Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 127 appraisals
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 →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 →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 →Seminars in musculoskeletal radiology
Artificial Intelligence (Pattern Recognition) in Musculoskeletal Imaging: The Future or Hype?
Artificial intelligence and automated pattern recognition, in particular, have been described as the next frontier in musculoskeletal imaging. However, as the initial hype phase transitions into clinical reality, an essential evaluation of these technologies is required. This narrative review examines the dichotomy between a potential future in which artificial intelligence offers unprecedented efficiency in automatizing multiple tasks in musculoskeletal radiology, from fracture detection, automated segmentation, to automated reporting, versus the hype, characterized by deep learning models that lack generalizability across different scanner vendors and patient populations. We explore the black box nature of deep learning and the ethical implications of automation. By analyzing current barriers to deployment, including workflow integration and regulatory hurdles, this article argues that although artificial intelligence holds transformative potential for musculoskeletal radiology, its success depends on moving beyond narrow diagnostic tasks toward robust multi-institutional validation, to evolve from a speculative trend into an essential clinical copilot tool.
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 →Genome biology
IDEAL-Age: an interpretable deep learning framework for single-cell resolution profiling of immunological aging
Immunosenescence increases susceptibility to infection and reduces vaccine responsiveness, yet bulk transcriptomic clocks obscure the cellular heterogeneity underlying this process. Here, we present IDEAL-Age, an interpretable deep learning framework that operates directly on single-cell PBMC transcriptomes. Benchmarking against 35 methods across independent cohorts demonstrates superior predictive performance. The framework's interpretability uncovers linear and non-linear gene contribution trajectories that reveal phase-specific physiological transitions, and identifies youth-associated or aging-associated cellular roles. Application to systemic lupus erythematosus reveals accelerated immunological aging driven by interferon-associated monocyte shifts. IDEAL-Age establishes a high-resolution computational framework for deciphering systemic immune aging.
27 July 2026
Read appraisal →Science advances
A wearable biomechanical system for medical evaluation of soft tissue disorders
Evaluating soft tissue elasticity provides critical biomechanical insights essential for the precise characterization of various physiological and pathological conditions. Here, we present the clinical validation of a wireless, compact wearable system designed for direct, location-specific monitoring of the elastic modulus of the skin and underlying tissues via vibro-rotational biomechanical dynamics. Validated by computational models and experiments, the device uses a tunable skin interface to enable depth-controlled measurements across diverse anatomical sites. Two human subject studies, one involving patients with cancer-related lymphedema and the other involving patients with systemic scleroderma, yield data that correlate with standard clinical metrics. This technology offers the potential for longitudinal assessments in these and other contexts, in both clinical and home settings.
20 July 2026
Read appraisal →American journal of physical medicine & rehabilitation
Virtual Reality-assisted Physiotherapeutic Training for Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis
OBJECTIVE: To evaluate the effectiveness of virtual reality (VR)-assisted physiotherapy in improving pain, physical function, and balance in patients with knee osteoarthritis (KOA) compared with traditional rehabilitation treatments. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). RESULTS: This analysis included 5 randomized controlled trials (RCTs). The pooled results showed that, compared with consistency rehabilitation, virtual reality (VR)-assisted physiotherapy produced significantly better outcomes in patients with knee osteoarthritis (KOA) for pain relief (SMD = 0.40, 95% CI: 0.14-0.65, P = 0.002), physical function (SMD = 0.37, 95% CI: 0.05-0.70, P = 0.003), and balance (SMD = 0.44, 95% CI: 0.16-0.72, P = 0.002). CONCLUSIONS: Virtual reality-assisted physiotherapy is an effective intervention for patients with knee osteoarthritis, showing superior outcomes in pain reduction, functional improvement, and balance enhancement compared to traditional rehabilitation approaches.
18 July 2026
Read appraisal →The Journal of the American Academy of Orthopaedic Surgeons
Clinical Outcomes and Safety Profile of Open and Arthroscopic Subtalar Joint Arthrodesis: A Systematic Review
BACKGROUND: Open and arthroscopic subtalar arthrodesis are safe and effective surgeries for patients with notable arthritis; however, not an established superiority among them has been found. This systematic review aims to present all of the available literature on studies directly comparing both surgeries. METHODS: Two independent authors completed a systematic literature search using the following databases: PubMed, Embase, and the Cochrane library. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol and the Cochrane Handbook guidelines were followed. In addition, the MINORS score was used to evaluate the quality and bias of the nonrandomized controlled trials. Our search criteria included only studies that included both open and arthroscopic subtalar arthrodesis. RESULTS: A total of four studies including 125 open and 130 arthroscopic surgeries met the inclusion criteria for the current systematic review. The mean age and body mass index of patients in the open and arthroscopic groups were 50.0 ± 2.3 and 47.9 ± 1.4 years and 29.0 ± 3.7 and 29.5 ± 2.6 kg/m 2 , respectively. Patients in the open cohort and arthroscopic cohort were followed for a mean of 16.9 ± 6.5 and 15.8 ± 4.7 months, respectively. Union rate was 95.4% ± 4.6% vs. 93.6 ± 4.0%, and the time to fusion was 14 ± 1.6 vs. 10.5 ± 1.6 weeks. The overall complication rate among patients who underwent open arthrodesis was 44.0%, whereas the complication rate was 39% among patients who underwent arthroscopic arthrodesis. Patients stayed in the hospital for 2.2 ± 0.9 days following an open procedure versus 1.1 ± 0.5 days following minimally invasive procedures. CONCLUSION: The current systematic review found a high rate of union among both group of patients. Although trends suggested higher union rates and fewer complications in the arthroscopic cohort, no notable differences were found. Although limited, we hope that this systematic review may help to guide evidence-based decisions when planning the surgical management of patients with severe subtalar arthritis.
17 July 2026
Read appraisal →Metabolomics : Official journal of the Metabolomic Society
A metabolomic signatures in hyperuricemia: a systematic review
BACKGROUND: Hyperuricemia (HUA) is traditionally viewed as a disorder of purine metabolism. However, its broader metabolic alterations remain incompletely understood. Metabolomics provides a useful approach for exploring metabolite changes associated with HUA, but a comprehensive synthesis of existing findings is still lacking. AIM OF REVIEW: This systematic review and meta-analysis aimed to characterize the systemic metabolic signature of HUA beyond purine pathways. By synthesizing data from 27 metabolomics studies involving 12,335 participants, the study sought to identify consistent metabolite biomarkers and key dysregulated pathways to provide new insights for diagnosis and therapeutic targeting. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review included 27 metabolomics studies involving 12,335 participants and identified 1,187 metabolites reported in association with HUA. Qualitative synthesis showed 54 consistently elevated and 20 consistently decreased blood metabolites, mainly involving amino acids, lipid-related metabolites, energy-related compounds, vitamins and their derivatives, and purine nucleoside metabolites. The meta-analysis was limited to two eligible studies, with one study contributing most of the statistical weight; it suggested higher levels of Alanine, Leucine, Phenylalanine, and Tyrosine and lower Histidine levels in HUA. Pathway enrichment analysis highlighted "One carbon pool by folate," "Arginine biosynthesis," "Glutathione metabolism," and related amino acid and energy metabolism pathways. Overall, these findings suggest that HUA may be associated with metabolic perturbations beyond purine metabolism alone, but the candidate metabolites and pathways require further validation in longitudinal, standardized, and mechanistic studies.
13 July 2026
Read appraisal →BMJ open
Shared decision making in pain care: a systematic review study protocol of decision aids
INTRODUCTION: Shared decision making (SDM) in healthcare is an ethical imperative and essential to patient-centred care. SDM is particularly useful when several preference-sensitive treatment options exist and in the setting of chronic conditions or longitudinal management. Chronic pain management embodies these characteristics, yet SDM often remains insufficient in this population. Decision aids are designed to facilitate SDM by helping patients and clinicians understand treatment options, clarify patient values, and guide collaborative decision processes. Despite their importance, the use of decision aids in pain management is inconsistent and their reported effectiveness has been variable. However, the current landscape of decision aids for pain management has not been described. This lack of understanding of what tools exist, how they are structured, what decisions they address and how they were developed makes it difficult to advance implementation efforts or identify meaningful gaps in available resources. As such, the purpose of this systematic review is to identify and characterise decision aids for pain management across the lifespan. Specifically, this review will describe the clinical decisions addressed, decision aid structures and delivery formats, development processes and outcomes used to evaluate the impact of existing decision aids. METHODS AND ANALYSIS: Electronic searches were performed in PubMed, CINAHL and Ovid Embase from inception through January 2026. Studies will be assessed for quality using the Mixed Methods Appraisal Tool. Data will be extracted and presented with the aim of describing the: (a) content and structures of pain-related decision aids, (b) development processes used to create existing pain-related decision aids and (c) outcome measures used to evaluate the impact of decision aids in clinical care. ETHICS AND DISSEMINATION: This review does not require ethics approval. Findings will be disseminated to clinicians, researchers and patients through journal publications, conference presentations and in collaboration with patient partners. PROSPERO REGISTRATION NUMBER: CRD420251085288.
11 July 2026
Read appraisal →British journal of sports medicine
Comparative effectiveness of physical therapy interventions in adults with rotator cuff tendinopathy: a systematic review and network meta-analysis
OBJECTIVE: To compare the effects of different physical therapy interventions and identify the most effective intervention on pain, function, quality of life (QoL) and adverse events (AEs) in adults with rotator cuff (RC) tendinopathy. DESIGN: Systematic review and network meta-analysis (NMA) of randomised clinical trials (RCTs). DATA SOURCES: Seven databases and two trial registries were searched up to March 2024. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: RCTs comparing physical therapy interventions to any other physical therapy intervention, sham, placebo, waiting list or no treatment on pain, function, QoL and AEs in adults with RC tendinopathy. DATA SYNTHESIS: A frequentist NMA using a random-effects model was performed. Risk of bias and certainty of the evidence were assessed using the revised Cochrane risk-of-bias tool and the Grading of Recommendations, Assessment, Development and Evaluation approach, respectively. RESULTS: 89 RCTs (5532 participants) were included. Exercises targeting the shoulder muscles may reduce pain (standardised mean difference (SMD) -0.79, 95% CI -1.33 to -0.26) and improve function (SMD 0.74, 95% CI 0.34 to 1.14) compared with no treatment but the evidence is very uncertain. Exercises targeting shoulder and scapular muscles in addition to percutaneous electrolysis (SMD -1.58, 95% CI -2.68 to -0.48) and to trigger point dry needling (SMD 3.10, 95% CI 1.99 to 4.22) seem to be the most effective interventions on pain and function at the end of treatment, respectively. CONCLUSION: Most of the interventions identified may not be superior to isolated shoulder exercises alone, which might be considered a reasonable first-line approach, but the evidence is very uncertain and most interventions are informed by limited data. High-quality research is needed to improve evidence of physical therapy interventions in adults with RC tendinopathy. PROSPERO REGISTRATION NUMBER: CRD42024527176.
8 July 2026
Read appraisal →Journal of medical Internet research
Sensor-Based Monitoring of Knee Osteoarthritis Symptoms in Free-Living Settings: Scoping Review
BACKGROUND: Knee osteoarthritis is a heterogeneous condition characterized by chronic pain, stiffness, and fatigue that fluctuate rapidly over time. Traditional clinical assessments provide only static diagnoses of disease severity, failing to capture the dynamic, day-to-day symptom variability that impacts patient quality of life. While wearable technologies offer the potential for continuous, high-frequency monitoring, previous reviews have examined general technological interventions for knee osteoarthritis management, yet they lack a specific synthesis of technologies for symptom monitoring. OBJECTIVE: This study aims to synthesize current research on sensor technologies used for the continuous monitoring of knee osteoarthritis symptoms in free-living or simulated daily environments. Specifically, the review seeks to (1) map sensor modalities to specific symptom domains (biomechanical, physiological, and behavioral); (2) evaluate the alignment between objective sensor metrics and patient-reported outcome measures; and (3) identify gaps in current monitoring paradigms. METHODS: A systematic literature search was conducted across PubMed, Embase, Web of Science, and IEEE Xplore. The review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Eligibility criteria included studies involving participants with knee osteoarthritis using wearable or portable sensors capable of continuous monitoring (eg, inertial measurement units and electrocardiography) and assessing clinical symptoms (eg, pain, fatigue, and stiffness). Studies relying solely on stationary laboratory equipment (eg, force plates) without a portable component were excluded to ensure relevance to real-world applicability. Data regarding sensor types, sampling frequencies, monitored symptoms, and the statistical association between objective features and subjective symptom severity (key findings) were extracted. RESULTS: A total of 16 studies met the inclusion criteria. The summary constructed from the results revealed a distinct technological saturation: the majority of studies (n=6) used inertial measurement units to quantify biomechanical deficits (eg, gait asymmetry and range of motion), which showed robust correlations with functional limitations. In contrast, there was a notable scarcity of research using physiological sensors (eg, electrocardiography and bioimpedance) to monitor systemic symptoms. Crucially, findings highlighted a significant discrepancy between subjective and objective data, particularly in sleep monitoring, where poor self-reported sleep quality predicted pain exacerbations despite stable objective actigraphy metrics. Furthermore, most systems operated as passive data loggers, with a lack of integration into active feedback loops. CONCLUSIONS: Unlike previous reviews focused solely on biomechanics, this study innovatively maps the use of sensors across a multidimensional symptom spectrum, revealing a critical gap in the monitoring of fatigue and physiological stress. The findings suggest that current sensor applications are limited by a lack of integration with subjective patient experiences. Real-world implementation requires a hybrid monitoring paradigm that combines the ecological validity of wearable sensors with the clinical relevance of patient-reported outcomes. This approach paves the way for digital phenotyping and active feedback systems, offering a personalized strategy for managing the complex symptom burden of knee osteoarthritis.
3 July 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 →Calcified tissue international
Artificial Intelligence Approaches for Osteoporotic Fracture Risk Prediction Using Administrative Health Data: A Systematic Review
To systematically review Machine Learning (ML) fracture risk prediction models developed solely using administrative data, evaluating their development, performance, risk of bias, and concerns regarding applicability. A systematic search was conducted in PubMed, Embase, IEEE, and Web of Science following PRISMA guidelines (up to November 2025). We included studies developing or validating ML models for osteoporotic fracture risk in adults using administrative data without clinical measurements. Risk of bias and concerns for applicability were assessed using the PROBAST tool. Seven studies were included from 3435 initial records. A range of of ML models were utilized, including Random Forests, XGBoost, LASSO-regularized Logistic Regression and Neural Networks. Discriminative performance was moderate-to-good, with best Area Under the Curve (AUC) values ranging from 0.818 for osteoporotic fractures in general to 0.905 for hip fractures only. While five studies showed low risk of bias, five raised applicability concerns due to using specific subpopulations or features with database characteristics. Only two studies used external validation and none directly evaluated clinical utility of the models. ML models using solely administrative data show some promise as scalable, automated tools for fracture risk prediction without requiring manual clinical input. However, clinical implementation is hindered by limited external validation and a lack of formal utility evaluation of the models. Future research should prioritize more rigorous external validation and recalibration of the existing models, more so than the development of novel models, ensuring they are robust, interpretable, and integrable into future clinical workflows.
28 June 2026
Read appraisal →Science advances
Smart contact lens-trained digital twin for device-free personalized uric acid prediction
Tears contain valuable biomarkers and offer potential for noninvasive disease monitoring. However, the lack of correlation analysis between serum uric acid (SUA) and tear uric acid (TUA) has limited their clinical application in personalized medicine. Here, we present a wireless smart contact lens capable of real-time, noninvasive monitoring of TUA as an alternative to blood-based UA testing. We validated the device through correlation analysis in rabbits and human participants, including individuals with hyperuricemia and gout. Daily-life monitoring enabled personalized characterization of TUA fluctuations in response to food intake and physical activity, together with individualized lag time profiling. A strong linear relationship allowed development of a regression model to derive estimated SUA from TUA. Building on these temporal profiles, lifestyle-informed digital twins were constructed to predict daily uric acid dynamics without continuous lens wear. This digital twin-enabled, device-free framework provides a practical route toward unobtrusive and personalized metabolic health monitoring.
27 June 2026
Read appraisal →Acta dermato-venereologica
Recurrent Cutaneous Eosinophilic Vasculitis: A Systematic Review of Clinicopathologic Features and Treatment Outcomes
Recurrent cutaneous eosinophilic vasculitis is a rare, predominantly cutaneous vasculitis described mainly in isolated reports. We aimed to systematically synthesize published evidence on its clinico-pathological features, treatment and outcomes. We reviewed case reports and case series of recurrent cutaneous eosinophilic vasculitis and related entities identified in PubMed, Scopus and reference lists (last searched 16 February 2026), using structured report and case-level extraction, duplicate handling, Joanna Briggs Institute critical appraisal and descriptive synthesis. Twenty reports comprising 24 unique cases were included. Most patients presented with relapsing pruritic purpura of the lower extremities. Peripheral eosinophilia was frequent, antineutrophil cytoplasmic antibodies were negative in all reported cases and histopathology consistently showed eosinophil-rich vasculitis, usually with fibrinoid and/or necrotizing change. Systemic corticosteroids often induced improvement, but relapse during tapering or after withdrawal was common. The evidence was limited by small, heterogeneous reports and incomplete follow-up. Overall, the findings support a recognizable cutaneous-predominant, relapse-prone pattern, highlight the importance of assessing extracutaneous involvement in differential diagnosis and support provisional refinement of the previously proposed diagnostic framework.
26 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 →BMC oral health
Can poor nutrition and diet influence temporomandibular disorder? A systematic review.
BACKGROUND: The relationship between diet, nutrition, and painful temporomandibular disorders (TMD) is not well established, despite increasing interest in lifestyle factors in chronic pain. This systematic review aimed to synthesize available evidence on how dietary patterns and nutritional status may be associated with painful TMD. METHODS: An electronic search was conducted in the databases MEDLINE, CINAHL, EMBASE, the Cochrane Central Registry of Controlled Trials (CENTRAL) and Web of Science for clinical and observational trials from the beginning of each database to November 2025. Risk of bias was performed using the Study Quality Assessment Tools from the National Heart, Lung, and Blood Institute (NHLBI). RESULTS: Out of 7,760 records and after the risk of bias assessment, only seven studies judged as having a low risk of bias were included. Overall, the included studies indicate that the association between dietary factors and TMD remains unclear. Prospective cohort studies did not demonstrate that prenatal or adolescent diet quality independently predicted TMD. Cross-sectional studies suggested that specific dietary patterns may be related to TMD-related symptoms. Women with myogenous TMD showed lower intake of several nutrients compared with controls. Experimental evidence indicated that monosodium glutamate ingestion increased pain intensity in myofascial TMD, while the only randomized trial found no significant pain differences between vitamin D supplementation and diclofenac. CONCLUSIONS: Current evidence suggests that some dietary components and nutritional factors may be associated with TMD-related symptoms or pain responses; however, the findings are limited, heterogeneous, and insufficient to support firm causal or therapeutic conclusions.
25 June 2026
Read appraisal →Lasers in medical science
Effect of photobiomodulation on pain and quality of life in fibromyalgia syndrome: a systematic review
Fibromyalgia Syndrome (FMS) is a chronic pain disorder characterized by widespread pain and central sensitization that significantly impacts the quality of life (QoL). For management to be effective, a multidisciplinary approach to care is typically required. Photobiomodulation therapy (PBMT), a non-pharmacological treatment, has garnered attention lately, though its clinical relevance and applications are not well defined. The objective of this review was to assess the effectiveness of PBMT in reducing FMS symptoms. This systematic review was registered at PROSPERO (CRD420251084730) and conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines. A total of seven randomized controlled trials were identified following an extensive literature search across various databases, including PubMed, Scopus, Web of Science, the Cochrane Library, Embase, Ovid and ProQuest. To evaluate the methodological quality of these studies, the Cochrane Risk of Bias (RoB 2.0) tool was applied. PBMT demonstrated consistent short-term reductions in pain intensity and improvements in QoL. Additional positive effects on sleep quality and psychological well-being were observed, indicating that PBMT may provide additional therapeutic benefits beyond pain reduction, including improvements in sleep quality and psychological well-being. PBMT has shown promise as a safe, non-pharmacological adjunct therapy that may provide short-term improvements in pain levels and QoL, but substantial heterogeneity limits generalizability. Clinical trials with large samples and standardized methodologies should be conducted to better clarify the role of PBMT in multidisciplinary therapy for FMS.
24 June 2026
Read appraisal →Acta orthopaedica
Registration and reporting characteristics of trials investigating exercise therapy following total knee arthroplasty: a systematic review.
BACKGROUND AND PURPOSE: Prospectively registering the primary trial outcome is important to reduce selective outcome reporting and increase the trustworthiness of findings, which guide clinical practice. The objectives of our systematic review were to explore and compare the reporting characteristics of prospectively and non-prospectively registered trials investigating exercise therapy following total knee arthroplasty. METHODS: Randomized trials comparing effects of exercise therapy after total knee arthroplasty for osteoarthritis were identified in 4 databases from 2000 to August 12, 2024. One primary outcome per trial was extracted, using a pre-specified hierarchical algorithm, irrespective of outcome domain. Pooled standardized mean differences (SMDs) were calculated on pre-specified outcome domains, and risk-of-bias assessed using the Cochrane Risk-of-Bias tool v2. RESULTS: 94 trials, comprising 9,396 participants, were included, of which 13 were prospectively registered, 33 retrospectively registered, and 48 unregistered. A single primary outcome was defined in 44% of the 94 trials, and 4 trials reported a primary outcome consistent with a prospective registration. The pooled SMD of primary outcomes was 0.06 (95% confidence interval [CI] -0.03 to 0.16) for prospectively registered trials, 0.67 (CI 0.22-1.11) for retrospectively registered trials, and 0.59 (CI 0.32-0.86) for unregistered trials. Lower risk-of-bias ratings and higher proportions of intention-to-treat adherence, dropout reporting, and adverse event reporting were observed among prospectively registered trials. CONCLUSION: Among prospectively registered trials we showed smaller effect size estimates between interventions with lower risk-of-bias ratings, and higher proportions of intention-to-treat adherence, dropout reporting, and adverse event reporting in contrast to trials without prospective registration; furthermore, clear specification of a single primary outcome was uncommon among trials evaluating exercise therapy after total knee arthroplasty.
23 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 →Acta orthopaedica
Predicting persistent pain after total knee arthroplasty using different machine learning algorithms
BACKGROUND AND PURPOSE: After total knee arthroplasty (TKA), 10-20% of patients remain unsatisfied. Well-performing clinical prediction models can provide individualized risk estimates and stratification in terms of poor outcomes, resulting in unnecessary surgeries being avoided and patients being counseled preoperatively. We aimed to create a precise, well-performing prediction model for clinical application using different machine learning algorithms to predict those patients who will have residual pain, a low total Oxford Knee Score (OKS) and the patient group who do not achieve minimally clinical important difference (MCID) in OKS 1 year after TKA. METHODS: We conducted a retrospective cohort study based on patients who had undergone primary TKA at our institution combined with 751 patient-related variables. The multivariable models used were based on the results of univariate analysis. We used the machine learning method Extreme Gradient Boosting (XGBoost). The discrimination capability of the models was measured with the area under the curve (AUC). RESULTS: 11,755 patients were included in this study. There were 850 (7.2%) patients who experienced persistent pain 1 year after TKA. The AUC was 0.67. For the secondary outcomes, the AUC values were similar. The most important variables in the model were lower preoperative OKS, younger age, valgus malalignment, lower preoperative pain OKS, use of mild opioid, neuropathic pain medicine and thyroxine, and higher body mass index. CONCLUSION: The prediction models achieved poor AUCs. It seems clear that the prediction of pain and functional outcome after TKA is difficult, even with a large patient cohort combined with 751 patient-related variables and sophisticated machine-learning algorithms.
