-100% (≥96% in studies with n ≥ 100). Periprocedural complications were reported in 0%-5% of patients in most studies. Long-term complication rates ranged from 0%-8% at 0.5-1.5 years of follow-up and 1%-14% beyond 1.5 years. All-cause mortality ranged from 1%-5% within 6 months and increased to 16%-26% at 4-8 years. Clinical defibrillation success was consistently high (95%-100%). Incidence of inappropriate shock generally ranged from 7%-13% at 1 year and 2%-18% at later timepoints. Appropriate shock incidence ranged from 2% to 9% within 1 year and increased with longer follow-up. Risk of bias was predominantly moderate, with limited variation using NOS and greater discrimination observed with JBI. CONCLUSIONS: Non-transvenous ICD systems demonstrate favorable safety and effectiveness profiles, with high procedural and defibrillation success and acceptable complication and inappropriate shock rates across studies. Overall, the available evidence supports their use in appropriately selected adult patients with standard ICD indications. Non-transvenous implantable cardioverter-defibrillators (ICDs) are devices placed outside the blood vessels and heart, designed to treat life-threatening heart rhythm problems while avoiding complications related to transvenous ICDs.This review summarized results from 25 published studies including 4,600 patients to understand how safe and effective these devices are.Across studies, non-transvenous ICDs showed high implant procedure success, effective therapy delivery, and had generally low rates of short- and long-term complications.
23 May 2026
Read appraisal →Current obesity reports
Burden of Intrapancreatic Fat Deposition in Type 2 Diabetes and the Role of Obesity: A Systematic Review and Meta-Analysis
BACKGROUND: Growing evidence supports a role for high intrapancreatic fat deposition (IPFD) in the pathogenesis of type 2 diabetes mellitus (T2DM); however, the magnitude of this association and the extent to which it is influenced by body mass index (BMI), liver fat content (LFC), and age remain uncertain. OBJECTIVE: To quantitatively evaluate IPFD measured by magnetic resonance imaging (MRI) in individuals with T2DM and to investigate study-level factors contributing to between-study variability. METHODS: We systematically searched PubMed and Embase for observational studies comparing MRI-measured IPFD in individuals with T2DM versus non-diabetic controls, excluding studies in which IPFD quantification was performed using AI-based models. Pooled standardized mean differences (SMDs) were estimated using a restricted maximum likelihood approach with Hartung-Knapp adjustment. Heterogeneity was explored through subgroup, meta-regression, and sensitivity analyses. RESULTS: Thirty studies (n=3,980) were included. Individuals with T2DM had significantly higher IPFD than non-diabetic controls (SMD 1.13, 95% CI 0.74 to 1.51), with no significant differences when stratified by pancreatic region, MRI technique, geographic region, sample size, and risk of bias. In multivariable models, BMI remained the only consistent moderating covariate, and the excess IPFD in T2DM persisted after adjusting for BMI, LFC, and age (intercept=0.797, p=0.010, false discovery rate-adjusted p=0.018). Advanced heterogeneity exploration identified no structural outliers, and the pooled effect size remained consistent across multiple sensitivity analyses. CONCLUSION: T2DM is associated with substantially higher MRI-quantified IPFD, independent of study-level differences in BMI, LFC, and age. Although causality cannot be inferred, these findings support the hypothesis that IPFD may be involved in the underlying mechanism of T2DM. They also suggest that high IPFD could represent a metabolic hallmark, with potential implications for risk stratification and therapeutic targeting.
22 May 2026
Read appraisal →Open heart
Prognostic value of CT-derived fractional flow reserve for major adverse cardiovascular events in patients with suspected or known coronary artery disease: a systematic review and meta-analysis
BACKGROUND: Fractional flow reserve derived from CT (FFR-CT) enables non-invasive functional assessment of coronary stenoses in patients with suspected or known coronary artery disease, but evidence regarding its prognostic value remains fragmented. We conducted a systematic review and meta-analysis to quantify the association between abnormal FFR-CT and major adverse cardiovascular events (MACE), updating the 2022 meta-analysis by Nørgaard et al METHODS: We searched PubMed, Embase and Scopus through December 2025 for studies comparing outcomes in patients with suspected or known coronary artery disease with FFR-CT ≤0.80 versus >0.80 (PROSPERO: CRD420261276897). Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was performed. Subgroup analyses examined FFR-CT technology, geography and follow-up duration. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. RESULTS: Twenty-two studies with 20 067 patients were included, representing a fourfold increase from the prior meta-analysis. Follow-up ranged from 12 to 120 months. Patients with FFR-CT ≤0.80 had significantly higher MACE risk (HR 3.94; 95% CI 2.92 to 5.31; p<0.0001) with substantial heterogeneity (I²=79.9%). However, restricting to hard endpoints (death/myocardial infarction; k=6) yielded HR 3.28 (95% CI 2.25 to 4.79) with zero heterogeneity (I²=0%). No significant differences emerged across FFR-CT technologies (p=0.812), including HeartFlow, machine learning and deep learning algorithms. Trim-and-fill analysis suggested possible publication bias, with adjusted HR 2.35. GRADE certainty was moderate. CONCLUSIONS: Abnormal FFR-CT is associated with nearly fourfold increased risk of MACE in patients with suspected or known coronary artery disease, with consistent prognostic value across technologies. The absence of heterogeneity for hard endpoints supports FFR-CT as a reliable prognostic marker. These findings address the evidence gap identified by current guidelines regarding FFR-CT prognostic utility. PROSPERO REGISTRATION NUMBER: CRD420261276897. CLINICAL TRIAL NUMBER: Not applicable (as this is a Systematic Review and Meta-Analysis and not a Clinical Trial).
22 May 2026
Read appraisal →Postgraduate medical journal
Efficacy of tirzepatide in glycemic control and weight management in adults with type 2 diabetes: a systematic review and meta-analysis of real-world studies
A systematic review and meta-analysis of real-world studies on tirzepatide is essential to strengthen evidence of its effectiveness in improving glycated hemoglobin (HbA1c) and body weight in patients with type 2 diabetes. 13 real-world studies (N = 89 296; duration 3-18 months) with moderate to serious bias revealed a mean HbA1c reduction of 0.91% (95% confidence interval [CI]: -1.04 to -0.79), weight loss of 9.7 kg (95% CI: -14.05 to -5.35), and body mass index decrease of 2.09 kg/m2 (95% CI: -3.27 to -0.92). Overall, 64% of tirzepatide users reached HbA1c <7%. Furthermore, tirzepatide lowered HbA1c (mean difference [MD] -0.38%; 95% CI: -0.44 to -0.33) and body weight (MD -6.27 kg; 95% CI: -9.22 to -0.33) more than the control. 47%, 23%, 9%, and 4% of tirzepatide users lost ≥5%, ≥10%, ≥15%, and ≥ 20% of their baseline weight, respectively. Tirzepatide's effects on HbA1c and weight in observational studies support clinical trial findings.
22 May 2026
Read appraisal →Rheumatology international
Targeting type I interferon in lupus panniculitis: a case-based systematic literature review
Lupus panniculitis (LEP) is a rare form of cutaneous lupus (CLE) characterised by progressive, often disfiguring course and poor response to treatment. Type I interferon inhibition through anifrolumab (ANF) is effective in CLE but limited data are available for its use in LEP. To address this issue, we screened patients with CLE and/or systemic lupus erythematosus (SLE) for biopsy-proven diagnoses of LEP and treatment with ANF. Besides demographics, general clinical features, concomitant treatments before and after ANF and safety signals, we measured disease activity and damage with the SLE disease activity index 2000 (SLEDAI-2 K), the CLE Disease Area and Severity Index activity (CLASI-A) and damage scores and the SLE International collaborating clinics/American College of Rheumatology damage index. The same data were retrieved, when available, from existing cases extracted from systematic literature review. Sixteen cases were identified, including 3/421 newly described patients, with two receiving ANF as first-line immunosuppressant and one as an early treatment devoid of oral corticosteroids. All patients had a good response to treatment and most of them could taper or discontinue corticosteroids. CLASI-A scores were markedly reduced after ANF treatment [11.5 (7-29)] to 0 (0-2); p = 0.005]. The time to response was within five months in most cases. No significant adverse events were reported. Taken together, our data suggest that ANF might be effective in LEP and used as a first-line treatment to prevent LEP-related damage accrual.
21 May 2026
Read appraisal →European heart journal. Acute cardiovascular care
Guided de-escalation of antiplatelet treatment in patients at high atherothrombotic risk presenting with acute coronary syndrome: a post hoc analysis of the TROPICAL-ACS trial
AIMS: Platelet function testing (PFT)-guided de-escalation of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) has been shown to reduce bleeding risk without increasing ischaemic events. Patients with high atherothrombotic risk (ATR) remain a challenging subgroup for such strategies. This study evaluated the safety and efficacy of early PFT-guided DAPT de-escalation according to ATR status. METHODS AND RESULTS: In the TROPICAL-ACS trial, 2610 ACS patients were randomized to standard 12-month prasugrel therapy or PFT-guided DAPT de-escalation. For this post hoc analysis, patients were stratified by ATR. High ATR was defined as age ≥ 65 years, polyvascular disease, or ≥2 risk factors (diabetes, smoking, or renal dysfunction). Hazard ratios (HRs) for clinical endpoints were derived using multistate Cox regression. High-ATR patients (n = 990) had a higher incidence of the primary net clinical benefit endpoint-composite of cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium 2-5 bleeding-compared with low-ATR patients (n = 1620) (11.0% vs. 6.7%; HR 1.67, 95% confidence interval 1.28-2.18; P < 0.001). Platelet function testing-guided de-escalation showed no significant interaction by ATR status for the primary endpoint [high ATR: 10.5% vs. 11.5%, HR 0.90 (0.61-1.32), P = 0.586; low ATR: 5.6% vs. 7.7%, HR 0.71 (0.48-1.04), P = 0.082; Pinteraction = 0.394] or ischaemic events [high ATR: 3.7% vs. 4.4%, HR 0.83 (0.44-1.56); low ATR: 1.8% vs. 2.6%, HR 0.68 (0.35-1.34); Pinteraction = 0.666]. CONCLUSION: Early PFT-guided de-escalation from prasugrel to clopidogrel was safe across atherothrombotic risk categories, supporting individualized DAPT optimization in ACS patients with both low and high ischaemic risk.
21 May 2026
Read appraisal →BMJ open
Evaluation of a deep learning model applied to chest X-rays of patients with suspected pneumonia presenting to the emergency department designed to predict admission risk: a retrospective training and prospective non-intervention validation.
OBJECTIVES: To develop, train and test a deep learning model Image-based PROgnostication applied to Chest X Rays (IPRO-X) tool that predicts the inpatient (IP) admission risk in patients with suspected pneumonia presenting to the emergency department (ED). DESIGN: The study consists of a retrospective (training) and prospective non-interventional shadow deployment (validation) of a deep learning model. SETTING: Three-hospital tertiary care system with two EDs. PARTICIPANTS: Consecutive adult patients (18 years old or older) who presented to the ED from December 2022 to February 2023 with a chief clinical complaint potentially related to pneumonia were reviewed for eligibility (n=5567), with a final number of 3677 included in the validation study. PRIMARY AND SECONDARY OUTCOME MEASURES: IPRO-X was developed using standard two-dimensional convolutional neural network InceptionNet architecture and processes chest radiographs (CXRs) acquired at admission generating a continuous value from 0 (IP-negative) to 1 (IP-positive). We examined IPRO-X's ability to predict IP admission using accuracy, area under the curve (AUC), receiver operating characteristic, sensitivity, specificity, positive predictive value and negative predictive value. IPRO-X scores were compared against observed outcomes (admission and discharge) to determine clinical utility in an ED setting. Four thresholds were defined from the retrospective phase: Youden optimal, highest specificity and thresholds equivalent to 30-day mortality rates of Pneumonia Severity Index (PSI) Risk class IV and Confusion, Respiratory Rate, Blood Pressure and Age 65 or older Score (CRB-65) scores 1 and 2. Performance was also analysed per group of chief complaints. RESULTS: In the validation set, 3677 patients (1777 (48%) female, median age 56 years (min 18, max 99)) were included. IPRO-X predicted IP admissions with an AUC of 0.795, and in the pneumonia-specific chief complaints, AUC increased to 0.828, whereas in non-related pneumonia chief complaints, the AUC decreased to 0.755. IPRO-X score was significantly higher in admitted patients compared with discharged patients (p<0.001). The accuracy of IPRO-X when using the PSI-anchored threshold was 0.751 and with the CRB-anchored threshold was 0.729, with a specificity of 0.803 and 0.968, respectively. CONCLUSIONS: IPRO-X applied to CXR of patients with signs and symptoms commonly related to pneumonia in the ED can accurately predict IP admission.
21 May 2026
Read appraisal →Journal of the American Heart Association
Residual Angina Following Complete Revascularization in the ISCHEMIA Trial: Frequency, Clinical Characteristics, Health Status, and Cardiovascular Outcomes
BACKGROUND: The frequency of residual angina and its impact on health status and death following anatomic complete revascularization in symptomatic patients with chronic coronary disease are unknown. METHODS: Data were analyzed from ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial participants randomized to invasive management with baseline angina (Seattle Angina Questionnaire Angina Frequency score <100), no prior coronary artery bypass graft surgery, and anatomic complete revascularization within 90 days of randomization. The primary outcome was frequency of residual angina after revascularization, defined as a Seattle Angina Questionnaire Angina Frequency score <100 within 6 months of randomization. Secondary outcomes included 6-month health status and medication use and 5-year all-cause and cardiovascular death. RESULTS: Among 2588 participants randomized to invasive management, 1442 (56%) had baseline angina and no prior coronary artery bypass graft surgery; 1034 underwent revascularization within 90 days, and 436 achieved anatomic complete revascularization. Of these, 184 (42.2%) had residual angina within 6 months. Baseline characteristics were similar between those with and without residual angina. Percutaneous coronary intervention was more common than coronary artery bypass graft surgery in those with residual angina (88% versus 80%, P=0.03). At 6 months, residual angina participants reported lower quality of life (Seattle Angina Questionnaire Quality of Life: 70±20 versus 83±20, P<0.001), greater physical limitation (Seattle Angina Questionnaire Physical Limitation: 84±20 versus 95±11, P<0.001), more dyspnea (Rose Dyspnea Scale score: 1±1.3 versus 0.4±0.8, P<0.001), and more antianginal medication use (P=0.006). Five-year all-cause and cardiovascular death did not differ significantly between groups. CONCLUSIONS: Residual angina is common (>40%) following anatomic complete revascularization for chronic coronary disease and is associated with reduced quality of life and greater antianginal medication use but no increase in death. REGISTRATION: Unique Identifier: NCT01471522.
20 May 2026
Read appraisal →Journal of the American Heart Association
Incremental Prognostic Power of Coronary Flow Reserve and Artificial Intelligence-Enabled ECG-Derived Filling Pressure in Angina With Nonobstructive Coronary Arteries
BACKGROUND: Coronary flow reserve reflects microvascular function, whereas filling pressure indicates myocardial hemodynamic burden. In angina with nonobstructive coronary arteries, abnormalities in either could contribute to a supply-demand mismatch; however, their combined prognostic significance remains unclear. METHODS: Patients with angina with nonobstructive coronary arteries who underwent invasive coronary reactivity tests were studied retrospectively. Coronary microvascular dysfunction (CMD) was coronary flow reserve <2.5. An artificial intelligence-enabled ECG marker of elevated filling pressure (AIEFP) was applied as a scalable prognostic marker of myocardial hemodynamic stress. Associations with major adverse cardiovascular events were evaluated using Cox regression and propensity score overlap weighting. RESULTS: Among 1957 patients with angina with nonobstructive coronary arteries (median age, 51.8 years; 67.2% women), CMD+ was identified in 26.4% and AIEFP+ in 6.6%. Over 8 years, 204 patients (10.4%) experienced major adverse cardiovascular events. In nested models, both CMD (hazard ratio [HR]=1.42 [95% CI=1.13-1.78]; P=0.002) and AIEFP (HR=2.28 [95% CI=1.67-3.11]; P<0.001) remained associated with major adverse cardiovascular events after adjustment. Adding AIEFP to the base model improved model fitness (Δχ2=23.65, P<0.001; ΔAkaike Information Criterion=-21.7) and modestly improved discrimination (ΔHarrell concordance index=0.02, P=0.02). In a 4-group model, adjusted risks increased in a graded manner. Overlap-weighted analysis after covariate balance demonstrated distinct temporal risk trajectories: CMD+/AIEFP+ had the highest 1-year risk (12.7%), and AIEFP+ had the highest cumulative 8-year risk (57% in CMD- and 51.8% in CMD+). CONCLUSIONS: CMD and AIEFP provide complementary prognostic information, with AIEFP remaining significantly associated with outcomes after multivariable adjustment. A dual-axis framework integrating myocardial hemodynamic stress (AIEFP) and microvascular function (coronary flow reserve) may enhance risk stratification and enable identification of clinically distinct angina with nonobstructive coronary arteries phenotypes with divergent trajectories.
20 May 2026
Read appraisal →JAMA
Tucidinostat Plus R-CHOP vs R-CHOP in MYC/BCL2 Double-Expressor Diffuse Large B-Cell Lymphoma: A Randomized Clinical Trial
IMPORTANCE: Epigenetic dysregulation is associated with the pathogenesis and progression of diffuse large B-cell lymphoma (DLBCL). MYC/BCL2 double-expressor lymphoma (DEL), a distinct population of DLBCL defined by MYC and BCL2 coexpression, refers to poor prognosis after standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy. Tucidinostat (or chidamide), an oral, selective histone deacetylase inhibitor, has shown promising activity in DEL. OBJECTIVE: To evaluate efficacy and safety of tucidinostat plus R-CHOP vs R-CHOP alone as first-line treatment for patients with DEL. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, placebo-controlled phase 3 trial enrolled patients from May 21, 2020, through July 25, 2022, with follow-up to June 26, 2025. The trial was conducted at 40 study centers in China; a total of 423 eligible patients were enrolled. INTERVENTIONS: Patients were randomly assigned in a 1:1 ratio to receive oral tucidinostat (20 mg on days 1, 4, 8, and 11 of each 21-day cycle) or matching placebo, plus 6 cycles of R-CHOP. Patients with a complete response after combination therapy received either tucidinostat or placebo maintenance up to 24 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was event-free survival. Secondary end points included complete response rate, progression-free survival, disease-free survival, overall survival, and tolerability. RESULTS: Among 423 patients randomized (median age, 63 years; 47.5% male), the median follow-up duration from randomization was 41.3 months. The tucidinostat group demonstrated a 28% lower risk of disease progression, relapse after complete response, death, or initiation of new therapy for residual disease compared with the placebo group (stratified hazard ratio, 0.72 [95% CI, 0.54-0.96]; P = .02), with a 2-year event-free survival rate of 60.3% vs 50.5%, respectively. The complete response rate was 73.0% vs 61.8% (difference, 11.1% [95% CI, 2.3%-20.0%]), respectively. Increased toxicity associated with treatment was observed in the tucidinostat group but generally manageable with supportive care. CONCLUSIONS AND RELEVANCE: Tucidinostat plus R-CHOP significantly improved event-free survival, with manageable toxicity in patients newly diagnosed with DEL. This trial is the first to demonstrate the benefit of an epigenetic modulator in DLBCL, offering a new first-line therapeutic approach dually targeting MYC and BCL2 oncoprotein for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04231448.
20 May 2026
Read appraisal →Emerging microbes & infections
Clinical outcomes of carbapenem therapy in OXA-48-producing Enterobacterales infections: a French multicentre cohort, systematic review, and meta-analysis
OXA-48-producing Enterobacterales (OXA-48-PE) represent a growing global health threat. Most of OXA-48-PE remain categorized susceptible to carbapenems, which might encourage their use despite uncertain clinical efficacy. This study evaluated clinical outcomes of infections caused by OXA-48-PE treated with carbapenem compared with alternative active therapies. The analyses were performed at three levels: a descriptive analysis of the French cohort, a comparative descriptive analysis of all published studies, and a meta-analysis restricted to studies providing direct comparisons between carbapenem-based and alternative active regimens. Between September 2021 and March 2023, 59 patients with monomicrobial OXA-48-PE infections were included in a French multicenter retrospective cohort. In parallel, a systematic review was conducted to identify clinical studies published through 31 December 2024, reporting outcomes of OXA-48-PE infections. In the French cohort, the overall 30-day mortality was 49.1%. Clinical failure occurred in 57.1% of patients receiving meropenem monotherapy, including patients infected with isolates exhibiting meropenem MICs within the susceptible range. Across 12 clinical studies (817 patients), carbapenem therapy was associated with high and variable crude mortality (52%), whereas newer agents active against OXA-48-PE, particularly ceftazidime-avibactam, were associated with lower and more consistent crude mortality (30.7%). In the primary meta-analysis of 6 human comparative studies, carbapenem therapy was associated with an increased risk of clinical failure compared with alternative active regimens (OR = 2.02; 95% CI = 1.05-3.88). Despite apparent in vitro susceptibility, carbapenem therapy was consistently associated with unfavourable clinical outcomes in OXA-48-PE infections, supporting the prioritization of alternative active agents whenever available.
20 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Efficacy and Safety of Once-Weekly Lonapegsomatropin in Adults With Growth Hormone Deficiency: foresiGHt Trial Results
CONTEXT: Adult growth hormone (GH) deficiency (GHD) is characterized by metabolic abnormalities caused by insufficient GH production. Lonapegsomatropin, a prodrug administered once weekly, was designed to provide sustained release of unmodified somatropin to reduce the burden of daily somatropin injections. OBJECTIVE: This work aimed to evaluate the efficacy and safety of lonapegsomatropin vs placebo as treatment for adults with GHD. METHODS: The foresiGHt trial was a multicenter, randomized, parallel-arm, placebo-controlled (double-blind) and active-controlled (open-label) trial (NCT04615273) conducted at 116 centers in North America, Europe, and Asia-Pacific. The trial randomly assigned and dosed 259 adults with GHD. Participants were randomly assigned 1:1:1 to receive once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin for 38 weeks. The primary efficacy end point was change from baseline in trunk percent fat at week 38. Secondary efficacy end points included change from baseline in trunk fat mass and total body lean mass. RESULTS: At week 38, lonapegsomatropin significantly reduced trunk percent fat (-1.68% vs +0.37%; least squares [LS] mean difference -2.04%; P < .001), increased total body lean mass (+1.60 kg vs -0.11 kg; LS mean difference 1.70 kg; P < .0001), and reduced trunk fat mass (-0.48 kg vs +0.22 kg; LS mean difference -0.70 kg; P = .0053) vs placebo. The safety and tolerability profile of lonapegsomatropin was comparable to somatropin. CONCLUSION: The foresiGHt trial met its primary efficacy end point by demonstrating superiority of lonapegsomatropin vs placebo with similar safety and tolerability, supporting its potential as a once-weekly treatment option for adults with GHD.
19 May 2026
Read appraisal →Physiological measurement
Machine learning-based information flow analysis of ECG signals for long QT syndrome
Objective. Cardiovascular diseases remain the leading cause of death worldwide, highlighting the need for non-invasive and cost-effective risk assessment tools. Biological systems, including the heart, exhibit complex nonlinear dynamics arising from interactions between their subsystems. Information-theoretic measures, particularly entropy-based methods, provide a framework to quantify these interactions. Using ECG recordings, we investigate information flow between heart rhythm and ventricular repolarization to identify potential markers of pathological alterations in cardiac electrical activity.Approach. Entropy-based measures of information transfer were derived from beat-to-beat ECG time series using a window-based approach and subsequently averaged at the subject level. These features were used as inputs to supervised machine learning models to discriminate patients with congenital long QT syndrome (LQTS) from healthy controls. Model performance was evaluated using repeated stratified train-test splits, and classification robustness was assessed across multiple runs using standard performance metrics, including the area under the receiver operating characteristic curve. The explainable artificial intelligence techniques were applied. SHapley Additive exPlanations were used to quantify the contribution of entropy-based features to the model predictions. This post-hoc explainability analysis enabled systematic assessment of feature importance while preserving the predictive performance of the models.Results. The proposed approach achieved high and stable classification performance across repeated validation runs. Both random forest (RF) and support vector machine (SVM) classifiers demonstrated high discrimination between LQTS patients and healthy controls, with consistently high area under the curve. For RF a mean accuracy of 95.9%, mean sensitivity of 95.9%, and mean specificity of 92.9% were achieved across repeated runs. For SVM the corresponding mean values were 93.1%, 93.1%, and 92.0%, respectively.Conclusions.Explainability analysis revealed a dominant contribution of multivariate and conditional information flow features compared with single-source entropy measures, highlighting the relevance of joint and conditional interactions in the classification patterns.
19 May 2026
Read appraisal →European heart journal
Mitral transcatheter edge-to-edge repair and outcomes according to baseline health status: the RESHAPE-HF2 trial
BACKGROUND AND AIMS: Mitral transcatheter edge-to-edge repair (M-TEER) using the MitraClip device improves clinical outcomes in patients with moderate-to-severe ventricular secondary mitral regurgitation (vSMR) and heart failure (HF). This study evaluated whether the effects of M-TEER on clinical outcomes vary by baseline health status, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), and assessed the impact of M-TEER on health status post-randomization. METHODS: The RESHAPE-HF2 trial included patients with symptomatic HF and moderate-to-severe vSMR (mean effective regurgitant orifice area .25 cm2; 14% >.40 cm2, 23% <.20 cm2). The impact of baseline KCCQ-clinical summary score (CSS) on the effect of M-TEER on clinical outcomes was assessed using Cox proportional hazards models. Changes post-randomization in health status and responder analyses were performed to assess the odds ratio (OR) of improvement and deterioration in KCCQ scores. RESULTS: Among 505 patients, M-TEER reduced cardiovascular death or HF hospitalization risk [hazard ratio (HR): .71 (.48-1.05), .50 (.29-.85), and .73 (.38-1.41)] across KCCQ-CSS tertiles of <38.9, 38.9-66.1, and >66.1, respectively (P-trend = .53). Similar results were seen for total HF hospitalization (P-trend = .48). M-TEER improved KCCQ-CSS, total symptom score, and overall summary score at 1, 6, 12, and 24 months compared to medical therapy alone (P < .05 at all time points). More patients in the M-TEER arm experienced a ≥5-point [OR 3.38 (2.09-5.45)], ≥10-point [OR 3.12 (1.93-5.02)], and ≥15-point [OR 3.25 (1.94-5.45)] improvement, and less patients had a ≥5-point deterioration [OR .34 (.19-.57)] in KCCQ-CSS at 6 months. Similar results were seen across other KCCQ domains and all time points. CONCLUSIONS: In patients with HF and moderate-to-severe vSMR, M-TEER showed a consistent trend towards a lower risk of HF hospitalization, with or without cardiovascular death, across all KCCQ-CSS tertiles and improved health status over time.
19 May 2026
Read appraisal →Lupus science & medicine
Incidence of serious infections, herpes zoster and hepatitis B virus reactivation among patients with SLE: a cohort study using a health claims database in Japan
OBJECTIVES: To investigate the real-world incidence of serious infections (SI), herpes zoster (HZ) and hepatitis B virus (HBV) reactivation among patients with SLE. METHODS: This retrospective, non-interventional cohort study used an insurance claims database in Japan to calculate the incidence of SI requiring hospitalisation, HZ and HBV reactivation in patients with SLE from 1 April 2017 to 31 March 2021. As an exploratory analysis, HRs and 95% CIs were estimated for clinically relevant patient characteristics for SI and HZ, adjusting for age and sex. RESULTS: Among 10 865 patients with SLE (female: 83.1%, median age: 53.0 years), including those who had previously experienced each complication, the incidence rates (per 100 patient-years) for SI, HZ and HBV reactivation were 4.80 (95% CI 4.53 to 5.08), 0.52 (0.44 to 0.61) and 0.37 (0.30 to 0.45), respectively. For those who had no previous history of each complication, incidence rates were 3.67 (3.44 to 3.92), 0.48 (0.40 to 0.58) and 0.25 (0.20 to 0.32), respectively. Incidence rates in specific subgroups were as follows: history of each complication (SI: 37.93, HZ: 4.19, HBV reactivation: 72.01), history of SI (HZ: 1.51, HBV reactivation: 1.75) and glucocorticoid pulse therapy during follow-up (SI: 64.23, HZ: 3.10, HBV reactivation: 4.85). CONCLUSIONS: These results provide data on the occurrence of selected infections in SLE and may inform safety management.
18 May 2026
Read appraisal →Drug discoveries & therapeutics
Efficacy and safety of filgotinib versus tocilizumab in active rheumatoid arthritis: A randomized, open-label, multicenter study with clinical and musculoskeletal ultrasound evaluation (TRANSFORM study)
Janus kinase (JAK) and interleukin-6 (IL-6) inhibitors are therapeutic options for patients with rheumatoid arthritis (RA) with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs); however, no randomized controlled trial has compared their efficacy and safety. Since both act through the JAK-signal transducer and activator of transcription pathway, a comparative evaluation is warranted. We conducted a prospective, randomized, open-label trial at 55 centers in Japan, randomizing patients with active RA despite csDMARD therapy in a 1:1 ratio to receive 200 mg/day filgotinib or subcutaneous tocilizumab as monotherapy; the primary endpoint was American College of Rheumatology (ACR) 50 at week 12, and secondary endpoints included clinical disease activity indices, musculoskeletal ultrasonography scores, patient-reported outcomes, and serum biomarkers through 52 weeks. Twenty-six patients were enrolled (13 per group) before study termination due to insufficient recruitment, and descriptive analyses were performed. At week 12, ACR50 was achieved in 38.5% (5/13) patients in the filgotinib group and 46.2% (6/13) in the tocilizumab group (risk difference: -7.69%; 95% confidence interval: -42.26 to 28.8). Both groups showed early and sustained improvements in disease activity from week 2. The improvement in patient global assessment scores was greater with filgotinib at week 2 but the difference diminished thereafter, and serum IL-6 level decreased with filgotinib but increased with tocilizumab. Four serious adverse events occurred with filgotinib, including infections and cardiac events. Because this study was underpowered and the analysis was descriptive, larger studies are needed to confirm these findings and define optimal use. (The study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) as jRCTs071200107 and in ClinicalTrials.gov as NCT05090410.).
18 May 2026
Read appraisal →Journal of pharmacokinetics and pharmacodynamics
Development of a novel rabeprazole modified release formulation to reduce the dosing frequency: A trial and triumph with physiologically based biopharmaceutics modeling.
Advanced in silico tools, such as physiologically based biopharmaceutics models (PBBM) and physiologically based pharmacokinetic models (PBPK), play a pivotal role in model-informed formulation development (MIFD). In the present study, these methodologies were utilized in the development of a novel rabeprazole modified-release (MR) formulation for improved patient compliance by reducing the dosing frequency relative to existing delayed-release (DR) formulation. A MR formulation containing combination of delayed release and pulsatile release components was designed based on the hypothetical dissolution targets. A PBBM was first established using literature-derived clinical data and used to simulate the performance of formulations with varied dissolution profiles. Initial MR formulation prototypes (once a day) were evaluated in pilot-1 bioequivalence (BE) study against reference formulation (twice a day) but results indicated infra bioequivalence outcome. After pilot-1 study, the formulation and the dissolution method were optimized and then model was refined to predict the pilot 1 outcomes. The validated model was then employed to select suitable pilot-2 prototypes and to prospectively predict their BE outcomes under fasted and fed conditions. The predicted BE ratios were in good agreement with the observed pilot-2 study results. Therefore, the same model was used to make prospective predictions with increased subjects to understand the in vivo performance of pivotal test formulation and lead to the successful bioequivalence outcome, product commercialization, ultimately aiding in increased patient compliance. This work highlights the value of a model-informed strategy in accelerating formulation optimization, reducing development timelines and costs, and strengthening decision-making within pharmaceutical development programs.
18 May 2026
Read appraisal →Lancet (London, England)
Efficacy and safety of cefepime-nacubactam and aztreonam-nacubactam compared with imipenem-cilastatin for complicated urinary tract infection or acute uncomplicated pyelonephritis (Integral-1): a double-blind, randomised phase 3 trial
BACKGROUND: Nacubactam (OP0595) is a newly developed diazabicyclooctane β-lactamase inhibitor used in combination with cefepime or aztreonam. We assessed the efficacy and safety of cefepime-nacubactam and aztreonam-nacubactam versus imipenem-cilastatin in complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis. METHODS: The Integral-1 global, phase 3, multicentre, randomised, double-blind study recruited adults (aged ≥18 years) with cUTI or acute uncomplicated pyelonephritis at 79 sites in Bulgaria, China, Czech Republic, Estonia, Georgia, Japan, Latvia, Lithuania, and Slovakia. Patients were randomly assigned (2:1:1) to receive intravenous cefepime (2 g) plus nacubactam (1 g), aztreonam (2 g) plus nacubactam (1 g), or imipenem (1 g) plus cilastatin (1 g) every 8 h for 5-14 days. Randomisation was stratified by diagnosis and geographical region. The primary endpoint was the proportion of patients achieving composite clinical and microbiological success at test of cure in the microbiological modified intention-to-treat population-all patients who were randomly assigned, received any amount of the study drug, and had a baseline qualifying pathogen that was susceptible to imipenem and meropenem. The prespecified non-inferiority margin was more than 15 percentage points difference; the superiority margin was more than zero percentage points difference, for the lower bound of the two-sided 95% CI for imipenem-cilastatin. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT05887908. FINDINGS: Between May 22, 2023, and Nov 26, 2024, 614 patients were randomly assigned and 431 were included in the primary efficacy analysis (cefepime-nacubactam [n=214], aztreonam-nacubactam [n=112], or imipenem-cilastatin [n=105]); 228 patients (53%) were male and 203 (47%) were female. The primary endpoint was achieved by 176 (82%) of 214, 81 (72%) of 112, and 64 (61%) of 105 patients in the cefepime-nacubactam, aztreonam-nacubactam, and imipenem-cilastatin groups, respectively. The percentage difference in the success rate versus imipenem-cilastatin was 21·3% (95% CI 10·9 to 32·0) for cefepime-nacubactam (non-inferior and superior), and 11·4% (-1·2 to 23·7) for aztreonam-nacubactam (non-inferior). Treatment-emergent adverse events were reported in 100 (33%) of 306, 45 (30%) of 152, and 65 (43%) of 150 patients in the cefepime-nacubactam, aztreonam-nacubactam, and imipenem-cilastatin groups, respectively. No treatment-related deaths occurred. INTERPRETATION: Cefepime-nacubactam and aztreonam-nacubactam are potential treatment options for Gram-negative cUTI and acute uncomplicated pyelonephritis, including infections caused by antimicrobial-resistant strains. FUNDING: Meiji Seika Pharma and Japan Agency for Medical Research and Development.
18 May 2026
Read appraisal →European journal of preventive cardiology
Targeting better hypertension control with the usage of the ESH smartphone application
AIMS: Uncontrolled blood pressure is a main issue in the management of hypertensive patients, while mobile health (mHealth) offers a new perspective. This study aimed to investigate the efficacy of an mHealth app-based intervention, the European Society of Hypertension (ESH) CARE, in the management of uncontrolled hypertensive patients. METHODS AND RESULTS: This was a two-arm randomized, controlled trial conducted among 107 hypertensive patients, with uncontrolled office (≥140/90 mmHg) and 24-h ambulatory blood pressure (≥130/80 mmHg). After antihypertensive drug treatment initiation or intensification, patients were 1:1 randomized to application assisted strategy (AAS) group or usual care group, with scheduled visits at 1 and 3 months. In ASS group there was a virtual visit, while in usual care group there was an office visit. At 6 months, there was a final visit assessment with office and ambulatory blood pressure (BP) measurement. The mean age of the total population (n = 107) was 52.9 ± 9.6 years, 50.5% were women, without any significant differences in the baseline characteristics. At 6 months, 50% in the usual care group and 78.2% in the AAS group (P = 0.002) achieved both systolic and diastolic ambulatory BP targets (<130/80 mmHg). Regarding office BP, there was a reduction of 19.9 ± 9.1/12.4 ± 7.7 mmHg in the usual care group and 25.1 ± 6.4/16.3 ± 6.3 mmHg in the AAS group, while regarding ambulatory BP, there was a reduction of 6.6 ± 9.2/3.3 ± 6.2 mmHg and 10.9 ± 9.1/6.4 ± 5.5 mmHg, respectively. CONCLUSION: Follow-up of hypertensive patients with the ESH Care App is feasible and contributes to a significantly better office and out-of-office BP control after 6 months. Uncontrolled blood pressure is a main issue in the management of hypertensive patients, while mobile health (mHealth) offers a new perspective. This study aimed to compare the efficacy of an mHealth app-based—ESH Care App—intervention to usual clinical care, in the management of uncontrolled hypertensive patients. Telemonitoring with the ESH Care App is associated with: Significantly improvement in office and ambulatory blood pressure control. Significantly greater reduction in office and ambulatory BP measurements.
