Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 220 appraisals
European journal of radiology
A CT-based deep learning model to differentiate between benign and malignant adrenal lesions
OBJECTIVE: To develop a deep learning model to differentiate benign from malignant adrenal lesions. MATERIALS AND METHODS: A total of 380 patients with 385 pathologically confirmed adrenal lesions (101 malignant, 284 benign) were retrospectively included. Adrenal lesions were manually segmented on CT images and analyzed in a deep learning pipeline aimed at differentiating benign from malignant lesions. Four predictive models were developed that incorporated combinations of radiological data (tumor size, and spontaneous attenuation) and non-radiological data (i.e., medical history and laboratory results). Data of 267 patients were used as a training set and those of 113 patients for the test set. The diagnostic capabilities of the four models were estimated using sensitivity, specificity, accuracy, and areas under the receiver operating characteristic curves (AUC) using histopathological findings as the gold standard. The reproducibility of manual segmentation was estimated using the Dice similarity coefficient after blinded resegmentation of 40 adrenal lesions by an independent radiologist. RESULTS: Segmentation reproducibility achieved a mean Dice similarity coefficient of 0.92 ± 0.03 (range: 0.72-0.97). The most accurate model, which combined clinical, biological, and radiological data, achieved 84.2% accuracy (95% confidence interval: 79.9, 88.6) and an AUC of 0.93 (95% confidence interval: 89.9, 97.9) in the test set for diagnosis of malignant adrenal lesion. CONCLUSION: A deep learning model integrating preoperative clinical, biological, and radiological features demonstrates high capabilities in differentiating benign from malignant adrenal lesions on initial CT examination.
3 Aug 2026
Read appraisal →Journal of chemical information and modeling
A Unified Molecular Graph and Protein Language Model Framework for Predicting Human Drug-Hormone Receptor Interactions with Structure-Aware Validation
Hormones regulate many essential biological processes by interacting with specific receptors that control gene expression, metabolism, growth, and immune function. Because numerous therapeutic compounds can influence or disrupt hormone signaling pathways, understanding drug-hormone receptor interactions (DHRI) is crucial for ensuring both therapeutic efficacy and endocrine safety. However, computational approaches for predicting DHRI remain limited, and most existing models do not explicitly incorporate hormone receptor-specific information. In this study, we propose a receptor-aware deep learning framework for DHRI prediction that integrates structural drug features with contextually embedded hormone receptor information. Drug molecules are represented using a hybrid encoding strategy that combines Morgan fingerprints and graph transformer-based molecular features to capture both global chemical properties and local structural information, while hormone receptor sequences are encoded using the pretrained ESM2 protein language model to obtain biologically meaningful sequence representations. The fused drug-hormone receptor features are then processed through a multilayer neural network to predict interaction probabilities. Model performance was evaluated using three splitting strategies, including random split, cold-drug split, and scaffold-based split, to assess both predictive accuracy and generalization ability. Under the random split setting, the model achieved an accuracy of 0.93, sensitivity of 0.94, specificity and precision of 0.92, F1-score of 0.93, and MCC of 0.86 on an independent data set, while also maintaining comparable performance under the more stringent cold-drug and scaffold-based settings. Feature importance analysis showed that atomic identity, hybridization, atom degree, and bond type were key shared determinants, while receptor-stratified results revealed receptor-dependent contributions from secondary features such as aromaticity, chirality, etc. In addition, t-SNE visualization showed clear class separation after training, and molecular docking across estrogen, androgen, and glucocorticoid receptors further supported the biological relevance of the predictions. Together, these findings demonstrate that incorporating hormone receptor-specific sequence information enables more reliable and biologically meaningful prediction of drug-hormone receptor interactions.
28 July 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Differential effects of hormone therapy formulations on Parkinson's disease risk: a systematic review and meta-analysis
BACKGROUND: The relationship between menopausal hormone therapy (HT) and Parkinson's disease (PD) risk remains controversial, with inconsistent findings potentially driven by differences in hormonal formulations. METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. MEDLINE/PubMed and EMBASE were searched between January 8 and March 14, 2026. Observational studies evaluating the association between menopausal HT and PD risk were included. Effect estimates were pooled using random-effects models. Subgroup analyses were performed according to HT formulation (estrogen-only vs. combined estrogen-progestin therapy). A multilevel meta-analysis was conducted to account for within-study dependence. RESULTS: Fourteen studies including 753,749 participants (4,433 PD cases) were analyzed. Overall, HT was not significantly associated with PD risk (RR 1.08; 95% CI 0.94-1.23; I² = 49.4%). In subgroup analyses, combined therapy was associated with an increased PD risk (RR 1.40; 95% CI 1.07-1.82), whereas estrogen-only therapy showed no significant association (RR 1.01; 95% CI 0.81-1.27). Multilevel analysis yielded consistent results (combined: RR 1.33; 95% CI 1.00-1.77; estrogen-only: RR 1.03; 95% CI 0.83-1.27), with no statistically significant interaction between formulations (p = 0.12). CONCLUSIONS: Combined menopausal HT was associated with an increased risk of PD, while estrogen-only therapy showed no significant association. Although differences between formulations were not statistically significant, these findings suggest that hormone composition may influence neurological outcomes and warrant further investigation into individualized HT strategies.
23 July 2026
Read appraisal →International ophthalmology
Machine learning-based model for identifying liver injury in patients with thyroid-associated ophthalmopathy
PURPOSE: To explore the relationship between thyroid-associated ophthalmopathy (TAO) and liver injury and establish a model for identifying liver injury by using machine learning so as to provide an effective diagnostic tool for liver injury in patients with TAO. METHOD: A single-center retrospective study was conducted to collect the clinical data of 318 patients with TAO admitted to a hospital from 2016 to 2022. The patients were divided into a TAO liver injury group (104 cases) and TAO normal liver function group (214 cases) according to whether the patients had normal liver function. The multivariate binomial logistic regression model was used to analyse the risk factors for liver injury in patients with TAO. Feature selection was performed using the random forest algorithm. The research data were divided into a training set and a test set at a ratio of 6:4. Taking whether accompanied by liver injury (0 = no, 1 = yes) as the outcome variable, models were established based on logistic regression, random forest, support vector machine, and decision tree. The performance of the models was evaluated using metrics, including sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and accuracy. RESULT: The random forest method was used for feature screening, and variables ranked among the top 10 according to either mean decrease accuracy or mean decrease Gini were selected for model construction. In five-fold cross-validation, the RF model showed the highest accuracy of 0.937 and AUC of 0.977. In the test set, the RF model also showed good discrimination, with an AUC of 0.973, and the SVM model showed the highest AUC of 0.986, while SVM and LR achieved the highest accuracy of 0.914. CONCLUSION: This study shows that a classification model based on machine learning can effectively identify the risk of liver damage in patients with TAO.
18 July 2026
Read appraisal →Clinica chimica acta; international journal of clinical chemistry
Cortisol as a stress biomarker: analytical perspectives and challenges
Point-of-care testing (POCT) has emerged as a transformative approach in modern healthcare for the rapid detection of physiological abnormalities through minimally or non-invasively collected samples. Biological matrices such as saliva, urine, hair, blood, and interstitial fluid contain clinically significant biomarkers that may serve as indicators of physiological disorders. Among these, cortisol is the key stress biomarker and exerts substantial effects on body metabolism, acting on both peripheral tissues and the CNS. This review comprehensively outlines the evolution of cortisol detection strategies, progressing from conventional laboratory-based immunoassays to advanced analytical platforms, including electrochemical biosensors, wearable devices, and microfluidic systems. Accurate and reliable detection of elevated cortisol levels is crucial for improving diagnostic, therapeutic, and preventive strategies for stress-related disorders. By tracing the analytical window, the work describes the detection of cortisol from traditional immunoassays to innovative biosensing platforms. Moreover, recent advances in nanomaterials, sensor design, and data integration have enabled continuous, on-site monitoring of cortisol levels, thereby enhancing their applicability across diverse clinical and non-clinical settings. This integration of physiological insight with technological advancement provides a comprehensive overview of developments in cortisol assessment, connecting fundamental endocrine science with practical diagnostic applications. The review underscores the potential of next-generation POCT systems to improve early diagnosis, therapeutic monitoring, and personalized healthcare through real-time biomarker analysis.
17 July 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
The effects of glucose-dependent insulinotropic polypeptide on net splanchnic blood flow in lean humans.
CONTEXT: Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with potent vasoactive and metabolic effects in adipose tissue, but its effects on splanchnic blood flow (SBF) in humans remain unclear. Investigating potential regional differences is important for understanding the vascular actions of GIP in humans. OBJECTIVE: The aim of this study was to examine the effects of GIP on SBF, both independently and in combination with hyperglycemia and hyperinsulinemia. METHODS: In a randomized, controlled crossover study, 8 healthy, lean male participants underwent 4 separate experimental conditions. The interventions included intravenous infusions of either GIP at a rate of 1.5 pmol-1 kg-1 minute-1 or saline, administered alone or in combination with a hyperglycemic and hyperinsulinemic clamp, respectively. Splanchnic blood flow was measured by Fick's Principle after catheterization of a hepatic vein, using indocyanine green as indicator. RESULTS: Splanchnic blood flow remained comparable across all experimental conditions, including GIP and saline infusions, both with and without the hyperglycemic and hyperinsulinemic clamp (P = .42). CONCLUSION: Under the applied conditions, GIP does not appear to play a substantial role in the acute regulation of net SBF, either alone or in combination with induced hyperglycemia and hyperinsulinemia.
17 July 2026
Read appraisal →Nano letters
Regulating the Nano-Bio Interface: Converging Electrochemical and Photonic Biosensing for Wearable Diagnostics
The development of wearable biosensors has accelerated due to the combination of nanomaterials, integrative electronics, and miniaturized transduction mechanisms, enabling continuous monitoring of physiological and environmental markers. Electrochemical and photonic modalities have been shown to exhibit complementary capabilities in wearable applications, with each offering distinct advantages in sensitivity, selectivity, miniaturization, and power efficiency. Beyond single-modality functionality, the next generation of wearable diagnostics integrates electrochemical and optical transduction within the same platforms. In this short review, we examine the physical and functional demands of such convergence in wearable systems, highlighting model electrochemical systems, such as textile-integrated wound monitoring and hormone sensors, and how optical modalities provide orthogonal observables of interfacial and biochemical conditions. We further explore new emerging device architectures that leverage electrochemical and optical interrogation to generate robust, information-rich data sets, supporting long-term, real-world deployment of wearable diagnostic technologies for personalized healthcare and continuous monitoring applications.
16 July 2026
Read appraisal →ACS biomaterials science & engineering
A Review of Biomass-Derived Nanomaterials as Functional Interfaces for Advanced Electrochemical Hormone Detection
The study of high-performance sensing platforms is essential to achieve a high sensitivity for hormonal analytes, short response times, and cost-effectiveness. Nevertheless, standard analytical procedures, such as high-performance liquid chromatography, inductively coupled plasma mass spectrometry, and gas chromatography mass spectrometry (HPLC, ICP-MS, and GC-MS), are rather limited because their sensitivity is low at pM/nM concentrations, and the costs of these processes are too high. Moreover, modern sensor technology can be ill-equipped to selectively respond to intricate biological sample types, and there is no single standard used to quantify sensor signals. This review addresses these knowledge gaps by providing a comprehensive discussion on the role of biomass-derived materials as useful interfaces in electrochemical hormone sensing systems. To achieve improved results, we critically investigated the recent advances in the electrode modification process through biomass-based nanomaterials to promote electron transfer kinetics and interfacial engineering. The present article also discusses contemporary issues such as problems with stability, reproducibility, and selectivity in complex matrices. Furthermore, we highlighted some of the new approaches, such as the development of artificial intelligence, Internet of Things, and wearable point-of-care devices, to create the next generation hormone sensors. Overall, this current review is a comprehensive overview of biomass-derived materials, which have the prospect of enhancing surface modification at the advanced phase, AI integration, and the development of point-of-care diagnostics.
14 July 2026
Read appraisal →European journal of clinical pharmacology
Clomiphene citrate versus testosterone replacement therapy in male hypogonadism: a systematic review of literature and meta-analysis
INTRODUCTION: Male hypogonadism, including age-related and functional forms, is characterized by insufficient testosterone production often associated with obesity and metabolic comorbidities. Testosterone replacement therapy (TRT) increases serum testosterone but suppresses spermatogenesis and may cause adverse effects. Selective estrogen receptor modulators (SERMs), such as clomiphene citrate, have emerged as an alternative approach to restore endogenous testosterone while preserving fertility. This study aimed to compare the efficacy of clomiphene citrate versus testosterone replacement therapy (TRT) in increasing serum testosterone levels in men with hypogonadism. METHODS: We conducted a systematic review of the literature in PubMed, Embase, Scopus, The Cochrane Library, and Google Scholar to identify studies comparing clomiphene citrate and testosterone replacement therapy (TRT) in men with male hypogonadism'. The primary outcome was the change in serum testosterone levels before and after treatment. Secondary outcomes included variations in other hormonal parameters, and clinical symptom improvement assessed through standardized instruments. RESULTS: A total of 11 studies with 1512 patients were included (764 on clomiphene citrate; 748 on testosterone replacement therapy, TRT). For serum testosterone, the overall pooled effect showed no significant difference between clomiphene and TRT (MD = 6.64 ng/dL; 95% CI -35.35 to 48.63; I² = 80.6%). Subgroup analyses indicated injectable testosterone achieved higher levels than clomiphene (1 study, 62 patients; MD = -290.50; 95% CI -518.78 to -62.22), whereas gel-based TRT showed no difference (8 studies, 1012 patients; MD = 24.29; 95% CI -18.91 to 67.48; I² = 76.1%). For sexual function, three studies (199 patients; 85 on clomiphene; 114 on TRT) assessing post-treatment libido (ADAM 1-5) showed lower libido scores with clomiphene than TRT (MD = - 0.54; 95% CI - 0.87 to - 0.21; P = 0.009; I² = 18.8%). CONCLUSIONS: No statistically significant difference in serum testosterone levels was observed between clomiphene citrate and testosterone gel, although the evidence is limited by high heterogeneity and some concerns to high risk of bias. TRT was associated with greater improvements in libido. These findings should be interpreted as preliminary, and large-scale randomized trials incorporating clinical and fertility endpoints are needed.
13 July 2026
Read appraisal →European journal of nutrition
Nutrition interventions in women with polycystic ovary syndrome: a systematic review.
PURPOSE: This systematic review aimed to synthesize current evidence on the effects of various dietary interventions on anthropometric, metabolic, hormonal, inflammatory, and oxidative stress parameters in women with polycystic ovary syndrome (PCOS). METHODS: The review followed the PRISMA guidelines and was prospectively registered in PROSPERO (CRD42025641781). Searches were conducted in PubMed, Cochrane Library, EBSCO, Science Direct, Web of Science, National Thesis Center, Google Scholar, and DergiPark Academic for studies published between February 2015 and February 2025. Experimental and observational studies were included if they evaluated the independent effect of dietary interventions in adult women with PCOS. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. RESULTS: A total of 38 studies were included, covering interventions such as calorie-restricted diets, low-glycemic index/load diets, ketogenic diets, intermittent fasting, dietary approaches to stop hypertension, Mediterranean-style, and other diets. Most dietary interventions demonstrated beneficial effects on body weight, body mass index, and waist circumference, as well as improvements in insulin sensitivity, reproductive hormone regulation, and menstrual regularity. However, findings related to lipid metabolism, inflammatory markers, and oxidative stress outcomes were inconsistent. CONCLUSION: Current evidence indicates that dietary interventions are crucial in improving the management of metabolic, anthropometric, hormonal, and clinical outcomes in women with PCOS. Nevertheless, the heterogeneity of dietary approaches, study designs, and outcome measures highlights the need for long-term randomized controlled trials to establish more conclusive recommendations.
30 June 2026
Read appraisal →Medical science monitor : international medical journal of experimental and clinical research
Development and Validation of Machine-Learning-Based Prediction Models for Thyroid Diseases During Pregnancy
BACKGROUND International guidelines recommend early screening based on targeted risk factors to identify thyroid disease during pregnancy. The complexity of these risk factors makes accurate prediction challenging. This study aimed to develop and compare multiple machine-learning-based predictive models for thyroid disease during pregnancy. MATERIAL AND METHODS This retrospective study analyzed the clinical characteristics of 5461 women who gave birth at a single center. The dataset was divided into training and test sets. In the training set, feature variables associated with thyroid disease during pregnancy were selected using the Boruta algorithm. Eight models were developed: logistic regression, Bayesian approach, k-nearest neighbors, support vector machine, neural network, classification and regression tree, extreme gradient boosting, and random forest (RF). Model performance was evaluated using the receiver operating characteristic (ROC) curve, precision-recall curve (PRC), calibration curve, and decision curve analysis. RESULTS Nine feature variables were identified: age, height, pre-pregnancy weight, gravidity, parity, primiparity or multiparity, hypertensive disorders of pregnancy, scarred uterus, and autoimmune disease. The RF model demonstrated the best performance, with accuracy of 0.98387819 and 0.99597990, Matthews correlation coefficient of 0.96794139 and 0.97781292, log loss of 0.12670703 and 0.09442025, Brier score of 0.02495798 and 0.01921069, area under the ROC curve of 0.99877170 and 0.99991140, and area under the PRC of 0.99864486 and 0.99922572 in the training and test sets, respectively. CONCLUSIONS The RF model demonstrates excellent discriminative performance, accuracy, consistency, and generalizability in predicting thyroid disease during pregnancy.
23 June 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Diabetes technology: an update.
Diabetes is one of the most prevalent chronic diseases worldwide, with rates that continue to increase. More than 30 years ago, the Diabetes Control and Complications Trial demonstrated that intensive glucose management decreased long-term vascular complications. Unfortunately, many people with diabetes still struggle to meet glycemic goals. In this mini-review, we highlight advances in diabetes technology that are associated with improvements in glycemic management. Continuous glucose monitoring (CGM) and automated insulin delivery systems are associated with significant improvements in glycated hemoglobin (HbA1c), time in range (70-180 mg/dL), and decreases in severe hypoglycemia and diabetic ketoacidosis in people with both type 1 and type 2 diabetes. Recent data show that these technologies improve outcomes early in the course of type 1 diabetes. CGM is also being explored as a tool to monitor progression through early-stage type 1 diabetes (2 antibodies positive) to identify individuals who may benefit from disease-modifying therapies as well as to prevent the onset of diabetic ketoacidosis at onset of stage 3 (insulin-requiring) type 1 diabetes. Adjunctive pharmacologic therapies and artificial intelligence may further expand and improve therapies, offering potential synergistic benefits. However, there continue to be significant disparities in access to diabetes technologies and access to insulin worldwide. This mini-review summarizes recently published data, highlights emerging applications, and underscores the need to pair technological innovation with strategies that promote equitable access and support for diabetes care to improve outcomes for all people with diabetes.
19 June 2026
Read appraisal →The American journal of cardiology
Efficacy and Safety of Olezarsen for the Management of Dyslipidemia: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
This updated systematic review and meta-analysis evaluated the efficacy and safety of olezarsen in patients with dyslipidemia. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched through September 2025 for randomized controlled trials comparing olezarsen with placebo. Seven trials (n = 2,121) were included. Olezarsen significantly reduced triglycerides (mean difference [MD] -59.20 mg/dL), very-low-density lipoprotein cholesterol (MD -52.68 mg/dL), apolipoprotein B (MD -10.74 mg/dL), non-HDL cholesterol (MD -17.06 mg/dL), and apolipoprotein C-III (MD -64.16 mg/dL), and increased HDL cholesterol (MD 30.97 mg/dL), with no significant effect on LDL cholesterol. Injection site reactions (risk ratio [RR] 3.93) and platelet counts <140,000/µL (RR 4.76) were increased, whereas serious adverse events and significant liver enzyme elevations were comparable to placebo. Certainty of evidence ranged from moderate to low. In conclusion, olezarsen produces substantial improvements in triglyceride-rich lipoproteins with an acceptable safety profile; long-term cardiovascular outcome trials are warranted.
16 June 2026
Read appraisal →Life sciences
The interplay of plant polysaccharide structure, gut microbiota metabolism, and host health: Mechanisms and perspectives
Plant polysaccharides, as natural biomolecules, possess the capability to modulate the structure and function of gut microbiota, subsequently influencing host health. Nevertheless, the molecular mechanisms underlying their interactions remain insufficiently understood. This article presents a systematic review of the impact of the chemical structure of plant polysaccharides, including monosaccharide composition and types of glycosidic bonds, on the metabolic preferences of gut microbiota. It emphasizes how structural variations in polysaccharides can promote the proliferation of specific gut microbiota, such as Bacteroidetes and Firmicutes. Additionally, the study analyzes critical enzymatic systems, including glycoside hydrolases (GHs) and polysaccharide lyases (PLs), alongside metabolic pathways associated with the production of short-chain fatty acids (SCFAs) that facilitate the degradation of plant polysaccharides by gut microbiota. Furthermore, it explores the influence of these metabolites on conditions such as obesity, diabetes, inflammatory bowel disease (IBD), and non-alcoholic fatty liver disease. The findings provide a robust theoretical framework for enhancing the utilization efficiency of bioactive polysaccharide components through targeted extraction and characterization techniques, thereby fostering potential advancements in innovative nutritional formulations and pharmacological applications.
16 June 2026
Read appraisal →Life sciences
Intermittent fasting and cardiometabolic responses under cardiac stress: a systematic review of preclinical studies
Intermittent fasting (IF) has emerged as a dietary strategy with benefits that extend beyond weight management and glycemic control. Although growing evidence supports its favorable effects on cardiometabolic health, the impact of IF under conditions of cardiac stress remains poorly characterized. Since clinical trials cannot ethically expose patients to acute cardiac stress during IF protocols, preclinical models are essential to elucidate its potential cardioprotective mechanisms. This systematic review aimed to synthesize the preclinical evidence on the effects of IF in models of cardiac stress. Following a registered protocol (PROSPERO:#CRD42023466215), we searched databases for preclinical studies evaluating IF under cardiac stress. Models included atherosclerosis induction, diet modulation, hypercholesterolemic mice, doxorubicin-induced cardiotoxicity, pulmonary arterial hypertension, myocardial infarction, ischemia-reperfusion injury, among others. All IF regimens, encompassing variations in timing, frequency, and type, were considered. Clinical trials, observational studies, reviews, meta-analyses, updates, guidelines were excluded. Thirty-two studies involving 451 predominantly male animals were included. Approximately 80% reported that IF improved cardiovascular outcomes, reducing blood pressure, cardiac hypertrophy, fibrosis, and ischemic injury while enhancing vascular and metabolic function. Mechanistically, IF protects the heart under stress by downregulating NF-κB, IL-1β, and TNF, and activating SIRT3 and AMPK pathways, improving mitochondrial function, lipid metabolism, and cardiac energy homeostasis. Cardioprotective benefits were dependent on fasting duration and regimen, emphasizing the importance of metabolic context. In conclusion, IF appears to enhance cardiovascular resilience under stress through multiple metabolic and molecular pathways. These findings support further clinical investigation of IF as a potential adjunct strategy for cardiometabolic protection under stress.