23 June 2026
Read appraisal →International journal of biometeorology
Impact of balneotherapy on drug consumption: a systematic review and an economic evaluation of drug deprescribing
Some previous studies have suggested that balneotherapy could be associated with a decrease in drug consumption. No study has investigated pharmacoeconomic consequences in terms of monetary savings. The present study was performed to evaluate potential savings (according to societal perspective) associated with decreased drug consumption resulting from spa treatments using randomized clinical trials (RCT) identified after a systematic review. Among 48 RCT, 8 trials investigating rheumatological diseases (low back or shoulder pain, osteoarthritis, ankylosing spondylitis, fibromyalgia), were included in the economic evaluation of direct costs (€) using 2024 data of drug reimbursements according to French health insurance data. Savings calculated related to non-steroidal anti-inflammatory drugs (NSAIDs') decrease were between €0.05 million and €1.03 million at 6 months (mean value: €504.900) for the 441,776 patients who underwent rheumatology-oriented spa treatment in France in 2024 versus controls. For analgesics, values ranged from €0.73 million to around €2.31 million (mean value: €1,547.400). Despite several limitations that could not be overlooked (heterogeneity of studied populations, interventions, duration, outcome measures), the study showsfor the first timethat decreased drug consumption resulting from balneotherapy is associated with important savings regarding NSAIDs and, to a greater extent, analgesics. Balneotherapy is a unique opportunity for deprescribing, enabling both significant monetary savings for national health insurance, complementary health insurances and patients, while preventing adverse drug reactions or decreasing physiotherapy sessions or hospitalizations.
11 June 2026
Read appraisal →Medicine
Machine learning identifies traffic-related pollutant mixtures as potential factors suggestive of association with osteoporosis in a cross-sectional analysis of NHANES
The combined effect of traffic-related pollutant mixtures on osteoporosis (OP) remains unclear. This study aimed to evaluate such associations using machine learning and mixture modeling approaches. A cross-sectional analysis was conducted among 3053 participants from the National Health and Nutrition Examination Survey 2015 to 2018. Eighteen exposures were assessed, including heavy metals, polycyclic aromatic hydrocarbons, phthalates, per- and polyfluoroalkyl substances, volatile organic compounds, diesel exhaust, and behavioral factors. OP was defined by femoral neck bone mineral density T-score ≤-2.5. Weighted quantile sum regression and 5 machine learning models were applied, accounting for complex survey design. OP prevalence was 12.97%. Weighted quantile sum regression showed a positive but nonsignificant mixture odds ratio (odds ratio = 1.21; 95% confidence interval: 0.77-2.63; P = .412). The largest positive weights were daily outdoor work duration (0.240) and occupational diesel exhaust (0.136). Random forest identified female sex, age, vitamin D, blood lead, and body mass index as top predictors. Least Absolute Shrinkage and Selection Operator achieved the highest test area under the receiver operating characteristic curve (0.81) with the lowest cross-validation standard deviation (0.0167). Its coefficients highlighted occupational diesel exhaust (β = 0.40) as a notable environmental factor alongside female sex (β = 0.95) and age (β = 0.70). Traffic-related pollutant mixtures showed a cross-sectional association with OP in a nationally representative US population, with occupational diesel exhaust and prolonged outdoor work emerging as key contributors in mixture models. However, the nonsignificant overall mixture effect and potential for reverse causation warrant caution in interpretation. These findings support considering environmental and occupational factors in OP prevention, although the overall mixture effect did not reach statistical significance.
31 May 2026
Read appraisal →Medicine
Effect of aerobic exercise of different intensity on articular cartilage metabolism in patients with knee osteoarthritis: A randomized controlled trial
BACKGROUND: Osteoarthritis (OA) of the knee is a leading cause of disability worldwide, yet optimal exercise intensity for cartilage protection remains unclear. This randomized controlled trial investigated dose-response effects of aerobic exercise intensity on cartilage metabolism, clinical symptoms, and structural outcomes in knee OA patients. METHODS: One hundred twenty participants with knee OA (Kellgren-Lawrence grade 2-3) were randomly assigned to low-intensity (50-60% heart rate reserve [HRR]), moderate-intensity (60-70% HRR), high-intensity (70-80% HRR) treadmill walking or stationary cycling, or a control group for 12 weeks (3 sessions/week). Heart rate was continuously monitored using Polar H10 chest-strap monitors. Primary outcomes were serum C-terminal telopeptide of type II collagen and cartilage oligomeric matrix protein levels. Secondary outcomes included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, Visual Analog Scale (VAS) pain, 6-minute walk test, and magnetic resonance imaging-assessed cartilage morphology. Data were analyzed using mixed-model repeated measures analysis of variance with IBM SPSS Statistics version 26.0 (IBM Corp.). RESULTS: The high-intensity group demonstrated the greatest reductions in C-terminal telopeptide of type II collagen (-28.5%, P < .001) and cartilage oligomeric matrix protein (-22.3%, P < .001), the largest improvements in WOMAC scores (-45.3%, P < .001) and VAS pain (-52.5%, P < .001), and the greatest increases in cartilage thickness (+4.2%) and volume (+3.8%). A significant dose-response relationship was confirmed (group × time interaction: F (3108) = 4.82, P = .003). Among participants in the high-intensity group, 73% achieved the minimal clinically important differences (MCID) for WOMAC total score and 80% achieved the MCID for VAS pain. The 6-minute walk test improvement in the high-intensity group (71 m) exceeded the established MCID of 26 m. No serious adverse events were reported; minor events (transient knee pain exacerbation and delayed-onset muscle soreness) resolved spontaneously within 48 to 72 hours. CONCLUSIONS: Appropriately prescribed high-intensity aerobic exercise safely and effectively improved cartilage metabolism, alleviated symptoms, and enhanced functional capacity in knee OA patients. These findings support revising current conservative exercise recommendations upward when tolerable.
31 May 2026
Read appraisal →BMC musculoskeletal disorders
The effectiveness of telerehabilitation in upper limb musculoskeletal disorders: a systematic review.
BACKGROUND: Telerehabilitative services have been increasingly used in recent years, raising questions about their effectiveness. In musculoskeletal disorders, evidence supports telerehabilitation but methodological quality of evidence is limited and focused on lower limb disorders. Hence, this systematic review aimed to assess the effectiveness of telerehabilitation in upper limb musculoskeletal disorders. METHODS: We conducted electronic searches in MEDLINE, Embase, and AMED (up until 11/27/2024), complemented by hand searches. Randomized (RCTs) and non-randomized studies of interventions (NRSIs) assessing upper limb musculoskeletal disorders reporting on pain, activities of daily living (ADL), or health-related quality of life (HrQol) were included. We focused on studies from high-income countries in English or German. Risk of bias was assessed using RoB 2 and ROBINS-I. Standardized mean differences (SMDs) and 95% confidence intervals were derived from meta-analysis, where negative values favor telerehabilitation. Certainty of evidence was rated using GRADE. We grouped studies comparing telerehabilitation to standard care (subgrouped into in-person or minimal intervention) and separately examined studies with a tele-adjunct. Compared to in-person rehabilitation we assessed whether outcomes were similarly improved with telerehabilitation. For tele-interventions as adjunct or compared to minimal care we assessed whether telerehabilitation improved outcomes. RESULTS: We included twenty RCTs representing 1,285 participants. All NRSIs were excluded due to critically high risk of bias. Compared to in-person rehabilitation, telerehabilitation showed similar improvements with very low certainty of evidence in pain (SMD: -0.33 [-1.16 to 0.5] VAS/NRS), moderate in ADL (SMD: -0.07 [-0.31 to 0.17] QuickDASH/DASH), and low in HrQol (SMD: -0.26 [-0.82 to 0.31]). Compared to brochure-based exercising, certainty of evidence was low for improved pain (SMD: -0.28 [-0.58 to 0.03]), moderate in ADL (SMD: -0.56 [-0.88 to -0.24]), and low in HrQol (SMD: -0.31 [-0.65 to 0.02]). Tele-adjunct yielded low certainty of evidence for improvements in pain (SMD: -0.38 [-0.71 to -0.05]) and moderate in ADL (SMD: -0.51 [-0.88 to -0.14). CONCLUSIONS: Our results tend to support the effectiveness of telerehabilitation across different comparisons although certainty of evidence is inconclusive. Future studies should particularly investigate the non-inferiority of telerehabilitation compared to in-person rehabilitation and the added benefit of tele-adjunct. TRIAL REGISTRATION: Prospero registration ID: CRD42024622465.
31 May 2026
Read appraisal →Journal of translational medicine
Mesenchymal stem cell-derived extracellular vesicles for osteochondral defect regeneration: a systematic review and meta-analysis of preclinical studies
BACKGROUND: In recent years, the number of animal studies investigating mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) therapy for osteochondral defects has steadily increased. However, a comprehensive and systematic quantitative analysis is lacking. This meta-analysis aimed to evaluate the efficacy of MSC-EVs in animal models of osteochondral defect through a meta-analysis. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched up to January 31, 2025, to identify and select preclinical studies on MSC-EVs therapy for osteochondral defect models. No restrictions were applied regarding the specific characteristics of MSC-EVs or animal models. A random-effects model was used to perform pooled analyses of osteochondral repair scores, bone structural parameters, and histological scores. Subgroup analyses were conducted to explore potential sources of heterogeneity. Sensitivity analyses, funnel plots, and Egger's test were employed to assess the robustness and stability of the results. RESULTS: A total of 19 studies met the inclusion criteria. MSC-EVs intervention improved International Cartilage Repair Society (ICRS) and Modified O'Driscoll Scale (MODS) scores at both 3 and 6 months, and significantly increased BV/TV, Tb.Th, as well as histological scores of cartilage and subchondral bone. Subgroup analyses indicated that none of the examined subgroups were significant sources of heterogeneity. Sensitivity analyses demonstrated the robustness of the results. CONCLUSIONS: MSC-EVs improved osteochondral repair scores, bone structural parameters, and histological outcomes in preclinical models, indicating their potential for promoting osteochondral regeneration. However, the evidence is primarily derived from small animal models with methodological variability and publication bias. Future studies should focus on large-animal models, standardized EVs preparation and dosing protocols, and long-term safety evaluations to facilitate clinical translation.
31 May 2026
Read appraisal →The Cochrane database of systematic reviews
Botulinum toxin type A for subacute/chronic neck pain
RATIONALE: Botulinum toxin type A (BoNT-A) intramuscular injections are commonly administered for neck pain unresponsive to other therapies, but the benefit-harm profile remains uncertain. OBJECTIVES: To assess the benefits and harms of intramuscular BoNT-A injection for people with subacute to chronic neck pain. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registers, together with reference checking, citation searching and contact with study authors up to 4 March 2026. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs), including cross-over, pragmatic, or cluster designs, were included for adults with subacute to chronic neck disorder without radicular findings, with or without cervicogenic headache, and compared BoNT-A to placebo or no-treatment. OUTCOMES: Our outcomes were pain, function-disability, health-related quality of life, participant-reported treatment success, adverse events and costs at both short-term (< 24 weeks) and long-term (≥ 24 weeks) follow-up. RISK OF BIAS: We assessed the risk of bias (RoB) using the ROB 2 tool. SYNTHESIS METHODS: We synthesised results using meta-analyses with random-effects models to calculate mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CIs), or using SWiM (Synthesis Without Meta-analysis) methods. We assessed certainty with GRADE. INCLUDED STUDIES: This update included 16 trials (855 participants) compared to six (252 participants) in the previous review: 13 parallel RCTs and three cross-over RCTs. One other trial is awaiting classification. Short-term follow-up ranged from 3 to 12 weeks post-treatment, and long-term follow-up was six months. Participants (mean age 45 years; 64% female; pain severity 56 on the Visual Analogue Scale (VAS 0 to 100)) were from ambulatory care settings in North America (five trials), Central America (one trial), Europe (six trials), the Middle East (one trial), Central Asia (one trial), and the East Asia & Pacific region (two trials), from upper (12 trials) or upper-middle (four trials) income economies. Disorder classifications included non-specific neck pain - myofascial (eight trials), whiplash-associated disorder (four trials), and cervicogenic headache (four trials). Overall, 88% of participants had chronic pain. The dose varied from 10 to 400 units over 1 to 10 trigger points. The RoB was high or raised some concern across all outcomes. SYNTHESIS OF RESULTS: Since 2011, evidence has shifted from no benefit to a potentially slight-to-small short-term benefit for BoNT-A compared with placebo. No trials compared BoNT-A with no treatment, and evidence was limited by bias (no studies with an overall low RoB), imprecision, and potential publication bias. For pain intensity measured on the VAS (scale 0 to 100), BoNT-A may result in a slight-to-small improvement in the short term (MD 5.95 points lower, 95% CI 10.89 lower to 1.02 lower; I2 = 0%; 12 studies, 393 participants; low-certainty evidence; downgraded two levels due to high overall RoB and indirectness), but not in the long term (MD 11.74 points lower, 95% CI 35.63 lower to 12.16 higher; I² = 50%; 2 studies, 43 participants; low-certainty evidence; downgraded two levels due to high RoB and imprecision). Mean pain in the placebo group was 46.66 points compared to 40.71 in the BoNT-A group, representing an absolute improvement of 6% (95% CI 11% better to 1% better). Additionally, there may be a moderate risk reduction in pain events in the short term (RR 0.68, 95% CI 0.56 to 0.83; I² = 0%; 2 studies, 292 participants; low-certainty evidence; downgraded two levels due to high overall RoB and dissemination bias, including potential conflict of interest from funding sources that may overestimate effects). Assuming a 70% risk with placebo, the corresponding risk with BoNT-A is 47%, representing a 23% absolute risk reduction. Five people (95% CI 3 to 9) would need BoNT-A treatment for one person to benefit. For physical function measured on the Neck Disability Index (scale 0 to 100), BoNT-A may have little to no effect in the short term, but the evidence is very uncertain (MD 2.49 points higher, 95% CI 9.72 lower to 14.70 higher; I² = 0%; 3 studies, 76 participants; very low-certainty evidence; downgraded three levels due to high overall RoB, indirectness, and wide confidence intervals). For health-related quality of life (change score), BoNT-A may make little to no difference in the short term (MD 2.30 points higher, 95% CI 12.57 lower to 17.17 higher; 1 study, 28 participants; low-certainty evidence; downgraded two levels due to imprecision). For participant-reported treatment success, BoNT-A may provide a small improvement in the global rating of change. Short-term results: MD 1.16 points lower on a 1 to 5 Verbal Rating Scale (95% CI 1.86 lower to 0.46 lower; 1 study, 31 participants; low-certainty evidence), corresponding to an absolute improvement of 20% (95% CI 10% to 36%). Long-term results were similar: MD 2.00 points lower on a 0 to 10 Patient Global Assessment (95% CI 3.80 lower to 0.20 lower; 1 study, 19 participants; 20% absolute risk reduction, low-certainty evidence). Evidence was downgraded by two levels for RoB and imprecision. No studies evaluated participant satisfaction or serious adverse events. For non-serious adverse events, participants treated with BoNT-A may have a small, negligible increased risk (RR 1.51, 95% CI 1.04 to 2.20; I² = 28%; number-needed-to-treat for an additional harmful outcome (NNTH) 6, 95% CI 4 to 12; 7 studies, 489 participants; low-certainty evidence; downgraded two levels due to RoB and indirectness). Participants treated with BoNT-A have a 16% increased absolute risk of experiencing non-serious adverse events lasting up to three weeks, such as injection soreness, muscle fatigue, and headache. AUTHORS' CONCLUSIONS: BoNT-A may provide slight-to-small short-term pain relief (6%) and perceived treatment success (20%) for subacute and chronic neck pain, but may offer no long-term physical function or health-related quality of life benefits. The moderate (23%) risk reduction in pain events may be overestimated due to publication bias. Non-serious adverse events are 16% more frequent. Uncertainty remains due to wide confidence intervals, short-term single-dose trials, and dose variation, highlighting the need for larger, high-quality studies with comprehensive adverse event reporting. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol and previous versions available via doi.org/10.1002/14651858.CD008626, doi.org/10.1002/14651858.CD008626.pub2 and doi.org/10.1002/14651858.CD008626.pub3 (withdrawn).
30 May 2026
Read appraisal →The Cochrane database of systematic reviews
Surgery for thumb (trapeziometacarpal joint) osteoarthritis
RATIONALE: Surgery is used to treat persistent pain and dysfunction due to osteoarthritis at the base of the thumb, when conservative management is no longer effective. This is an update of a Cochrane review first published in 2005. OBJECTIVES: To evaluate the benefits and harms of different surgeries for people with thumb (trapeziometacarpal) osteoarthritis. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase up to 19 May 2025. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs that compared at least two surgical techniques for trapeziometacarpal osteoarthritis. We excluded studies that used non-surgical interventions as the sole comparator (e.g. splinting). OUTCOMES: Pain, physical function, quality of life, patient global assessment, adverse events, treatment failure and trapeziometacarpal joint imaging. RISK OF BIAS: We assessed risk of bias using the Cochrane Risk of bias 1.0 tool (RoB 1). SYNTHESIS METHODS: Two authors screened studies, extracted data, assessed risk of bias, and judged the certainty of evidence using the GRADE criteria. We synthesised effect estimates for both dichotomous (risk ratio (RR) using Mantel-Haenszel method) and continuous outcomes (standardised mean difference (SMD) or MD using the inverse-variance method) using a random-effects meta-analysis model. INCLUDED STUDIES: We included 25 studies with 1591 participants. We identified 11 surgical procedures: trapeziectomy with ligament reconstruction and tendon interposition (LRTI), trapeziectomy, trapeziectomy with ligament reconstruction, trapeziectomy with interpositional arthroplasty, Artelon joint implant, arthrodesis, trapeziometacarpal joint replacement, trapeziectomy and haematoma distraction arthroplasty, trapeziectomy with interpositional arthroplasty with allograft, arthroscopic hemitrapeziectomy, and suture tape suspensionplasty. Other than arthrodesis, no studies compared surgeries that did not involve at least partial trapeziectomy (e.g. first carpometacarpal joint denervation). We found no studies with placebo or non-surgical comparators. SYNTHESIS OF RESULTS: More than 90% of the included studies were at high or unclear risk of performance, detection and selective reporting biases. Below, we summarise the evidence for trapeziectomy with LRTI, the most widely utilised technique. We did not summarise single-study comparisons for trapeziectomy with LRTI. Quality of life, patient global assessment and treatment failure were not reported. Pain was measured on a 100-point visual analogue scale (mm); physical function on a relevant scale (typically the Disabilities of the Arm, Shoulder and Hand questionnaire) presented as a mean difference; adverse events as the proportion of participants who experienced any adverse events; trapeziometacarpal joint imaging as the scapho-metacarpal distance at rest reported in mm. Trapeziectomy with LRTI versus trapeziectomy: compared to trapeziectomy, trapeziectomy with LRTI may make little to no difference to pain (MD -2.80 mm, 95% CI -9.82 to 4.21; I2 = 0%; 3 studies, 162 participants), physical function (SMD 0.01, 95% CI -0.70 to 0.72 translated to an MD of 0.03 points (95% CI -1.95 to 1.98); I2 = 19%; 3 studies, 211 participants), adverse events (RR 1.89, 95% CI 0.96 to 3.73; I2 = 0%; 4 studies, 328 participants) or scapho-metacarpal distance (MD -0.10 mm, 95% CI -0.81 to 0.61; 1 study, 42 participants); all low-certainty evidence. Trapeziectomy with LRTI versus trapeziometacarpal joint replacement: we are uncertain of the effects of trapeziectomy with LRTI compared to trapeziometacarpal joint replacement on pain (MD 1.38 cm, 95% CI 0.7 to 2.07; 2 studies, 206 participants) and physical function (MD 12.53, 95% CI 3.71 to 21.35; I2 = 78%; 2 studies, 207 participants); both very low-certainty evidence. There may be little to no difference in adverse events (RR 0.36, 95% CI 0.12 to 1.06; I2 = 0%; 3 studies, 261 participants; low-certainty evidence). Trapeziectomy with LRTI versus haematoma distraction arthroplasty: compared to haematoma distraction arthroplasty, we are uncertain of the effects of trapeziectomy with LRTI on pain (MD 0.34 cm, 95% CI -1.19 to 1.87; I2 = 97%; 2 studies, 172 participants) and physical function (MD 1.96 points, 95% CI -0.40 to 4.32; I2 = 55%; 2 studies, 172 participants); both very low-certainty evidence). LRTI may make little to no difference to adverse events (RR 16.66, 95% CI 0.99 to 279.94; 1 study, 120 participants) or scapho-metacarpal distance (MD 0.0 mm, 95% CI -2.12 to 2.12; 1 study, 120 participants); both low-certainty evidence. Trapeziectomy with LRTI versus trapeziectomy with interpositional arthroplasty: compared to trapeziectomy with interpositional arthroplasty, trapeziectomy with LRTI may slightly reduce pain (MD -0.57cm, 95% CI -1.10 to -0.04; I2 = 0%; 2 studies, 98 participants), and may make little to no difference to adverse events (RR 1.29, 95% CI 0.49 to 3.44; 2 studies, 146 participants) and scapho-metacarpal distance (MD -0.70 mm, 95% CI -1.44 to 0.04; 1 study, 46 participants); all low-certainty evidence. We are uncertain of the effects of trapeziectomy with LRTI on physical function (MD -6.75 points, 95% CI -15.88 to 2.39; I2 = 70%; 2 studies, 98 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There are no placebo-controlled trials or studies comparing surgery with non-operative treatment. Low-certainty evidence showed that compared to trapeziectomy, trapeziectomy with LRTI for people with thumb osteoarthritis, may result in little to no difference in pain, function or scapho-metacarpal distance. Compared to trapeziectomy with interpositional arthroplasty, trapeziectomy with LRTI may slightly reduce pain. Trapeziectomy with LRTI may make little to no difference to scapho-metacarpal distance compared to haematoma distraction arthroplasty or trapeziectomy with interpositional arthroplasty. Very low-certainty evidence showed that we are uncertain of the effects of trapeziectomy with LRTI on pain and function compared to trapeziometacarpal joint replacement or haematoma distraction arthroplasty. We are uncertain of the effects of trapeziectomy with LRTI on function compared to trapeziectomy with interpositional arthroplasty. Overall, low-certainty evidence showed that trapeziectomy with LRTI may make little to no difference to adverse events. Low- to very low-certainty evidence from small studies limits our ability to draw conclusions on the benefits and harms of surgical procedures for thumb osteoarthritis. FUNDING: None. REGISTRATION: Protocol (2004) DOI: 10.1002/14651858.CD004631 Original review (2005) DOI: 10.1002/14651858.CD004631.pub2. Review update (2009) DOI: 10.1002/14651858.CD004631.pub3 Review update (2015) DOI: 10.1002/14651858.CD004631.pub4 Review update (2017) DOI: 10.1002/14651858.CD004631.pub5.
30 May 2026
Read appraisal →European radiology experimental
Enhancing resolution and image quality in musculoskeletal MRI using deep learning reconstruction
OBJECTIVE: Deep learning-based noise reduction enhances image quality, overcoming the tradeoff among acquisition time, spatial resolution, and signal-to-noise ratio (SNR). We implemented deep learning reconstruction (DLR) into a 1.5-T musculoskeletal (MSK) magnetic resonance imaging (MRI) protocol to improve image quality without compromising SNR. MATERIALS AND METHODS: We retrospectively analyzed 39 MRI examinations performed on a 1.5-T scanner using standard-resolution (SR) sequences and sequences with higher resolution reconstructed with DLR (HR-DLR). Exams of the knees, shoulders, ankles, and hips were evaluated. The included sequences were: three-dimensional T2-weighted fast advanced spin-echo; T1-weighted and proton density-weighted fast spin-echo. One expert reader and two junior readers in agreement evaluated the visibility of various structures using a 5-point Likert scale in a blind manner. A fourth reader estimated the SNR and contrast-to-noise ratio (CNR) in bone and muscle. A mixed model was used to compare HR-DLR versus SR measures. The agreement between radiologists was assessed with the Kendall τ coefficient. RESULTS: The HR-DLR sequences globally had a smaller pixel size and shorter acquisition time. A good inter-reader agreement was obtained for SR sequences (0.613 ≤ τ ≤ 0.788) and even higher levels of agreement for HR-DLR sequences (0.682 ≤ τ ≤ 0.961). All the structures had higher or similar Likert scores in HR-DLR sequences (p < 0.001), regardless of joint and sequence contrast. Apparent SNR and CNR of HR-DLR and SR were similar. CONCLUSION: Incorporating DLR into 1.5-T MSK MRI protocols enhances resolution and maintains SNR and CNR, improving MSK structure visualization. RELEVANCE STATEMENT: This study demonstrated the effectiveness of deep learning reconstruction in improving the efficiency of 1.5-T musculoskeletal MRI exams. Despite shorter acquisition times, the visibility of key MSK structures was consistently rated as superior or similar in higher-resolution images with DLR. KEY POINTS: MRI is one of the primary diagnostic tools for evaluating MSK injuries and disorders. Deep learning reconstruction (DLR) implemented in a 1.5-T MSK protocol improved resolution, still preserving SNR and CNR. Higher scores were assigned by different raters to the DLR images, showing image quality improvement.