18 May 2026
Read appraisal →European journal of preventive cardiology
Effect of intensive blood pressure control in patients with resistant hypertension: insights from the STEP trial
AIMS: Resistant hypertension is defined as uncontrolled blood pressure (BP) despite the use of ≥3 antihypertensive drugs or controlled BP with ≥4 antihypertensive drugs. Whether intensive BP control is beneficial for the management of resistant hypertension is unknown. METHODS AND RESULTS: Intensive (<130 mmHg) BP control in patients is compared with standard (130-150 mmHg) BP control in patients with resistant hypertension, using the Strategy of Blood Pressure Intervention in Older Hypertensive Patients (STEP) trial data. Patients were divided into those with and without resistant hypertension. The primary outcome was a composite of cardiovascular events. Hazard ratios (HRs) were calculated using the Fine-Gray sub-distribution hazard model for primary and secondary events and the Cox regression model for all-cause death. In patients with resistant hypertension, intensive BP control was associated with a lower risk of primary outcomes (HR, 0.36; 95% CI, 0.14-0.93; P = 0.035). Results were consistent across different BP thresholds used to define resistant hypertension and in patients with true resistant hypertension. The benefit of intensive BP control was consistent across resistant hypertension status. Intensive BP control was not associated with an increased risk of adverse events in patients with resistant hypertension. Patients with resistant hypertension had increased cardiovascular risk compared with those without (HR, 1.78; 95% CI, 1.13-2.81; P = 0.012). CONCLUSION: Intensive BP control is associated with reduced risk of cardiovascular events in patients with resistant hypertension without increased risk of adverse events. REGISTRATION: https://www.clinicaltrials.gov/ct2/show/NCT03015311. The present study is a secondary analysis of the effect of intensive blood pressure control in patients with resistant hypertension in the STEP trial. Resistant hypertension is characterized as elevated blood pressure (BP) despite three antihypertensive agents or controlled BP with four or more agents. Intensive BP control in patients with resistant hypertension may reduce the risk of cardiovascular events. Further research is needed to investigate multifaceted treatment approaches, including both pharmacological and non-pharmacological interventions.Intensive blood pressure (BP) control is associated with a reduced risk of cardiovascular events and death in patients with resistant hypertension, compared with standard BP control, without increasing the risk of adverse events.Patients with resistant hypertension remain at higher risk of cardiovascular events compared with patients without resistant hypertension. Intensive BP control in this population may lower the risk of cardiovascular events.
18 May 2026
Read appraisal →Pituitary
Pituitary adenoma and intracerebral aneurysms: case series, systematic review and meta-analysis
PURPOSE: Intracranial aneurysms (IAs) and Pituitary Adenoma (PA) coexistence has been reported for decades, yet available evidence remains fragmented. We performed a systematic review and meta-analysis following PRISMA 2020 guidelines to assess clinical features of patients with both conditions and quantify the prevalence of IAs in PA patients. METHODS: PubMed and Embase were searched up to December 15, 2025. Studies reporting coexistence of IAs and PAs were included. Individual patient-level data (Group 1) and aggregate prevalence data (Group 2) were analyzed separately. Risk of bias (RoB) was assessed using Joanna Briggs Institute tools. All analyses were performed using metaprop function from the meta package in R software. RESULTS: Seventy-one studies met inclusion criteria. Most studies have a low RoB. In Group 1 (74 patients), PAs were predominantly macroadenomas (91.9%), most frequently non-functioning (40.5%). IAs were mainly in the cavernous segment of the internal carotid artery (33%). IA diagnosis occurred significantly later than PA diagnosis (p < 0.01). In Group 2 (5264 patients), the pooled prevalence of IAs among PAs was 4% (95% CI 2-4%; I² = 92.1%, τ² = 1.1050, p < 0.0001). Sex-stratified prevalence was 8% (95% CI: 6%-9%) in females and 6% (95% CI: 4%-7%) in males. IAs sex-specific prevalence was significantly higher in both male and female PA patients as compared to the general population (p < 0.01). CONCLUSION: Patients with PAs show a higher IAs prevalence compared with the general population, likely reflecting combined hemodynamic, anatomical, and endocrine influences.
18 May 2026
Read appraisal →Computers in biology and medicine
A unified multimodal framework for chest X-ray retrieval and disease prediction for clinical decision support
Recent advances in medical imaging and natural language processing enable new opportunities for automated diagnostic support. Chest X-rays (CXRs) remain the most common imaging modality for screening pulmonary, cardiovascular, and systemic diseases; however, the growing volume of studies and free-text reports can overwhelm clinicians. We propose a unified multimodal retrieval and prediction framework that jointly leverages DICOM-format CXRs and radiology reports by projecting visual and textual features into a shared semantic space. Trained with contrastive and multi-label objectives, the system supports disease classification, case-based retrieval, and explainable AI. Experiments on the Open-I dataset demonstrate strong performance, achieving a Macro AUROC of 0.95 and Macro F1-score of 0.71 across 22 diagnostic categories. The retrieval module attains high ranking quality (MRR and nDCG >0.93) with sub-millisecond query latency. Quantitative explainability analysis further shows strong agreement between attention- and gradient-based attribution maps (Pearson ρ≈0.92), supporting trustworthy clinical decision-making.
17 May 2026
Read appraisal →Clinica chimica acta; international journal of clinical chemistry
AI in the Prediction of Hepatic Fibrosis Progression Using Non-Coding RNAs
Hepatic fibrosis is a dynamic and progressive condition that can lead to cirrhosis and hepatocellular carcinoma (HCC) if left untreated. Appropriate assessment of the disease progression of fibrosis is critical for early intervention and individualized treatment regimens. Traditional biopsy techniques are invasive and prone to sampling errors, highlighting the need for less invasive predictive techniques. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as key regulators of hepatic fibrogenesis and as a possible biomarker for disease staging and prognosis. The emergence of artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), has revolutionized the comprehensive large-scale analysis of transcriptomic data, enhancing the identification of ncRNA biomarkers and predictive modeling. The AI-based algorithms have been found to be more precise in anticipating fibrosis progression by means of integrating multi-omics data, ncRNA interaction networks, and by improving non-invasive diagnostic tools. This review involves the analysis of AI and ncRNA research in hepatic fibrosis, highlighting recent discoveries, possible challenges, and future opportunities. We address the necessity of standardization of data and clinical validation, as well as discuss the role of AI in identifying biomarkers of ncRNA, predicting the stage of fibrosis and risk stratification. ncRNA analysis with AI has a tremendous potential of transforming the diagnostics and prognostics of hepatic fibrosis, enabling precision hepatology.
17 May 2026
Read appraisal →PloS one
Effect of intra-dialytic pedaling exercise on dialysis adequacy: A randomized controlled trial
BACKGROUND: In patients with chronic kidney disease undergoing hemodialysis, physical activity and rehabilitation are crucial for preventing declines in muscle strength and functional capacity. This study aimed to assess the impact of physical activity during hemodialysis on dialysis adequacy in patients undergoing hemodialysis. METHODS: This randomized controlled trial (RCT) investigated the impact of pedaling exercise on dialysis effectiveness in 84 hemodialysis patients at hospitals in Bushehr. Participants were randomly assigned to either an experimental group (n = 42) that performed 30 minutes of pedaling exercise during their 4-hour dialysis sessions or a control group (n = 42) that received routine hemodialysis. Dialysis adequacy was assessed by comparing pre- and post-dialysis blood samples obtained from the arterial line. A conservative intradialytic exercise protocol, blood samples, and patient weight were measured using a calibrated digital scale. Data analysis was performed using SPSS version 24 software. RESULTS: The experimental and control groups were similar in demographic characteristics, except for age (X2 = -3.84, p = 0.001) and education levels (X2 = 10.100, p = 0.006). While there was no significant difference in weight between the groups before and after the intervention (t = 0.223, p = 0.82 before; t = 0.203, p = 0.84 after), both groups showed a substantial weight reduction overall (p < 0.0001). There were no statistically significant differences in weight change (t = 0.80, p = 0.25), BUN (t = 0.13, p = 1.52), or Kt/V (t = 1.62, p = 0.11) between the experimental and control groups. CONCLUSION: This study found that incorporating pedaling exercise during hemodialysis did not significantly improve dialysis effectiveness, as measured by weight change, BUN levels, or Kt/V. While both groups showed weight loss, there were no statistically significant differences between them. However, the study was limited by its small sample size and the specific exercise protocol employed. Further research with larger cohorts and a broader range of physical activities is needed to determine whether physical activity during hemodialysis can improve dialysis adequacy and overall patient outcomes. TRIAL REGISTRATION: IRCT code number 20150529022466N15 and trial Code of Ethics IR.BPUMS.REC.1398.130E.
16 May 2026
Read appraisal →European journal of preventive cardiology
Cuffless Blood Pressure Monitoring Devices: Technical Foundations and Clinical Implications
Cuffless blood pressure (BP) monitoring devices represent a promising innovation in hypertension management. This scientific statement provides a comprehensive update on these emerging technologies, their specific validation requirements, their potential clinical applications, and their present and future challenges. These devices generate considerable interest by enabling non-invasive BP measurement without arterial occlusion, thereby eliminating the discomfort associated with traditional cuff-based monitoring, particularly during sleep. The technologies on which these devices are based comprise a heterogeneous group, primarily utilizing pulse wave propagation time or waveform analysis through contact or non-contact sensors. They can be categorized as continuous or intermittent, automated or manual, calibration-free or requiring cuff/demographic calibration, and wearable or stationary. This technological diversity necessitates validation protocols distinct from those used for conventional cuff-based monitors, with specific requirements for each device category. Potential clinical applications include widespread out-of-office BP monitoring, unbiased assessment of circadian BP patterns and BP variability, improved detection of nocturnal hypertension, enhanced treatment adherence and long-term BP control, and continuous monitoring in hospital settings. Additionally, their lower cost compared with conventional technologies could enhance the early detection of hypertension in resource-limited settings. However, due to insufficient accuracy validation, this scientific statement does not recommend their use in clinical decisions in spite of their potential interest, in line with international guidelines not recommending their use in hypertension management. Key challenges ahead include developing standardized validation protocols, establishing normative BP data, managing the resulting burden on clinicians in handling huge volumes of data, exploring additional haemodynamic parameters, and advancing sensor technology, mathematical models, and algorithms.
16 May 2026
Read appraisal →PloS one
D-dimer and lower limb ultrasound as prognostic factors for recurrent deep venous thrombosis and pulmonary embolism: A systematic review and meta-analysis
Venous thromboembolic disease is a chronic, recurrent condition. The optimal duration of anticoagulation therapy remains uncertain. We aim to evaluate D-dimer and lower limb ultrasonography as prognostic tools for the recurrence of venous thromboembolism. A search was conducted on May 28, 2022, in the Medline, Embase, and Cochrane databases. Inclusion criteria encompassed cohort studies, case-control studies, and clinical trials. Two reviewers independently screened all records and analyzed studies for inclusion/exclusion criteria, as well as risk of bias, using a structured framework (PROSPERO ID: CRD42022341082). The initial search yielded 4652 titles and abstracts. After removing 777 duplicates and reviewing 3875 titles and abstracts, 48 articles providing information on D-dimer and/or lower limb ultrasonography as prognostic factors were finally included. Very low-certainty evidence suggests that both residual vein thrombosis (RVT) at anticoagulation discontinuation and a positive post-treatment D-dimer are significantly associated with an increased risk of recurrent venous thromboembolism (VTE). For RVT, the pooled analysis showed a two-fold increase in risk (OR 2.00, 95% CI 1.02 to 3.94; I² = 85.7) while for positive D-dimer, the risk was similarly elevated (OR, 2.48; 95% CI, 1.85-3.33; I² = 56.0). In conclusion, very low-quality evidence suggests that abnormal D-dimer and RVT are associated with recurrent VTE; however, this association is inconsistent due to significant heterogeneity and wide prediction intervals. These biomarkers should be interpreted with caution as isolated predictors in clinical practice.
16 May 2026
Read appraisal →European heart journal
Foundation models for electrocardiogram interpretation: clinical implications.
BACKGROUND AND AIMS: The 12-lead electrocardiogram (ECG) remains a cornerstone of cardiac diagnostics, yet existing artificial intelligence (AI) solutions for automated interpretation often lack generalizability, remain closed source, and are primarily trained using supervised learning (SL), which requires extensive labelled datasets and may limit adaptability across diverse clinical settings. Self-supervised learning (SSL) can potentially overcome these limitations by learning robust representations from unlabelled data. To address these challenges, this study developed and compared two open-source foundational ECG models: DeepECG-SL, a supervised multilabel ECG model, and DeepECG-SSL, a self-supervised model. METHODS: Both models were trained on over 1 million ECGs using a standardized preprocessing pipeline and automated free-text extraction from ECG reports to predict 77 cardiac conditions. DeepECG-SSL leveraged unlabelled data through self-supervised contrastive learning and masked lead modelling before fine-tuning for downstream tasks, while DeepECG-SL was trained directly on labelled diagnostic data in an end-to-end fashion. Performance was evaluated across seven private, multilingual healthcare systems and four public ECG repositories, with assessment of fairness by age and sex, and investigation of privacy vulnerabilities as well as memory and compute requirements. RESULTS: DeepECG-SSL achieved micro-averaged area under the receiver operating characteristic curves (AUROCs) across all 77 cardiac conditions for ECG interpretation of 0.990 [95% confidence interval (CI): 0.990, 0.990] on the internal dataset (MHI-ds), 0.981 (95% CI: 0.981, 0.981) on external public datasets (UKB, CLSA, MIMIC-IV and PTB), and 0.983 (95% CI: 0.983, 0.983) on external private datasets (UW, UCSF, JGH, NYP, MGH, CSH and CHUM), while DeepECG-SL demonstrated AUROCs of 0.992 (95% CI: 0.992, 0.992), 0.980 (95% CI: 0.980, 0.980), and 0.983 (95% CI: 0.983, 0.984), respectively. Fairness analyses revealed minimal disparities (true-positive rate and false-positive rate difference <0.1) across age and sex groups for both models. DeepECG-SSL demonstrated superior performance on limited-data digital biomarker tasks, with the largest improvements in long QT syndrome (LQTS) genotype classification (AUROC 0.931 vs 0.850, P = .026, n = 127 ECGs) and 5 year atrial fibrillation risk prediction (AUROC 0.742 vs 0.734, P < 0.001, n = 132 050 ECGs), while achieving superior performance in left ventricular ejection fraction ≤40% classification (AUROC 0.926 vs 0.917, P < 0.001, n = 25 252 ECGs) and comparable performance in LQTS detection (AUROC 0.767 vs 0.735, P = 0.117, n = 934 ECGs). CONCLUSIONS: This study establishes SSL as a promising paradigm for ECG analysis, particularly in settings with limited annotated data, enhancing accessibility, generalizability, and fairness in AI-driven cardiac diagnostics. By releasing model weights, preprocessing tools, and validation code, this work aims to support robust, data-efficient AI diagnostics across diverse clinical environments and questions.
16 May 2026
Read appraisal →European heart journal
Deep learning electrocardiogram model for risk stratification of coronary revascularization need in the emergency department
BACKGROUND AND AIMS: Identification of patients with acute coronary syndrome requiring coronary revascularization can be challenging due to inconclusive electrocardiogram (ECG) findings or biomarker results. A deep learning model to detect ECG patterns associated with revascularization likelihood was developed, aiming to guide further assessment and reduce diagnostic uncertainty. METHODS: A convolutional neural network model was trained on 144 691 ED visits from a US cohort (60 ± 19 years; 53% female; 0.6% revascularization), tested on a separate test cohort (n = 35 995), and benchmarked against clinician ECG interpretation and cardiac troponin T (TnT). External validation was performed for the outcomes revascularization and Type 1 myocardial infarction (MI) on 18 673 ED visits from Europe (55 ± 21 years; 49% female; 1.5% revascularization; 1% Type 1 MI). Primary performance metric was area under the receiver operating characteristic curve (AUROC). RESULTS: In the test cohort, the model achieved an AUROC of 0.91 (95% confidence interval [CI] 0.91-0.91), outperforming clinician ECG interpretation (AUROC 0.65, 95% CI 0.54-0.76) and conventional cardiac TnT (AUROC 0.71). In the external validation cohort, ECG model AUROC was 0.81 (95% CI 0.81-0.82) for revascularization, and 0.85 (95% CI 0.84-0.85) for Type 1 MI, compared with 0.70 (95% CI 0.57-0.83) and 0.74 (95% CI 0.56-0.92) for clinician interpretation, and 0.85 and 0.87 for high-sensitivity (hs)-TnT, respectively. The ECG model had higher specificity but lower sensitivity compared with high-sensitivity-troponin T. CONCLUSIONS: The model was able to detect revascularization and Type 1 MI with competitive performance, suggesting a potential role to complement current clinical assessment.
16 May 2026
Read appraisal →The Journal of infectious diseases
Cytomegalovirus DNAemia in Hospitalized Adults With SARS-CoV-2 Infection Requiring Supplemental Oxygen: Virologic and Clinical Characteristics and Association With Outcomes
BACKGROUND: Cytomegalovirus (CMV) reactivation occurs in the context of coronavirus disease 2019 (COVID-19); however, the viral kinetics, risk factors, and clinical outcomes are poorly defined. METHODS: We examined the association of CMV DNAemia with clinical outcomes among participants of a randomized trial of remdesivir with or without baricitinib (National Institute of Allergy and Infectious Diseases [NIAID], Adaptive COVID-19 Treatment Trial 2 [ACTT-2]). Plasma CMV DNAemia from CMV-seropositive participants with COVID-19 (NIAID ordinal scale [OS] 5, 6, or 7 at entry) were assessed longitudinally by quantitative polymerase chain reaction. Factors associated with CMV DNAemia, and clinical outcomes were analyzed by Cox regression and proportional odds models. RESULTS: Of 772 trial participants with available samples, 643 (83%) were CMV seropositive. Baseline CMV serostatus was not associated with COVID-19 outcomes. The cumulative incidence of CMV DNAemia among seropositive persons by day 28 was overall 11% (baseline OS 5, 6.3%; OS 6, 16.4%; OS 7, 24.7%), and was associated with older age, baseline OS, male sex, lymphopenia, and systemic corticosteroid use, while remdesivir and baricitinib did not affect risk. CMV DNAemia was associated with a lower probability of improvement by day 29 (adjusted hazard ratio, 0.3 [95% confidence interval, .17-.56]), with a more pronounced delay of recovery with higher CMV viral load. CMV DNAemia was also associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and death. CONCLUSIONS: In hospitalized adults with COVID-19 requiring oxygen, CMV viremia occurs within well-defined clinical risks and is independently associated with delayed recovery from illness, higher SARS-CoV-2 viral load, and increased mortality.
16 May 2026
Read appraisal →Journal of neurology, neurosurgery, and psychiatry
Intravenous methylprednisolone as add-on induction therapy for chronic inflammatory demyelinating polyradiculoneuropathy: a randomised controlled trial
BACKGROUND: Most patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) require maintenance treatment. We aimed to determine whether combined treatment with intravenous immunoglobulin (IVIg) and intravenous methylprednisolone (IVMP) increases remission rates compared with IVIg and placebo. METHODS: We performed a randomised, double-blind, placebo-controlled study. Adults with CIDP who were treatment naive, relapsed after a remission or required continued treatment after a single IVIg dose were included. Participants were treated with IVMP (1000 mg) or placebo (sodium chloride) every 3 weeks for 18 weeks. All participants received IVIg treatment consisting of a loading dose (2 g/kg) and serial maintenance treatments (1 g/kg). The primary outcome was remission, defined as sustained improvement on disability scales at 52 weeks without need for further treatment. RESULTS: Enrolment was halted after the inclusion of 77 of the 96 planned participants because of safety concerns: four thromboembolic events occurred in the IVIg/IVMP group compared with none in the IVIg/placebo group. 14 of 37 (38%) participants in the IVIg/IVMP group were in remission at 52 weeks compared with 11 out of 40 (28%) in the IVIg/placebo group, with a difference of 10% (95% CI -11 to 31; p=0.47). Several secondary outcomes showed a greater magnitude of improvement in disability and impairment at 18 and 52 weeks in the IVIg/IVMP group. CONCLUSIONS: The study was prematurely stopped due to safety concerns after four thromboembolic events in the IVIg plus IVMP group. Combined treatment did not lead to significantly more frequent remissions than IVIg alone in the doses used in this study. TRIAL REGISTRATION NUMBER: ISRCTN15893334.
16 May 2026
Read appraisal →Computers in biology and medicine
Artificial intelligence for metabolic dysfunction-associated steatotic liver disease diagnosis: A systematic review
Metabolic dysfunction-associated steatotic liver disease (MASLD) poses significant diagnostic challenges. We conducted a systematic review of artificial intelligence (AI) applications in MASLD diagnosis, focusing on predictive modeling, screening, imaging analysis, and therapeutic assistance. Following PRISMA guidelines, we searched five databases (Web of Science, SciFinder, Elsevier ScienceDirect, EBSCOhost, Springer) for studies published January 2020-January 2026. Of 1247 initially identified records, 191 studies met inclusion criteria. AI models demonstrate high diagnostic performance across multiple modalities. Deep learning analysis of US, CT, and MRI enables automated steatosis quantification and fibrosis staging with accuracy comparable to expert interpretation. AI integration with multi-omics data facilitates novel biomarker discovery and therapeutic target identification. Despite these advances, model generalisability, standardization, and clinical integration remain challenges. AI holds substantial potential to transform MASLD diagnostics, but prospective validation and implementation strategies are needed before widespread clinical adoption.
16 May 2026
Read appraisal →Renal failure
Comparative efficacy and safety of apixaban and rivaroxaban versus warfarin in atrial fibrillation patients with end-stage renal disease: a systematic review and meta-analysis
This study aimed to evaluate the comparative efficacy and safety of apixaban and rivaroxaban versus vitamin K antagonists (VKAs) in anticoagulation management in a dialysis population. PubMed, Embase, and the Cochrane Library were searched for studies comparing apixaban or rivaroxaban with VKAs in patients with atrial fibrillation (AF) undergoing dialysis. The primary efficacy endpoints included stroke/systemic embolism (SSE) and all-cause mortality. Safety outcomes encompassed major bleeding, intracranial hemorrhage, and gastrointestinal bleeding. Risk ratios (RR) with 95% confidence intervals (CI) were synthesized using random-effects models. The meta-analysis included three randomized controlled trials (RCTs) and eight observational studies. Pooled analyses showed that apixaban and rivaroxaban were associated with lower risks of major bleeding (RR 0.57, 95% CI: 0.51-0.63), gastrointestinal bleeding (RR 0.66, 95% CI: 0.57-0.76), and intracranial hemorrhage (RR 0.54, 95% CI: 0.36-0.83) compared with VKAs. Additionally, apixaban and rivaroxaban were associated with reduced risk of SSE (RR 0.57, 95% CI: 0.46-0.72) and all-cause mortality (RR 0.73, 95% CI:0.63-0.83), although substantial heterogeneity was present. Exploratory dose-stratified analyses suggested both standard- and low-dose apixaban regimens were associated with favorable efficacy and hemostatic safety relative to warfarin. Consistent numerical trends were observed in the RCT-only analysis, though none reached statistical significance owing to limited sample size. In conclusion, apixaban and rivaroxaban are associated with lower risks of bleeding compared with VKAs in patients with AF and ESRD. However, evidence regarding their efficacy in preventing SSE, all-cause mortality and the optimal apixaban dosing regimen remains inconclusive and requires validation in large, dedicated RCTs.
15 May 2026
Read appraisal →BMJ open
Prevalence of anxiety and depression in adults who are high users of healthcare services and magnitude of associated costs: a systematic review
OBJECTIVES: Anxiety and depression are common and associated with higher use of general healthcare services. The aims of this systematic review were to (1) estimate the prevalence of anxiety and depression in adults who are high or costly users of general healthcare services in comparison to routine users and (2) estimate the magnitude of healthcare costs associated with the presence of anxiety and depression. DESIGN: Systematic review of the available literature. DATA SOURCES: MEDLINE, PsycINFO, EMBASE, CINAHL, PROSPERO and Cochrane Library were systematically searched without language restriction from inception to 1 April 2019 and updated on 25 October 2022, 16 October 2024 and 18 February 2026. ELIGIBILITY CRITERIA: Eligible studies described adults aged ≥18 years who were defined as high or costly general healthcare users and where the prevalence and/or associated costs of anxiety and/or depression were quantified. DATA EXTRACTION AND SYNTHESIS: Three reviewers independently extracted information on study characteristics, exposure and outcomes. RESULTS: From the 38 412 identified articles, 27 studies from 10 countries (in Europe, North America and Asia) involving 6 145 907 participants met eligibility criteria and were included. There were wide variations in the estimated prevalence of anxiety (3.8-67.2%) and depression (4.7-77.9%) among high healthcare users. The prevalence of both disorders was higher among high healthcare users than routine users in all studies with non-high user comparator groups. Only four studies investigated healthcare costs associated with depression. These uniformly reported that general healthcare costs are higher for those with depression than those without. No studies investigated costs associated with anxiety. CONCLUSIONS: Anxiety and depression are over-represented among high or costly healthcare users, although accurate quantification of the magnitude of difference is precluded by significant methodological heterogeneity and variability in definitions used. Improved identification of covert mental health problems is essential for the provision of effective interventions for patients and healthcare expenditure reduction. Future research should prioritise a standardised approach, with agreed definitions for high and/or costly healthcare use in different contexts. PROSPERO REGISTRATION NUMBER: CRD42018102628.
15 May 2026
Read appraisal →JMIR medical informatics
Development Process of a Clinical Decision Support System for Empiric Antibiotic Therapies in Patients With Sepsis: Case Study
BACKGROUND: Antibiotic therapies are the main treatment for bacterial infections, but growing antibiotic resistance is a major global health threat, severely impacting patients with sepsis. Rapid selection of the most effective antibiotic therapy is critical for survival and for preventing further resistance. Physicians must consider numerous factors for proper empiric treatment selection. A clinical decision support system (CDSS) aims to support physicians in this process, facilitating rapid and targeted therapy. OBJECTIVE: The purpose of this work is to explore the extent to which the realization of a CDSS is possible based on the data available to us and to document insights gained during the development of a foundational model designed to assist physicians in determining empiric treatment options for patients with sepsis. In this regard, rather than aiming to develop a CDSS for clinical application, we highlight the importance of close interprofessional collaboration between scientists from various disciplines and analyze the effects of data quality and quantity on the performance of our statistical models. METHODS: Empirical scientists conducted interviews with medical practitioners to acquire the medical knowledge required to develop sound statistical models. We developed and applied 2-step cross-sectional, as well as time-series classification models, to carefully preprocessed data of patients with sepsis admitted to the intensive care unit of a German hospital. RESULTS: We identified several factors as crucial information for valid decisions on empiric therapy for treating patients with sepsis. These include the patients' core data, especially the infection focus. To prevent further resistance, individual risk factors such as travel history and professional background should be considered. The evaluation of a therapy's effectiveness is mainly based on the patient's general condition and blood values such as procalcitonin and interleukin 6. One key factor in the acceptance of a CDSS is the explainability of the results produced by the applied methods. Our models demonstrated mainly weak predictive ability for all considered empiric antibiotic therapies. However, they are not yet suitable for use in clinical practice, especially as they are based on prescribing habits rather than on optimal treatment decisions. CONCLUSIONS: This work highlights the importance of interprofessional collaboration between medical experts and model developers, ensuring that data quality and clinical relevance are central to the process. It emphasizes the urgent need for high-quality, comprehensive data to overcome challenges such as data discontinuity and improve model performance, particularly through enhanced digitization in health care. This feasibility study will facilitate future efforts to develop a CDSS for treating patients with sepsis and to translate it into clinical use.
15 May 2026
Read appraisal →The New England journal of medicine
A Phase 3 Trial of Brepocitinib in Dermatomyositis
BACKGROUND: Brepocitinib is a first-in-class, oral, selective TYK2-JAK1 inhibitor that blocks cytokine signaling, which has been implicated in dermatomyositis. METHODS: In this phase 3, double-blind, randomized, placebo-controlled trial, adults with dermatomyositis were assigned in a 1:1:1 ratio to receive once-daily oral brepocitinib at a dose of 30 mg, brepocitinib at a dose of 15 mg, or placebo for 52 weeks. Standard therapies were continued, and glucocorticoids were tapered. The primary end point was the Total Improvement Score, a validated composite myositis index (with scores ranging from 0 to 100 and higher scores indicating greater improvement) at week 52. Key secondary end points, including skin disease activity, glucocorticoid tapering, and physical function, were tested in a multiplicity-controlled sequence. RESULTS: A total of 241 patients underwent randomization: 81 to receive brepocitinib 30 mg, 81 to receive brepocitinib 15 mg, and 79 to receive placebo. At week 52, the mean Total Improvement Score was 46.5, 37.5, and 31.2, respectively (difference with brepocitinib 30 mg vs. placebo, 15.3; 95% confidence interval [CI], 6.7 to 24.0; P<0.001; difference with brepocitinib 15 mg vs. placebo, 6.3; 95% CI, -2.4 to 14.9). Brepocitinib 30 mg was superior to placebo across all nine key secondary end points, including skin disease activity, systemic glucocorticoid tapering, and functional disability, with improvements observed as early as week 4. Serious infections were more frequent in the brepocitinib 30-mg group than in the placebo group (10% vs. 1%). No deaths occurred during the trial. CONCLUSIONS: In adults with dermatomyositis that was resistant to previous therapy, the use of brepocitinib at a dose of 30 mg (but not at a dose of 15 mg) resulted in significant benefits with respect to a composite myositis index, skin disease severity, glucocorticoid tapering, and functional disability. (Funded by Priovant Therapeutics; ClinicalTrials.gov number, NCT05437263.).
15 May 2026
Read appraisal →Journal of the American College of Cardiology
Blood Pressure Levels and Outcomes in Type 2 Diabetes: Dose-Response Meta-Analysis of 5.87 Million Cohort Participants
BACKGROUND: The dose-response relationships between systolic and diastolic blood pressure (SBP and DBP) levels and risks of all-cause mortality, cardiovascular and renal outcomes in type 2 diabetes remain poorly characterized, particularly at lower blood pressure (BP) levels. OBJECTIVE: This study aimed to examine risk patterns of major clinical outcomes across a wide range of BP levels in participants with type 2 diabetes. METHODS: We systematically searched PubMed, Embase, and Web of Science from inception to November 30, 2024, for cohort studies assessing associations of BP levels with all-cause mortality, cardiovascular, and renal outcomes. One-stage mixed-effects dose-response meta-analysis was conducted to assess the curvilinear associations. RESULTS: A total of 89 cohorts from 113 articles of 5,875,364 participants with type 2 diabetes were identified. A J-shaped association was observed for SBP with all-cause mortality. J-shaped associations were also observed for SBP with cardiovascular events and for DBP with all-cause mortality, with flattened risks at lower BP levels. After excluding studies with participants who had baseline cardiovascular diseases or cancer, a significantly lower risk of cardiovascular events was observed at lower SBP levels, as well as a flattened risk of all-cause mortality. Positive linear or monotonic trends were observed for renal events, estimated glomerular filtration rate decline, and development or progression of albuminuria. CONCLUSIONS: In type 2 diabetes, BP is linearly or monotonically associated with most cardiovascular and renal outcomes. Low SBP does not appear to be associated with an elevated risk of all-cause mortality compared with higher BP targets, suggesting that previously reported associations are likely due to reverse causation and unmeasured confounding.
15 May 2026
Read appraisal →Journal of clinical microbiology
Diagnostic performance of β-(1→3)-D-glucan, two Candida antigen, and five anti-Candida antibody assays in ICU patients with sepsis and high risk for invasive candidiasis: a secondary endpoint of the CandiSep randomized clinical trial
Invasive Candida infection (ICI) is the most common fungal infection in critically ill patients. This study analyzed the performance of various biomarkers in sera from the CandiSep trial, a randomized, multicenter trial including 342 sepsis patients at high risk for ICI across 18 German intensive care units. ICI and candidemia were diagnosed in 48 (14.0%) and 14 (4.1%) patients, respectively. Sera collected on 2 consecutive days at sepsis onset were analyzed for β-(1→3)-D-glucan (BDG; Fungitell), mannan (Platelia-Candida-Ag-Plus [Platelia-Mn] and Serion-ELISA-antigen-Candida [Serion-Mn]), and anti-Candida antibodies (Platelia-Candida-Ab-Plus, Serion-ELISA-Candida albicans-IgA/IgM/IgG, and Virclia-Candida albicans-germ-tube-antibody-IgG-Monotest). Only antigen levels (BDG, Platelia-Mn, Serion-Mn), but not anti-Candida antibody levels, were significantly elevated in ICI patients. Antigen levels were unaffected by Candida colonization, while antibody levels were significantly increased. Sensitivity and specificity at the manufacturer's cutoffs were unsatisfactory. Performance improved by adjusting cutoffs: BDG required a 3-fold increase, while all others required lowering. At 80% specificity, sensitivities (95% confidence intervals) for the diagnosis of ICI and candidemia were as follows: BDG (cutoff >280 pg/mL), 46% (31.4-60.8) and 64% (35.1-87.2); Platelia-Mn (cutoff >50 pg/mL), 38% (24.0-52.6) and 64% (35.1-87.2); Serion-Mn (cutoff >0.7 U/mL), 38% (24.0-52.6) and 50% (23.0-77.0), and below 28% and 43% for all antibody assays. Area under the receiver operating characteristic curve comparisons showed no significant differences between antigen assays. Combining biomarkers, either simultaneously or sequentially, offered no diagnostic advantage over single-biomarker use. In conclusion, anti-Candida antibody assays are likely influenced by colonization and have limited diagnostic utility. Antigen assays offer similar diagnostic value but require cutoff optimization. Combining biomarkers did not enhance diagnostic yield in our cohort.IMPORTANCEOur main findings based on our specific ICU cohort were as follows: (i) only Candida antigen levels, not anti-Candida antibody levels, were significantly elevated in ICI and candidemia. (ii) In patients without ICI, Candida colonization was not associated with altered antigen levels, but with elevated antibody levels. (iii) Sensitivity and specificity at the manufacturer's cutoffs were unsatisfactory, and cutoffs should be significantly adjusted. Potential optimal cutoff values are proposed by us. (iv) The evaluated antigen assays demonstrated overall comparable diagnostic performance in this study. (v) Anti-Candida antibody assays did not provide a meaningful diagnostic contribution. (vi) The combination of biomarkers offered no diagnostic advantage over the use of individual biomarkers, neither simultaneously nor sequentially. Our results suggest that the use of a single Candida antigen test with a cohort-adapted cutoff value may be sufficient. Furthermore, avoiding biomarker combinations could potentially reduce healthcare costs. The clinical implications of these findings should be interpreted with caution, given the limited data with associated large confidence intervals for candidemia and the cohort-specific nature of the study. Our results should therefore be confirmed in larger studies and additionally with other patient groups.
15 May 2026
Read appraisal →Journal of the American College of Cardiology
Single-Pill Low-Dose Triple Combination Therapy vs Standard-Dose Monotherapy in Patients With Mild-to-Moderate Hypertension
BACKGROUND: Single-pill low-dose combination (LDC) antihypertensive therapy is an emerging strategy for improving blood pressure (BP) control. Although previous phase II and pragmatic studies suggested promise, these are the first phase III, double-blind, active-controlled trials comparing a single-pill ultra-low-dose triple combination with standard-dose monotherapy. OBJECTIVES: In these studies, we sought to compare a single-pill combination of 1.67 mg amlodipine, 16.67 mg losartan potassium, and 4.17 mg chlorthalidone (LDC-ALC) with standard-dose monotherapy-5 mg amlodipine or 50 mg losartan potassium-in patients with mild-to-moderate hypertension. METHODS: HM-APOLLO-301 (Study 301, May 2022-June 2023) and HM-APOLLO-302 (Study 302, March-December 2024) were multicenter, randomized, double-blind, active-controlled, phase III studies in South Korea. Study 301 compared LDC-ALC and amlodipine; Study 302 compared LDC-ALC and losartan. Adults (≥19 years of age) with systolic blood pressure (SBP) 140 to <180 mm Hg and diastolic blood pressure (DBP) <110 mm Hg after 4-week placebo run-in were randomized to 8 weeks of treatment. The primary endpoint was SBP reduction at week 8, assessed first for noninferiority, then for superiority. RESULTS: In Study 301, LDC-ALC exhibited noninferiority to amlodipine in reducing SBP at week 8 (upper bound of 1-sided 97.5% CI: 2.8 mm Hg [<3 mm Hg noninferiority margin]), and similar efficacy (least-squares mean change: -19.1 vs -19.9 mm Hg; 95% CI: -1.5 to 3.1; P = 0.495), with similar DBP reduction and blood pressure control rate. In Study 302, LDC-ALC was both noninferior (upper bound of one-sided 97.5% CI: -0.6 mm Hg) and superior to losartan (least-squares mean change: -19.9 vs -16.4 mm Hg; 95% CI: -6.6 to -0.2; P = 0.037) in SBP reduction at week 8, with greater DBP reduction and a higher blood pressure control rate than losartan. Adverse events were similar between groups (LDC-ALC vs amlodipine: 11.7% vs 13.9%; LDC-ALC vs losartan: 6.4% vs 3.3%), with ≤1% treatment withdrawals and no serious drug-related events. CONCLUSIONS: Single-pill LDC-ALC achieved BP reductions similar to those with amlodipine and greater than those with losartan monotherapy over 8 weeks, with similar short-term tolerability. These findings support LDC-ALC as an effective and well tolerated alternative initial therapy for mild-to-moderate hypertension, expanding the set of validated strategies alongside established monotherapies. (A Study to Evaluate Efficacy and Safety of HCP1803 in Patients With Essential Hypertension [HM-APOLLO-301; NCT05362110]; A Study to Evaluate Efficacy and Safety of HCP1803 Compared to RLD2001-1 in Patients with Essential Hypertension [HM-APOLLO-302, NCT06438172]).
14 May 2026
Read appraisal →Physiological measurement
A teacher-student deep learning framework for enhanced clinical screening of heart failure from 12-lead electrocardiograms
Objective.Identifying heart failure (HF) from electrocardiograms (ECGs) is challenging due to the lack of definitive features. This study aims to develop a deep learning-based clinical decision support system, CTTSnet, for accurate and automated HF screening using ECGs.Approach.We propose a novel teacher-student framework, CTTSnet, which synergistically integrates a transformer as the teacher and a convolutional neural network as the student. This architecture combines global context-awareness with efficient local feature extraction. The model was trained and evaluated on a large-scale, real-world dataset of 27 018 ECGs and further validated on two external public datasets to assess generalizability.Main results.CTTSnet achieved an AUROC of 0.941 on the primary clinical dataset, surpassing strong baselines. The model attained an accuracy of 87.3%, with a recall of 88.6% and specificity of 85.8%. External validation on two additional public datasets further confirmed the model's generalizability.Significance.CTTSnet provides a scalable, high-accuracy tool for HF triage from routine ECG recordings. Its potential clinical value lies in assisting early identification of patients at risk of HF, thereby helping reduce missed diagnoses and facilitating timely referral for further evaluation.