15 June 2026
Read appraisal →Journal of global health
mHealth for chronic disease management: effects on adherence in Ghanaian patients with diabetes and hypertension
BACKGROUND: Medication non-adherence remains a major barrier to effective chronic disease management, particularly in low- and middle-income countries. In Ghana, limited access to continuous care and patient engagement tools contributes to poor adherence among individuals living with type 2 diabetes and hypertension. Mobile health interventions, including smartphone applications, may offer scalable solutions to support long-term medication use and self-management. Here, we assess the effect of a smartphone-based intervention on medication adherence among adults with these conditions. METHODS: We conducted a quasi-experimental study among 874 adults with type 2 diabetes or hypertension in Ghana. Participants were assigned to either a smartphone-based intervention, which included medication reminders, educational content, and self-monitoring tools, or standard care involving routine outpatient management and follow-up without access to the smartphone-based intervention. We measured medication adherence at baseline and six months using the Medication Adherence Rating Scale and assessed it through generalised estimating equations and difference-in-differences analyses, adjusting for baseline adherence, age, sex, and treatment setting. RESULTS: Use of the smartphone application was associated with a greater improvement in medication adherence over six months in the overall study population (adjusted beta coefficient (aβ) = 0.062; 95% confidence interval (CI) = 0.010-0.123). Similar improvements were observed among participants with type 2 diabetes (aβ = 0.067; 95% CI = 0.012-0.135) and hypertension (aβ = 0.068; 95% CI = 0.005-0.134). However, there was no statistically significant difference in adherence between the intervention and control groups at six months. CONCLUSIONS: Smartphone-based interventions were associated with modest improvements in medication adherence over time, although between-group differences at follow-up were not statistically significant. As access to mobile technology expands across Africa, such interventions may provide scalable strategies to support chronic disease management.
14 June 2026
Read appraisal →Scandinavian journal of primary health care
The diagnostic accuracy of AI-assisted diabetic retinopathy screening in primary care: a prospective validation study
OBJECTIVES: This study investigated the diagnostic accuracy of AI-assisted diabetic retinopathy screening in primary care, using ophthalmologist-led screening as the reference standard. METHODS: Patients with type 2 diabetes attending routine appointments at 10 primary care clinics underwent AI-assisted screening, followed by re-screening at an ophthalmology clinic. The quality of fundus images captured in primary care was independently assessed, and diagnostic accuracy was evaluated by comparing AI-assisted results with ophthalmologist results, including sensitivity, specificity, PPV, NPV, and AUC. Two analyses were conducted: one including all images and one excluding those of poor quality. RESULTS: Among 183 patients (336 images), 18.6% of images were classified as poor quality. When all images were included, the AI-assisted screening achieved a sensitivity of 73.7%, specificity of 90.2%, PPV of 31.1%, NPV of 98.3%, and AUC of 0.82. Excluding poor-quality images improved sensitivity to 80.0%, NPV to 98.7%, and AUC to 0.84. Additional ocular findings unrelated to diabetic retinopathy were observed in 96 patients, including confirmed or non-specific signs of glaucoma, cataract, age-macular degeneration, benign nevus and reduced visual acuity. CONCLUSION: AI-assisted screening in primary care shows potential for clinical application, but further validation in larger populations and improvements in image quality are needed before clinical implementation.
14 June 2026
Read appraisal →Journal of medical Internet research
Telehealth Usability, Engagement Patterns, and Technical Infrastructure in Managing Noncommunicable Diseases Among Health Care Professionals in Brazil, Ghana, Honduras, and the United Kingdom: Multinational Cross-Sectional Study
BACKGROUND: Noncommunicable diseases (NCDs) account for over 70% of global deaths, with hypertension and diabetes serving as major contributors. The COVID-19 pandemic disrupted traditional health care services for NCDs and highlighted telehealth as a crucial alternative. Telehealth-encompassing synchronous and asynchronous electronic communication to deliver clinical services remotely-can overcome geographical barriers and enhance patient engagement. However, telehealth usability among health care professionals (HCPs) remains under-studied across low-, middle-, and high-income countries. OBJECTIVE: This study aimed to examine which telehealth engagement patterns, technical infrastructure factors, and user profiles were most strongly associated with usability among HCPs and to descriptively compare these across 4 diverse countries: Brazil (high- to middle-income country), Ghana (low- to middle-income country), Honduras (low- to middle-income country), and the United Kingdom (high-income country). METHODS: A multinational cross-sectional survey was conducted with 290 HCPs across 4 countries. Participants completed the System Usability Scale and provided data on telehealth engagement (eg, frequency, duration, and number of systems used), technical infrastructure (connection stability and support satisfaction), and their user profile (demographics, job role, and training received). Descriptive statistics summarized these patterns and usability scores. Multiple linear regression with bootstrap-based sensitivity analyses identified factors associated with telehealth usability. Given the nonprobability design, no formal inferential comparisons were made between countries. Instead, observed patterns were reported descriptively. RESULTS: Higher telehealth usability scores were associated with greater connection stability (b=5.06, 95% CI 3.06-7.05), higher satisfaction with online support information (b=5.02, 95% CI 3.27-6.75), more frequent use (b=3.05, 95% CI 1.36-4.73), longer duration of use (b=1.59, 95% CI 0.49-2.68), and being a physician by profession (b=3.82, 95% CI 0.23-7.40). Average usability scores were highest among users in Ghana (mean 79.75, SD 14.19) and the United Kingdom (mean 79.00, SD 14.71), followed by Brazil (mean 72.01, SD 14.62) and Honduras (mean 63.09, SD 15.57). According to System Usability Scale guidelines, scores corresponded to "good" usability for users in Ghana, the United Kingdom, and Brazil and were below the "good" threshold for users in Honduras. While most users in Ghana (97/111, 87.4%), Honduras (31/38, 81.6%), and Brazil (57/80, 70.4%) reported using only 1 telehealth system, two-thirds of UK users (40/60, 66.7%) reported using 2 or more systems. User profiles also varied; prepandemic use was highest in Ghana (84/111, 75.7%) and lowest in Honduras (7/38, 18.4%). Other engagement patterns across countries were reported. CONCLUSIONS: Telehealth usability is driven by technical infrastructure reliability, a robust online support infrastructure, and an "experience effect" from frequent and long-term engagement. Descriptive differences in engagement patterns and infrastructure highlight the need for tailored strategies to address setting-specific challenges. These are essential to optimize telehealth integration and improve health care outcomes for patients with NCDs worldwide.
14 June 2026
Read appraisal →Current atherosclerosis reports
Comparative Efficacy of Nutraceuticals on Endothelial Function: A Systematic Review and Network Meta-Analysis
PURPOSE OF REVIEW: This network meta-analysis (NMA) compares the efficacy of dietary interventions in improving flow mediated dilation (FMD) as a measure of endothelial function among individuals with cardiovascular diseases (CVDs) and hypertension. This work can be a basis for the design of future clinical trials and for the development of evidence-based nutritional guidelines to improve cardiovascular outcomes. RECENT FINDINGS: The most substantial improvements in FMD were observed with magnesium (MD: 8.17; CoE: High), vitamin D3 (MD: 7.84; CoE: High), flaxseed (MD: 7.39; CoE: Low), barberry (MD: 6.64; CoE: Moderate), folic acid (MD: 3.36; CoE: Low), and omega-3 (MD: 1.83; CoE: Very low). Sensitivity analyses confirmed the robustness of these findings. Several dietary interventions, particularly magnesium and vitamin D₃, have been shown to improve endothelial function in individuals with CVDs and hypertension. These findings highlight the potential role of nutritional strategies as adjunct therapies for preserving vascular health. TRIAL REGISTRATION: Systematic review registered with PROSPERO, registration number CRD420251041093.
14 June 2026
Read appraisal →BMJ open
Effect of a culturally adapted heart-healthy diet with phytosterols and/or krill oil on lipid-related outcomes in familial hypercholesterolaemia: protocol for a multicentre randomised controlled trial in Brazil
INTRODUCTION: An affordable heart-healthy dietary approach is essential for the management of familial hypercholesterolaemia (FH); however, the optimal dietary pattern and the role of adjunctive nutrient supplementation remain uncertain. This study aims to evaluate the effects of the Brazilian Cardioprotective Diet (DICA Br), adapted from the Portfolio Diet, with or without phytosterol and/or krill oil supplementation in individuals with probable or definite FH according to the Dutch Lipid Clinic Network (Dutch MEDPED) criteria. METHODS AND ANALYSIS: The DICA-FH study is a national, multicentre, randomised, factorial, parallel-group, superiority, placebo-controlled clinical trial with a 1:1:1:1 allocation ratio. Participants aged ≥16 years receiving age-appropriate lipid-lowering therapy will be randomised into four groups: (1) adapted cardioprotective diet (DICA-FH) plus phytosterol placebo and krill oil placebo; (2) DICA-FH plus phytosterol 2 g/day and krill oil placebo; (3) DICA-FH plus phytosterol placebo and krill oil 2 g/day or (4) DICA-FH plus phytosterol 2 g/day and krill oil 2 g/day. All participants will undergo whole-genome sequencing and receive appropriate genetic counselling. Primary outcomes will be means of low-density lipoprotein cholesterol and lipoprotein(a) levels after 120 days. Secondary outcomes will include additional lipid biomarkers, adherence to protocol and adverse events. The planned sample size is 300 participants. Follow-up is expected to conclude in July 2026. ETHICS AND DISSEMINATION: This study was registered under CAAE 65549622.2.1001.0060 and received ethical approval from the Hcor Research Ethics Committee (approval number 5.805.072) and the Brazilian National Research Ethics Commission (CONEP; approval number 6.864.951). Written informed consent will be obtained from all participants prior to enrolment. The study findings will be disseminated through peer-reviewed publications, scientific conferences and channels aimed at the general public. TRIAL REGISTRATION NUMBER: NCT06331195.
14 June 2026
Read appraisal →JMIR mHealth and uHealth
WeChat-Delivered Mobile Medical Nutrition Therapy Intervention in Gestational Diabetes Mellitus: Randomized Controlled Trial
BACKGROUND: Medical nutrition therapy (MNT) serves as the foundational intervention in the clinical management of gestational diabetes mellitus (GDM) management. However, inadequate supportive care often hinders patients' ability to sustain dietary modifications and self-management behaviors, particularly for complex regimens. Flexible online interventions are thus gaining interest as adjuncts to clinical care, with the potential to improve the outcomes of GDM self-management. OBJECTIVE: This study sought to evaluate the benefits of WeChat-delivered medical nutrition therapy (WeMNT), a WeChat-delivered MNT intervention, for patients with GDM. METHODS: A parallel-group, single-blind randomized controlled trial (with outcome assessor blinding) was implemented at a university hospital's obstetric clinic. Eligible participants were those with a 24- to 28-week singleton pregnancy, a GDM diagnosis confirmed by the 75 g oral glucose tolerance test, no requirement for insulin therapy, and the ability to use a smartphone and WeChat, as well as to communicate in Chinese. Participants were randomized 1:1 to the intervention (n=47, 50%) or control group (n=47, 50%) using a random number table. The WeMNT intervention was designed per the behavior change wheel framework: (1) analyze capability-, opportunity-, and motivation-based barriers related to MNT adherence; (2) formulate targeted intervention functions; and (3) select evidence-based behavior change techniques. Three WeChat mini-programs served as the core delivery platform to implement the multifaceted intervention functions. The primary outcomes measured in this study included fasting blood glucose, 2-hour postprandial glucose (2hPG), hemoglobin A1c (HbA1c), and gestational weight gain (GWG). The secondary outcomes assessed included obstetric complications and neonatal parameters. Intention-to-treat analysis using adjusted generalized linear mixed models was conducted to evaluate the effects of the intervention. RESULTS: From March 2023 to October 2023, a total of 94 participants were enrolled in this study. Among the participants, 88 (93.62%) individuals (mean age 32.18, SD 5.04 years) successfully completed the study, 44 (46.81%) in the intervention group and 44 (46.81%) in the control group. Approximately 68.18% (30/44) of the participants in the intervention group demonstrated sustained adherence, as expected, adhered to the diet plan ≥60% of the days. Compared with the control group, the intervention group showed a significantly greater decrease in GWG over time (group×time interaction: β=-1.96, 95% CI -3.58 to -0.34; P=.02), with no significant effects on fasting blood glucose. Conversely, significant decreases in 2hPG (β=-0.12, 95% CI -0.19 to -0.04; P<.001) and HbA1c (β=-0.49, 95% CI -0.74 to -0.23; P<.001) were noted in the intervention group. No unexpected maternal adverse events occurred, and no significant effects on other health outcomes were detected. CONCLUSIONS: As a WeChat-delivered, behavior change wheel-informed intervention, WeMNT successfully reduced 2hPG, HbA1c, and GWG in GDM management. Its integrated self-management model yields robust evidence, validating this patient-centered tool as a viable option for clinical adoption.
14 June 2026
Read appraisal →Lancet (London, England)
Atrasentan in patients with IgA nephropathy (ALIGN): final 2·5-year results from a randomised, double-blind, placebo-controlled, phase 3 trial
BACKGROUND: Atrasentan, a selective endothelin A receptor antagonist, reduced proteinuria in the prespecified interim analysis (week 36) of the ALIGN trial in adults with IgA nephropathy. We assessed whether atrasentan slowed estimated glomerular filtration rate (eGFR) decline after 2·5 years' treatment. METHODS: We performed a randomised, double-blind, placebo-controlled, phase 3 trial (133 sites, 20 countries). Adults with biopsy-proven IgA nephropathy, eGFR of at least 30 mL/min per 1·73 m2, and urinary protein excretion of at least 1·0 g/day while receiving renin-angiotensin system inhibition were enrolled (main stratum). An exploratory stratum enrolled participants also receiving an SGLT2 inhibitor. Participants were randomly assigned (1:1) to oral atrasentan 0·75 mg once daily or placebo for 132 weeks, followed by a 4-week off-treatment follow-up. The key secondary endpoint was change from baseline to week 136 in eGFR in the main stratum, assessed in all randomised patients (excluding data after intercurrent events, defined as initiation of restricted or alternative IgA nephropathy medications or kidney replacement therapy). Safety was assessed in all randomised patients who received at least one dose of study treatment. ALIGN is registered with ClinicalTrials.gov, NCT04573478; the double-blind section is complete, and the open-label extension is ongoing. FINDINGS: Between March 15, 2021, and April 28, 2023, 404 participants were randomly assigned (main stratum: 340; SGLT2 inhibitor stratum: 64). In the main stratum, change from baseline in eGFR at week 136 was -7·5 mL/min per 1·73 m2 (95% CI -9·2 to -5·8) with atrasentan and -9·9 mL/min per 1·73 m2 (-11·7 to -8·1) with placebo (between-group difference 2·4 mL/min per 1·73 m2; 95% CI -0·1 to 4·8; p=0·057). The between-group difference in eGFR change from baseline at end of treatment (week 132) was 2·6 mL/min per 1·73 m2 (95% CI 0·1-5·0), and the difference in total eGFR slope (baseline to week 136) was 1·4 mL/min per 1·73 m2 per year (95% CI 0·5-2·3). In the SGLT2 inhibitor stratum, the difference in eGFR change from baseline at week 136 between atrasentan and placebo was 9·1 mL/min per 1·73 m2 (95% CI 3·0-15·2). Treatment-emergent adverse events were well balanced between atrasentan and placebo, with no new safety signals. In the main stratum, fluid retention adverse events occurred in 24 (14%) of 169 patients receiving atrasentan and 20 (12%) of 170 receiving placebo. INTERPRETATION: Atrasentan reduced proteinuria and preserved kidney function after 2·5 years. This effect was present with or without concomitant SGLT2 inhibitor use. Atrasentan was well tolerated. FUNDING: Novartis.
14 June 2026
Read appraisal →Lancet (London, England)
Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial
BACKGROUND: Retatrutide is a GIP, GLP-1, and glucagon triple hormone receptor agonist, under clinical development for type 2 diabetes, obesity, and related complications. We aimed to assess the efficacy and safety of retatrutide as a monotherapy in people with type 2 diabetes that is inadequately controlled by diet and exercise alone. METHODS: In this 40-week, phase 3, randomised, double-blind, placebo-controlled trial at 48 sites in the USA, Mexico, and India, we recruited adults (aged ≥18 years) with type 2 diabetes that is inadequately controlled by diet and exercise alone, glycated haemoglobin (HbA1c) between 7·0% and 9·5% (53-80 mmol/mol), and BMI of at least 23 kg/m2. Participants were randomly assigned (1:1:1:1) to receive retatrutide (4 mg, 9 mg, or 12 mg) or placebo by once-weekly subcutaneous injection. The primary endpoint was the change in HbA1c concentration from baseline to week 40. A key secondary endpoint was the percentage change in bodyweight from baseline to week 40. This trial is registered with ClinicalTrials.gov, NCT06354660, and is completed. FINDINGS: Between April 10, 2024, and April 21, 2025, 930 participants were screened and 537 (296 [55%] female and 241 [45%] male) were randomly assigned: 134 to retatrutide 4 mg, 133 to retatrutide 9 mg, 136 to retatrutide 12 mg, and 134 to placebo. Baseline mean age was 48·8 years (SD 12·1), mean HbA1c concentration was 7·9% (SD 1·1), mean duration of diabetes was 2·5 years (SD 4·4), and mean BMI was 35·8 kg/m2 (SD 7·0). 490 (91%) participants completed the treatment period on study drug and 504 (94%) completed the study. For the treatment regimen estimand, the mean change from baseline in HbA1c concentration was -1·69% (SE 0·11) with retatrutide 4 mg, -1·86% (0·10) with 9 mg, and -1·94% (0·08) with 12 mg, versus -0·81% (0·12) with placebo, resulting in estimated treatment differences versus placebo of -0·88% (95% CI -1·18 to -0·59) with retatrutide 4 mg, -1·04% (-1·32 to -0·76) with 9 mg, and -1·12% (-1·39 to -0·85) with 12 mg (all p<0·0001). The mean percentage change from baseline in bodyweight was -11·5% (SE 0·7) with retatrutide 4 mg, -13·9% (0·8) with 9 mg, and -15·3% (0·8) with 12 mg, versus -2·6% (0·5) with placebo. The most frequent adverse events with retatrutide were generally mild to moderate gastrointestinal events, which subsided over time. Study intervention discontinuations due to adverse events were 2-5% with retatrutide and 0% with placebo. No severe hypoglycaemia was reported. Two deaths occurred during the study, both in the retatrutide 4 mg group and unrelated to the study drug. INTERPRETATION: Retatrutide showed significant improvements in glycaemic control and bodyweight reduction as a monotherapy in adults with type 2 diabetes that is inadequately controlled with diet and exercise alone, with an adverse event profile consistent with molecules with GLP-1 agonist activity, supporting its potential as an effective treatment for type 2 diabetes. FUNDING: Eli Lilly and Company.
13 June 2026
Read appraisal →BMJ open
Diabetic retinopathy treatment cascade and care continuum in the USA: a systematic review
OBJECTIVES: To characterise engagement across the diabetic retinopathy (DR) care continuum in the USA using a cascade-of-care framework and identify gaps contributing to preventable vision loss. DESIGN: Systematic review. DATA SOURCES: From September to November 2025, with an updated search in March to April 2026 using the same eligibility criteria, we systematically searched Ovid MEDLINE and Ovid Embase supplemented by reviewing reference lists of relevant articles and opportunistic searches of the Centers for Disease Control and Prevention publications. ELIGIBILITY CRITERIA: We included English-language US-based cross-sectional, cohort and case-control studies and systematic reviews containing US-based data published between 1 January 2018 and 31 December 2025 relevant to one of the defined DR cascade stages: (1) diagnosis of diabetes, (2) adherence to DR screening, (3) diagnosis of DR, (4) adherence to DR care and (5) DR-related blindness. We included systematic reviews only to inform DR-related blindness, where primary data were limited and excluded them from other stages to avoid double-counting. Exclusion criteria included studies not relevant to one of the defined DR cascade stages and editorial, perspective or commentary pieces. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened studies, extracted data and assessed risk-of-bias using the Newcastle-Ottawa Scale and Risk of Bias in Systematic Reviews tool. We synthesised data narratively and organised via the DR treatment cascade framework. RESULTS: Of 14 893 studies screened, 46 met the inclusion criteria. Cascade analysis revealed substantial losses in patient engagement at three stages: (1) only 15.5%-78.7% (median 59.4%, IQR 33.9%-74.0%) of individuals with diabetes obtain biennial DR screening; (2) a substantial 54.9%-88.5% (median 70.1%, IQR 62.5%-79.3%) of individuals with DR are unaware of their diagnosis; (3) only 30.9%-62.7% (median 52.0%, IQR 40.9%-59.1%) of individuals diagnosed with DR are initially linked to care and 55.3%-77.8% (median 70.3%, IQR 59.2%-77.7%) have a lapse in DR follow-up. CONCLUSIONS: This review identifies major gaps in the DR care continuum, particularly in diagnosis awareness, linkage to care and follow-up adherence. The cascade framework highlights key points of disengagement and provides a basis for prioritising future research.
13 June 2026
Read appraisal →Journal of medical Internet research
Text Messaging Support for Patients Diagnosed With Impaired Glucose Tolerance During Pregnancy: Nonrandomized Pre-Post Implementation Study Assessing Impact on Postpartum Transitions of Care
BACKGROUND: Patients with impaired glucose tolerance (IGT) identified during pregnancy who do not develop gestational diabetes mellitus (GDM) often do not receive additional interventions for their long-term metabolic risks. OBJECTIVE: This nonrandomized pre-post implementation study reports the design process and initial program evaluation for Better Follow-up of Impaired Glucose Tolerance (BRIDGE), a 12-week text-based postpartum support program promoting hemoglobin A1c (HbA1c) completion and primary care provider (PCP) visit scheduling for patients diagnosed with IGT during pregnancy, assessing improvement in desired postpartum transition milestones. The 19-month program was divided into 2 arms lasting 9.5 months each, BRIDGE- (SMS text messaging support alone; October 2021-July 2022) and BRIDGE+ (SMS text messaging and IGT-focused postpartum visit; July 2022-April 2023). We aimed to assess whether BRIDGE improved desired postpartum transition milestones. METHODS: Patients were eligible for BRIDGE if they received prenatal care at the study site (a northeastern US academic tertiary care center), were diagnosed with IGT during pregnancy, never developed GDM, and could receive English text messages. We performed a program evaluation using a pre/postimplementation design, comparing outcomes for the BRIDGE population to a 19-month historical population. Primary outcomes were (1) completion of HbA1c testing by 1 year postpartum and (2) PCP visit scheduling by 12 weeks postpartum. A comparative analysis between BRIDGE- and BRIDGE+ was performed. Multivariable logistic regressions controlled for the history of IGT after stepwise backward elimination. RESULTS: In the program evaluation, 503 individuals were included (n=342 in historical population, n=82 in BRIDGE- population, and n=79 in BRIDGE+ population), with similar demographic and clinical characteristics across populations. A total of 212 individuals were screened for eligibility in BRIDGE, and 161 individuals participated in the program. BRIDGE participants had increased odds of HbA1c completion by 1 year postpartum (39.8% vs 12.5%; adjusted odds ratio [aOR] 4.28, 95% CI 2.71-6.78) and PCP visit scheduling (31.0% vs 12.0%; aOR 9.58, 95% CI 4.39-20.9) compared to the historical population. BRIDGE+ patients were more likely to complete HbA1c testing by 12 weeks postpartum than BRIDGE- participants. Most patients attended scheduled PCP visits, but rates of IGT counseling at PCP visits were low. CONCLUSIONS: Individuals with IGT rarely receive targeted interventions during pregnancy or delivery hospitalization. This innovative study demonstrates that individuals with IGT have high rates of uptake for postpartum SMS text messaging support, which tripled completion rates of HbA1c screening within 1 year postpartum and doubled the scheduling rate for PCP visits by 12 weeks postpartum. While attendance at scheduled PCP visits was very high, <60% of PCP visits included IGT counseling, highlighting key improvement areas in the quality of postpartum transitions to primary care. While a randomized trial is needed to ascertain definitive impact, SMS text messaging support may be an effective tool to improve postpartum transitions of care for this underserved population.