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 →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 →ChemMedChem
A 24-Day MicroCycle Journey to Interleukin-17 Inhibitors: From Library Design to Central Core Prioritization and Capping Group Identification
We herein report an application of the MicroCycle platform, which leverages advanced machine learning models, automation, and miniaturization of processes to accelerate the exploration of chemical space through libraries. This approach was applied to a novel thiazole-based series targeting interleukin-17, enabling rapid prioritization of central cores and identification of compelling new capping groups, thereby guiding further optimization efforts.
27 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 →Rheumatology international
Home-based postural exercise as an adjunct to duloxetine improves sleep quality, physical quality of life, and trunk mobility in fibromyalgia: a randomized controlled trial
In fibromyalgia syndrome (FMS), current guidelines recommend combining pharmacological treatments such as duloxetine with exercise interventions. This randomized controlled trial aimed to evaluate the effectiveness of a home-based postural exercise program as an adjunct to pharmacological treatment in individuals with FMS. Fifty-one patients diagnosed with FMS according to the 2016 American College of Rheumatology criteria were randomly assigned to an exercise group (EG, n = 26) or a control group (CG, n = 25). Both groups received duloxetine therapy, while the EG additionally performed a home-based postural exercise program three times per week for four weeks. Outcomes included pain intensity, pressure pain threshold (PPT), sleep quality, anxiety and depression, quality of life, and trunk range of motion (ROM). Significant improvements over time were observed in pain intensity, psychological symptoms, sleep quality, quality of life, and PPT in both groups (p < 0.05). Significant group × time interactions favored the EG for sleep quality assessed using the Pittsburgh Sleep Quality Index (F = 11.07, p = 0.002, η²=0.184), the physical component of the Short Form-12 (F = 4.31, p = 0.043, η²=0.081), trunk flexion (F = 20.85, p < 0.001, η²=0.299), trunk extension (F = 8.34, p = 0.006, η²=0.146), and global trunk ROM (F = 35.10, p < 0.001, η²=0.417). No significant group × time interactions were observed for pain intensity, anxiety, depression, mental quality of life, or PPT (p > 0.05). Adding a home-based postural exercise program to pharmacological treatment may provide short-term additional benefits in sleep quality, physical quality of life, and spinal mobility in individuals with FMS; however, these findings should be interpreted cautiously due to the short intervention duration and absence of follow-up assessment.
25 May 2026
Read appraisal →Rheumatology international
Cost-effectiveness of artificial intelligence interventions for musculoskeletal disorders of the spine: a systematic review
Musculoskeletal disorders (MSDs) represent a substantial global health burden, and artificial intelligence (AI)-based technologies are emerging as potential approaches for their management. However, evidence regarding the cost-effectiveness of these interventions remains limited. This systematic review synthesised the available evidence on the cost-effectiveness of AI-based technologies for managing MSDs of the spine. This systematic review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. PubMed, Medline, CINAHL, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and Directory of Open Access Journals (DOAJ) databases were searched. After title and abstract screening, the remaining articles underwent full-text review by two independent reviewers, who extracted economic outcome data comparing AI-based interventions versus control. A total of 347 studies were identified, with 59 duplicates removed and 251 excluded based on title and abstract. After full-text review, seven eligible studies were included in the review. These studies represented five countries (United States (n = 2), Germany (n = 2), Denmark (n = 1), Australia (n = 1) and South Korea (n = 1)). The studies adopted a healthcare perspective (n = 4), a societal perspective (n = 2) and a healthcare and societal perspective (n = 1). Time durations varied widely, from four weeks to twelve months in trials to three years or lifetime in models, with one study using a 20-month post-implementation period. The AI components of the interventions encompassed a range of technologies, including a deep learning-based diagnostic and exercise prescription platform, AI-driven chest radiograph screening, the self-BACK application, standardised Magnetic Resonance Imaging (MRI) protocols, the Back Pain Choices online decision support tool, and the Kaia back pain application. In three studies, AI-based interventions for MSDs of the spine showed consistent positive QALY gains. Across the seven studies, five interventions (71%) were found to be cost-effective or cost-saving, four (57%) were dominant, while two (29%) were not cost-effective, indicating that most AI-based and digital interventions for MSDs of the spine provide favourable economic value compared with standard care. This is the first systematic review to synthesise evidence on the cost-effectiveness of AI-based technologies for the management of MSDs of the spine. The results suggest that AI-based interventions have the potential to contribute to more efficient healthcare resource use and may support policy and decision-making. However, their impact on reducing the economic burden of MSDs of the spine and improving health outcomes is not yet conclusive, and further standardised economic evaluations are needed to strengthen the evidence base. PROSPERO registration number: https://www.crd.york.ac.uk/PROSPERO/view/CRD42025642775 .
25 May 2026
Read appraisal →PloS one
Effectiveness of tele-rehabilitation using AI-guided exercise and pain neuroscience education for fibromyalgia (FIBROIA): Protocol for a randomized controlled trial
INTRODUCTION: Fibromyalgia (FM) is a chronic condition characterized by widespread pain and cognitive dysfunction, with pharmacological treatments offering limited efficacy. Although Pain Neuroscience Education (PNE) and therapeutic exercise are evidence-based interventions, accessibility and adherence remain major challenges particularly in underserved regions such as Latin America. This trial investigates the effectiveness of a 12-week tele-rehabilitation program (FIBROIA) that integrates Artificial Intelligence (AI)-guided exercise with PNE to enhance access to comprehensive multimodal care. METHODS AND ANALYSIS: This multicentre, randomized, assessor-blinded, parallel-group controlled trial will enroll fifty adults meeting the 2016 ACR criteria for FM. Participants will be randomly assigned (1:1) to either the intervention group or enhanced usual care. The intervention consists of three personalized exercise sessions per week delivered through the Rehbody AI platform, which provides real-time biomechanical feedback, along with a weekly PNE module designed to reconceptualize pain. The primary outcome is the change in pain intensity, measured using the Visual Analogue Scale (VAS), at week 13 (±7 days), immediately following completion of the 12-week program. Secondary outcomes include the Fibromyalgia Impact Questionnaire-Revised (FIQ-R), lower-limb strength assessed by the 30-Second Sit-to-Stand test, and health-related quality of life measured with the EQ-5D-3L. Statistical analyses will follow an intention-to-treat (ITT) framework. DISCUSSION: The FIBROIA protocol addresses the urgent need for scalable, evidence-based interventions in resource-limited settings. By combining AI-driven biomechanical feedback with cognitive reappraisal through PNE, this study seeks to reduce fear-avoidance behaviors and improve exercise adherence. This integrative approach aims to overcome the limitations of passive tele-rehabilitation by simulating asynchronous professional supervision, thereby ensuring both safety and technical precision in movement execution. CONCLUSIONS: If effective, this protocol will offer a robust, technology-enabled framework for remote FM management. The results could help establish a new clinical standard for accessible, patient-centered rehabilitation, bridging the gap between high-level evidence and real-world practice across diverse socioeconomic contexts. TRIAL REGISTRATION: ClinicalTrials.gov NCT06672419.
24 May 2026
Read appraisal →Calcified tissue international
Performance of Large Language Models in Answering Osteoporosis-Related Frequently Asked Questions: A Systematic Comparative Evaluation Based on International Associations
To systematically evaluate and compare the performance of large language models (LLMs) in answering osteoporosis-related frequently asked questions (FAQs) derived from international osteoporosis-related associations. A standardized question bank was constructed based on FAQs summarized from three international osteoporosis-related associations. Six LLMs were prompted to generate responses to all questions under uniform conditions. Two osteoporosis experts independently and blindly evaluated all responses using 5-point Likert scales for accuracy and comprehensiveness. Inter-rater reliability was assessed using Cohen's κ coefficient. Nonparametric statistical analyses, including Kruskal-Wallis tests with Dunn's post hoc comparisons and Wilcoxon signed-rank tests, were performed to compare models' performance. A total of 528 responses were generated from 88 association-based questions. Inter-rater agreement was good for both accuracy and comprehensiveness (κ = 0.668 and 0.702, respectively). Significant differences were observed among models, with Claude Sonnet 4.5 demonstrating the highest overall performance on association-based FAQs. Although most models showed solid medical knowledge and basic reasoning ability, substantial variability was observed across question types and prompt formulations. Current LLMs demonstrate promising potential as auxiliary tools for osteoporosis-related health management. However, it is necessary to optimize the strategies for integrating medical knowledge and designing prompts, so as to better improve the accessibility of its clinical application.
24 May 2026
Read appraisal →Medicine
Mechanisms linking primary biliary cholangitis and osteoporosis: A combined clinical and molecular analysis
Primary biliary cholangitis (PBC) is an immune-mediated cholestatic liver disease, and osteoporosis (OP) is a prevalent comorbidity that aggravates the disease burden of PBC patients. Although the co-occurrence of the 2 diseases has been widely observed, the underlying molecular mechanisms remain unclear. Herein, we evaluated the causal link between PBC and OP using Mendelian randomization (MR) and explored shared molecular mechanisms through bioinformatics and machine learning. We performed two-sample MR using genome-wide association study summary data for PBC and OP from the Integrative Epidemiology Unit database. Inverse-variance weighting was used as the primary MR method, with heterogeneity and horizontal pleiotropy tests performed to exclude potential biases. To explore shared molecular mechanisms, we analyzed transcriptomic datasets from the Gene Expression Omnibus database, identified comorbidity-associated differentially expressed genes, and applied multiple machine learning algorithms for biomarker screening and validation, combined with immune infiltration analysis. Our study showed that MR demonstrated that PBC significantly increases the risk of OP, while transcriptomic analysis identified 36 shared differentially expressed genes enriched in key biological pathways such as ribonucleic acid splicing and ubiquitin-mediated proteolysis. Furthermore, using 3 machine learning algorithms, we identified 12 PBC-specific and 4 OP-specific diagnostic genes, whose intersection revealed vacuolar protein sorting 37 homolog C (VPS37C) as a common diagnostic biomarker. In both diseases, VPS37C exhibited an area under the receiver operating characteristic curve value >0.7, demonstrating its robust predictive performance. In addition, VPS37C expression was found to be significantly correlated with the infiltration landscape of multiple immune cell types in both PBC and OP. This study identified VPS37C as a shared diagnostic gene linking PBC and OP, providing new insights into their comorbidity at both genetic and immune levels. Our findings further elucidate the molecular mechanisms underlying the comorbidity of PBC and OP, offer novel clues for understanding their pathogenesis, and highlight promising diagnostic and therapeutic targets for clinical application.
24 May 2026
Read appraisal →Archives of osteoporosis
Management of osteoporosis in older men: a systematic review of randomized trials of pharmacological and non-pharmacological strategies
INTRODUCTION: Osteoporosis in older men is often underdiagnosed and undertreated, increasing the risk of fractures and functional decline. Despite its clinical relevance, evidence specific to this population remains limited. This systematic review evaluated the effectiveness of pharmacological and non-pharmacological interventions in reducing fracture risk and improving bone mineral density (BMD) in older men with primary or secondary osteoporosis. METHODS: Searches were conducted in PubMed, EMBASE, Scopus, Cochrane Library, Web of Science, SciELO, PEDro, and LILACS, in addition to gray literature sources. Randomized controlled trials (RCTs) evaluating pharmacological and non-pharmacological interventions were included. Analyses were performed using RStudio (v. 4.3.3), and risk of bias was assessed using the RoB 2 tool. Results Twelve RCTs were included (10 pharmacological, one nutritional, and one exercise-based). The mean age was 60.9 ± 5.2 years, with baseline T-scores of - 2.9 ± 0.3 at the lumbar spine and - 2.7 ± 0.4 at the femoral neck. Bisphosphonates and teriparatide showed modest improvements in BMD, while effects on fracture risk were inconsistent. Resistance exercise (60-90 min/day) and L-carnitine supplementation were associated with BMD benefits, although evidence was limited by methodological constraints. Risk of bias varied across studies. CONCLUSION: Pharmacological therapies improve BMD in older men; however, evidence remains insufficient to demonstrate consistent fracture risk reduction. Non-pharmacological interventions show potential benefits but are supported by limited evidence. Larger randomized trials with clinically relevant outcomes are needed.
24 May 2026
Read appraisal →Medwave
Effects of manual therapy on pain and function in patients with plantar fasciitis: A systematic review of the literature
OBJECTIVE: Plantar fasciitis is common and impairs people's ability to move. Manual therapy is frequently used to treat plantar fasciitis. However, its effects are inconclusive. For this reason, the purpose of this systematic review is to determine the effect of manual therapy on plantar fasciitis. METHODS: A systematic review of the literature was conducted, following the PRISMA checklist. Five databases (CINAHL, Scopus, PubMed, Web of Science, and OVID) were searched, along with a review of the gray literature and a manual search. Randomized clinical trials from 2014 to 2024 were selected that examined the efficacy of manual therapy in reducing pain intensity and improving function in patients aged 18 to 60 years with a clinical diagnosis of plantar fasciitis. Methodological quality (PEDro scale) and risk of bias (risk of bias scale) were assessed. RESULTS: Four randomized clinical trials (n = 224) were included, reporting controversial statistical differences in pain and function. In addition, two studies reported clinically relevant changes favoring manual therapy. PEDro scale scores ranged from 4 to 6, and three studies presented a high risk of bias. CONCLUSIONS: The effects of manual therapy on pain and function in patients with plantar fasciitis are uncertain. The evidence is limited, heterogeneous, and lacking in methodological rigor. A larger number of randomized clinical trials with more consistent, replicable protocols are needed to determine the contributions of manual therapy to improving pain and function in patients with plantar fasciitis. Similarly, the inconsistency and limited evidence on indicators of clinical significance in the selected studies preclude an assessment of the clinical impact of this intervention. PROSPERO REGISTRATION: CRD42024501550. OBJETIVO: La fascitis plantar es común y genera alteraciones en la capacidad de moverse de las personas. La terapia manual se aplica frecuentemente en la fascitis plantar. Sin embargo, sus efectos no son concluyentes. Por esta razón, el propósito de esta revisión sistemática es determinar del efecto de la terapia manual sobre la fascitis plantar. MÉTODOS: Se realizó una revisión sistemática de la literatura, considerando la lista de verificación de PRISMA. Se consultaron cinco bases de datos (CINAHL, Scopus, PubMed, y OVID) junto con consulta de la literatura gris y búsqueda manual. Se seleccionaron ensayos clínicos aleatorios de 2014 a 2024 que consideraron la eficacia de la terapia manual en el cambio de la intensidad del dolor y funcionalidad en pacientes con diagnóstico clínico de fascitis plantar entre 18 y 60 años. Se determinó la calidad metodológica (escala PEDro) y riesgo de sesgo (escala riesgo de sesgo). RESULTADOS: Se incluyeron cuatro ensayos clínicos aleatorizados (n = 224), que reportaron diferencias estadísticas controversiales para dolor y la funcionalidad. Además, dos estudios reportaron cambios clínicamente relevantes a favor de la terapia manual. Los puntajes de la escala PEDro variaron de 4 a 6, y tres estudios presentaron alto riesgo de sesgo. CONCLUSIONES: Los efectos de la terapia manual sobre el dolor y la funcionalidad en pacientes con fascitis plantar son inciertos. La evidencia es limitada, heterogénea y con bajo rigor metodológico. Es necesario un mayor número de ensayos clínicos aleatorizados, con protocolos más consistentes y replicables para concluir definitivamente sobre los aportes de la terapia manual en los efectos clínicos en el dolor y funcionalidad de pacientes con fascitis plantar. De igual forma, la inconsistencia y limitada evidencia de indicadores de significancia clínica en los estudios seleccionados, no permite evaluar el impacto clínico de esta intervención. REGISTRO DEL PROTOCOLO: PROSPERO CRD42024501550.
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 →BMJ evidence-based medicine
Tramadol versus placebo for chronic pain: a systematic review with meta-analysis and trial sequential analysis
OBJECTIVES: The objective of our study was to assess the benefits and harms of tramadol vs placebo in adults with chronic pain. DESIGN: The research method was a systematic review of randomised clinical trials with meta-analysis. The review followed the Trial Sequential Analysis and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. DATA SOURCES: The Cochrane Library, MEDLINE, Embase, Science Citation Index and BIOSIS were searched for trials published from inception to 6 February 2025. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were eligible for inclusion if they were published and unpublished randomised clinical trials comparing tramadol vs placebo in adults with any type of chronic pain. Risk of bias was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. MAIN OUTCOME MEASURES: The main outcome measures were pain level, adverse events, quality of life, dependence, abuse and depressive symptoms. RESULTS: We included 19 randomised placebo-controlled clinical trials enrolling 6506 participants. All outcome results were at high risk of bias. Meta-analysis and Trial Sequential Analysis showed evidence of a beneficial effect of tramadol on chronic pain (mean difference numerical rating scale (NRS) -0.93 points; 97.5% CI -1.26 to -0.60; p<0.0001; low certainty of evidence). However, the effect size was below our predefined minimal important difference of 1.0 point on NRS. Beta binomial regression showed evidence of a harmful effect of tramadol on serious adverse events (OR 2.13; 97.5% CI 1.29 to 3.51; p=0.001; moderate certainty of evidence), mainly driven by a higher proportion of cardiac events and neoplasms. It was not possible to conduct a meta-analysis of the quality of life due to a lack of data. Meta-analysis and Trial Sequential Analysis showed that tramadol increased the risk of several non-serious adverse events including nausea (number needed to harm (NNH) 7), dizziness (NNH 8), constipation (NNH 9), and somnolence (NNH 13) (all very low certainty of evidence). CONCLUSION: Tramadol may have a slight effect on reducing chronic pain levels (low certainty of evidence) while likely increasing the risk of both serious (moderate certainty of evidence) and non-serious adverse events (very low certainty of evidence). The potential harms associated with tramadol use for pain management likely outweigh its limited benefits.
23 May 2026
Read appraisal →Surgical and radiologic anatomy : SRA
Proximal femoral morphometry and its association with hip fracture patterns: a systematic review with meta-analysis
PURPOSES: Proximal femoral fractures (PFFs) represent a major cause of morbidity and mortality in the elderly population. Beyond bone mineral density, proximal femoral (PF) and hip joint (HJ) morphometry have been implicated in fracture susceptibility and fracture pattern. However, the relative contribution of individual geometric parameters remains incompletely defined. The purpose of this study was to systematically evaluate the association between PF and HJ morphometry and hip fracture (HF) patterns, and to assess the predictive value of radiographic morphometric parameters derived from standard anteroposterior radiographs. MATERIALS AND METHODS: A systematic review with meta-analysis was conducted in accordance with PRISMA guidelines. PubMed and MEDLINE databases were searched up to September 2025 for observational studies reporting radiographic morphometric parameters in patients with unilateral PFFs. Statistical meta-analysis was performed with random-effect models to compare intracapsular-ICF/subcapital-SCF fractures with intertrochanteric (ITF) and extracapsular (ECF) fracture patterns. RESULTS: Twenty-two studies comprising 4184 patients (77.8% female; pooled mean age 77.4 years) were included. Meta-analysis using a random-effects model revealed that ITF were significantly associated with a smaller femoral head diameter (p < 0.001) and increased medial neck cortex thickness (p = 0.021) compared with ICF. ECF demonstrated significantly longer femoral neck axis length (p = 0.012), increased horizontal offset (p = 0.048), smaller absolute offset (p = 0.026) and shorter hip axis length (p = 0.026) than ICFs. Angular parameters provided the most robust stratification. ITFs and ECFs exhibited significantly lower (more varus) neck-shaft angles (p < 0.001) and significantly higher Wiberg angles (p < 0.001) compared with the ICF group. CONCLUSIONS: PF and HJ morphometry are associated with distinct HF patterns, independently of bone mineral density. Simple linear and angular measurements obtained from standard anteroposterior radiographs may assist fracture pattern stratification, risk assessment, and preoperative planning in elderly patients.
22 May 2026
Read appraisal →BMJ (Clinical research ed.)
Calcium, vitamin D, or combined supplementation to prevent fractures and falls: systematic review and meta-analysis
OBJECTIVE: To assess the effect of calcium, vitamin D, or combined supplementation on fractures and falls in adults. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Trials included in systematic reviews from 2014, three databases (Medline, Embase, CENTRAL) to 19 February 2025, clinical trial registries, abstracts from scientific meetings, and references from included studies. ELIGIBILITY CRITERIA: Randomised controlled trials comparing calcium, vitamin D, or combined supplementation with placebo or no treatment in adults (≥18 years) not receiving drug treatment for osteoporosis. DATA EXTRACTION AND SYNTHESIS: The primary outcome was the risk of any fracture. Secondary outcomes included the risk of hip fracture, non-vertebral fracture, vertebral fracture, and falling, as well as the total number of falls. Pairs of reviewers independently screened trials, extracted data, and assessed risk of bias using the second version of Cochrane's risk of bias tool. Findings were synthesised using random effects meta-analyses and appraised using Grading of Recommendations Assessment, Development and Evaluation, with application of thresholds for absolute effects considered important. RESULTS: This review included 69 trials involving 153 902 participants. Participants in most of the trials were community dwelling (87%) and not at high risk of fractures or falls (73%). For the primary outcome of any fracture, little to no effect was found from use of calcium supplements (11 trials, 9067 participants; risk ratio 0.91, 95% confidence interval 0.81 to 1.01; moderate certainty), vitamin D supplements (36 trials, 92 045 participants; 1.00, 0.95 to 1.06; high certainty), or combined supplementation (15 trials, 51 126 participants; 0.91, 0.84 to 0.99; high certainty). Calcium, vitamin D, or combined supplementation appeared to have little to no effect on other fracture and fall outcomes, based largely on moderate to high certainty of evidence. The findings remained robust after an extensive exploration of heterogeneity across multiple subgroup analyses. Evidence for high risk patients or those requiring residential care was limited for many outcomes for calcium monotherapy and for combined supplementation. CONCLUSION: Based on absolute risk reductions and thresholds considered clinically meaningful, this review found little to no benefits from use of calcium, vitamin D, or combined supplementation on the prevention of fractures and falls. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023483915.
22 May 2026
Read appraisal →The Cochrane database of systematic reviews
Dose reduction and discontinuation of non-tumor necrosis factor (TNF) biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for people with rheumatoid arthritis in remission or low disease activity
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determine the benefits and harms of dose reduction or discontinuation of non-TNF biologic or targeted synthetic DMARDs in people with rheumatoid arthritis who are in remission or have low disease activity.
21 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 →The Journal of clinical endocrinology and metabolism
Mortality risk and causes of death in exogenous Cushing's syndrome: a systematic review and meta-analysis
CONTEXT: Chronic oral glucocorticoids (GCs) are widely prescribed for multiple diseases. Although long-term GC exposure causes systemic toxicity, the magnitude, dose-response relationship, and causes of GC-associated mortality remain incompletely defined. OBJECTIVE: To quantify overall and cause-specific mortality associated with chronic oral GC exposure and evaluate dose-response relationships across underlying disease groups. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO CRD42017067530). PubMed/MEDLINE, EMBASE, Cochrane Library, Web of Science, and CINAHL were searched from 1945 to March 2019. Eligible studies reported standardized mortality ratios (SMRs) or absolute deaths among adults receiving chronic oral GCs. Random-effects meta-analysis and mixed-effects meta-regression were used to synthesize mortality and dose-response associations across GC exposure metrics, exposure duration, and disease subgroups. RESULTS: One-hundred and sixteen studies encompassing 128 cohorts and 51 380 patients were included. Chronic GC exposure was associated with excess mortality (pooled SMR 1.87; 95%CI 1.32-2.61; I2 74.0%). The pooled proportion of death was 12.0% (95%CI 10-14%). Mortality risk was highest in inflammatory diseases (30.0%) and the vasculitides (18.0%). Higher cumulative dose (≥5 g prednisolone-equivalent), average daily dose >5 mg/day, and higher initial dose were each independently associated with increased mortality. Cardiovascular disease was the leading causes of death (25.6%), followed by malignancy (15.7%) and infection (13.4%). CONCLUSION: Chronic oral GC exposure was associated with increased mortality across disease groups, with higher cumulative and early-treatment doses correlating with higher risk. However, causal attribution remains uncertain due to confounding by indication, limited disease-severity data, and exposure misclassification. These findings support GC stewardship and targeted cardiovascular and infection risk mitigation, rather than indiscriminate dose reduction.
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 →Oral and maxillofacial surgery
Does adjunctive low-level laser therapy provide additional benefit following temporomandibular joint arthrocentesis with hyaluronic acid? A randomized clinical trial.