14 May 2026
Read appraisal →European journal of heart failure
Effect of influenza vaccination in patients with decompensated heart failure: a systematic review and meta-analysis
AIMS: In patients with heart failure (HF) influenza vaccination has shown beneficial effects in preventing cardiac decompensations. However, no conclusive results have been achieved in the few studies that have evaluated the impact of vaccination during episodes of acute HF (AHF) decompensation. We conducted a systematic review and meta-analysis to determine the possible effects of influenza vaccination on all-cause mortality in patients diagnosed with AHF. METHODS: PubMed, Medline, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews databases were searched for longitudinal studies comparing patients with AHF vaccinated against influenza with unvaccinated patients. The primary outcome selected for meta-analysis was 1-year all-cause mortality, and secondary outcomes consisted of other outcomes reported in at least in two different studies. Statistical heterogeneity was determined by calculating the I² statistic. Individual adjusted results were pooled using a random effects model. Sensitivity analysis was run for the primary outcome by removing each individual study and then re-doing the meta-analysis. RESULTS: Up to 30 June 2025, five observational cohort studies examining the effect of influenza vaccination on 1-year all-cause mortality in AHF patients had been published. Statistical heterogeneity was low (I2 = 33.7%), meaning that between-study results were consistent. Pooled analysis of confounder-adjusted hazard ratio (HR) for all-cause mortality in vaccinated patients was 0.89 (95% CI 0.83-0.96) compared with unvaccinated patients. All sensitivity analyses rendered very similar results. In-hospital and 90-day mortality were reported in three and two studies and showed similar reductions in risk, with an adjusted odds ratio of 0.85, 95% CI 0.70-1.01, and adjusted HR of 0.86, 95% CI 0.76-0.96; respectively. Isolated data from single studies suggest no effect on hospitalization following discharge after the AHF episode. CONCLUSIONS: Influenza vaccination is associated with a lower short- and long-term all-cause mortality in patients with decompensated HF; however, as all the studies included in this meta-analysis were observational, these results could be subject to residual confounding and causality cannot be directly inferred from them.
14 May 2026
Read appraisal →European journal of clinical pharmacology
Comparison of loop diuretics for chronic heart failure: a systematic review and meta-analysis
BACKGROUND: Loop diuretics relieve congestion in chronic heart failure (CHF). We systematically reviewed randomised clinical trials (RCTs) evaluating their effects. METHODS: A systematic search was conducted across major databases. We included RCTs that compared a loop diuretic to another loop diuretic, placebo, or "no intervention". The primary outcome was all-cause mortality, and secondary outcomes were all-cause hospitalisation, serious adverse events (SAEs), and change in body weight (kg). RESULTS: This review included 23 RCTs that enrolled 4,902 patients. Treatment with alternative loop diuretics (torsemide, azosemide and piretanide) compared with furosemide did not reduce all-cause mortality (risk ratio 1.00, 95% CI 0.89, 1.12); I2 = 0%; p = 0.95), nor did it reduce all-cause hospitalisations (risk ratio 0.99, 95% CI 0.84, 1.17); I2 = 53,46%, p = 0.92). In a pooled analysis of alternative loop diuretics (including torsemide and piretanide) the risk of SAEs was higher compared to furosemide (risk ratio 1.32, 95% CI 1.03, 1.68); I2 = 0%), although this finding was based on a limited number of trials with inconsistent definitions and should therefore be interpreted cautiously. The pooled meta-analysis of change in body weight did not show a difference between loop diuretics (mean difference 0.00 kg, 95% CI -1.19, 1.20; I2 = 92.43), indicating substantial heterogeneity. Azosemide resulted in a significant weight loss reduction compared to furosemide (mean difference - 1.00 kg, 95% CI -1.42, -0.58) based on a single small study. CONCLUSIONS: The choice of loop diuretic did not seem to influence the risk of mortality. In a pooled analysis of torsemide and piretanide, the risk of SAEs was higher when compared to furosemide, but the certainty of this finding is limited. Azosemide was associated with weight loss compared to furosemide in one small trial.
14 May 2026
Read appraisal →European journal of heart failure
Finerenone, polypharmacy, and clinical outcomes in heart failure: pre-specified analysis from the FINEARTS-HF trial
AIMS: Patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) have a high comorbidity burden, which may necessitate numerous medications. Patients and clinicians may be hesitant about initiating another medication, especially among those already experiencing polypharmacy. This pre-specified analysis sought to examine the efficacy and safety of adding finerenone based on the concomitant medication number. METHODS: In the FINEARTS-HF trial, baseline medication use was collected in all 6001 participants with HFmrEF/HFpEF. Clinical outcomes and treatment effects were assessed by the categories of total medication count ('non-polypharmacy': ≤4 medications; 'polypharmacy': 5-9 medications; and 'hyper-polypharmacy': ≥10 medications) and as continuous variables. The primary outcome was a composite of cardiovascular death and total HF events. RESULTS: Overall (age: 72 ± 10 years; 46% women), the total number of medications at baseline ranged from 0 to 29 (mean: 8.4 ± 3.6), with 3588 (60%) meeting polypharmacy and 1878 (31%) meeting hyper-polypharmacy. Incidence rates for the primary outcome increased across medication categories: non-polypharmacy, 10.2; polypharmacy, 12.3; and hyper-polypharmacy, 26.1 per 100 person-years. The treatment benefits of finerenone in reducing the primary outcome were consistent across the spectrum of total medication count (Pinteraction = 0.94). Any serious adverse events and study drug discontinuation were not more frequent with finerenone vs placebo, regardless of polypharmacy categories. CONCLUSION: In FINEARTS-HF, >90% of patients with HFmrEF/HFpEF met the criteria for polypharmacy or hyper-polypharmacy, and these patients faced excess risks of cardiovascular events. Finerenone safely reduced cardiovascular death and total HF events across a broad range of baseline medication use.
14 May 2026
Read appraisal →Blood advances
Belantamab mafodotin, carfilzomib, lenalidomide, and dexamethasone for relapsed or refractory multiple myeloma
Belantamab mafodotin (belamaf), an antibody-drug conjugate targeting B-cell maturation antigen, has demonstrated single-agent activity in relapsed/refractory multiple myeloma (RRMM) but is associated with ocular toxicity. This phase 1/2 study evaluated the safety and preliminary efficacy of belamaf administered every 8 weeks in combination with carfilzomib, lenalidomide, and dexamethasone (KRd-b) in patients with RRMM. Eligible patients had received at least 1 previous line of therapy and had not progressed on full-dose lenalidomide. In the dose-escalation phase (3+3 design), belamaf was administered at 1.4 or 1.9 mg/kg every 8 weeks. The recommended phase 2 dose was 1.9 mg/kg, with no dose-limiting toxicities at this level. Among 19 patients treated, the overall response rate was 89.5%, and 78.9% achieved very good partial response or better, with minimal residual disease negativity in all complete responders. At a median follow-up of 19.3 months, 24-month progression-free survival and overall survival rates were 74.3% and 85.1%, respectively. Keratopathy occurred in 94.7% of patients but was mostly grade 1 to 2, reversible, and manageable without permanent discontinuation. Grade ≥3 keratopathy (31.6%) was comparable with historical rates despite the less frequent dosing. Other adverse events, including hematologic and gastrointestinal toxicities, were manageable and consistent with known profiles of KRd or belamaf. The combination demonstrated deep and durable responses, including in patients at high-risk and with lenalidomide maintenance dose-refractory disease. These results support the feasibility of KRd-b with extended-interval belamaf and warrant further evaluation in phase 2 trials to confirm its clinical benefit in RRMM. This trial is registered at www.clinicaltrials.gov as NCT04822337.
13 May 2026
Read appraisal →Annals of medicine
Ceftriaxone for methicillin-susceptible Staphylococcus aureus bloodstream infections is associated with increased short-term mortality: a systematic review and meta-analysis
BACKGROUND: Bloodstream infections (BSIs) by methicillin-susceptible Staphylococcus aureus (MSSA) are a significant cause of morbidity and mortality, traditionally treated with antistaphylococcal penicillins (ASPs) or cefazolin. Ceftriaxone has emerged as an alternative due to its once-daily dosing regimen and favourable safety profile; however, its efficacy compared to the standard of care (SoC) remains controversial. This evidence synthesis aimed to assess the role of ceftriaxone in treating MSSA-BSIs. METHODS: A systematic literature search was conducted in PubMed, Embase, and Scopus up to December 31, 2025 (PROSPERO protocol CRD42024595748). Studies comparing ceftriaxone to ASPs or cefazolin for MSSA-BSIs were included. Primary outcomes were 30-day and 90-day all-cause mortality . Pooled effect sizes with their 95% confidence intervals (CIs), were calculated using random-effects models, odds ratios (ORs) and mean differences (MDs) according to the type of outcome. RESULTS: Eleven studies totalling 2,568 patients were included. Ceftriaxone was associated with significantly increased 30-day mortality (OR 3.33; 95% CI: 2.17-5.10), although differences at 90 days were not significant (OR 1.71; 95% CI: 0.75-3.90). No significant differences were noted for clinical success (OR 0.49; 95% CI: 0.19-1.26), microbiological clearance (OR 1.66; 95% CI: 0.73-3.82). Adverse event rates were similar between groups. CONCLUSION: Given the availability of various alternatives and the consistent short-term mortality signal observed, routine use of ceftriaxone for MSSA-BSIs, especially as initial therapy, is not supported by current evidence. Only novel findings from randomized studies may change the place in therapy of the drug in this context.
13 May 2026
Read appraisal →Lancet (London, England)
Enpatoran, a Toll-like receptor 7/8 inhibitor, in moderate-to-severe systemic lupus erythematosus: findings from Cohort B of a multicentre, international, double-blind, placebo-controlled dose-finding phase 2 trial
BACKGROUND: Toll-like receptors (TLR) 7 and 8 (TLR7/8) are activators of innate and adaptive immunity contributing to lupus pathogenesis. In Cohort B of WILLOW, a phase 2, randomised, placebo-controlled, double-blind, basket, dose-finding study, enpatoran, an oral small molecule inhibitor of TLR7/8, was evaluated in participants with active systemic lupus erythematosus (SLE). METHODS: Participants were eligible if they were aged 18-75 years with moderate-to-severe SLE, with or without cutaneous manifestations, had a disease duration of at least 6 months, and were receiving a stable dose of medication before the screening period. Participants were recruited from 132 centres in 22 countries. In Part 1, participants were randomly allocated in a 1:2 ratio to receive either placebo or 100 mg enpatoran, both twice-daily. Following the enrolment of 60 participants, Part 2 was activated and additional participants were randomly allocated in a 1:1:1:1 ratio to 25 mg, 50 mg, or 100 mg of enpatoran or placebo, all twice-daily, for 24 weeks. Random allocation was stratified by region, biomarker status, and hybrid Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index score. The primary objective was to evaluate the dose-response relationship of enpatoran, using British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rate at week 24, based on multiple comparison procedure-modelling analysis. Study visits were scheduled from week 0 to week 24, followed by a 2-week safety follow-up period for participants who chose not to enter the long-term extension. From weeks 2 to 12, glucocorticoid doses were tapered to a prednisone-equivalent dose of no more than 5 mg/day, as clinically tolerated. Adverse events were monitored continuously throughout the study; safety parameters (including physical examination, vital signs, and routine chemistry and haematology) were assessed at all study visits. The trial was registered at ClinicalTrials.gov (NCT05162586) and a long-term extension study is ongoing. FINDINGS: Between May 4, 2022, and Feb 6, 2024, participants were screened for eligibility for WILLOW cohorts A and B; 715 participants were screened and 354 were randomly allocated and included in the Cohort B safety population (95 to placebo, 71 to 25 mg enpatoran, 74 to 50 mg enpatoran, and 114 to 100 mg enpatoran). One patient allocated to the placebo group was found to be ineligible and was excluded from the full analysis set for the efficacy analyses. 335 (95%) of 353 participants were female, 18 (5%) were male, and median age was 41 years (IQR 33-51). At week 24, the study did not meet its primary objective of identifying a statistically significant dose-response relationship for enpatoran in BICLA response rate (p=0·14). BICLA response rates at week 24 were higher with all doses of enpatoran (25 mg: 41 [58%] of 71; odds ratio [OR] vs placebo 2·2 [95% CI 1·1-4·0], 50 mg: 36 [49%] of 74; OR 1·5 [95% CI 0·8-2·8], and 100 mg: 56 [49%] of 114; OR 1·6 [95% CI 0·9-2·8]) versus placebo (37 [39%] of 94). The most common treatment-emergent adverse event was diarrhoea, in four (6%) of 71, two (3%) of 74, and two (2%) of 114 participants in the 25 mg, 50 mg, and 100 mg enpatoran groups, respectively, and seven (7%) of 95 participants in the placebo group. Serious adverse events were reported in one (1%) of 71, three (4%) of 74, five (4%) of 114, and three (3%) of 95 participants treated with 25 mg, 50 mg, and 100 mg enpatoran and placebo, respectively. INTERPRETATION: In this study of participants with moderate-to-severe SLE, enpatoran improved BICLA response rates versus placebo; however, the primary objective of a statistically significant dose-dependent effect on disease activity based on BICLA response was not met. Enpatoran was well tolerated across all dose groups. FUNDING: Merck Healthcare (Darmstadt, Germany).
13 May 2026
Read appraisal →PloS one
Machine learning-based model for predicting recanalization in isolated distal deep vein thrombosis and analysis of predictors
BACKGROUND: Isolated distal deep vein thrombosis (IDDVT) is common, yet tools for predicting poor recanalization remain limited. We aimed to develop and compare machine learning models for predicting poor recanalization in patients with IDDVT and to identify the most informative predictors. METHODS: A total of 1600 patients with IDDVT were retrospectively enrolled. The dataset was randomly divided into a development set (n = 1280) and an independent test set (n = 320) using stratified sampling. Six predictive models were developed and compared: logistic regression (LR), support vector machine (SVM), random forest (RF), multilayer perceptron (MLP), extreme gradient boosting (XGBoost), and a Voting Ensemble. Model training and hyperparameter tuning were performed in the development set using five-fold stratified cross-validation, and optimal classification thresholds were determined using the Youden index. Model performance was evaluated by discrimination, calibration, and classification metrics, with 95% confidence intervals estimated by bootstrap resampling (10,000 iterations). SHAP analysis was applied to interpret the final model. RESULTS: In the independent test set, all models showed acceptable to strong discrimination, with AUC values ranging from 0.808 to 0.908. XGBoost achieved the best overall performance, with an optimal threshold of 0.183, an AUC of 0.908 (95% CI, 0.855-0.952), a Brier score of 0.077 (95% CI, 0.058-0.096), an accuracy of 0.900 (95% CI, 0.866-0.931), a precision of 0.650 (95% CI, 0.529-0.767), a recall of 0.803 (95% CI, 0.686-0.906), an F1-score of 0.717 (95% CI, 0.615-0.806), and a specificity of 0.918 (95% CI, 0.884-0.950). The calibration intercept and slope of the XGBoost model were 0.149 (95% CI, -0.192 to 0.454) and 1.410 (95% CI, 1.098-1.809), respectively, indicating acceptable overall calibration. SHAP analysis identified D-dimer rate, provoking-factor-related variables, anticoagulant use, and age group as the most influential predictors. CONCLUSION: Among six candidate models, XGBoost showed the best overall performance for predicting poor recanalization in patients with IDDVT. This study establishes an interpretable machine learning-based prediction framework focused specifically on poor recanalization in IDDVT and highlights the contribution of dynamic laboratory information, particularly D-dimer rate. The model may support early risk stratification and individualized follow-up planning, but external validation is required before routine clinical implementation.
13 May 2026
Read appraisal →PloS one
Systematic evaluation of the DeepSeek large language model for clinical diagnostic reasoning
BACKGROUND: Artificial intelligence (AI) is undergoing an era of transformative advancement, particularly through the emergence of Transformer-based large language models (LLMs). While these systems demonstrate strong reasoning and generalization capabilities, their clinical applicability, particularly in emergency and critical care decision-making, remains underexplored.. In time-sensitive settings, diagnostic reasoning must align rigorously with evidence-based standards and ensure the relevance of timing to clinical decisions. OBJECTIVE: This study aims to provide a preliminary evaluation of the decision-support performance of the DeepSeek model in acute medical scenarios. We systematically evaluate its diagnostic reasoning, temporal consistency of recommendations, and adherence to evidence-based critical care protocols using standardized case-based assessments. METHODS: Twenty-nine representative clinical cases were extracted from the Merck Manual of Diagnosis and Therapy, a widely used medical reference providing standardized case descriptions. The model's outputs were evaluated across four decision-making dimensions: differential diagnosis, diagnostic testing, final diagnosis, and management planning. Human raters scored each response for accuracy, and multivariable linear regression was applied to assess associations between performance and case parameters (age, gender, and Rapid Emergency Medicine Score [REMS]). RESULTS: DeepSeek achieved an overall mean accuracy of 82.9% (95% CI: 80.2-85.6%) across all cases. Accuracy peaked in final diagnosis (97.7%), but declined in differential diagnosis (73.0%). Model performance showed no significant variation across demographic or severity strata. CONCLUSIONS: DeepSeek shows promising performance in structured case-based diagnostic tasks, particularly in confirmatory diagnostic reasoning. However, its early-stage reasoning and handling of ambiguous cases require enhancement. Future studies using larger and more diverse clinical datasets are needed to further evaluate the model's robustness and potential clinical applicability.
13 May 2026
Read appraisal →BMJ open
Understanding patient preferences, experiences and engagement with ambulatory heart rhythm monitoring: a scoping review.
OBJECTIVE: To review the literature reporting patient preferences for ambulatory heart rhythm monitoring (AHRM) and what factors affect experience and engagement. BACKGROUND: The prevalence of arrhythmia continues to rise and contributes significantly to outpatient care burden. There is limited understanding of patient experience and compliance with monitoring. As innovative technologies are developed and healthcare strategies move towards surveillance and prevention, understanding this is key. METHODS: A scoping review was conducted using guidance from the Joanna Briggs Institute and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. The review included studies of adults under investigation or surveillance for arrhythmia with a range of devices (Holter monitor, patch device, event recorder, mobile cardiac telemetry, external and implantable loop recorders, wearables and other implantable cardiac devices) in ambulatory care settings worldwide. The final search was conducted on 3 January 2026 across Medline (PubMed), Embase (Ovid), Web of Science (Clarivate Analytics), Cumulative Index to Nursing and Allied Health Literature (EBSCOhost), PsycINFO (Ovid) and Google Scholar. Quantitative, qualitative, mixed methods, multiple methods and any type of review articles were included. RESULTS: 54 studies were eligible for inclusion from the initial search that identified 1320 articles. Two overarching themes emerged from the quantitative and qualitative data: patient factors and device factors affecting experience and engagement. Patient factors included clinical and demographic factors, education and expectations, experience and preferences and impact on daily life and healthcare. Device factors could be common to several devices, for example, skin irritation or device specific, for example, the nature of activation. CONCLUSION: Patient and device factors influence preferences for and experience and engagement with AHRM. While existing literature is incomplete and heterogeneous, it identifies key considerations that should be integrated into the development and testing of novel approaches for arrhythmia surveillance in healthcare contexts. REGISTRATION: https://doi.org/10.17605/OSF.IO/6K3W8 (Open Science Framework).
12 May 2026
Read appraisal →Palliative & supportive care
Manic and hypomanic states in cancer patients: A systematic review
OBJECTIVES: While there have been reports on the relationship between cancer and depression, reports on the association between cancer and manic states, a reciprocal state of depression, have been relatively few. Therefore, we conducted a systematic review on the relationships between cancer and manic states, focusing on their etiology, clinical course, and impact on cancer treatments. METHODS: A systematic review was conducted using four electronic databases, following the PRISMA guidelines. The scope of the study included research on manic or hypomanic states associated with cancer in patients with no prior history of mental illness, published from 1950 to August, 2021. The study protocol was registered with PROSPERO (CRD42020182372). RESULTS: Fifty-six studies, including 67 cases, were identified. The etiology of manic states in cancer patients was classified into organic, drug-induced, and psychogenic, with steroids being the most predominant causative agent. Approximately half of the patients discontinued cancer treatment following the onset of manic states. This was associated with a low rate of pharmacological treatment during the acute and maintenance phase of mania. The onset of manic states was most frequent during cancer treatment; however, about 15% of the cases exhibit manic symptoms before cancer diagnosis. SIGNIFICANCE OF RESULTS: This systematic review illustrated the clinical characteristics of manic state regarding differences in the etiology, timing of onset, pharmacological treatments, duration to remission, recurrence, and impact on cancer treatment. Manic states, which are comorbid with cancer, have significant clinical impacts on cancer prognosis. Therefore, appropriate pharmacological treatment for manic states is critical to consolidate appropriate cancer treatment. A substantial proportion of patients exhibit manic symptoms prior to the diagnosis of cancer, warranting further investigation into the possibility of the concept of "premonitory mania."
12 May 2026
Read appraisal →European journal of clinical pharmacology
Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on lipid profiles in patients with chronic kidney disease: a systematic review and meta-analysis
BACKGROUND: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel oral agents for treating anemia in chronic kidney disease (CKD), with potential effects on lipid modulation. We aimed to systematically evaluate the effects of HIF-PHIs on lipid profiles and cardiovascular outcomes in CKD patients. MATERIALS AND METHODS: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase (Ovid) were searched for randomized controlled trials comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in dialysis-dependent (DD) or nondialysis-dependent (NDD) CKD patients. Primary outcomes included changes in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). Secondary outcomes included cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and all-cause mortality. RESULTS: A total of 20 trials involving 12,155 patients were analyzed in this review. Roxadustat significantly reduced LDL-C (mean difference [MD], -16.07 mg/dL; 95% CI, -17.92 to -14.21; 14 randomized controlled trials [RCTs], 10,510 patients), total cholesterol (MD, -25.25 mg/dL; 95% CI, -29.70 to -20.81; 10 RCTs, 5,538 patients), triglycerides (MD, -19.70 mg/dL; 95% CI, -30.78 to -8.61; 9 RCTs, 4,616 patients), but also decreased HDL-C (MD, -4.91 mg/dL; 95% CI, -6.80 to -3.02; 9 RCTs, 5,132 patients). Desidustat significantly reduced LDL-C and total cholesterol, but showed no significant effects on triglycerides or HDL-C, whereas molidustat showed no significant lipid-lowering effects. Overall, treatment with HIF-PHIs was not associated with significant differences in cardiovascular death (RR, 1.00; 95% CI, 0.84 to 1.18; 10 RCTs, 9,371 patients), myocardial infarction (RR, 1.12; 95% CI, 0.90 to 1.38; 15 RCTs, 11,265 patients), stroke (RR, 1.18; 95% CI, 0.86 to 1.61; 14 RCTs, 11,136 patients), or all-cause mortality (RR, 1.06; 95% CI, 0.96 to 1.17; 19 RCTs, 11,903 patients), compared with ESAs or placebo. CONCLUSION: Roxadustat showed the most substantial lipid-lowering effects, while desidustat showed significant reductions in LDL-C and total cholesterol but no significant effects on triglycerides or HDL-C, and molidustat showed no significant effects. Despite these changes in lipid profiles, no significant differences in cardiovascular outcomes were observed for these three HIF-PHIs, compared with ESAs or placebo.
11 May 2026
Read appraisal →European heart journal
Cardiovascular benefit of continuous positive airway pressure according to high-risk obstructive sleep apnoea: a multi-trial analysis
BACKGROUND AND AIMS: Randomized trials of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnoea (OSA) in patients with cardiovascular disease have not detected reduced risk of major adverse cardiovascular and cerebrovascular events (MACCEs). This study tested whether the cardiovascular benefit of CPAP occurs preferentially in high-risk OSA, characterized by greater OSA-related heart rate acceleration or hypoxaemia. METHODS: In a post hoc analysis of pooled Randomized Intervention with Continuous Positive Airway Pressure in Coronary Artery Disease and Obstructive Sleep Apnoea, Impact of Continuous Positive Airway Pressure on Patients with Acute Coronary Syndrome and Nonsleepy Obstructive Sleep Apnoea, and Sleep Apnoea Cardiovascular Endpoints Study randomized trials; outcomes were stratified by high-risk OSA status, defined by heart rate response following OSA respiratory events >9.4 b.p.m. (third tertile) or oxygen desaturation area under baseline (hypoxic burden) > 87.1% min/h (third tertile). Cox mixed models quantified the CPAP treatment effect on MACCE (including cardiovascular mortality, myocardial infarction, and stroke) within high-risk OSA and the difference vs low-risk status (primary test). Secondary analyses examined participants without excessive sleepiness (Epworth <11 points) or without increased blood pressure (systolic/diastolic <140/90 mmHg). RESULTS: In 3549 participants, 16.6% and 16.3% reached the MACCE endpoint with CPAP (n = 1778) and usual care (n = 1771), respectively. The CPAP treatment effect was greater in participants with vs without high-risk OSA [interaction hazard ratio (iHR) .69, 95% confidence interval (CI) .50-.95, Pinteraction = .024; Nhigh-risk = 1832]. The differential effect was stronger in those without excessive sleepiness (iHR .59, 95% CI .41-.84; Nhigh-risk = 1509), or without increased blood pressure (iHR .54, 95% CI .36-.81; Nhigh-risk = 1244). Continuous positive airway pressure benefits in high-risk OSA were observed alongside harm in low-risk OSA. CONCLUSIONS: Continuous positive airway pressure preferentially improves cardiovascular outcomes in high-risk OSA, while harm in low-risk OSA may counteract this effect. These findings provide a pathway to identify patients likely to benefit.
11 May 2026
Read appraisal →European heart journal
Temporal modulation of antiplatelet therapy in high-risk patients undergoing complex percutaneous coronary intervention: the TAILORED-CHIP randomized clinical trial
BACKGROUND AND AIMS: Limited data exist on optimal antiplatelet strategies for high-risk patients undergoing complex percutaneous coronary intervention (PCI). This study aimed to investigate the efficacy and safety of tailored antiplatelet treatment with temporal modulation of the intensity of platelet inhibition in patients undergoing complex high-risk PCI. METHODS: We randomly assigned 2018 patients with high-risk anatomical or clinical characteristics undergoing complex PCI to a tailored antiplatelet strategy with early escalation (low-dose ticagrelor at 60 mg twice daily plus aspirin <6 months) and late de-escalation (clopidogrel monotherapy >6 months) or dual antiplatelet therapy (clopidogrel plus aspirin for 12 months). The primary outcome was a composite of death from any cause, myocardial infarction, stroke, stent thrombosis, unplanned urgent revascularization, and clinically relevant bleeding (Bleeding Academic Research Consortium Type 2, 3, or 5) at 12 months. RESULTS: The mean age was 64.0 years, 22.6% had left main PCI, 19.5% had complex bifurcation PCI, 84.1% had diffuse long lesions, 93.7% had multivessel PCI, and 36.7% had medically treated diabetes. At 12 months, a primary outcome event occurred in 105 patients (10.5%) assigned to tailored antiplatelet therapy and in 89 patients (8.8%) assigned to dual antiplatelet therapy [hazard ratio, 1.19; 95% confidence interval (CI), 0.90-1.58; P = .21]. The incidence of major ischaemic events appeared to be similar in both groups. The incidence of clinically relevant bleeding at 12 months was 7.2% in the tailored-therapy group and 4.8% in the dual-therapy group (difference, 2.45% points; 95% CI, 0.37-4.53). CONCLUSIONS: Among high-risk patients undergoing complex PCI, tailored antiplatelet strategy with early escalation and late de-escalation, as compared with dual antiplatelet therapy, did not decrease the incidence of primary net adverse events at 12 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03465644.
11 May 2026
Read appraisal →PloS one
Association between hemoglobin dynamic trajectories and 28-day mortality in elderly patients with sepsis: A retrospective cohort study using the MIMIC-IV database
BACKGROUND: Anemia is a common complication in sepsis and is associated with poor prognosis. However, there are few studies on the dynamic changes in hemoglobin (Hb) levels and their relationship with prognosis in elderly patients with sepsis. This study aims to retrospectively investigate the relationship between Hb trajectories and 28-day mortality in this population. METHODS: This retrospective observational study used data from 4,961 elderly patients with sepsis extracted from the MIMIC-IV database(2008-2019). Hb trajectories were identified using a Joint Latent Class Model (JLCM) for longitudinal pattern classification. Following validation of proportional hazards assumptions (Schoenfeld residual test), we assessed the prognostic relationship between Hb trajectories and 28-day mortality using multivariable Cox regression models and Kaplan-Meier survival curves. Sensitivity analyses included sex-stratified multivariable Cox regression, subgroup analysis, and E-value assessment. RESULTS: Hb trajectories were classified into three patterns: Class 1 with persistently low levels, Class 2 with medium levels and a gradual decline, and Class 3 with a rapid decline from higher levels. Using Class 2 as the reference, multivariable Cox regression showed that Class 1 (HR = 1.38, 95% CI = 1.18-1.62, p < 0.001) and Class 3 (HR = 1.21, 95% CI = 1.03-1.42, p = 0.020) were associated with higher 28-day mortality. Kaplan-Meier curves indicated the lowest survival probability in Class 1 and the highest in Class 2. Gender-specific analysis revealed consistent trajectory patterns between males and females, but higher Hb values in males. The predictive power of the rapid decline pattern for early mortality was stronger in males. CONCLUSION: The Hb trajectories in elderly sepsis patients are significantly associated with early mortality. Persistently low levels and rapid declines in Hb are indicators of poor prognosis.
10 May 2026
Read appraisal →Palliative & supportive care
Definitional confusion in nurses' and physicians' attitudes toward euthanasia in India: A systematic review and meta-analysis
INTRODUCTION: In India, the term euthanasia is frequently used to describe a wide range of end-of-life practices, including withdrawal of life-sustaining treatment and administration of lethal drugs. Such usage diverges from more narrow definitions that restrict euthanasia to the intentional administration of lethal drugs. OBJECTIVES AND SIGNIFICANCE OF THE RESULTS: This systematic review and meta-analysis examines how euthanasia has been defined and operationalized in quantitative studies of Indian physicians' and nurses' attitudes, and estimates the prevalence of approval when euthanasia is defined narrowly. METHODS: Following PRISMA 2020 guidelines, searches were conducted in PubMed, EMBASE, PsycINFO, and CINAHL for studies published from 2010 onward. Two investigators independently screened studies, extracted data, and assessed risk of bias using the Mixed Methods Appraisal Tool (MMAT). Studies were included in the meta-analysis only if they reported attitudes toward euthanasia as narrowly defined. RESULTS: Nine studies met inclusion criteria for the systematic review. Definitions of euthanasia varied considerably, and several studies combined attitudes toward treatment withdrawal with attitudes toward the administration of lethal drugs. Four studies reporting on 519 nurses and physicians provided data suitable for meta-analysis. Approval of euthanasia, defined as the intentional administration of lethal drugs, ranged from 12% to 20%, with a pooled prevalence of 16% (95% confidence interval: 0.13-0.19). This prevalence is notably lower than in earlier reports on Indian healthcare professionals' attitudes. CONCLUSION: Definitional inconsistency substantially affects reported attitudes toward euthanasia in Indian research. When euthanasia is defined narrowly, approval among healthcare professionals is low and consistent across studies. These findings highlight the need for conceptual clarity in future research to support accurate interpretation of empirical data and to strengthen the contribution of studies on ethical attitudes to ethical and palliative care scholarship.
10 May 2026
Read appraisal →The Journal of dermatological treatment
A safety checklist before initiating second-generation immunomodulating drugs for inflammatory dermatoses: a systematic review
BACKGROUND/AIM: Second-generation immunomodulating drugs for inflammatory dermatoses have expanded over the past decades. Contraindications and special warnings must be considered before starting any treatment, but identifying all relevant safety information can be time-consuming. The objective is to provide an overview of contraindications, special warnings, and boxed warnings with the aim to establish a safety checklist, covering second-generation immunomodulatory therapies. METHODS: We identified contraindications, special warnings and boxed warnings provided by the European Medicines Agency and the US Food and Drug Administration, for second-generation immunomodulating drugs approved for inflammatory dermatoses. Both topical and systemic therapies were included. RESULTS: Most drug classes had warnings related to infections. Herpes zoster was listed for anti-CD20, IL-12/23i, INFi, JAKi and TYK2i, where hepatitis reactivation was reported for anti-CD20, TNFi, IL-17i, anti-BAFF, JAKi and TYK2i. Malignancy risk including skin cancer was mentioned for most classes, except IL-23i, IL-17i, IL-13i, IL-4/13i, IL-31i, IL-36i and PDE4i. Other serious warnings included neurological, cardiovascular, thrombotic, hepatic, renal, gastrointestinal, and psychiatric adverse events. CONCLUSION: This work provides a simple stepwise approach to managing contraindications and special warnings. Our safety checklist gives clinicians a rapid overview of contraindications, special warnings, and boxed warnings for the available drug classes approved for inflammatory dermatoses.
10 May 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Modified Frailty Index-11 (mFI-11) measured frailty as a predictor of post-transplant outcomes in non-Hodgkin's lymphoma patients undergoing hematopoietic stem cell transplantation: a retrospective analysis of National Inpatient Sample database
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a critical treatment for non-Hodgkin lymphoma (NHL) but involves significant post-transplant risks. Frailty, measured by the Modified Frailty Index-11 (mFI-11), may influence outcomes. METHODS: We analyzed NHL patients undergoing autologous or allogeneic HSCT from the Nationwide Inpatient Sample (2016-2020). Frailty was defined by mFI-11, and outcomes included in-hospital mortality, unfavorable discharge, prolonged length of stay (LOS), complications, and costs. Multivariable regression models with stratification by age and Charlson Comorbidity Index were applied. RESULTS: Of 2807 patients (ages 18-85), frail patients were older and had more comorbidities. In autologous HSCT, frailty was linked to higher mortality (2.02% vs. 0.27%, p < 0.001), increased unfavorable discharges (19.75% vs. 10.80%, p < 0.0001), and prolonged LOS (15.92% vs. 7.75%, p < 0.0001). Similar trends were observed in the allogeneic cohort. CONCLUSIONS: Frailty predicts worse post-transplant outcomes in NHL patients undergoing HSCT, emphasizing the need for pre-transplant frailty screening.
10 May 2026
Read appraisal →European journal of heart failure
Efficacy of finerenone in patients with heart failure and mildly reduced or preserved ejection fraction: a prespecified analysis of heart rate and heart rhythm in the FINEARTS-HF trial
AIMS: The association between heart rate (HR) and clinical outcomes is well understood in patients with heart failure with reduced ejection fraction (HFrEF) but less clear in those with HFmrEF/HFpEF, especially among individuals with atrial fibrillation (AF). In a prespecified analysis of the FINEARTS-HF trial, we examined the association between baseline HR and clinical outcomes by heart rhythm and evaluated finerenone's effect across the spectrum of HR. METHODS: The primary outcome was a composite of cardiovascular death and total (first and recurrent) HF events. Heart rhythm (sinus rhythm or AF) was determined from the baseline ECG. Patients with pacemaker rhythm or missing HR/rhythm data were excluded. RESULTS: Among patients with sinus rhythm (SR n = 3497; 62%), higher baseline HR was associated with a higher incidence rate for the primary outcome. In patients with AF (n = 2190; 38%), no association between HR and outcomes was observed. The effect of finerenone on the primary outcome was consistent across the HR spectrum, regardless of rhythm (P for interaction = 0.96 in SR; 0.49 in AF). In patients with SR, there was no significant HR change with finerenone versus placebo. In AF patients, finerenone led to a small but statistically significant HR reduction: a placebo-corrected decrease of 1.35 bpm (95% CI: 0.41-2.29) from baseline to 12 months. CONCLUSIONS: Among patients with HFpEF/HFmrEF in FINEARTS-HF, higher baseline HR was associated with a higher risk of the primary outcome in patients with SR but not in those with AF. Finerenone's effect on the primary outcome was consistent across the HR spectrum, irrespective of rhythm. TRIAL REGISTRATION: ClinicalTrials.gov NCT04435626.
10 May 2026
Read appraisal →Annals of hematology
Hematologic and molecular response to ropeginterferon alfa-2b in patients with polycythemia vera: a systematic review and meta-analysis
Ropeginterferon alfa-2b is an interferon used in the treatment of myeloproliferative neoplasms, particularly polycythemia vera. Its efficacy in achieving hematologic and molecular responses has been demonstrated in clinical trials, but pooled data on long-term outcomes and sustained response remain limited. This systematic review and meta-analysis aimed to evaluate the hematologic and molecular response over 36 months. PubMed, Scopus, Science Direct, and Google Scholar databases were searched to identify studies reporting hematologic and molecular responses to ropeginterferon alfa-2b. Studies were included if they provided data on complete hematologic response (CHR) and JAK2V617F variant allele frequency (VAF) reduction. Pooled proportions and mean reductions were calculated using random-effects models. The pooled proportion of CHR increased progressively from 0.19 (95% CI: 0.04-0.57) at 3 months to 0.73 (95% CI: 0.17-0.97) at 36 months. Molecular response, measured by VAF reduction, deepened over time from - 7.33 (95% CI: -9.85 to -4.81) at 3 months to -54.90 (95% CI: -65.61 to -43.99) at 36 months. Subgroup analyses revealed significant variability in response rates, particularly in early follow-up periods. Ropeginterferon alfa-2b achieves significant and sustained hematologic and molecular responses over 36 months. This makes it a promising treatment for polycythemia vera. While variability in early responses needs further investigation, the sustained long-term efficacy compared to hydroxyurea supports its use in clinical practice. Future studies should focus on identifying predictors of response and optimizing treatment protocols to maximize patient outcomes.