12 June 2026
Read appraisal →World journal of urology
The urologic impact of long-term finasteride 1-mg use for androgenic alopecia: a matched-cohort database analysis
INTRODUCTION AND OBJECTIVES: Since its approval in 1997, finasteride-1 mg (F1) can be taken daily to treat androgenic alopecia (AA) by reducing serum dihydrotestosterone (DHT). When finasteride is prescribed at the 5 mg dosage, the DHT reduction is known to affect sexual function, reduce serum prostate-specific antigen (PSA) levels and treat benign prostatic hyperplasia (BPH). However, there is no literature on the urologic function of men using long-term F1. Thus, we aimed to address this knowledge gap by analyzing a database for the impact of F1 on urologic function. METHODS: Using the Truveta database, we identified men aged 18 + diagnosed with AA per International Classification of Diseases (ICD) coding, with at least 90 days of F1 use and ≥ 5 years of follow-up. Exclusions included patients with a history of anti-depressant usage, prior diagnosis (Dx) or treatment (Tx) of erectile dysfunction (ED), BPH, or prostate cancer (PC). A control cohort with AA but no F1 use was matched based on age, race, ethnicity, and marital status. We compared Dx rates, Tx rates, and time to Dx or Tx using Chi-square and Kruskal-Wallis Rank sum tests. Survival analysis was performed with restricted mean survival time. RESULTS: We identified 3470 patients with long-term F1 use and 3470 matched patients with AA but no F1 use. The average age for the F1 group was 40.59 and 39.75 for the control. Average F1 use duration was 2011.5 days. Median follow-up was 2554.7 days for the F1 group, and 3129.5 days for the control. The F1 group had higher phosphodiesterase type 5 inhibitor (PDE5i) prescription rate (13.6% vs. 10.5%, p < 0.001) and earlier prescription by 238.6 days (95% CI -304.3, -172.9, p < 0.0001). The control group had a higher -blocker prescription rate (4.4% vs. 2.9%, p = 0.001). There were no significant differences in ED diagnosis, BPH Dx rates or time-to BPH diagnosis or α-blocker prescription. The F1 group had lower elevated PSA Dx and PC Dx rates (2.9% vs. 4.4%, p < 0.001; 0.9% vs. 1.8%, p = 0.001). CONCLUSIONS: Though ED diagnosis did not differ significantly, patients on long-term F1 for AA were more likely to be prescribed PDE5i and sooner by approximately 230 days, compared to non-F1 users. F1 did not significantly affect BPH Dx or Tx rates. F1 use was associated with decreased PC and elevated PSA Dx rates. More research on urologic effects of chronic F1 use in AA patients is needed.
9 June 2026
Read appraisal →Journal of proteome research
AI-Based Digital Pathology-Enabled Spatial-Omics Data Analyses of the Human Kidney
Identification of tissue-region-specific changes in glycosylation is crucial for understanding the pathogenesis of kidney diseases, yet it remains a great challenge. We developed a workflow that combines matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) data with AI-based digital pathology annotations of kidney functional tissue units (FTUs) to profile N-glycan distributions within biopsy tissues. This approach can generate molecular-level data relevant to diverse pathological outcomes, thereby aiding in the elucidation of disease mechanisms. As a proof-of-concept, we demonstrate that this AI-based digital pathology approach to MALDI data segmentation enables the detection and differentiation of N-glycosylation within FTUs of healthy kidney tissue. We then elucidated differences in N-glycosylation between the diseased kidney tissue samples from patients with different diagnoses. Sialic acid N-glycans, which have been linked to various kidney diseases, displayed enrichment in the glomeruli and tubules of tissues from patients diagnosed with diabetic kidney disease (DKD), whereas they were enriched in the tubules and arteries from patients with acute kidney injury (AKI), in comparison to healthy tissue. Furthermore, we found that polylactosamine N-glycans were enriched only in the AKI samples, indicating their potential roles in tubular injury and inflammation. This workflow has the potential to bridge the gap between region-specific glycosylation and its implications on FTUs in diseases, paving the way for targeted molecular imaging studies in the kidney and other tissues.
7 June 2026
Read appraisal →PloS one
The application of large language models in bariatric surgery: A scoping review
BACKGROUND: Exploratory applications of large language models within the specialized field of metabolic and bariatric surgery have begun to emerge. Nevertheless, existing research remains fragmented, lacking comprehensive integration. OBJECTIVE: To conduct a scoping review of studies on the application of large language models in the field of metabolic and bariatric surgery, aiming to provide a reference for clinical practice and future research. METHODS: This scoping review adhered to the Joanna Briggs Institute methodological framework and followed the preferred reporting items for systematic reviews and meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines.PubMed, Web of Science, The Cochrane Library, Embase, CINAHL, CNKI, Wanfang, and VIP databases were searched for relevant studies, with the search timeframe from database inception to November 2025. The included literature was summarized and analyzed. RESULTS: A total of 21 English-language studies were included. LLMs were primarily applied in scenarios such as patient education and information consultation, clinical decision support, and professional knowledge assessment. While LLMs performed well in information-provision tasks, they showed low consistency with expert opinions in complex clinical tasks such as individualized surgical recommendations. Performance varied across different models, with GPT-4 generally demonstrating superior performance, and domain-specific models showing professional potential. Current research still faces challenges regarding information accuracy, readability, and clinical applicability. CONCLUSION: Large language models hold auxiliary potential in the field of metabolic and bariatric surgery, particularly for knowledge dissemination and patient education. However, their reliability in complex clinical decision-making remains limited. Future efforts should focus on conducting high-quality studies, advancing model specialization and standardized evaluation, and exploring safe and effective human-AI collaboration models.
7 June 2026
Read appraisal →Annals of medicine
A body roundness index (BRI)-based predictive model for metabolic syndrome in perimenopausal and postmenopausal women-from a cross-sectional machine learning study to a longitudinal dynamic assessment
BACKGROUND AND AIMS: Metabolic syndrome (MetS) is highly prevalent among perimenopausal and postmenopausal women and poses a major public health challenge because of its association with cardiovascular disease, type 2 diabetes, and premature mortality. However, prediction tools for this population remain limited. Therefore, this study aimed to develop a Body Roundness Index (BRI)-based prediction model for MetS by integrating cross-sectional machine learning and longitudinal assessment. METHODS AND RESULTS: Cross-sectional models were trained using NHANES 2007-2020 and validated in the Affiliated Hospital of Dalian University (2023-2024). Sixteen predictors were selected via LASSO and Boruta, and eight models were evaluated using AUC, calibration, and decision curve analysis. SHAP ranked high-contribution factors. Longitudinal analysis used a 10-year cohort. Annualized change rates and cumulative exposure metrics of five key predictors were combined with baseline values to build Cox models, compared by C-index and time-dependent ROC.The artificial neural network (ANN) demonstrated optimal cross-sectional performance (internal AUC: 0.854; external AUC: 0.878) with good calibration and clinical benefit. SHAP identified BRI, WBC, ALT, MCV, and AST as top contributors, with BRI showing the strongest impact. Longitudinal analysis revealed that integrating annual change rates and annual cumulative exposure of these five predictors achieved optimal discriminative ability (C-index: 0.847), with time-dependent AUCs of 0.853, 0.859, and 0.847 at 1, 3, and 5 years, respectively. CONCLUSION: BRI is significantly associated with MetS in perimenopausal and postmenopausal women. The ANN model provides an efficient cross-sectional screening tool, while incorporating longitudinal trajectories of BRI and key laboratory indicators enhances long-term MetS risk prediction.
7 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 →The New Zealand medical journal
Cancer risk and screening in transgender and gender-diverse individuals on gender-affirming hormone therapy: a review article for the Australasian context
AIM: We aimed to synthesise current evidence on the association between gender-affirming hormone therapy (GAHT) and cancer risk in transgender and gender-diverse (TGD) individuals and to provide evidence-based cancer screening recommendations for Australasian general practitioners. METHODS: A systematic review of epidemiological studies, case reports and clinical guidelines was conducted in accordance with PRISMA 2020 guidelines. Searches were performed across PubMed/MEDLINE, Embase, Scopus and the Cochrane Library for literature published up to December 2025. Key evidence sources were narratively synthesised to develop practical recommendations tailored to the Australasian context. RESULTS: The available evidence, although limited by short follow-up durations and small cohort sizes, does not demonstrate a consistent, statistically significant increase in common cancers among TGD individuals receiving GAHT. However, emerging case reports highlight novel clinical concerns, including malignancies in surgically constructed tissues (neophallus and neovagina). Breast cancer risk in trans women appears to increase with the duration of oestrogen therapy, though it remains lower than in cisgender women. Prostate cancer may present at a higher grade in trans women receiving oestrogen. Screening participation is consistently lower in TGD populations, often resulting in later-stage diagnoses. CONCLUSION: Cancer screening for TGD individuals should be guided by an organ-inventory approach, based on the organs a person has rather than their gender identity. Clinicians should maintain a low threshold for investigating suspicious lesions, particularly in surgically altered tissues. The development of culturally safe and inclusive primary care environments is paramount to improving screening uptake and ensuring equitable health outcomes for TGD communities in Australia and New Zealand.
31 May 2026
Read appraisal →Science (New York, N.Y.)
Strain-resilient intrinsically stretchable electrochemical biointerfaces
Stretchable bioelectronics promise seamless integration with dynamic tissues, yet their electrochemical performance often collapses under strain owing to cracking, interlayer delamination, and signal distortion. We introduce an intrinsically stretchable interface for resilient electrochemical sensing (SIRES) built from a strain-resilient conductor, an electrically tunable interlayer, and a stretchable functional coating. By offsetting strain-induced resistance increases with gains in active surface area, SIRES maintains near-constant resistance and high-fidelity electrochemical readouts under strains up to 300%. The platform supports voltammetric, potentiometric, and amperometric modalities and enables multiplexed molecular monitoring across dynamically deforming tissues in wearable and implantable formats. Its unified architecture provides delamination-resistant interfaces suitable for long-term use, and the design rules generalize to affinity-based transduction, establishing a pathway toward strain-resilient molecular sensing for precision diagnostics and therapy.
31 May 2026
Read appraisal →Medicine
Triple oral therapy combining metformin, SGLT-2 and DPP-4 inhibitors versus dual therapy in type 2 diabetes mellitus: A systematic review and meta-analysis
BACKGROUND: Triple oral therapy combining metformin, sodium-glucose cotransporter 2 inhibitor, and a dipeptidyl peptidase-4 inhibitor has been proposed as a synergistic approach to intensify glycemic control in patients with type 2 diabetes mellitus. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of triple therapy compared to dual therapy (metformin plus either sodium-glucose cotransporter 2 or dipeptidyl peptidase-4 inhibitor). METHODS: Following preferred reporting items for systematic review and meta-analysis guidelines, we searched PubMed, Embase, Scopus, and Web of Science through January 2026. Studies included randomized controlled trials comparing triple versus dual therapy in adults with type 2 diabetes mellitus. Outcomes included hemoglobin A1c (HbA1c), fasting plasma glucose, body weight, achievement of HbA1c < 7%, and adverse events (AEs). Pooled standardized mean differences (SMDs) and risk ratios (RRs) were calculated using random-effects models. RESULTS: Eight studies encompassing 2606 participants were included. Findings indicate triple therapy significantly reduced HbA1c levels compared to dual therapy, with a SMD of - 0.54 (95% confidence interval [CI]: -0.92 to -0.16; P = .005). Triple therapy resulted in greater reduction in fasting plasma glucose, with an SMD of -0.30 (95% CI: -0.62 to 0.01; P = .06). Patients on triple therapy were more likely to achieve HbA1c levels below 7% (RR: 2.02; 95% CI: 1.55-2.63; P < .0001). Weight reduction was modest, with an SMD: -0.14 (95% CI: -0.22 to -0.07; P = .0002). No significant differences were found in total AEs (RR = 0.97; P = .69) or hypoglycemia (RR = 1.32; P = .32), although there was higher discontinuation due to AEs (RR = 2.62; P = .03). CONCLUSION: Triple therapy offers superior glycemic control over dual therapy without major safety trade-offs, though tolerability may affect long-term adherence.
31 May 2026
Read appraisal →Lancet (London, England)
Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials
BACKGROUND: Evidence, including animal, clinical, and real-world studies in individuals with type 2 diabetes and/or obesity, suggests reduced risk of dementia and Alzheimer's disease after GLP-1 receptor agonist exposure. The evoke and evoke+ trials aimed to investigate the efficacy and safety of oral semaglutide in individuals with early Alzheimer's disease. METHODS: evoke and evoke+ were multicentre, randomised, double-blind, placebo-controlled phase 3 trials conducted across 566 sites in 40 countries. The trials assessed the efficacy and safety of oral semaglutide up to 14 mg once daily in participants with amyloid-confirmed Alzheimer's disease, aged 55-85 years, with mild cognitive impairment or mild dementia due to Alzheimer's disease. In evoke+, participants with significant small vessel pathology were included. Participants were randomly assigned (1:1) to once-daily semaglutide 14 mg (flexible dose) or placebo for up to 156 weeks. The primary endpoint was change in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score from baseline to week 104, assessed in all randomised participants. Safety was assessed in all randomised participants and reported for those receiving at least one dose of study drug. These trials were registered at ClinicalTrials.gov (NCT04777396 and NCT04777409); both trials have been discontinued due to negative clinical outcome. FINDINGS: Between May 18, 2021, and Sept 8, 2023, 9981 participants were screened, of whom 3808 were randomly assigned; 1855 in evoke (semaglutide, n=928; placebo, n=927) and 1953 in evoke+ (semaglutide, n=976; placebo, n=977). Mean age was 72·2 years (SD 7·1), and mean CDR-SB score was 3·7 (SD 1·6) at baseline. In evoke+, 54 (2·8%) participants had small vessel pathology. In evoke and evoke+, mean changes in CDR-SB score from baseline to week 104 were 2·3 (SE 0·1) and 2·2 (0·1) with semaglutide, compared with 2·3 (0·1) and 2·1 (0·1) with placebo (estimated difference -0·08 [95% CI -0·35 to 0·20], p=0·57 in evoke and 0·10 [-0·17 to 0·38], p=0·46 in evoke+). Treatment-emergent adverse events were reported in 1729 (91·2%) of 1896 participants receiving semaglutide versus 1613 (84·8%) of 1902 receiving placebo. There were five fatalities considered treatment-related by the investigators (one in the semaglutide group and four in the placebo group). INTERPRETATION: Oral semaglutide was not efficacious in slowing clinical progression in participants with early Alzheimer's disease. Safety and tolerability of semaglutide in early Alzheimer's disease is consistent with studies in other indications. FUNDING: Novo Nordisk.
31 May 2026
Read appraisal →Medicine
Associations of TyG-related indices with NAFLD-related outcomes: A systematic review and meta-analysis
BACKGROUND: The triglyceride-glucose (TyG) index and related composite indices have been increasingly studied as accessible metabolic markers for fatty liver disease. However, evidence remains difficult to interpret because different TyG-related indices have been evaluated across heterogeneous populations and nonalcoholic fatty liver disease (NAFLD)-related outcomes. We conducted a systematic review and meta-analysis to clarify the pooled associations that could be formally synthesized and to summarize the broader descriptive evidence. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, VIP Database, and China Biology Medicine Database from inception to December 2025. Observational studies evaluating the TyG index or related composite indices, including TyG-body mass index, TyG-waist circumference, and TyG-waist-to-height ratio, in relation to NAFLD-related outcomes were eligible. Random-effects meta-analyses were performed in R. Only studies with sufficient comparability in exposure operationalization, outcome definition, and effect-size reporting were quantitatively pooled; the remaining studies were retained in the descriptive synthesis. RESULTS: Nineteen studies involving 212,618 participants were included in the systematic review, including 16 cross-sectional studies and 3 cohort studies. Of these, 8 studies contributed to at least 1 quantitative synthesis. In continuous-scale analyses, higher TyG levels were associated with increased odds of NAFLD/steatosis (5 studies; pooled odds ratio [OR], 2.72; 95% confidence interval [CI], 2.08-3.55; I2 = 85.7%). In highest-versus-lowest analyses, the association remained significant (4 studies; pooled OR, 4.36; 95% CI, 3.39-5.61; I2 = 92.8%). TyG-body mass index (2 studies; pooled OR, 1.04; 95% CI, 1.03-1.05; I2 = 0.0%) and TyG-waist circumference (2 studies; pooled OR, 1.01; 95% CI, 1.01-1.01; I2 = 15.1%) were also positively associated with NAFLD/steatosis. TyG-waist-to-height ratio showed a positive association in supportive synthesis, but evidence for liver fibrosis and nonalcoholic steatohepatitis remained limited and was mainly descriptive. CONCLUSION: TyG-related indices were consistently associated with NAFLD/steatosis across the available literature. The basic TyG index had the broadest evidence base, whereas composite indices suggested possible additional value in selected settings. These markers may be useful for metabolic fatty liver risk stratification, but further studies with standardized outcome definitions and clearer exposure parameterization are needed.
31 May 2026
Read appraisal →PloS one
Probiotics, synbiotics and berberine in Type 2 diabetes mellitus: A systematic review, meta-analysis, and molecular dynamics simulation study
BACKGROUND: Type 2 diabetes mellitus is characterized by impaired regulation of blood glucose. Probiotics, synbiotics, and berberine (BBR) have been proposed as adjunctive interventions, but their overall effectiveness remains uncertain. OBJECTIVE: To evaluate the effects of these interventions on glycemic control and to explore a potential molecular interaction of BBR with a key carbohydrate-digesting enzyme. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted. Pooled effects were estimated for fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) using random-effects models. A subgroup analysis compared probiotics with placebo. An exploratory computational analysis examined the interaction of BBR with α-glucosidase. RESULTS: More than 30 trials involving over 2,000 participants were included. The pooled analysis showed significant but modest reductions in FPG (-0.71 mmol·L ⁻ ¹) and HbA1c (-0.19%), with substantial between-study variability. Probiotics alone also reduced FPG (approximately -0.80 mmol·L ⁻ ¹) and HbA1c (approximately -0.21%) compared with placebo. Computational analysis indicated weaker enzyme binding for BBR than for the reference inhibitor acarbose. CONCLUSIONS: Probiotics, synbiotics, and BBR provide statistically significant but clinically modest improvements in glycemic control. These findings support their use as adjunctive, rather than primary, therapeutic options and highlight the need for larger and longer trials with standardized interventions. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251116387, identifier CRD420251116387.
30 May 2026
Read appraisal →Pituitary
The hook effect in macroprolactinomas: tumor size thresholds, prolactin patterns, and clinical consequences - a systematic review.
PURPOSE: The immunoassay "hook effect" may cause spuriously low prolactin (PRL) measurements in patients with macroprolactinomas, leading to misdiagnosis and inappropriate management. This systematic review aimed to determine the tumor size threshold and distribution at which the hook effect has been documented, characterize the pre-dilution PRL pattern, quantify the magnitude of PRL underestimation, and assess the clinical consequences of unrecognized hook effect. METHODS: PubMed, Embase, Scopus, Google Scholar, and Web of Science were searched for articles published between January 2000 and August 2025. Studies reporting individual patient data with confirmed hook effect (pre- and post-dilution PRL, tumor size, and confirmation by serial dilution) were included. Quality was assessed using the JBI Critical Appraisal Checklist for Case Reports. Data were synthesized using individual patient data (IPD) quantitative methods. The review was registered on PROSPERO (CRD420261375863) and reported per PRISMA 2020 guidelines. RESULTS: Twenty-three patients from 14 studies across 9 countries were included, with a median maximum tumor diameter of 48.0 mm (IQR 35.5-55.0; range 22-100 mm); the smallest confirmed hook-effect tumor diameter measured 22 mm, reported in two independent cases, and 9 of 23 cases (39.1%) occurred in tumors below the conventional giant adenoma threshold (≥ 40 mm). Median pre-dilution PRL was 100.0 ng/mL (IQR 62.0-164.5), while median post-dilution PRL was 6,460.0 ng/mL (IQR 3,608.5-16,657.5), yielding a median fold increase of 64.7× (IQR 46.8-141.5). Pre-dilution PRL ranged from 26 to 200 ng/mL in 82.6% of cases (95% CI: 62.9-93.0%), values often misattributed to stalk effect. Unrecognized hook effect led to unnecessary surgery in 55.6% of cases with documented clinical outcomes. The hook effect was documented across multiple immunoassay platforms. CONCLUSIONS: Pre-dilution PRL values often overlap with the range attributed to stalk effect, and serial dilution testing should be considered for pituitary macroadenoma with PRL disproportionately low relative to tumor size, regardless of whether the tumor meets the giant adenoma threshold to prevent misdiagnosis, unnecessary surgical intervention and delayed initiation of dopamine agonist therapy.
30 May 2026
Read appraisal →Endocrine
Female sexual dysfunction in type 1 diabetes: a systematic review and meta-analysis
BACKGROUND: Female sexual dysfunction (FSD) in type 1 diabetes mellitus (T1DM) is an under-appreciated complication. Despite its profound impact on female health, including reduced quality of life and psychological distress, it remains underrepresented in major diabetes guidelines. Current data synthesis is limited, often excluding older populations or failing to compare diabetes subtypes. We aimed to collate the prevalence of FSD in T1DM, pool the risk of FSD in T1DM compared to controls, compare the risk in T1DM vs. T2DM and to investigate the impact of different variables on these effects. METHODS: PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched to identify cross-sectional/cohort studies including T1DM participants. Proportion of women with FSD in T1DM versus age-matched control/T2DM population (if reported), and population characteristics were extracted. RESULTS: The pooled analysis of 18 studies (N = 2476) indicated FSD prevalence of 37% in adults with T1DM (95% CI: 30%, 43%; I2 = 89%; random-effects model). Analysis restricted to studies (n = 12) using standard FSFI cut-off ≤ 26.5 confirmed the summary estimate as 34% (95% CI: 26%, 41%; I2 = 89%). Trim and fill analysis for publication bias found higher FSD risk in T1DM versus age-matched controls (N = 10, adjusted Risk ratio 2.10; 95% CI: 1.30, 3.39; p = 0.002; I2 = 76%). The higher incidence of FSD in T1DM versus T2DM on subgroup analysis (p-interaction < 0.01) appeared to be influenced by diabetes duration (p < 0.01, R2 = 70%). Depression and diabetes control indicators were among most consistent predictors of FSD, whereas continuous subcutaneous insulin infusion had a protective role. CONCLUSIONS: FSD is prevalent in approximately one-third of women with T1DM, with a higher risk compared to those with T2DM, likely due to earlier onset and longer diabetes duration. Comprehensive care strategies that address both the physiological and psychological aspects of T1DM are warranted to improve sexual health and overall well-being in affected women.