PURPOSE: This study aimed to evaluate whether adjunctive low-level laser therapy (LLLT) provides additional clinical benefit over an optimized arthrocentesis protocol with hyaluronic acid in patients with ADDwoR. MATERIALS AND METHODS: From December 2022 to December 2023, a single-blinded prospective randomized clinical trial was conducted at The British University in Egypt's Department of Oral and Maxillofacial Surgery. The study involved 40 female participants diagnosed with Anterior Disc Displacement without Reduction (ADDwoR). Following TMJ arthrocentesis, subjects were assigned to one of two parallel cohorts: Group A received ten subsequent sessions of low-level laser therapy (LLLT), while Group B served as the control, receiving arthrocentesis alone. Treatment efficacy was evaluated based on pain intensity measured via a Visual Analogue Scale (VAS) and maximum mouth opening (MMO). Clinical assessments were performed at 2-week intervals over a 12-week follow-up period. RESULTS: No significant age-related differences were detected when comparing the intervention group to the control group (p = 0.087). No significant intergroup differences were observed in maximum mouth opening (MMO) or pain scores (VAS) at any follow-up time point (p > 0.05). Over the 12-week period, both study arms demonstrated significant clinical enhancement in terms of MMO and pain intensity (p < 0.001). Improvements in MMO were large in both groups, with postoperative values significantly higher than preoperative measurements. Pain scores decreased markedly following treatment, with preoperative scores significantly higher than all postoperative values. Overall, both interventions resulted in significant functional improvement and pain reduction, with no added benefit of the intervention over the control. CONCLUSION: While both TMJ arthrocentesis alone and arthrocentesis supplemented with LLLT significantly improved maximum mouth opening and reduced pain, LLLT did not provide a significant incremental benefit over arthrocentesis with hyaluronic acid. These findings suggest that clinical improvements are primarily driven by the main intervention and may reflect a possible therapeutic ceiling effect, beyond which adjunctive LLLT does not confer measurable short-term benefit. CLINICAL TRIAL NUMBER: Not applicable.
18 May 2026
Read appraisal →Journal of the International Society of Sports Nutrition
Creatine monohydrate for lean mass, strength, and bone density in postmenopausal women: a systematic review and meta-analysis
BACKGROUND: Menopause is accompanied by accelerated losses in muscle mass and strength and declining bone density. Whether creatine monohydrate benefits postmenopausal women are uncertain. METHODS: We systematically reviewed randomized, placebo-controlled trials examining creatine supplementation, with or without resistance training (RT), in postmenopausal women. MEDLINE, Embase, Scopus, Web of Science, SPORTDiscus, and Cochrane CENTRAL were searched from 2000 to August 2025, supplemented by trial registries and reference-list screening. Eligible studies included postmenopausal women aged ≥40-45 years, intervention durations ≥6 weeks for primary analyses, and outcomes including DXA-derived lean mass, one-repetition maximum (1RM) strength, bone mineral density, physical function, and safety. Dual screening, duplicate extraction, and Cochrane RoB 2 assessment were performed. Random-effects meta-analysis used the Paule-Mandel estimator for τ² with Hartung-Knapp-Sidik-Jonkman adjustment. Heterogeneity (τ², I²), 95% prediction intervals, subgroup analyses by RT status, exploratory dose/duration meta-regression, small-study effects, and GRADE certainty were assessed. RESULTS: Seven RCTs (n = 608 randomized; duration 12-104 weeks, median 38 weeks) enrolled postmenopausal women (mean age ≈ 62 y). Lean mass (k = 5; n = 338) favored creatine: mean difference (MD) + 0.37 kg (95% CI + 0.05 to + 0.69; I² = 25%; τ² = 0.01; 95% PI -0.10 to + 0.84). Leg-press 1RM (k = 3; n = 111) improved with creatine: MD + 7.5 kg (95% CI + 2.2 to + 12.8; I² = 0%). Benefits were evident when creatine ≥ 5 g·day⁻¹ was combined with RT; trials using ≤ 3 g·day⁻¹ without RT showed no measurable effect. Bone density was unchanged overall. Adverse events were mild and similar to placebo; renal indices were unchanged. Risk of bias was mostly "some concerns;" one large, preregistered, double-blind RCT was at low risk. CONCLUSIONS: In postmenopausal women, creatine, particularly ≥ 5 g·day⁻¹ with RT, yields small but meaningful gains in lean mass and strength without evidence of harm. Effects on bone density remain unclear.Registration: This review was not prospectively registered. De-identified data and supplementary materials were deposited on OSF after completion of the analysis (DOI: 10.17605/OSF.IO/BVTRZ).
18 May 2026
Read appraisal →Journal of rehabilitation medicine
Efficacy of ultrasound-guided intra-articular hyaluronic acid injection in the management of adhesive capsulitis: a randomized controlled trial
OBJECTIVE: To compare the efficacy and safety of ultrasound-guided intra-articular hyaluronic acid injection versus supervised rehabilitation in patients with frozen-phase adhesive capsulitis. DESIGN: Single-center, parallel-group, randomized controlled trial with 26-week follow-up. SUBJECTS/PATIENTS: Forty-six adults aged 40-70 years with clinically and radiologically confirmed frozen-phase adhesive capsulitis. METHODS: Participants were randomly assigned to receive either three weekly ultrasound-guided intra-articular hyaluronic acid injections or supervised physical therapy twice weekly for six weeks. Outcomes assessed at baseline and at weeks 4, 6, 8, and 26 included the Shoulder Pain and Disability Index (SPADI) and shoulder range of motion. RESULTS: Both groups achieved significant within-group improvements in SPADI and range of motion over 26 weeks (all p < 0.01 vs. baseline). No statistically significant between-group differences were observed in total SPADI or its pain and disability subscales at any follow-up time point (all p > 0.05). At week 26, the hyaluronic acid group's mean total SPADI decreased from 43.0 ± 17.7 to 16.1 ± 12.8 (p < 0.01), while the rehabilitation group improved from 52.0 ± 18.4 to 23.2 ± 21.8 (p < 0.01). Pain subscores were reduced by 64.3% (hyaluronic acid) and 56.1% (rehabilitation); function subscores decreased by 60.9% and 54.8%, respectively (all p < 0.01). Both groups showed significant gains in active and passive flexion, abduction, and external rotation, without significant between-group differences (all p > 0.05). No treatment-related adverse events were observed. CONCLUSION: Ultrasound-guided hyaluronic acid injection and supervised rehabilitation produced comparable and clinically meaningful improvements in pain, function, and shoulder mobility in frozen-phase adhesive capsulitis.
17 May 2026
Read appraisal →Spine
Automated Classification of Cervical Spinal Stenosis Using Deep Learning on Computed Tomography Scans
STUDY DESIGN: Retrospective study. OBJECTIVE: To develop and validate a computed tomography-based deep learning (DL) model for diagnosing cervical spinal stenosis (CSS). BACKGROUND: Although magnetic resonance imaging (MRI) is widely used for diagnosing CSS, its inherent limitations, including prolonged scanning time, limited availability in resource-constrained settings, and contraindications for patients with metallic implants, make computed tomography (CT) a critical alternative in specific clinical scenarios. The development of CT-based DL models for CSS detection holds promise in transcending the diagnostic efficacy limitations of conventional CT imaging, thereby serving as an intelligent auxiliary tool to optimize health care resource allocation. MATERIALS AND METHODS: Paired CT/MRI images were collected. CT images were divided into training, validation, and test sets in an 8:1:1 ratio. The 2-stage model architecture employed: (1) A Faster R-CNN-based detection model for localization, annotation, and extraction of regions of interest (ROI), (2) Comparison of 16 Convolutional Neural Network (CNN) models for stenosis classification to select the best-performing model. The evaluation metrics included accuracy, F1-score, and Cohen κ coefficient, with comparisons made against diagnostic results from physicians with varying years of experience. RESULTS: In the multiclass classification task, 4 high-performing models (DL1-b0, DL2-121, DL3-101, and DL4-26d) achieved accuracies of 88.74%, 89.40%, 89.40%, and 88.08%, respectively. All models demonstrated >80% consistency with senior physicians and >70% consistency with junior physicians. In the binary classification task, the models achieved accuracies of 94.70%, 96.03%, 96.03%, and 94.70%, respectively. All 4 models demonstrated consistency rates slightly below 90% with junior physicians. However, when compared with senior physicians, 3 models (excluding DL4-26d) exhibited consistency rates exceeding 90%. CONCLUSIONS: The DL model developed in this study demonstrated high accuracy in CT image analysis of CSS, with a diagnostic performance comparable to that of senior physicians.
16 May 2026
Read appraisal →The Journal of neuroscience : the official journal of the Society for Neuroscience
Stable Mechanoreceptive Somatotopy in Chronic Low Back Pain: Is Cortical Map Reorganization a Myth?
Chronic low back pain (CLBP) has been linked to maladaptive cortical plasticity in sensorimotor regions, which may contribute to pain persistence through less distinct ("smudged") somatotopic maps of afferent input from the back. However, empirical support for such functional reorganization, especially in the primary somatosensory cortex (S1), is limited. To delineate precise sensory representations of the back in humans and test for altered somatotopic processing in CLBP, we utilized an MR-compatible pneumatic vibration device and applied frequency-specific vibrotactile stimuli at nine thoracolumbar paraspinal sites in 45 patients with CLBP and 41 healthy controls (53 females in total). Representational similarity analysis was employed via a whole-brain searchlight method, and the neural representational patterns were contrasted against theoretical models including a segmental (based on anatomical proximity), simple (upper vs lower back division), and a random model. In addition, a machine learning classifier was trained to predict afferent input from the upper versus lower back in healthy controls and tested in CLBP patients. Both groups displayed well-organized segmental representations spanning somatosensory, motor, and posterior parietal cortices. Posterior parietal regions exhibited the best model fits, followed by S1. No evidence for differences in representational patterns between groups was found. In CLBP patients, these patterns did not show associations with pain duration, severity, and self-reported back perception. The classifier, trained on healthy controls, accurately predicted upper versus lower back afferent input in CLBP patients. These findings indicate preserved cortical maps of the back in CLBP, challenging the hypothesis of sensory cortical reorganization in this condition.
16 May 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
Yield and safety of different biopsy types in interstitial lung disease: a systematic review and meta-analysis
BACKGROUND: Lung biopsy remains an important consideration in the management of interstitial lung disease (ILD). Transbronchial lung cryobiopsy (TBLC) offers an alternative to traditional surgical lung biopsy (SLB) and transbronchial forceps biopsy (TBB); however, up-to-date comparisons between these methods in ILD, particularly fibrotic ILD, remain limited. METHODS: A comprehensive literature search of Medline, Embase and Evidence-Based Medicine Reviews was performed for studies published between January 2000 and September 2025 to identify all citations reporting yield and complications of the three main lung biopsy methods for ILD. RESULTS: A total of 143 studies were included. Pooled multidisciplinary yield (following multidisciplinary discussion) in TBB, TBLC and SLB was 35.3% (95% CI 21.3-52.5), 84.3% (95% CI 81.7-86.5) and 88.6% (95% CI 83.4-92.3), respectively. For fibrotic ILD, the multidisciplinary yield was 12.5% (only one eligible study), 87.6% (95% CI 83.5-90.7) and 87.3% (95%CI 80.5-92.0), respectively. Meta-regression showed an increasing multidisciplinary yield of TBLC with more recent years of patient recruitment and an increasing percentage of fibrotic ILD in each study. The multidisciplinary yield of both TBLC and SLB was 85-90%, suggesting a biopsy "ceiling effect". All evaluated complications were more frequent in TBLC compared to TBB and some were more frequent in SLB compared to TBLC. Several complications were more frequent in fibrotic ILD compared to all ILD. CONCLUSIONS: The multidisciplinary yield of TBLC and SLB is equivalent, with both offering an acceptable safety profile. TBB has low yield, particularly in fibrotic ILD. These findings support using either TBLC or SLB as an initial diagnostic tool in fibrotic ILD, mainly based on patient-physician shared decision-making.
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 →JMIR medical informatics
Adverse Pregnancy Outcomes in Women With Immune Abnormalities: Machine Learning Model Development and Validation Using First-Trimester Sonographic Features
BACKGROUND: The maintenance and progression of pregnancy rely on immune homeostasis at the maternal-fetal interface. However, pregnancy complicated by autoimmune abnormalities can disrupt this balance and significantly increase the risk of adverse pregnancy outcomes (APOs). OBJECTIVE: This study aimed to (1) develop an interpretable predictive tool for APOs in patients with immune abnormalities and (2) interpret the models using Shapley additive explanations (SHAP) values. METHODS: This study retrospectively analyzed clinical data from 288 patients with autoimmune abnormalities at Yichang Central People's Hospital between 2019 and 2024. Feature selection was performed using both the Boruta algorithm and Least Absolute Shrinkage and Selection Operator regression to identify optimal predictive factors associated with APOs. Nine machine learning models were developed and subsequently underwent a comprehensive comparative evaluation of their predictive performance, leading to the identification of the optimal predictive model. SHAP values were generated to provide interpretable insights into model predictions. RESULTS: A total of 288 patients were included in the study, 124 (43.06%) of whom had APOs. The extreme gradient boosting algorithm was shown to be the optimal model after a comparison of 9 different models utilizing various metrics. The SHAP analysis showed that crown-rump length at 6+0 to 8+6 weeks, the number of other drugs, the number of complications during pregnancy, gestational sac volume at 6+0 to 8+6 weeks, and yolk sac diameter change at 6+0 to 8+6 weeks were the key predictive factors affecting APOs. CONCLUSIONS: The study developed an interpretable predictive tool for APOs in patients with immune abnormalities, which may assist clinicians in making early intervention decisions.
14 May 2026
Read appraisal →Annals of work exposures and health
Occupational mechanical exposures and upper-body musculoskeletal disorders: an overview of systematic reviews
OBJECTIVES: The aim was to provide a comprehensive overview of systematic reviews with meta-analyses of the association between occupational mechanical exposures and upper-body musculoskeletal disorders. METHODS: A systematic literature search was conducted in PubMed, Web of Science, Embase, and CINAHL. Systematic reviews were considered eligible if they included occupational mechanical exposures and provided weighted measures of association in relation to specific musculoskeletal disorders. From each systematic review, data on eg databases searched, exposure, outcome, effect estimates, and quality of evidence of the association were extracted. The methodological quality of each systematic review was assessed using AMSTAR 2. RESULTS: The screening of 1,756 articles resulted in the inclusion of 17 systematic reviews with meta-analysis covering 6 musculoskeletal disorders: subacromial pain syndrome (n = 3), lateral epicondylitis (n = 2), carpal tunnel syndrome (n = 7), Dupuytren's disease (n = 4), hand-arm vibration syndrome (n = 1), and hand osteoarthritis (n = 1). The weighted odds ratios from the meta-analyses generally ranged between 1.5 and 3.0. Approximately 35% of the included systematic reviews assessed the quality of evidence of the association, and among these, 48% graded the evidence as being low to very low. CONCLUSIONS: In general, this overview found an increased risk associated with most mechanical exposures in relation to specific upper-body musculoskeletal disorders. However, grading of evidence quality was rarely applied, and when present, showed substantial variability. Future research related to primary studies should prioritise high-quality prospective studies and objective exposure assessments, and systematic reviews would benefit from standardised methodologies and improved reporting transparency to further strengthen the evidence quality.
14 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 →European journal of clinical pharmacology
The impact of gene polymorphisms on the response of methotrexate-based treatments
PURPOSE: Methotrexate (MTX) is a long-standing drug used to treat leukemia (at high doses to inhibit DNA/RNA synthesis) and rheumatoid arthritis (at low doses for anti-inflammatory effects). Its characteristic narrow therapeutic range, in terms of efficacy and safety associated with MTX, are important factors to consider when deciding whether to prescribe it. A major challenge in its use is interindividual variability which is largely attributed to germline genetic polymorphisms in genes encoding proteins that control the pharmacokinetics or pharmacodynamics of MTX. METHODS: This study updates a previous 2018 review using a systematic literature search in PubMed/MEDLINE, Scopus, and SciELO. The search, conducted according to the PRISMA protocol, employed predefined keywords to identify studies published up to June 2025. RESULTS: This systematic review identified that, to date, only a few genetic polymorphisms influence clinical decision-making. Specifically, the MTHFR 677T allele and the MTHFR 677T-1298 A haplotype (rs1801133- rs1801131) have been associated with toxicity in both adults and children. Furthermore, the 677T-1298 A haplotype has been linked with reduced event-free survival in Caucasian patients with either adult RA or pediatric ALL. Regarding other markers, the TYMS rs34743033 3R allele has been implicated with reduced efficacy in adult patients receiving low-dose MTX, while the FPGS rs1544105 T allele has shown an association with diverse toxicities in ALL pediatric patients. CONCLUSION: Although considerable research has been conducted and numerous results have been obtained, the available evidence remains predominantly of moderate quality. Consequently, current guidelines from CPIC and the DPWG do not recommend routine MTX dose adjustments based solely on single gene variants. It is, therefore, imperative to develop and validate multifactorial risk prediction tools that integrate a range of other clinical factors. Accordingly, the establishment of a comprehensive pharmacogenetics-guided dosing guideline for MTX remains an elusive goal.
13 May 2026
Read appraisal →Journal of ethnopharmacology
Moxibustion with Artemisia argyi H.Lév. & Vaniot in rheumatoid arthritis animal models: A meta-analysis linking clinical efficacy to inflammasome and cytokine signaling mechanisms
ETHNOPHARMACOLOGICAL RELEVANCE: Moxibustion, a traditional Chinese healing method, uses mugwort (Artemisia argyi H.Lév. & Vaniot) to apply heat to specific points, treating conditions like "Bi Zheng", which is akin to rheumatoid arthritis (RA). According to traditional theory, its therapeutic actions are attributed to warming the meridians and regulating the flow of Qi and blood. AIM OF THE STUDY: To quantitatively evaluate the therapeutic efficacy of moxibustion and to map its anti-arthritic mechanisms in animal models of RA. MATERIALS AND METHODS: The protocol was registered with PROSPERO (CRD42024503829) and reported according to PRISMA 2020. Eight databases were searched through 28 July 2025 for randomized controlled animal studies comparing moxibustion with the control in RA models. The primary outcome was arthritis severity, assessed by the arthritis index, paw volume, and histopathological score. Secondary endpoints included serum or tissue levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6), immunomodulatory cytokines (IL-10, IL-4), and key signaling proteins (NF-κB, NLRP3, TLR4, MyD88). The SYRCLE tool was used to assess the risk of bias. RESULTS: Seventy-three studies were included. Meta-analysis showed that moxibustion significantly reduced arthritis severity (arthritis index: SMD -3.72, 95% CI -4.25 to -3.20; paw volume: SMD -4.59, 95% CI -5.54 to -3.63; histopathological score: SMD -2.24, 95% CI -2.80 to -1.67). Moxibustion also lowered the levels of pro-inflammatory cytokines: IL-1β (SMD -3.52, 95% CI -4.19 to -2.86), IL-6 (SMD -3.17, -4.17 to -2.16), and TNF-α (SMD -3.38, -3.97 to -2.79) and suppressed key signaling pathways, including NF-κB (SMD -2.29, 95% CI -3.20 to -1.37), NLRP3 (SMD -1.74, 95% CI -2.49 to -0.99), TLR4 (SMD -6.72, 95% CI -12.54 to -0.90), and MyD88 (SMD -9.16, 95% CI -15.28 to -3.04). CONCLUSION: This meta-analysis suggests that moxibustion alleviates arthritis severity and histopathological damage in RA animal models, potentially through modulating inflammatory networks and inhibiting key pathways such as NF-κB and NLRP3. These findings provide preclinical evidence supporting the rationale for future clinical investigation of moxibustion as a potential adjunct therapy for RA.
13 May 2026
Read appraisal →Journal of medical systems
Use of Generative Artificial Intelligence in the Management of Low Back Pain: a Scoping Review
BACKGROUND CONTEXT: Low back pain (LBP) is common and a major cause of disability globally. Generative artificial intelligence (GenAI) such as ChatGPT may have the potential to improve LBP, but it is unknown how GenAI is being used in clinical care settings. PURPOSE: This scoping review aimed to map and synthesise the existing literature on the use of GenAI in the management of LBP across all settings. STUDY DESIGN: This review followed the scoping review methodology of the Joanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. METHODS: We searched the Cochrane Library, Medline, Scopus, Embase, Web of Science, CINAHL, and preprint platforms for studies published between January 2012 and July 2025, on the use of GenAI in the management of LBP across all healthcare settings. The included studies were categorised according to the primary purpose of GenAI implementation. RESULTS: A total of 31 studies were included. Seventeen studies evaluated GenAI as a potential support tool for diagnosis and treatment, including answering specific questions about LBP (n = 8), generating advice from clinical cases (n = 4), and generating advice from diagnostic imaging (n = 5). Eight studies examined the use of GenAI to provide educational advice for patients. Other uses included research support (n = 5) and clinical documentation support (n = 1). GenAI advice for the management of LBP demonstrated higher agreement when using simpler tasks, more detailed prompts, or newer generation models. Reported errors in GenAI advice included inconsistency with guidelines or clinicians' advice, hallucination, low accuracy for complex questions, sensitivity to prompt design, and challenges with interpretability. CONCLUSION: Thirty-one studies reported the use of GenAI in LBP management, mainly supporting diagnosis and treatment planning, patient education, research, and clinical documentation. Despite authors' claims about promising uses of GenAI, it typically requires further refinement or review by human end-users. Critically, no studies addressed end-user experience, or clinical effectiveness, underscoring the need for robust clinical evaluation beyond the lab-based environment.
12 May 2026
Read appraisal →Journal of ethnopharmacology
Anti-inflammatory properties of Dendrobium: A systematic review of pharmacological mechanisms
ETHNOPHARMACOLOGICAL RELEVANCE: In Traditional Chinese Medicine (TCM), Dendrobium species have long been used to alleviate various inflammatory conditions, particularly those characterized by Yin deficiency with internal heat and stomach deficiency-heat, including impaired fluid production, stomach Qi dysfunction, and poor appetite. The inflammatory response is regulated by multiple signaling pathways that drive disease pathogenesis, making these pathways promising targets for anti-inflammatory therapy. Medicinal Dendrobium, enriched with anti-inflammatory bioactive constituents, exhibits substantial systemic anti-inflammatory activity. Its growing research interest stems from favorable properties such as low toxicity, broad therapeutic efficacy, and minimal risk of drug resistance. AIM OF THE STUDY: Medicinal Dendrobium and its bioactive constituents have demonstrated significant anti-inflammatory properties, underscoring their pharmacological potential. Nevertheless, substantial efforts remain an urgent priority to advance the translation of basic research findings into clinical applications. Therefore, pharmacological studies published within the past six years were systematically reviewed to elucidate the mechanisms by which Medicinal Dendrobium and its bioactive constituents modulate inflammatory processes, thereby evaluating their potential as multi-targeted natural anti-inflammatories. This will facilitate the translation of anti-inflammatory research on medicinal Dendrobium from basic research to clinical investigation, thereby laying a solid foundation for its eventual clinical application in managing inflammatory diseases. MATERIALS AND METHODS: A literature search and screening strictly followed the PRISMA 2020 guidelines and employed a predefined Boolean strategy. A comprehensive search was conducted across Web of Science, PubMed, Elsevier, ScienceDirect, Scopus, CNKI, Wanfang Data, Baidu Scholar, and Google Scholar. No language restrictions were applied; this review includes key findings from Chinese-language literature. The predefined keywords included "Dendrobium," "Shihu," "bioactive constituents," "anti-inflammatory," "cytokines," "signaling pathways," as well as their corresponding Chinese terms. Taxonomic validation was conducted using the World Flora Online (http://www.worldfloraonline.org) and the Medicinal Plant Names Services (http://mpns.kew.org) databases. RESULTS: Eight Medicinal Dendrobium species and their bioactive constituents-such as polysaccharides, alkaloids, flavonoids, bibenzyls, polyphenols and stilbenoids-exert anti-inflammatory effects by modulating multiple signaling cascades, including NF-κB, MAPK/NF-κB, TLR4/NF-κB, PI3K/AKT, Nrf2/HO-1, JAK/STAT, and AMPK/SIRT1 pathways, indicating their multi-target therapeutic potential for inflammatory diseases. This review further underscores the innovative role of Dendrobium in regulating these pathways and its potential for integration with conventional pharmacological treatments, supporting its synergistic use in precision medicine. CONCLUSIONS: Medicinal Dendrobium represents a promising ethnopharmacological resource, exhibiting broad-spectrum anti-inflammatory effects through multi-target, multi-pathway, and multi-organ mechanisms. To advance its modernization, therapeutic development, and clinical translation, future research should prioritize several key directions: establishing standardized quality control system and prioritizing the structures of core bioactive constituents; applying a multi-omics approach combined with artificial intelligence-assisted modeling, network pharmacology and advanced molecular imaging techniques to systematically map its systemic anti-inflammatory regulatory network; strengthening systematic pharmacokinetic and bioavailability studies; exploring precision and synergy delivery formulations; and conducting rigorous assessments of safety profiles and side-effect management. By focusing on these priorities, research can further elucidate the systemic anti-inflammatory mechanisms of medicinal Dendrobium, thereby bridging its traditional use with contemporary precision medicine, and supporting integrated interventions for complex inflammatory diseases.