10 May 2026
Read appraisal →European journal of heart failure
Erythropoiesis-stimulating agents to reduce heart failure hospitalization: a systematic review and meta-analysis
AIMS: Anaemia is common in patients with chronic heart failure (CHF), worsening functional status and prognosis. The role of erythropoiesis-stimulating agents (ESAs) to reduce hospitalization remains unclear. METHODS AND RESULTS: A pre-registered systematic search was performed of randomized controlled trials in adults with CHF and anaemia, comparing any ESA at any dose versus placebo or no treatment.Fourteen trials were included with 3128 participants, with moderate quality of evidence for most outcomes and variable risk of bias. Meta-analysis during 5604 person-years of follow-up demonstrated no significant difference in first CHF hospitalization comparing ESAs with control: Peto odds ratio (OR) 0.93, 95% CI 0.78-1.10, P = .37; trial heterogeneity I2 = 36%. ESAs significantly reduced total CHF hospitalization with 622 events/2698 person-years, compared with 761/2914 person-years for control: incidence rate ratio 0.81, 95% CI 0.73 to 0.90, P < .001; no heterogeneity between trials, I2 = 0%. There were no significant differences between treatment groups for all-cause mortality (OR 1.01, 95% CI 0.86-1.18, P = .88; I2 = 35%) or incident adverse events. Patients randomized to ESAs increased their haemoglobin level [mean difference (MD) 1.6 g/dL compared with control, 95% CI 1.6-1.7, P < .001] and exercise tolerance (MD 69 metres, 95% CI 17-122, P = .009), with lower NYHA class on follow-up (MD -0.73 class, 95% CI -1.11 to -0.36, P < .001). CONCLUSION: ESA treatment in patients with CHF and mild anaemia can reduce recurrent CHF hospitalization and improve functional capacity, without any impact on adverse events. Including ESAs in CHF management could be considered in patients with anaemia at high risk of recurrent hospital admissions.
10 May 2026
Read appraisal →European journal of heart failure
The efficacy and safety of qiliqiangxin according to baseline ejection fraction in patients with heart failure and reduced ejection fraction in QUEST.
AIMS: Qiliqiangxin (QLQX), a Chinese traditional medicine, improved outcomes in patients with heart failure and reduced ejection fraction (HFrEF) when added to guideline-directed therapy. As treatment effects in heart failure (HF) may vary with left ventricular ejection fraction (LVEF), this post hoc analysis of the QUEST (Qiliqiangxin in Heart Failure: Assessment of Reduction in Mortality) trial examined whether baseline LVEF modified the efficacy and safety of QLQX. METHODS: QUEST randomized 3110 patients with symptomatic HF and LVEF ≤40%. The primary outcome was cardiovascular death or first HF hospitalization. Baseline LVEF was categorized as ≤25% (n = 482), >25-30% (n = 692), >30-35% (n = 829), and >35% (n = 1107). RESULTS: Mean LVEF was 32% (median 33%, interquartile range 28%-37%). Patients with LVEF ≤25% had the highest rate of the primary outcome (25.4 per 100 patient-years), while rates were similar across higher LVEF groups (18.7-19.8). After multivariable adjustment, lower LVEF was independently associated with higher risks of the primary outcome and mortality. The effect of QLQX on the primary outcome was consistent across LVEF categories (hazard ratio [95% CI] from the lowest to highest: 0.91 [0.64-1.30], 0.65 [0.47-0.89], 0.94 [0.71-1.26], and 0.71 [0.55-0.91], respectively; Pinteraction = .28), and as a continuous variable (Pinteraction = .45). Similar results were observed for individual components and total HF hospitalizations (all Pinteraction > .10). The safety of QLQX was also consistent across LVEF categories. CONCLUSION: In patients with HFrEF, lower LVEF was associated with worse cardiovascular outcomes. QLQX reduced cardiovascular events consistently across the range of LVEF examined in QUEST, despite the limited use of sodium-glucose co-transporter 2 inhibitors. CHICTR REGISTRATION: ChiCTR1900021929.
10 May 2026
Read appraisal →Clinical oral investigations
Does endodontic treatment modify serum inflammatory markers of cardiovascular risk in individuals with asymptomatic apical periodontitis? a systematic review and meta-analysis.
OBJECTIVE: Plasma inflammatory biomarkers linked to cardiovascular risk have been associated with asymptomatic apical periodontitis. However, it remains unclear whether endodontic treatment can reverse these alterations. This review evaluated the effect of endodontic treatment on inflammatory markers in individuals with asymptomatic apical periodontitis. MATERIALS AND METHODS: A comprehensive search was conducted in PubMed/Medline, Embase, Web of Science, Scopus, VHL, gray literature, and reference lists between October and November 2022, with an update in September 2025. Risk of bias was assessed using the Newcastle-Ottawa Scale, and the certainty of evidence using the GRADE approach. Random-effects meta-analysis estimated pooled mean differences (MD) and 95% confidence intervals (95%CI) for serum inflammatory markers concentrations between treated individuals and controls (α = 5%). RESULTS: The search identified 6,295 records; sixteen studies were assessed and eight included in the quantitative synthesis. All studies showed moderate risk of bias, and evidence certainty was very low. Meta-analysis suggested possible reductions in C-reactive protein (CRP) [MD = 0.76 (95% CI: - 0.15, 1.67)] , interleukin-6 (IL-6) [MD = 0.81 (95% CI:-0.27, 1.90)], and tumor necrosis factor-alpha (TNF-α) [MD = 1.04 (95% CI:-0.38, 2.46)] after endodontic treatment, with levels similar to control groups. CONCLUSION: Evidence, although limited, suggests endodontic treatment may lower serum CRP, IL-6, and TNF-α levels in asymptomatic apical periodontitis patients. CLINICAL RELEVANCE: Endodontic treatment of asymptomatic apical periodontitis may help reduce systemic inflammatory biomarkers associated with cardiovascular risk, reinforcing its potential role beyond local infection control.
10 May 2026
Read appraisal →Science (New York, N.Y.)
Performance of a large language model on the reasoning tasks of a physician.
More than 65 years ago, complex clinical diagnostic reasoning cases were introduced as the gold standard for the evaluation of expert medical computing systems, a standard that has held ever since. In this study, we report the results of a physician evaluation of a large language model (LLM) on challenging clinical cases across five experiments with a baseline of hundreds of physicians. We then report a real-world study comparing human expert and artificial intelligence (AI) second opinions in randomly selected patients in the emergency room of a major tertiary academic medical center. In all experiments, the LLM outperformed physician baselines and displayed continued improvement from prior generations of AI clinical decision support. Our study suggests that LLMs have eclipsed most benchmarks of clinical reasoning, motivating the urgent need for prospective trials.
5 May 2026
Read appraisal →Journal of advanced research
Flexible wearable medical devices: from material innovations and data processing to intelligent healthcare applications
BACKGROUND: Flexible wearable medical devices drive healthcare transformation via non-invasive, real-time physiological monitoring and personalized management. Traditional rigid devices lack long-term comfort, while chronic disease care and telemedicine demand reliable, patient-centered solutions. Advances in materials (carbon nanomaterials, liquid metals, hydrogels) enable stretchable, biocompatible substrates adapting to bodily movements. Innovative sensing (PPG, EEG, sweat-based detection) tracks blood pressure, glucose, and neural signals accurately. Key challenges include insufficient sensor flexibility, lagging supervision, data security issues, and large-scale production difficulties, requiring interdisciplinary collaboration. AIM OF REVIEW: This review integrates cutting-edge advances in flexible wearable medical devices, covering material innovations, sensing breakthroughs, power management, and AI-driven data analysis. It evaluates strategies to enhance biocompatibility of carbon composites, liquid metals, and hydrogels, analyzing improvements in device sensitivity, biocompatibility, and real-world applicability. It critically discusses machine learning's role and limitations in chronic disease management, telemedicine, and sports optimization. Key unresolved challenges include lagging regulations, privacy risks in multi-source data fusion, mismatched sensing development, and large-scale production difficulties. The aim is to provide a scalable, secure, and clinically translatable roadmap for future research. KEY SCIENTIFIC CONCEPTS OF REVIEW: Core technologies involve carbon nanomaterials (e.g., graphene), liquid metals (structurally optimized for balanced conductivity and flexibility), and hydrogels (preferred as flexible substrates for mimicking natural soft tissues' mechanics and biocompatibility). Sensing technologies (PPG, EEG, sweat-based detection) enable non-invasive, real-time monitoring of vital parameters like blood pressure, glucose, and neural signals. AI decodes complex physiological data for predictive diagnosis, while IoT/5G integration advances telemedicine. Current limitations include poor sensor flexibility, lagging regulations, and large-scale production hurdles, contrasting with trends like advanced sensing, new materials, and hybrid diagnostic-therapeutic systems-highlighting flexible wearables' potential in intelligent healthcare.
5 May 2026
Read appraisal →IEEE transactions on bio-medical engineering
Extending Multiscale Characterization of Heart Rate Variability via Deep Learning for Mortality Risk Prediction
OBJECTIVE: To improve mortality risk prediction from heart rate variability (HRV) signals by capturing nonlinear scaling patterns often overlooked by traditional linear analyses. METHODS: This study combines detrended moving average (DMA) analysis with convolutional neural networks (CNNs). DMA curves were computed from 2-hour overlapping windows of 24-hour Holter ECG recordings in 916 survivors and 70 nonsurvivors. A CNN was trained to extract features from these curves and benchmarked against models using traditional HRV and clinical features. RESULTS: The CNN achieved an ROC-AUC of 0.72 and an adjusted hazard ratio of 2.129 for daytime recordings, outperforming standard models. Two patient groups emerged based on DMA scaling patterns. Group 1, with dominant short-term scaling, exhibited reduced slopes in nonsurvivors, suggesting impaired autonomic adaptability. Group 2 showed earlier transitions between short- and long-term behavior, where reduced long-term slopes more strongly predicted mortality. Integrated gradients analysis identified key timescales in the DMA curve driving model predictions. CONCLUSION: DMA combined with CNNs enhances HRV-based mortality risk stratification and reveals distinct physiological scaling patterns associated with survival outcomes. SIGNIFICANCE: This study highlights the potential of DMA and CNNs in improving mortality risk stratification and providing mechanistic insights into HRV dynamics, with implications for personalized health monitoring.
4 May 2026
Read appraisal →FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Lysosomal Membrane Proteins: Key Regulators of Glucose Metabolism and Its Associated Diseases
Glucose homeostasis, which is critical for maintaining energy supply and health, involves glycogen metabolism, glycolysis, and gluconeogenesis. Lysosomal membrane proteins (LMPs) play core roles in regulating these processes. However, no focused systematic review of the topic has been reported. This review provides an in-depth analysis of the central roles of LMPs in glucose metabolism, focusing on the regulation of glucose homeostasis and their potential effects on metabolic diseases through the regulation of autophagy, signaling networks, specialized transporter functions, and other relevant mechanisms. In general, LMPs play core roles in lysosomal biosynthesis, and an in-depth study of their relationship with glucose metabolism could significantly highlight the important contribution of lysosomes in the development of related diseases.
3 May 2026
Read appraisal →Polish archives of internal medicine
Systematic review and meta-analysis of the safety and efficacy of transvenous lead extraction in octogenarian patients
INTRODUCTION: As the global population ages and the use of cardiac implantable electronic devices (CIEDs) increases, transvenous lead extraction (TLE) is being performed more frequently in elderly patients. Concerns remain regarding its safety and efficacy in octogenarians, and age‑specific recommendations are limited. OBJECTIVES: We aimed to assess procedural success, complication rates, and mortality associated with TLE in patients aged 80 years or older in comparison with younger individuals. PATIENTS AND METHODS: A systematic search of PubMed, Cochrane CENTRAL, SciELO, and ScienceDirect was conducted up to December 2024. Studies reporting TLE outcomes in octogenarians and younger patients were included according to predefined criteria. A meta‑analysis was performed to compare procedural success, complications, and mortality between the age groups. RESULTS: Seventeen studies including 15 984 patients were analyzed. Complete lead extraction success was 96.7% in octogenarians and 96.2% in the patients aged below 80 years. No significant differences were observed in major or minor procedural complications. In‑hospital mortality was low and comparable between the groups. Although long‑term mortality was higher in the octogenarians, this reflected greater baseline comorbidity and frailty rather than increased procedural risk. None of the included studies demonstrated higher periprocedural danger of TLE in elderly patients. CONCLUSIONS: TLE is safe and effective in patients aged 80 years and older, with outcomes comparable to younger individuals. Advanced age alone should not preclude referral for lead extraction.
3 May 2026
Read appraisal →Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Bacterial quantitation in clinical infection: a systematic review
Pivotal clinical studies of new anti-infective drugs enrol patients with strictly defined clinical syndromes, with clinical and laboratory endpoints used to define treatment success. Assessing bacterial killing in the host by serial quantitation has potential as a more efficient pharmacometric approach to assess antibiotic efficacy. We conducted a systematic review of the use of bacterial quantitation in clinical infection. The main syndromes studied in the 222 included articles were bacteraemia, chronic respiratory disease, diarrhoea, pneumonia and sexually transmitted infections. Most reports (135 articles, 61%) quantified bacterial load in different specimen types using quantitative polymerase chain reaction (qPCR). For bacteraemias, bacterial DNA load measured in whole blood by qPCR at clinical presentation was typically 2-3 log10 copies ml-1, usually substantially higher than the estimates from quantitative culture. Higher bacterial loads were associated with increased mortality in 28 of 35 studies. Faster bacterial clearance was correlated with appropriate antibiotic therapy and improved outcome in the majority of studies. Most studies sampled too infrequently for accurate characterization of bacterial clearance rates. The rate of bacterial clearance from blood or other compartments is an informative pharmacodynamic endpoint in the assessment of antibacterial therapeutic effects, but standardized approaches to assessment are needed based on optimal study design. This article is part of the Theo Murphy meeting issue 'Evaluating anti-infective drugs'.
3 May 2026
Read appraisal →Journal of the American College of Cardiology
Intravascular Imaging- vs Angiography-Guided Complex PCI: 5-Year Outcomes From a Randomized Trial
BACKGROUND: Data regarding long-term outcomes of intravascular imaging-guided percutaneous coronary intervention (PCI) for complex coronary artery lesions, compared with angiography-guided PCI, remain limited. OBJECTIVES: The authors sought to present long-term clinical outcomes of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. METHODS: Eligible patients with complex coronary artery lesions were randomly assigned 2:1 to undergo intravascular imaging-guided PCI or angiography-guided PCI in this prospective multicenter open-label superiority trial performed in South Korea. The primary endpoint was a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: A total of 1,639 patients underwent randomization with 1,092 assigned to imaging-guided PCI and 547 assigned to angiography-guided PCI. At a median follow-up of 5.3 years (Q1-Q3: 4.4-6.2 years), the primary endpoint occurred in 109 of 1,092 patients (10.5%) in the intravascular imaging-guided PCI group and 78 of 547 patients (14.9%) in the angiography-guided PCI group (HR: 0.68; 95% CI: 0.51-0.91; P = 0.009). Cardiac death or target vessel-related myocardial infarction occurred in 78 patients (7.6%) in the intravascular imaging-guided PCI group and in 56 patients (10.7%) in the angiography-guided PCI group, clinically driven target vessel revascularization in 45 (4.4%) and 32 (6.2%), and definite stent thrombosis in 1 (0.1%) and 4 (0.7%), respectively. There were no apparent differences in procedure-related safety events between the groups. CONCLUSIONS: In patients with complex coronary artery lesions undergoing PCI, intravascular imaging guidance reduced the risk of a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization at median follow-up of 5.3 years, compared to angiography guidance. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention for Complex Coronary Artery Disease [RENOVATE-COMPLEX-PCI]; NCT03381872).
3 May 2026
Read appraisal →Current allergy and asthma reports
Interception of Regulatory RNAs on TGF-β Signaling in the Pathogenesis of Idiopathic Pulmonary Fibrosis: A Systematic Review
PURPOSE OF REVIEW: Idiopathic Pulmonary Fibrosis is a type of interstitial lung disease characterized by lung scarring due to excessive extracellular matrix (ECM) deposition. The transforming growth factor-beta (TGF-β) signaling pathway is the master regulator of fibrosis, driving myofibroblast activation and differentiation, epithelial-mesenchymal transition (EMT), and inhibition of ECM degradation. While individual classes of non-coding RNAs (ncRNAs) have been studied in IPF, a comprehensive understanding of how microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (LncRNAs) collectively regulate canonical TGF-β signaling remains lacking. Addressing this gap, this systematic review was conducted which presents current evidence on the integrated roles of ncRNAs in modulating TGF-β signaling in IPF pathogenesis. RECENT FINDINGS: A comprehensive search of PubMed and Web of Science databases (2015-2025), identified 45 eligible studies. miRNAs (19 antifibrotic, 11 profibrotic) directly targeted the core components of the TGF-β signaling pathway, whereas circRNAs (5 antifibrotic, 5 profibrotic) and LncRNAs (6 profibrotic) acted as competing endogenous RNAs and sponged their target miRNAs. Notably, all identified LncRNAs were profibrotic, amplifying the fibrotic signaling pathway. We found that ncRNAs critically fine-tune TGF-β signaling at multiple regulatory nodes, including ligand activation, receptor expression, Smad protein phosphorylation, nuclear translocation, and inhibitory feedback mechanism. The ncRNA-mediated regulatory mechanisms provide valuable insight into IPF pathogenesis and may help identify potential biomarkers and therapeutic targets. Future efforts should prioritize validating in vitro and animal model data in human samples, integrating regulatory network analysis, in vivo functional validation of RNA-based therapeutics, and exploring therapeutic delivery systems to develop an effective ncRNA-based antifibrotic therapy.
3 May 2026
Read appraisal →Biomedizinische Technik. Biomedical engineering
Blood pressure estimation using single photoplethysmography signal based on ResNet-BiGRU
OBJECTIVES: Conventional cuff-based blood pressure (BP) measurement provides only intermittent readings, whereas photoplethysmography (PPG)-based methods enable continuous and noninvasive monitoring. This study aims to develop a deep learning framework for accurate, cuffless BP estimation using a single PPG signal. METHODS: A hybrid deep neural network, termed ResNet-BiGRU, was developed by integrating residual convolutional blocks with bidirectional gated recurrent units to jointly capture morphological and temporal features. The UCI Cuff-Less Blood Pressure Estimation Dataset (a subset of MIMIC-II), which contains synchronized PPG and arterial blood pressure (ABP) signals from 942 subjects, was used for model training and validation. After applying a 0.5-8 Hz bandpass filter and segmenting into 5 s windows, the data were split 80/20 for training and validation. External evaluation was conducted using the VitalDB dataset, which provides synchronized PPG and ABP recordings from surgical patients under diverse physiological conditions. RESULTS: The model achieved mean absolute errors (MAE) of 4.78 mmHg for systolic BP (SBP) and 2.98 mmHg for diastolic BP (DBP) on UCI, and 8.15 mmHg for SBP and 4.59 mmHg for DBP on VitalDB. CONCLUSIONS: The ResNet-BiGRU model demonstrates accurate, robust, and generalizable cuffless BP estimation, showing strong potential for wearable health monitoring applications.
28 Apr 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Cardiac adverse events associated with axitinib: A real-world pharmacovigilance study based on the Japanese adverse drug event report database
OBJECTIVE: To evaluate the disproportionality, times to onset, and outcomes of cardiac adverse events (AEs) associated with axitinib, using data from the Japanese Adverse Drug Event Report (JADER) database. METHODS: We analyzed data for the period from April 2004 to December 2024. Those on cardiac AEs were extracted and the disproportionality of axitinib-associated AEs was assessed by calculating reporting odds ratios (RORs). RESULTS: Of the 2,988,681 reports with sex and age information, we identified 4788 reports of AEs associated with axitinib, including 508 cardiac AEs. Signals were detected for 16 cardiac AEs after adjustment for sex and age. Fatal outcomes were reported for five of these events with particularly high rates observed for cardiac failure, myocarditis, and immune-mediated myocarditis. Median times to onset indicated that cardiac AEs associated with axitinib occurred 14 to 420 days after administration. Weibull distributions showed that seven AEs (blood pressure increased, myocardial infarction, acute myocardial infarction, blood pressure systolic increased, oedema peripheral, oedema, and generalised oedema) occurred constantly throughout the exposure period (random failure type), and stress cardiomyopathy and immune-mediated myocarditis developed in a dose-dependent manner (wear-out failure-type). CONCLUSIONS: We focused on cardiac AEs associated with axitinib as post-marketing AEs. Some with fatal outcomes may occur not only early in treatment but also later in the course. Continuous monitoring is essential to ensure timely detection and management of these potentially serious AEs in clinical practice.
28 Apr 2026
Read appraisal →PloS one
Effects of a spore-forming probiotic blend on bowel habits and physical well-being in adults with functional constipation: A randomized, double-blind, placebo-controlled trial
We aimed to evaluate the efficacy and safety of a spore-forming probiotic blend containing Clostridium butyricum IDCC 1301, Weizmannia coagulans IDCC 1201, and Bacillus subtilis IDCC 1101 for improving bowel function and well-being in adults with functional constipation (FC). In a randomized, double-blind, placebo-controlled trial, 78 adults with FC (Rome IV criteria) received either probiotic blend (n = 40) or placebo (n = 38) daily for 4 weeks. Primary outcomes were changes in weekly spontaneous bowel movements (WSBM) and stool form. Secondary outcomes included physical functioning scores from the 36-Item Short Form Health Survey. The probiotic blend group showed significant improvements in irritant bowel movements (p = 0.0458), incomplete evacuation (p = 0.0374), and abdominal pain before defecation (p = 0.0090). Stool consistency shifted toward normal types (Bristol types 3-4, p = 0.0176). Physical functioning improved only in the probiotic blend group (p = 0.0300). Probiotic blend effectively alleviated symptoms of FC and improved physical well-being. Trial registration: Clinical Research Information Service (CRIS), KCT0010085.
28 Apr 2026
Read appraisal →Heart (British Cardiac Society)
Revascularisation strategies for non-acute myocardial ischaemic syndromes
BACKGROUND: Contemporary guidelines by the European Society for Cardiology and American College of Cardiology/American Heart Association for the treatment of non-acute myocardial ischaemic syndromes dispute the value of revascularisation and differ in their recommendation to perform revascularisation. A Bayesian network meta-analysis was performed, evaluating the strength of evidence for the comparative incremental effectiveness of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) over medical therapy on long-term outcomes. METHODS: A hierarchical Bayesian network meta-analysis was designed (PROSPERO CRD42024541215, date 20 May 2024), including randomised controlled trials (RCTs) published between 2005 and 10 June 2025, which consisted of three initial treatment modalities: optimal medical therapy (OMT), PCI+OMT and CABG+OMT. The primary outcome was all-cause mortality at maximum follow-up; secondary outcomes were trates of the rates of myocardial infarction, stroke and re-revascularisation at maximum follow-up, expressed in HRs and 95% credible intervals (CrIs), accompanied by surface under the cumulative ranking curve (SUCRA) scores. RESULTS: 10 RCTs, comprising 10 742 patients, were included. For all-cause mortality, the estimated median HR of CABG+OMT versus OMT was 0.84 (95% CrI 0.68-1.07); the HR of PCI+OMT versus OMT was 0.93 (0.79-1.16); and the HR of CABG+OMT versus PCI+OMT was 0.91 (0.71-1.13). The SUCRAs of a CABG+OMT strategy ranking as the optimal revascularisation treatment regarding mortality, myocardial infarction, stroke and re-revascularisation were 88.1%, 99.7%, 17.5% and 99.5%, respectively. Results were consistent across sensitivity analyses, including in the node-splitting models. CONCLUSIONS: This Bayesian network meta-analysis found that an initial CABG (+OMT) revascularisation strategy was associated with higher probabilities of optimal outcomes, with the exception of stroke, compared with an initial PCI (+OMT) revascularisation strategy, although CrIs overlapped, suggesting that some uncertainty remains. PROSPERO REGISTRATION NUMBER: CRD42024541215.
27 Apr 2026
Read appraisal →Open heart
Relative apical sparing of left ventricular longitudinal strain for the diagnosis of cardiac amyloidosis: a systematic review and meta-analysis
BACKGROUND: Cardiac amyloidosis (CA) is underdiagnosed due to non-specific clinical and echocardiographic features. This systematic review and meta-analysis evaluated the diagnostic accuracy of the left ventricular relative apical sparing (RELAPS) pattern on speckle-tracking echocardiography. METHODS: A literature search of PubMed, Scopus and Cochrane was conducted through August 2025. RELAPS was defined as the average apical longitudinal strain divided by the sum of average basal and average middle left ventricular longitudinal strains. Diagnostic accuracy was assessed using a bivariate random-effects model. Subgroup analyses by CA subtype and echocardiogram software, and meta-regression for clinical variables, were performed. Optimal cut-offs were determined by maximising the Youden index. Analyses were conducted in R V.4.4.1. RESULTS: Forty-one studies (3473 CA; 4525 comparators) were included. Pooled analysis yielded an area under the receiver operating characteristic curve (AUC-ROC) of 0.818, with sensitivity 65.9% (95% CIs 59.2% to 72.0%) and specificity 83.1% (CI 78.5% to 86.8%). The diagnostic oods ratio (DOR) was 9.54 (CI 7.41 to 12.10). In subtype analyses, immunoglobulin light chains (AL-CA) showed AUC-ROC 0.876, sensitivity 59.8% (CI 41.1% to 76.0%) and specificity 92.7% (CI 83.6% to 96.9%); transthyretin (ATTR-CA) showed AUC-ROC 0.822, sensitivity 63.8% (CI 51.2% to 74.8%) and specificity 84.4% (CI 76.7% to 89.9%), with no significant differences between subtypes (sensitivity p=0.760; specificity p=0.172). Three echocardiography software systems were evaluated. GE EchoPAC (26 studies) achieved an AUC-ROC of 0.822 (sensitivity 70.4% (CI 64.1% to 76.0%), specificity 81.2% (CI 75.7% to 85.7%)). Philips QLAB (four studies) performed comparably (AUC-ROC 0.904; sensitivity 67.6% (CI 31.2% to 90.6%), specificity 92.7% (CI 73.6% to 98.3%)). In contrast, TomTec (four studies) had an AUC-ROC of 0.806, but its sensitivity (31.1% (CI 9.4% to 66.3%)) was significantly lower than GE EchoPAC's (p<0.001), despite a similar specificity (93.6% (CI 78.8% to 98.3%)). CONCLUSION: RELAPS provides moderate diagnostic accuracy for identifying CA, with good specificity and modest sensitivity. Performance varies by analysis software and threshold, underscoring the need for standardised measurement and prespecified cut-offs.
27 Apr 2026
Read appraisal →JMIR medical informatics
Deep Learning Model Using Transfer Learning for Detecting Left Ventricular Systolic Dysfunction: Retrospective Algorithm Development and Validation Study
BACKGROUND: Artificial intelligence-augmented electrocardiogram (AI-ECG) models for detecting left ventricular systolic dysfunction (LVSD) often exhibit degraded performance in patients with comorbidities. OBJECTIVE: This study aimed to introduce and validate a recalibration method using longitudinal patient data to enhance prediction accuracy and simulate its clinical utility for ongoing monitoring. METHODS: We conducted a multicenter, retrospective cohort study using data from 2 hospitals in Korea. A dataset of paired transthoracic echocardiograms (TTEs) and electrocardiograms (ECGs) matched within a 2-week interval was constructed, separating pairs into baseline (first for each patient) and follow-up assessments. In addition to conventional supervised learning, we developed a patient-wise recalibration strategy that incorporated historical left ventricular ejection fraction measurements and prior AI-ECG outputs to adjust for future predictions, thus empirically mitigating confounding effects. Pretraining was also implemented to enhance the model's performance. RESULTS: The recalibrated 12-lead DeepECG LVSD model achieved an area under the receiver operating curve of 0.956 (95% CI 0.946-0.965) for internal validation and 0.940 (95% CI 0.936-0.945) for external validation of follow-up TTE-ECG pairs. The uncalibrated 12-lead DeepECG LVSD model also showed modest performance, with an area under the receiver operating curve of 0.953 (95% CI 0.941-0.965) in the internal validation and 0.947 (95% CI 0.943-0.951) in the external validation when tested on baseline TTE-ECG pairs. Recalibration yielded statistically significant improvements in the 12-lead DeepECG LVSD models (P<.001), with enhanced and more balanced performance across all clinical subgroups. CONCLUSIONS: Patient-wise recalibration improved accuracy and consistency across various comorbidities by mitigating performance degradation and bias. This broadens the application of AI-ECG for LVSD detection from low-risk screening to high-risk longitudinal monitoring.
27 Apr 2026
Read appraisal →European journal of hospital pharmacy : science and practice
Algorithm-managed dosing and pharmacist-managed dosing of erythropoietin stimulating agents in renal anaemia: a systematic review
OBJECTIVES: The goal of this systematic review was to identify and summarise algorithm-managed and pharmacist-managed dosing of erythropoietin stimulating agents (ESA) in patients with renal anaemia and to determine the effects on available outcome parameters. METHODS: We followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines for systematic reviews. Studies investigating algorithm-managed and pharmacist-managed dosing of ESA in adult patients with renal anaemia were evaluated for inclusion. No restrictions were set on outcome parameters. Observational and interventional studies available as full-text articles with a control group and follow-up ≥6 months were eligible for inclusion. Relevant databases were searched from their inception through August 2024. Two independent reviewers evaluated all studies. The risk of bias was assessed by the ROBINS-I and RoB1 tools. The protocol of this study was registered in PROSPERO (CRD42021243678). RESULTS: After screening 140 articles, 17 articles and 4313 patients could be included. Available evidence was of low to moderate quality with a high risk of bias. Data were summarised and tabulated. Meta-analysis was not possible due to the substantial heterogeneity in participants, study design, interventions, comparisons, and outcome parameters. However, standardised metrics could be identified and calculated for haemoglobin and ESA dose. The percentage in target range for haemoglobin varied between 3.5% lower (95% CI -18.67% to +11.67%) to 32.0% higher (95% CI 14.07% to 49.93%) in the pharmacist-managed group versus the control group (n=1401). The range in reduction in ESA dose was 5.45% (95% CI -7.97% to +18.87%) to 49.97% (95% CI 20.32% to 79.61%) in the pharmacist-managed group versus the control group (n=2115). CONCLUSION: Low-quality data with high risk of bias suggest that pharmacist-managed renal anaemia may improve the percentage of haemoglobin within target range and reduce the ESA dose. However, meta-analysis was impossible due to substantial heterogeneity. Therefore, no definite conclusions could be drawn on the effectiveness of pharmacist-managed dosing of ESA in renal anaemia. PROSPERO REGISTRATION NUMBER: CRD42021243678.
26 Apr 2026
Read appraisal →Renal failure
Dapagliflozin improves hemoglobin and anemia in chronic kidney disease: a systematic review and meta-analysis
Anemia becomes increasingly prevalent as kidney function declines. Current treatments carry multiple safety risks. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), dapagliflozin, have emerged as background anemia modulator, a promising alternative, showing protective effects against anemia. This study synthesizes evidence on dapagliflozin's potential to improve anemia in chronic kidney disease (CKD) patients. A systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, including eight studies identified from six databases. Risk of bias was assessed using tools appropriate for each study design (RoB 2, NOS, JBI). Data were pooled using a random-effects model with RevMan 5.4. The primary analysis for hemoglobin demonstrated significant increase (MD = 4.37; 95% CI = 0.71-8.03; p = 0.02) and remained significant in the sensitivity analysis (MD = 4.11; 95% CI = 0.19-8.04; p = 0.04). A sensitivity analysis for hematocrit revealed a highly significant increase (MD = 2.15; 95% CI = 1.86-2.44; p < 0.00001). In the sensitivity analysis for adverse events dapagliflozin significantly reduced the overall risk (RR = 0.77; 95% CI = 0.59-0.99; p = 0.04). This finding was associated with significantly lower mortality (RR = 0.67; p = 0.02), while no significant differences were observed for cardiovascular (p = 0.22) or genitourinary events (p = 0.70). Dapagliflozin is associated with clinically meaningful improvements in hemoglobin and anemia outcomes in CKD. These findings suggest a potential erythropoietic benefit beyond glycemic control, although dedicated anemia-focused trials are needed to confirm clinical applicability.
25 Apr 2026
Read appraisal →Nutricion hospitalaria
Refeeding syndrome ‒ What we know and what remains to be explored.
Background: refeeding syndrome (RS) is a serious metabolic complication that occurs upon reintroducing nutrition to malnourished individuals. Although formally recognized for more than 70 years, significant gaps in its understanding remain. Objective: to conduct a narrative review on the current state of knowledge regarding RS, its recent advances, existing gaps, and future perspectives. Methods: an integrative review was conducted using articles published between 2000 and 2024 from international databases, following a systematic methodology of literature search, selection, and analysis. Results: the main pathophysiological mechanisms of RS, its multisystemic clinical manifestations, current diagnostic criteria, and risk-based therapeutic strategies were identified. Despite advances in biomarkers and personalized nutrition, challenges remain in early diagnosis, prevention, and treatment, especially in vulnerable populations. Conclusions: RS continues to pose a complex clinical challenge that requires standardized protocols, identification of reliable biomarkers, and increased clinical research, particularly in underrepresented regions such as Latin America. Prevention, based on a multidisciplinary approach, is important to reducing its impact. Introducción: el síndrome de realimentación (SR) es una complicación metabólica grave que ocurre tras reintroducir la nutrición en personas desnutridas. Aunque formalmente reconocido desde hace más de 70 años, aún existen importantes lagunas en su comprensión. Objetivo: realizar una revisión narrativa sobre el estado actual del conocimiento del SR, sus avances recientes, las brechas existentes y las perspectivas futuras. Métodos: se realizó una revisión integrativa de artículos publicados entre 2000 y 2024 en bases de datos internacionales, siguiendo una metodología sistemática de búsqueda, selección y análisis de la literatura. Resultados: se identificaron los principales mecanismos fisiopatológicos del SR, sus manifestaciones clínicas multisistémicas, los criterios diagnósticos actuales y las estrategias terapéuticas basadas en el riesgo. A pesar de los avances en términos de biomarcadores y nutrición personalizada, persisten desafíos en el diagnóstico precoz, la prevención y el tratamiento, especialmente en las poblaciones vulnerables. Conclusiones: el SR sigue siendo un reto clínico complejo que exige protocolos estandarizados, identificación de biomarcadores fiables y una mayor investigación clínica, especialmente en regiones poco estudiadas como América Latina. La prevención basada en un enfoque multidisciplinario es clave para reducir su impacto.
25 Apr 2026
Read appraisal →BMJ open diabetes research & care
Sex differences in glycemic outcomes: a systematic review and meta-analysis of diabetes treatments
UNLABELLED: Sex differences in glycemic outcomes following insulin therapy remain underexplored despite biological and psychosocial factors that may influence individual responses. This systematic review examines sex-specific differences in glycemic control to guide personalized diabetes care and promote health equity. We searched PubMed, Scopus, Cochrane Library, and Google Scholar (August 2014-December 2025) for randomized and observational studies involving adults of both sexes on insulin. Twenty-four studies were included, with certainty of evidence assessed using GRADE. In type 1 diabetes, women showed no significant difference in achieving HbA1c <7% (RR 1.05, 95% CI 0.91 to 1.22; very low certainty) and toward higher time-in-range (SMD 0.78, -0.01 to 1.57; moderate certainty). In type 2 diabetes, men were more likely to achieve HbA1c targets (RR 0.86, 95% CI 0.72 to 1.03; low certainty), while women required higher weight-adjusted insulin doses (SMD 0.55, 0.23 to 0.86; very low certainty). Hypoglycemia risk showed opposing trends in inpatient (RR 0.78, 95% CI 0.33 to 1.83; very low certainty) versus outpatient settings (RR 1.08, 95% CI 0.61 to 1.89; low certainty) with substantial heterogeneity (I2>70%). These findings suggest that sex-related differences in glycemic outcomes vary by diabetes type and treatment context. Given the low certainty and heterogeneity of current evidence, results should be interpreted as hypothesis-generating. This review supports the consideration of biological sex within a broader, individualized diabetes management framework and highlights the need for future sex-stratified analyses with rigorous control of lifestyle and physiological factors. INTRODUCTION: Sex differences in glycemic outcomes following the same insulin therapy in diabetes remain underexplored. Numerous factors, encompassing both biological and psychosocial aspects, could potentially influence individual responses to insulin therapy. This systematic review examines sex-specific differences in glycemic control to guide personalized diabetes care and promote health equity. METHODS: PubMed, Scopus, Cochrane Library, and Google Scholar were searched (August 1, 2014-December 31, 2025) for randomized and observational studies. Eligible studies included adults of both sexes on insulin reporting sex-specific data for predefined outcomes. Data on glycated hemoglobin (HbA1c), blood glucose metrics, hypoglycemia, and insulin dose were extracted. Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: Twenty-four studies were included. In type 1 diabetes, women showed no significant difference in achieving HbA1c <7% (risk ratio (RR) 1.05, 95% CI 0.91 to 1.22; very low certainty) and toward higher time-in-range (standardized mean difference (SMD) 0.78, -0.01 to 1.57; moderate certainty). In type 2 diabetes, men were more likely to achieve HbA1c targets (RR 0.86, 95% CI 0.72 to 1.03; low certainty), whereas women required higher weight-adjusted insulin doses (SMD 0.55, 0.23 to 0.86; very low certainty). Hypoglycemia risk showed opposing trends in inpatient (RR 0.78, 95% CI 0.33 to 1.83; very low certainty) versus outpatient settings (RR 1.08, 95% CI 0.61 to 1.89; low certainty), with substantial heterogeneity (I2 >70%). CONCLUSION: Sex-related differences in glycemic outcomes under insulin therapy were observed, with patterns varying by diabetes type, treatment context, and outcome. Given the low certainty and heterogeneity of the evidence, these findings should be interpreted as hypothesis-generating rather than directive for clinical practice. The results support consideration of biological sex as one component within a broader, individualized diabetes management framework. Future studies should prioritize sex-stratified analyses with rigorous control of polypharmacy, body composition, and lifestyle factors to determine whether sex-specific insulin strategies provide meaningful clinical benefit. PROSPERO REGISTRATION NUMBER: CRD420251144696.