30 May 2026
Read appraisal →PloS one
Burden and patterns of dyslipidaemia among adult Ghanaians: A systematic review
BACKGROUND: Dyslipidaemia is a major modifiable risk factor for cardiovascular disease and has become an increasing public health concern in sub-Saharan Africa. Rapid urbanisation, dietary transitions, and sedentary lifestyles have contributed to the rising incidence of cardiometabolic diseases in Ghana. However, evidence on the overall burden and patterns of dyslipidaemia in adults remains unclear. This systematic review aimed to synthesise the evidence on the prevalence and lipid profile patterns of adult Ghanaians. METHODS: A comprehensive search of PubMed, Scopus, Web of Science, African Journals Online, Africa-Wide Information and African Index Medicus databases was conducted for studies published between January 1980 and November 2025. Eligible studies reported the prevalence or distribution of dyslipidaemia in Ghanaian adults (≥ 18 years). Two reviewers independently screened, extracted, and assessed the quality of included studies. Findings were synthesised narratively and summarised in descriptive tables and figures, due to heterogeneity in study designs and data reporting. RESULTS: Twenty-four studies published between 2003 and 2023, comprising approximately 11,400 participants, met the inclusion criteria. Across the included studies, the reported prevalence of dyslipidaemia ranged from 3.0% to 72.4%, reflecting differences in study populations, diagnostic criteria and study settings. Low high-density lipoprotein cholesterol (HDL-C) was the most frequent abnormality, followed by elevated total and low-density lipoprotein cholesterol (LDL-C), whereas hypertriglyceridaemia was the least common. Studies from southern and middle regions-particularly Ashanti, Brong-Ahafo, and Greater Accra-reported a higher dyslipidaemia prevalence than those from northern Ghana. Considerable variation in diagnostic criteria, study populations and sampling strategies limited comparability and precluded meta-analysis. CONCLUSION: Dyslipidaemia is common among adult Ghanaians, with low HDL-C emerging as the predominant abnormality. Methodological differences and sampling biases limit the precise estimation of the national burden, but the available evidence indicates a growing cardiometabolic risk. Future studies should prioritise community-based sampling and context-appropriate lipid thresholds to support evidence-based cardiovascular risk-reduction strategies.
30 May 2026
Read appraisal →Journal of neuro-oncology
Predicting late radiation-associated neurocognitive and endocrine toxicity in patients with brain tumors
PURPOSE: Neurocognitive and endocrine dysfunction are potential complications of cranial irradiation. However, risk factors are poorly understood, impeding accurate prognostication and exploration of potential preventive interventions. The objective of this study was to evaluate the prognostic value of various vascular and genotypic risk factors for the development of radiation-related toxicities. METHODS: This single-institution retrospective cohort study included patients with metastatic and malignant primary brain tumors who received cranial irradiation as part of their initial tumor-directed therapy. Demographic and treatment characteristics were collected, as well as putative vascular and genotypic risk factors. Univariate, multivariate, and machine-learning analyses were performed using five pre-specified measures of radiation-related toxicity. The primary outcome was change in mini-mental status exam (MMSE). RESULTS: Eighty patients (53% male, mean age 55.7, 53% primary and 44% metastatic brain tumors) were included. Elevated homocysteine and ApOE4 genotype were the strongest predictors of MMSE decline in the multivariate model (OR 3.96 [6.5-200, p < 0.001 and 2.85 [1.92-27.6], p = 0.004). Elevated homocysteine was associated white matter change on MRI and both physician and patient assessment. ApoE4 allele was associated with new endocrine deficiency, and physician assessment. An online nomogram provides risk predictions for each of the five late toxicity outcomes: ( https://afranklin22.shinyapps.io/PRMMSERadiationRiskFactors/ ) CONCLUSION: Two pre-treatment laboratory values (elevated homocysteine and ApOE genotype) were strongly associated with post-radiation neurocognitive and endocrine dysfunction using a variety of domains. Our predictive algorithm can aid clinicians in stratifying baseline risk and should be validated in prospective trials and with additional metrics of ND.
30 May 2026
Read appraisal →JMIR formative research
Self-Monitoring Risk Factors for Diabetic Foot Ulceration With the Feetchecker App: Mixed Methods Study
BACKGROUND: A prevalent and serious complication of diabetes mellitus is the development of diabetic foot ulcer (DFU). There is a need for effective solutions that help prevent DFU to support our increasingly stressed health care systems. The use of mobile health (mHealth) tools has been shown to improve awareness and effective self-care management skills in people at risk of developing diabetic foot ulceration. OBJECTIVE: In this study, we aimed to investigate the perceived usefulness, engagement, and overall user experience of the Feetchecker app, a self-monitoring mHealth app for people at risk of DFU. METHODS: A total of 24 patients (mean age 71, SD 8.6 years) with type 2 diabetes mellitus at risk of developing diabetic foot ulceration completed a 3-month evaluation period (70 recruited, 36 included, 12 dropped out) of a self-monitoring mobile app called Feetchecker app. A mixed methods approach was used to combine insights from app data with qualitative data from a pre- and postsurvey as well as interviews with patients and involved podiatrists. Data were analyzed using descriptive statistics and thematic analysis. We evaluated overall use of the app, patient engagement, and user experiences. RESULTS: Patients who fully completed the study conducted 393 feetchecks. In total, 7 patients sent in 9 pictures; all 7 were called for follow-up by a podiatrist. Overall, patients had a positive experience with the app and perceived the Feetchecker app as a valuable tool to monitor their feet for potential risk factors of DFU. Ease of use in performing a feetcheck and sending the podiatrist a picture was described as an important feature. Three main types of engagement with the Feetchecker app emerged: continuous, frequent, and no to little engagement. These patterns highlight enablers for self-monitoring such as ease-of-use, easy access to a podiatrist, and social support, as well as barriers such as digital skills and sustained engagement. Podiatrists highlighted the benefits of having patients report potential issues quicker and the ability to monitor their patients remotely. Challenges remain in integrating the promotion of the Feetchecker app into their consultations. CONCLUSIONS: The Feetchecker app supported patients in self-monitoring risk factors associated with DFU through routine checks and quick contact with a health care professional in case of a potential issue. Overall, patients described a positive user experience and considered the app helpful. While mHealth tools are not for everyone, user engagement for many patients was high and shows that such apps can offer support for people able to use them. Future research should focus on improving usability and engagement with the app as well as extend the way patients can communicate with health care professionals beyond a picture.
29 May 2026
Read appraisal →PloS one
Development and evaluation of AI model with deep learning for segmentation of extraocular muscles in thyroid eye disease
PURPOSE: To develop and evaluate an AI model for the segmentation of extraocular muscles (EOMs) using Magnetic Resonance Imaging (MRI). DESIGN: Single-center study with retrospective study. METHODS: The study included 52 patients with thyroid eye disease (TED) who underwent MRI examination of the orbital region at the Department of Ophthalmology, Osaka Metropolitan University, between October 2020 and June 2023. Manual labelling of all EOMs was performed on all slices. An AI model was created and compared with the manually labelled data using 5-fold cross validation on data sets of 12, 32, and 52 cases. The average signal intensity ratio (SIR) within the EOMs was measured. The primary outcome was the comparison of DICE similarity coefficients (DSC) as the agreement rate between AI's result and manual labelling amongst the three data sets (52 cases vs 32 cases vs 12 cases). The secondary outcome was the correlation of SIR between the AI and manual labelling. RESULTS: A significant difference in DSC was observed between the 12-, 32-, and 52-case data sets for the inferior rectus muscle and medial rectus muscle. A significant correlation was observed between the AI and manual labelling for SIR in all EOMs. CONCLUSIONS: An AI model was successfully developed for the automatic segmentation of EOMs. There was little measurement error between AI and manual labelling, and the AI model using 52 cases had improved measurement accuracy compared to the AI models using 32 and 12 cases.
29 May 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
Nutrition and growth of primary ciliary dyskinesia patients: a systematic review.
BACKGROUND: Growth, nutritional status and intake can be crucial for the management and prognosis of chronic lung diseases, including primary ciliary dyskinesia (PCD); yet research in PCD is scarce. In this study, we systematically reviewed the existing literature and summarised the evidence on growth, nutritional status and intake of patients with PCD. METHODS: We conducted searches in Medline, Embase, Scopus and PubMed limited to the past 20 years, due to changes in the diagnosis of PCD. Eligible studies included cross-sectional, case-control and prospective studies, and case series with >5 people that reported on the growth, nutritional status or intake of patients with PCD. We performed additional searches through reference list checking and in medRxiv for relevant preprints. The review was registered in PROSPERO (CRD420251065699). RESULTS: 50 studies were included in the qualitative synthesis. We observed variability in growth-related outcomes, with some studies reporting reduced z-score for height, body weight or BMI, while others reported no growth differences in patients with PCD. The prevalence of undernutrition ranged from 4 to 11%; underweight ranged from 0 to 50%. Overweight and obesity estimates ranged from 3 to 25%. The prevalence of vitamin D insufficiency was 54%, while deficiency was reported in 18-26% of study participants. Only three studies reported on the nutritional intake of patients with PCD. DISCUSSION: We observed considerable variability in growth-related outcomes and a lack of nutritional intake-related data in patients with PCD. The findings we noted related to malnutrition and vitamin D insufficiency/deficiency are alarming and warrant further investigation.
29 May 2026
Read appraisal →African journal of reproductive health
A systematic review of pregnancy outcomes and management in polycystic ovary syndrome
Polycystic Ovary Syndrome (PCOS), affects 5-20% of women of reproductive age, it is the leading cause of anovulatory infertility accounting for 70-90% of cases and resulting in lower natural conception rates and a significant contributor to adverse pregnancy outcomes. Following PRISMA 2020 guidelines, this systematic review synthesized evidence from 2014-2025, evaluating the evolving landscape of PCOS pregnancy management. It explores the relationship between PCOS and reproductive outcomes, details specific maternal and perinatal complications, and discusses the latest evidence-based interventions and emerging therapies to improve pregnancy outcomes and the long-term health of both mother and child. The findings revealed that the syndrome's pathophysiology driven by hyperandrogenism, insulin resistance, and obesity significantly increases the risks of early pregnancy loss, gestational diabetes, and pre-eclampsia. There is a paradigm shift toward individualized, multidisciplinary care. Evidence-based strategies highlight the superiority of letrozole for ovulation induction, the metabolic benefits of metformin, and the necessity of nuanced lifestyle interventions over simple weight-loss models. Furthermore, emerging research into immune-metabolic pathways, such as Interleukin-22, suggests novel therapeutic directions. The review concludes that recognizing PCOS as a high-risk obstetric condition and integrating early metabolic screening into standard care are essential to improving maternal and neonatal outcomes. Le syndrome des ovaires polykystiques (SOPK), qui touche 5 à 20 % des femmes en âge de procréer, est la principale cause d'infertilité anovulatoire (70 à 90 % des cas). Il entraîne une diminution des taux de conception naturelle et contribue significativement aux complications de la grossesse. Conformément aux recommandations PRISMA 2020, cette revue systématique a synthétisé les données probantes de 2014 à 2025, évaluant l'évolution de la prise en charge des grossesses chez les femmes atteintes de SOPK. Elle explore la relation entre le SOPK et les issues de la reproduction, détaille les complications maternelles et périnatales spécifiques et présente les interventions fondées sur des données probantes les plus récentes ainsi que les thérapies émergentes visant à améliorer les issues de grossesse et la santé à long terme de la mère et de l'enfant. Les résultats ont révélé que la physiopathologie du syndrome, caractérisée par un hyperandrogénisme, une résistance à l'insuline et une obésité, augmente significativement les risques de fausse couche précoce, de diabète gestationnel et de prééclampsie. On observe un changement de paradigme vers une prise en charge individualisée et multidisciplinaire. Les stratégies fondées sur des données probantes soulignent la supériorité du létrozole pour l'induction de l'ovulation, les bénéfices métaboliques de la metformine et la nécessité d'interventions nuancées sur le mode de vie plutôt que de simples programmes de perte de poids. De plus, les recherches émergentes sur les voies immunométaboliques, telles que l'interleukine-22, suggèrent de nouvelles pistes thérapeutiques. Cette revue conclut que la reconnaissance du SOPK comme une pathologie obstétricale à haut risque et l'intégration d'un dépistage métabolique précoce dans les soins courants sont essentielles pour améliorer les issues maternelles et néonatales.
29 May 2026
Read appraisal →European journal of clinical pharmacology
Efficacy and safety of Ongericimab in patients with hypercholesterolemia: a systematic review and meta-analysis
BACKGROUND: Hypercholesterolemia represents abnormally elevated cholesterol levels and constitutes a major modifiable risk factor for cardiovascular diseases (CVDs). Low-density lipoprotein cholesterol (LDL-C) reduction remains the primary therapeutic target. However, many high-risk patients fail to achieve recommended LDL-C targets with conventional lipid-lowering therapies. Ongericimab is a new humanized recombinant monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9). We aimed to evaluate the efficacy and safety of Ongericimab compared to placebo in patients with hypercholesterolemia. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Cochrane Library, Web of Science and Google Scholar through February 2025 for randomized controlled trials (RCTs) comparing Ongericimab versus placebo. Outcomes were pooled as mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CIs) using random-effects models. RESULTS: Five RCTs comprising 1421 patients were included. Ongericimab significantly reduced LDL-C across all dosing regimens: 150 mg every 2 weeks (MD -69.48%, 95% CI: -73.02 to -65.94), 300 mg every 4 weeks (MD -61.82%, 95% CI: -66.66 to -56.98), and 450 mg every 4 weeks (MD -73.11%, 95% CI: -89.56 to -56.65); all p < 0.00001. Significant reductions were also observed in lipoprotein(a) (MD range: -44.81% to -50.06%), apolipoprotein B, non-HDL cholesterol, triglycerides, and total cholesterol, along with significant increases in HDL cholesterol and apolipoprotein A1. Adverse event rates were comparable between groups, with a pooled reduction OR of 0.85 (95% CI: 0.73-0.99) for overall treatment-emergent adverse events, favoring Ongericimab. CONCLUSION: This meta-analysis demonstrates that Ongericimab is effective and safe for improving lipid parameters in patients with hypercholesterolemia and dyslipidemia. These findings support Ongericimab as a valuable therapeutic option for patients requiring additional LDL-C reduction beyond conventional therapy. Further long-term studies are recommended to confirm cardiovascular outcomes.
28 May 2026
Read appraisal →The Cochrane database of systematic reviews
Steroid avoidance or withdrawal for kidney transplant recipients.
RATIONALE: Steroid-sparing strategies aim to reduce the adverse effects associated with steroid use. The main concern has been a potential increase in the risk of rejection, as reported in previous systematic reviews. In recent years, improvements in immunosuppressive regimens and a significant decline in the incidence of acute rejection have renewed interest in steroid-sparing strategies. More contemporary trials suggest that reducing steroid exposure might be safe. This is an updated review, previously published in 2009 and 2016. OBJECTIVES: To evaluate the benefits and harms of steroid withdrawal or avoidance for kidney transplant recipients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register, CENTRAL, MEDLINE, Embase and two trials registers up to 29 April 2025. ELIGIBILITY CRITERIA: All randomised and quasi-randomised controlled trials that evaluated steroid avoidance or withdrawal after kidney transplantation. OUTCOMES: Critical outcomes were all-cause death, graft loss and biopsy-proven acute rejection. Important outcomes were post-transplant diabetes mellitus, cardiovascular events, infection, malignancy, and kidney function measures. RISK OF BIAS: Risk of bias was assessed with the Cochrane RoB 1 tool. SYNTHESIS METHODS: Assessment of risk of bias and data extraction were performed independently by at least two authors, and disagreements were resolved through discussion. Statistical analyses were performed using the random-effects model, and dichotomous outcomes were reported as risk ratios (RRs) and continuous outcomes as mean differences (MDs) with 95% confidence intervals (CIs). The certainty of the evidence was assessed using the GRADE approach. INCLUDED STUDIES: This updated review includes 53 studies (261 reports, 8317 randomised kidney transplant recipients). Of these, three studies were conducted in children (204 randomised participants). SYNTHESIS OF RESULTS: The overall certainty of the evidence of the included studies was low, ranging from moderate to very low. Factors downgraded on GRADE were primarily risk of bias and imprecision. Over 50% of the included studies did not adequately report random sequence generation or allocation concealment. Only five of 53 studies blinded participants and investigators. Incomplete outcome data was judged to be low in 26 studies, and 41 were free of selective reporting. Studies in adult kidney transplant recipients Steroid avoidance versus steroid maintenance The evidence is very uncertain about the effect of steroid avoidance on all-cause death up to one year (RR 0.84, 95% CI 0.51 to 1.39; 13 studies, 2126 participants; very-low-certainty evidence). Steroid avoidance may reduce death by one to five years (RR 0.61, 95% CI 0.39 to 0.96; 9 studies, 1607 participants; low-certainty evidence), and has little to no effect on graft loss censored for death up to one year (RR 0.95, 95% CI 0.62 to 1.46; moderate-certainty evidence). Steroid avoidance may increase the risk of biopsy-proven acute rejection up to one year (RR 1.58, 95% CI 1.11 to 2.25; 10 studies, 1845 participants; low-certainty evidence), although subgroup analysis showed no increase in risk when steroid avoidance was used in combination with tacrolimus, an antimetabolite and induction therapy. Steroid avoidance may reduce the risk of post-transplant diabetes mellitus up to five years (RR 0.70, 95% CI 0.59 to 0.84; 13 studies, 2390 participants; low-certainty evidence), but may have little to no effect on cardiovascular events (RR 0.73, 95% CI 0.46 to 1.18; 6 studies, 1417 participants; low-certainty evidence), infection (all) (RR 0.96, 95% CI 0.87 to 1.05; 11 studies, 2426 participants; low-certainty evidence), and probably has little to no effect on cytomegalovirus (CMV) infection (RR 1.01, 95% CI 0.80 to 1.27; 9 studies, 2155 participants; moderate-certainty evidence). Steroid withdrawal versus steroid maintenance Compared to steroid maintenance, steroid withdrawal may have little to no effect on all-cause death up to one year (RR 0.69, 95% CI 0.35 to 1.37; 9 studies, 1884 participants; low-certainty evidence) or one to five years (RR 1.17, 95% CI 0.67 to 2.03; 8 studies, 1189 participants; low-certainty evidence), and probably has little to no effect on graft loss censored for death up to one year (RR 1.19, 95% CI 0.72 to 1.96; 8 studies, 1854 participants; moderate-certainty evidence). Steroid withdrawal may have little to no effect on biopsy-proven acute rejection up to one year (RR 1.41, 95% CI 0.89 to 2.23; 5 studies, 1406 participants; low-certainty evidence). Steroid withdrawal probably has little to no effect on post-transplant diabetes mellitus up to five years (RR 0.82, 95% CI 0.55 to 1.21; 8 studies, 1647 participants; moderate-certainty evidence), and may have little to no effect on cardiovascular events up to five years (RR 0.91, 95% CI 0.42 to 1.97; 3 studies, 712 participants; low-certainty evidence) or infection (all) up to five years (RR 1.06, 95% CI 0.83 to 1.36; 6 studies, 1924 participants; low-certainty evidence). Steroid withdrawal probably has little to no effect on CMV infection up to five years (RR 1.10, 95% CI 0.85 to 1.43; 7 studies, 1956 participants; moderate-certainty evidence). Steroid avoidance versus steroid withdrawal The evidence is very uncertain regarding the effects of steroid avoidance compared with steroid withdrawal (4 studies, 466 randomised participants). Studies in paediatric kidney transplant recipients The evidence is very uncertain regarding the effects of steroid-sparing regimens in paediatric kidney transplant recipients (3 studies, 204 randomised participants). AUTHORS' CONCLUSIONS: There was no evidence to suggest a difference in patient death or graft loss up to one year after transplantation with steroid avoidance or withdrawal compared to maintenance, but steroid avoidance may reduce patient death at five years in adult kidney transplant recipients. Steroid avoidance may increase the risk of biopsy-proven acute rejection, but the risk may be similar when steroid avoidance is paired with tacrolimus, antimetabolite and induction therapy. The risk of biopsy-proven acute rejection in steroid withdrawal regimens may be similar to steroid maintenance regimens. We found no evidence to suggest differences in cardiovascular events or infection, but steroid avoidance compared to steroid maintenance may reduce the risk of post-transplant diabetes mellitus. FUNDING: LO is supported by a Río Hortega predoctoral fellowship from the Instituto de Salud Carlos III. REGISTRATION: Protocol and previous versions available via https://doi.org/10.1002/14651858.CD005632, https://doi.org/10.1002/14651858.CD005632.pub2, and https://doi.org/10.1002/14651858.CD005632.pub3.
27 May 2026
Read appraisal →The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
Integrated cell-free DNA and omics genetic scores for early detection of gestational diabetes: evidence from a nationwide multicenter study
BACKGROUND: Gestational diabetes mellitus (GDM) affects 15.6% of pregnancies globally, with Vietnam exhibiting one of the highest prevalences at 21%. Current diagnostic approaches at 24-28 weeks limit early intervention opportunities. We developed a multi-modal machine learning framework integrating cell-free DNA (cfDNA) structural features and genetic information for early GDM prediction at 10-12 weeks of gestation in Vietnamese women. METHODS: We analyzed blood samples from 1,086 pregnant women (435 GDM cases, 651 controls) collected at 9-12 weeks. Two parallel analytical pathways were employed: cfDNA profiling extracting cfDNA-specific features (fragment length, end motifs, GC content, nucleosome patterns), and whole-genome imputation generating predictions for ∼19,000 omics traits. Component scores were developed using TabPFN classifier and integrated via logistic regression into a unified master score. RESULTS: Genome-wide analysis identified five omics traits with significant GDM associations: HSD11B1, NEK7, COMMD10, KLRC4, and OCEL1. Component score optimization revealed distinct patterns-cfDNA scores peaked at 200 features (AUC = 71.53), while genetics-based scores improved with up to 2,000 omics traits (AUC = 77.21). The final master score, integrating three components (gbSC2000, gbSCBH, cfSC200), achieved AUCs of 86.82-87.19 across validation cohorts with 70% sensitivity and 89% specificity. Addition-deletion analysis confirmed that both cfDNA and genetic components provided essential, non-redundant contributions. CONCLUSIONS: This multi-modal framework demonstrates superior performance compared to single-biomarker approaches, enabling risk stratification from very low (4% GDM prevalence) to very high risk (90% prevalence). At the cutoff 0.4, the model identifies 78% of future GDM cases at 10-12 weeks while maintaining an 18% false-positive rate, potentially enabling early interventions to prevent GDM development and associated complications.