12 May 2026
Read appraisal →Scandinavian journal of pain
Breathing therapy as a supplement to opioid management for complex chronic non-cancer pain conditions - a systematic review
OBJECTIVES: The purpose of this systematic review was to analyze whether breathing therapy is effective in reducing pain, improving health-related quality of life, improving physical functioning/activity, and improving sleep quality in patients suffering from complex chronic non-cancer pain conditions (CNCP). CONTENT: An electronic literature search was conducted in MEDLINE, CINAHL, EMBASE, Cochrane Library, PEDro, and PsycINFO from inception to October 2024. The inclusion criteria were randomized clinical trials (RCT) examining breathing therapy as a sole or central intervention component in adult patients with CNCP. From 2,369 abstracts, a total of 10 RCTs (n=638) met the inclusion criteria. The population in the selected studies were patients with chronic neck pain, chronic low back pain, fibromyalgia, or tension-typed headache. Breathing therapy significantly improved pain and/or health-related quality of life in six studies. However, the quality of the included RCTs ranged from high to critically low, and substantial heterogeneity in participants, intervention, and methods prevented synthesis of results across studies. SUMMARY: This systematic review highlights breathing therapy as a promising pain management strategy in patients suffering from CNCP. We evaluated two RCTs examining similar daily slow diaphragmatic breathing for 15 min to have a low risk of bias; both demonstrating statistically significant relevant pain reduction up to 37 %. However, the strength of recommendations for clinical practice depends on the level of evidence as indicated by a risk of bias assessment (internal validity), consistency of results between studies, and generalizability (external validity). Based on the findings of this systematic review evidence of breathing therapy invention in patients suffering from CNCP conditions remains sparse. OUTLOOK: Striving to eliminate or minimize opioid management for complex CNCP, high-quality research is needed to reinforce the evidence base for non-pharmacological interventions such as breathing therapy to support modern pain management rather than former traditional pharmacological treatment. Trial registry number: PROSPERO #CRD42023460181.
12 May 2026
Read appraisal →Journal of Crohn's & colitis
Safety of advanced therapies during pregnancy in women with immune-mediated inflammatory diseases: a systematic review and meta-analysis
BACKGROUND AND AIMS: We aimed to assess the safety of advanced therapies, excluding tumor necrosis factor inhibitors (anti-TNFs), for the treatment of immune-mediated inflammatory diseases (IMIDs), on pregnancy and neonatal outcomes. METHODS AND ANALYSIS: We performed a systematic review and meta-analysis. Study selection and data extraction were conducted independently by two reviewers. Primary outcomes included live births, major congenital malformations (MCMs), miscarriages, and stillbirths. Risk of bias was assessed using ROBINS-I, and the certainty of evidence was evaluated using GRADE. Meta-analyses of prevalence and odds ratios (ORs) comparing advanced therapies with anti-TNFs were conducted using fixed and random effect models. RESULTS: Of 14 661 manuscripts screened, 49 studies met the inclusion criteria: eight cohorts, nine case series, and 32 case reports. Most cohort studies were at a critical risk of bias. The majority of the available data related to ustekinumab (1324 exposed offspring) and vedolizumab (585 exposed offspring) whereas data on other biologics and JAK inhibitors were very limited. Pregnancies exposed to biologics had a pooled prevalence of 82.43% for live births, 0.55% for MCMs, 8.16% for miscarriage, and 0.00% for stillbirths. No significant differences in adverse pregnancy or neonatal outcomes were observed compared with women exposed to anti-TNFs. Overall, the level of evidence was very low, due largely to reliance on small observational studies and case reports. CONCLUSION: Current evidence does not suggest an increased risk of adverse pregnancy or neonatal outcomes with advanced therapies for IMIDs. However, larger, high-quality studies are needed, and these findings should be interpreted as hypothesis-generating.
12 May 2026
Read appraisal →Molecular biology reports
Genetic modulation of pain pathways: toward a new era in pain therapy- a systematic review
Gene therapy represents a new strategy in pain management targeting the causes of pain rather than its symptoms. This review summarizes recent advances across RNA interference (RNAi), viral vector delivery systems, CRISPR/Cas9, gene replacement therapy, and endogenous opioid gene delivery, emphasizing efficacy, safety, and mechanisms of action in pain conditions. RNAi and gene replacement techniques remain powerful tools for reducing pain and improving the quality of life by modulating pain-associated genes. Long-term relief may also be achieved with CRISPR/Cas9 and site-directed delivery using nanoparticle systems. Safety profiles especially with CRISPR/Cas9 remains a concern. A systematic search of Web of Science, Medline, Scopus, and Google Scholar identified 512 records (January 2010-March 2023). Following PRISMA screening, 18 studies met inclusion criteria. These studies evaluated strategies of gene therapy in neuropathy, arthritis, fibromyalgia, and complex regional pain syndrome. The review outlines available options and highlights preclinical findings.
11 May 2026
Read appraisal →Journal of medical Internet research
Rheumatic Digital Twin: Proposed Machine Learning-Based Multimodal Framework to Inform Clinical Decision-Making
Rheumatic diseases are chronic, immune-mediated conditions characterized by significant heterogeneity in presentation and disease course. However, current clinical approaches often rely on snapshot-based assessments that fail to capture the complex longitudinal evolution of these conditions. To address these limitations and support the implementation of precision medicine, we present the design for the Rheumatic Digital Twin, a novel, modular conceptual framework intended to integrate heterogeneous multimodal data, ranging from electronic health records and clinical notes to imaging and omics, into a dynamic, computational representation of the patient journey. Our theoretical architecture addresses challenges related to data silos and variable availability of data modalities through a multistage approach that envisions the use of domain-specific foundation models to independently process distinct data modalities. To effectively model the temporal progression inherent in chronic diseases, the proposed design utilizes Transformer architectures, leveraging self-attention mechanisms to treat patient events, such as lab results or medication changes, as sequential data tokens. We describe how these unimodal representations would subsequently be fused via joint embedding techniques to construct a shared, multimodal representational space. Envisioned to function analogously to a recommender system, the Rheumatic Digital Twin framework is modeled to map patients into a latent space where proximity reflects clinical and biological similarity. By identifying "nearest neighbors," historical patients with comparable trajectories, the system aims to enable in silico cohorting, theoretically allowing clinicians to forecast key clinical events, predict treatment responses, and identify likely disease courses based on the outcomes of similar peers.
11 May 2026
Read appraisal →AJNR. American journal of neuroradiology
High-Resolution 2D versus 3D Lumbar Spine MRI Optimized with a Deep Learning Reconstruction Algorithm and Prototype Conformal Coil
BACKGROUND AND PURPOSE: Lumbar spine MRI is predominantly performed using 2D FSE sequences. 3D FSE sequences offer potential advantages over 2D, especially with recent advances in deep-learning reconstruction (DLR) and the use of conformal high-density coil arrays to improve the SNR. This study aimed to compare image quality and diagnostically relevant differences between 2D and 3D lumbar spine protocols, both using a prototype conformal coil and DLR. MATERIALS AND METHODS: Subjects with lumbar curvature referred for routine lumbar spine MRI were prospectively recruited (n=31). A prototype, conformal spine coil array with 70 total posterior receiver elements was used at 3T. DLR was applied to both the 2D- and 3D-protocols to improve sharpness and reduce noise. For 3D, a prototype DLR ("Sonic DL") technique was applied to provide higher acceleration factors. Three attending musculoskeletal radiologists assessed 2D and 3D T1-weighted (T1), T2-weighted (T2), and STIR sequences for image quality and diagnostic performance. The Gwet agreement coefficient (AC1, AC2) or intraclass correlation (ICC) was used to assess interrater agreement, while the Wilcoxon signed rank test or a sign test with Bonferroni correction assessed differences between 2D and 3D sequences. RESULTS: There was an overall 14% scan time reduction of 3D compared with 2D sequences, and a 38% time reduction for T2 sequences. All 3D sequences exhibited similar image quality to 2D. 3D T2 sequences had less CSF flow artifact than 2D T2 sequences. Interrater agreement was mostly comparable between all 2D and 3D assessments, including excellent agreement for the spinal canal area (ICC = 0.952 [95% CI: 0.907-0.976] for 2D, 0.941 [0.866-0.973] for 3D), good agreement for foraminal stenosis assessments on T2 sequences (AC2 = 0.713 to 0.795 for 2D, 0.706-0.832 for 3D), and good agreement for fracture detection on T1 sequences (AC1 = 0.869 for 2D, 0.815 for 3D). CONCLUSIONS: DLR-enabled 3D lumbar spine MRI offers comparable image quality to 2D with reduced overall scan time.
11 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 →Lancet (London, England)
Efficacy and safety of cemdisiran siRNA in myasthenia gravis (NIMBLE): a double-blind, randomised, placebo-controlled, phase 3 trial
BACKGROUND: Autoantibody-mediated complement activation drives pathology in acetylcholine receptor (AChR) antibody-positive generalised myasthenia gravis. Newer targeted therapies lower overall antibody concentrations or inhibit complement activity. We aimed to evaluate an siRNA (cemdisiran) targeting complement component 5 (C5) as monotherapy and in combination with a C5 antibody (pozelimab) in generalised myasthenia gravis. METHODS: NIMBLE is a randomised, double-blind, placebo-controlled, phase 3 trial conducted at 86 centres in 13 countries. We enrolled patients aged 18 years or older with a diagnosis of generalised myasthenia gravis, positive serology for anti-AChR or anti-LRP4 antibodies, and a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or greater. Patients were randomly allocated to receive cemdisiran monotherapy (600 mg every 12 weeks; cemdisiran group), pozelimab monotherapy (200 mg every 4 weeks; pozelimab group), combined cemdisiran (200 mg every 4 weeks) and pozelimab (200 mg every 4 weeks; combination group), or placebo, all administered subcutaneously, during a 24-week double-blind treatment period. The primary endpoint was change from baseline in MG-ADL scores at week 24, assessed in the modified intention-to-treat (mITT) primary analysis set (the first 245 randomly allocated patients who received any dose of study treatment and had at least one post-baseline assessment). A prespecified hierarchal statistical testing strategy was used; multiplicity was controlled for comparisons of cemdisiran versus placebo and combination versus placebo (pozelimab was not statistically tested against placebo and was used only to assess the contribution of components to the combination treatment). Safety was mainly assessed by recording of treatment-emergent adverse events in all patients who received any dose of study treatment. This study is registered with ClinicalTrials.gov (NCT05070858); the current status is active, not recruiting. FINDINGS: Between Jan 20, 2022 and July 18, 2025, 390 participants were screened and, as of the data cut-off presented in this report (July 8, 2025), 284 were randomly allocated to the cemdisiran group (79 [28%] patients), pozelimab group (50 [18%]), combination group (80 [28%]), and placebo group (75 [26%]). Of 277 patients who received any study treatment, 263 (95%) completed the double-blind treatment period. In the mITT primary analysis set, at week 24, the least-squares mean change from baseline in MG-ADL total score was -4·5 (SE 0·4) in the cemdisiran group (n=64), -4·0 (0·4) in the combination group (n=67), and -2·2 (0·5) in the placebo group (n=59). Placebo-adjusted least-squares mean differences in MG-ADL score at week 24 were -2·3 (SE 0·7; 95% CI -3·6 to -1·0; p=0·0005) in the cemdisiran group and -1·7 (0·7; -3·0 to -0·4; p=0·0086) in the combination group. The proportion of participants with at least one adverse event during the double-blind treatment period was 54 (69%) of 78 in the cemdisiran group, 65 (81%) of 80 in the combination group, 40 (82%) of 49 in the pozelimab group, and 54 (77%) of 70 in the placebo group. The most common adverse event in the cemdisiran group was upper respiratory tract infection (nine [12%] of 78 patients), which occurred at a similar incidence in the placebo group (eight [11%] of 70). No serious or meningococcal infections occurred in the cemdisiran group. Adverse events leading to treatment discontinuation occurred in two participants (3%) in the placebo group and one participant (2%) in the pozelimab group. No deaths occurred during the double-blind treatment period. Two deaths occurred after the double-blind treatment period, one of which was assessed as treatment-related by the investigator but not treatment-related by the sponsor. INTERPRETATION: Cemdisiran monotherapy and combination therapy were effective in the treatment of generalised myasthenia gravis, and were generally well tolerated. Subcutaneous dosing of cemdisiran, administered every 3 months, could provide a convenient treatment approach for generalised myasthenia gravis. FUNDING: Regeneron Pharmaceuticals.
10 May 2026
Read appraisal →Current osteoporosis reports
The Use of Statistical Shape and Appearance Modelling for Predicting Osteoporotic Fracture Risk
PURPOSE OF REVIEW: Osteoporotic fractures remain a major cause of morbidity and mortality worldwide. Current clinical assessment metrics (e.g., bone mineral density) are limited in their ability to identify fracture risk and bone strength. Statistical Shape and Appearance Modelling (SSAM) offers a method to quantify anatomical geometry and density patterns. This review examines advancements in SSAM for osteoporosis research. RECENT FINDINGS: Recent literature demonstrates that SSAM can capture detailed bone geometry and internal density distribution. Increasingly, these models are combined with computational analytics, including finite element analysis and machine learning, to assess the mechanical and structural behavior of bone. SSAM provides a robust quantitative framework for bone research. Notably, SSAM is used to reconstruct 3D subjects from clinical 2D images for biomechanical evaluation. Although clinical adoption remains limited by generalizability, the advancement of deep learning and complex SSAM pipelines supports its potential for osteoporosis screening and fracture risk prediction.
10 May 2026
Read appraisal →Abdominal radiology (New York)
Advancing osteoporosis opportunistic screening: multicenter validation of a deep learning algorithm using abdominal CT scans
OBJECTIVES: To develop and do multicenter validation on an algorithm that screens for osteoporosis from abdominal CTs. METHODS: This is a diagnostic accuracy study with retrospective data from January 2022 to July 2022 consisting of two steps: a segmentation step of the lumbar vertebral bodies, involving outpatient non-contrast abdominal CTs from Diagnósticos da América S/A (Dasa), and a multicenter validation step incorporating data from four additional institutions. The segmentation employed a 2D UNet with a ResNet34 backbone. We determined the Pearson correlation coefficient (r) between the mean of the slices' mean attenuations (MSMA) on CT scans against the bone mineral density (BMD) on recent DEXA scans, calculated AUCs and performance metrics for osteoporosis prediction, including 95% confidence intervals, and evaluated calibration plots. RESULTS: The multicenter validation included 504 participants (median age, 66 years, interquartile range 56-72; 388 women). A linear regression analysis showed an r of 0.62 (95% CI, 0.56-0.67) between MSMA (HU) and BMD (g/cm2). The AUCs (95% CI) for distinguishing between normal and osteoporosis were 0.96 (0.89, 1.0) for the internal dataset and 0.82 (0.74, 0.89) for the external dataset, and the performance metrics (95% CI), for a globally optimized threshold of 202.6 HU, were 100% sensitivity (44, 100) and 91% specificity (84, 95) for internal data and 79% sensitivity (61, 90) and 81% specificity (76, 84) for external sites. MSMA was independently associated with osteoporosis on a mixed-effects logistic regression analysis. The model showed good calibration, with Brier score of 0.054. CONCLUSION: We developed and performed a multicenter validation of a DL model for osteoporosis prediction on CT.
6 May 2026
Read appraisal →European radiology
Enhancing vertebral fracture prediction using multitask deep learning computed tomography imaging of bone and muscle
OBJECTIVES: To develop and externally validate a computed tomography (CT)-based multitask learning model to predict fracture risk. MATERIALS AND METHODS: This study was conducted in two parts, using a multitasking learning approach. We developed a cross-sectional vertebral fracture (VF) detection model using abdominal CT scans of 2553 patients aged 50-80 years. Then, we leveraged this detection model within a multitask learning framework to develop a longitudinal VF prediction model over a 5-year follow-up period. External testing was performed on 1506 patients from two independent hospitals. The performance was compared between the single-task and multitask models, bone-only and bone+muscle images, and image-only and clinical models. RESULTS: For the cross-sectional fracture detection model, the mean age of the patients was 76.2 years, and 66.7% were female. In the classification task for detection of VF, the model using both bone and muscle showed an area under the receiver operating characteristic curve (AUROC) of 0.82 in the development set and 0.80 in the external test sets. Using multitask learning, the bone + muscle image model showed a c-index of 0.68 and had superior performance than the bone-only model in the external test set for 2-year, 3-year, and 5-year AUROCs (0.79 vs. 0.75, 0.71 vs. 0.68, and 0.71 vs. 0.68, respectively, all p < 0.01). Also, the multitask model significantly outperformed the Fracture Risk Assessment Tool (FRAX) (c-index: 0.68 vs. 0.66, p < 0.01). CONCLUSION: The CT-based multitask learning model integrating both bone and muscle data showed superior predictive performance for VFs compared with models using bone images only and traditional clinical models. KEY POINTS: Question Vertebral fracture risk remains underestimated in many individuals undergoing CT scans for other reasons, highlighting the need for improved opportunistic prediction tools. Findings A multitask deep learning model integrating both bone and muscle features from CT scans demonstrated superior performance compared to bone-only and traditional clinical models, including FRAX. Clinical relevance The proposed model enables accurate vertebral fracture risk prediction using routinely acquired CT scans, facilitating early identification and intervention without the need for additional tests.
6 May 2026
Read appraisal →International journal of medical informatics
BackTracker: Machine learning to identify kinematic phenotypes for personalised exercise management in non-specific low back pain.
BACKGROUND: Low back pain (LBP) is a leading cause of global disability. Most cases are non-specific (NSLBP) and lack identifiable causes. Early active management is endorsed by clinical guidelines; however, exercises are rarely customised despite substantial variability in impairments. Existing classification systems can support targeted rehabilitation but require extensive clinical training and lengthy assessment procedures, limiting timely personalised care. OBJECTIVE: This study used AI methods to identify the two most common motor control impairments (MCIs)-flexion and extension patterns (FP/EP)-in NSLBP. The approach used spinal silhouettes extracted from movement videos to enable self-phenotyping and guide personalised exercise selection. METHODS: Data were collected from a research fellowship involving ninety NSLBP participants classified by an expert physiotherapist (LS) into FP or EP MCIs. Participants performed standard forward- and backward-bend tasks recorded in the sagittal plane. Pose estimation and instance segmentation techniques were applied to extract motion features and spine silhouettes. From each participant, a curated set of 80 black-and-white back images captured at specific bending angles was produced. These features were used to train a feedforward neural network. Model performance was assessed using five-fold cross-validation with accuracy, sensitivity, specificity, F1 score and AUC. RESULTS: The model achieved a diagnostic accuracy of 91.91% (95% CI 84.8-99.1) for backward-bend videos, exceeding reported inter-examiner agreement rates for trained physiotherapists. Robustness was supported by a mean AUC of 0.9422. Accuracy was lower for forward-bend images (86.69%), combined tasks (86.29%), or PROMs alone (63.82%). Adding PROMs to forward- or backward-bend tasks provided only modest improvements (66.32% and 71.62%, respectively). CONCLUSION: The model reliably distinguished between FP and EP NSLBP subgroups, demonstrating the potential of AI to support timely personalised rehabilitation. The integration of PROMs with motion features reduced classification accuracy, suggesting that self-reported outcomes may provide limited benefit when tailoring exercises to specific physical impairments.
5 May 2026
Read appraisal →Biosensors & bioelectronics
Peptide-responsive photonic hydrogels integrated with deep learning assistance for early MMP-9 detection
Matrix metalloproteinase-9 (MMP-9) is crucial for extracellular matrix remodeling, and its dysregulation is associated with inflammatory diseases and different forms of cancer. Conventional MMP-9 detection methods such as enzyme-linked immunosorbent assay (ELISA) are limited by complexity, expensive equipment, and lengthy antibody incubation times. These limitations prevent their use in point-of-care testing. An MMP-9 responsive photonic crystal (PC/PEG-M9SP) hydrogel has been developed to address these challenges. The hydrogel is synthesized from 4-arm polyethylene glycol-acrylate and an MMP-9 sensitive peptide via Michael-type addition reaction. Upon MMP-9-specific enzymatic cleavage, the hydrogel undergoes a structural reconfiguration, resulting in a distinct color shift. Integrated with a deep learning-based smartphone app, this platform enables both visual and quantitative detection within 10 min, achieving high sensitivity (10.60 nm mL/ng) and a detection limit of 0.62 ng/mL. Validation in complex biological fluids demonstrated strong concordance with ELISA, confirming the analytical reliability of the hydrogel. This system provides a rapid, portable, and cost-effective solution for accurate MMP-9 detection, with strong potential for clinical and point-of-care applications.
5 May 2026
Read appraisal →Journal of proteome research
NetMHCIIphosPan: A Machine Learning Tool for Predicting HLA Class II Antigen Presentation of Phosphorylated Peptides
Phosphorylated peptides presented by human leukocyte antigen (HLA) class II molecules play pivotal roles in immune regulation, yet their characterization and prediction remain challenging due to data noise and limited HLA coverage. Here, we introduce NetMHCIIphosPan, a prediction method for HLA-II antigen presentation of phosphorylated peptides, developed using mass spectrometry (MS)-based immunopeptidomics data sets. Employing a refined peptide identification workflow, we reanalyzed earlier HLA-II phospholigand data sets and trained predictive models, achieving superior performance compared to models trained on the original data. Binding motif analysis revealed that HLA-specific preferences for phospholigands closely aligned with those of unmodified ligands. Incorporating unmodified ligands into training further enhanced predictive accuracy, particularly for HLA-DP and HLA-DQ molecules. NetMHCIIphosPan outperformed existing tools, such as NetMHCIIpan-4.3 and MixMHC2pred-1.3, for prediction of HLA antigen presentation of phosphorylated peptides, demonstrating robustness and utility. This work establishes NetMHCIIphosPan as a state-of-the-art tool for understanding the HLA-II phospholigandome, with potential applications in immunotherapy and vaccine design.
4 May 2026
Read appraisal →NMR in biomedicine
Deep Learning Reconstruction Enables Diagnostic-Quality 0.4T Knee and Spine MRI in One-Third of the Time
There has been a growing interest in low-field MRI due to its lower costs, enabling an increase in accessibility of MRI worldwide. Long scan times are currently needed to obtain high-quality images. The aim of our study was to accelerate low-field 0.4T musculoskeletal MRI using deep learning and evaluate maximum acceleration via assessment by two expert radiologists. A cascades of independently recurrent inference machines (CIRIM) model was trained using knee and spine 2D multislice scans, retrospectively undersampled in k-space. The heterogeneous dataset included varied contrasts, orientations, and matrix sizes. To determine the maximum possible acceleration factor, the undersampling pattern and loss function of the CIRIM were optimized using the knee dataset. Models were trained for acceleration factors 1.5-4. The different acceleration factors were evaluated quantitatively and clinically, with radiologist scores compared using Kendall's Tau and Cohen's Kappa. To assess the model's generalizability, two prospectively undersampled scans were evaluated, and the knee-trained models were tested on spine data. CIRIM accurately reconstructed all data, with slight metric degradation at higher accelerations. Combining L1, structural similarity index measure (SSIM), and perceptual loss improved sharpness, while undersampling pattern differences were minimal. Clinical scores from both radiologists declined with acceleration, reflected in Kendall's Tau values of 0.64, 0.64, 0.54, and 0.55 for image quality, sharpness, anatomical conspicuity, and artifacts. Inter-observer agreement was low (Cohen's kappa: 0.227-0.299). The model generalized well, reconstructing spine data with a knee-trained model at comparable quality and successfully handling prospectively undersampled scans. CIRIM consistently delivered high-quality reconstructions, demonstrating excellent robustness to variations in contrast, orientation, matrix size, and anatomy. Its ability to generalize across anatomies and handle prospectively undersampled scans highlights its practical utility. The differences in reading for higher accelerations between radiologists suggest that the optimal acceleration factor is context-dependent and should be tailored to the specific diagnostic task.