25 Apr 2026
Read appraisal →Cell reports. Medicine
A metabolite-augmented FIB-4 machine learning panel achieves superior liver fibrosis staging in chronic liver disease
Accurate, non-invasive liver fibrosis detection is essential for chronic liver disease management, particularly with rising metabolic dysfunction-associated liver disease (MASLD) and chronic hepatitis B (CHB). While the Fibrosis-4 (FIB-4) index is widely used, its performance for advanced fibrosis is limited. We develop Met-FIB using metabolomics and machine learning, integrating FIB-4 parameters (age, aspartate aminotransferase, alanine aminotransferase, and platelet count) with tyrosine and taurocholic acid identified in a CHB discovery cohort (n = 3,251). Validation includes one CHB cohort (n = 729) and two MASLD cohorts (n = 149, n = 155). Met-FIB outperforms FIB-4, FibroScan, and other serum markers across all fibrosis stages. In CHB, Met-FIB achieves 96.3% rule-out sensitivity and 85.4% rule-in specificity for significant fibrosis, with rule-in specificity reaching 98.6% and 98.8% for advanced fibrosis and cirrhosis. In MASLD, corresponding values are 93.9% and 90.2% for significant fibrosis, with >97.9% specificity for late-stage disease. Met-FIB demonstrates clinical utility for non-invasive fibrosis staging across diverse etiologies.
25 Apr 2026
Read appraisal →Renal failure
Explainable machine learning integrating bioelectrical impedance for 6-month cardiovascular risk in peritoneal dialysis
Peritoneal dialysis (PD) is a common treatment for end-stage renal disease, yet cardiovascular disease (CVD) remains a major cause of morbidity. Inadequate fluid management can elevate CVD risk, and bioelectrical impedance spectroscopy (BIS) is increasingly used to assess fluid status. This study aimed to develop an artificial intelligence model integrating BIS measurements and medical history to predict major adverse cardiovascular events (MACEs) within six months in clinically stable PD patients. Data were stratified by MACE occurrence and subject, with 80% assigned to training and 20% to testing. Class imbalance was addressed using the synthetic minority over-sampling technique. Four algorithms - logistic regression, random forest, XGBoost, and deep neural networks - were trained using fivefold cross-validation and grid search for optimal hyperparameters. Model performance was evaluated with area under the ROC curve (AUC), calibration plots, and decision curve analysis (DCA). Feature ablation experiments compared models using all 15 features, only 11 BIS-recorded features, and only 4 medical history features. The random forest model achieved the highest performance (AUC = 0.88), with CVD history as the most influential predictor. Isotonic regression calibration improved probability alignment (brier score = 0.0451). DCA suggested potential clinical benefit. While the model relied on four medical history features, its initial sensitivity was modest (0.68). Integrating BIS features significantly enhanced diagnostic sensitivity (0.84). The random forest model, based on 15 clinically accessible features, accurately predicts the risk of MACE within six months in clinically stable PD patients, demonstrating strong discriminatory ability with a performance reaching 88%.
24 Apr 2026
Read appraisal →European heart journal
Predictors of recurrent venous thromboembolism and bleeding in patients with cancer: a meta-analysis
BACKGROUND AND AIMS: Patients with cancer and venous thromboembolism (VTE) have a high risk of recurrent VTE and anticoagulant-related bleeding. This study aimed to identify prognostic factors for these complications. METHODS: A systematic review was performed for randomized trials and cohort studies evaluating prognostic factors for recurrent VTE or anticoagulant-related bleeding in adult patients with cancer and VTE. Adjusted hazard ratios (aHRs) for factors were pooled using random-effects meta-analysis. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: Thirty-three studies (n = 96 753) were included in the meta-analyses. Factors with high certainty of association with increased risk of recurrent VTE included a previous history of VTE [aHR 1.50 (95% CI 1.08-2.09)], Eastern Cooperative Oncology Group (ECOG) performance status >0 [1.81 (1.34-2.46)] or >1 [2.44 (1.55-3.84)], advanced cancer [1.38 (1.15-1.65)], and specific cancer sites including lung [1.78 (1.29-2.46)], hepatobiliary [2.37 (1.70-3.30)], pancreas [3.20 (2.06-4.96)], and genitourinary [1.38 (1.14-1.67)]. Conversely, recent surgery [aHR 0.56 (95% CI 0.40-0.76)] and breast cancer [0.43 (0.23-0.81)] had a high certainty of association with a decreased risk. Factors with a high certainty of association with an increased risk of anticoagulant-related bleeding included a history of bleeding [aHR 2.41 (95% CI 1.50-3.88)], ECOG performance status ≥2 [2.10 (1.48-2.99)], advanced cancer [1.60 (1.29-1.97)], and cancers of the brain [2.25 (1.64-3.09)], gastrointestinal system [1.74 (1.44-2.11)], genitourinary system [1.90 (1.48-2.45)], and prostate [1.72 (1.26-2.34)]. CONCLUSIONS: The prognostic factors identified in this meta-analysis should be considered as part of risk stratification frameworks for anticoagulation management in patients with cancer and VTE.
24 Apr 2026
Read appraisal →Renal failure
Decoding the renal-cochlear axis: explainable machine learning and phenotype clustering reveal high-risk hearing loss subtypes in CKD
This study develops a dual-level machine learning framework for risk stratification and phenotyping of hearing loss (HL) in patients with chronic kidney disease (CKD) using data from the National Health and Nutrition Examination Survey (NHANES). From a cohort of 3,402 CKD patients, feature selection via univariate and multivariate logistic regression identified key predictors, which were used to construct predictive models with nine machine learning algorithms. The eXtreme Gradient Boosting (XGBoost) model demonstrated superior performance, with mean area under the curve (AUC) values of 0.984 (training), 0.984 (validation), and 0.939 (testing). SHapley Additive exPlanations (SHAP) interpretation identified age as the predominant risk determinant. Subsequent Gaussian mixture modeling (GMM) clustered patients into two distinct subtypes: a low-risk subgroup (n = 1,075) with a 1.58% HL prevalence and a high-risk subgroup (n = 2,316) characterized by older age, elevated blood urea nitrogen and bicarbonate levels, and a 48.2% HL prevalence. A classifier trained on these subtypes achieved discrimination (AUC = 0.99974). A clinically a web-based tool was also developed based on the six most influential features. The findings establish a dual-level predictive framework integrating explainable ML and unsupervised clustering for HL risk assessment in CKD. This approach provides a robust strategy for the precision screening of high-risk subpopulations and supports the integration of hearing assessments into routine CKD.
24 Apr 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Secukinumab in Moderate-to-Severe Graves Orbitopathy: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study
CONTEXT: Interleukin (IL)-17, a key proinflammatory cytokine, drives inflammation and fibrosis in Graves orbitopathy (GO), and elevated IL-17 and Th17 cells correlate with disease activity and severity. OBJECTIVE: The ORBIT study aimed to evaluate the efficacy and safety of secukinumab, an IL-17A inhibitor, in individuals with active, moderate-to-severe GO. METHODS: A randomized, double-blind, placebo-controlled, parallel-group, multicenter trial was conducted. Adults with active, moderate-to-severe, non-sight-threatening GO randomly (1:1) received secukinumab 300 mg or placebo subcutaneously over a 16-week double-blind treatment period, followed by an additional 16-week open-label treatment phase for proptosis nonresponders. Safety parameters, thyroid-related hormones, and autoantibodies were also assessed. The primary end point was overall response of reduced Clinical Activity Score (CAS) of 2 or more points and a reduction of 2 mm or greater in proptosis from baseline without worsening in the fellow eye at week 16. RESULTS: Twenty-eight adult GO patients with a CAS of 4 or greater were enrolled (secukinumab, n = 14; placebo, n = 14). None in either the secukinumab or placebo group achieved an overall response at weeks 16 and 32, respectively, when all patients received open-label secukinumab. No clinically meaningful changes were observed in ophthalmic symptoms and signs, proptosis, lid aperture, eye muscle motility, CAS, and health-related quality of life either at week 16 or week 32. No meaningful effect on serum levels of thyroid-related hormones and antibodies was observed. Secukinumab was well tolerated, with mostly mild adverse events. Neither treatment-induced study discontinuation nor new safety signals were registered. CONCLUSION: Secukinumab did not show clinical efficacy vs placebo when treating patients with active, moderate-to-severe GO.
24 Apr 2026
Read appraisal →Annals of medicine
The effect of nutrition education interventions on dialysis patients' outcomes: a systematic review and meta-analysis
BACKGROUND: Non-adherence to dietary and fluid restrictions among dialysis patients is associated with adverse clinical outcomes. Quantifying the effectiveness of nutrition education interventions can inform practice and policy. METHODS: We searched MEDLINE, EMBASE, CINAHL, CENTRAL, PsycINFO, Web of Science, and Scopus up to 15 July 2025, supplemented by trial registries and Google Scholar, with an updated search through 8 April 2026. Eligible studies included randomized and non-randomized trials evaluating nutritional education interventions in adult dialysis populations. Risk of bias was assessed using RoB-2 and ROBINS-I, certainty graded using GRADE, and random-effects meta-analyses conducted alongside subgroup, sensitivity, and meta-regression analyses. Publication bias was assessed with Egger and Begg tests and trim-and-fill where applicable. RESULTS: Forty-four studies comprising 4,106 participants were included. Nutrition education significantly improved knowledge (SMD = 1.09; 95% CI: 0.67-1.51) and health-related quality of life (SMD = 1.43; 95% CI: 0.86-2.00; I² = 0%), and reduced serum potassium (SMD = -0.52; 95% CI: -0.91 to -0.14; I² = 92%) and serum phosphate (SMD = -0.35; 95% CI: -0.56 to -0.15; I² = 81%). Results for albumin, creatinine, sodium, calcium, and BUN were inconsistent and non-significant. Most outcomes were rated low or very low certainty by GRADE, reflecting inconsistency, indirectness, and imprecision. Potential publication bias was identified for certain outcomes. CONCLUSIONS: Nutrition education consistently improves knowledge and quality of life and may modestly reduce serum phosphate and potassium in dialysis patients. High-quality registered trials with standardized outcomes and longer follow-up are needed to establish effectiveness and sustainability. PROSPERO REGISTRATION: CRD420251119567.
24 Apr 2026
Read appraisal →European heart journal
Pre-treatment lysis time of plasma-derived fibrin clots and bleeding in patients on oral anticoagulants for atrial fibrillation in the ARISTOTLE trial
BACKGROUND AND AIMS: Oral anticoagulation reduces stroke risk in patients with atrial fibrillation (AF) but increases bleeding. Longer fibrin clot lysis time has been shown to predict adverse cardiovascular outcomes in acute coronary syndromes. This study explored relationships between fibrin clot lysis time at randomization and clinical outcomes in patients with AF enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in AF (ARISTOTLE) trial. METHODS: Plasma samples were obtained from anticoagulation-naïve participants, before initiation of study medication (n = 1841). Fibrin clot turbidimetry was performed, and lysis time determined. Associations between lysis time and characteristics, biomarkers, and on-treatment bleeding and cardiovascular events were assessed by lysis time quartile (Q1-4, shortest to longest). RESULTS: A shorter lysis time was associated with being older, male, permanent AF, lower body mass index, estimated glomerular filtration rate and C-reactive protein, and higher N-terminal pro-B-type natriuretic peptide. Major and clinically relevant non-major bleeding was significantly more frequent in lysis time Q1 vs. Q4 [6.3%/yr vs. 2.1%/yr; HR, 2.99 (95% CI, 1.75-5.12); P = .001], including after multifactorial adjustment [HR, 2.61 (1.45-4.69); P = .016]. Those in Q2 and Q3 had intermediate bleeding risk vs. Q4 [HR, 2.21 (1.27-3.87); 2.08 (1.18-3.66) respectively], suggesting a graduated effect. Treatment allocation to apixaban vs. warfarin did not affect the relationship between lysis time and bleeding (interaction-P = .80). There was no significant association between lysis time and a composite of cardiovascular death, stroke, systemic embolism or myocardial infarction. CONCLUSIONS: Shorter pre-treatment fibrin clot lysis time independently predicted higher bleeding risk in patients receiving oral anticoagulation for AF.
24 Apr 2026
Read appraisal →European heart journal
Venous thromboembolism and bleeding in cancer patients: role of inflammatory and cardiac biomarkers.
BACKGROUND AND AIMS: Patients with cancer have increased risk of venous thromboembolism (VTE) and bleeding. Inflammatory and cardiac biomarkers may predict these complications, but their role remains unclear. This study examined associations between two inflammatory-related markers (C-reactive protein and growth differentiation factor-15) and two cardiac markers [N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T (hs-TnT)] with VTE and clinically relevant bleeding in cancer patients. METHODS: A post hoc analysis of the AVERT trial, which evaluated apixaban for VTE prevention in ambulatory cancer patients with a Khorana score of ≥2, was performed. Biomarkers were measured at baseline and 1 month, with C-reactive protein also at 3 months. Fine and Gray regression, accounting for competing risk of death and adjusted for age and advanced cancer, estimated subdistribution hazard ratios (SHRs) for VTE and clinically relevant bleeding. RESULTS: Of 574 patients, 514 provided baseline samples. One- and 3-month samples were available from 454 and 447, and 378 and 364, patients without prior VTE and bleeding events, respectively. Elevated baseline growth differentiation factor-15 was associated with increased VTE risk [SHR 1.36, 95% confidence interval (CI) 1.01-1.84]. N-terminal pro-B-type natriuretic peptide (SHR 1.44, 95% CI 1.08-1.92) and C-reactive protein (SHR 1.38, 95% CI 1.07-1.76) were linked to bleeding risk. Increasing high-sensitivity troponin T from baseline to 1 month was associated with higher VTE risk (SHR 1.89, 95% CI 1.14-3.16). Nomograms were developed to estimate VTE and clinically relevant bleeding risks. CONCLUSIONS: Select inflammatory-related and cardiac markers were associated with VTE and bleeding risks in cancer patients, which can be determined using developed nomograms. Prospective research is needed to confirm these findings.
23 Apr 2026
Read appraisal →Journal of medical genetics
Clinically significant DNA variation from the GENCOV and HostSeq COVID-19 genome sequencing studies
BACKGROUND: Vast amounts of genome sequencing data generated from large-scale research studies like HostSeq provide an opportunity to summarise the spectrum of pathogenic variation in a subset of the Canadian population. Sharing variant-level data with public databases, like ClinVar, is crucial for advancing our understanding of genomic variants related to Mendelian diseases. However, such entries are often incomplete or contain discrepancies which render interpretation and classifications less useful. METHODS: The GENCOV and HostSeq cohorts were annotated and summarised using custom workflows to identify variants with a pathogenic and likely pathogenic (P/LP) classification in ClinVar. These variants were further filtered using custom gene panels, gnomAD frequency, variant type, gene-disease relationship and the number of reputable ClinVar laboratory submissions. Manually assessed variants from the GENCOV study were compared with ClinVar classifications to identify discrepancies. RESULTS: A total of 1956 unique variants were manually classified as P/LP through the GENCOV study. Of these, 65% (1276) were also identified in ClinVar, and among those, 69% (889) had concordant P/LP classifications. The manual assessment of unique exonic variants in GENCOV yielded a higher number of putative P/LP variants (1595), including truncating and missense variants compared with the 127 unique exonic P/LP variants in HostSeq. CONCLUSION: These results highlight that a large proportion of P/LP variation is either absent or has conflicting evidence for pathogenicity in ClinVar, emphasising the importance of periodic reassessment, discrepancy resolution and updates to ensure completeness and accuracy of public databases.
23 Apr 2026
Read appraisal →PloS one
Prevalence of antimicrobial resistance in Tanzania: A systematic review and meta-analysis
Antimicrobial resistance (AMR) threatens global health, and understanding resistance patterns aids in effective treatment and promotes responsible antimicrobial use. Despite the urgency of resistant pathogens, systematic reviews focusing specifically on Tanzania are limited, and while several studies report resistance patterns for individual pathogens, a consolidated analysis of overall prevalence is needed to inform policymaking and public health interventions. Therefore, this review and meta-analysis assessed the prevalence of antimicrobial resistance among clinically relevant pathogens in Tanzania, providing a comprehensive overview to support surveillance, infection control, and stewardship efforts. A total of 1865 studies identified from Google Scholar (1600), PubMed (13), and Science Direct (252) underwent screening and full article review. Finally, 28 studies were included. A subgroup analysis was performed to evaluate the resistance patterns within antibiotic classes for specific pathogens. Descriptive statistics were used to describe the characteristics of the studies, while the prevalence of antimicrobial resistance was estimated through Meta-analysis. Inconsistency and heterogeneity between studies were quantified by the I2 index. Among the included studies, most isolates (25.0%) were obtained from urine samples. Of these studies, 75% were cross-sectional studies and 92.9% were conducted in hospital settings. The analysis revealed high resistance to penicillin, particularly amoxicillin-clavulanic and ampicillin, with Klebsiella pneumoniae (0.96 [0.83-0.99]), Acinetobacter baumannii (0.94 [0.67-0.99]) and Escherichia coli (0.90 [0.81-0.95]). Similarly, erythromycin resistance was most prevalent in Campylobacter spp. (0.85 [0.80-0.89]). Ciprofloxacin resistance was highest in Acinetobacter baumannii (0.54 [0.33-0.73]), whereas amikacin resistance was highest in Proteus spp. (0.86 [0.35-0.99]). Ceftriaxone resistance was particularly high in Acinetobacter baumannii (0.91 [0.70-0.98]) and Pseudomonas aeruginosa (0.85 [0.74-0.92]). Meropenem resistance was lowest among Escherichia coli (0.04 [0.01-0.10]) and Klebsiella spp. (0.07 [0.03-0.15]), while the pooled resistance across ESKAPE-E pathogens was (0.11[0.06-0.19]). Imipenem and clindamycin each had an overall pooled resistance of (0.06[0.02-0.14]) against both Escherichia coli and Klebsiella pneumoniae. The findings highlight widespread resistance among bacterial pathogens, ESKAPE-E, particularly in the Access and Watch groups of antibiotics. The variability in resistance patterns underscores the need for the Ministry of Health to re-evaluate empirical treatment protocols (STG/NEMLIT) to ensure effective treatment regimens, strengthen antimicrobial stewardship, enhance surveillance systems, and promote rational antibiotic use.
23 Apr 2026
Read appraisal →Critical care explorations
The Effects of Conservative Fluid Management and Active Deresuscitation on Markers of Tissue Perfusion, Kidney Injury, and Vascular Injury in Critically Ill Adults: A Secondary Analysis of the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) Trial
OBJECTIVES: Test the hypothesis that conservative fluid management with active deresuscitation would not adversely affect tissue perfusion or kidney injury and would be associated with reduced vascular injury compared with usual care. DESIGN: Secondary analysis of the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) trial. SETTING: ICUs. PATIENTS OR SUBJECTS: Critically ill patients enrolled in the RADAR-2 trial. INTERVENTIONS: Conservative fluid management with active deresuscitation vs. usual care. MEASUREMENTS AND MAIN RESULTS: Measures of tissue hypoperfusion (whole blood lactate), acute kidney injury (AKIRisk score and urinary cystatin-C), and vascular injury (plasma hyaluronan, syndecan-1, and angiopoietin-2) were compared between groups. For each analyte, change from baseline was compared between groups and the median inter-group difference at each timepoint was estimated with bootstrapped CIs. Exploratory logistic regression examined associations between plasma biomarker levels (including N-terminal pro-B-type natriuretic peptide [NT-proBNP]), 28-day mortality, and treatment allocation. Whole blood lactate levels were similar between groups at all timepoints. Using change from baseline comparisons, no statistically detectable between-group differences were observed in AKIRisk scores or urinary cystatin-C levels. Plasma vascular injury biomarkers showed no statistically detectable between-group differences at any timepoint. High baseline hyaluronan (adjusted odds ratio [aOR], 5.75; 95% CI, 1.94-17.02; p = 0.002), syndecan-1 (aOR, 8.82; 95% CI, 2.67-29.15; p < 0.001), and NT-proBNP greater than 2500 pg/mL (aOR, 21.48; 95% CI, 3.57-129.41; p < 0.001) were independently associated with increased 28-day mortality. There was no evidence of differential treatment response based on these biomarker levels. CONCLUSIONS: Conservative fluid management and active deresuscitation were not associated with worsening tissue perfusion or acute kidney injury. A reduction in vascular injury markers was not observed. Given the modest sample size and resultant imprecision, clinically important effects cannot be excluded.
23 Apr 2026
Read appraisal →Circulation
Memantine for Premature Atrial Contractions: A Phase 2 Randomized Clinical Trial
BACKGROUND: Premature atrial contractions (PACs) are independently associated with atrial fibrillation, stroke, and heart failure, yet no pharmacological therapy is approved for PAC suppression. Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology. Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias. METHODS: We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Symptomatic adults with frequent PACs (≥1000/24 h) were randomly assigned to receive memantine or placebo for 6 weeks. The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment. The primary analysis was performed in the intention-to-treat population. Prespecified secondary end points included the responder rate (≥50% PAC reduction), percentage change in nonsustained atrial tachycardia burden, and cumulative incidence of new-onset atrial fibrillation. RESULTS: Among 241 patients included in the efficacy analysis, memantine resulted in a greater reduction in PAC count than placebo (between-group difference, 47.1 percentage points; P=0.0045). The responder rate was higher with memantine than with placebo (52.4% versus 23.1%; P<0.0001). Memantine also reduced nonsustained atrial tachycardia burden (between-group difference, 30.98 percentage points; P=0.0043) and was associated with a lower cumulative incidence of new-onset atrial fibrillation (4.8% versus 23.9%; P<0.0001). No clinically meaningful differences were observed in electrocardiographic intervals or left ventricular function, and no drug-related serious adverse events occurred. CONCLUSIONS: In patients with frequent symptomatic PACs, memantine reduced atrial ectopy and atrial tachyarrhythmia burden and demonstrated a favorable safety profile. These findings provide proof of concept for a novel, non-ion channel-based therapeutic strategy targeting the cardiac glutamatergic system. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06501638.
23 Apr 2026
Read appraisal →Journal of hematology & oncology
Uncoupling toxicity from efficacy in donor selection for allogeneic hematopoietic cell transplantation: a retrospective cohort study using double machine learning
Haploidentical hematopoietic cell transplantation (HCT) offers potent graft-versus-tumor effects but is historically limited by higher non-relapse mortality (NRM) compared to matched unrelated (MUD) or related donors (MRD). To algorithmically decouple the competing risks of NRM and relapse, we analyzed 1,713 adult patients (MD Anderson discovery cohort) and 6,829 patients (registry replication cohorts) using a double machine-learning framework of Causal Survival Forests to estimate individualized treatment effects, while Random Survival Forests defined absolute prognostic risk. We found biological uncoupling of relapse and NRM: relapse was driven by disease biology, while NRM was governed by physiological reserve. Specifically, cardiovascular or cerebrovascular comorbidities acted as selective amplifiers of haploidentical toxicity-a "vascular penalty" that doubled mortality risk in the bootstrapped model (sub-distribution hazard ratio 2.09, 95% confidence interval 1.26-3.35). We developed a 3-factor nomogram (recipient age, vascular comorbidity, B-leader matching status) to identify an "Optimized Haploidentical" phenotype. Exploratory multivariable modeling suggested MUD consistently maximized predicted disease-free survival across all subgroups. Among haploidentical versus MRD comparisons, B-leader mismatch appeared to favor MRD across ages, while B-leader matched haploidentical donors in older patients (≥ 60 years) modeled near-equivalent DFS to MRD, representing a hypothesis-generating "zone of equivalence" requiring prospective validation.
22 Apr 2026
Read appraisal →Annals of medicine
Comparative evaluation of oxidative stress biomarkers F2-isoprostanes and 8-OHdG in Parkinson's disease and Type 2 Diabetes Mellitus: a systematic review and meta-analysis of human studies
BACKGROUND: Oxidative stress is central to type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). However, the utility of biomarkers for lipid peroxidation (F2-isoprostanes) and DNA damage (8-OHdG) in the comorbidity of PD and T2DM remains unclear. METHODS: We conducted a systematic review and meta-analysis of 54 unique studies of human subjects aged ≥ 50 years (n = 7,521: 3,522 with T2DM, 722 with PD, and 3,277 controls), measuring biomarkers in serum, plasma, or leukocytes. Mixed-effects models quantified standardized differences (Hedges' g) across subgroups. RESULTS: In T2DM, F2-isoprostanes (g = 1.60, 95% CI: 0.95-2.25) and 8-OHdG (g = 2.64, 95% CI: 2.13-3.14) were markedly elevated (p < 0.001). Stronger effects were observed in younger cohorts and serum/plasma samples, with complications like nephropathy exhibiting extreme oxidative stress (g = 5.24). In PD, 8-OHdG was moderately elevated (g = 0.78, 95% CI: 0.18-1.39; p = 0.011), particularly in randomized controlled trials and plasma samples, whereas F2-isoprostanes were not significantly elevated (g = 0.47, 95% CI: -0.43-1.38). High heterogeneity in T2DM (I2 > 90%) reflected methodological variability. CONCLUSION: Distinct profiles - both markers elevated in T2DM but only 8-OHdG in PD - underscore 8-OHdG's potential in PD-T2DM comorbidity. Future research should focus on standardized assays, multi-compartmental or multi-modal sampling, and longitudinal studies to clarify mechanisms and therapeutic targets.
21 Apr 2026
Read appraisal →Scientific reports
End-to-end pipeline for automated heart failure diagnosis with clinical notes using SNOMED-CT
Diagnosis of heart failure is complex but crucial for patient outcomes and often hindered by the untapped potential of unstructured clinical notes. We introduce a novel end-to-end pipeline for heart failure diagnosis, leveraging electronic health records (EHR) and German clinical notes from 846 patients. Our pipeline synthesizes abbreviation disambiguation, translation of German clinical notes to English, medical entity linking to SNOMED-CT, and subsequent classification. The classification was performed using a Support Vector Machine (SVM) and compared against a fine-tuned medBERT.de neural baseline. We reduced the reliance on training data with zero-shot learning to address limitations with abbreviation disambiguation and entity linking approaches. Validation against benchmark datasets and cardiologists demonstrates high accuracy for real clinical use. Abbreviation disambiguation achieved an accuracy of up to 96.1%. Entity linking achieved competitive performance compared to state-of-the-art approaches on selected evaluation datasets. The SVM classification approach utilizing SNOMED-CT concepts and EHR data achieved an F1-score of 65.3%, on par with the medBERT.de neural baseline using clinical notes and EHR data. Despite challenges regarding limited language-specific resources and reference dataset availability for SNOMED-CT annotations in German, our pipeline demonstrates high potential for real-world clinical use and clinical decision support grounded in the standardized SNOMED-CT ontology.
21 Apr 2026
Read appraisal →Medicine
Saturation effect of anion gap in predicting long-term mortality in critically ill patients with chronic obstructive pulmonary disease (COPD): A retrospective cohort study based on the MIMIC-IV database
The relationship between anion gap (AG) and long-term mortality in intensive care unit has been widely reported, but whether this association exists in critically ill patients with chronic obstructive pulmonary disease (COPD) is still unknown. The data of this study were collected from the Medical Information Mart for Intensive Care-IV. First of all, we used the Cox regression analysis and Kaplan-Meier curves to measure the relationship between AG and 365-day mortality for critically ill patients with COPD. Next, a restricted cubic spline was used to analyze the relationship between AG and mortality. Finally, age, sex, weight, hypertension, type 2 diabetes mellitus, heart failure, myocardial infarction, and chronic kidney disease were considered for subgroup analysis. A total of 2594 eligible subjects were sampled, of which 36.24% died within 365 days of intensive care unit admission. Cox regression analysis, after adjusting for confounders, demonstrated a significant association between AG and 365-day mortality in patients with COPD (hazard ratio = 1.03, 95% confidence interval: 1.01-1.05. P < .05). Stratifying AG into quartiles revealed higher levels of AG associated with an increased risk of death (Q1: 1.00, Q2: 1.34 [1.09-1.66], Q3: 1.44 [1.17-1.78], and Q4: 1.49 [1.19-1.87]). Additionally, restricted cubic spline analysis indicated a nonlinear relationship, with a critical value of AG at 14 mmol/L. Subgroup analysis highlighted AG as a significant predictor of long-term mortality in COPD patients across different subgroups, with an interaction effect observed in the subgroup with type 2 diabetes mellitus. In critically ill patients with COPD, there was a significant positive association between AG and 365-day mortality. In addition, there is a saturation effect at AG of 14 mmol/L.
20 Apr 2026
Read appraisal →PloS one
Comparison of OneChoice AI-based clinical decision support recommendations with infectious disease specialists and non-specialists for bacteremia treatment in Lima, Peru
Bacteremia is a major contributor to global morbidity and mortality, particularly in low- and middle-income countries where diagnostic delays and empirical antimicrobial misuse exacerbate resistance. This study assessed the accuracy of OneChoice®, an artificial intelligence (AI)-based Clinical Decision Support System (CDSS), in guiding antimicrobial therapy for bloodstream infections (BSIs) in Lima, Peru. A cross-sectional, observational design was used, comparing therapeutic recommendations generated by OneChoice®-based on molecular (FilmArray®) and phenotypic (MALDI-TOF MS, VITEK2) data-with the clinical decisions of 94 physicians (35 infectious disease [ID] specialists and 59 non-specialists) across 366 survey-based evaluations of bacteremia cases. Concordance between CDSS and physician decisions was analyzed using Cohen's Kappa and logistic regression. The overall concordance rate was 96.1% when considering any suggested treatment, and 74.6% for the top recommendation, with a substantial agreement (κ = 0.70). ID specialists showed significantly higher concordance (κ = 0.78) than non-ID physicians (κ = 0.61), and specialization was the strongest predictor of agreement (OR = 2.26, p = 0.001). Escherichia coli cases had the highest concordance, while Pseudomonas aeruginosa showed the lowest. The CDSS reduced inappropriate antibiotic use, particularly unnecessary carbapenem prescriptions. These findings support the utility of AI-CDSS tools in enhancing antimicrobial stewardship and standardizing care, especially in resource-limited healthcare settings.
20 Apr 2026
Read appraisal →Gut microbes
Re-establishing bile acid composition after treatment of recurrent Clostridioides difficile infection with fecal microbiota transplantation compared with oral vancomycin or a 12-strain bacterial mixture
Patients with Clostridioides difficile infection have high colonic levels of primary bile acids, which are potent germinators of Clostridioides difficile. Several studies have suggested that re-establishing a normal bile acid composition is a key factor in fecal microbiota transplantation (FMT) for recurrent C. difficile infection, yet former studies supporting this lacked controls. In a subgroup from a randomized controlled trial, we compared the bile acid composition in patients with recurrent C. difficile infection treated with either FMT, a bacterial mixture, or vancomycin. The fecal bile acid content was analyzed several times before and after treatments. Furthermore, we used 16S rDNA gene sequencing to analyze the presence of some bacterial species involved in bile acid metabolism. Stool donors served as healthy controls. We observed a higher proportion of primary bile acids in patients with recurrent C. difficile infection than in donors, yet a donor-like dominance of secondary bile acids was observed after successful treatment in all groups. The shift seemed to occur earliest in the FMT group, followed by the vancomycin group, and the latest in the bacterial mixture group. In approximately half of the participants, the rise in secondary bile acids was timely associated with the detection of bile acid-transforming bacteria that were absent before treatment. Our findings indicate that FMT re-establishes the bile acid composition faster than vancomycin, reducing the time of susceptibility to recurrences of C. difficile infection. Hence, bacterial mixtures developed as an alternative to donor stool for treating recurrent C. difficile infection might benefit from including bile acid-metabolizing bacteria.
19 Apr 2026
Read appraisal →PloS one
Treatment sequence patterns of urate-lowering therapy in Korean patients with gout: A common data model-based study
BACKGROUND: A treat-to-target strategy involving treatment modification improves outcomes in gout, but evidence remains limited regarding the optimal approach when initial urate-lowering therapy (ULT) fails. This study aimed to investigate real-world ULT sequence patterns and evaluate treatment retention based on the initial agent, modification type, and comorbidities. METHOD: We analyzed electronic health record data collected from 2010 to 2022 from the common data model databases of two hospitals. Adults aged 18 years or older diagnosed with gout who initiated ULT and were followed for at least 2 years were included. Outcomes included the frequency and sequence of ULT prescriptions. Treatment modification, defined as switching to another ULT or adding an additional agent, was considered the end of retention for the previous regimen. Subgroup analyses were performed based on comorbidity. RESULTS: Among 2220 patients, febuxostat was the most common first-line agent (51.4%), with 90.9% maintaining therapy. Among those who modified febuxostat therapy, switchers and add-on users continued treatment similarly (91.5% vs. 86.8%, P = 0.33). Of allopurinol initiators, 55.8% changed therapy, mainly switching to febuxostat or benzbromarone rather than adding another agent (51.4% vs. 4.1%, P < 0.001), with similar retention rates (91.5% vs. 86.8%, P = 0.33). Among benzbromarone initiators, 57.2% changed therapy (switchers, 56.7%; add-on users, 0.5%; P < 0.001), and retention rates were 90.5% and 100%, respectively (P = 1.00). Chronic kidney disease was associated with low variability in ULT sequence. CONCLUSIONS: ULT demonstrated durable retention when used as first- or second-line treatment, with switching being more common than add-on therapy and maintaining similar retention rates.
19 Apr 2026
Read appraisal →Open heart
Non-invasive endotyping improves treatment satisfaction and prescribing appropriateness in patients with angina and no obstructive coronary artery disease.
BACKGROUND: Patients with angina and no obstructive coronary artery disease (ANOCA) frequently receive empirical antianginal therapy that fails to target underlying pathophysiological mechanisms. Whether stress perfusion cardiac magnetic resonance (CMR)-guided endotyping and stratified medical therapy improves treatment satisfaction and appropriate medication prescribing in this population is uncertain. METHODS: In the Coronary Microvascular Angina CMR Imaging Trial, 250 patients with suspected ANOCA, who had undergone invasive coronary angiography demonstrating no obstructive disease, were enrolled and underwent stress perfusion CMR with quantification of myocardial blood flow. Participants were randomised 1:1 to CMR-guided management (intervention) or angiography-guided management (control). Treatment satisfaction was assessed using the validated Treatment Satisfaction Questionnaire for Medication (TSQM-9) at baseline, 6 months and 12 months. Medication prescriptions were documented at these time points. RESULTS: Stress CMR imaging led to diagnostic reclassification in 53.0% of patients, with microvascular angina diagnosed in 51.0%. At 12 months, global treatment satisfaction was significantly higher in the intervention group compared with controls (adjusted difference, 19.30 units (95% CI 13.89 to 24.71); p<0.001), with consistent improvements across the effectiveness and convenience domains. CMR-guided management was associated with more appropriate prescribing, including higher use of preventive therapies (85.5% vs 67.5%; p=0.001), and more targeted antianginal prescribing, including calcium channel blockers (43.5% vs 27.0%; p=0.008) and long-acting nitrates (56.5% vs 32.5%; p<0.001). CONCLUSIONS: In patients with ANOCA, non-invasive CMR-guided endotyping substantially improves treatment satisfaction and enables more appropriate, mechanism-targeted pharmacotherapy compared with angiography-guided care. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID NCT04805814.
19 Apr 2026
Read appraisal →The American journal of cardiology
Mavacamten and Aficamten in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis of Randomized Trials
Myosin inhibitors represent a novel therapeutic class for hypertrophic cardiomyopathy (HCM). While both mavacamten and aficamten have been evaluated in randomized trials, comparative evidence across the 2 agents remains limited. We performed a systematic review and meta-analysis of 8 randomized controlled trials of myosin inhibitors in HCM. Outcomes included improvement in the New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), postexercise and resting left ventricular outflow tract (LVOT) gradients, mean rest LVOT peak gradient, mean Valsalva LVOT peak gradient, change in left ventricular ejection fraction (LVEF), peak oxygen uptake, N-terminal pro-B-type natriuretic peptide (NT-proBNP), treatment-emergent adverse events, and serious adverse events. Pooled effects were estimated twice using random-effects models, once stratified by drug and once pooled altogether. Results showed that myosin inhibitors improved clinical and hemodynamic outcomes versus placebo. Both mavacamten and aficamten yielded improvements in New York Heart Association functional class and KCCQ-CSS, while reducing LVOT gradients and proBNP levels. Effect magnitudes were generally larger with mavacamten; aficamten demonstrated concordant but smaller effects and was the only agent to increase peak oxygen uptake. Safety was favorable for both agents, with pooled estimates indicating a marginally more favorable safety profile for aficamten. In conclusion, myosin inhibitors improve functional status, quality of life, and hemodynamics in HCM with an acceptable safety profile. Mavacamten generally demonstrates more robust benefits, while aficamten appears to have a more favorable safety profile. Additional trials directly comparing these agents are warranted to better clarify relative efficacy and safety.
17 Apr 2026
Read appraisal →Sleep
Multimodal cardiovascular risk profiling using self-supervised learning of polysomnography
STUDY OBJECTIVES: Polysomnography (PSG) provides a comprehensive assessment of brain, cardiac, and respiratory activity during sleep. While it is widely used for diagnosing sleep disorders, its potential to assess future health risks has not been fully explored. This study aimed to develop and evaluate an interpretable framework to identify physiological patterns in PSG data linked to cardiovascular disease (CVD) outcomes, without relying on manual annotations (e.g. sleep stages). METHODS: We developed a self-supervised deep learning model that extracts meaningful patterns from multi-modal signals (electroencephalography [EEG], electrocardiography [ECG], and respiratory signals [Resp]). The model was trained on data from 4398 participants. Projection scores were derived by contrasting embeddings from individuals with and without CVD outcomes. External validation was conducted in an independent cohort with 1093 participants. The source code is available on https://github.com/miraclehetech/sleep-ssl. RESULTS: The projection scores revealed distinct and clinically meaningful patterns across modalities. ECG-derived features were predictive of both prevalent and incident cardiac conditions, particularly CVD mortality. EEG-derived features were predictive of incident hypertension and CVD mortality. Resp added complementary predictive value. Combining projection scores with the Framingham Risk Score consistently improved prediction, with area under the curve values ranging from 0.607 to 0.965 in the Sleep Heart Health Study test cohort and 0.710 to 0.807 across four of five outcomes in the external validation cohort, demonstrating robust cross-cohort generalizability. CONCLUSIONS: Our findings demonstrate that the proposed framework can generate individualized CVD risk scores directly from PSG data. The resulting projection scores have the potential to be integrated into clinical practice, enhancing risk assessment and supporting personalized care. Statement of Significance This study is among the first to apply a self-supervised framework for cardiovascular risk profiling using polysomnography (PSG) data. By transforming electroencephalography, electrocardiography, and Resp into interpretable projection scores, we identified physiological markers predictive of multiple cardiovascular outcomes. These risk profiles, combined with traditional risk scores, significantly improved prediction across both internal and external cohorts. Our findings highlight the untapped potential of PSG signals beyond sleep staging, providing an interpretable, scalable, and clinically actionable approach for personalized cardiovascular risk stratification.