27 May 2026
Read appraisal →Neurology
Glucagon-like Peptide-1 Receptor Agonists and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy: Systematic Review and Meta-Analysis
BACKGROUND AND OBJECTIVES: Recent observational studies have reported conflicting evidence regarding an association between glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly semaglutide, and nonarteritic anterior ischemic optic neuropathy (NAION). We aimed to synthesize the pooled evidence assessing the association between GLP-1RA use and NAION risk. METHODS: Embase, Medline, and Cochrane CENTRAL databases were searched from inception to April 5, 2025. Observational studies and randomized controlled trials comparing NAION risk in GLP-1RA users with non-GLP-1RA users were included. Title/abstract and full-text screening were conducted in duplicate by 2 independent reviewers. Discrepancies were resolved through discussion or adjudication by a third reviewer. Risk of bias was assessed using the Risk of Bias In Nonrandomized Studies of Interventions (ROBINS-I) tool, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation framework. Pooled relative risks (RRs) were estimated using Bayesian random-effects models, incorporating half-normal, between-study, and weakly informative priors. The RR with 95% credible interval (CrI) was computed to analyze the development of NAION associated with GLP-1RA exposure. RESULTS: Five studies were included in the primary analysis, encompassing 1,593,554 patients (682,456 semaglutide users and 911,098 non-GLP-1RA users). Semaglutide use was associated with a high probability of increased risk of NAION compared with non-GLP-1RA use (RR: 2.52, 95% CrI [1.56, 4.72], I2: 57.8%, P(RR > 1): 99.9%). This association was particularly pronounced among patients with diabetes (RR: 2.41, 95% CrI [1.57, 4.10], I2: 47.2%, P(RR > 1): 99.9%). The overall incidence of NAION across 5 studies and 7 comparisons, encompassing 1,460,760 patients (semaglutide: 1,108,542; dulaglutide: 326,282; and exenatide: 25,936) and 272 NAION events (semaglutide: 198; dulaglutide: 54; and exenatide: 20) was 85 cases per 100,000 GLP-1RA users (95% CrI [29, 263], I2: 98.8%, P(incidence >0.00001): 100%). The incidence of NAION across 1,108,542 semaglutide users was 118 cases per 100,000 (95% CrI [32, 451], I2: 98.8%, P(incidence >0.00001): 100%). Leave-one-out sensitivity analyses consistently supported these findings. DISCUSSION: Low-to-moderate certainty evidence indicates that semaglutide significantly increases risk of NAION relative to non-GLP-1RAs, particularly among patients with diabetes. These findings warrant further investigation and should inform clinical risk-benefit discussions.
26 May 2026
Read appraisal →Renal failure
Unveiling the role of air pollution in diabetic kidney disease: an integrated study combining network toxicology, machine learning, and Mendelian randomization
Diabetic kidney disease (DKD) is a major and severe complication associated with diabetes. Air pollution is not only an independent risk factor for metabolic disorders but also an "accelerator" of DKD progression. This study seeks to investigate the molecular pathways connecting air pollution to DKD. Multiple databases were integrated to obtain potential target genes of 10 common air pollutants. The gene expression omnibus (GEO) database was employed to acquire DKD datasets. Differential expression analysis and weighted correlation network analysis (WGCNA) were performed to identify DKD-related genes. 12 machine learning algorithms were utilized to generate 113 unique predictive models, which were employed to select hub genes. Subsequently, MR, single-cell, gene set enrichment analysis (GSEA), and immune infiltration analyses were performed, followed by molecular docking of hub genes with air pollutants. A total of 714 targets were identified from 10 air pollutants, and 80 potential targets were identified from DKD transcriptomic data. Machine learning methods identified 5 hub genes that are closely associated with DKD. Mendelian randomization (MR) analysis indicated that, among the five hub genes, only NOS3 demonstrated a statistically significant causal association with DKD. Immune infiltration analysis found that hub genes were closely related to immune cells. Molecular docking validation indicated that certain air pollutants can stably bind with hub genes such as NOS3 and PTGS2. Air pollutants may be linked to alterations in various biological processes, potentially involving key genes such as ADH5, CASP3, NOS3, PTGS2, and SDHB, including potential metabolic reprogramming, inflammatory processes, and immune microenvironment changes.
26 May 2026
Read appraisal →European journal of clinical pharmacology
Dysesthesia associated with GLP-1 agonist therapies: data-mining analysis and literature review
PURPOSE: An increasing number of anecdotal reports on social media platforms and medical blogs describe dysesthesia, particularly burning skin sensations, in association with glucagon-like peptide-1 receptor (GLP-1R) agonists. We performed a pharmacovigilance data-mining analysis to characterise cases of dysesthesia related to GLP-1R. METHODS: We conducted a disproportionality analysis using VigiBase data on GLP-1R (Anatomical Therapeutic Chemical classification: ATC code A10BJ) and tirzepatide, focusing on the HLT (High Level Term) "Paraesthesia and dysesthesia", with the Information Component (IC). Additionally, we reviewed all narratives of dysesthesia cases in the French Pharmacovigilance database to extract clinical and pharmacological characteristics. A literature review complemented this analysis. RESULTS: Exenatide was significantly associated with hypoesthesia or oral paraesthesia, semaglutide and tirzepatide with hyperaesthesia, and semaglutide with dysesthesia and burning sensation. Dysesthesia appears to be dose-dependent, occurring more frequently at higher doses and with more potent GLP-1R, whether used for weight management or type 2 diabetes. Discontinuation was often performed, followed by spontaneous favourable outcomes, and cases of rechallenge were observed. Skin burning sensations represent a distinctive form of dysesthesia. CONCLUSION: Pharmacovigilance quantitative and qualitative data strengthens evidence for dysesthesias associated with GLP-1R agonists already observed in clinical trials of semaglutide, tirzepatide, and retatrutide.
25 May 2026
Read appraisal →Journal of medical systems
Machine Learning-Predicted Risk Trajectories for Incident Chronic Kidney Disease and Associations with Post-CKD Outcomes
Chronic kidney disease (CKD) is a progressive condition where risk accumulates before clinical onset. However, strategies for evaluating CKD risk remain limited, and the trajectories of risk over time are poorly understood. We enrolled 51,156 individuals without CKD in the University of California health system between 2012 and 2024. A debiased XGBoost model was developed to predict CKD risk, and the predicted probabilities from this model at each visit were used to derive risk trajectories through latent class growth mixture modeling. The model achieved a time-dependent area under the curve of 0.95 (95% confidence interval (CI), 0.94-0.96), a C-index of 0.93 (0.92-0.94), and a Brier score of 0.027 (0.026-0.028) for predicting 5-year CKD occurrence. Similar predictive performance was observed for 1 to 4 years. Longitudinal patterns of predicted CKD risk revealed three distinct trajectories: gradual (75.9%), progressive (10.1%), and rapid increase (14.0%). Compared to the gradual trajectory, the progressive trajectory was associated with a higher risk of estimated glomerular filtration rate (eGFR) decline of ≥ 25% (adjusted hazard ratio (HR) 1.31; 95% CI, 1.06-1.61) and ≥ 50% (HR 1.59; 95% CI, 1.09-2.31) following CKD onset. The progressive and rapid trajectory was linked to an increased risk of cardiovascular events (HR 1.84; 95% CI 1.18-2.91) and all-cause mortality (HR 2.36; 95% CI 1.49-3.73). Our machine learning model demonstrated strong predictive performance for incident CKD risk and identified three distinct risk trajectories that were associated with different post-CKD outcomes, highlighting the importance of early risk monitoring.
25 May 2026
Read appraisal →PloS one
A hybrid BiLSTM and rule-based system for integrated diabetes prediction and personalized guidance
Diabetes is a common chronic disease that needs early diagnosis and proper management to avoid severe complications. While current Artificial Intelligence (AI) tools generate predictive information, they often lack an integrated element for post-diagnosis support in order to fill in this critical gap in patient self-management. This research proposes and validates a hybrid System which aims to bridge this gap. The methodology is based on a novel, fused dataset (PIMA and Type 2 Diabetes) that was carefully preprocessed following a leakage-safe protocol in order to increase generalizability. The system architecture is a combination of two different critical components: Strong Bidirectional Long Short term Memory (BiLSTM) model for prediction and rule based engine for creating personalized lifestyle recommendations. In order to validate the efficacy of the BiLSTM model, seven traditional machine learning (ML) models and standard deep learning (DL) models have been comparatively tested, in which BiLSTM model has demonstrated a better generalization and prediction performance. Rigorous 10-fold cross validation was used to validate the system, which came up with an accuracy of 84.02%, precision of 87.89%, and recall of 80.50%. This research concludes that by successfully combining the high-performance predictive engine and real-time guidance module, it is possible to develop a holistic clinically relevant tool to close the loop between diagnosis and proactive self-management.
25 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 →International journal of yoga therapy
Systematic Review on the Effect of Yoga Nidra on Menstrual Disorders Among Adult Women
Menstrual disorders including amenorrhea, premenstrual syndrome, and dysmenorrhea significantly disrupt the normal menstrual cycle and negatively impact quality of life. Yoga nidra, a guided meditation technique, has been explored for its potential therapeutic benefits in menstrual health, although comprehensive evidence remains limited. The present systematic review aimed to assess the effect of yoga nidra on menstrual disorders by analyzing existing research and synthesizing findings. The review followed PRISMA guidelines and involved searches in PubMed/MEDLINE, Cochrane Library, Science Direct, and Google Scholar using keywords related to yoga nidra and menstrual disorders. Studies were selected based on predefined inclusion criteria. A total of seven randomized controlled trials were included. The findings indicated improvements across four key areas of women's health: (1) psychological well-being, (2) hormonal balance, (3) hematological profile, and (4) physiological parameters. These results suggest that yoga nidra may be an effective complementary therapy for managing menstrual disorders because of its noninvasive and low-cost nature. However, further high-quality randomized controlled trials are necessary to confirm its efficacy.
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 →Studies in health technology and informatics
Design and Evaluation of an Episodic Guideline-Driven Decision Support Engine
Clinical guidelines (GLs) standardize care but are complex to implement. Most clinical decision support systems (CDSSs) assume continuous use, which does not reflect real-world episodic workflows. We developed and evaluated e-Picard, a CDSS providing GL-based recommendations for episodic, on-demand consultations, enabling prospective decision support informed by retrospective quality assessment. At runtime, e-Picard analyzes offline patient data, computes fuzzy-logic-based compliance, identifies missed actions and generates context-specific recommendations. The system was applied to longitudinal geriatric data managed under pressure ulcers (PU) and diabetes (DM) GLs. Manual technical validation using 3,110 PU and 12,538 DM data instances (43 PU and 82 DM patients) achieved ≥99% correctness and up to 98% completeness. Retrospective simulation on 1,000 patients per domain (57,860 PU and 100,940 DM data instances) demonstrated potential adherence improvements from 68%-69% to 89%-97% for PU and from 14%-15% to 60%-87% for DM, with higher consultation frequencies increasing compliance and reducing care variability. These results demonstrate that episodic CDSSs can deliver accurate, context-aware support even under intermittent use.
24 May 2026
Read appraisal →Studies in health technology and informatics
Usability of Mobile Health Apps from the Patient Perspective: A Systematic Review
Mobile Health (mHealth) apps are widely used to support care, but patient-focused usability evidence remains fragmented. We conducted a systematic review (January 2012-September 2025) of PubMed, IEEE Xplore, and Scopus to identify studies assessing usability from the patient perspective using standardized questionnaires or structured interviews. Of 490 records retrieved, 146 studies met the inclusion criteria. Fifteen disease categories were represented, most commonly mental health, neurology, metabolic/endocrine, and oncology. Overall, 24 distinct usability assessment methods were reported, and most studies relied on a single method. Among standardized instruments, the System Usability Scale (SUS) was most common (50 studies, 34.3%); the mean SUS score across these studies was 76.37, above the acceptability benchmark of 68. Overall, mHealth apps were generally rated as usable by patients, but future work should adopt mHealth-specific standardized measures, enroll larger samples, and report methods transparently to enable benchmarking and inform better app design.
24 May 2026
Read appraisal →Journal of ethnopharmacology
Efficacy and safety of medicine-food homology Shenqi paste in older adults with diabetic sarcopenia: A randomized, double-blind, placebo-controlled trial
ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic sarcopenia (DS), an emerging diabetes complication, poses an increasing challenge to the elderly population. Shenqi paste (SQP) consists of 8 medicine-food homology substances: Astragalus membranaceus (Fisch.) Bge., Codonopsis pilosula (Franch.) Nannf., Polygonatum sibiricum Red., Dioscorea opposita Thunb., Poria cocos (Schw.) Wolf, Eucommia ulmoides Oliv., Hordeum vulgare L., and Ophiopogon japonicus (L.f.) Ker Gawl. SQP has shown potential benefits for sarcopenia in clinical practice. Its efficacy and safety in DS have not been validated in a randomized controlled trial. AIM OF THE STUDY: This study aimed to evaluate the efficacy, safety, and limitations, and provide insights into methods and strategies for utilizing SQP in DS management. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, community-dwelling older adults (≥60 years) with DS and spleen-kidney deficiency syndrome were allocated 1:1 to receive either SQP or placebo paste for 12 weeks. Primary outcomes were skeletal muscle mass index (SMI), handgrip strength, and five-time chair stand test (FCST) duration. Secondary outcomes included health-related scales and biochemical indicators. Assessments were conducted at the baseline (T0), week 6 (T1), and week 12 (T2). Safety evaluation included blood routine, liver and kidney function tests. Intention-to-treat analysis was applied to the primary outcomes data from all participants, with per-protocol analysis for sensitivity. Generalized estimating equations with covariate adjustment and t-tests or Wilcoxon rank-sum tests were used for statistical analysis. RESULTS: Of 90 randomized participants, the SQP group showed greater improvements in handgrip strength (T2: interact p < 0.001), SMI (T2: interact p < 0.001), and FCST (T2: interact p < 0.001) versus control. Secondary outcome measures of 74 participants, including frailty, nutrition, physical activity, sleep quality, depression, and TCM syndrome scores, significantly improved (p < 0.05), with significant fasting blood glucose reduction (T2: interact p = 0.018) and C-reactive protein decrease (T2: interact p < 0.001). There was no statistically significant difference in the change in the difference between the two groups in fasting insulin, glycated hemoglobin and insulin resistance index before and after intervention (p > 0.05). Within-group analysis demonstrated significant reductions of SQP group in inflammatory cytokines, and sarcopenia-related biomarkers (p < 0.001) post-intervention. No serious adverse events occurred. CONCLUSION: A 12-week SQP intervention enhanced muscle mass, strength, function, and metabolic and inflammatory profiles in older adults with DS, with good tolerability, supporting its potential as a safe, complementary therapy.
23 May 2026
Read appraisal →JMIR research protocols
Effect of a Personalized Mobile Health Intervention Using Artificial Intelligence (the WARIFA App) Versus a Nonpersonalized Intervention on User-Defined Objectives, Healthy Lifestyles, and Management of Type 1 Diabetes (T1D): Protocol for a Randomized Controlled Trial
BACKGROUND: Noncommunicable diseases are the leading cause of death worldwide. Cardiovascular and respiratory diseases, cancer, and type 2 diabetes share common risk factors that can be addressed: physical activity, a healthy diet, and avoiding smoking and alcohol. The Watching the Risk Factors (WARIFA) mobile health app was created for general health awareness and to support users in adopting healthier behaviors, as well as to support type 1 diabetes (T1D) self-management. OBJECTIVE: This study aims to evaluate the effectiveness of the WARIFA app with personalized artificial intelligence (AI)-driven messages, compared to a nonpersonalized version, in promoting health-related behavior change among the general population and individuals with T1D. METHODS: A total of 108 European participants, including individuals with T1D, were to be randomized (computer-generated sequence, double-blind, 1:1 ratio) to an intervention or control group. In the intervention group, participants used the WARIFA app with personalized messages and the use of AI. This applied to certain functionalities, such as providing recommendations on healthy dietary habits based on food logging and offering advice and encouragement through daily step tracking. It also provided risk predictions for cardiovascular and respiratory diseases, cancer, and type 2 diabetes. Participants with T1D were offered glucose predictions based on previous measurements. In the control group, participants used a WARIFA app without personalized messages or AI. Both WARIFA app versions offered access to air quality and UV index information for the geographical area, as well as displaying physical activity in the form of daily steps and sleep hours, as well as glucose results for participants with T1D. Both groups were provided with an activity monitor and used the WARIFA app for 8-12 weeks. The primary outcome is a self-defined goal, chosen from a set of proposed objectives at baseline and assessed at the end of the study using a Likert scale (1 to 10 points, 0 being no achievement at all and 10 being full achievement of the objective). Secondary outcomes include: engagement with the app, changes in lifestyle behavior, body composition, lipid profile, glycated hemoglobin (T1D only), hypoglycemic events (T1D only), and health-related quality of life, as well as acquired knowledge, self-efficacy, and usability. RESULTS: The clinical trial took place between January and June 2025. A total of 88 participants were finally recruited. The data are being analyzed, and the results are expected to be published in 2026. CONCLUSIONS: There is evidence that improving lifestyle behavior can prevent noncommunicable diseases. In this study, we aim to evaluate the effectiveness of the WARIFA app to improve lifestyle behaviors and T1D management. TRIAL REGISTRATION: ClinicalTrials.gov NCT06918444; https://clinicaltrials.gov/study/NCT06918444. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/84510.
23 May 2026
Read appraisal →BMJ open diabetes research & care
Topical therapies for diabetic foot ulcers: a systematic review and network meta-analysis
OBJECTIVE: Diabetic foot ulcer (DFU) is a life-threatening complication associated with high amputation and mortality rates. While numerous topical therapies exist, their comparative efficacy and safety remain unclear. We aimed to compare the efficacy and safety of topical therapies for DFUs to identify optimal treatment strategies. RESEARCH DESIGN AND METHODS: We searched PubMed, Embase, and CENTRAL from inception to February 1, 2025, for randomized clinical trials (RCTs) evaluating topical therapies for DFUs. We excluded non-topical interventions to ensure clinically relevant comparisons. A Bayesian network meta-analysis was performed. The primary outcome was wound healing rate. RESULTS: We included 51 RCTs involving 6161 patients and 23 interventions. 12 topical therapies, including placenta-derived products, platelet-related products, ON101, epidermal growth factor, and tissue-engineered skin substitutes, significantly improved wound healing rates vs standard of care (SOC). Placenta-derived products showed the greatest efficacy (OR 7.85 (95% credible interval (CrI) 4.62 to 14.15)) and were the only intervention to significantly reduce adverse events vs SOC (0.25 (95% CrI 0.10 to 0.60)). No interventions differed significantly from SOC in time to wound healing, serious adverse events, or infections. CONCLUSIONS: Placenta-derived products and other biological or advanced topical therapies may demonstrate greater efficacy than the SOC in facilitating the healing of DFUs. Nevertheless, the certainty of evidence for most comparisons remains in the low-to-moderate range. These findings suggest potential benefits in integrating these therapies into the management of DFUs. However, high-quality RCTs are necessary to verify long-term outcomes.
23 May 2026
Read appraisal →ACS sensors
Recent Advances in Electrospun Nanofiber-Based Wearable Sweat Sensors
Electrospun nanofibers, owing to their high porosity, flexibility, straightforward fabrication, and tunable physicochemical properties, have been widely employed in wearable sensors for gas detection, temperature monitoring, pulse measurement, gesture recognition, and other applications. In recent years, research on employing electrospun nanofibers in wearable sweat sensors has grown substantially. This paper provides the first comprehensive review of the research progress in electrospun nanofiber-based wearable sweat sensors, focusing on structural design, device fabrication, and potential applications. The review begins with a concise introduction to the fundamental aspects of electrospun nanofibers, including their formation principles, processing routes, material selection, and morphological characteristics. It then delves into the key components involved in constructing wearable sweat sensors based on electrospun nanofibers, such as reagent immobilization matrices, signal-enhancing materials, flexible substrates, and sweat collection components. A detailed analysis of the functional mechanisms of nanofibers in these contexts is provided, accompanied by an assessment of their advantages and limitations. Furthermore, recent applications of electrospun nanofiber-based wearable sweat sensors are systematically reviewed. Finally, the review discusses the challenges and potential future applications of electrospun nanofibers in wearable sweat sensors. This comprehensive overview aims to keep researchers informed of the latest advancements in the field and to stimulate further innovative developments.
23 May 2026
Read appraisal →The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
Integrated metabolic and inflammatory biomarkers for early association and prediction of adverse pregnancy outcomes: a multicenter validation study
BACKGROUND: Adverse pregnancy outcomes (APOs) affect long-term maternal and offspring health. Conventional metabolic markers, including the triglyceride-glucose (TyG) index, inadequately capture pregnancy-related immuno-inflammatory dysregulation. We propose a composite index, TyNIR, integrating metabolic and inflammatory parameters, and assess its associations with APOs and predictive performance using machine learning. METHODS: Data were collected from two tertiary centers in Fujian, China (2023-2025), including 1,741 pregnancies and an external validation cohort of 300. Early-pregnancy parameters were used to derive TyNIR. Primary outcomes were gestational diabetes mellitus (GDM), gestational hypertension (GH), preterm birth (PB), low birth weight (LBW), and premature rupture of membranes (PROM). Multivariable regression, subgroup, and interaction analyses assessed associations between TyNIR and APOs. A feature selection approach developed the PREMIER model, which was compared with TyG and other models and externally validated. RESULTS: TyNIR was positively associated with GDM, GH, and PB. After adjustment, the highest quartile showed increased risks, with odds ratios (ORs) of 3.86 (95% CI 2.33-6.39) for GDM, 3.05 (1.74-5.36) for GH, and 3.45 (1.24-9.66) for PB. No associations were observed for LBW or PROM. The PREMIER model achieved area under the curve (AUC) values of 0.710 ± 0.031, 0.736 ± 0.040, and 0.742 ± 0.073, outperforming TyG and other models. External validation confirmed consistent associations and superior predictive performance. CONCLUSIONS: TyNIR consistently predicts risks of GDM, GH, and PB. The TyNIR-based PREMIER model shows robust predictive performance with external validation. These findings support early identification of high-risk pregnancies and may guide personalized management of APOs.
22 May 2026
Read appraisal →Current obesity reports
Burden of Intrapancreatic Fat Deposition in Type 2 Diabetes and the Role of Obesity: A Systematic Review and Meta-Analysis
BACKGROUND: Growing evidence supports a role for high intrapancreatic fat deposition (IPFD) in the pathogenesis of type 2 diabetes mellitus (T2DM); however, the magnitude of this association and the extent to which it is influenced by body mass index (BMI), liver fat content (LFC), and age remain uncertain. OBJECTIVE: To quantitatively evaluate IPFD measured by magnetic resonance imaging (MRI) in individuals with T2DM and to investigate study-level factors contributing to between-study variability. METHODS: We systematically searched PubMed and Embase for observational studies comparing MRI-measured IPFD in individuals with T2DM versus non-diabetic controls, excluding studies in which IPFD quantification was performed using AI-based models. Pooled standardized mean differences (SMDs) were estimated using a restricted maximum likelihood approach with Hartung-Knapp adjustment. Heterogeneity was explored through subgroup, meta-regression, and sensitivity analyses. RESULTS: Thirty studies (n=3,980) were included. Individuals with T2DM had significantly higher IPFD than non-diabetic controls (SMD 1.13, 95% CI 0.74 to 1.51), with no significant differences when stratified by pancreatic region, MRI technique, geographic region, sample size, and risk of bias. In multivariable models, BMI remained the only consistent moderating covariate, and the excess IPFD in T2DM persisted after adjusting for BMI, LFC, and age (intercept=0.797, p=0.010, false discovery rate-adjusted p=0.018). Advanced heterogeneity exploration identified no structural outliers, and the pooled effect size remained consistent across multiple sensitivity analyses. CONCLUSION: T2DM is associated with substantially higher MRI-quantified IPFD, independent of study-level differences in BMI, LFC, and age. Although causality cannot be inferred, these findings support the hypothesis that IPFD may be involved in the underlying mechanism of T2DM. They also suggest that high IPFD could represent a metabolic hallmark, with potential implications for risk stratification and therapeutic targeting.