4 May 2026
Read appraisal →Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA
Synthetic computed tomography from magnetic resonance imaging: An editorial on deep learning approaches for hip and knee image translation.
This editorial provides a concise overview of synthetic computed tomography (CT) generation from magnetic resonance imaging (MRI) for musculoskeletal care, with a focus on hip and knee applications. We outline why interest in this area is growing, including the potential to reduce radiation exposure, consolidate imaging into a single visit, and align measurements across modalities for preoperative planning and longitudinal follow-up. At a high level, we summarize how deep learning methods transform MRI into CT-like volumes and what that could mean for bone morphology, implant planning, and combined assessment of bone and soft tissue. We briefly introduce representative model classes, including conditional generative adversarial networks that pair realism objectives with voxelwise constraints and diffusion models that replace adversarial training with iterative denoising for stable optimization and strong anatomical fidelity. Our goal is to orient clinicians, engineers, and researchers to the key promises and open questions, and to motivate collaborative studies that test whether synthetic CT can deliver reliable, reproducible, and clinically useful information at the point of care.
4 May 2026
Read appraisal →Physics in medicine and biology
Few shots transfer learning for universal SPECT denoising across diverse acquisition protocols
Objective.Accelerated single photon emission computed tomography (SPECT) imaging, achieved by reducing either the number of projection angles or the acquisition time per angle, enhances clinical workflow efficiency but introduces elevated noise. This study aims to develop and validate a universal DL-based reconstruction framework that effectively generalizes across diverse, clinically-realistic SPECT acceleration protocols by overcoming the data scarcity challenge.Approach.SPECT bone scans from 103 patients were acquired under a standard scan (60 views, 12 s/view, 60v12s) followed by a fast scan using one of five acceleration protocols (60v6s, 60v3s, 30v12s, 30v6s, 16v12s). AU-Net-based reconstruction framework was implemented using three strategies: (1) single model, trained on individual acceleration protocol), (2) base model, trained on aggregated datasets from five acceleration protocols, and (3) transfer model, fine-tuned from the base model for protocol-specific optimization. Pixel-level accuracy and structural similarity were assessed using peak signal-to-noise ratio (PSNR), structural similarity index (SSIM) metrics, and maximum pixel value of lesions. Clinical evaluation of image quality, radionuclide detail, artifacts, and diagnostic confidence was conducted using a 5-point system.Main results.Quantitative evaluation showed the transfer model achieved better PSNR and SSIM across all protocols (highest 48.02 PSNR and 0.9918 SSIM in 30v6 s protocol). Qualitative analysis confirmed enhanced structural fidelity. Clinical evaluations rated the transfer model highest across metrics, with scores of 4.667 ± 0.508 (image quality, 30v12 s), 4.800 ± 0.250 (radionuclide detail, 60v6 s), 1.150 ± 0.173 (artifact reduction, 60v6 s), and 4.800 ± 0.250 (diagnostic confidence, 60v6 s), surpassing full-scan results in most cases.Significance. The proposed transfer learning (TL) framework effectively addressed data scarcity and improved reconstruction performance across diverse SPECT acceleration scenarios. The adoption of a TL strategy mitigates data scarcity by utilizing shared features and fine-tuning for specific protocols. The framework demonstrates potential for integration into fast SPECT workflows, facilitating reliable use across diverse imaging scenarios.
2 May 2026
Read appraisal →Stem cells (Dayton, Ohio)
Quiescence in the resting zone of the growth plate: a systematic review
Postnatal skeletal growth in childhood and adolescence depends on cartilage organs called (epiphyseal) growth plates. Studies in the last decade have identified populations of skeletal stem cells within mouse growth plates' resting zones. While cellular quiescence is vital for the maintenance of many tissue-resident stem cell populations, the resting zone chondrocytes have been labeled "quiescent" for decades. However, the features of cellular quiescence that have been reported in the postnatal resting zone, how they were defined or experimentally assessed, and knowledge gaps relative to other quiescent cell types, remain to be well described. To address this, we conducted a systematic review, using the PRISMA guidelines, to identify studies of resting zone chondrocytes including the prefix "quiescen*." Definitions, keywords, chronological data and experimental findings were extracted. Our analysis demonstrated that, compared to those in other well-studied tissues, features of cellular quiescence in RZ chondrocytes remain poorly reported and underexplored, with limited molecular and functional characterization. Furthermore, while most identified studies reported changes in cell division parameters, integration between cues controlling resting zone cell quiescence is incomplete and heterogeneity among the various sub-populations of RZ cells/potential quiescent states is yet to be fully determined. This review identifies consensuses and knowledge gaps between studies and between quiescent RZ cells and those in other tissues and can act to enhance consistency and comparability in future studies of "quiescence" in the RZ chondrocytes.
30 Apr 2026
Read appraisal →Physics in medicine and biology
Confounding factors in the generalisation of synthetic CT to diagnostic spine MRI
Objective. Generalisation of synthetic CT (sCT) generation to diagnostic MRI data in the spine faces many challenges, particularly when aiming at accurate visualisation of pathologies for orthopaedic treatment management. In this study we assessed the effect of potential confounding factors on the performance of sCT generation from diagnostic MR images.Approach. Paired spinal diagnostic MR and CT scans from two centres (51 patients) were collected retrospectively, spanning multiple spinal pathologies and regions. Each patient's dataset contained 3D T1-/T2-weighted and 2D T1- and T2-weighted scans. 3D U-Nets were trained per centre on the 3D MR data and CT using a mean absolute error (MAE) loss. The performance was assessed on sCTs derived from original 2D and 3D data and from simulated 2D data with varying orientation (axial/coronal/sagittal) and slice spacing (1.1-6.6 mm). The sCTs were compared to the CTs using MAE, peak signal-to-noise ratio, and dice similarity coefficient.Main results. We identified MR resolution, orientation and contrast as confounding factors for sCT generation from diagnostic MR. Additionally, CT noise and CT-to-MR registration were identified to influence the performance evaluation. Performance degraded with larger slice spacings and significant differences between orientations occurred more often at larger slice spacings. The effect of slice spacing and orientation was stronger inside the vertebrae than outside. While the networks performed better overall on contrasts more similar to the training contrasts, they demonstrated promising performance when trained on 3D T2w images and tested on 2D T1w images. Finally, higher CT noise levels resulted in worse sCT performance metrics, reflected in a significant correlation between noise and MAE.Significance. This work demonstrates that generalisation of sCT generation to diagnostic spine MRI data is hampered primarily by MRI acquisition related aspects including MR resolution, orientation and contrast, which provides guidance for future work on generalisable sCT from diagnostic MR.
27 Apr 2026
Read appraisal →Journal of medicinal chemistry
Automated Molecular Design in BRADSHAW, Applied to the Optimization of ERAP1 Inhibitors
Generative design and machine learning are increasingly prevalent in medicinal chemistry. To pilot the comprehensive use of automated molecular design on a project, the BRADSHAW platform was used to optimize a series of inhibitors of Endoplasmic Reticulum Aminopeptidase 1 (ERAP1), an emerging target in cancer immunotherapy and autoimmune diseases. Through four consecutive iterations applying in silico molecular generation, property prediction and filtering, we conducted a multiparameter optimization of potency, physicochemical properties and pharmacokinetics. Continuous refinement of Machine Learning (ML) models led to improved scoring accuracy and compound quality, culminating in identification of in vitro and in vivo tool molecules. We also discuss our reflections on the pilot and integration of automated design into medicinal chemistry projects, including observations of the human factors resulting from increased use of computational design, and recommendations for future projects.
25 Apr 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Pharmacological interventions to improve bone density in functional hypothalamic amenorrhea: a systematic review and network meta-analysis of randomized clinical trials
CONTEXT: Women with functional hypothalamic amenorrhea (FHA) are at high risk of poor bone health. When lifestyle measures fail to restore menses, pharmacological interventions are needed for bone health, but comparative efficacy remains unclear. OBJECTIVE: To compare the efficacy of available pharmacological interventions to improve bone mineral density (BMD), in women with FHA, employing network meta-analysis (NMA). DATA SOURCES: Medline, Embase, Emcare, Cochrane CENTRAL, ISRCTN, and ClinicalTrials.gov were searched up to 20 September 2025. STUDY SELECTION: Eligible randomized-controlled trials evaluated pharmacological interventions for lumbar spine (LS), femoral neck (FN), or total hip (TH) BMD in women with FHA. Two independent reviewers screened titles, abstracts, and texts. DATA EXTRACTION: Two reviewers independently extracted data following the Preferred Reporting Items for Systematic Reviews-network meta-analysis guidelines. Outcomes were expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects NMA. Evidence certainty was assessed with CINeMA. DATA SYNTHESIS & RESULTS: Thirteen randomized-controlled trials (n = 897 participant observations across all pharmacotherapy comparisons) were included (LS BMD: n = 897; FN BMD: n = 370; TH BMD: n = 750). Transdermal hormone replacement therapy (HRT) was superior to control (placebo or no intervention) for LS BMD with SMD: 0.34 (0.03, 0.64) and FN BMD with SMD: 0.57 (0.04, 1.10). Oral HRT and the combined oral contraceptive pill (COCP) showed no significant benefit for any BMD site. Teriparatide was superior to transdermal HRT and COCP for LS BMD with SMDs: 1.48 (0.38, 2.59) and 1.75 (0.66, 2.83), but not FN or TH BMD. CONCLUSIONS: Transdermal HRT and teriparatide improve LS BMD in women with FHA, with transdermal HRT also improving FN BMD. STUDY REGISTRATION: PROSPERO (CRD42024576872).
25 Apr 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Health and adverse events associated with extended oral bisphosphonates among postmenopausal women: a systematic review
BACKGROUND: International guidelines recommend the use of oral bisphosphonates (oBP) for up to 5 years in the treatment of postmenopausal osteoporosis. However, benefits and risks of extending oBP therapy beyond this duration remain uncertain. AIM: To determine the health outcomes (bone mineral density [BMD], fracture risk) and adverse effects (atypical fracture, osteonecrosis of the jaw [ONJ]) of extended oBP therapy beyond 5 years among postmenopausal women. METHODOLOGY: A systematic search of Medline©, EMBASE©, and CINAHL© was conducted from inception to 15 March 2024. Interventional and observational studies published in English were included. Two authors independently performed screening, quality appraisal using the NIH Quality Appraisal tool, and data extraction. The review followed PRISMA guidelines and was registered on PROSPERO (CRD42024475332). High heterogeneity precluded meta-analysis. RESULTS: Eleven studies (4 controlled trials, 7 observational) were included: 3 rated as good quality, 7 as fair, and 1 as poor. Extended oBP therapy beyond 5 years increased BMD at the hip (3/3 studies), femoral neck (3/3 studies) and lumbar spine (5/5 studies). Prolonged oBP use reduced clinical vertebral fracture risk (1/6 studies) but increased the risk of atypical fractures (3/3 studies) and incomplete atypical femoral fractures (1/1 study). None of the included studies assessed or reported ONJ. CONCLUSION: Substantial heterogeneity and limited high-quality evidence preclude definitive conclusions regarding extended oBP use in postmenopausal women. While extended treatment may improve bone density and reduce vertebral fractures, it could also increase atypical fractures. Future high-quality studies are required to inform decisions regarding optimal treatment duration.
25 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 →American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
Feasibility and acceptability of incorporating telemedicine into pharmacy services in the rheumatology clinics of the School of Medicine of the University of Puerto Rico
PURPOSE: Incorporating telemedicine into pharmacist services can promote medication adherence, reduce polypharmacy, and prevent adverse drug events as part of identification of drug-related problems. Our primary aim was to measure the acceptability to patients of telemedicine services using a standardized patient satisfaction survey and compare it to that for face-to-face services. Our secondary aim was to assess the feasibility of the telemedicine modality for pharmaceutical care interventions by measuring, quantifying, and categorizing drug-related problems identified during the service. METHODS: The study followed a prospective crossover design from October 2021 to September 2022. Adult patients (21 years or older) with rheumatic diseases evaluated at a university-based outpatient clinic were eligible to be enrolled. After the intervention, patients completed a survey regarding satisfaction and perception of their appointment. Descriptive statistics were used for patient demographic characteristics. Patient satisfaction with the modalities was compared using a t test. RESULTS: In this study, 296 patients were enrolled with a mean (SD) age of 50.4 (12.5) years. Participating patients were utilizing a mean (SD) of 10.2 (4.7) medications. No significant differences (P < 0.05) were observed for any of the survey questions when comparing responses for the face-to-face and telemedicine encounters. In general, patients strongly agreed that they were satisfied with the services they received and perceived the services as unique and valuable in both types of encounters. CONCLUSION: Overall satisfaction was very high, and no differences were found in the perception of or satisfaction with services between the telemedicine and face-to-face modalities.
24 Apr 2026
Read appraisal →PloS one
Identification and clinical implications of immune-related hub genes in psoriasis
BACKGROUND: Psoriasis, a chronic inflammatory skin disease affecting 2-3% of the global population, is driven by dysregulated immune responses. Despite advancements in biologic therapies, treatment challenges persist due to high recurrence rates. This study aimed to identify immune-related hub genes and elucidate their clinical implications in psoriasis pathogenesis and therapy. METHODS: Multiple microarray datasets from psoriasis patients (GSE30999, GSE106992, GSE14905, GSE78097, and GSE117468) were obtained to identify immune-key genes by differential gene analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Subsequently, immune-related hub genes were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and Protein-Protein Interaction (PPI) networks, with further validation through Gene Set Enrichment Analysis (GSEA) and Receiver Operating Characteristic (ROC) curves to assess exploratory within-sample discrimination. Pearson correlation analysis evaluated the relationship between hub genes, skin lesion severity, and treatment outcomes. The study also conducted immune infiltration by using the Cell-type Identification by Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm and identified potential therapeutic targets by the Drug-Gene Interaction Database (DGIdb). RESULTS: Thirty-one immune-related key genes were identified, and six hub genes (CLEC7A, CXCL1, IRF1, S100A12, S100A8, S100A9) were validated as central players in immune signaling pathways. These genes exhibited within-sample discrimination (AUC > 0.9) and correlated with disease severity and biological therapy efficacy. Immune infiltration analysis revealed increased activated memory CD4+ T cells and M1 macrophages in lesional skin, which was strongly associated with hub gene expression. Additionally, drug-gene interaction analysis identified potential therapeutic agents targeting these genes. CONCLUSION: This study identified six immune-related hub genes that were closely linked to the severity of psoriasis, the effectiveness of biological treatments, and infiltrated activated memory CD4+ T cells and M1 macrophages. Our findings elucidate a novel immune-related hub gene network in psoriasis and provide potential targets for the development and application of biologics.
23 Apr 2026
Read appraisal →Proceedings of the National Academy of Sciences of the United States of America
Making invisible excited-state structures of pro-interleukin-18 visible by combining NMR and machine learning
NMR spectroscopy is a powerful tool for studies of protein dynamics over timescales extending more than twelve orders of magnitude, with motion queried at many of the backbone and sidechain positions in the molecule of interest. NMR experiments can, in principle, provide atomic resolution descriptions of excited conformational states that are sparsely populated and transiently formed-i.e., invisible, and there are examples of such structures in the literature. However, in other cases, the NMR data are not sufficient for generating structural ensembles of rare and transient higher energy conformers of the protein of interest. One example is provided by the precursor form of the proinflammatory cytokine interleukin-18, pro-IL-18, studied here. Although NMR studies show that pro-IL-18 adopts two sparsely populated (<0.5%) and transiently formed (ms lifetimes) excited-state conformations in exchange with a highly populated ground state conformer and localize regions undergoing exchange to a pair of short β-strands that are preserved in at least one of the excited states, additional structural information is not forthcoming. Here, we develop a protocol whereby the NMR data are used to select alternative conformers of pro-IL-18 from ensembles predicted by the generative machine learning model AlphaFlow that are then evaluated through further NMR experiments. The method identifies distinct conformers that correspond to the pair of excited states reported by NMR, combining experiment with computation to characterize the pro-IL-18 energy landscape in ways that are not possible with either approach alone.
20 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 →Medicine
Safety assessment of intravenous immunoglobulins in pediatric population: A systematic review of adverse events
BACKGROUND: Intravenous immunoglobulin (IVIG) is a therapeutic intervention utilized in various disorders due to its antimicrobial, antiinflammatory, and immunomodulatory properties. The market offers a range of IVIG products, leading to variations in efficacy and safety profiles. This study aimed to systematically evaluate the safety profile of IVIG administration in pediatric patients. METHODS: A systematic search was conducted on PubMed, Embase, and Cochrane databases using predetermined MeSH terms, covering the period from January 1, 2000, to October 15, 2022. Two independent reviewers performed relevance screening. Inclusion criteria encompassed English-language studies involving patients below 18 years of age who received IVIG treatment. Included studies were limited to peer-reviewed full-text publications with a minimum of 5 patients. A total of 8 studies met the inclusion criteria, encompassing 1088 pediatric patients. RESULTS: Eight studies met the inclusion criteria (total 1088 pediatric patients). Five studies reported patient-level adverse event data suitable for pooling (688 patients). Among these 688 patients, 267 (38.8%) experienced adverse events (AEs). Among reported AEs, the most frequent were headache 68/267 (25.5%) and fever 47/267 (17.6%). Less common AEs included nausea 12/267 (4.5%) and fatigue 12/267 (4.5%). Four studies recorded a total of 2960 IVIG infusions, with 12.6% of infusions accompanied by AEs. The predominant AEs during infusions were headache (54.3%) and fever (29.4%). Cough (0.8%) and nausea (1.6%) were the least commonly observed AEs. Other AEs such as rash, vomiting, and abdominal pain were also reported. Of the 23 full-text articles reviewed, 8 were included. The remaining 15 were excluded due to the following reasons: 6 for duplicate data, 4 for inappropriate study design, 3 for not meeting the minimum number of patients, and 2 for incomplete adverse event reporting. These reasons are now detailed in the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. CONCLUSION: IVIG therapy demonstrates good tolerability in pediatric patients, with an overall favorable safety profile, aside from mild AEs associated with its administration. Serious AEs were infrequent and mainly observed in high-risk patients. Headache was the most prevalent AE, which seldom required hospitalization and could be effectively managed with acetaminophen. Other AEs were generally mild systemic reactions. Notably, AEs appear to be more frequent during the initial exposure to IVIG.
19 Apr 2026
Read appraisal →BMJ open
Patients' experiences of the path to sarcoma diagnosis: a qualitative systematic review and thematic synthesis
OBJECTIVE: To explore existing qualitative research on patients' experiences from the onset of symptoms to the diagnosis of sarcoma, with the purpose of identifying patient-perceived barriers at both patient and healthcare system levels and to highlight opportunities for improvement. DESIGN: Systematic review of qualitative studies using thematic synthesis. METHODS: We systematically searched Medline [Ovid], Embase [Ovid], PsycINFO [EBSCOhost] and CINAHL [EBSCOhost] from database inception to 11 April 2025 for qualitative studies reporting sarcoma patients' experiences during their diagnostic trajectory. The final search was conducted on 11 April 2025. All articles were screened against predefined inclusion and exclusion criteria and methodological quality was appraised using the Critical Appraisal Skills Programme qualitative checklist. Six studies conducted in Australia, the Netherlands and the UK were included. Data were analysed using a thematic synthesis approach guided by Thomas and Harden (2008). Confidence in the synthesised findings was assessed using the Grading of Recommendations Assessment, Development and Evaluation - Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERqual) approach. RESULTS: Four overarching themes emerged: patients' experience and interpretation of symptoms, diagnostic pathways, healthcare system factors, and reflections and recommendations. Key contributors to delayed diagnosis were symptom normalisation, misattribution by both patients and healthcare professionals, limited continuity of care and communication challenges. These findings were consistent across multiple countries, indicating relevance and validity in many settings. Patients emphasised the importance of disease awareness, persistence of patients and coordinated care. CONCLUSIONS: Diagnostic delays in sarcoma are influenced by both patient and healthcare systemic factors. Addressing these factors requires increased disease awareness among healthcare professionals and the public, improved coordination within the healthcare system, and targeted research to guide future interventions. This review provides cross-country insights into barriers to early sarcoma diagnosis, informing future priorities in clinical practice and research. PROSPERO REGISTRATION NUMBER: CRD420251030726.
18 Apr 2026
Read appraisal →Spine
An Unsupervised Learning Approach for Multimodal Low Back Pain Stratification
STUDY DESIGN: Cross-sectional study. OBJECTIVE: This study proposes a novel stratification framework for individuals with low back pain (LBP). The method integrates Northern Finland Birth Cohort data comprising imaging biomarkers from deep learning (DL)-based analysis of lumbar spine MRI with the data on smoking status, demographics (sex and BMI), self-reported data from Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) short and the STarT Back Tool (SBT). Furthermore, the utility of this stratified approach was validated by demonstrating a superior net benefit compared with "treat-all" strategy. BACKGROUND: Current risk stratification for individuals with LBP relies on ÖMPSQ short and SBT among others. While these tools are invaluable for capturing psychosocial characteristics predictive of future disability and functional outcomes, LBP's multifactorial nature necessitates a more comprehensive framework for effective risk stratification. MATERIALS AND METHODS: A method for multimodal unsupervised patient stratification has been developed that allows for the integration of imaging biomarkers of disc degeneration (DD) and facet tropism (FT), extracted using DL models, with nonimaging data. The framework utilized robust K-Means clustering to stratify individuals. Clusters were characterized using LBP frequency and bothersomeness, and their robustness was validated with a multi-class logistic regression model. Net benefit was assessed through decision curve analysis. RESULTS: Three distinct subgroups were characterized by LBP frequency and bothersomeness. One subgroup was dominated by psychosocial characteristics (psychosocial risk P < 0.05), the second by physical degenerative changes (DD P < 0.05), and the third by a mix of both. Predictive models for cluster assignment were robust, achieving high mean accuracies (SBT-based: 0.89; ÖMPSQ-short-based: 0.87). The net benefit is superior throughout a range of threshold probabilities compared with a "treat-all" strategy. CONCLUSION: A novel framework was developed that integrates multimodal data to identify distinct subgroups differentiated by their physical and psychosocial characteristics in a population-based cohort, demonstrating potential for advancing personalized care.
17 Apr 2026
Read appraisal →Theory in biosciences = Theorie in den Biowissenschaften
Analytical and AINN-based investigation of surface wave propagation in dry long bones with initial stress, magnetic field, and rotation effects
This study presents a comprehensive analytical and artificial intelligence neural network (AINN)-based investigation of wave propagation in dry long bones, modeled as an orthotropic hollow cylindrical structure. The proposed model incorporates the combined effects of initial stress, magnetic field, and rotational motion to capture the complex behavior of bone-like media under coupled physical influences. The governing equations are formulated within a continuum mechanics framework and solved analytically using displacement potential methods, yielding solutions in terms of Bessel functions that satisfy the cylindrical geometry and boundary conditions. Two distinct cases, corresponding to the absence and presence of rotation, are examined to assess the influence of rotational effects on wave dynamics. A detailed parametric analysis is carried out to evaluate the variation of phase velocity and frequency with respect to wave number, initial stress, magnetic parameter, density, and geometric ratios. The analytical results indicate that initial stress enhances wave propagation, while magnetic effects introduce damping and rotation significantly modifies dispersion characteristics. To improve computational efficiency and predictive capability, an AINN model is developed and trained using analytically generated data. The AINN predictions show excellent agreement with the analytical results, as confirmed through parity plots, error analysis, residual distribution, and loss convergence behavior. The novelty of the study lies in the unified analytical-AINN framework that integrates mechanical, electromagnetic, and rotational effects within a single model. The findings provide important insights for wave-based characterization of bone structures and have potential applications in non-destructive evaluation, ultrasonic diagnostics, and advanced biomedical sensing systems.