17 Apr 2026
Read appraisal →Journal of the American College of Surgeons
Predictive Model for Mild Autonomous Cortisol Secretion in Patients Evaluated in Artificial Intelligence-Driven Adrenal Incidentaloma Clinic
BACKGROUND: Mild autonomous cortisol secretion (MACS) is present in approximately 20% to 50% of adrenal incidentalomas. These patients do not exhibit the clinical manifestations of overt Cushing's syndrome, and differentiation from nonfunctional adrenal incidentalomas (NFAI) is typically made after a low-dose dexamethasone suppression test. The objective of this study was to develop predictive models to distinguish MACS from NFAI using clinical and radiological parameters. STUDY DESIGN: This retrospective study included patients evaluated in an adrenal incidentaloma clinic between February 2022 and August 2024 who were diagnosed with either NFAI or MACS. Demographic characteristics, medical and medication history, and radiological features were collected. Patients were randomly divided into training and test cohorts in a 3:1 ratio. Predictive models for MACS were developed using Least Absolute Shrinkage and Selection Operator (LASSO) regression and random forest (RF) algorithms. RESULTS: A total of 397 patients were included, with 297 allocated to the training set and the remaining 100 to the test set. The mean age was 62.3 years, and 55% of participants (n = 220) were women. MACS was present in 34% of the study population (n = 136). The most influential predictive factors of MACS were BMI, Posterior Adiposity Index, and the number of antihypertensive medications. The LASSO and RF models achieved discrimination with area under the curve values of 0.686 and 0.736, respectively. At Youden Index thresholds balancing sensitivity and selectivity, the LASSO model had 58.8% sensitivity, 75.8% specificity, and 70% accuracy, whereas the RF model had 64.7% sensitivity, 75.8% specificity, and 72% accuracy. CONCLUSIONS: Predictive models incorporating clinical and radiological characteristics offer a promising approach for distinguishing MACS from NFAI in patients with adrenal incidentalomas.
17 Apr 2026
Read appraisal →BMJ open respiratory research
Personalised management of community-acquired pneumonia and the role of Clinical Decision Support Software
Community-acquired pneumonia (CAP) is one of the most common causes of hospital admission and is associated with significant morbidity and mortality. National and international guidelines are available to guide the management of CAP, including antibiotic prescribing. However, these guidelines are often not adhered to and there is significant overprescribing of broad-spectrum antibiotics, contributing to the growing pandemic of antimicrobial resistance. Clinical Decision Support Software (CDSS) are electronic tools that use individual patient data to generate patient specific assessments or recommendations, that can then be acted on by the patient or clinical decision maker. This article reviews the evidence surrounding the initial management of CAP in hospital and considers the potential of CDSS to support CAP management.
17 Apr 2026
Read appraisal →The Journal of clinical investigation
Disrupted neurovascular-endocrine coupling in type 1 diabetes with impaired awareness of hypoglycemia
BACKGROUNDRecurrent hypoglycemia in type 1 diabetes (T1D) may culminate in impaired awareness of hypoglycemia (IAH). While neuroimaging studies identified affected brain regions, more complex perspectives integrating vascular dynamics with endocrine profile are needed.METHODSHere, 26 healthy adults, 30 T1D patients with normal hypoglycemia awareness (NAH), and 25 T1D patients with IAH underwent a hyperinsulinemic stepped clamp (euglycemia → hypoglycemia 50 mg/dL) combined with pseudo-continuous arterial spin-labeling MRI. Cerebral blood flow (CBF) and sympathetic vasomotor range (0.02-0.05 Hz) CBF oscillations were modeled against serially sampled plasma cortisol, epinephrine, norepinephrine, and glucagon.RESULTSIn healthy individuals treated as controls, hypoglycemia evoked robust thalamo-striatal and salience-interoceptive CBF increases (mean Cohen's d across significant clusters = 0.93) and suppression of vasomotor oscillations (d = 0.71). T1D retained CBF response but failed to attenuate oscillations (dT1D>controls = 0.43). IAH further blunted hypoglycemia-associated CBF increase, especially in thalamus, striatum, and insula (dNAH>IAH = 0.51). Hormone-CBF coupling differed quantitatively: cortisol/epinephrine-CBF correlations were positive in controls (r = 0.37/0.26), negative in NAH (-0.16/-0.40), and strongly positive in IAH (0.42/0.46).CONCLUSIONThus, our findings indicate that T1D disrupts dynamic, sympathetic modulation of CBF, whereas IAH additionally impairs perfusion reserve and shows maladaptive catecholamine-dependent CBF regulation, suggesting a qualitatively distinct neurovascular phenotype.TRIAL REGISTRATIONClinicalTrials.gov: NCT02747680 and NCT02866435.FUNDINGNIH (P41-EB-015894, P30-NS-076408, R01-DK-099137, R56-DK-099137, and DP1 AG093028); National Center for Advancing Translational Sciences of the NIH (KL2-TR-000113 and UL1-TR-000114); DP1 AG093028; Charles University, Czech Republic (Cooperatio Program, research area NEUR), Brain Dynamics (grant number CZ.02.01.01/00/22_008/0004643); General University Hospital in Prague (MH CZ-DRO-VFN64165).
16 Apr 2026
Read appraisal →The New England journal of medicine
Ianalumab plus Eltrombopag in Immune Thrombocytopenia
BACKGROUND: Current second-line treatments for immune thrombocytopenia (ITP) require long-term administration. Ianalumab, a monoclonal antibody targeting B cells, is being assessed as a short-course second-line therapy in ITP. METHODS: In this phase 3, randomized, double-blind trial, we assigned, in a 1:1:1 ratio, adults with primary ITP and an insufficient response or a relapse after first-line glucocorticoid therapy to receive ianalumab at a dose of 9 mg or 3 mg per kilogram of body weight or placebo once monthly for 4 months. Eltrombopag, an oral thrombopoietin-receptor agonist, was administered once daily in each group according to local prescribing information; the dose was tapered until discontinuation by the end of week 24 in eligible patients. The primary end point was freedom from treatment failure, as determined in a time-to-event analysis, with treatment failure defined by a platelet count of less than 30×109 per liter more than 8 weeks after randomization, initiation of rescue therapy more than 8 weeks after randomization, initiation of new ITP therapy, inability to taper or discontinue eltrombopag because of an inadequate platelet count, or death from any cause, whichever occurred first. The key secondary end point was a stable response at 6 months, defined by a platelet count of at least 50×109 per liter in at least 75% of the measurements between weeks 19 and 25 without use of rescue therapy or new ITP therapy. Safety was assessed. RESULTS: A total of 152 patients underwent randomization: 50 to the 9-mg ianalumab group, 51 to the 3-mg ianalumab group, and 51 to the placebo group. The estimated probability of being free from treatment failure at 12 months was 54% (95% confidence interval [CI], 39 to 67) in the 9-mg group, 51% (95% CI, 36 to 64) in the 3-mg group, and 30% (95% CI, 18 to 43) in the placebo group. The time to treatment failure was significantly longer with ianalumab plus eltrombopag than with placebo plus eltrombopag; the estimated hazard ratio for treatment failure (ianalumab vs. placebo) was 0.55 (P = 0.04) in the 9-mg group and 0.58 (P = 0.045) in the 3-mg group. The percentage of patients with a stable response at 6 months was significantly higher in the 9-mg group than in the placebo group (62% vs. 39%; P = 0.045). The overall frequency of adverse events during the treatment period was generally similar in the three groups. The frequency of serious adverse events was 16% in the 9-mg group, 6% in the 3-mg group, and 4% in the placebo group. CONCLUSIONS: Ianalumab plus eltrombopag led to a longer time to treatment failure than placebo plus eltrombopag. (Funded by Novartis; VAYHIT2 ClinicalTrials.gov number, NCT05653219.).
16 Apr 2026
Read appraisal →Modern rheumatology
Epidemiological and clinical insights into Behçet's disease in Japan: a 2019 nationwide analysis
OBJECTIVES: To clarify contemporary epidemiological and clinical trends of Behçet's disease in Japan by analysing the 2019 National Database of Designated Intractable Diseases (MHLW), describing patient demographics, organ involvement, impact on daily life, and treatment patterns. METHODS: This study analysed the 2019 data from the National Database of Designated Intractable Diseases of Japan, provided by the Japanese Ministry of Health, Labour and Welfare. We focused on age distribution, symptom frequency, daily life impact, and treatment trends. RESULTS: In the 2019 database, 10 406 patients with BD were registered. The median age was 55 years, with a higher proportion of women affected (53.2%). Serious manifestations such as ocular, vascular, and central nervous system involvement were more frequent in males, whereas females showed more mucocutaneous and articular symptoms, representing mild forms of the disease. Pharmacological treatment was common (93.8%), with corticosteroids (44.3%), colchicine (50.9%), infliximab (17.0%), and adalimumab (9.6%) being frequently used. BD significantly affected daily life, with nearly one-third experiencing impaired mobility or depression. CONCLUSIONS: This nationwide analysis highlighted sex-based differences in clinical features and found that BD continues to substantially affect quality of life. The widespread use of biologics suggests a shift in therapeutic strategies.
16 Apr 2026
Read appraisal →Clinica chimica acta; international journal of clinical chemistry
Artificial intelligence and machine learning applications in dialysis: Current applications, challenges, and future directions.
Artificial intelligence (AI) and machine learning (ML) applications have emerged as transformative technologies in nephrology, particularly in dialysis care. The availability of multimodal datasets including electronic health records, hemodialysis machine data, laboratory values, and imaging has enabled the development of sophisticated prognostic, diagnostic, and treatment support tools. This comprehensive review narratively examines current AI/ML applications in dialysis, evaluates their clinical performance, and identifies future research directions. We conducted a comprehensive literature search of PubMed, Web of Science, and other major databases from 2020 to 2025, focusing on peer-reviewed studies that employed AI/ML techniques in dialysis care. Studies were categorised by application domain and analysed for methodology, performance metrics, and clinical implications. Our analysis identified five major application domains: (1) prediction and prognosis, including intradialytic hypotension (IDH) prediction with AUROC values ranging 0.89-0.95, mortality prediction achieving C-indices up to 0.83, and hospitalisation risk assessment; (2) early detection of chronic kidney disease (CKD) progression and dialysis risk; (3) clinical decision support for anaemia management and treatment optimisation; (4) vascular access monitoring with AI-driven image analysis achieving AUROC ≈ 0.96; and (5) natural language processing (NLP) applications for symptom detection. Federated learning (FL) approaches are emerging to enable multi-centre collaboration while preserving data privacy. AI/ML technologies demonstrate significant promise in enhancing dialysis care through improved prediction accuracy, personalised treatment approaches, and clinical decision support. However, widespread clinical adoption remains limited due to challenges including data privacy concerns, model interpretability issues, regulatory complexity, and the need for diverse, representative datasets.
16 Apr 2026
Read appraisal →Renal failure
Benefits of physical exercises in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials
Physical exercise has been proven to be beneficial for chronic kidney disease (CKD) patients; however, there is a lack of a comprehensive summary of existing literature, especially the results from randomized controlled trials (RCTs). We had conducted a systematic review and meta-analysis to evaluate the benefits of physical exercise in chronic kidney disease. Outcomes were classified into all-cause mortality, cardiovascular, pulmonary, and renal outcomes, inflammatory indices, laboratory tests, and physical indices. The risk of bias was assessed using the Cochrane criteria. Relative risk ratios with 95% confidence intervals (CIs) for categorical variables, and weighted mean difference or standardized mean differences with 95% CIs for continuous variables were pooled using a random-effects model. Publication bias was assessed using Funnel plot analysis and Egger's Test. At last, 82 studies were included, and the results of the meta-analysis show that the physical exercises can significantly reduce all-cause mortality, particularly in dialysis dependent patients. Cardiovascular function, reflected by 6-minute walk test and blood pressure and pulmonary function, reflected by peak oxygen uptake, forced expiratory volume in 1 second, and forced vital capacity, all improved after physical exercise interventions. Physical exercises helped to increase the dialysis adequacy and preserve the residual renal function. C-reactive protein and interleukin-6 levels decreased, and hemoglobin and albumin levels increased upon physical exercise interventions. The fat mass decreased after physical exercise interventions in non-dialysis patients. We concluded that physical exercise is beneficial for CKD patients, independent of the modes or locations of exercise.
16 Apr 2026
Read appraisal →International immunopharmacology
Multicentre development and validation of a risk model integrating immunotherapy and coagulation biomarkers for thrombosis in autoimmune neurological disorders
PURPOSE: Patients with Autoimmune Neurological Disorders (ANDs) require routine immunomodulatory therapy, which inherently increases thrombosis risk. Despite this recognised association, reliable tools for thrombosis prediction remain limited, highlighting the need for accurate risk stratification to inform targeted prevention strategies. PATIENTS AND METHODS: This multicentre retrospective study developed a machine learning-based thrombosis risk prediction model using data from 786 patients with ANDs receiving immunomodulatory therapy. The model was trained on data from three centres and externally validated on an independent fourth centre, evaluating six algorithms based on the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and Brier score. Feature selection and Shapley Additive Explanations (SHAP) analysis were applied to ensure model interpretability. RESULTS: Among all algorithms tested, XGBoost (XGB) demonstrated the best performance. On the external validation set, the XGB model achieved an AUROC of 0.949, AUPRC of 0.544, and Brier score of 0.045, significantly outperforming the traditional Padua score. SHAP analysis identified the top three thrombotic risk factors: elevated D-dimer levels, prolonged immobilisation, and advanced age. The total doses of intravenous immunoglobulin and glucocorticoid were also confirmed as significant contributors. The model further enabled stratification into low-, intermediate-, and high-risk groups, offering a practical tool for individualised thromboprophylaxis. CONCLUSION: This study presents a high-performing, interpretable model for early thrombosis risk prediction in patients with ANDs, which facilitates timely clinical decision-making and targeted preventive strategies to reduce thromboembolic complications.
15 Apr 2026
Read appraisal →Neurology
Outcomes After Minor Ischemic Stroke in Older Patients Treated With IV Thrombolysis vs Standard of Care in the TEMPO-2 Trial
BACKGROUND AND OBJECTIVES: There are few high-quality data on thrombolysis outcomes in the oldest patients, especially for minor stroke. We examined safety and efficacy outcomes of thrombolysis in patients older than 80 years, compared with those ≤80 years, in the Tenecteplase Versus Standard of care for Minor Ischaemic Stroke With Proven Occlusion (TEMPO-2) trial. METHODS: In this post hoc analysis of the TEMPO-2 randomized controlled trial, we compared outcomes and adverse events in patients with minor stroke and symptomatic intracranial occlusion or focal perfusion lesion within 12 hours of symptom onset, assigned to tenecteplase vs nonthrombolytic standard of care, in those >80 years and ≤80 years. The primary outcome was responder analysis of the 90-day modified Rankin Scale (responder was mRS = 0-1 if premorbid mRS = 0-1, 0-2 if premorbid mRS = 2). Secondary outcomes included neurologic recovery according to the NIH Stroke Scale (NIHSS) at 5 days/discharge, vessel recanalization, Lawton Instrumental Activities of Daily Living Scale, EuroQol-5 Dimension (EQ-5D), and adverse events. We used mixed-effects Poisson, ordinal logistic, and quantile regression as appropriate, adjusted for sex, baseline NIHSS, and treatment assignment as fixed-effects and enrolling site as random effects. RESULTS: Among 884 patients in the intention-to-treat analysis (208 [23.5%] >80 years, 365 [41.6%] female). Significant interactions between age and treatment were observed for mRS responder, mRS 0-1, return to baseline function, EQ-5D index, and vessel recanalization. Patients >80 years generally fared worse with tenecteplase for mRS outcomes (mRS 0-1 in 49 [46.2%] vs 61 [59.8%] with control, adjusted risk ratio [aRR] 0.83, 95% CI 0.72-0.97), while among patients ≤80 years, there was no significant difference (249 [76.4%] vs 260 [74.7%], aRR 1.01, 95% CI 0.98-1.03). However, in both age groups, patients were more likely to achieve recanalization of visible occlusions (aRR ≤80 years 2.06, 95% CI 1.60-2.65, >80 years 2.77, 95% CI 2.21-3.47) and NIHSS = 0 at 5 days/discharge when assigned to tenecteplase (aRR ≤80 years 1.14, 95% CI 1.04-1.26, >80 years 1.21, 95% CI 1.10-1.33). Serious adverse events (SAEs) were more frequent with tenecteplase among patients >80 years (risk ratio 2.29, 95% CI 1.27-4.13), particularly hemorrhages and stroke progression/recurrence (any extra/intracranial hemorrhage in 5 [4.7%] vs 0 with standard of care, p = 0.026). DISCUSSION: Older patients (>80 years) with minor stroke and visible occlusion or perfusion lesion assigned to tenecteplase were more likely to achieve recanalization of occlusions and short-term neurologic recovery, as were younger patients, but they experienced worse 90-day outcomes with more frequent hemorrhagic and stroke progression/recurrence-related SAEs. Overall, these results, while post hoc, do not support thrombolysis for minor strokes in older patients. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT02398656. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients >80 years with minor stroke and visible occlusion or perfusion lesion, IV thrombolysis with tenecteplase is associated with worse functional outcomes at 90 days compared with nonthrombolytic standard of care therapies.
15 Apr 2026
Read appraisal →Toxicology mechanisms and methods
Introducing AutoML framework for drug-drug interaction prediction: application of AutoGluon.
Drug-drug interactions (DDIs) remain a major concern in medication safety. Although advanced artificial intelligence methods such as deep learning have improved DDI prediction, their adoption is limited by the need for specialized expertise and complex model development. This study introduces the first application of the AutoGluon AutoML framework to DDI prediction using molecular features, aiming to automate and simplify model development. A curated subset of 100,000 drug pairs from DrugBank was used, employing three molecular representations: 2D molecular descriptors, 2048-bit Morgan fingerprints, and their combination. Models were trained using AutoGluon-Tabular with no manual hyperparameter tuning. The descriptor-only model achieved the best performance, with 84.4% test accuracy and an AUC of 0.916, outperforming fingerprint-based and hybrid models. Feature importance analysis identified key physicochemical and topological descriptors-such as drug-likeness, electrotopological indices, and hydrophobic surface area-as critical predictors of DDIs. These results demonstrate that AutoML can extract chemically meaningful patterns while reducing technical barriers. Overall, our results validate AutoGluon as a scalable approach to DDI prediction that provides chemically meaningful, feature-level interpretability, and lay the groundwork for future applications involving larger datasets and more complex chemical representations.
15 Apr 2026
Read appraisal →Blood advances
Pirtobrutinib, a highly selective, noncovalent (reversible) BTKi in R/R marginal zone lymphoma: phase 1/2 BRUIN study.
Marginal zone lymphoma (MZL) is a group of indolent B-cell malignancies with a remitting and relapsing course. For systemic disease, available first-line therapies include anti-CD20 antibody as monotherapy or in combination with chemotherapy (chemoimmunotherapy), with second-line options including covalent Bruton tyrosine kinase inhibitors (cBTKi). However, management of relapsed and refractory (R/R) MZL remains challenging. Pirtobrutinib, a highly selective, noncovalent BTKi has shown promising efficacy and tolerability in poor-prognosis B-cell malignancies following prior therapy, including cBTKi. Here, we report the safety and efficacy of pirtobrutinib in MZL from the phase 1/2 BRUIN study. Endpoints included investigator-assessed objective response rate (ORR) by Lugano 2014 criteria, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Among 36 patients with R/R MZL (extranodal [n = 6]; nodal [n = 17]; splenic [n = 13]), median age was 68 years (range, 22-83) and median prior lines of therapy were 3 (range, 2-10). The ORR was 55.6% (95% confidence interval [CI], 38.1- 72.1), including 3 (8.3%) complete responses and 17 (47.2%) partial responses. Median DOR was 17.8 months (95% CI, 7.4 to nonestimable [NE]), and median PFS was 16.6 months (95% CI, 9.0-22.1). With median follow-up of 32.4 months (IQR, 28.0-41.3), median OS was NE (95% CI, 29.5-NE). The ORR for patients with prior cBTKi therapy was 53.8% (95% CI, 33.4-73.4). Pirtobrutinib was well tolerated with dose reductions in 4 patients (11.1%) and permanent discontinuation due to treatment emergent adverse events in 4 patients (11.1%). Pirtobrutinib showed promising efficacy and safety in patients with heavily pretreated R/R MZL, including prior cBTKi. This trial was registered at www.clinicaltrials.gov as #NCT03740529.
15 Apr 2026
Read appraisal →Hepatology communications
Seladelpar in patients with primary biliary cholangitis and compensated cirrhosis: Efficacy and safety from RESPONSE and ASSURE studies
BACKGROUND: Treatment options are limited for patients with primary biliary cholangitis (PBC) and cirrhosis. Seladelpar, a first-in-class delpar (selective PPAR-δ agonist), had generally similar efficacy and safety among patients with versus without compensated cirrhosis in the phase 3 RESPONSE study. Here we provide additional data on seladelpar in patients with compensated cirrhosis from the phase 3 program. METHODS: In RESPONSE, patients with PBC and an inadequate response or intolerance to UDCA were randomized 2:1 to seladelpar 10 mg or placebo for 1 year. Upon completion, patients rolled over into the open-label (seladelpar 10 mg) phase 3 ASSURE study, which also enrolled patients from earlier seladelpar legacy PBC studies. Here, we assessed the composite endpoint [alkaline phosphatase (ALP) <1.67×upper limit of normal (ULN), ALP decrease ≥15%, and total bilirubin ≤ULN], other laboratory changes, and safety in all patients with cirrhosis from RESPONSE and an interim analysis of the ongoing ASSURE study through January 2024. RESULTS: Twenty-seven patients with compensated cirrhosis enrolled in RESPONSE (18 seladelpar, 9 placebo). At month 12, 38.9% and 22.2% of patients in the seladelpar and placebo groups, respectively, met the composite endpoint; mean percent change from baseline in ALP was -37.1% and -10.1%, respectively. Upon rollover to ASSURE (13 seladelpar, 6 placebo), ALP declines were maintained for up to 18 months. An additional 35 patients with compensated cirrhosis in ASSURE from legacy studies had similar reductions in ALP with up to 2 years of treatment. Bilirubin remained overall stable. No treatment-related serious adverse events occurred. Variceal bleeding and/or ascites developed in 3 patients after ≥9 months. CONCLUSIONS: Seladelpar decreased markers of cholestasis and was overall safe and well-tolerated in patients with PBC and compensated cirrhosis.
15 Apr 2026
Read appraisal →JMIR medical education
Developing and Validating a Coding Scheme for Clinical Reasoning in History Taking Using Generative AI-Based Virtual Patients: Systematic Text Condensation Approach
BACKGROUND: Effective history taking helps clinicians identify key symptoms and form accurate hypotheses. Generative artificial intelligence (GenAI)-based virtual patients (VPs) are increasingly used to simulate and practice history taking. However, there is currently no straightforward approach to effectively identify students' clinical reasoning activities during these interactions, which limits the ability to provide instructional feedback. OBJECTIVE: This study aims to develop and validate a coding scheme to identify medical students' history-taking behaviors during interactions with GenAI-based VPs. METHODS: Second-year medical students (N=210) participated in 5 history-taking cases with GenAI-based VPs, yielding 1030 dialogues. Researchers applied the systematic text condensation method to these dialogue data from cases 1 to 4 to inductively develop a coding scheme and validate coding consistency. Subsequently, the dialogue data from case 5 were used to assess the correlation between the students' history-taking behaviors and their academic performance, including diagnostic accuracy, history-taking checklist scores, clinical knowledge test scores, and postencounter form scores. RESULTS: A coding scheme comprising 12 behaviors across 3 dimensions-clinical reasoning behaviors, information gathering behaviors, and social interaction behaviors-was developed with high interrater reliability (κ≥0.85). The correlation analysis revealed that key clinical reasoning behaviors, such as summarizing and integrating and logical organization, showed significant positive correlations with multiple performance metrics, underscoring their importance in fostering clinical competence. In contrast, information gathering behaviors such as specifying symptoms and routine question were associated with clinical knowledge and thoroughness of history taking but were less predictive of diagnostic accuracy. CONCLUSIONS: This study developed a reliable, theory-informed coding scheme that can identify students' questioning behaviors during history taking with GenAI-based VPs. The scheme effectively captures higher-order cognitive strategies and provides valuable insights into the development of clinical reasoning in medical students. This approach offers a scalable and efficient way to integrate real-time feedback into future medical education, fostering personalized learning and advancing competency-based assessments in clinical training.
14 Apr 2026
Read appraisal →Blood advances
Neutrophil CD14 is a driver and a therapeutic target for deep vein thrombosis.
Neutrophil-mediated persistent inflammation and neutrophil extracellular trap formation (NETosis) are critical in the pathogenesis of deep vein thrombosis (DVT). Identifying the mechanisms controlling these proinflammatory and prothrombotic functions is critical for designing and developing new therapeutics for DVT. However, how neutrophils acquire these phenotypes during the early stages of DVT remains poorly understood. Here, multiomic analyses (RNA sequencing, proteomics, and flow cytometry) of bone-marrow neutrophils 3 hours after DVT, revealed consistent overexpression of CD14. Concurrently, mice with DVT exhibited significantly elevated plasma granulocyte colony-stimulating factor (G-CSF) and neutrophil hyperactivation. Mechanistic studies using a geometric deep learning model (DeepPBS) and chromatin immunoprecipitation revealed that elevated G-CSF drives CD14 overexpression by upregulating the transcription factor C/EBPα (leucine zipper CCAAT-enhancer binding protein α). Importantly, neutrophil-specific CD14 knockdown using a novel lentiviral short hairpin RNA approach significantly improved DVT outcomes by lowering thrombus burden, thrombosis incidence, and intrathrombus neutrophil and citrullinated histone H3 accumulation. Studies in G-CSF stimulated primary human neutrophils revealed that CD14 inhibition reduces markers of inflammation and NETosis (activated gasdermin D, citrullinated histone H3, and S100A8/A9), while increasing apoptosis, thus demonstrating translational relevance. Collectively, our study uncovers an essential role of neutrophil CD14 in DVT pathogenesis and establishes it as a promising therapeutic target for DVT.
14 Apr 2026
Read appraisal →Blood advances
How to determine the optimal duration of anticoagulation for VTE: an evidence-based decision-analytical approach
When advising patients on the optimal duration of anticoagulation for venous thromboembolism (VTE), current management often relies on the intuition of treating physicians and guideline panels, an approach that remains opaque to outside observers. We present a decision-analytical framework adopted in our practice. This approach formalizes the intuition of physicians and guideline panels, providing an explicit and transparent integration of the best available evidence on benefits and harms. It also incorporates a systematic method for eliciting patient values and preferences to determine the optimal duration of anticoagulation. To demonstrate the practical utility of the decision-analytical approach, we apply it to 3 clinical scenarios: unprovoked VTE, VTE related to long-haul travel, and portal vein thrombosis in cirrhosis. By transparently synthesizing evidence and patient values, this method supports individualized, evidence-based, patient-centered recommendations for the duration of anticoagulation, and it is applicable to solving similar clinical problems in hematology and medicine.
14 Apr 2026
Read appraisal →Medicine
Association of blood urea nitrogen to serum albumin ratio with mortality in ICU patients with sepsis-induced coagulopathy: A Retrospective Cohort Study from MIMIC-IV database
The blood urea nitrogen to serum albumin ratio (BAR) has shown promise as a prognostic marker in sepsis, yet its specific role in sepsis-induced coagulopathy (SIC) remains unclear. We aimed to clarify whether BAR informs mortality risk in critically ill intensive care unit (ICU) patients with SIC. Using the Medical Information Mart for Intensive Care IV database, we identified consecutive ICU patients admitted between 2008 and 2022 who fulfilled Sepsis-3 criteria and had an SIC score ≥4. BAR was calculated from the 1st available laboratory values. Multivariable Cox regression and restricted cubic splines were used to estimate mortality associations after adjustment for demographics, comorbidities, interventions, severity scores (Sequential Organ Failure Assessment, Simplified Acute Physiology Score II), and laboratory parameters. The primary end-point was 30-day mortality; 90- and 365-day mortality were secondary. Among 4244 patients, higher admission BAR independently predicted increased mortality at 30, 90, and 365 days. Each 10-unit rise in BAR conferred a 30% higher hazard of death within 30 days (unadjusted hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.25-1.35; P < .001). After full adjustment, the association persisted (HR 1.18, 95% CI 1.12-1.24; P < .001). Similar patterns were seen for longer-term outcomes. A clear dose-response relationship was observed across BAR tertiles; patients in the highest tertile (BAR ≥ 10 mg/g) had markedly higher mortality risk (adjusted HR 1.69, 95% CI 1.43-2.00; P < .001) than those in the lowest. Nonlinear analysis revealed a curvilinear BAR-mortality relationship, and subgroup analyses showed consistent findings, with significant effect modification by age. In critically ill patients with SIC, an elevated admission BAR independently predicts short- and long-term mortality and may aid risk stratification and early intervention planning.
12 Apr 2026
Read appraisal →Medicine
Prognostic factors for mortality in age-stratified elderly sepsis patients: A retrospective cohort study based on the MIMIC-IV database
Sepsis represents a major cause of death among elderly patients; however, prognostic factors specific to different age strata within this population remain insufficiently characterized. This retrospective cohort study aimed to identify early predictors of mortality in elderly sepsis patients using the MIMIC-IV database. We included 13,461 sepsis patients aged ≥60 years, stratified into younger-old (60-74 years; n = 7618) and older-old (75-90 years; n = 5843) groups. Propensity score matching was applied to balance baseline characteristics, yielding 4657 matched patients per group. Multivariable logistic regression, receiver operating characteristic analysis, and Kaplan-Meier survival curves were employed to assess clinical and biochemical markers for 28-day mortality and to identify age-specific prognostic indicators. These findings underscore the importance of age-stratified prognostic models to guide targeted clinical interventions and potentially improve outcomes in elderly patients with sepsis. Lactate dehydrogenase (LDH) and the PaO2/FiO2 ratio emerged as key mortality predictors in the younger-old group, whereas urea nitrogen and hypoalbuminemia were predominant in the older-old group. Urine output served as a common predictor across both strata, with oliguria associated with a 2.5-fold increase in mortality risk among older patients. While a combination of predictors enhanced prognostic accuracy in younger-old patients, this was not observed in the older-old group, suggesting a greater influence of frailty and comorbidities in advanced age.
12 Apr 2026
Read appraisal →Medicine
Real-world safety profile of anifrolumab: An observational disproportionality analysis of the FAERS database
Anifrolumab is a type I interferon receptor antagonist approved for the treatment of moderate-to-severe systemic lupus erythematosus. While its efficacy has been demonstrated in clinical trials, its long-term safety remains understudied in the real world. This study extracted relevant data from the FDA Adverse Event Reporting System (FAERS) to evaluate the post-marketing safety profile of anifrolumab in real-world clinical practice and to identify potential safety signals. We analyzed 1293 reports involving 3542 adverse events (AEs) from the FAERS database (Q3 2021-Q1 2025) using disproportionality analysis. Reports in which anifrolumab was designated as the "primary suspect" drug were included. Safety signals were identified using the reporting odds ratio and the Bayesian confidence propagation neural network, with a signal defined as positive only if it met both criteria: a lower limit of the reporting odds ratio's 95% confidence interval > 1 and the 95% lower credibility interval for the information component of the Bayesian confidence propagation neural network > 0. Additionally, multivariable logistic regression analyses were performed for key AEs to rule out potential confounding. The study identified 97 positive safety signals associated with anifrolumab. In addition to the labeled AEs, such as infusion-related reactions and infections, several unexpected AEs were also identified, including renal-related, cardiovascular-related, and neurological AEs. Multivariable logistic regression analyses for key AEs showed that concomitant immunosuppressants, comorbidities, and disease severity were not significant independent predictors (all P > .05), supporting the robustness of the identified signals. This pharmacovigilance study provides hypothesis-generating evidence on the post-marketing safety profile of anifrolumab and highlights several potential safety signals that warrant further evaluation. It is crucial to emphasize that these findings are derived from the FAERS, a spontaneous reporting database that cannot establish causality due to inherent limitations, such as underreporting, missing data, and lack of exposure information. Therefore, these results require confirmation in well-designed observational studies and clinical trials. Clinicians should be aware of these potential associations and consider appropriate monitoring.
12 Apr 2026
Read appraisal →PloS one
Integrative bioinformatics and machine learning identify shared molecular mechanisms and diagnostic biomarkers between Helicobacter pylori infection and atrial fibrillation
BACKGROUND: Helicobacter pylori (H. pylori) infection and atrial fibrillation(AF) are major global health concerns. Emerging evidence has suggested a potentially chronic inflammation-mediated link between them, but the shared genetic mechanisms remain unclear. METHODS: We analyzed multidataset gene expression profiles from the Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment, and machine learning were employed to identify common genes, pathways, and diagnostic biomarkers. Protein-protein interaction (PPI) networks, drug-gene analysis, and molecular docking were used to identify hub genes and potential therapeutics. RESULTS: We identified 73 common differentially expressed genes (DEGs) between H. pylori infection and AF, which were predominantly enriched in immune-related processes including leukocyte activation, neutrophil migration, and myeloid cell-mediated immunity. Machine learning identified 15 and 23 key feature genes for H. pylori and AF, respectively, with S100A8 emerging as a shared diagnostic biomarker. Ten hub genes including TYROBP, ITGB2, and SPI1, were identified from the PPI network. Drug repositioning analysis suggested retinoic acid, indirubin, and ropivacaine as candidate therapeutics targeting these key hub genes. CONCLUSION: Our integrative analysis highlights the central role of immune-inflammatory pathways in linking H. pylori infection to AF. We propose S100A8 and other identified hub genes as potential biomarkers and therapeutic targets. The predicted candidate therapeutics, particularly retinoic acid, may offer novel avenues for intervention, warranting further experimental validation.
12 Apr 2026
Read appraisal →Heart (British Cardiac Society)
Subphenogroups of acute heart failure with preserved ejection fraction: comprehensive proteomics and pathway analysis
BACKGROUND: Heterogeneity of heart failure with preserved ejection fraction (HFpEF) results in significant challenges for treatment development. Identifying and characterising distinct HFpEF phenogroups may aid in tailoring therapeutic strategies for these patients. The objective of this study was to assess proteomic patterns of HFpEF phenogroups identified through a machine-learning-based clustering model, with the aim of uncovering specific biological pathways associated with each phenogroup. METHODS: This study represents a post-hoc analysis of the ongoing Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction (PURSUIT-HFpEF) study, which is a multicentre prospective observational study of hospitalised patients with acute decompensated HFpEF. Of the overall cohort (N=1238), this study analysed 198 patients with HFpEF with available proteomics data. These patients were classified into four phenogroups using the machine-learning-based clustering model. The SomaScan assay V.4.1 was used to measure levels of >7000 plasma proteins, and subsequent pathway analysis was conducted to determine the biological differences among the phenogroups. RESULTS: We identified four distinct phenogroups: Phenogroup 1 ('rhythm trouble'), Phenogroup 2 ('ventricular-arterial uncoupling'), Phenogroup 3 ('low output and systemic congestion') and Phenogroup 4 ('systemic failure'). The proteomics revealed distinct protein expression profiles among the phenogroups, with ribonuclease 4, tax1-binding protein 1, regenerating islet-derived protein 3-gamma and alpha-1-antichymotrypsin being the most significant markers to specific identified phenogroups. Pathway analysis suggested differences in immune response, autonomic activation, cellular homeostasis and tissue repair mechanisms across the phenogroups. CONCLUSIONS: Using a comprehensive plasma proteomics approach, our study identified distinct proteomic profiles of HFpEF phenogroups, which in turn suggest specific underlying biological processes. These profiles suggest the involvement of inflammatory activation, tissue injury and regenerative responses, immune modulation and systemic stress signalling as key components of HFpEF pathophysiology. TRIAL REGISTRATION NUMBER: UMIN-CTR ID: UMIN000021831.
12 Apr 2026
Read appraisal →PloS one
Association between hypertension and impaired lung function among adults: A systematic review and meta-analysis
BACKGROUND: Impaired lung function and hypertension are both significant global public health concerns, and their potential association has recently drawn considerable interest. This systematic review and meta-analysis aims to investigate the association between impaired lung function and hypertension, and vice versa. METHODS: We searched CINAHL (EBSCOhost), MEDLINE (PubMed), Scopus and Web of Science up to 22nd July 2025 for observational studies involving adults (≥ 18 years) reporting hypertension and impaired lung function. Grey literature was also searched, and data extraction was verified independently. The review was registered with PROSPERO (CRD42023427631). Random effects models estimated pooled ORs with 95% CIs. Subgroup analysis and meta-regression were performed to identify potential sources of heterogeneity. Quality assessment was conducted using Newcastle-Ottawa Scale and JBI checklist and publication bias were appraised. RESULTS: This systematic review included 28 articles, of which 26 articles were selected for the meta-analysis. Of these, 17 studies (n = 134823) examined impaired lung function as the exposure, while 9 studies (n = 12522) investigated hypertension as the exposure. Our findings revealed that the pooled unadjusted effect of lung function impairment on hypertension was 1.70 (95% CI: [1.53-1.88]), while the pooled adjusted effect was lower at 1.40 (95% CI: [1.31-1.49]). In contrast, the pooled unadjusted effect of hypertension on lung impairment was 3.00 (95% CI: [1.86-4.82]), but the pooled adjusted effect decreased to 1.94 (95% CI: [1.51-2.50]). The findings indicate that obstructive, restrictive and mixed lung function impairments are significantly associated with hypertension. Restrictive lung impairment consistently shows a stronger association with hypertension compared to obstructive impairment when impaired lung function is the exposure. CONCLUSION: This study concludes that there is a significant positive association between impaired lung function and hypertension in both directions, with stronger temporal evidence suggesting that impaired lung function may precede hypertension, while the reverse causal direction lacks such evidence.