22 May 2026
Read appraisal →BMJ open
Patient preferences and willingness-to-pay for AI-enabled blended type 2 diabetes care by digital experience and socioeconomic status: a discrete-choice experiment in China
OBJECTIVES: To elicit stated preferences and willingness-to-pay (WTP) for artificial intelligence (AI)-enabled blended care in type 2 diabetes mellitus (T2DM), and to examine preference heterogeneity by digital experience and socioeconomic status (SES). DESIGN: Cross-sectional discrete choice experiment (DCE). SETTING: 12 community health centres in Jiaozuo and Puyang, Henan Province, China. Data were collected between June and August 2025. PARTICIPANTS: 423 adults diagnosed with T2DM for at least 6 months, recruited using consecutive convenience sampling from routine follow-up appointments. Of 769 participants who completed the survey, 346 were excluded following prespecified data quality criteria (retention rate: 55.0%). OUTCOME MEASURES: Outcome measures included preference weights and WTP (in Chinese Yuan, ¥) for five DCE attributes: monthly subscription fee, recommendation source, feedback modality, in-person follow-up frequency and expert oversight, estimated using mixed logit models. Simulated uptake probabilities for tailored service packages across four user profiles were computed. RESULTS: Among 423 participants, 80.6% had never used AI tools. Price was the dominant driver of choice (62.7% relative attribute importance). Profound preference heterogeneity emerged across subgroups: rural residents (n=78) were highly price-sensitive but preferred physician endorsement (WTP ¥17.58 (US$2.55), 95% CI ¥5.98 to ¥29.17); female participants (n=224) valued guideline recommendations (WTP ¥18.45 (US$2.67), 95% CI ¥7.81 to ¥29.40); and diabetes app users (n=34) were the least price-sensitive but showed a negative preference for AI instant feedback, instead preferring human dietitian feedback. Expert oversight carried a consistent negative WTP across all profiles. Targeting tailored service bundles to intended subgroups increased uptake by 8-16 percentage points compared with non-targeted bundles. CONCLUSIONS: A 'digital experience paradox' exists whereby digitally experienced users view human interaction as a premium service, while underserved groups rely on specific trust markers such as physician endorsement. To avoid widening the digital divide, AI-enabled blended diabetes care must move beyond standardised models towards configurable, equity-driven service pathways.
22 May 2026
Read appraisal →Cell systems
GFETM: Genome foundation-based embedded topic model for scATAC-seq modeling
Single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq) enables investigation of open chromatin landscapes at single-cell resolution. However, analyzing scATAC-seq data remains challenging due to inherent sparsity and noise. Genome foundation models (GFMs), pre-trained on extensive DNA sequence datasets, have demonstrated effectiveness in genome analysis. Because open chromatin regions (OCRs) harbor salient sequence features, we hypothesized that leveraging GFMs' sequence embeddings could enhance scATAC-seq modeling accuracy and generalizability. We introduce the genome foundation embedded topic model (GFETM), an interpretable deep learning framework combining GFMs with the embedded topic model (ETM) for scATAC-seq analysis. By integrating DNA sequence embeddings extracted by a GFM from OCRs, GFETM demonstrates superior accuracy and generalizability and captures cell-state-specific transcription factor (TF) activity with both zero-shot inference and attention-mechanism analysis. Finally, the topic mixtures inferred by GFETM reveal biologically meaningful epigenomic signatures of kidney diabetes. A record of this paper's transparent peer review process is included in the supplemental information.
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 →Postgraduate medical journal
Efficacy of tirzepatide in glycemic control and weight management in adults with type 2 diabetes: a systematic review and meta-analysis of real-world studies
A systematic review and meta-analysis of real-world studies on tirzepatide is essential to strengthen evidence of its effectiveness in improving glycated hemoglobin (HbA1c) and body weight in patients with type 2 diabetes. 13 real-world studies (N = 89 296; duration 3-18 months) with moderate to serious bias revealed a mean HbA1c reduction of 0.91% (95% confidence interval [CI]: -1.04 to -0.79), weight loss of 9.7 kg (95% CI: -14.05 to -5.35), and body mass index decrease of 2.09 kg/m2 (95% CI: -3.27 to -0.92). Overall, 64% of tirzepatide users reached HbA1c <7%. Furthermore, tirzepatide lowered HbA1c (mean difference [MD] -0.38%; 95% CI: -0.44 to -0.33) and body weight (MD -6.27 kg; 95% CI: -9.22 to -0.33) more than the control. 47%, 23%, 9%, and 4% of tirzepatide users lost ≥5%, ≥10%, ≥15%, and ≥ 20% of their baseline weight, respectively. Tirzepatide's effects on HbA1c and weight in observational studies support clinical trial findings.
22 May 2026
Read appraisal →Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Effects of Semaglutide on Cognitive Function in People With HIV: A Randomized, Controlled Trial
BACKGROUND: People with human immunodeficiency virus (HIV, PWH) are at higher risk for visceral adiposity, enhanced inflammation, and cognitive decline than controls who do not have HIV. We previously demonstrated that PWH with lipohypertrophy had a decrease in weight, visceral adipose tissue, and several inflammatory markers after receiving semaglutide, a glucagon-like peptide-1 receptor agonist. Our aim was to investigate the effect of semaglutide on cognitive function in PWH and the possible mediation of this effect by changes in adiposity or inflammation. METHODS: In this randomized, double-blind, placebo-controlled phase 2b clinical trial, PWH on antiretroviral therapy were randomized 1:1 to receive 32 weeks of subcutaneous semaglutide or placebo. The primary outcome was the change in cognitive function at 32 weeks. Secondary measures included changes in body composition and inflammatory markers. Causal mediation analysis assessed semaglutide's direct and indirect effects on Cognivue scores through changes in adiposity and inflammation. RESULTS: 108 participants were included (54 per arm); 65% were non-White, 40% were female, and median age was 53 years. Compared with placebo, PWH on semaglutide significantly increased visuospatial, naming/language, and delayed recall scores at 32 weeks (P = .01, .05, and .04, respectively). After adjusting for sex and absolute CD4 count, only visuospatial score remained statistically significant (P = .05). Semaglutide's total natural direct effect maintained a positive effect on the visuospatial score while accounting for potential changes in high-sensitivity C-reactive protein and soluble CD163 levels (P = .04). CONCLUSIONS: Semaglutide may have a beneficial impact on visuospatial cognitive function in PWH through its effect on inflammation. Clinical Trials Registration . NCT04019197.
22 May 2026
Read appraisal →Journal of medical Internet research
A Digital Toolkit for Weight Loss Maintenance in European Adults (NoHoW): 2×2 Factorial Randomized Controlled Trial
BACKGROUND: Digital approaches to weight management have the potential to produce cost-effective and scalable weight management solutions. Effective behavior change interventions typically promote self-regulation of energy balance behaviors, which may be enhanced by incorporating emotion regulation strategies. OBJECTIVE: This study aimed to evaluate the effectiveness of a digital behavior change toolkit for weight loss maintenance in European adults who had achieved ≥5% weight loss in the previous 12 months. We hypothesized that a combined intervention targeting self-regulation or motivation and emotion regulation would be more effective than either component alone, and that each would outperform an active control. METHODS: The Navigating to a Healthier Weight (NoHoW) trial was a 2×2 factorial randomized, single-blind, controlled trial involving 1627 adults who had achieved ≥5% weight loss in the previous 12 months (initial BMI ≥25 kg/m2) across 3 European centers (the United Kingdom, Denmark, and Portugal). The trial evaluated a digital toolkit for weight management subsequent to an initial ≥5% weight loss in the prior 12 months. Participants were assigned using adaptive stratified sampling to one of four groups: (1) self-regulation or motivation (n=403), (2) emotion regulation (n=416), (3) combined motivation and emotion (n=408), or (4) active control (generic content, regular self-weighing, and Fitbit use, n=400). The primary outcome was weight change from baseline to 12 months. Prespecified secondary outcomes included cardiometabolic markers. Linear models adjusted for recruitment center, sex, age group, BMI group, and pretrial weight loss. Subgroup analyses were conducted by sex. RESULTS: At 12 months, 76% (364/1627) of participants remained in the study. In the primary ITT analysis in all participants, none of the intervention arms (motivation, emotion, or combined) differed significantly from the active control for weight change at 12 months. Completer and per-protocol analyses produced similar patterns and did not change the overall interpretation. In the per-protocol sample, men regained 0.14 kg, and women regained 0.54 kg of their pretrial weight loss. Subgroup analyses indicated a small effect of the motivation intervention in men, but this was not clinically meaningful and did not alter the primary null findings. Nearly half of ITT participants regained weight, and no significant intervention effects were observed for cardiometabolic secondary outcomes. CONCLUSIONS: The NoHoW trial was the first large-scale, multicountry 2×2 factorial randomized controlled trial to evaluate a digital-only toolkit based on self-regulation or motivation and emotion regulation techniques for weight loss maintenance. NoHoW found no evidence in the primary ITT analysis that digital interventions targeting self-regulation or emotion regulation improved weight loss maintenance compared with the active control. A small subgroup effect in men should be interpreted cautiously and does not change this conclusion. The trial provides evidence on both the limitations and potential of digital behavior change interventions for long-term weight outcomes. Future digital interventions may benefit from enhanced engagement and tailored content to improve long-term weight outcomes.
21 May 2026
Read appraisal →European radiology experimental
MRI radiomics-based approach to predict pituitary neuroendocrine tumor invasiveness
OBJECTIVES: To assess the diagnostic potential of magnetic resonance imaging (MRI) radiomics and machine learning models using T2-weighted and contrast-enhanced (CE)-T1-weighted images, individually and combined, to predict the invasiveness of pituitary neuroendocrine tumors (PitNETs). MATERIALS AND METHODS: Patients with macro-PitNETs were retrospectively enrolled from 2019 to 2022. Radiomic features were extracted from manually segmented lesions on preoperative T2-weighted and CE-T1-weighted images and, after a feature selection step, used to assess invasiveness, defined following Trouillas' classification. Five machine learning models (logistic regression, random forest, gradient boosting, AdaBoost, XGBoost) were trained using CE-T1-weighted, T2-weighted, and CE-T1-weighted plus T2-weighted features. Performance was evaluated on a test set using the area under the receiver operating characteristic curve (AUC). RESULTS: Two hundred patients were included in the study: 95 PitNETs were noninvasive (74 grade 1a; 21 grade 1b) and 105 invasive (70 grade 2a; 35 grade 2b). A total of 102 radiomic features were extracted per sequence. The best-performing model was the XGBoost, using five combined CE-T1-weighted and T2-weighted features, with an AUC of 0.85 (95% confidence interval: 0.75‒0.95). Lower AUC values were obtained for logistic regression using CE-T1-weighted images (0.80) and AdaBoost using T2-weighted images (0.78). CONCLUSION: The XGBoost model, incorporating tumor shape, texture, and first-order features extracted from both CE-T1-weighted and T2-weighted MRI, showed high performance in predicting PitNETs invasiveness. This radiomic model might help identify tumors with a higher risk of disease persistence, recurrence, or progression. RELEVANCE STATEMENT: The radiomic model based on contrast-enhanced T1-weighted and T2-weighted MRI demonstrated high discriminative ability in predicting invasiveness of pituitary neuroendocrine tumors and could aid in identifying tumors that may be at higher risk for recurrence or progression, ultimately improving patient outcomes through personalized treatment strategies. KEY POINTS: Pituitary neuroendocrine tumors (PitNETs) represent a significant challenge in clinical practice. Accurate preoperative prediction of PitNET invasiveness is crucial for surgery and prognosis. Contrast-enhanced T1-weighted and T2-weighted MRI-based radiomic model effectively predicts PitNET invasiveness. The developed radiomic model could help optimize individualized treatment decisions before surgery.
21 May 2026
Read appraisal →Oral health & preventive dentistry
Screening for Periodontitis Using Blood Biomarkers and Demographic Data: A Machine Learning Study
PURPOSE: Periodontitis is a common chronic disease associated with systemic conditions such as diabetes and cardiovascular disease. Diagnosis typically relies on dental examinations and radiographs, which may be underutilised by individuals who avoid, delay, or lack dental care. This study evaluated the potential of routine blood biomarkers and demographic data for screening moderate-to-severe periodontitis. METHODS AND MATERIALS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 adults aged ≥ 30 years (N = 3,338). Periodontal status was classified using CDC/AAP definitions. An XGBoost classifier was trained on 77 features spanning demographics, complete blood count, glycemic and hemo-globin markers, heavy metals, and additional biochemical assays. Model performance was assessed with Accuracy, Precision, Recall, and F1 score. SHapley Additive exPlanations (SHAP) were used for interpretability. Subgroup analyses were conducted by age and gender. RESULTS: The model achieved 61.1% Accuracy, 57.4% Precision, 94.6% Recall, and an F1 score of 71.5%. Performance was higher in males (F1 = 78.2) than in females (F1 = 63.9%). SHAP identified age, gender, blood cadmium, blood lead, and glycohaemoglobin (HbA1c) as top predictors. CONCLUSION: Routine blood biomarkers and demographics can be leveraged for non-dental screening of periodontitis, offering a feasible preventive strategy in primary care. The model achieved high recall, minimising false negatives, and identified biologically plausible predictors. This approach may help flag at-risk individuals, particularly in underserved populations, and support integration of oral health into general medical care.
21 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Sustained Action of Imapextide, A Glucagon-Like Peptide-1 Receptor Antagonist, in Healthy Volunteers
CONTEXT: After weight-loss surgery, some patients experience postbariatric hypoglycemia (PBH). Although PBH is customarily managed by dietary modifications with continuous glucose monitoring, advanced treatment options are needed. Imapextide is a sustained-action, selective, reversible glucagon-like peptide-1 (GLP-1) receptor antagonist designed for once-weekly administration for PBH treatment. OBJECTIVE: This work aimed to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple ascending doses (SAD/MAD) of imapextide in healthy volunteers (HVs). METHODS: This 3-part, phase 1, double-blind study enrolled healthy adults. In the SAD/MAD parts, randomly assigned participants (3:1) received subcutaneous imapextide (SAD, 10-200 mg; MAD, 10-30 mg once weekly, 4 doses) or placebo. The primary end point was safety/tolerability (treatment-emergent adverse events [TEAEs]). PK (SAD/MAD; time-to-maximal concentration [tmax] and half-life [t1/2]) and PD (MAD; GLP-1 and glycemic parameters during a mixed meal tolerance test [MMTT]) were assessed. Imapextide drug-drug interactions (DDIs) of OATP1B1/OATP1B3 inhibition and accelerated gastric emptying were evaluated with coproporphyrin-I, rosuvastatin, and acetaminophen. RESULTS: Overall, 69 HVs were randomly assigned (32 SAD, 23 MAD, 14 DDIs). Imapextide TEAE rates ranged from 33.3% to 50.0% (SAD), 33.3% to 100% (MAD), and 14.3% (DDIs) across cohorts. The most common TEAEs included injection site erythema (SAD, MAD) and injection site swelling (MAD). Imapextide exposure was dose proportional (median tmax 24-48 hours; mean t1/2 ∼90 hours). During the MMTT, imapextide increased GLP-1 concentrations at early time points, while effects on other glycemic parameters were variable. Minimal nonclinically relevant DDIs occurred with rosuvastatin. Imapextide slightly accelerated gastric emptying. CONCLUSION: Imapextide was generally well tolerated in HVs. PK findings supported weekly dosing. PD showed consistent effects on GLP-1 levels, supporting a potential role for imapextide in modulating PBH pathophysiology.
21 May 2026
Read appraisal →JMIR medical informatics
Machine Learning Prediction Model for Dyslipidemia and Its Association With Atherothrombotic Events in 3 Independent Cohorts From South Korea, Japan, and the United Kingdom: Algorithm Development and Validation Study
BACKGROUND: Dyslipidemia is a multifactorial and complex condition that warrants investigation through advanced analytical approaches such as machine learning (ML). Few previous ML studies predicting dyslipidemia have been validated across multiple international populations. OBJECTIVE: This study aimed to develop an ML model to predict the 5-year incidence of dyslipidemia using routinely collected health examination data. To ensure generalizability, the model was externally validated in populations from South Korea, Japan, and the United Kingdom. Furthermore, the clinical relevance of the model-derived risk was evaluated by examining its association with atherosclerotic outcomes, including acute myocardial infarction and cerebral infarction. METHODS: This study was conducted using 3 independent, large-scale, population-based cohorts. The discovery cohort from South Korea (n=471,650) was used for model training and internal validation, while 2 validation cohorts from Japan (validation A; n=7,255,685) and the United Kingdom (validation B; n=408,725) were used for external validation. We evaluated various ML-based models using 23 features extracted from regular health screening data to predict the new onset of dyslipidemia within 5 years. Shapley Additive Explanations values were calculated to assess feature importance. To ensure the robustness of the proposed ML model, we evaluated the risk of atherothrombotic events (acute myocardial infarction or cerebral infarction) based on the model probability (tertiles; T1, T2, and T3) using a Cox proportional hazards model. RESULTS: In the discovery cohort, soft-voting ensemble learning with Light Gradient Boosting Machine and categorical boosting exhibited performance metrics of area under the receiver operating characteristic curve (AUROC) of 0.783, precision of 37.9%, and area under the precision-recall curve of 0.469. The model showed moderate discriminatory performance in the external validation cohorts (cohort A: AUROC 0.744; precision 27.2%; and cohort B: AUROC 0.687; precision 5.07%). Shapley Additive Explanations value analysis identified smoking, alcohol intake, and physical activity as the most important features for predicting dyslipidemia. Finally, a higher model probability (T3 vs reference) was pronounced with an increased risk of acute myocardial infarction (adjusted hazard ratio 2.34, 95% CI 1.84-2.97) and cerebral infarction (adjusted hazard ratio 2.43, 95% CI 2.19-2.71). CONCLUSIONS: This multinational study developed and validated an ML-based model using routine health checkup data to predict the 5-year risk of new-onset dyslipidemia, which was also associated with atherosclerotic events.
21 May 2026
Read appraisal →Journal of the American Heart Association
Effect of Different Types of Whole Dietary Pulses on Established Therapeutic Lipid Targets for Cardiovascular Risk Reduction: An Updated Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials
BACKGROUND: Although dietary pulses are recognized by major clinical practice guidelines to reduce cholesterol and coronary heart disease risk, intake is low. There are no health claims for any pulse for cholesterol reduction, which could support uptake. We therefore conducted a systematic review and dose-response meta-analysis of randomized trials of the effect of different types of whole dietary pulses on lipid targets. METHODS: MEDLINE, Embase, and the Cochrane Library were searched through March 2025 for trials ≥3 weeks. The primary outcome was low-density lipoprotein-cholesterol. Secondary outcomes were other lipid targets. Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Thirty-eight trials (52 trial comparisons, n=2095) with a median of 6 weeks and dose of 130 g/d (0.5-0.67 cup/d) showed that whole dietary pulses decreased low-density lipoprotein-cholesterol (mean difference, -0.14 mmol/L [95% CI, -0.19 to -0.08]), non-high-density lipoprotein-cholesterol (-0.22 mmol/L [95% CI, -0.30 to -0.14]), apoB (apolipoprotein B) (-0.08 g/L [95% CI, -0.13 to -0.03]) and high-density lipoprotein-cholesterol (-0.03 mmol/L [95% CI, -0.05 to -0.01]) with no effects on other lipids. Analyses by pulse type showed similar results. A linear inverse relationship was shown for beans up to 1 cup/d for low-density lipoprotein-cholesterol (coefficient, -0.25 mmol/L/0.5 cup [95% CI, -0.48 to -0.02]) and non-high-density lipoprotein-cholesterol (-0.45 mmol/L/0.5 cup [95% CI, -0.71 to -0.18]). Grading of Recommendations Assessment, Development, and Evaluation was moderate-to-high for all outcomes, except apoB (very low). CONCLUSIONS: Whole dietary pulses likely result in small important-to-moderate reductions in lipid targets and trivial reductions in high-density lipoprotein-cholesterol. Similar effects were observed across pulse types with an inverse dose-response gradient for beans up to 1 cup/d. Future studies on chickpeas, dried peas, and lentils are warranted. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023432826; Unique identifier: CRD42023432826.
20 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Predicting incident type 2 diabetes using wearable activity and polygenic risk: A survival-modeling study in All of Us
BACKGROUND: Evidence is limited on whether daily step counts are uniform across individuals or whether combining them with genetic risk improves prediction of type 2 diabetes (T2D), both essential for precision prevention. We aimed to assess whether objectively measured daily step count and Polygenic Risk Score (PRS) predict the incidence of T2D, and to evaluate the predictive performance of machine-learning models. METHODS: We conducted a prospective cohort study of 4589 adults in the National Institutes of Health's All of Us Research Program with valid Fitbit step data and whole-genome-derived PRS, excluding individuals with T2D before or within a 180-day lead-in period. Incident T2D was defined by HbA1c ≥ 6.5%, plasma glucose ≥126 mg/dL, or an All of Us T2D condition record. We evaluated Cox and machine-learning survival models. FINDINGS: Over a median of 2.92 years (15 340 person-years), 265 participants developed T2D (5.77% cumulative incidence; 17.27 per 1000 person-years). Risk-reducing thresholds were ∼7000 steps/day (P < .001) but differed by PRS group (∼7800 high vs ∼5800 low; P < .001). Each additional 1000 steps/day was associated with lower T2D risk (adjusted hazards ratio, 0.83; 95% CI, 0.79-0.88; P < .005), whereas each 1-SD higher PRS was associated with higher T2D risk (adjusted hazards ratio, 2.62; 2.32-2.96; P < .005). Adding steps to a clinical model increased the C-index from 0.748 to 0.774; adding PRS increased it to 0.867. Penalized Cox achieved the highest discrimination (C-index 0.859), followed by survival support vector machine (0.85) and classical Cox (0.846). Calibration was best with Random Survival Forests. INTERPRETATION: Step-count thresholds for reducing T2D risk varied across genetic risk groups, indicating that step counts do not confer uniform protection. Step counts and PRS provided independent, complementary predictive information, and their combination improved prediction of incident T2D.