17 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 →JMIR research protocols
Integrating Gait Analysis and AI Into Knee Osteoarthritis Care: Protocol for a 3-Phase Participatory Qualitative Study
BACKGROUND: Knee osteoarthritis (OA) leads to pain, disability, and reduced quality of life. For advanced stages, knee arthroplasty surgery is the standard treatment, yet dissatisfaction and persistent mobility deficits remain common. Current surgical decision-making processes seldom incorporate objective predictors of outcomes, such as biomechanical data. Advances in computer vision, wearable sensors, and artificial intelligence now enable efficient capture and interpretation of clinically prognostic gait features in real-world settings. However, the clinical adoption of such innovations remains limited, hindered by usability challenges, misalignment with stakeholder needs, and system-level barriers. OBJECTIVE: This study aims to inform the development of a knee OA clinical decision support (CDS) tool that integrates gait analysis and artificial intelligence with clinical decision-making. More broadly, it seeks to advance a framework for participatory digital health CDS tool implementation by identifying and addressing suboptimal workflows, stakeholder priorities, and organizational challenges. METHODS: This study uses a 3-phase participatory design process, with in-depth interviews conducted in each phase to generate insights that inform subsequent stages. Phase 1 investigates perceived barriers to and facilitators of the implementation of a digital CDS tool and examines current workflow processes in knee OA management. Phase 2 focuses on identifying and defining user requirements to guide solution ideation for translational digital decision support. Phase 3 assesses user acceptance of prototyped solutions. Field observations in phase 1 and usability testing in phase 3 will supplement interview findings with real-world evidence. RESULTS: The study was funded in November 2024. Ethics approval was granted by the Nova Scotia Health Research Ethics Board on July 28, 2025. Data collection began in September 2025. As of February 2026, a total of 6 clinicians have been interviewed, with all 6 interviews transcribed and 4 coded as part of phase 1 analysis. Study completion is anticipated by August 2026. Findings will be published by January 2027. CONCLUSIONS: Our stakeholder-driven approach prioritizes both technological rigor and practical usability, addressing key human factors for successful implementation. While initially focused on Nova Scotia's orthopedic setting, this research provides a scalable framework for integrating digital decision support tools into broader clinical environments, advancing innovation in knee OA care and beyond.
16 Apr 2026
Read appraisal →Spine
Predictors for Unsuccessful Outcome of Lumbar Spinal Stenosis Surgery: A Secondary Analysis of the 2 Randomized NORDSTEN Trials
STUDY DESIGN: Observational cohort study. OBJECTIVE: To evaluate potential predictors of unsuccessful outcomes after surgery in patients with lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: LSS is a common cause of disability in adults and the leading indication for spine surgery in Norway. Despite advances in surgical techniques, nearly one-third of patients report either minor or no improvement or worsening of symptoms after surgery. Identifying predictors of unsuccessful outcomes is essential for improving patient selection and shared decision-making. MATERIALS AND METHODS: This secondary analysis used data from the 2 NORwegian Degenerative spondylolisthesis and spinal STENosis (NORDSTEN) randomized trials, which included 704 surgically treated patients with LSS, with (n=267) or without (n=437) degenerative spondylolisthesis. The Oswestry Disability Index (ODI) was the primary outcome measure. A reduction in ODI score of <30% from baseline to 2 years postoperatively was defined as an unsuccessful outcome. Multivariable logistic regression analysis was used to evaluate whether carefully selected baseline variables were associated with an unsuccessful outcome at 2-year follow-up. RESULTS: Longer duration of radiating pain (>12 mo; OR: 2.58, 95% CI: 1.54-4.29), psychological distress (HSCL-25 ≥1.75; OR: 1.60, 95% CI: 1.01-2.53), and advanced disc degeneration (Pfirrmann grades 4-5; OR: 1.98, 95% CI: 1.26-3.12) were independently associated with an unsuccessful outcome. Commonly discussed factors such as age, BMI, smoking, ASA grade, and predominant back pain did not reach statistical significance for association with the outcome. CONCLUSION: Among patients undergoing surgery for LSS, longer symptom duration, psychological distress, and advanced disc degeneration were associated with a higher risk of unsuccessful postoperative outcomes.
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 →International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
Effects of locally applied water-filtered infrared a irradiation adjunctive to iloprost and carbon dioxide hand baths in patients with systemic sclerosis and severe Raynaud's phenomenon - a randomized controlled trial
BACKGROUND: Almost all patients with systemic sclerosis (SSc) experience Raynaud's phenomenon (RP) with risk of digital ulcers (DU). In severe RP, intravenous iloprost is standard, yet additive hyperthermic therapy may enhance vasodilation and microcirculation. However, whether more intensive or alternative hyperthermic modalities offer benefits beyond commonly used CO2 hand baths remains unclear. METHODS: In this randomized, controlled trial, all patients received a baseline therapy of iloprost plus CO2 hand baths. The intervention group (IG) received additional water-filtered infrared-A (wIRA; 2 × 30 min/day, 8 days), while the control group (CG) received baseline therapy alone. The primary endpoint was the difference in RP-associated pain (VAS 0-100 mm) after treatment. Secondary outcomes included changes in RP duration, frequency, and intensity, Health Assessment Questionnaire (HAQ), serum interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). RESULTS: Of 46 randomized patients, 38 (IG = 19, CG = 19) completed the study. Pain decreased from 70.4 ± 27.8 to 56.7 ± 21.4 mm with wIRA and from 73.9 ± 27.5 to 65.3 ± 26.8 mm in controls. Multivariable ANCOVA showed a mean difference of -14.7, 95% CI [-28.8;-0.7], p = 0.041 in favor of wIRA. RP duration improved more in the wIRA group (day 23: β = -3.8, 95% CI [-7.4;-0.2], p = 0.041), while RP frequency, intensity, HAQ, IL-6, and VEGF showed no significant differences (all p > 0.05). No adverse events occurred. CONCLUSIONS: Adjunctive wIRA during iloprost therapy was safe and yielded modest, short-term improvements in pain and RP duration. These exploratory effects warrant confirmation in larger controlled trials.
15 Apr 2026
Read appraisal →Medicine
Bibliometric and visual analysis of artificial intelligence-related research in osteoarthritis: Trends and frontiers (2008-2025)
Osteoarthritis (OA) causes joint pain, functional impairment, and significantly impacts patients' quality of life. Recent advancements in artificial intelligence (AI) technology have provided new opportunities for OA diagnosis, treatment, and management. This study aims to understand the knowledge structure and research frontiers of "AI and OA" using bibliometric methods. Literature on "AI and OA" from January 1, 2008, to March 31, 2025, was retrieved from the Web of Science Core Collection database. VOSviewer, CiteSpace, and the R package "bibliometrix" were used for analysis. The study included 659 articles from 59 countries. Since 2019, the number of scientific outputs related to OA and AI has increased annually. The United States, China, and the United Kingdom are the main contributing countries, with Harvard University, Seoul National University, and the University of California system as leading institutions. The "JOURNAL OF ARTHROPLASTY" and "OSTEOARTHRITIS AND CARTILAGE" are the most contributing journals. Among the 2404 authors, GUERMAZI A and ROEMER FW are the most influential. Thematic trend analysis shows that AI and machine learning are driving new trends in OA research, especially in diagnosis, treatment planning, and patient monitoring. This paper summarizes the bibliometric trends and development in "AI and OA" studies over 18 years, identifying the latest research frontiers and hot topics. It provides valuable references for related research and highlights the importance of interdisciplinary collaboration as research topics diversify.
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 →BMJ open respiratory research
Occupational exposure to toxic particles and risk of pulmonary sarcoidosis: a systematic review and meta-analysis
INTRODUCTION: The onset of sarcoidosis is likely the result of a complex genetic-environment-immunological interaction. This systematic review and meta-analysis aimed to identify occupational toxic particles associated with an increased risk of developing pulmonary sarcoidosis. METHODS: Publications in English, published from January 2000 to January 2025, were searched in PubMed, Scopus and JSTOR. The risk of bias was assessed for all included studies. Sensitivity analyses stratified by study quality were conducted to evaluate the robustness of the findings and potential bias. To assess publication bias, a funnel plot was used when more than six studies were included in the analysis. RESULTS: Five categories of toxic particles were identified to be associated with increased risk of the onset of sarcoidosis: chemicals, inorganic dusts, metals, mixed dusts and fumes and organic dusts. The quantitative analysis includes data from 13 studies. The results suggested that occupational silica, pesticides, mould/mildew and World Trade Center ((WTC) dust exposures were associated with increased odds of pulmonary sarcoidosis. Sensitivity analysis confirmed the robustness of the association for WTC dust and mould, whereas the risk associated with silica appeared attenuated in high-quality studies. However, gold exposure was identified as a protective factor. CONCLUSION: Pulmonary sarcoidosis is associated with occupational silica, pesticides, WTC dust and mould. Future research should prioritise gene-environment interactions and granuloma mineralogy to refine preventive strategies and disease management.
12 Apr 2026
Read appraisal →PloS one
The effectiveness of dry needling at myofascial trigger points for knee disorders: A quantitative synthesis of randomized controlled trials
PURPOSE: Dry needling (DN) targeting myofascial trigger points (MTrPs) has been proposed as a treatment for knee disorders, including knee osteoarthritis (KOA) and patellofemoral pain syndrome (PFPS). This meta-analysis evaluated the effectiveness of DN in improving pain and function in patients with knee disorders. METHODS: This meta-analysis was conducted in accordance with PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD420261294603). Systematic searches were performed in PubMed, Embase, Web of Science, Cochrane CENTRAL, CNKI, Wanfang, and VIP databases from inception to December 2025 for randomized controlled trials (RCTs) comparing DN targeting MTrPs with sham DN, no intervention, or other active treatments for knee disorders. Primary outcomes were pain intensity measured by the Visual Analog Scale (VAS) and Numeric Pain Rating Scale (NPRS). Secondary outcomes included functional status assessed by the WOMAC functional subscale and the Kujala Patellofemoral Score. Weighted mean differences (WMDs) were calculated using random-effects models. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and certainty of evidence was evaluated using the GRADE framework. RESULTS: Twenty RCTs (n = 1,234; mean age range: 22-69 years) met the inclusion criteria. Compared with controls, DN significantly reduced knee pain across all pain measures: NPRS (WMD = -1.00, 95% CI: -1.25 to -0.76; I² = 0.0%), VAS (WMD = -1.19, 95% CI: -1.73 to -0.66; I² = 80.4%), and WOMAC Pain subscale (WMD = -1.76, 95% CI: -2.57 to -0.95; I² = 67.6%), with an overall pooled pain reduction of WMD = -1.25 (95% CI: -1.58 to -0.92; I² = 74.7%). DN also significantly improved knee function as measured by the WOMAC functional subscale (WMD = -6.59, 95% CI: -8.88 to -4.29; I² = 61.6%) and the Kujala Patellofemoral Score (WMD = 6.39, 95% CI: 4.64 to 8.14; I² = 30.1%). Pre-specified sensitivity analyses using standardized mean differences confirmed the robustness of these findings. The overall risk of bias was moderate, with concerns primarily related to inadequate blinding of participants and outcome assessors. The GRADE certainty of evidence was rated as moderate for all primary outcomes. CONCLUSION: DN targeting MTrPs provides significant short-term pain relief and functional improvement in KOA and PFPS, with pain reductions approaching clinically important thresholds. However, substantial heterogeneity, blinding limitations, and short follow-up necessitate cautious interpretation, and high-quality long-term RCTs are needed.
12 Apr 2026
Read appraisal →Medicine
Influence of alteration of foot progression angle on three-dimensional pelvic kinematics in individuals with knee osteoarthritis during walking: A randomized crossover study
BACKGROUND: Foot progression angle (FPA) modification trials during walking have been used to reduce knee adduction moments in medial compartment knee osteoarthritis. However, few studies have confirmed the impact of FPA modification as a clinical intervention on pelvic segment kinematics. METHODS: Kinematic pelvic data were obtained from 37 participants with medial knee osteoarthritis using a three-dimensional motion capture system under varying FPA walking conditions. A repeated-measures analysis of variance was conducted to assess the influence of each FPA condition on kinematic values. RESULTS: During maximal internal foot rotation gait trials, participants exhibited decreased depression, reduced external rotation, and increased internal rotation of the pelvis compared to the free walking condition (P < .05). In contrast, under the maximal external foot rotation condition, significantly less internal rotation and increased external rotation of the pelvis were observed compared to the free walking condition (P < .05). CONCLUSION: The findings of this study suggest that additional musculoskeletal dysfunctions and clinical implications, including back pain and pelvic instability, should be considered when implementing FPA modification gait in individuals with medial compartment knee osteoarthritis.
11 Apr 2026
Read appraisal →PloS one
Voxel-wise deep learning segmentation of hydroxyapatite and iodine in spectral photon-counting CT: A quantitative phantom study
Accurate non-invasive identification of hydroxyapatite (HA) deposits is important for diagnosing calcific musculoskeletal disease and quantifying vascular calcification, but conventional and dual-energy CT often struggle to distinguish HA from iodinated contrast because of overlapping attenuation, noise, and beam-hardening artifacts. Spectral photon-counting CT (SPCCT) offers improved energy resolution and spatial fidelity, yet most deep-learning approaches in spectral CT focus on continuous density regression or anatomical segmentation rather than direct voxel-wise material labeling. We developed SPFF-UNet, a spectral-preserving 3D segmentation model for direct classification of HA and iodine concentrations from five-bin SPCCT volumes without material-decomposition preprocessing. A cylindrical phantom containing twelve materials was scanned at 0.1 mm isotropic resolution, including five HA concentrations, three iodine concentrations, three soft-tissue equivalents, and water. SPFF-UNet integrates spectral squeeze-excitation, EnergyFiLM, and FourierGate to preserve and exploit multi-energy information throughout the network. The model was trained for thirteen-class voxel-wise segmentation and compared with five established 3D architectures under matched training conditions. SPFF-UNet achieved the best macro-averaged performance on a held-out phantom scan (Dice 0.72 ± 0.01, IoU 0.59 ± 0.01, sensitivity 0.73 ± 0.01, precision 0.71 ± 0.01), outperforming the strongest comparator, ResUNet++ (Dice 0.66 ± 0.02, IoU 0.46 ± 0.02, sensitivity 0.67 ± 0.02, precision 0.61 ± 0.03). Performance gains were concentrated in mid/low-contrast HA and low-concentration iodine, with reduced slice-wise variability and fewer HA-iodine misclassifications. These results suggest that preserving spectral information and applying targeted spectral modulation can improve concentration-aware voxel classification from SPCCT. This phantom-based proof-of-concept provides a basis for future in vivo validation.
11 Apr 2026
Read appraisal →Acta orthopaedica
Effect of an in-consult patient decision aid on decisional quality and involvement for patients with severe hip or knee osteoarthritis: a multicenter, cluster randomized controlled trial
BACKGROUND AND PURPOSE: Shared decision-making (SDM) is important in managing patients with severe hip and knee osteoarthritis, where treatment decisions often depend on patient preferences and values. We aimed to evaluate the effectiveness of an in-consult patient decision aid in improving decision quality and patient involvement compared with usual care. METHODS: In a cluster-randomized controlled trial, surgeons from 2 Danish orthopedic departments were randomized to use in-consult patient decision aids or provide usual care. The primary outcome was decision quality assessed using the Hip/Knee OA Decision Quality Instrument (HK-DQI). Patients who were well informed and received their preferred treatment received an Informed Patient-Centered (IPC) score of 1, indicating good decisional quality; all others scored 0. Secondary outcomes included patient-experienced engagement and involvement in decision-making, assessed using CollaboRATE and the decision-process domain of the Hip/Knee OA Decision Quality Instrument and consultation duration. Relative risks (RR) and mean differences (MD) with 95% confidence intervals (CIs) were estimated using multilevel regression models. RESULTS: 20 surgeons were randomized to either use in-consult patient decision aids (n = 10) or provide usual care (n = 10). Of the 1,038 patients screened for severe hip or knee osteoarthritis, 581 were included in the study. Decision quality was similar between groups, with a score of 43 (36-51) in the intervention group and 44 (37-52) in the usual care group (RR 0.9, CI 0.7-1.2; P = 0.8), likewise, patient-experienced engagement assessed with CollaboRATE (RR 1.1, CI 0.8-1.4; P = 0.6). Consultations were longer in the intervention group, with a mean difference of 3.9 minutes (CI 0.1-7.7; P = 0.04). CONCLUSION: Decision quality and patient-reported engagement were similar between groups, while consultation time was longer with in-consult patient decision aids use. In the absence of prespecified minimal important differences, the clinical relevance of these findings remains uncertain.
10 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 →JMIR formative research
A Gamified Pain Management Intervention for Adults With Chronic Pain in Mainland China: Single-Arm Pre-Post Pilot Study With Machine Learning Predictive Modeling
BACKGROUND: The widespread prevalence of chronic pain (CP) significantly impacts daily functioning worldwide. In mainland China, maintaining engagement in biopsychosocial interventions remains challenging. Gamification, designed based on self-determination theory, can enhance motivation, while machine learning (ML) algorithms can assist clinicians in dynamically optimizing pain management. OBJECTIVE: This study aimed to (1) evaluate the preliminary effectiveness of a gamified pain management (GPM) program on CP and psychological outcomes and (2) identify key factors of significant pain improvements through the application of ML to guide intervention adjustments. METHODS: A single-arm, pre-post study was conducted with 16 participants with CP in mainland China, recruited via social media using convenience sampling. Participants engaged in a 10-week web-based GPM intervention consisting of education, physical activities, and gamified elements, including points, avatars, and feedback. Primary outcomes were pain intensity and interference measured by the Brief Pain Inventory. Secondary outcomes included anxiety, depression, and quality of life. Analysis included paired t tests, and ML models were trained to predict clinically meaningful pain reductions. Shapley additive explanations, least absolute shrinkage and selection operator regression, association rule mining, and Kaplan-Meier survival analysis were used to identify key predictors and optimal sessions and intervention durations across subgroups. RESULTS: A total of 16 participants were engaged, with a mean age of 27.63 (SD 9.584) years. Results from paired t tests reported significant improvements in pain intensity (decreased by 27.3%, 95% CI 1.061 to 3.064; P=.001), pain interference (decreased by 27.3%, 95% CI 8.159-17.216; P<.001), and psychological distress, including anxiety (t15=3.538, 95% CI 0.969 to 3.906; P=.003) and depression (t15=4.559, 95% CI 2.230 to 6.145; P<.001). The gradient boosting model demonstrated the highest predictive accuracy (area under the curve=0.89 and accuracy=0.82). Least absolute shrinkage and selection operator regression identified session 3 (β=-0.45, 95% CI -0.68 to -0.22; P<.001) and session 5 (β=-0.32, 95% CI -0.59 to -0.05; P=.02) as most predictive of clinical success, while association rule mining revealed effective session combinations for different patient subgroups. Time-to-event analyses indicated that individuals with low back pain and higher baseline severity required longer intervention durations for improvement (5 wk; P=.03). CONCLUSIONS: This pilot study presents an innovative method that combines ML with dynamic engagement data from a GPM program during interventions, rather than relying on static baseline data in prior studies. The results show preliminary efficacy and identify specific optimal session combinations and personalized treatment durations for different pain subgroups. These exploratory findings contribute to the field by providing a data-driven method for adaptive, personalized digital health interventions that move beyond one-size-fits-all strategies, potentially enabling clinicians to modify content and dosage to improve engagement and outcomes if validated in larger sample trials.
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 →Lupus science & medicine
Unsupervised clustering of clinical and laboratory features of systemic lupus erythematosus: insights from a multicentre cohort
OBJECTIVE: This study explored the relationship between clinical phenotypes and immuno-molecular features of systemic lupus erythematosus (SLE) using unsupervised machine learning and multi-omics integration. METHODS: A multicentre cohort of 1065 SLE patients from five teaching hospitals was studied. Unsupervised clustering was performed using integrated clinical and laboratory data to identify distinct phenotypic clusters. Multi-omics profiling, including proteomics and transcriptomics, was conducted for each cluster, comparing with healthy controls. In addition, 899 patients were prospectively followed for over 1 year to assess therapeutic responses and remission outcomes. RESULTS: Unsupervised clustering identified five distinct clusters of SLE based on clinical phenotypes and immunological signatures, and an intrinsic association was found between each cluster and immune-inflammatory features. Cluster 1 (renal; 14.27%) had predominant renal involvement (87.5%) and high disease activity. Cluster 2 (mucocutaneous; 39.53%) exhibited mainly cutaneous manifestations (72.45%) with mild visceral involvement and the highest rates of achieving low disease activity state (46.42%). Cluster 3 (neuropsychiatric; 14.74%) had a high frequency of neuropsychiatric manifestations (96.18%) and anti-U1 ribonucleoprotein antibodies positivity (42.04%). Cluster 4 (haematologic; 22.63%) was characterised by haematologic involvement, predominantly cytopenia (95.85%), with frequent antiphospholipid antibody positivity and direct Coombs positivity (87.55%). Cluster 5 (cardiopulmonary; 8.83%) exhibited prominent cardiopulmonary involvement (97.87%) and serositis, with enrichment of inflammatory CD161+ regulatory T cells. Transcriptomic and proteomic analyses confirmed distinct molecular signatures and cluster-specific enrichment of biological pathways. Key molecule apolipoprotein A4 was validated using enzyme-linked immunosorbent assay. Regarding therapeutic outcomes at 1 year follow-up, Cluster 2 had the highest proportions achieving lupus low disease activity state (46.42%) and tapering glucocorticoids. Cyclophosphamide use was associated with greater clinical improvement (r=0.284; p=0.023) in Cluster 3, while in Cluster 5, rituximab use was associated with favourable responses (r=0.286; p=0.019). CONCLUSIONS: We identified five SLE clusters with distinct clinical, immunological features and treatment outcomes, demonstrating an intrinsic link between clinical involvement and immune-inflammatory alterations.
9 Apr 2026
Read appraisal →European journal of pediatrics
Predicting coronary artery abnormalities in Kawasaki disease: Model development and validation
Routine echocardiography at one month after diagnosis is the current standard for screening coronary artery abnormalities (CAA), a major complication of Kawasaki disease. The study aimed to develop and validate models to predict CAA and assess whether routine echocardiography could be safely reduced in low-risk patients. Two prospective multicenter Japanese registries were utilized: PEACOCK (development/internal validation) and Post-RAISE (external validation). Variables obtained within one week of diagnosis were used to predict CAA at one month after diagnosis, defined as a maximum coronary artery Z score (Zmax) ≥ 2. The models included simple models using the previous maximum Z score only, logistic regression models, and machine learning models (LightGBM and XGBoost). Discrimination, calibration, and clinical utility were assessed. Among 4,973 PEACOCK and 2,438 Post-RAISE patients, the CAA incidence was 5.5% and 6.8%, respectively. Twenty-two models were developed using 29 variables. For external validation, a simple model using the maximum Z score at week 1 produced an area under the curve (AUC) of 0.79; adding other variables or using more complex models did not increase the AUC by more than 0.02. The models failed to efficiently reduce the number of echocardiographic examinations while minimizing missed cased of CAA.Conclusion: Until superior predictors are identified, routine echocardiography at one month after diagnosis should remain the standard practice.
9 Apr 2026
Read appraisal →BMJ open
Identification of immunomodulators associated with atrial fibrillation reporting to better understand AF immunologic mechanisms: a Vigibase retrospective disproportionality analysis and a literature review
OBJECTIVES: Growing evidence exists about the pivotal role of immune mechanisms in the physiopathology of atrial fibrillation (AF). Drugs that modulate the immune system (immunomodulators) may contribute to the development of AF. We aimed to identify immunomodulators that are associated with AF to better define their safety profile, and elucidating their mechanisms of action could yield novel insights into AF's immune physiopathology. DESIGN: A descriptive and disproportionality analysis of claims data. SETTINGS: World pharmacovigilance database VigiBase until 1 March 2025. PRIMARY AND SECONDARY OUCTOMES: First, we ascertained the association of immunomodulators with AF over-reporting with a disproportionality analysis evaluating the multivariable-adjusted reporting odds ratio (aROR) for AF reporting performed for 141 immunomodulators in VigiBase. Then, a literature review was done to explore the underlying mechanisms of AF through immunomodulator mechanisms. RESULTS: A total of 6 148 556 reports encompassing at least one of the 141 immunomodulators were identified in Vigibase. Our primary analysis revealed 20 immunomodulators associated with AF over-reporting. The three immunomodulators with the greatest signal were: recombinant interleukin-11 with an aROR=20.91 (99.96% CI 12.08 to 36.17), efgartigimod alfa with an aROR=6.75 (99.96% CI 3.96 to 11.52) and recombinant interleukin-2 with an aROR=6.15 (99.96% CI 3.62 to 10.45). A derivative literature review posited a hypothetical immune 'vicious circle' promoting AF, involving T helper cells, macrophages and natural killer cells which could lead to electrophysiologic and histologic atrial remodelling. CONCLUSIONS: Twenty Food and Drug Administration (FDA)-labelled immunomodulators are associated with AF overreporting in Vigibase with a substantial signal on recombinant IL-11. These data contribute substantively to the prevailing understanding of the safety profile of these immunomodulators. Moreover, these findings support a multidirectional interaction between the immune system and AF development and might lead to considering future therapeutic targets. TRIAL REGISTRATION NUMBER: NCT06095791.