11 Apr 2026
Read appraisal →JCI insight
Cutaneous adipose tissue carries a strong inflammatory signature in patients with psoriasis.
This study provides a comprehensive evaluation of the cutaneous adipose tissue (CAT) transcriptome in patients with psoriasis and investigates the effects of IL-17 blockade on CAT inflammation through a randomized placebo-controlled trial using secukinumab (ObePso-S study, ClinicalTrials.gov NCT03055494). RNA sequencing analysis of CAT biopsies from 82 patients with psoriasis revealed 2132 differentially expressed transcripts compared with healthy controls. Notably, significant gene dysregulation was observed in both lesional skin (LS)-CAT and non-lesional (NL)-CAT, including activation of IL-17-driven pathways, antimicrobial peptide-related, and neutrophil degranulation signatures. Stratification by obesity demonstrated that obese psoriatic CAT exhibited a more than 2-fold higher number of differentially expressed genes than non-obese counterparts, suggesting a synergistic interaction between psoriasis and obesity in driving CAT inflammation. Treatment with secukinumab markedly improved inflammatory signatures in psoriatic CAT, with greater improvements observed in obese patients. These findings reveal a pronounced and partially IL-17-dependent inflammatory phenotype in psoriatic CAT, challenge the conventional concept of psoriasis as a solely superficial skin disease, and highlight CAT as an important contributor to systemic inflammation in psoriasis.
10 Apr 2026
Read appraisal →Blood
A decade of ibrutinib for CLL with and without TP53 aberration: final report on an investigator-sponsored phase 2 study
Bruton tyrosine kinase inhibitors improve outcomes for patients with chronic lymphocytic leukemia (CLL). Long-term data with continuous therapy are limited. With a median follow-up of 10.0 years, we report final results on 84 patients with TP53 aberrations (deletion of chromosomal arm 17p or TP53 mutation) or ≥65 years of age treated with 420 mg of single-agent ibrutinib daily until progression or unacceptable toxicity. A total of 52 (61.9%) patients were previously untreated; 56 (66.7%) had unmutated immunoglobulin heavy-chain variable region; and 53 (63.1%) had TP53 aberrations, including 34 treatment naïve patients. As of 31July 2024, 9 (10.7%) patients continued ibrutinib, 39 (46.4%) discontinued ibrutinib for progressive disease, 31 (36.9%) for adverse events, and 5 (5.9%) withdrew consent. The median progression-free survival (PFS) was 7.2 years; median overall survival (OS) was not reached. In patients with and without TP53 aberrations, median PFS was 5.6 years and not reached, and 10-year OS was 51.3% and 75.3%, respectively. The estimated 10-year PFS and OS for patients with TP53-aberrant CLL treated in first line was 38.6% and 65.7%, respectively. Minimal residual disease (MRD) was quantified by peripheral blood flow cytometry annually. Undetectable MRD (uMRD; at 10-4) was achieved in 13 (15.5%) patients after a median of 5 years. Twelve patients maintained uMRD, the longest observation ongoing at 8.0 years. Seventeen (42.5%) patients with best response of high MRD (>10-2) remained progression-free for >5 years. These results highlight durable benefits and deepening responses with ibrutinib, including in high-risk CLL. Whether patients maintaining uMRD for years can safely discontinue therapy should be assessed prospectively. This trial was registered at www.clinicaltrials.gov as NCT01500733.
10 Apr 2026
Read appraisal →Blood
A phase 3 study of intensive chemotherapy with or without dasatinib in core-binding factor acute myeloid leukemia
Core-binding factor acute myeloid leukemia (CBF-AML) is associated with KIT mutations and deregulated expression of KIT. We report results from the randomized, open-label, phase 3 trial of intensive chemotherapy with or without the multikinase inhibitor dasatinib in adult patients with CBF-AML. Patients received "3+7" induction therapy, followed by 4 cycles of high-dose cytarabine; in the investigational arm, patients received dasatinib 100 mg daily on days 8 to 21 in induction, and on days 6 to 28 in consolidation cycles, followed by 12-month single-agent dasatinib 100 mg daily. Primary end point was event-free survival (EFS). Secondary end points included overall survival, relapse-free survival, and cumulative incidence of relapse. A total of 202 patients were randomly assigned to the standard arm (n = 102) and to the dasatinib arm (n = 100). Median age was 49 years (range, 18-77); 94 patients had t(8;21), 108 had inv(16)/t(16;16); and 58 (28.7%) patients had a KIT comutation. There was no statistically significant difference in EFS (hazard ratio, 0.92; 95% confidence interval, 0.63-1.33; P = .66) or secondary end points between treatment arms. There was also no significant difference in EFS in subgroup analyses according to age, CBF-AML type, and KIT mutation status. The incidence of serious adverse events was higher in the investigational arm (64%) than in the standard arm (36%). In patients with CBF-AML, the addition of dasatinib to intensive chemotherapy failed to improve survival outcomes. The addition of dasatinib was associated with an increase in toxicity. This trial was registered at www.ClinicalTrials.gov as NCT02013648.
10 Apr 2026
Read appraisal →Lupus science & medicine
Efficacy and safety of anifrolumab in patients with systemic lupus erythematosus without prior immunosuppressant use: post hoc analysis of phase 3 TULIP-1 and TULIP-2 trials
OBJECTIVE: Although current treatment recommendations for systemic lupus erythematosus (SLE) provide the option for biologic agents without prior failure of immunosuppressants (IS), data on this treatment approach are limited. This study evaluates the efficacy and safety of anifrolumab by IS exposure. METHODS: Pooled data from the Phase 3 TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) trials were analysed post hoc to compare patients with moderate-to-severe SLE treated with intravenous anifrolumab 300 mg or placebo alongside standard therapy by reported IS use. Efficacy outcomes by IS use included Definition of Remission in SLE (DORIS) remission and Lupus Low Disease Activity State (LLDAS) attainment, analysed using a stratified Cochran-Mantel-Haenszel approach; all p values are nominal. Safety was summarised descriptively. RESULTS: In this analysis, 257 patients had no reported IS use (IS-inexperienced; anifrolumab 300 mg, n=127; placebo, n=130), and 469 were IS-experienced (anifrolumab 300 mg, n=233; placebo, n=236). At Week 52, DORIS remission and LLDAS attainment rates were higher with anifrolumab versus placebo in both IS subgroups (DORIS, IS-inexperienced, 16.2% vs 6.0%, p=0.0242; IS-experienced, 14.6% vs 7.3%, p=0.0304; LLDAS, IS-inexperienced, 34.0% vs 26.2%, p=0.1718; IS-experienced, 27.7% vs 16.2%, p=0.0038). Anifrolumab was well tolerated, regardless of reported IS history; safety was more favourable among IS-inexperienced versus IS-experienced patients. CONCLUSIONS: This post hoc analysis of pooled TULIP-1/TULIP-2 data supports the efficacy and tolerability of anifrolumab in patients with moderate-to-severe SLE regardless of IS treatment history.
10 Apr 2026
Read appraisal →Journal of medical Internet research
Machine Learning in Predicting the Risk of Esophagogastric Variceal Bleeding Among Patients With Liver Cirrhosis: Systematic Review and Meta-Analysis
BACKGROUND: Liver cirrhosis (LC) can lead to several complications. Esophageal variceal bleeding (EVB) and esophagogastric variceal bleeding (EGVB) are particularly severe, leading to a high risk of mortality. Early identification of esophageal varices and esophagogastric varices is essential. Several studies have constructed prediction models for EVB and EGVB in patients with LC. However, robust systematic evidence to prove their performance is lacking. OBJECTIVE: We included original studies that developed prediction models for esophageal or gastric variceal bleeding in patients with LC under different modeling variables. This study aimed to review the predictive performance of various models for EVB or EGVB in patients with LC, providing insights into the development or updating of simplified scoring tools in the future. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched up to August 21, 2024, to collect original full-text studies on machine learning (ML) in the prediction of EVB and EGVB in patients with LC. The models were evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Subgroup analyses were carried out based on the modeling variables. RESULTS: In total, 21 studies were included, with 7011 patients with LC, among whom 1412 (20.14%) developed EVB and 733 (10.45%) developed EGVB. The meta-analysis results suggested that the pooled c-index, sensitivity, and specificity of the prediction model for predicting EVB in the validation set were 0.85 (95% CI 0.77-0.92), 0.93 (95% CI 0.87-0.96), and 0.66 (95% CI 0.46-0.82), respectively. The pooled c-index, sensitivity, and specificity of the prediction model for predicting EGVB in the validation set were 0.89 (95% CI 0.85-0.94), 0.77 (95% CI 0.66-0.85), and 0.81 (95% CI 0.67-0.90), respectively. The subgroup analysis based on modeling variables revealed that, for predicting EVB, the c-index in the validation set was 0.84 (95% CI 0.80-0.88) for models based on clinical features, 0.82 (95% CI 0.69-0.96) for radiomics-based models, 0.78 (95% CI 0.67-0.89) for models based on radiomics and clinical features, and 0.97 (95% CI 0.95-1.00) for models based on endoscopic features. Subgroup analyses based on modeling variables revealed that, for predicting EGVB, the c-index in the validation set was 0.91 (95% CI 0.86-0.96) for models based on clinical features and 0.85 (95% CI 0.75-0.96) for models based on radiomics and clinical features. CONCLUSIONS: ML methods are feasible for predicting EVB and EGVB in patients with LC. Nevertheless, the number of included original studies is limited. In the future, more studies with larger sample sizes are needed to promote the application of ML in the early assessment of EVB and EGVB in patients with LC in clinical practice.
9 Apr 2026
Read appraisal →The New England journal of medicine
A Phase 2 Randomized Trial of Mezagitamab in Primary Immune Thrombocytopenia
BACKGROUND: Immune thrombocytopenia (ITP) is a disorder of increased platelet destruction and reduced platelet production and is associated with an increased bleeding risk and a compromised quality of life. Available therapies are ineffective in at least 20% of cases. Mezagitamab is an anti-CD38 antibody that targets plasma cells, plasmablasts, and natural killer cells. METHODS: We conducted this multicenter, double-blind, randomized, placebo-controlled trial to assess the safety and efficacy of mezagitamab at a dose of 100 mg, 300 mg, or 600 mg, as compared with placebo, administered subcutaneously once weekly for 8 weeks in adults with persistent or chronic ITP (mean platelet count on ≥2 measurements, <30,000 per microliter). The primary end point was adverse events. A key secondary efficacy end point was a platelet response (defined by a platelet count of ≥50,000 per microliter and ≥20,000 per microliter above the baseline value) on at least two visits at any time through week 16. RESULTS: In the combined mezagitamab groups (28 participants), the mean age was 50 years (range, 24 to 88) and the mean number of previous ITP therapies was 4 (range, 1 to 9); in the combined placebo groups (13 participants), the mean age was 39 years (range, 20 to 65) and the mean number of previous ITP therapies was 4 (range, 1 to 13). The mean baseline platelet count was 19,100 and 17,300 per microliter, respectively. Adverse events were reported in 19 of 28 participants (68%) in the combined mezagitamab groups and in 9 of 13 participants (69%) in the combined placebo groups; adverse events of grade 3 or higher in 5 of 28 participants (18%) and in 3 of 13 participants (23%), respectively; and serious adverse events in 4 of 28 participants (14%) and in 1 of 13 participants (8%). Through week 16, a platelet response was observed in 10 of 11 participants (91%) in the mezagitamab 600-mg group and in 3 of 13 participants (23%) in the combined placebo groups. CONCLUSIONS: Treatment with mezagitamab led to increased platelet counts, with a safety profile that appeared to be similar to that of placebo among participants with persistent or chronic ITP. (Funded by Takeda Development Center Americas; ClinicalTrials.gov number, NCT04278924.).
9 Apr 2026
Read appraisal →PloS one
Dizziness in the emergency department and risk of stroke: A systematic review and meta-analysis
BACKGROUND: Dizziness is a frequent emergency department (ED) presentation, and a subset of patients, especially those with isolated dizziness without focal neurological deficits, have stroke but are prone to misdiagnosis and adverse outcomes. Reported stroke prevalence in ED dizziness cohorts is highly heterogeneous, and comprehensive assessments of isolated dizziness remain limited. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Web of Science, Embase, and the Cochrane Library for relevant studies. We included cross-sectional studies reporting stroke prevalence among all ED patients with dizziness or isolated dizziness. A random-effects model was used for meta-analysis to calculate pooled prevalence. Subgroup analyses and Egger's test were employed to explore heterogeneity and publication bias. The diagnostic accuracy of bedside diagnostic tools was also systematically reviewed. RESULTS: Twenty-nine studies involving 161,013 ED patients presenting with dizziness were included. The pooled stroke prevalence among all ED dizziness patients (n = 158,583) was 5.5% (95% CI: 4.1-7.1). Among patients with isolated dizziness (n = 2,559), the pooled prevalence was 13.9% (95% CI: 8.2-20.9), substantially higher than in the overall dizziness cohort. Subgroup analyses indicated diagnostic methods and hospital level as major contributors to heterogeneity. Summary analysis of bedside diagnostic tools showed that HINTS and STANDING examinations have high diagnostic accuracy overall, while the TriAGe+ score can be applied flexibly for screening or confirmation based on different cut-off points. CONCLUSIONS: ED patients with dizziness carry a meaningful, setting-dependent stroke risk. Standardized bedside exams (HINTS, STANDING) improve early triage, and selectively deploying neuroimaging helps prevent missed strokes when risk is high.
9 Apr 2026
Read appraisal →Journal of clinical microbiology
Etiologies of community-acquired febrile illness identified by TaqMan Array Card qPCR on blood samples: a systematic review and meta-analysis
UNLABELLED: Community-acquired febrile illness presents a significant diagnostic challenge. The TaqMan Array Card (TAC) enables simultaneous detection of many bacterial, viral, parasitic, and fungal pathogens. This systematic review aimed to characterize the etiologies of community-acquired fever diagnosed by TAC directly on blood specimens. A systematic search of PubMed, Scopus, Embase, and Web of Science (from inception to January 2026 in English) identified studies using TAC to detect pathogens directly in human blood to identify the etiology of community-acquired febrile illness. Eligible studies were appraised using a modified Joanna Briggs Institute (JBI) checklist. Pooled proportions and meta-analyses were conducted using a random-effects model. A total of 16 studies comprising 8,937 participants from 12 African and Asian countries met inclusion criteria. TAC detected at least 1 pathogen in 0.43 (95% CI [0.32; 0.54]), with high between-study heterogeneity (I² = 99%). Parasitic infections were most common (56%), nearly all due to Plasmodium spp., followed by bacterial (26%), viral (22%), and fungal (0.5%) etiologies. Plasmodium spp., Rickettsia spp., dengue virus, Lassa fever virus, Streptococcus pneumoniae, Orientia tsutsugamushi, Mycobacterium tuberculosis complex, and Salmonella spp. were the most frequently identified pathogens. Culture-negative bacteria accounted for 56% of bacterial detections. Positivity with more than 1 organism occurred in 6% of cases. TAC showed strong concordance with blood culture for culturable organisms (positive agreement: 73%, 95%CI [0.53; 0.89]; negative: 98%, 95%CI [0.95; 1.00]). TAC provides culture-independent pathogen detection and reveals overlooked causes of febrile illness, such as culture-negative bacteria. Its application may improve clinical diagnosis and surveillance programs. IMPORTANCE: Accurate identification of the causes of community-acquired febrile illness is essential for guiding clinical decision-making, surveillance programs, and public health response. This systematic review and meta-analysis synthesizes data from more than 8,937 patients across Africa and Asia tested with blood-based TaqMan Array Card (TAC) assays. TAC enabled broad, culture-independent detection of bacterial, viral, parasitic, and fungal pathogens-revealing both expected causes, such as Plasmodium spp. and dengue virus, and neglected culture-negative bacteria including Orientia tsutsugamushi, Coxiella burnetii, and Rickettsia spp. By uncovering these underrecognized etiologies, TAC provides valuable pathogen-level data to strengthen fever surveillance, inform outbreak detection, and refine regional disease prioritization frameworks. These findings highlight the potential of high-throughput molecular diagnostics to enhance infectious disease control, particularly in resource-limited settings.
9 Apr 2026
Read appraisal →Journal of the American Heart Association
Patient Care Pathways and Outcomes Following Newly Diagnosed Atrial Fibrillation
BACKGROUND: Care pathways for patients with atrial fibrillation (AF) are poorly understood and may influence the likelihood of guideline concordant oral anticoagulation or antiarrhythmic drug therapy and associated outcomes. METHODS: Adult patients in the Optum Clinformatics Database (2015-2023) with incident AF were identified. Care pathways, by treating clinician specialty (primary care, cardiology, electrophysiology) during each AF-related visit in the 1 year post diagnosis were examined. Cox regression models were used to assess associations between an electrophysiologist visit and AF-related treatments including antiarrhythmic drug therapy and oral anticoagulation and outcomes including AF-related hospitalizations, heart failure hospitalizations, and stroke. RESULTS: Of the 37 370 patients included, 7700 (20.6%) had a care pathway including an electrophysiologist visit. Older patients (70-79 and 80+ versus 18-49 years: hazard ratio [HR], 0.71 [95% CI, 0.64-0.78] and HR, 0.57 [95% CI, 0.51-0.63], respectively) and those with a higher CHA2DS2-VASc score (2-3 and ≥4 versus 0-1: HR, 0.79 [95% CI, 0.74-0.85] and HR, 0.76 [95% CI, 0.68-0.84], respectively) were less likely to have an electrophysiologist visit. Electrophysiologist visits were associated with a significant increase in rates of treatment with antiarrhythmic drug and oral anticoagulation. Patients aged ≥80 years with an electrophysiologist visit had significantly lower risks of stroke compared with those without an electrophysiologist visit (HR, 0.63 [95% CI, 0.42-0.95]). CONCLUSIONS: Certain demographic groups including older patients had lesser likelihood of electrophysiologist consultation, but guideline concordant care was more likely associated with electrophysiology care pathways. Electrophysiology care pathways were associated with improved outcomes especially among the groups with greatest stroke risk.
8 Apr 2026
Read appraisal →Gut
High versus gradually increasing energy nutrition in the early phase of acute pancreatitis (GOULASH): a multicentre double-blind randomised clinical trial
BACKGROUND: Acute pancreatitis (AP) is among the most common gastrointestinal diseases requiring hospitalisation, often with severe outcomes and no disease-specific therapy. Nutritional support has been proven to improve outcome, but little is known regarding optimal timing and composition. OBJECTIVE: This clinical trial aimed to compare high (30 kcal/kg/day, high energy (HE)) versus gradually increasing energy (0 increased to 30 kcal/kg/day over 4 days, low energy (LE)) strategies for enteral nutritional support in AP. DESIGN: This was a multicentric, double-blind, randomised clinical trial, enrolling patients with AP regardless of predicted severity (January 2017 to April 2023). The primary outcome was a combination of mortality and severe acute pancreatitis (Revised Atlanta Criteria); secondary outcomes included severity, rate of infection, organ failure and pain relapse. Interim analysis was planned after 50% enrolment. The Benjamini-Hochberg false discovery rate (FDR) method was used to correct p value for multiple testing. RESULTS: The trial was stopped early after enrolling 636 patients. Interim analysis showed that the primary outcome showed no difference between groups in the modified intention-to-treat (mITT) population (HE: 28/312, 9.0% vs LE: 18/307, 5.7%, p(uncorrected/corrected)=0.19/0.42). Secondary outcomes showed no difference in the mITT analysis. Without correction for multiplicity testing, results favoured a low gradual energy strategy in terms of organ failure (HE: 52/312, 16.7% vs LE: 28/307, 9.1%, p(uncorrected)=0.007) and pain relapse (80/312, 27.1% vs 54/307, 19.0% p(uncorrected)=0.03) but showed no differences between groups after correction for multiple testing (p=0.13 and p=0.23, respectively). It was determined that the superiority of the intervention would not be shown even with an increased sample size, and thus the trial was terminated based on a post hoc decision on ethics and futility. CONCLUSION: Based on this early terminated trial, a high-energy strategy for early nutrition in pancreatitis does not decrease mortality/severity, but potentially increases organ failure and pain relapse rate. TRIAL REGISTRATION NUMBER: ISRCTN63827758.
8 Apr 2026
Read appraisal →Archives of endocrinology and metabolism
Cushing's syndrome: a systematic review of psychiatric and cognitive symptoms in case studies
OBJECTIVE: Cushing's syndrome, characterized by chronic hypercortisolism, is associated with various health risks, including psychiatric symptoms and cognitive impairments. This systematic review of case studies aimed to map and categorize these symptoms. MATERIALS AND METHODS: We hypothesized that a broader range of psychiatric and cognitive manifestations would be observed beyond anxiety, depression, and memory impairment. The review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024433186). We conducted searches in PsycINFO, Embase, PubMed, and Scopus, identifying 273 potentially relevant studies. After screening, 66 studies were included, comprising 74 cases (81% female; mean age 35.7 years, range 13-81). RESULTS: revealed that 93% of cases presented psychiatric complaints, including depression (39.2%), psychosis/schizophrenic symptoms (35.1%), suicidal ideation/attempts (20.3%), anxiety (17.5%), panic attacks (2.7%), and post-traumatic stress disorder (1.4%). Cognitive complaints were reported in 32% of cases, primarily as general cognitive complaints (18.9%), memory impairment (9.5%), and attentional deficits (5.4%). An overlap of psychiatric and cognitive symptoms was observed in 26% of cases. CONCLUSION: This review underscores the clinical relevance of symptoms such as mania, psychosis, and suicidal behavior in Cushing's syndrome, which are often underreported. Individualized clinical assessment informed by these case studies is crucial for comprehensive management that extends beyond the typical focus on depression and memory. Moreover, greater awareness of the full spectrum of neuropsychiatric manifestations in hypercortisolism is needed.
8 Apr 2026
Read appraisal →Neurology
Efficacy and Safety of Amifampridine in Myasthenia Gravis: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial
BACKGROUND AND OBJECTIVES: Amifampridine, a short-acting potassium-channel blocker, is the first-line treatment for Lambert-Eaton myasthenic syndrome. Its benefit as add-on to pyridostigmine in acetylcholine receptor (AChR)-positive myasthenia gravis (MG) has been proposed, but no randomized controlled trials have been conducted. We aimed to evaluate the efficacy and safety of amifampridine in AChR-MG with insufficient symptom control on pyridostigmine. METHODS: A randomized, double-blind, placebo-controlled crossover trial was conducted at Leiden University Medical Center, a tertiary center for the treatment of MG in the Netherlands, as part 2 of the IMPACT-MG trial. Eligible patients had either completed part 1 (pyridostigmine vs placebo) or failed the initial 2-day pyridostigmine washout, and had an Myasthenia Gravis Impairment Index (MGII) score >10. Participants were randomized (1:1:1) to 1 of 3 treatment sequences. Each treatment period lasted 5 days, with a 2-day washout between treatments, during which participants received either 30 mg or 60 mg of amifampridine modified release, or placebo. The primary outcome was the difference in MGII score between the 2 amifampridine dosages and placebo. Pharmacokinetics, safety, and tolerability were assessed throughout the trial. RESULTS: Between March 2023 and April 2024, 20 patients were enrolled (median age 60 years, 55% female). For the MGII score, the estimated mean differences were -1.0 (95% CI -4.1 to 2.0, p = 0.681) for amifampridine 30 mg vs placebo and -1.7 (95% CI -4.7 to 1.4, p = 0.379) for amifampridine 60 mg vs placebo. No statistically significant association was observed between pharmacokinetic parameters and the MGII. No serious adverse events were reported. Adverse events were more common with amifampridine 30 mg (12 patients [60%]) and 60 mg (15 patients [75%]), compared with placebo (6 patients [30%]), with paresthesia, fatigue, numbness, dizziness, and sleep disturbances most frequently reported. Three patients discontinued amifampridine early due to adverse events. DISCUSSION: The addition of amifampridine to pyridostigmine was not superior to treatment with pyridostigmine alone and was associated with a higher incidence of adverse events. TRIAL REGISTRATION INFORMATION: The trial was registered at EudraCT (2021-004110-20, registration date: July 12, 2022) and ClinicalTrials.gov (NCT05919407, registration date: June 16, 2023). First patient enrolled: March 23, 2023. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with AChRAb+ MG, the addition of amifampridine to pyridostigmine was not superior to treatment with pyridostigmine alone and was associated with a higher incidence of adverse events.
8 Apr 2026
Read appraisal →Journal of the American Heart Association
Development and Validation of a Machine Learning Model for Incident Heart Failure Prediction in Chronic Kidney Disease: A Multicenter Cohort Study
BACKGROUND: Chronic kidney disease (CKD) and heart failure (HF) share pathophysiological mechanisms, rendering HF one of the most burdensome cardiovascular complication in CKD. Current HF prediction models, derived from the general population, exhibit limited accuracy in CKD, thus necessitating a CKD-specific risk model and clinical implementation. METHODS: The development set comprised 52 251 patients with CKD from the China Renal Data System (70% training; 30% internal validation). External validation used 21 798 patients from independent Chinese hospitals and 3323 UK Biobank participants. Outcome was 5-year new-onset HF. Five machine learning models were developed, with performance assessed via area under the curve and compared using DeLong test. The top-performing extreme gradient boosting model was simplified via forward stepwise selection; feature importance quantified using Shapley additive explanations. RESULTS: In the Chinese external validation cohort, the extreme gradient boosting model outperformed others (area under the curve, 0.879 [95% CI, 0.871-0.887]; DeLong P<0.05), with an area under the curve of 0.851 (95% CI, 0.831-0.870) in the UK Biobank cohort. The model was simplified to 9 predictors; Shapley additive explanations analysis ranked estimated glomerular filtration rate and albuminuria as among the most important features. In Chinese and UK Biobank external validation sets, the simplified extreme gradient boosting model showed a ΔC-statistic of 0.050 (0.045-0.056) and 0.006 (-0.013-0.024) versus the Atherosclerosis Risk in Communities risk score, and 0.194 (0.183-0.204) and 0.145 (0.107-0.182) versus the Predicting Risk of Cardiovascular Disease Events Equation, respectively. A web-based calculator was deployed (https://clinician.shinyapps.io/HF_Risk_Predictor_for_CKD/). CONCLUSIONS: The 9-variable extreme gradient boosting model tailored for patients with CKD may help predict HF risk in this high-risk population. Validation across diverse populations is warranted to confirm its generalizability.
8 Apr 2026
Read appraisal →Journal of the American Heart Association
Left Atrial Volume Index and Left Ventricular Mass Index Determine the Benefits of Spironolactone in Patients With Heart Failure With Preserved Ejection Fraction
BACKGROUND: It is unclear whether patients with heart failure with preserved ejection fraction respond to spironolactone based on cardiac structure or function. METHODS: A post hoc analysis was performed among participants with left ventricular (LV) ejection fraction ≥50% and evidence of abnormal LV diastolic function or filling pressures in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial). Log-rank tests and Cox regression models were used for comparison between groups. RESULTS: Totally, 757 subjects were qualified and stratified by parameters on cardiac structure or function. In patients with increased left atrial volume index, spironolactone reduced cardiovascular mortality (adjusted hazard ratio [HR], 0.48 [95% CI, 0.24-0.98]; P=0.042, log-rank; interaction P=0.045). Meanwhile, in patients with increased LV mass index, spironolactone decreased heart failure hospitalization (adjusted HR, 0.51 [95% CI, 0.32-0.80]; P=0.009, log-rank; interaction P=0.041) and the composite outcome of cardiovascular mortality, heart failure hospitalization, and aborted sudden death (adjusted HR, 0.63 [95% CI, 0.43-0.93]; P=0.045, log-rank; interaction P=0.029). Then, in participants with increased left atrial volume index and LV mass index, who matched at 1:1 ration by propensity score matching, spironolactone reduced cardiovascular mortality (adjusted HR, 0.31 [95% CI, 0.11-0.92]; P=0.039, log-rank), heart failure hospitalization (adjusted HR, 0.26 [95% CI, 0.10-0.68]; P=0.005, log-rank), and the composite outcome (adjusted HR, 0.33 [95% CI, 0.15-0.72]; P=0.006, log-rank). CONCLUSIONS: Spironolactone reduced cardiovascular mortality, heart failure hospitalization, or the composite outcome of cardiovascular mortality, heart failure hospitalization, and aborted sudden death in patients with heart failure with preserved ejection fraction with increased left atrial volume index or LV mass index.
8 Apr 2026
Read appraisal →Journal of the American Heart Association
Predicting Recurrence and Outcomes After Stressor-Associated Atrial Fibrillation Using ECG-Based Deep Learning
BACKGROUND: Stressor-associated atrial fibrillation (AF) refers to new-onset AF that occurs with a reversible, acute stressor. Identifying individuals at highest risk for AF recurrence is essential to guide management. Although clinical factors have shown limited value, the utility of contemporary artificial intelligence (AI)-enabled models using the 12-lead ECG to estimate recurrence risk remains unknown. METHODS: We retrospectively analyzed consecutive primary care and cardiology patients with stressor-associated AF occurring during hospitalization. We quantified the cumulative incidence of recurrence accounting for death as a competing risk. We investigated the relationship between time-varying recurrence and a composite end point of AF-related adverse events (stroke, heart failure, all-cause death) using Cox models. We then developed and validated a penalized regression model to predict recurrence using clinical factors, stressor type, and AF risk estimates from a previously validated ECG-based AI model. RESULTS: We analyzed 3371 patients with stressor-associated AF (mean age, 69±12 years; 40% women). Over a median of 3.7 years (interquartile range, 1.8-7.2), the 10-year cumulative incidence of AF recurrence was 41% (95% CI, 39-44). AF recurrence was strongly associated with AF-related adverse events (hazard ratio, 2.24 [95% CI, 1.81-2.76]). A model incorporating clinical factors, stressor type, and ECG-based AI model AF risk estimates (clinical-AI) discriminated AF recurrence (area under the receiver operating characteristic curve, 0.768 [95% CI, 0.707-0.830]) favorably compared with clinical features (area under the receiver operating characteristic curve, 0.707 [95% CI, 0.642-0.772]; P<0.05). CONCLUSIONS: AF recurrence rates following stressor-associated AF are considerable and are associated with substantially higher risk of adverse cardiovascular events. Models incorporating ECG-based AI risk estimates may prioritize individuals for intensive monitoring and preventive interventions.
8 Apr 2026
Read appraisal →Pulmonology
Low-dose theophylline in mild to moderate Chronic Obstructive Pulmonary Disease: A randomized clinical trial in China
BACKGROUND: Low-dose theophylline has anti-inflammatory effects, but its efficacy in mild to moderate COPD remains controversial. RESEARCH QUESTION: Is low dose theophylline effective and safe in patients with mild to moderate COPD? METHODS: In this prospective, parallel-group, randomised, double-blind, placebo-controlled trial across ten centres in China, subjects with mild to moderate COPD were randomized 2:1 to oral low-dose theophylline sustained-release tablets (100 mg twice daily) or matching placebo for 12 months. Primary endpoints were between-group differences in pre-bronchodilator FEV1 change from baseline to 12 months and annual exacerbation rate. FINDINGS: 734 subjects were randomized; 615 completed the study. Compared with placebo, low-dose theophylline significantly ameliorated FEV1 before bronchodilator use by 30 ml [95% CI, 3 to 57 ml] (p = 0.031) at month 12, with a between-group difference in mean change from baseline of 28 ml/year [95% CI, -2 to 58 ml/year] (p = 0.063). The annual exacerbation rate did not differ between groups (0.46 ± 0.03 vs 0.43 ± 0.04 per patient-year; RR, 1.07 [95% CI, 0.84 to 1.36]; p = 0.607). In addition, the incidence of adverse events was comparable between both groups. INTERPRETATION: In mild to moderate COPD, low-dose theophylline was well-tolerated but did not reduce exacerbation rates. A modest improvement in pre-bronchodilator FEV1 was observed, though its magnitude was limited. Larger trials are needed to further evaluate its potential to improve lung function in this population. What is already known on this topic:The efficacy of low-dose theophylline specifically in the mild to moderate COPD population remains unclear.What this study adds:Our study indicated that low-dose theophylline treatment alone was associated with a significant improvement in pre-bronchodilator FEV1 and demonstrated good tolerability in patients with mild to moderate COPD.How this study might affect research, practice or policy:What we found in this study presented promising opportunities for intervention with theophylline alone in patients with mild to moderate COPD.
8 Apr 2026
Read appraisal →BMJ open quality
Feasibility and early outcomes of a multi-site TeleHospitalist admissions programme: staff and patient perspectives from a large health system
BACKGROUND: Staffing shortages contribute to admission delays, fragmented care and hospitalist burnout. Although telemedicine has been widely adopted in critical care and subspecialties, its use in general inpatient admissions remains understudied. This study evaluated the feasibility, operational performance and early perceptions of a TeleHospitalist admissions programme designed to address nocturnal staffing shortages in a large academic health system. METHODS: In October 2024, Houston Methodist launched a nocturnal TeleHospitalist programme. The programme provided centralised coverage via audio-video technology, operating from 18:00 to 02:00 initially and expanding to 18:00-06:00. Adult patients admitted from the emergency department (ED) between October 2024 and August 2025 and clinical staff involved in admission workflows, were surveyed. Operational data on admission timeliness were extracted from the Epic electronic medical record, and patient and staff experiences were evaluated through structured surveys and qualitative feedback. RESULTS: Over 10 months, 1575 TeleHospitalist encounters were completed (median age 65 years (IQR 49 to 75); 56% were ≥65 years). Median hospital length of stay was 38.5 hours (IQR 17.3 to 66.3), and median ED arrival-to-admission time was 7.3 hours (IQR 4.7 to 12.8). Among 311 patient respondents (19.7%; median age 66.5 years (IQR 52.3 to 75.6); 5% were ≥65 years), satisfaction scores were high (median 4 (IQR 3 to 5). Staff responses (n=29) demonstrated strong endorsement: 86% favoured continuation, 79% reported comfort with the technology and 75% rated admission processes as better than traditional workflows. CONCLUSIONS: A system-wide TeleHospitalist admissions programme was feasible and well accepted by patients and staff. Older adults reported positive experiences, suggesting age is not a barrier to virtual inpatient care. Early findings indicate improved timeliness, communication and workflow efficiency while mitigating overnight staffing gaps. Future studies will evaluate long-term outcomes, cost-effectiveness and strategies to enhance privacy and patient engagement.
8 Apr 2026
Read appraisal →Pulmonology
Comparative diagnostic performance of advanced endoscopic techniques in suspected sarcoidosis: A systematic review and network meta-analysis
BACKGROUND: While various endoscopic techniques are used for minimally invasive tissue sampling in suspected sarcoidosis, comprehensive evidence comparing their diagnostic efficacy is limited, and the optimal approach remains unclear. RESEARCH QUESTION: Which endoscopic technique provides the greatest diagnostic advantage for sarcoidosis? STUDY DESIGN AND METHODS: We systematically searched 3 databases for studies published up to 22 April 2025. A network meta-analysis was conducted within a Bayesian framework, with diagnostic yield as the primary outcome. RESULTS: A total of 35 studies were included. Compared to TBLB, both EBUS-guided intranodal forceps biopsy (EBUS-IFB) (RR 3.50, 2.14-5.84) and EBUS-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) (RR 3.52, 1.97-6.48) showed higher diagnostic yield. SUCRA rankings placed EBUS-IFB (0.912) and EBUS-TMC (0.910) at the top, followed by EBUS-guided core needle biopsy (EBUS-CNB) (0.587), EUS-FNA (0.582), and EBUS-TBNA (0.560), EUS-B-FNA (0.498). Conventional techniques, including cTBNA (0.279), TBLB (0.168), and EBB (0.001), ranked lowest. All procedures had a favourable safety profile. CONCLUSIONS: In centres with appropriate expertise, EBUS-IFB and EBUS-TMC may offer superior diagnostic performance for sarcoidosis. However, given the low certainty of evidence, these conclusions should be interpreted with caution. Clinical decisions should be individualised, considering the patient's condition when determining the final diagnostic strategy.
8 Apr 2026
Read appraisal →EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
Ischaemic and bleeding events after complex versus non-complex PCI: a systematic review and meta-analysis
BACKGROUND: Complex percutaneous coronary intervention (PCI) is increasingly performed among patients undergoing myocardial revascularisation. AIMS: We conducted a systematic review and meta-analysis to evaluate the association between complex PCI and the risk of ischaemic and bleeding outcomes. METHODS: Hazard ratios (HRs) were pooled using a random-effects model within a Bayesian framework. The primary analysis was restricted to studies providing adjusted risk estimates, whereas the secondary analysis included unadjusted risk estimates. The primary outcomes were myocardial infarction and major bleeding. The secondary outcomes were all-cause death, stent thrombosis, cardiovascular death, target lesion or vessel revascularisation, and stroke. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for prognostic studies was used to determine the level of certainty in the association between complex PCI and the risk of events. RESULTS: We included 290,039 patients, of whom 94,633 (33%) underwent complex PCI. Compared with non-complex PCI, patients undergoing complex PCI had a higher risk of myocardial infarction (adjusted HR 1.71, 95% credible interval [CrI]: 1.49-1.96), major bleeding (adjusted HR 1.24, 95% CrI: 1.14-1.35), all-cause death (adjusted HR 1.21, 95% CrI: 1.12-1.32), cardiovascular death (adjusted HR 1.29, 95% CrI: 1.15-1.46), stent thrombosis (adjusted HR 1.76, 95% CrI: 1.49-2.14), target lesion or vessel revascularisation (adjusted HR 1.99, 95% CrI: 1.58-2.50), and stroke (adjusted HR 1.21, 95% CrI: 1.03-1.42). The posterior probability of a higher risk associated with complex versus non-complex PCI was >99% for all study outcomes. Except for stroke (which was low certainty), the certainty of evidence was moderate to high for all other outcomes. Secondary analysis, including unadjusted risk estimates, provided consistent results. CONCLUSIONS: Patients undergoing complex PCI have an increased risk of both ischaemic and bleeding events compared with patients undergoing non-complex PCI (PROSPERO: CRD420250656254).