20 May 2026
Read appraisal →Archives of disease in childhood
Effects of metformin on anthropometric indices and hormones and adipocytokine concentrations in children with overweight or obesity: a systematic review and meta-analysis of randomised controlled trials
OBJECTIVE: The aim of this systematic review was to assess the effect of metformin on anthropometric indices, hormones and adipocytokine concentrations in children with overweight or obesity. METHODS: Eligible studies were searched via PubMed, Scopus, Cochrane Central Register of Controlled Trials, alongside clinical trial registries and the reference lists of included studies, from inception to October 2024. Screening was carried out independently by two reviewers, involving title-abstract screening for relevance, followed by full-text review for eligibility confirmation. Data extraction was performed by two independent investigators using an identical Excel spreadsheet. A meta-analysis was conducted using the random-effects model. RESULTS: A total of 19 original studies were deemed eligible for this systematic review. Metformin was more effective than placebo in improving Body Mass Index (BMI), BMI-Z score, body weight, fasting insulin and leptin concentrations (mean difference (MD) -1.07 kg/m2, 95% CI -1.62 to -0.52; MD -0.09, 95% CI -0.13 to -0.05; MD -3.20 kg, 95% CI -4.21 to -2.19; MD -3.38 μU/mL, 95% CI -6.00 to -0.75; MD -3.73 ng/mL, 95% CI -6.28 to -1.18, respectively). There was no difference between metformin and placebo on adiponectin and resistin concentrations, as well as adiponectin to leptin ratio. CONCLUSION: Metformin may have a role as an adjuvant therapy in managing overweight and obesity among the paediatric population. Regarding the concentrations of adipokines and hormones, the results are inconclusive. More randomised controlled trials with rigorous methodology and homogeneity in population and intervention characteristics are needed to shed light on this topic. TRIAL REGISTRATION NUMBER: PROSPERO CRD42023401732.
20 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Diazoxide Choline Extended-release Tablets in Prader-Willi Syndrome: A Randomized, Double-blind, Withdrawal Period Study
CONTEXT: The hallmark condition of Prader-Willi syndrome, a rare, genetic neurobehavioral/metabolic disorder, is life-threatening hyperphagia. OBJECTIVE: We assessed the efficacy and safety of diazoxide choline extended-release (DCCR) tablets for the treatment of hyperphagia in adults and children four years of age and older with Prader-Willi syndrome. METHODS: We conducted a 16-week, randomized withdrawal study in children and adults with Prader-Willi syndrome and hyperphagia. Participants who previously completed randomized (13-week DCCR or placebo) and open-label (2.5-4.5 years DCCR) studies were randomized 1:1 to receive once-daily DCCR or placebo. The primary endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) total score change from baseline to 16 weeks. Secondary endpoints included Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I); exploratory endpoints included weight and body mass index (BMI) z-score. RESULTS: Seventy-seven participants were randomized (DCCR:38; placebo:39). Statistically significant increases in HQ-CT from baseline to week 16 were observed with placebo vs DCCR [least square (LS) mean (standard error) change 7.6 (1.09)] with placebo and 2.6 (1.12) with DCCR; P = .0022. CGI scores favored DCCR but were not significantly changed. Consistent with the hyperphagia response, the placebo cohort gained more weight and increased their BMI z-score more than the DCCR cohort [LS mean weight difference (95% confidence interval) -1.6 kg (-3.1, -0.1)]; LS mean z-score difference was -0.09 (-0.17, -0.01). Adverse events were similar with both treatments, with no serious adverse events in the DCCR arm. CONCLUSION: Continued DCCR treatment was superior to placebo for hyperphagia. DCCR appears to offer meaningful therapeutic benefits for people with Prader-Willi syndrome.
19 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Associations of Metabolic Phenotypes with Cardiac Structure and Clinical Outcomes: Insights from the UK Biobank
CONTEXT: Metabolic syndrome and obesity represent major cardiovascular risk factors, yet their combined effects on cardiac structure and clinical outcomes remain incompletely understood. OBJECTIVE: To examine associations between metabolic phenotypes, cardiac magnetic resonance imaging (CMR), and clinical outcomes. DESIGN: Prospective study with a median 5.1-year follow-up. SETTING: Population-based cohort from the UK Biobank. PARTICIPANTS: A total of 22 789 participants (mean age 64.1 ± 7.5 years, 52.6% female) were categorized as metabolically healthy nonobese (MHN) vs obese (MHO) or unhealthy nonobese (MUN) vs obese (MUO), based on obesity (body mass index ≥30 kg/m²) and metabolic status (prevalent diabetes or both hypertension and hyperlipidemia). MAIN OUTCOME MEASURE(S): Primary and secondary endpoints were major adverse cardiovascular events (MACE) and all-cause mortality, respectively. CMR included left ventricular ejection fraction (LVEF, %), end-diastolic volume (LVEDV, mL), myocardial mass (g), wall thickness (mm), cardiac output (L/min), and left atrial volume (mL). Linear regression and Cox proportional hazards models, adjusted for age, sex, and smoking, assessed associations between metabolic phenotypes, CMR, and clinical outcomes. RESULTS: In adjusted models, all phenotypes demonstrated increased WT (MHO: β=.53 [.50, .55]; MUN: β=.24 [.21, .27]; MUO: β=.66 [.61, .70]), compared to MHN. LVEDV was increased in obesity phenotypes (MHO: β=4.67 [4.07, 5.27]; MUO: β=5.14 [4.05, 6.22]) and decreased in MUN (β=-1.25 [-1.95, -.55]), while MUO showed reduced LVEF (β=-.48 [-.91, -.04]). MACE risk was increased in unhealthy phenotypes (MUN: adjusted hazard ratio (aHR) = 1.55 [1.16-2.07]; MUO: aHR = 1.95 [1.28-2.97]). All phenotypes showed increased all-cause mortality risk (MHO: aHR = 1.65 [1.23-2.21]; MUN: aHR = 1.41 [1.05-1.90]; MUO: 2.10 [1.41-3.15]). CONCLUSION: Metabolic phenotypes show distinct cardiac structural changes and increased mortality risk, supporting their potential in cardiovascular risk stratification.
19 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Efficacy and Safety of Once-Weekly Lonapegsomatropin in Adults With Growth Hormone Deficiency: foresiGHt Trial Results
CONTEXT: Adult growth hormone (GH) deficiency (GHD) is characterized by metabolic abnormalities caused by insufficient GH production. Lonapegsomatropin, a prodrug administered once weekly, was designed to provide sustained release of unmodified somatropin to reduce the burden of daily somatropin injections. OBJECTIVE: This work aimed to evaluate the efficacy and safety of lonapegsomatropin vs placebo as treatment for adults with GHD. METHODS: The foresiGHt trial was a multicenter, randomized, parallel-arm, placebo-controlled (double-blind) and active-controlled (open-label) trial (NCT04615273) conducted at 116 centers in North America, Europe, and Asia-Pacific. The trial randomly assigned and dosed 259 adults with GHD. Participants were randomly assigned 1:1:1 to receive once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin for 38 weeks. The primary efficacy end point was change from baseline in trunk percent fat at week 38. Secondary efficacy end points included change from baseline in trunk fat mass and total body lean mass. RESULTS: At week 38, lonapegsomatropin significantly reduced trunk percent fat (-1.68% vs +0.37%; least squares [LS] mean difference -2.04%; P < .001), increased total body lean mass (+1.60 kg vs -0.11 kg; LS mean difference 1.70 kg; P < .0001), and reduced trunk fat mass (-0.48 kg vs +0.22 kg; LS mean difference -0.70 kg; P = .0053) vs placebo. The safety and tolerability profile of lonapegsomatropin was comparable to somatropin. CONCLUSION: The foresiGHt trial met its primary efficacy end point by demonstrating superiority of lonapegsomatropin vs placebo with similar safety and tolerability, supporting its potential as a once-weekly treatment option for adults with GHD.
19 May 2026
Read appraisal →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 →The Journal of clinical endocrinology and metabolism
Lifestyle intervention before and during fertility treatment in women with obesity or with overweight and PCOS-a RCT
CONTEXT: Lifestyle interventions are recommended for women with obesity and infertility, but trial evidence is scarce, and studies have not investigated interventions that continue during fertility treatment. OBJECTIVE: Evaluate effectiveness of a lifestyle intervention compared with usual care on fertility outcomes in women with obesity and infertility. DESIGN: The Obesity-Fertility randomized controlled trial (RCT), at an academic fertility clinic, included 127 women aged 18 to 40 years with infertility and obesity (body mass index ≥30 kg/m2, or ≥27 kg/m2 with polycystic ovary syndrome [PCOS]), excluding those unlikely to conceive naturally. The intervention group (IG) received a 6-month lifestyle intervention alone (individual follow-up with a dietician and kinesiologist, and group sessions) before adding fertility treatments. The control group (CG) received usual fertility care directly. Rate of live birth conceived within 18 months of randomization was analyzed. RESULTS: Compared to CG, the IG lost more weight (-3.21% ± 4.73% vs -0.40% ± 3.66%, P = .003) and waist circumference (-2.62 ± 4.46 cm vs -0.23 ± 3.81 cm, P = .01) at 6 months. The live-birth rate was 44.4% in the IG (n = 63) vs 35.9% in the CG (n = 64) (risk ratio [RR] = 1.24 [95% CI 0.81-1.90]). In IG vs CG, clinical pregnancy rates were 52.4% vs 37.5% (RR = 1.40 [0.94-2.07]) and natural pregnancy rates were 27.0% vs 12.5% (RR = 2.16 [1.01-4.64]). CONCLUSION: Compared with usual care, a lifestyle intervention alone for 6 months and then combined with fertility treatments did not increase the 18-month rate of pregnancies leading to a live birth, but significantly increased natural pregnancy rates, potentially reducing the need for costly assisted reproduction in this population.
19 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Efficacy and safety of pharmacologic therapies in acromegaly: a systematic literature review and network meta-analysis
CONTEXT: There are limited head-to-head trials comparing pharmacological treatments for acromegaly. OBJECTIVE: Systematically review the efficacy and safety of pharmacological treatments for acromegaly and conduct a network meta-analysis (NMA) enabling indirect comparisons. METHODS: MEDLINE and Embase were searched to identify randomized controlled trials (RCTs) of acromegaly therapies. Screening and data extraction followed PRISMA guidelines. Feasibility assessment evaluated homogeneity and consistency assumptions required for NMA. Bayesian NMAs estimated relative treatment effects and ranking probabilities. RESULTS: Twenty-two records covering 18 RCTs were included. Biochemical control rates were comparable among long-acting injectable somatostatin receptor ligands (SRLs), including lanreotide autogel (LAN-ATG), octreotide long-acting release (OCT-LAR), pasireotide, the GH receptor antagonist pegvisomant, oral octreotide (O-OCT), octreotide subcutaneous depot (SC-OCT-D), and the once-daily oral SRL paltusotine. Paltusotine demonstrated significantly higher biochemical control vs O-OCT and SC-OCT-D (odds ratios [ORs], 95% credible intervals [CrIs]: 7.34 [1.48-36.07] and 7.85 [1.72, 36.25]). Pasireotide showed significantly higher biochemical control vs OCT-LAR (OR: 2.03 [1.29-3.23]). Paltusotine had significantly lower discontinuations due to adverse events (AEs) vs O-OCT and SC-OCT-D, (ORs: 0.022 [0.001-0.424] and 0.022 [0.001-0.343]), with similar rates to other treatments. Treatment-emergent AEs (TEAEs) and serious TEAEs were comparable across treatments. Rankings suggested paltusotine as the treatment with the highest probability of ranking as the most effective (or tolerable) treatment across all endpoints studied. CONCLUSION: This systematic review and NMA consolidate recent high-quality RCT evidence for acromegaly treatments. Paltusotine emerges as a promising alternative to injectable SRLs, with favorable efficacy, safety, and AE-related discontinuation patterns. These findings may inform clinical decision-making and guideline development, if confirmed by clinical experience.
19 May 2026
Read appraisal →Circulation
Effect of APOC3 Inhibition With Olezarsen on Coronary Atherosclerosis: Essence-TIMI 73b Imaging Study
BACKGROUND: Whether lowering triglyceride-rich lipoproteins and remnant cholesterol favorably modifies coronary atherosclerosis is unclear. Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III, reduces triglycerides by ~60% and remnant cholesterol by ~70%, has a neutral effect on LDL (low-density lipoprotein) cholesterol (LDL-C), and reduces apoB (apolipoprotein B) by ~15% in moderate hypertriglyceridemia. We investigated the effect of olezarsen on coronary plaque in adults with largely moderate hypertriglyceridemia. METHODS: We conducted a coronary computed tomography angiography study within Essence-TIMI 73b, a randomized, placebo-controlled trial of olezarsen versus placebo that enrolled patients between November 2022 and February 2024. Inclusion criteria were triglycerides ≥150 mg/dL (2.26 mmol/L), presence of or high risk for cardiovascular disease, and, for this imaging study, noncalcified plaque on baseline coronary computed tomography angiography. The primary end point was percent change from baseline to 12 months in noncalcified plaque volume. RESULTS: Of 468 participants (349 olezarsen, 119 placebo), the median age was 63 years (interquartile range, 56-70); 31% were women, and 97% received lipid-lowering therapy. Median baseline triglycerides were 249 mg/dL (interquartile range, 197-331), and remnant cholesterol was 53 mg/dL (interquartile range, 38-76). Median baseline noncalcified plaque volume was 125.3 mm³ (interquartile range, 63.2-213.3). At 6 months, olezarsen reduced triglycerides by 63.9%, remnant cholesterol by 71.9%, and apoB by 16.0% over placebo, with no difference in LDL-C. The percent change in noncalcified plaque volume from baseline to month 12 did not differ between olezarsen and placebo (placebo-adjusted least-squares mean difference, 2.98% [95% CI, -3.4 to 9.3]; p=0.36). No significant differences between olezarsen and placebo were observed for changes in low-attenuation, calcified, or total plaque volumes at 12 months. CONCLUSIONS: Despite substantial triglyceride and remnant cholesterol lowering, treatment with olezarsen for 12 months on top of standard-of-care lipid-lowering therapy in patients with largely moderate hypertriglyceridemia did not affect noncalcified coronary plaque volume. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05610280.
19 May 2026
Read appraisal →Radiation oncology (London, England)
Comparative study between PET-CT simulation and CT for head and neck cancer treatment and their potential effect on the thyroid gland: a prospective comparative study
BACKGROUND: Radiotherapy (RT) plays a key role in multidisciplinary treatment of Head and neck cancers (HNCs). Over the past two decades, advances have improved RT's tumor control and toxicity profiles. Precise delineation of gross tumor volume and organs at risk using CT and PET-CT is crucial for safe and effective RT. Additionally, RT increases the risk of thyroid dysfunction, especially hypothyroidism. AIM: The present study compared PET-CT simulation and CT-alone planning in head and neck cancer (HNC) treatment, emphasizing their effects on thyroid gland function. METHODS: The patients were divided into two groups according to the simulation method (PET-CT or CT), two fresh blood samples (5 mL/ sample) were collected from each patient, before and after radiotherapy. TSH, FT3, and FT4 (Thyroid biomarkers) were assessed by electrochemiluminescent immunoassay (ECLIA). RESULTS: PET-CT simulation demonstrated a significant improvement in GTVp delineation accuracy by 71.8% compared with CT. After radiotherapy, TSH levels show minor decline changes, whereas FT3 and FT4 levels declined significantly, with greater declines observed in stages II and III. The most common tumor site was the larynx (60% in PET-CT, 75% in CT), followed by the tongue, nasopharynx, and parotid gland. CONCLUSION: PET-CT simulation offered superior GTVp delineation accuracy over CT, improving HNCs radiotherapy planning. Immediately after RT, radiotherapy caused significant declines in serum FT3 and FT4 levels, with only a minor, non-significant TSH declining, particularly in stage II/III disease. Notably FT4 is little more affected in PET-CT simulation patient group, highlighting the need for thyroid function monitoring. These results advocate PET-CT integration in planning and routine endocrine monitoring for treatment complications.
19 May 2026
Read appraisal →Scientific reports
RDE-DR: robust deep ensemble CNNs for automated diabetic retinopathy detection from fundus images
Diabetic retinopathy (DR) is a leading cause of preventable blindness, motivating the development of reliable automated screening systems. This work proposes a Robust Deep Ensemble for Diabetic Retinopathy detection (RDE-DR) by analyzing ensemble fusion strategies. Four pre-trained convolutional neural networks (ResNet50, VGG16, VGG19, and DenseNet121) are trained using CLAHE-enhanced APTOS 2019 fundus images and integrated through seven heterogeneous fusion mechanisms, including voting-based, rank-based, and fuzzy-integral-inspired strategies. A consistent evaluation protocol is adopted, incorporating threshold optimization and probabilistic calibration analysis to validate robustness, decision margins, and accuracy-precision trade-offs. Experimental results show that multiple fusion techniques achieve comparable high performance and stable behavior on the APTOS 2019 benchmark, with the best configuration reaching 98.64% accuracy, 98.40% precision, 98.92% recall, 98.66% F1-score, and 99.78% Area-Under-Curve (AUC). Beyond peak accuracy, the study provides insights into ensemble reliability, calibration characteristics, and practical design choices for medical image classification systems. These results show that integrating transfer learning with CLAHE preprocessing and ensemble fusion yields stable experimental performance on the APTOS 2019 benchmark, suggesting potential for future medical decision support.
18 May 2026
Read appraisal →African journal of reproductive health
Effect of a herbal galactagogic formula combined with auricular acupressure on breast milk production and hormonal profiles in women with postpartum hypogalactia: A randomized controlled study
Postpartum hypogalactia is a common condition that may impair breastfeeding and maternal-infant health. This randomized controlled study evaluated the efficacy of a herbal galactagogic decoction combined with auricular acupressure in improving lactation outcomes. A total of 104 women with postpartum hypogalactia were enrolled between July 2023 and June 2025 and randomly assigned to a control group (auricular acupressure alone, n=52) or an intervention group (auricular acupressure plus herbal decoction, n=52) for 2 weeks. Primary outcomes included breast milk production and formula supplementation, while secondary outcomes comprised serum hormone levels (estradiol, progesterone, and prolactin), symptom scores, psychological status, and clinical effectiveness. Both groups showed significant post-treatment improvements (P<0.05). Compared with the control group, the intervention group demonstrated lower estradiol and progesterone levels, higher prolactin levels, increased milk production, and reduced formula supplementation (P<0.05). Symptom scores and anxiety/depression levels were also significantly improved. The overall effective rate was higher in the intervention group (96.15% vs 80.77%, P<0.05), with comparable safety profiles. This combined therapy appears to be a safe and effective complementary approach for improving lactation in women with postpartum hypogalactia. L’hypogalactie post-partum est une affection fréquente pouvant compromettre l’allaitement et la santé maternelle et infantile. Cette étude randomisée contrôlée a évalué l’efficacité d’une décoction galactagogue à base de plantes associée à l’acupression auriculaire pour améliorer les résultats de lactation. Au total, 104 femmes atteintes d’hypogalactie post-partum ont été recrutées entre juillet 2023 et juin 2025 et réparties aléatoirement en un groupe témoin (acupression auriculaire seule, n=52) et un groupe intervention (acupression auriculaire associée à une décoction à base de plantes, n=52) pendant 2 semaines. Les critères de jugement principaux comprenaient la production de lait maternel et le volume de supplémentation en lait artificiel, tandis que les critères secondaires incluaient les niveaux hormonaux sériques (estradiol, progestérone et prolactine), les scores symptomatiques, l’état psychologique et l’efficacité clinique. Les deux groupes ont montré des améliorations significatives après le traitement (P<0,05). Comparé au groupe témoin, le groupe intervention présentait des niveaux plus faibles d’estradiol et de progestérone, des niveaux plus élevés de prolactine, une production de lait accrue et une réduction de la supplémentation (P<0,05). Les scores symptomatiques ainsi que les niveaux d’anxiété et de dépression ont également été significativement améliorés. Le taux global d’efficacité était plus élevé dans le groupe intervention (96,15 % vs 80,77 %, P<0,05), sans différence significative en termes d’effets indésirables. Cette thérapie combinée pourrait constituer une approche complémentaire sûre et efficace pour améliorer la lactation chez les femmes présentant une hypogalactie post-partum.
18 May 2026
Read appraisal →European journal of preventive cardiology
Effect of intensive blood pressure control in patients with resistant hypertension: insights from the STEP trial
AIMS: Resistant hypertension is defined as uncontrolled blood pressure (BP) despite the use of ≥3 antihypertensive drugs or controlled BP with ≥4 antihypertensive drugs. Whether intensive BP control is beneficial for the management of resistant hypertension is unknown. METHODS AND RESULTS: Intensive (<130 mmHg) BP control in patients is compared with standard (130-150 mmHg) BP control in patients with resistant hypertension, using the Strategy of Blood Pressure Intervention in Older Hypertensive Patients (STEP) trial data. Patients were divided into those with and without resistant hypertension. The primary outcome was a composite of cardiovascular events. Hazard ratios (HRs) were calculated using the Fine-Gray sub-distribution hazard model for primary and secondary events and the Cox regression model for all-cause death. In patients with resistant hypertension, intensive BP control was associated with a lower risk of primary outcomes (HR, 0.36; 95% CI, 0.14-0.93; P = 0.035). Results were consistent across different BP thresholds used to define resistant hypertension and in patients with true resistant hypertension. The benefit of intensive BP control was consistent across resistant hypertension status. Intensive BP control was not associated with an increased risk of adverse events in patients with resistant hypertension. Patients with resistant hypertension had increased cardiovascular risk compared with those without (HR, 1.78; 95% CI, 1.13-2.81; P = 0.012). CONCLUSION: Intensive BP control is associated with reduced risk of cardiovascular events in patients with resistant hypertension without increased risk of adverse events. REGISTRATION: https://www.clinicaltrials.gov/ct2/show/NCT03015311. The present study is a secondary analysis of the effect of intensive blood pressure control in patients with resistant hypertension in the STEP trial. Resistant hypertension is characterized as elevated blood pressure (BP) despite three antihypertensive agents or controlled BP with four or more agents. Intensive BP control in patients with resistant hypertension may reduce the risk of cardiovascular events. Further research is needed to investigate multifaceted treatment approaches, including both pharmacological and non-pharmacological interventions.Intensive blood pressure (BP) control is associated with a reduced risk of cardiovascular events and death in patients with resistant hypertension, compared with standard BP control, without increasing the risk of adverse events.Patients with resistant hypertension remain at higher risk of cardiovascular events compared with patients without resistant hypertension. Intensive BP control in this population may lower the risk of cardiovascular events.
18 May 2026
Read appraisal →The American journal of cardiology
CagriSema Versus Semaglutide Monotherapy or Placebo for Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Assessment
The obesity epidemic is a major health burden that enhances susceptibility to a broad spectrum of metabolic-associated comorbidities, ranging from fatty liver disease and endocrine dysfunction to traditional risks like type 2 diabetes mellitus and cardiovascular disease. Glucagon-like peptide-1 receptor agonists, including semaglutide, facilitate weight loss alongside glucose metabolism. The dual therapy CagriSema, which combines semaglutide with cagrilintide was developed. We systematically searched MEDLINE (via PubMed), Web of Science, Scopus, and Cochrane Library, from inception to July 2025, for randomized controlled trials (RCTs) comparing CagriSema with semaglutide monotherapy or placebo in patients with obesity. Four RCTs (n = 4,419) were included (CagriSema: 3,055; control: 1,364). Pooled analysis showed that CagriSema significantly reduced percent weight loss (Cohen's d: -1.38; 95% CI: -1.84 to -0.91; I² = 94.8%). CagriSema also resulted in greater absolute weight loss (MD: -11 kg), waist circumference (MD: -9.41 cm), and systolic blood pressure (MD: -7.06 mmHg). Gastrointestinal adverse events were more frequent (RR: 1.32). CagriSema therapy was associated with superior weight reduction compared with semaglutide or placebo. In conclusion, CagriSema achieves greater weight loss than semaglutide or placebo but increases gastrointestinal adverse events, warranting careful tolerability monitoring and longer-term data.