9 Apr 2026
Read appraisal →The bone & joint journal
Robotic-assisted surgery and functional alignment in total knee arthroplasty: the RASKAL registry-nested 2 × 2 factorial randomized trial
AIMS: Robotic-assisted surgery and functional alignment are increasingly being adopted in total knee arthroplasty (TKA). This study assessed the individual and combined effectiveness of robotic-assisted surgery and functional alignment in improving outcomes in TKA, compared with computer-assisted surgery and mechanical alignment, respectively. METHODS: A registry-nested, multicentre, blinded, 2 × 2 factorial, randomized trial was performed with 303 TKA patients randomized to robotic-assisted or computer-assisted surgery, and functional or mechanical alignment. The primary outcome was the between-group differences in postoperative change over two years in the mean Knee Injury and Osteoarthritis Outcome Score (KOOS-12). Secondary outcomes included knee-specific and general patient-reported outcome measures (PROMs), operative and functional outcomes, and adverse events. Primary modified intention-to-treat and secondary per-protocol analyses were performed. RESULTS: There were no differences comparing robotic-assisted with computer-assisted surgery in KOOS-12 at three months, six months, one year, and two years (mean two-year difference -2.8; 95% CI -6.4 to 0.9; p = 0.137), and no differences comparing functional with mechanical alignment at three months, six months, one year, and two years (mean two-year difference 0.3 (95% CI -3.4 to 4.0); p = 0.867). No differences were found in Oxford Knee Score, Forgotten Joint Score, EuroQol five-dimension five-level visual analogue scale, patient satisfaction, joint-related improvement, and pain comparing technology or alignment groups at three months, six months, one year, and two years. Robotic-assisted surgery had a shorter mean operating time by 11.5 minutes (95% CI 7.3 to 15.9; p < 0.001) and better mean posterior cruciate ligament macroscopic soft-tissue injury score (mean difference 0.7 (95% CI 0.3 to 1.1); p = 0.001) compared with computer-assisted surgery. Mechanical alignment had a higher soft-tissue release rate compared with functional alignment (44.8% vs 8.1%; OR 9.2 (95% CI 4.6 to 18.3); p < 0.001). In most cases, surgeons preferred the use of robotics and functional alignment. CONCLUSION: Robotic-assisted surgery and functional alignment were not superior to computer-assisted surgery and mechanical alignment, respectively, in improving clinical and functional outcomes up to two years post-TKA.
8 Apr 2026
Read appraisal →The Cochrane database of systematic reviews
Antibiotic treatment for low back pain, radicular pain, or both.
RATIONALE: Low back pain is the leading cause of disability worldwide. Research has associated Modic changes (signal changes in the vertebral endplate on magnetic resonance imaging (MRI)) with low back pain. Some hypothesise that Modic type 1 changes (oedema) may have an infective cause, and that antibiotics could serve as targeted treatment. OBJECTIVES: To assess the benefits and harms of antibiotic therapy, compared with placebo or another treatment, in people with low back pain, radicular pain, or both. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registries up to 26 August 2025, with no restrictions related to language or date of publication. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) that assessed antibiotics versus placebo (primary comparison) or other treatments. We assessed the evidence separately for four populations of adults with low back pain, radicular pain, or both: those with 1) Modic type 1 changes and evidence of disc herniation, 2) other Modic changes and evidence of disc herniation, 3) any Modic changes but no evidence of disc herniation, and 4) evidence of disc herniation without any Modic changes. OUTCOMES: Critical outcomes were pain intensity and disability or function up to 12 to 14 weeks, and the number of participants with any adverse events and serious adverse events at the end of the trial period. RISK OF BIAS: Two review authors independently evaluated the risk of bias using the Cochrane risk of bias tool RoB 1. SYNTHESIS METHODS: Two review authors independently screened studies and extracted data. We synthesised results for each outcome using random-effects meta-analysis. Where this was not possible due to the nature of the data, we reported the results descriptively. We used GRADE to assess the certainty of evidence. The primary comparison was antibiotics versus placebo in people with low back pain, radicular pain, or both, and Modic type 1 changes with evidence of disc herniation (population 1) up to 12 to 14 weeks. INCLUDED STUDIES: We included three trials, conducted in Denmark, Belgium, and Norway, with a total of 402 participants (mean ages ranged from 44.7 years to 51.0 years). Two trials recruited people with chronic (> 6 months) moderate-to-severe low back pain (with or without radicular pain), Modic changes, and disc herniation. One trial included people with Modic type 1 changes only (population 1) and compared oral amoxicillin-clavulanate 500 mg/125 mg to placebo (for both treatments, 1 or 2 tablets 3 times daily for 100 days). The second trial included people with either Modic type 1 changes (population 1) or Modic type 2 changes (population 2) and compared oral amoxicillin 750 mg to placebo (for both treatments, 3 times daily for 100 days). Follow-up was 12 months in both trials. The third trial recruited people with lumbar radicular pain (with or without low back pain) and disc herniation. Modic changes was not an inclusion criterion (population 4). This trial evaluated minocycline 100 mg versus amitriptyline 25 mg versus placebo and followed participants for 14 days (treatment duration). There were no trials with population 3. SYNTHESIS OF RESULTS: All three trials were at low risk of selection, performance, and detection bias. We rated one trial at high risk of attrition bias and unclear risk of reporting and other bias. The overall certainty of evidence is low to very low, primarily due to imprecision and indirectness. In people with low back pain, Modic type 1 changes, and disc herniation, the antibiotic oral amoxicillin (with or without clavulanate) may improve pain slightly and may result in a small to moderate improvement in disability at 12 to 14 weeks compared with placebo (low-certainty evidence, downgraded for imprecision and indirectness). At this time point, the mean back pain score was 50.6/100 (where a lower score indicates less pain) in the amoxicillin group versus 59/100 in the placebo group (mean difference (MD) -8.42 points, 95% CI -16.18 to -0.67; I² = 35%; 2 trials, 255 participants), and the mean disability score was 45.2/100 (where a lower score indicates less disability) in the amoxicillin group versus 55.7/100 in the placebo group (MD -10.52 points, 95% CI -15.94 to -5.09; I² = 0%; 2 trials, 255 participants). We are unsure if amoxicillin (with or without clavulanate) results in more people reporting adverse events (very low-certainty evidence, downgraded for imprecision, inconsistency, and indirectness). Adverse events were reported in 76 of every 100 people taking amoxicillin compared with 49 of every 100 people taking placebo (risk ratio (RR) 1.79, 95% CI 0.54 to 5.94; I² = 96%; 2 trials, 262 participants). We are unsure if amoxicillin (with or without clavulanate) results in more people reporting serious adverse events (very low-certainty evidence, downgraded for imprecision and indirectness). Serious adverse events were reported in three of every 100 people taking amoxicillin (with or without clavulanate) compared with two of every 100 people taking placebo (RR 1.43, 95% CI 0.11 to 18.35; I² = 45%; 2 trials, 262 participants). We are unsure of the effects of amoxicillin compared to placebo in people with low back pain, Modic type 2 change, and disc herniation. Similarly, we are unsure of the effects of minocycline compared to placebo or amitriptyline in people with low back pain, disc herniation, and no Modic changes. AUTHORS' CONCLUSIONS: In people with low back pain, Modic type 1 changes, and evidence of disc herniation, the antibiotic amoxicillin (with or without clavulanate) may provide slight to small benefits in reducing back pain and small to moderate benefits in improving disability compared to placebo at 12 to 14 weeks. The evidence on the risk of adverse events, including serious adverse events, with amoxicillin (with or without clavulanate) is very uncertain. Further research is likely to change our confidence in the estimates. FUNDING: This review had no dedicated funding. REGISTRATION: Protocol (2021): DOI 10.1002/14651858.CD014221.
8 Apr 2026
Read appraisal →JMIR research protocols
Targeted Real-Time Assessment of Chronic Pain (TRAC-Pain) in Youth: Protocol for a Digital Biosignature Development Through a Prospective Observational Cohort Study
BACKGROUND: Approximately 1 in 5 children and adolescents live with chronic pain, with musculoskeletal (MSK) pain being one of the most prevalent subtypes. Unfortunately, some studies show that less than half of youth (<18 years) experience improvements with existing evidence-based treatments. Self-report measures-the current gold standard for monitoring the pain experience-are limited in their use as a single point-of-care assessment and their vulnerability to recall bias. The ubiquitous adoption of wearable technology presents a promising solution for improved monitoring of the pain experience via real-time tracking through a multisystemic lens. OBJECTIVE: The purpose of this study is (1) to develop a digital biosignature of the pain experience in youth with chronic MSK pain and (2) to assess the feasibility, acceptability, and appropriateness of the captured data for future applications. METHODS: All aspects of this study were designed in partnership with people with lived experience and patient advocacy partners. This is a longitudinal observational cohort study, with all study activities taking place remotely over a 12-week period. Up to 500 youth (between 14 and 24 years old) with chronic MSK pain will be enrolled through a multipronged recruitment strategy to ensure a representative sample. The participants will wear an Apple Watch throughout the study to continuously monitor physiological, sleep, and physical activity metrics. In addition, participants will complete brief "daily check-in" surveys that include gold-standard measures of the pain experience (eg, pain interference, mood, fatigue) and the option to report a "pain flare" (ie, a temporary but noticeable worsening of the usual pain symptoms). Participants will also complete a modified online Trier Social Stress Test and a 30-second sit-to-stand task to capture individual responses to standardized challenges. Traditional machine learning and deep representation learning methods will be used to develop a digital biosignature of the pain experience. The accuracy of the biosignature will be assessed through measures of model performance as compared to gold-standard self-reports. RESULTS: This study was funded in September 2024, with data collection beginning in March 2025. As of December 15, 2025, 190 participants are enrolled, with data collection and analysis ongoing. CONCLUSIONS: This is the first study to leverage wearable health technology for real-time monitoring of the pain experience in youth with chronic MSK pain. The resulting digital end points are expected to heighten the rigor of clinical trials and provide opportunities for individually tailored interventions. The second phase of this study will investigate the implementation of "wellness alerts" triggered by abnormal smartwatch readings. Alerts would empower users toward preemptive self-management strategies, thereby enhancing self-efficacy in those living with chronic MSK pain. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/84781.
8 Apr 2026
Read appraisal →Rheumatology international
The effect of structured hand massage on hand function and grip strength in rheumatoid arthritis patients: a randomized controlled pilot study
INTRODUCTION: This study aimed to assess the impact of a 10-session hand massage protocol on hand function, grip strength, pinch strength, pain threshold, and tactile sensory threshold in patients with early-stage, seropositive rheumatoid arthritis (RA) without radiographic damage or hand deformity. METHODS: This study was a randomized controlled clinical trial. Thirty female RA patients with a diagnosis time of less than two years, seropositive, with low disease activity/remission, and without active arthritis in their hands were included in the study. Participants were randomized 1:1 to intervention and control groups. The intervention group underwent 10 hand massage sessions over a two-week period, in addition to regular medical care. The control group received only regular medical care. All assessments were performed at baseline (T1) and at week 2 (T2). Outcome measures included hand grip strength, pinch strength, pain threshold (dolorimetry), tactile sensory threshold (Semmes-Weinstein monofilament test), Duruöz Hand Index (DHI), and patient global assessment (PGA). RESULTS: A total of 30 RA patients were included in the study (intervention group, n = 15; control group, n = 15). At baseline, no significant differences were observed between the groups in demographic, laboratory, or clinical characteristics (p > 0.05). In the intervention group, significant improvements in hand grip strength and pinch force were observed at T2 compared with baseline (p = 0.008 and p = 0.023, respectively). Median hand grip strength increased from 55 (40-75) to 65 (45-80) kg, and median pinch strength increased from 15 (6-18) to 16 (11-21) kg. No significant alterations were noted in these parameters within the control group (p > 0.05). In the control group, median hand grip strength was 45 (25-80) kg at baseline and 45 (20-80) kg at week 2, while median pinch strength was 14 (6-18) kg at baseline and 14 (5-19) kg at week 2. In the intervention group, significant reductions in DHI and PGA scores were recorded at the end of therapy (p = 0.005 and p = 0.001, respectively). No significant differences were noted in DHI and PGA levels in the control group (p > 0.05). Moreover, median PGA scores were significantly lower in the intervention group than in the control group at T2 (4 [2-5] vs. 5 [3-6]; p < 0.001). No significant changes were found in dolorimeter and touch sensory thresholds in either group (p > 0.05). CONCLUSION: Hand massage interventions for patients with RA enhance grip strength, hand function, and overall patient evaluations. No effect on pain or tactile thresholds was observed. Further studies with larger sample sizes and longer follow-up periods are required to corroborate these findings.
6 Apr 2026
Read appraisal →PloS one
Patterns and predictors of variability in patient-generated daily pain severity collected via a mobile health smartphone app.
Digital-health technologies support the collection of patient-generated health data that is frequent, longitudinal, and collected in participant's own environments. Such high-frequency data could detect patterns of variation in disease and associated symptoms, but characterizing, interpreting, and understanding the reasons for this variability remain open questions. Here, we examine 2070 people living with chronic pain to quantify daily variability in pain severity across seven-day periods and identify factors associated with that variability. Data were collected via a smartphone application from a population-based mobile-health study, Cloudy with a Chance of Pain. Summary statistics and distributions of pain changes on consecutive days were calculated within 13,052 complete weeks of data, which had been assigned to one of four clusters via a previously published k-mediods clustering algorithm: no/low pain, mild pain, moderate pain, and severe pain. Cumulative-probit models were used to identify associations between changes in pain severity and changes in exposure data. Across the four clusters, the no/low-pain cluster had the highest proportion of weeks with no within-week changes (59%) in pain severity compared to the other clusters (48-53%). When pain did change, it changed one unit (out of five) about 20% of the time, but larger changes of two to four units also occurred. Changes in pain severity were associated most strongly with changes in pain interference (i.e., how pain impacts daily activities) and were also associated with changes in fatigue, morning stiffness, mood, and participant well-being. Thus, this study showed that data collected frequently through digital-health technologies can be used to explore variability in symptoms and their associations with other variables. That pain severity was associated with changes in modifiable variables (e.g., fatigue, mood) suggests opportunities for different treatment and self-management regimes for different patient subtypes within the four clusters.
5 Apr 2026
Read appraisal →IEEE transactions on medical imaging
Self-Paced Learning for Images of Antinuclear Antibodies
Antinuclear antibody (ANA) testing is a critical method for diagnosing autoimmune disorders such as Lupus, Sjögren's syndrome, and scleroderma. Despite its importance, manual ANA detection is slow, labor-intensive, and demands years of training. ANA detection is complicated by over 100 coexisting antibody types, resulting in vast fluorescent pattern combinations. Although machine learning and deep learning have enabled automation, ANA detection in real-world clinical settings presents unique challenges as it involves multi-instance, multi-label (MIML) learning. In this paper, a novel framework for ANA detection is proposed that handles the complexities of MIML tasks using unaltered microscope images without manual preprocessing. Inspired by human labeling logic, it identifies consistent ANA sub-regions and assigns aggregated labels accordingly. These steps are implemented using three task-specific components: an instance sampler, a probabilistic pseudo-label dispatcher, and self-paced weight learning rate coefficients. The instance sampler suppresses low-confidence instances by modeling pattern confidence, while the dispatcher adaptively assigns labels based on instance distinguishability. Self-paced learning adjusts training according to empirical label observations. Our framework overcomes limitations of traditional MIML methods and supports end-to-end optimization. Extensive experiments on one ANA dataset and three public medical MIML benchmarks demonstrate the superiority of our framework. On the ANA dataset, our model achieves up to +7.0% F1-Macro and +12.6% mAP gains over the best prior method, setting new state-of-the-art results. It also ranks top-2 across all key metrics on public datasets, reducing Hamming loss and one-error by up to 18.2% and 26.9%, respectively. The source code can be accessed at https://github.com/fletcherjiang/ANA-SelfPacedLearning.
4 Apr 2026
Read appraisal →Ann Anat
Epiphyseal interfaces.
This work explores interconnected articular and growth plate osteochondral interfaces, via complementary anatomical, biomechanical and structural analyses that combine benchtop micro-computed tomography (microCT) and high-resolution synchrotron CT (sCT) imaging approaches. We show that bony sclerosis, well-documented in late-stage OA in humans, and the osteoarthritic STR/Ort mouse model, is preceded by the amplified regionalised expansion of articular calcified cartilage (ACC) where vulnerability load-induced failure is greatest. We further observed marked alterations in the number and size of resident osteocyte lacunae in pre-OA and OA regions in comparison to controls, which age healthily, underscoring the value of CT-based approaches for elucidating early OA-related changes. Notably, our findings imply that excessive ACC formation is an early consequence of disrupted endochondral ossification that precedes and potentially drives OA sclerosis, osteophytosis and indeed, articular cartilage lesions. By applying digital volume correlation (DVC) to sCT images of loaded murine knee joints under physiological conditions, we demonstrate that the joints from a healthy parental control strain of CBA mice efficiently dissipate compressive strain, whereas OA-prone STR/Ort exhibit high strain foci in the epiphyseal compartment prior to cartilage degeneration; suggesting that early strain accumulation may therefore promote early joint vulnerability and subsequently prime degenerative progression with age. Finally, we examined how the cartilaginous growth plate (GP), responsible for all longitudinal bone growth, contributes to mechanical epiphyseal stability for articulation. Analysis of mineralised trans-physeal GP structures (bridges), revealed their dynamic and sexually dimorphic character as well as their regulation by mechanical loading and osteotropic agents. DVC analyses of sCT-imaged murine knee joints subjected to identical physiologically oriented load, identified that regionally heterogeneous load-induced strain patterns in the GP are spatially synchronised to bridge location; a relationship substantiated by finite element simulation. Together, these findings establish intra-physeal GP bridges as regulatable and mechanically sensitive structures that coordinate the transfer of local GP strains, while enhancing epiphyseal stability by distributing compressive and shear strains to thereby permit cessation of longitudinal growth.
1 Apr 2026
Read appraisal →Ophthalmology
Special AAO Report: Recommendations on Screening for Hydroxychloroquine Retinopathy (2025 Revision)
BACKGROUND: The American Academy of Ophthalmology recommendations on screening for hydroxychloroquine (HCQ) retinopathy are now a decade old. This revision provides an update based on current knowledge. Major points and changes are as follows. NATURE OF TOXICITY: The retina typically remains clinically normal for many years on HCQ, but there is an unpredictable point at which signs of toxicity may develop. PATTERN OF TOXICITY: Most eyes of patients of European heritage have a parafoveal pattern of toxicity, whereas eyes of East Asian patients tend to present with pericentral toxicity, but there are many exceptions, and screening examinations should look for both patterns. DOSAGE: The recommended daily dosage remains unchanged at ≤5.0 mg/day/kg real weight. Keep under 400 mg/day for severely obese patients. RISK FACTORS: Beyond dose and duration, concurrent renal disease and tamoxifen use increase risk, as does initiation of HCQ therapy at an older age. CLINICAL TESTS: The primary screening tool should be OCT, along with wide-pattern fundus autofluorescence (FAF). Visual field (VF) and multifocal electroretinography (mfERG) are secondary confirmatory tests. Newer VF algorithms such as 24-2C can screen parafoveal and pericentral regions simultaneously. SCREENING: A baseline screening examination, including fundus, OCT, and FAF, is advised soon after HCQ is begun, not only to rule out preexisting conditions but also for comparison with later results. Annual screening with OCT and FAF is recommended while using HCQ, but may be deferred during the first 5 years if there are no significant risk factors. PROGRESSION: Mild retinopathy is unlikely to progress after discontinuation of HCQ, but severe retinopathy may continue to worsen for many years. IMPLICATIONS OF EARLY SIGNS OF TOXICITY: With earlier recognition comes greater need to communicate with patients and their medical providers regarding options to stop HCQ or continue with cautious monitoring. NEW TECHNOLOGY: There have been experimental advances in imaging and artificial intelligence analysis for HCQ screening, but none have been validated for general use or are widely available at this time. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
1 Apr 2026
Read appraisal →Surv Ophthalmol
Relentless placoid chorioretinitis
Relentless placoid chorioretinitis (RPC) is a rare, vision-threatening posterior uveitis that predominantly affects young adults. The hallmark clinical findings are numerous scattered placoid chorioretinal lesions involving the midperipheral and far peripheral fundus as well as the posterior pole and a persistent or recurrent course resulting in lesions at different chronological stages, with fresh creamy placoid lesions and healing pigmented lesions being present at the same time. Although RPC is frequently described as a disease that is intermediate between acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis, it more closely resembles APMPPE. It is important to identify those patients with RPC who present with an APMPPE phenotype so that appropriate immunomodulatory therapy is instituted without delay, as most cases of RPC are refractory to corticosteroid monotherapy. Examination findings may help differentiate RPC and APMPPE. Multimodal imaging, including ultra-widefield imaging, and selective investigations aid in distinguishing RPC from other placoid diseases and types of posterior uveitis.
1 Jan 2026
Read appraisal →Artif Cells Nanomed Biotechnol
Unveiling the ageing-related genes in diagnosing osteoarthritis with metabolic syndrome by integrated bioinformatics analysis and machine learning
Ageing significantly contributes to osteoarthritis (OA) and metabolic syndrome (MetS) pathogenesis, yet the underlying mechanisms remain unknown. This study aimed to identify ageing-related biomarkers in OA patients with MetS. OA and MetS datasets and ageing-related genes (ARGs) were retrieved from public databases. The limma package was used to identify differentially expressed genes (DEGs), and weighted gene coexpression network analysis (WGCNA) screened gene modules, and machine learning algorithms, such as random forest (RF), support vector machine (SVM), generalised linear model (GLM), and extreme gradient boosting (XGB), were employed. The nomogram and receiver operating characteristic (ROC) curve assess the diagnostic value, and CIBERSORT analysed immune cell infiltration. We identified 20 intersecting genes among DEGs of OA, key module genes of MetS, and ARGs. By comparing the accuracy of the four machine learning models for disease prediction, the SVM model, which includes CEBPB, PTEN, ARPC1B, PIK3R1, and CDC42, was selected. These hub ARGs not only demonstrated strong diagnostic values based on nomogram data but also exhibited a significant correlation with immune cell infiltration. Building on these findings, we have identified five hub ARGs that are associated with immune cell infiltration and have constructed a nomogram aimed at early diagnosing OA patients with MetS.
1 Dec 2025
Read appraisal →Int J Surg
Multi-omic profiling reveals age-specific blood biomarkers and aging-driven B cell remodeling in osteoarthritis
BACKGROUND: Osteoarthritis (OA) pathogenesis involves age-related immune dysregulation, yet non-invasive diagnostic tools and mechanistic insights remain limited. METHODS: We integrated transcriptomic profiling of four OA-affected joint tissues with machine learning to identify potential peripheral blood biomarkers. Weighted gene co-expression network analysis was employed to explore gene modules and pathways associated with OA. Single-cell RNA sequencing was performed on 217 983 joint cells to delineate B cell differentiation trajectories. Flow cytometry was used to validate age-associated B cell imbalances in peripheral blood. RESULTS: We identified five peripheral blood biomarkers: MAPK1, MAP3K8, ING1, LDLR, and NUP153 in distinguishing OA patients from controls (the area under the curve [AUC] = 0.966). Importantly, these markers exhibited age-specific expression profiles; ING1, NUP153, and MAP3K8 were elevated, while MAPK1 was reduced in elderly compared to younger OA patients. A refined predictive model based on these age-specific markers demonstrated superior performance specifically for elderly Knee OA (KOA, AUC: 0.8 vs. 0.7 for younger KOA). These biomarkers correlated with immune cell infiltration and inflammatory cytokines. In osteoarthritic joint tissues, B cells predominantly originated from subchondral bone and synovium. Single-cell analysis identified age-specific B cell differentiation patterns, with elderly KOA patients enriched in an activated B cell cluster (C1). Furthermore, B cells from elderly KOA patients showed altered energy metabolism and increased proportions in peripheral blood, and functionally promoted chondrocyte damage. CONCLUSION: Our findings establish a novel blood-based diagnostic framework for OA and uncover aging-driven B cell remodeling as a key contributor to elderly OA pathogenesis. These findings offer non-invasive diagnostics and immunomodulatory targets for age-specific OA therapy.
1 Nov 2025
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