8 Apr 2026
Read appraisal →Lancet (London, England)
Percutaneous coronary intervention versus coronary artery bypass grafting for unprotected left main stenosis: 10-year final results from the randomised, open-label, non-inferiority NOBLE trial
BACKGROUND: Coronary artery bypass grafting (CABG) is recommended over percutaneous coronary intervention (PCI) for patients with significant unprotected left main coronary artery disease. We aim to provide long-term outcome data comparing PCI with newer generation drug-eluting stents and CABG, which are scarce. METHODS: This previously published, prospective, randomised, open-label, non-inferiority trial enrolled patients with unprotected left main coronary artery stenosis at 36 hospitals in Denmark, Estonia, Finland, Germany, Latvia, Lithuania, Norway, Sweden, and the UK. Eligibility was determined by a multidisciplinary heart team and defined by clinical criteria (chronic or acute coronary syndrome and a life expectancy of >1 year) and angiographic criteria (left main coronary artery diameter stenosis ≥50% or fractional flow reserve ≤0·80 in the left main ostium, mid-shaft, or bifurcation). Patients with ST elevation myocardial infarction within 24 h or considered at too high risk for CABG or PCI were excluded. Patients with angiographically confirmed significant left main coronary artery disease were randomly assigned (1:1) to PCI or CABG using an online system and stratified by site, sex, distal left main coronary artery bifurcation lesions, and diabetes. The primary outcome was the difference in 10-year all-cause mortality in the intention-to-treat (ITT) population, which was analysed using Kaplan-Meier estimates and unadjusted Cox regression. Patients were censored at the date of death, emigration, withdrawal, or loss to follow-up. Variation in all-cause mortality was assessed in prespecified subgroups. The trial is registered with ClinicalTrials.gov, NCT01496651 (active, not recruiting). FINDINGS: From Dec 9, 2008, to Jan 21, 2015, 1201 patients were randomly assigned to PCI (n=598) or CABG (n=603). 17 patients were lost to follow-up before 1 year. 592 patients in each group were included in the ITT population. Mean age was 66·2 years (SD 9·9) in the PCI group and 66·2 years (9·4) in the CABG group. 256 (22%) of 1184 participants were female and 928 (78%) were male. There was no difference in all-cause mortality at 10 years (136 [23%] of 592 in the PCI group and 145 [25%] of 592 in the CABG group; hazard ratio 0·93 [95% CI 0·74-1·18]; p=0·56). No significant difference in all-cause mortality with SYNTAX score was identified. INTERPRETATION: There was no significant difference in all-cause mortality at 10 years between PCI and CABG for patients with unprotected left main coronary artery disease and no additional complex lesions, indicating that PCI is equally as safe as CABG in patients eligible for both treatments. These results will aid heart teams in developing an individualised patient-centred strategy. FUNDING: Biosensors and Aarhus University Hospital.
6 Apr 2026
Read appraisal →PloS one
Real-world safety of aliskiren in primary hypertension: A cross-database study
Hypertension is one of the main causes of cardiovascular diseases worldwide, affecting over one billion people. Although aliskiren offers a valuable option for inhibiting the renin-angiotensin system, its safety profile in the real world remains insufficiently explored, especially for rare or under-recognized adverse events (AEs), which have not been fully clarified. Therefore, leveraging large-scale post-marketing surveillance data is crucial for identifying rare AEs and guiding safer clinical practice. This study aims to elucidate pharmacovigilance signals associated with aliskiren (an antihypertensive drug) by systematically analyzing the characteristics of adverse events (AEs) from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and WHO-VigiAccess database, which provides a reliable scientific basis for clinical practice and regulatory decision-making. We conducted a retrospective quantitative analysis of aliskiren-related AE reports from the aforementioned two databases, employing the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) algorithms for signal detection. The results indicate that there were 5,596 and 5,549 aliskiren-related reports in the FAERS and WHO-VigiAccess databases, respectively. The median duration of these AEs during the observation period was 62 days, with an interquartile range (IQR) of 7-282 days. In both databases, signals for aliskiren were distributed across 28 System Organ Classes (SOCs), among which investigations, cardiac disorders, renal and urinary disorders, vascular disorders, and metabolism and nutrition disorders exhibited significant signals based on specific criteria applied across the four algorithms. A total of 607 preferred terms (PTs) with significant disproportionality signals were detected using the four algorithms, including potential AEs not previously well-documented, such as palpitations, myalgia, proteinuria, muscular weakness, pulmonary edema, and pollakiuria. This study not only confirms the known adverse reactions of aliskiren but also uncovers new potential risks, highlighting the importance of strengthening drug safety monitoring to enhance therapeutic efficacy and reduce the risk of adverse reactions. It provides valuable safety insights for physicians considering the use of aliskiren in the management of primary hypertension.
5 Apr 2026
Read appraisal →Medicine
Prediction model for frailty risk in ischemic stroke patients: Application and validation of support vector machines and nomograms
This study aimed to develop a prediction model based on nomograms and support vector machines (SVM) to assess frailty risk in ischemic stroke patients. Clinical information of ischemic stroke patients admitted to our hospital from January 2023 to December 2024 was retrospectively collected. First, independent risk factors associated with frailty in ischemic stroke patients were identified through univariate and multivariate logistic regression analyses. Subsequently, a nomogram was constructed based on regression analysis results and validated using 10-fold cross-validation. Data were divided into training (70%) and validation (30%) sets. A SVM predictive model was constructed on the training set. The predictive performance of both models was compared using receiver operating characteristic curves. This study included 867 ischemic stroke patients, among whom 296 (34.14%) were classified as frail. The entire cohort was randomly divided into a training set (n = 607) and a validation set (n = 260) at a 7:3 ratio. Logistic regression analysis identified hypertension, impaired self-care ability, physical inactivity, reduced prognosis nutrition index, and depressive status as independent risk factors for frailty in ischemic stroke patients (P < .05). The nomogram demonstrated an area under the receiver operating characteristic curve (AUC) of 0.814 for frailty prediction, while the SVM model achieved an AUC of 0.842, indicating superior predictive capability. Further comparison revealed that while the nomogram offers greater intuitiveness and operational convenience in clinical practice, the SVM model demonstrated superior predictive accuracy. Hypertension, impaired self-care ability, physical inactivity, reduced prognosis nutrition index, and depressive states are independent risk factors for frailty in ischemic stroke patients. Both predictive models (nomogram and SVM) demonstrated high predictive accuracy; however, the SVM model outperformed the nomogram in predictive capability, while the latter retains unique advantages due to its simplicity and clinical applicability.
5 Apr 2026
Read appraisal →The European respiratory journal
Impact of positive airway pressure therapy on pulmonary arterial pressures in obstructive sleep apnoea or obesity hypoventilation syndrome: a systematic review and meta-analysis
BACKGROUND: There is limited and conflicting evidence on the impact of obstructive sleep apnoea (OSA) and its treatment with positive airway pressure (PAP) therapy on pulmonary hypertension (PH). Our research question was: does treatment of OSA and obesity hypoventilation syndrome (OHS) with PAP therapy improve pulmonary arterial pressures? METHODS: A systematic review and random effects meta-analysis was performed (PROSPERO: CRD42024595312). PubMed, Embase, Scopus, Web of Science, EBSCO, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov were searched using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Studies reporting pulmonary arterial pressure in patients with OSA and OHS pre- and post-PAP therapy were included. The primary outcome was post-PAP therapy change in pulmonary arterial pressures, with separate analyses on pulmonary arterial systolic pressure and mean pulmonary arterial pressure. Sensitivity analysis was performed to assess the impact of PAP therapy in patients with only OSA or OHS. RESULTS: 23 studies (20 observational and three randomised controlled trials) with 733 patients were included (19 with OSA (n=518) and four with OHS and concomitant OSA (n=215)). Most patients had severe OSA. PAP therapy was associated with a mean reduction in pulmonary arterial pressure of 5.96 (95% CI 3.20-8.73) mmHg; p<0.0001. In patients with baseline PH (n=233), the reduction was 11.41 (95% CI 8.66-14.15) mmHg; p<0.00001. The beneficial effect of PAP therapy was similar in OSA and OHS. There was no sex difference in the impact of PAP therapy. Heterogeneity was high across studies (I2>85%), reflecting differences in study design, patient populations and methodologies. CONCLUSIONS: PAP therapy reduces pulmonary arterial pressures in patients with mostly severe OSA or OHS, with a more pronounced effect in those with baseline PH. As such, our findings may not apply to patients with milder degrees of OSA. While reductions in pulmonary arterial pressures were observed in all groups, the low certainty necessitates cautious application of these findings in clinical practice.
5 Apr 2026
Read appraisal →Biomedical physics & engineering express
Detecting early signs of patient deterioration at home using wearable sensors: a personalized anomaly detection approach
In the rapidly emerging field of transferring healthcare from hospitals to patients' homes, it is essential that signs of remote deterioration at home should be detected early to timely upscale care when needed. As patient deterioration is a rare event, datasets have insufficient event data for supervised machine learning. Personalized anomaly detection (AD) may be a good alternative. Therefore, this study aimed to obtain insight into the use of personalized AD models in detecting early signs of patient deterioration at home using wearable sensor data. To address this, Isolation Forest and Local Outlier Factor models were applied to detect signs of deterioration in terms of mortality or unplanned readmission in the 24 preceding hours in two datasets: one of heterogeneous patients, the other of postoperative patients. A pipeline was developed for continuously updating personalized AD models over time and applying them to detection windows twice per day. Results were compared with the Remote Early Warning Score. Isolation Forest (AUROC: 0.69) and Local Outlier Factor (AUROC: 0.67) models were able to find some early signs of deterioration in heterogeneous patients (n = 113). However, in postoperative patients (n = 193), Isolation Forest (AUROC: 0.41) and Local Outlier Factor (AUROC 0.44) performed badly. The Remote Early Warning Score was able to find some early signs of deterioration for both groups (AUROC: 0.63-0.76). Based on these findings, three requirements were formulated that should be fulfilled for a potentially successful application of personalized AD. First, the training set should be normal and representative of non-deteriorating patients. Second, signs of deterioration should exhibit abnormal characteristics. Third, non-deteriorating patients should not exhibit abnormal characteristics.
5 Apr 2026
Read appraisal →American journal of human genetics
The Electronic Medical Records and Genomics study: Design and analytic framework for assessing the impact of genome-informed risk assessments.
The Electronic Medical Records and Genomics (eMERGE) Network developed and implemented a genome-informed risk assessment (GIRA) to communicate genomic (polygenic risk scores [PRSs], integrated risk scores [IRSs], and monogenic results), clinical, and family history-based risk for 11 chronic diseases and provide recommended healthcare recommendations. GIRA reports have now been returned to 23,840 participants and their providers in a large prospective cohort study. We present here the study design and analysis framework for assessing the attributable impact of GIRA return. Pre-specified outcomes include (1) provider/participant adoption of recommended healthcare actions, (2) new diagnosis of disease, (3) treatment initiation/intensification, and (4) clinical outcomes (surrogate markers or clinical events). We assess outcomes in high risk vs. not-high-risk participants, adjusting for covariates. We evaluate the effect of PRS/IRS at pre-established high-risk thresholds using regression discontinuity (RD), a quasi-experimental method that mimics randomization near a cutoff, enabling estimation of causal effects and controlling for unobserved confounders. Monogenic and family history-based risk stratification are analyzed using logistic regression. With 23,840 participants and 12 months of follow-up, the study is powered to detect differences of 2%-11% with 80% power (α = 0.05 in the adoption outcome). Longer follow-up will be required to enable assessment of new disease diagnosis, treatment changes, and clinical outcomes. Through innovative RD analyses and defined outcomes and comparison groups, this study will provide new insights into the real-world clinical impact of genomic risk assessment, address critical evidence gaps, advance understanding of genomic medicine outcomes, and inform future research.
5 Apr 2026
Read appraisal →Scientific reports
Potential of large language models for rapid clinical information support: evidence from acute kidney injury knowledge testing.
Large language models (LLMs) are increasingly applied in clinical contexts; however, to our knowledge, their performance in acute kidney injury (AKI) has not been directly compared with physician performance on standardized clinical knowledge assessments. We conducted a cross-sectional study to evaluate the performance of 13 publicly available LLMs and 123 volunteer participants at the 131st Annual Congress of the German Society of Internal Medicine in Wiesbaden, Germany. Both groups completed an identical AKI knowledge assessment consisting of two case vignettes and 15 single-best-answer multiple-choice questions. LLMs achieved a mean score of 13.5 out of 15 (90%), with several models reaching a perfect score, while human participants averaged 7.3 out of 15 (48.7%). Only 16.3% of participants scored 11 points or higher. As an illustrative example, ChatGPT-4o completed the test in approximately 0.5 minutes, whereas humans required a mean of 7.3 minutes. These findings demonstrate that LLMs substantially outperformed a heterogeneous group of medical professionals in AKI knowledge assessments and did so with markedly greater efficiency. While this highlights the potential of LLMs as rapid, cost-effective tools for clinical knowledge support, their role in real-world patient care remains undetermined, and human clinical judgment remains essential to ensure safe, context-sensitive, and patient-centered care.
5 Apr 2026
Read appraisal →Hematology (Amsterdam, Netherlands)
Machine learning in the prediction of liver iron concentration and iron chelation therapy adjustment
OBJECTIVES: Iron chelation therapy titration is managed by hematologists who monitor iron levels and adjust medication dosages to achieve patient outcomes. This study developed a machine learning (ML) algorithm to predict the liver iron concentration (LIC) and chelation therapy adjustments. METHODS: This retrospective, single-centre cohort study included adult patients who underwent FerriScan MRI to obtain LIC for chelation therapy monitoring. Using an XgBoost-based ML framework, the proximal-time model (PTM) utilised clinical/drug, laboratory and MRI data features from one visit prior to the target visit, whereas the all-time model (ATM) utilised the data from all prior visits. RESULTS: 94 patients with 892 consecutive visits between January 2008 and November 2018 were included in this study. We assessed the prediction capabilities of the PTM and ATM in LIC, changes to chelation drug type and dosage changes. The PTM model was superior to the ATM model in all the experiments. When drug features were excluded, the CLICT model for predicting patient iron overload status improved to an AUROC of 0.83 [95% CI 0.75-0.91] for PTM; compared to an AUROC of 0.73 [95% CI 0.66-0.80] when drug features were included.For predicting changes in chelation type, the CLICT model showed AUROC of 0.83 [95% CIs 0.77-0.89] for PTM. There is high concordance of the agreement of hematologists with ML in not changing the chelation drug type. DISCUSSION/CONCLUSION: The ML model is a step toward creating a clinical decision support system tool for the prediction of LIC and iron chelation therapy adjustment in patients with haemoglobinopathies or hemolytic anemias.
5 Apr 2026
Read appraisal →Medicine
Neuroendocrine neoplasms diagnosed in the setting of inflammatory bowel disease: A systematic review and proposed management algorithm
BACKGROUND: Patients with inflammatory bowel disease (IBD) are at higher risk of developing malignancies, including neuroendocrine neoplasms, but the specifics of that are not well known. We reviewed the existing literature to map the evidence surrounding this phenomenon. METHODS: Following PRISMA 2020 guidelines, we searched PubMed from inception to September 2024 for patients with gastrointestinal neuroendocrine neoplasms (NENs) and either Crohn disease (CD) or ulcerative colitis (UC). Eligible studies included case reports, case series, and larger retrospective IBD cohorts. We extracted demographic and clinical data including tumor grade, location, metastatic status, and mode of detection. Comparative analyses between UC and CD were performed using Fisher exact test, chi-square test, and independent t-tests. RESULTS: We identified 67 case studies with data available for a total of 108 patients (61.1% male), ranging from 14 to 87 years of age. The median duration from IBD diagnosis to NEN detection was 13 years. Fifty-five (50.9%) patients had CD and 53 (49.1%) had UC. UC patients were older at NEN diagnosis (mean 49 vs 40 years, P = .004) and had a higher metastatic rate (39.6% vs 18.2%, P = .019). Most NENs were low-grade (69.4%), while 20.4% were high-grade and 8.3% were mixed. The most common tumor locations were the rectum (29.6%) and appendix (27.8%), with rectal and colonic NENs more prevalent in UC and small bowel or appendiceal NENs more common in CD. At diagnosis, 71.3% of patients had localized disease. For high-grade NENs, 86.4% of cases were metastatic, compared to 9.3% for low-grade tumors. Only 10.2% of NENs were detected via endoscopic surveillance. CONCLUSIONS: NENs in IBD show distinct patterns by IBD type, with significant differences in tumor location, grade, and metastatic rates between UC and CD. These hypothesis-generating observations suggest heightened vigilance after approximately 10 years of IBD or around age 44, focusing on rectal lesions in UC and small bowel/appendiceal lesions in CD. Validation in prospective, population-based studies is needed before these findings can inform clinical practice.
4 Apr 2026
Read appraisal →The Cochrane database of systematic reviews
Pharmacotherapy for mild hypertension
RATIONALE: This is an update of a Cochrane review published in 2012 of initiation of antihypertensive monotherapy or step-up therapy in people with untreated mild hypertension (systolic blood pressure 140 to 159 mmHg or diastolic blood pressure 90 to 99 mmHg, or both) and no pre-existing cardiovascular disease. The original review demonstrated no difference in the incidence of all-cause mortality, total cardiovascular events (stroke, myocardial infarction, and congestive heart failure), stroke incidence, coronary heart disease, or withdrawal due to adverse effects (WDAEs). Evidence for antihypertensive pharmacotherapy in people with mild hypertension for primary prevention remains uncertain in the literature with conflicting studies. We therefore performed an update of the original Cochrane review to reassess whether initiation of antihypertensive pharmacotherapy compared to placebo or no treatment in people with untreated mild hypertension and no pre-existing cardiovascular disease reduces the risk of all-cause mortality, total cardiovascular events, stroke, coronary heart disease, or WDAEs. OBJECTIVES: To reassess the efficacy and risks of initiating antihypertensive pharmacotherapy in adults with untreated mild hypertension and no pre-existing cardiovascular disease. The primary objective was to reassess the risk of all-cause mortality and total cardiovascular events (defined as fatal and non-fatal strokes, myocardial infarction, and congestive heart failure). The secondary objectives were to reassess the risk of stroke (fatal and non-fatal), coronary heart disease (fatal and non-fatal myocardial infarction and sudden cardiac death), and WDAEs. SEARCH METHODS: We searched the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to June 2024. ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) of at least one-year duration comparing initiation on antihypertensive monotherapy or step-up therapy, or both, versus placebo or no treatment in participants with mild hypertension and no pre-existing cardiovascular disease. OUTCOMES: Our critical outcomes were all-cause mortality and total cardiovascular events. Important outcomes were stroke, coronary heart disease (fatal and non-fatal myocardial infarction and sudden cardiac death), and WDAEs. RISK OF BIAS: Two review authors assessed risk of bias independently and in duplicate using Cochrane's RoB 1 tool. SYNTHESIS METHODS: Two review authors performed title and abstract screening, full-text review, and data extraction independently and in duplicate. We calculated risk ratio (RR) along with 95% confidence interval (CI) for all-cause mortality, total cardiovascular events, stroke events, coronary heart disease events, and WDAEs with the Mantel-Haenszel test and a fixed-effect model. We assessed the certainty of the evidence using the GRADE approach. INCLUDED STUDIES: We included individual patient data from five trials involving a total of 9124 participants, of whom 4593 received antihypertensives and 4531 received placebo or no treatment. All five trials reported all-cause mortality; four trials reported total cardiovascular events and strokes; three trials reported coronary heart disease; and one trial reported WDAEs. SYNTHESIS OF RESULTS: There may be little to no reduction in all-cause mortality (RR 0.85, 95% CI 0.64 to 1.14; 5 trials, 9124 participants; low-certainty evidence), total cardiovascular events (RR 0.93, 95% CI 0.69 to 1.24; 4 trials, 7292 participants; low-certainty evidence), or coronary heart disease (RR 1.12, 95% CI 0.80 to 1.57; 3 trials, 7080 participants; low-certainty evidence). There may be a decreased risk of stroke (RR 0.41, 95% CI 0.20 to 0.84; 4 trials, 7292 participants; low-certainty evidence) and an increase in WDAEs (RR 4.80, 95% CI 4.14 to 5.57; 1 trial, 17,354 participants [aggregate trial-level data; individual patient data unavailable]; low-certainty evidence) with antihypertensives. We downgraded the certainty of evidence for all outcomes due to imprecision, indirectness, and risk of bias. AUTHORS' CONCLUSIONS: In people with untreated mild hypertension and no pre-existing cardiovascular disease, initiation of antihypertensive monotherapy or step-up therapy may not reduce all-cause mortality, total cardiovascular events, or coronary heart disease compared to those who received placebo or no treatment. There may be a reduction in stroke, but possibly also an increase in WDAEs. FUNDING: CIHR Grant to the Hypertension Review Group and British Columbia Ministry of Health Grant to the Therapeutics Initiative. REGISTRATION: Protocol (2007): doi.org/10.1002/14651858.CD006742. Original review (2012): doi.org/10.1002/14651858.CD006742.pub2.
4 Apr 2026
Read appraisal →The New England journal of medicine
Discontinuation of Beta-Blocker Therapy after Myocardial Infarction
BACKGROUND: The role of long-term beta-blocker therapy after a myocardial infarction in patients without left ventricular systolic dysfunction or heart failure is unclear in the era of contemporary coronary-artery reperfusion and secondary prevention interventions. METHODS: We conducted an open-label, randomized, noninferiority trial at 25 centers in South Korea. Patients whose condition remained stable after a myocardial infarction, who had a left ventricular ejection fraction of at least 40% and no heart failure, and who had received beta-blocker therapy for at least 1 year after the myocardial infarction were randomly assigned in a 1:1 ratio to discontinue or to continue beta-blocker therapy. The primary end point was a composite of death from any cause, recurrent myocardial infarction, or hospitalization for heart failure. The prespecified noninferiority margin was an upper limit of the 95% confidence interval for the hazard ratio of 1.4. RESULTS: A total of 2540 patients underwent randomization; 1246 were assigned to beta-blocker discontinuation and 1294 to beta-blocker continuation. The mean age of the patients was 63.2 years, and 12.8% were women. At a median follow-up of 3.1 years (interquartile range, 2.5 to 3.5), a primary end-point event had occurred in 58 patients (4-year Kaplan-Meier estimate, 7.2%) in the discontinuation group and in 74 patients (4-year Kaplan-Meier estimate, 9.0%) in the continuation group (hazard ratio, 0.80; 95% confidence interval, 0.57 to 1.13; P = 0.001 for noninferiority). The incidence of serious adverse events was similar in the two groups. CONCLUSIONS: Among patients who received beta-blocker therapy beyond the first year after a myocardial infarction, discontinuation of beta-blocker therapy was noninferior to continuation with respect to a composite of death from any cause, recurrent myocardial infarction, or hospitalization for heart failure. (Funded by Patient-Centered Clinical Research Coordinating Center in the Ministry of Health and Welfare, South Korea; SMART-DECISION ClinicalTrials.gov number, NCT04769362.).
4 Apr 2026
Read appraisal →Ultrasound in medicine & biology
From Recognition to Action: Integrating Deep Learning and Robotic Control in Transthoracic Echocardiography
Population aging has driven a rise in heart failure cases, increasing the clinical burden on cardiac diagnostics. As a first-line imaging method, transthoracic echocardiography (TTE) faces limitations due to operator dependence, patient variability, and workflow inefficiencies. Meanwhile, advances in artificial intelligence (AI) and robotic ultrasound systems offer new potential pathways toward automated diagnosis. This review examines the current landscape of AI-based image analysis and robotic-assisted echocardiography. It presents a detailed analysis of advancements in artificial intelligence (AI) applied to echocardiography and the evolution of robotic ultrasound systems, aiming to introduce a discussion on semantic-to-motion mapping. By synthesizing recent progress and outlining future directions, we can correctly recognize the current maturity level of artificial intelligence development in the field of ultrasound examination and prepare well for the subsequent work.
4 Apr 2026
Read appraisal →Angiology
Artificial Intelligence Techniques for Prognostic and Diagnostic Assessments in Peripheral Artery Disease: A Scoping Review
Peripheral artery disease (PAD) is a major public health concern worldwide, associated with high risk of mortality and morbidity related to cardiovascular and adverse limb events. Despite significant advances in both medical and interventional therapies, PAD often remains under-diagnosed, and the prognosis of patients can be difficult to predict. Artificial intelligence (AI) has brought a wide range of opportunities to improve the management of cardiovascular diseases, from advanced imaging analysis to machine-learning (ML)-based predictive models, and medical data management using natural language processing (NLP). The aim of this review is to summarize and discuss current techniques based on AI that have been proposed for the diagnosis and the evaluation of the prognosis in patients with PAD. The review focused on clinical studies that proposed AI-methods for the detection and the classification of PAD as well as studies that used AI-models to predict outcomes of patients. Through evaluation of study design, we discuss model choices including variability in dataset inputs, model complexity, interpretability, and challenges linked to performance metrics used. In the light of the results, we discuss potential interest for clinical decision support and highlight future directions for research and clinical practice.
4 Apr 2026
Read appraisal →Heart rhythm
External validation of an explainable electrocardiogram-only deep learning algorithm for the prediction of response after cardiac resynchronization therapy
BACKGROUND: Cardiac resynchronization therapy (CRT) can improve clinical outcomes in patients with dyssynchronous heart failure, but many patients selected according to the current guidelines do not respond. OBJECTIVE: This study aimed to externally validate an explainable deep learning algorithm (the FactorECG algorithm) for predicting response after biventricular pacing. METHODS: We previously trained a deep learning algorithm on >1 million electrocardiogram (ECG) median beats to learn the underlying generative factors of the ECG and applied it to 1306 patients with CRT from the Netherlands. Using the extracted 21 explainable factors, a model predicting the risk of volumetric nonresponse and poor clinical outcomes was developed. In the present analysis, this model was externally validated in a cohort of 161 patients with CRT from the University of Virginia for volumetric nonresponse only. Subsequently, the added value of clinical and cardiac magnetic resonance imaging-derived predictors was investigated. RESULTS: The original model significantly outperformed American Heart Association criteria for left bundle branch block for the prediction of nonresponse {C-statistic 0.67 (95% confidence interval [CI] 0.59-0.76) vs 0.51 (95% CI 0.41-0.60), respectively}. A refitted FactorECG-based model performed similarly to a model also integrating indices of mechanical dyssynchrony (C-statistic 0.74 [95% CI 0.66-0.82] vs 0.70 [95% CI 0.62-0.77], respectively). A combination of both models improved response prediction (C-statistic 0.79 [95% CI 0.71-0.85]). CONCLUSION: In this external validation study, an explainable ECG-only algorithm for the prediction of nonresponse after CRT device implantation generalized well to a lower-risk population from a different hospital. Adding indices of mechanical dyssynchrony and right ventricular function might be of additional value when evaluating volumetric response.
4 Apr 2026
Read appraisal →IEEE transactions on bio-medical engineering
Explainable Prediction of ICU Transfer in Acute Pancreatitis: A Neural Network Model With SHAP Interpretability for Clinical Decision Support
OBJECTIVE: Acute pancreatitis (AP) is a life-threatening disorder commonly observed in emergency departments. Patients with acute pancreatitis may necessitate transfer to the intensive care unit (ICU) if standard treatments prove ineffective. The development of a machine learning (ML) model that can precisely forecast the necessity for ICU admission in patients with acute pancreatitis might dramatically enhance in-hospital healthcare for patients. METHODS: For this study, data were extracted from the MIMIC-III Clinical Database Care-Vue subset (MIMIC-III v 1.4), Medical Information Mart for Intensive Care-IV (MIMIC-IV v 3.1), and eICU Collaborative Research Database (v 2.0). Fifteen features were identified through Boruta's algorithm, Least Absolute Shrinkage and Selection Operator (Lasso), and Recursive Feature Elimination (RFE) utilizing the XGBoost. RESULTS: Seven machine learning models, including Support Vector Machine (SVM), K-Nearest Neighbors (KNN), and Neural Network (NNET), etc. were developed based on these features. The neural network approach demonstrated the highest reliability, attaining an AUC of 0.891, sensitivity of 0.852, and specificity of 0.767 in the test set. Meanwhile, an interpretability assessment of the most robust models was performed utilizing SHapley Additive exPlanations (SHAP) to prioritize feature importance and elucidate the final model. This model has been deployed on a web platform: https://icupredict.shinyapps.io/shiny6/. CONCLUSIONS: The neural network model effectively predicted whether patients with AP would be transferred to the ICU, demonstrating optimal performance. SIGNIFICANCE: We developed an interpretable ML model for prediction of ICU admission in AP patients. It provides clinicians with a reliable tool for early identification and treatment.
4 Apr 2026
Read appraisal →BMJ open
Use of ambient AI scribe in physicians' clinical documentation: a protocol for a systematic review on effectiveness, efficiency, and satisfaction
INTRODUCTION: Clinical documentation is a significant driver of burnout among physicians. Ambient artificial intelligence (AI) scribes, which leverage generative large language models to automate the creation of clinical notes from patient-physician conversations, are rapidly emerging as a potential solution. While these tools promise to enhance efficiency and reduce administrative tasks, concerns about the quality, accuracy and potential biases persist. There is now a need for a systematic synthesis of evidence to evaluate the impact of these technologies in clinical practice. To assess the effects of ambient AI scribes on physicians' clinical documentation, the specific objectives are to: (1) evaluate the effectiveness of these tools on documentation, including accuracy and completeness; (2) synthesise evidence on the impact on physician efficiency after adoption, including time spent on documentation and (3) examine physicians' satisfaction with these tools, including physicians' perceived burden. METHODS AND ANALYSIS: A systematic review of quantitative or mixed-method studies as well as preprints will be conducted. We will perform a comprehensive search of four electronic databases (PubMed, IEEE Xplore, APA PsycInfo and Web of Science, along with medRix and ClinicalTrials.gov for preprints) for empirical studies published between January 2023 and March 2026. The review will synthesise studies comparing physicians' use of ambient AI scribes with traditional documentation approaches. Given the anticipated heterogeneity of the studies, a narrative synthesis will be employed to summarise the findings. Where common quantitative outcomes exist, effect sizes will be calculated using Hedges' g, mean differences or risk ratios/odds ratios as appropriate. The overall quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. ETHICS AND DISSEMINATION: As no patient data are involved in the data collection, no ethical approval is acquired. Results will be disseminated in a peer-reviewed, open-access journal, and presented at relevant academic conferences. PROSPERO REGISTRATION NUMBER: CRD420251149086.
4 Apr 2026
Read appraisal →Heart rhythm
Machine learning-enabled assessment of risk of drug-induced QT prolongation at the time of prescribing
BACKGROUND: Many medications are associated with long QTc. Current long QTc predictors have limited generalizability and/or modest performance. OBJECTIVE: This study aimed to compare the performance of machine learning-enabled approaches to drug-induced long QTc prediction with current risk scores, including Tisdale and RISQ-PATH. METHODS: We identified patients who began QTc-prolonging medications (QTdrugs) and had follow-up 12-lead electrocardiograms (ECGs) within 1 year. Using 5-fold cross-validation, we trained XGBoost (XGB), an ECG-based deep neural network, and combined models using electronic health record data and ECG traces to predict QTc of ≥500 ms within 1 year. We assessed performance using the area under the receiver operating characteristic (AUROC) curves and compared them with corresponding Tisdale and RISQ-PATH scores. RESULTS: QTdrug records were identified for 345,371 patients, 5.7% of whom had long QTc within 1 year. In the subset with baseline ECGs available (N = 182,448; 7.7% events), both the XGB and deep neural network models demonstrated high performance (AUROC 0.869 and 0.864, respectively) but their combination yielded no significant improvement (AUROC 0.874). Therefore, focusing on the XGB model, we observed superior performance vs RISQ-PATH in the overall population (AUROC 0.859 vs 0.701), as well as Tisdale in predominantly inpatients (N = 110,558; 8.8% events; AUROC 0.855 vs 0.770). Positive predictive value was 61.5% vs 28.35% and 54.0% vs 28.3% at equivalent operating points for the XGB model vs RISQ-PATH and Tisdale, respectively. CONCLUSION: Development and retrospective validation of 3 machine learning-based models for predicting drug-induced long QTc at the time of new QTdrug starts demonstrated superior performance compared with current clinical risk calculators and may be useful tools to support medical decision making when initiating new therapies.
4 Apr 2026
Read appraisal →Kidney360
Artificial Intelligence in Critical Care Nephrology: Current Applications, Emerging Techniques, and Challenges to Clinical Integration
Artificial intelligence (AI), including machine learning, deep learning, reinforcement learning, and generative AI, has the potential to advance critical care nephrology (CCN) by enhancing prediction accuracy, improving diagnostic capabilities, supporting clinical decision making, and streamlining workflow processes. Current applications in CCN include AKI prediction, nephrotoxin surveillance, intradialytic hypotension forecasting, and AI-guided dialysis and continuous KRT management, with performance often exceeding traditional models. However, the effect on patient-centered outcomes such as mortality, dialysis dependence, and cost-effectiveness remains uncertain. Emerging techniques, such as conformal prediction for calibrated risk estimates, causal inference for intervention modeling, and reinforcement learning for adaptive ultrafiltration, show promise in enhancing reliability, interpretability, and individualized care. Generative AI and large language models extend these applications to clinical documentation, reasoning, and patient education, while raising new challenges, including hallucinations, regulatory oversight, and clinician trust. Persistent barriers such as data heterogeneity, limited external validation, alert fatigue, and economic constraints hinder broad adoption. This review synthesizes the current evidence and outlines four priorities for advancing AI in CCN: ( 1 ) rigorous multicenter validation focused on clinical outcomes, ( 2 ) integration of uncertainty quantification and causal modeling into AI tools, ( 3 ) development of clinician-centered interfaces that minimize cognitive load, and ( 4 ) establishment of transparent, adaptive regulatory and governance frameworks. Realizing the promise of AI in CCN will require multidisciplinary collaboration, fairness and generalizability testing, and sustainable implementation strategies that align technologic innovation with measurable improvements in patient care.
1 Mar 2026
Read appraisal →J Clin Oncol
Genomics Define Malignant Transformation in Myeloma Precursor Conditions
Multiple myeloma (MM) is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). While these precursor conditions are asymptomatic, they are not entirely benign and carry a lifelong risk of progression to MM. Unlike other cancers defined by pathology, malignant transformation from MGUS or SMM to MM has so far relied on demonstration of clinical end-organ damage as morphology and cytogenetics cannot reliably distinguish them. In this study, using genomic data from 374 patients with MGUS or SMM (277 training, 97 validation), to our knowledge, we demonstrate for the first time the ability to identify malignant transformation in MGUS and SMM. We introduce the concept of genomic MM and genomic MGUS to differentiate the subsets of MGUS and SMM that are biologically malignant with genomic features indistinguishable from MM from the subset that is premalignant and unlikely to progress to malignancy. Importantly, we find that most SMM has biological features of malignant transformation indistinguishable from MM. As expected, this subset that we consider having genomic MM is associated with a high risk of progression to MM although some patients remained progression-free beyond 5 years. Conversely, 60% of MGUS and 10% of SMM have no evidence of malignant transformation (genomic MGUS), with no progression during follow-up. Integration of genomic features with the 2/20/20 International Myeloma Working Group model significantly improved the prediction of progression among genomic MM. These findings support the use of genomic criteria to refine the classification and the risk stratification in myeloma precursor conditions.
1 Jan 2026
Read appraisal →Gut Microbes
Machine-learning assisted discovery unveils novel interplay between gut microbiota and host metabolic disturbance in diabetic kidney disease
Diabetic kidney disease (DKD) is a serious healthcare dilemma. Nonetheless, the interplay between the functional capacity of gut microbiota and their host remains elusive for DKD. This study aims to elucidate the functional capability of gut microbiota to affect kidney function of DKD patients. A total of 990 subjects were enrolled consisting of a control group (n = 455), a type 2 diabetes mellitus group (DM, n = 204), a DKD group (n = 182) and a chronic kidney disease group (CKD, n = 149). Full-length sequencing of 16S rRNA genes from stool DNA was conducted. Three findings are pinpointed. Firstly, new types of microbiota biomarkers have been created using a machine-learning (ML) method, namely relative abundance of a microbe, presence or absence of a microbe, and the hierarchy ratio between two different taxonomies. Four different panels of features were selected to be analyzed: (i) DM vs. Control, (ii) DKD vs. DM, (iii) DKD vs. CKD, and (iv) CKD vs. Control. These had accuracy rates between 0.72 and 0.78 and areas under curve between 0.79 and 0.86. Secondly, 13 gut microbiota biomarkers, which are strongly correlated with anthropometric, metabolic and/or renal indexes, concomitantly identified by the ML algorithm and the differential abundance method were highly discriminatory. Finally, the predicted functional capability of a DKD-specific biomarker, Gemmiger spp. is enriched in carbohydrate metabolism and branched-chain amino acid (BCAA) biosynthesis. Coincidentally, the circulating levels of various BCAAs (L-valine, L-leucine and L-isoleucine) and their precursor, L-glutamate, are significantly increased in DM and DKD patients, which suggests that, when hyperglycemia is present, there has been alterations in various interconnected pathways associated with glycolysis, pyruvate fermentation and BCAA biosynthesis. Our findings demonstrate that there is a link involving the gut-kidney axis in DKD patients. Furthermore, our findings highlight specific gut bacteria that can acts as useful biomarkers; these could have mechanistic and diagnostic implications.
1 Dec 2025
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