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 →Pituitary
Pituitary adenoma and intracerebral aneurysms: case series, systematic review and meta-analysis
PURPOSE: Intracranial aneurysms (IAs) and Pituitary Adenoma (PA) coexistence has been reported for decades, yet available evidence remains fragmented. We performed a systematic review and meta-analysis following PRISMA 2020 guidelines to assess clinical features of patients with both conditions and quantify the prevalence of IAs in PA patients. METHODS: PubMed and Embase were searched up to December 15, 2025. Studies reporting coexistence of IAs and PAs were included. Individual patient-level data (Group 1) and aggregate prevalence data (Group 2) were analyzed separately. Risk of bias (RoB) was assessed using Joanna Briggs Institute tools. All analyses were performed using metaprop function from the meta package in R software. RESULTS: Seventy-one studies met inclusion criteria. Most studies have a low RoB. In Group 1 (74 patients), PAs were predominantly macroadenomas (91.9%), most frequently non-functioning (40.5%). IAs were mainly in the cavernous segment of the internal carotid artery (33%). IA diagnosis occurred significantly later than PA diagnosis (p < 0.01). In Group 2 (5264 patients), the pooled prevalence of IAs among PAs was 4% (95% CI 2-4%; I² = 92.1%, τ² = 1.1050, p < 0.0001). Sex-stratified prevalence was 8% (95% CI: 6%-9%) in females and 6% (95% CI: 4%-7%) in males. IAs sex-specific prevalence was significantly higher in both male and female PA patients as compared to the general population (p < 0.01). CONCLUSION: Patients with PAs show a higher IAs prevalence compared with the general population, likely reflecting combined hemodynamic, anatomical, and endocrine influences.
18 May 2026
Read appraisal →Journal of medical Internet research
Digital Patient Decision Aid for Antiobesity Medications: Mixed Methods Study of Human-Centered Design and Usability Evaluation
BACKGROUND: The global burden of obesity continues to rise, highlighting the need for patient-centered approaches to weight management. Shared decision-making is particularly important in the selection of antiobesity medications (AOMs), as treatment options differ in mechanism, effectiveness, side effects, routes of administration, and cost. Despite this preference-sensitive context, only a few patient decision aids (PDAs) have been culturally and clinically adapted for use in Asian populations. OBJECTIVE: This study aims to design, develop, and evaluate a digital PDA, OptiWeight, to support shared decision-making for AOM selection, incorporating perspectives from health care professionals and patients. METHODS: This mixed methods, multicenter study, conducted between August 2022 and November 2025, applied a 4-stage human-centered design process. An evidence-informed prototype was developed based on clinical guidelines, followed by 2 rounds of usability testing using think-aloud protocols to assess navigation structures, perceived usability (System Usability Scale [SUS]), and cognitive workload (NASA Task Load Index [NASA-TLX]). Semistructured interviews with health care professionals specializing in weight management, guided by the Consolidated Framework for Implementation Research, informed clinical implementation and workflow integration. Finally, patients with overweight or obesity evaluated usability, cognitive workload, and overall user experience in outpatient settings. Qualitative data were analyzed using content analysis, and 1-way analysis of variance examined changes in usability and workload across stages. RESULTS: A total of 174 individuals were included across all study stages (usability testing among adults: n=78; health care professional interviews: n=18; and clinical evaluation among patients: n=78). Iterative usability testing comparing system- and user-controlled navigation structures revealed complementary strengths and limitations, leading to the adoption of a hybrid navigation structure supporting both sequential guidance and flexible comparison. Additional design requirements included the use of icon arrays to enhance risk comprehension and localization features such as treatment cost displays and clarification of socially impactful side effects. Perceived usability increased from initial testing to clinical evaluation (SUS: 60.53-73.65, P<.001), meeting good usability thresholds, while cognitive workload decreased (NASA-TLX: 40.35-16.69, P<.001). CONCLUSIONS: Through a systematic human-centered design process integrating health care professional and patient perspectives, OptiWeight addresses the lack of culturally adapted PDAs for AOM decision-making in Mandarin-speaking populations while capturing user needs-particularly regarding navigation flexibility and risk visualization. The final tool demonstrated good usability and feasibility, and workflow considerations suggest potential for integration into routine weight-management care. Further research is needed to evaluate its impact on decision quality and real-world implementation outcomes.
17 May 2026
Read appraisal →International journal of cancer
Testicular cancer in intersex individuals: A systematic review for clinical practice
The objective of this systematic review was to identify the evidence of testicular cancer risk for people with intersex conditions. This assessment is hoped to help refine risk stratification tools for assessing gonadal malignancy risk and guide the development of more robust evidence-based management strategies. The literature was searched in Ovid MEDLINE, Embase, and Cumulative Index of Nursing and Allied Health using a search string developed by a multidisciplinary team. The protocol was registered at Prospective Register of Systematic Reviews as CRD42021231313. A total of 3608 articles were found. After selection, 301 publications were included (1215 individuals). The results identified significant evidence that pre-pubertal gonadectomy may be linked to lower rates of malignant gonadal changes for patients with partial gonadal dysgenesis, Turner's syndrome with Y-chromosome material, complete androgen insensitivity, partial androgen insensitivity, and patients with ovotestis/es. The evidence was not significant for patients with complete gonadal dysgenesis, Klinefelter syndrome, nor WT1-related syndromes. Specific cancer outcomes were unable to be assessed due to small sample sizes and thus it is unknown if clinically significant cancer outcomes are meaningfully altered by pre-pubertal gonadectomy. Importantly, the quality of data on the topic of gonadal malignancy in intersex patients with testicular tissue was determined to be poor overall. The quality was relatively more robust regarding the conditions of Complete Androgen Insensitivity, Klinefelter syndrome, and patients with ovotestis/es. More high-quality research is needed to draw specific conclusions on the risks and benefits of performing pre-pubertal gonadectomy for intersex patients. When counseling these patients, clinicians should be transparent regarding the paucity of data supporting pre-pubertal gonadectomy.
17 May 2026
Read appraisal →European journal of preventive cardiology
Effect of incretin-based therapies on blood pressure: a systematic review and meta-analysis
AIMS: Hypertension and obesity frequently coexist and synergistically increase cardiovascular (CV) risk. Incretin-based therapies with glucagon-like peptide-1 receptor agonists (GLP-1-RAs), gastric inhibitory polypeptide (GIP)/GLP1-RAs, and glucagon/GIP/GLP-1RAs lead to substantial weight loss. However, their antihypertensive efficacy and safety profile have not been comprehensively quantified. Our study aimed to evaluate the effects of incretin-based therapies on office systolic blood pressure (BP) (SBP), diastolic BP (DBP), all-cause mortality, and key safety outcomes, i.e. hypoglycaemia and pancreatitis episodes, in adults with overweight or obesity. METHODS AND RESULTS: We searched PubMed, EMBASE, and ClinicalTrial.gov from inception to 30 April 2024 for randomized controlled trials (RCTs) comparing incretin-based therapy with placebo and ≥1 month of follow-up. The primary outcome was change in SBP; secondary outcomes were change in DBP, all-cause mortality, hypoglycaemia, and pancreatitis. Random effects meta-analyses generated mean differences (MDs) or risk ratios (RRs) along with 95% confidence intervals (CIs). Heterogeneity was explored with I2 statistics, subgroup analyses, and meta-regression. Eighty-five RCTs encompassing 90 977 participants (median follow-up time 8 months) met the eligibility criteria. GLP1-RAs reduced SBP by 3.4 mmHg (95% CI 2.8-4.0) and DBP by 0.9 mmHg (95% CI 0.5-1.2). A higher weight loss was significantly associated with a greater reduction in BP. The most significant BP reduction was associated with dual (SBP 5.1 mmHg; DBP 1.8 mmHg) and triple (SBP 6.6 mmHg; DBP 2.1 mmHg) receptor agonists. All-cause mortality was reduced by 18% (RR 0.82, 95% CI 0.76-0.90). Incretin-based therapy did not increase the risk of hypoglycaemia (RR 1.05, 95% CI 0.83-1.33) or pancreatitis (RR 0.84, 95% CI 0.61-1.15). CONCLUSION: Incretin-based therapy led to a modest but clinically meaningful BP reduction and lower all-cause mortality in adults with overweight or obesity, without excess in hypoglycaemia or pancreatitis episodes. There was a significant association between weight loss and the reduction in SBP and DBP. Dual and triple agonists exhibited the most pronounced antihypertensive effect. These findings support the use of incretin-based therapies as part of an integrated and multidisciplinary approach to managing obesity and hypertension, with multiple agonists showing particular promise. Our findings also underscore the need for long-term RCTs to clarify weight-independent mechanisms and the durability effect of BP reduction. Incretin-based therapy, now widely used for weight loss, also modestly reduces blood pressure and mortality, providing an additional health benefit to people with obesity or diabetes.Across 85 clinical trials (more than 90 000 adults), incretin-based therapy lowered systolic blood pressure by about 3 mmHg; the most significant falls occurred with the dual and triple agonists, and every kilogram lost made the reduction larger.Incretin-based therapy use was associated with an 18% lower mortality, with no increase in hypoglycaemia or pancreatitis episodes, supporting their safe dual role in weight control and cardiovascular protection.
16 May 2026
Read appraisal →Journal of medical Internet research
A Digital Diabetes Self-Management Education and Support Program Integrated With Continuous Glucose Monitoring for Type 2 Diabetes: Randomized Controlled Trial
BACKGROUND: Previous research has demonstrated that the use of continuous glucose monitoring (CGM) can improve glycemic control in people with type 2 diabetes when used regularly alongside a digital diabetes self-management education and support (DSMES) program. However, to date, there is limited evidence showing the benefits of a digitally delivered DSMES program combined with real-time CGM for adults with type 2 diabetes. OBJECTIVE: The objective of this study is to evaluate the impact of a DSMES program coupled with CGM on hemoglobin A1c (HbA1c) and CGM-derived glycemic measures compared to usual care for adults with type 2 diabetes over 6 months. METHODS: Participants with type 2 diabetes and HbA1c of 8% or higher (64 mmol/mol) who were not using mealtime bolus insulin (aged 26-83 y; mean HbA1c 9.6%, SD 1.4% [mean 81.2 mmol/mol, SD 15.8 mmol/mol]) were randomly assigned to a digital DSMES+CGM integrated solution (n=51) or usual care (n=49) for 6 months. The primary outcome was HbA1c. The secondary outcomes were CGM-derived glycemic measures, including glucose management indicator, percent time in range 70 to 180 mg/dL, percent time above range (>180 mg/dL), percent time below range (<70 mg/dL), and mean glucose. Linear mixed effects models were used for intention-to-treat analyses. RESULTS: HbA1c was lower among the intervention group versus the usual care group at 3 months (difference=-0.7%, 95% CI -1.4% to -0.1% or difference=-8.1 mmol/mol, 95% CI -15.5 to -0.7 mmol/mol; P=.03) and at 6 months (difference=-0.6%, 95% CI -1.4% to 0.2% or difference=-6.9 mmol/mol, 95% CI -15.7 to 1.9 mmol/mol; P=.12) but only reached statistical significance at 3 months. CGM-derived glycemic measures, including glucose management indicator (difference=-0.9%, 95% CI -1.7% to -0.1%; P=.03), time in range (difference=14.6%, 95% CI 1.0% to 28.2%; P=.04), time above range (difference=-14.9%, 95% CI -29.0% to -0.9%; P=.04), and mean glucose (difference=-36.4 mg/dL, 95% CI -70.0 to -2.9 mg/dL; P=.03), also significantly improved for the intervention group versus the usual care group at 6 months. CONCLUSIONS: The combination of digital DSMES+CGM is effective for supporting adults with type 2 diabetes in managing their condition and has the potential to reduce the risk of long-term health complications.
16 May 2026
Read appraisal →BMC endocrine disorders
Effects of digital and remote exercise interventions on HbA1c in type 2 diabetes: a systematic review and network meta-analysis
BACKGROUND: To compare the effects of different digitally and remotely deliveredexercise interventions on glycated hemoglobin (HbA1c) in adults with type 2diabetes mellitus (T2DM) using a network meta-analysis (NMA), and to clarifythe relative effectiveness of distinct delivery models. METHODS: A systematic review and network meta-analysis of randomized controlledtrials was conducted following PRISMA-NMA guidelines and prospectivelyregistered in PROSPERO (CRD420261288210). Major databases were searched frominception to November 11, 2025. Exercise-centered digital and remoteinterventions were categorized as digital exercise interventions (DEX),structured exercise prescription (SEP), multi-behavior lifestyle interventions(MBLI), and tele-exercise/tele-rehabilitation (TEX). The primary outcome waschange in HbA1c. RESULTS: Fifty-four RCTs were included. Compared with control, TEX demonstratedthe greatest reduction in HbA1c (MD -0.51%, 95% CrI -0.88 to -0.14), followedby MBLI (MD -0.32%, 95% CrI -0.51 to -0.13). SEP showed a non-significanttrend, and DEX did not significantly reduce HbA1c. SUCRA rankings favored TEX(0.87), followed by MBLI (0.66), SEP (0.62), and DEX (0.24). Subgroup analysessuggested that HbA1c reductions with TEX and MBLI were more evident among olderadults (≥60 years) and those with longer diabetes duration（>10 years）;however, network inconsistency was detected in these subgroups, and findingsshould be interpreted cautiously. CONCLUSIONS: Digitally and remotelydelivered exercise interventions differ in their effectiveness for HbA1ccontrol in T2DM. Interventions incorporating ongoing professional supervisionare associated with the most consistent glycemic benefits, whereas largelyautomated approaches show limited effects, highlighting the importance ofdelivery structure and supervision intensity.
15 May 2026
Read appraisal →BMJ paediatrics open
Prevalence of dysglycemia following paediatric cardiac surgery: a systematic review and meta-analysis
BACKGROUND: Postoperative dysglycemia is a common but under-recognised complication in paediatric cardiac surgery, driven by physiologic stress, hormonal changes and cardiopulmonary bypass. Reported prevalence varies widely, and no meta-analysis has synthesised the evidence. Therefore, this study aimed to estimate the pooled prevalence of postoperative dysglycaemia and describe associated postoperative outcomes, such as intensive care unit (ICU) stay and mechanical ventilation duration. METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines and the Joanna Briggs Institute (JBI) methodology for prevalence studies. Eligible studies included paediatric patients (≤18 years) undergoing cardiac surgery reporting postoperative dysglycaemia (hyperglycaemia or hypoglycaemia). A random-effects model was used to calculate pooled prevalence and 95%CIs, with logit transformation applied to prevalence proportions and heterogeneity assessed using I² statistics. Subgroup analyses were performed by region/continent, study design, age group and glycaemic threshold. All included studies were critically appraised using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2 tool for randomised trials. The protocol was registered with PROSPERO (CRD420251161893). RESULTS: 22 studies involving 3864 patients were included. The pooled prevalence of postoperative dysglycemia was 68.6% (95% CI 52.8 to 81.0), with hyperglycaemia accounting for most cases (71.2%) and hypoglycaemia observed in 8.1%. Prevalence was higher in Asia and North America (~75%) than in Europe (45.2%), though not statistically significant. Studies using lower hyperglycaemia thresholds (126-139 mg/dL) reported significantly the highest prevalence (82.3%, p<0.032). The pooled mean ICU stay among dysglycemic patients was 180.3 hours (95% CI 82.3 to 279.3), and mean mechanical ventilation duration was 94.6 hours (95% CI 5.2 to 184.1). Sensitivity analyses showed that no single study disproportionately influenced the overall pooled estimates, and no publication bias was detected. The certainty of evidence assessed using the GRADE approach was moderate for overall dysglycemia prevalence. CONCLUSION: Dysglycaemia is highly prevalent following paediatric cardiac surgery, particularly hyperglycaemia, with prolonged ICU and mechanical ventilation times observed among affected patients. These findings underscore the need for vigilant perioperative glucose monitoring, standardised definitions of dysglycaemia, and evidence-based glycaemic management protocols. Future multicentre studies are warranted to establish optimal glycaemic thresholds and evaluate targeted interventions to improve postoperative outcomes in this vulnerable population.
15 May 2026
Read appraisal →Journal of the American College of Cardiology
Global Hypertension 2000 to 2020: Trends, Disparities, and Progress in Awareness, Treatment, and Control
BACKGROUND: Hypertension is the leading preventable risk factor for premature death worldwide. Accurate estimates of prevalence and control are critical for developing public health priorities. OBJECTIVE: This study sought to examine global variations in hypertension prevalence, awareness, treatment, and control by world economic region and compare secular changes from 2000 to 2020. METHODS: A systematic search of MEDLINE from January 1995 to November 2024 was supplemented with manual searches of article references. Population-based cross-sectional surveys reporting age- and sex-specific hypertension prevalence and using standardized blood pressure measurement methods were included. Sex- and age-specific prevalence by country was applied to population counts to calculate the number with hypertension regionally and worldwide. Country-specific percentages of awareness, treatment, and control were applied to numbers of adults with hypertension to obtain regional and global estimates. Hypertension was defined as mean systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of antihypertensive medication. RESULTS: We included 287 studies conducted in 6,060,567 adults from 119 countries. In 2020, 33.0% (95% CI: 32.5%-33.5%), or 1.71 (95% CI: 1.65-1.77) billion, of the world's adults had hypertension: 30.1% (95% CI: 29.4%-30.9%), or 395 (95% CI: 394-396) million, in high-income countries and 33.4% (95% CI: 32.8%-33.9%), or 1.32 (95% CI: 1.26-1.38) billion, in low- and middle-income countries. From 2000 to 2020, age-standardized prevalence decreased by 2.7% and absolute burden increased by 76 million in high-income countries compared with increases of 5.8% in prevalence and 651 million in absolute burden in low- and middle-income countries. From 2000 to 2020 in high-income countries, awareness increased from 57.7% to 69.2%, treatment from 42.9% to 66.3%, and control from 16.4% to 40.2%. More modest increases were observed in low- and middle-income countries: awareness from 29.1% to 46.1%, treatment from 20.7% to 30.8%, and control from 6.4% to 13.6%. CONCLUSIONS: The burden of hypertension is increasing, as are disparities between high-income countries and low- and middle-income countries. Urgent efforts are needed to address hypertension worldwide, particularly in low- and middle-income countries.
15 May 2026
Read appraisal →Journal of the American College of Cardiology
Blood Pressure Levels and Outcomes in Type 2 Diabetes: Dose-Response Meta-Analysis of 5.87 Million Cohort Participants
BACKGROUND: The dose-response relationships between systolic and diastolic blood pressure (SBP and DBP) levels and risks of all-cause mortality, cardiovascular and renal outcomes in type 2 diabetes remain poorly characterized, particularly at lower blood pressure (BP) levels. OBJECTIVE: This study aimed to examine risk patterns of major clinical outcomes across a wide range of BP levels in participants with type 2 diabetes. METHODS: We systematically searched PubMed, Embase, and Web of Science from inception to November 30, 2024, for cohort studies assessing associations of BP levels with all-cause mortality, cardiovascular, and renal outcomes. One-stage mixed-effects dose-response meta-analysis was conducted to assess the curvilinear associations. RESULTS: A total of 89 cohorts from 113 articles of 5,875,364 participants with type 2 diabetes were identified. A J-shaped association was observed for SBP with all-cause mortality. J-shaped associations were also observed for SBP with cardiovascular events and for DBP with all-cause mortality, with flattened risks at lower BP levels. After excluding studies with participants who had baseline cardiovascular diseases or cancer, a significantly lower risk of cardiovascular events was observed at lower SBP levels, as well as a flattened risk of all-cause mortality. Positive linear or monotonic trends were observed for renal events, estimated glomerular filtration rate decline, and development or progression of albuminuria. CONCLUSIONS: In type 2 diabetes, BP is linearly or monotonically associated with most cardiovascular and renal outcomes. Low SBP does not appear to be associated with an elevated risk of all-cause mortality compared with higher BP targets, suggesting that previously reported associations are likely due to reverse causation and unmeasured confounding.
15 May 2026
Read appraisal →Journal of robotic surgery
Longitudinal health-related quality of life after remote-access versus open thyroidectomy for thyroid cancer: a systematic review and meta-analysis
As remote-access thyroidectomy (RAT) becomes more widely used, evidence on patient- reported outcomes, particularly health-related quality of life (HRQoL), remains scarce and inconsistent. This meta-analysis compared postoperative HRQoL between thyroid cancer (TC) patients undergoing RAT and open thyroidectomy (OT) and assessed changes over time. A comprehensive search of five major databases was conducted from inception to August 2025. Studies reporting HRQoL after RAT or OT were included. Outcomes were grouped by postoperative timepoints. Outcomes were stratified across distinct postoperative timepoints to calculate pooled standardized mean difference (SMD) or mean difference (MD). Heterogeneity was explored through rigorous subgroup analyses encompassing surgical modalities, countries, and assessment instruments. Forty-one studies met the inclusion criteria, and 29 records were included in the quantitative synthesis. RAT demonstrated early advantages in comprehensive quality of life at 1 month and 3 months, and these advantages dissipated long term. Pain trajectories exhibited a biphasic pattern: RAT was associated with lower pain scores on postoperative day 1 but paradoxically higher scores during the 1-2 week period, with subsequent convergence. Cosmetic satisfaction and swallowing function consistently favored RAT from 1-2 weeks through 6 months, while voice outcomes showed no discernible differences. RAT appears to confer selected short- to medium-term patient-reported advantages over OT, particularly in cosmetic satisfaction and swallowing function. But these benefits are heterogeneous and not consistently maintained across all domains or timepoints. Future studies should standardize cross-culturally validated PRO instruments and adopt harmonized follow-up intervals and reporting guidelines to clarify the patient-centered value of RAT.
15 May 2026
Read appraisal →Journal of the American College of Cardiology
Natriuretic Peptide Receptor-1 Agonist for Resistant Hypertension: A Randomized Phase 2 Trial
BACKGROUND: XXB750 is a potent and long-acting human monoclonal antibody agonist of the natriuretic peptide receptor-1 (NPR-1), the receptor for atrial natriuretic peptide and B-type natriuretic peptide. Activation of NPR-1 may lower blood pressure (BP) in patients with resistant hypertension through increases in the second messenger cyclic guanosine monophosphate. OBJECTIVES: The aim of this study was to determine the effect of NPR-1 agonism on 24-hour BP. METHODS: This phase 2, multicenter, randomized, double-blind, placebo-controlled trial evaluated 4 once-monthly subcutaneous doses of XXB750 (30 mg, 60 mg, 120 mg, and 240 mg) administered at baseline, week 4, and week 8 in patients with resistant hypertension. Resistant hypertension was defined as 24-hour systolic BP (SBP) ≥135 mm Hg despite treatment with 3 or 4 guideline-directed antihypertensive agents. The primary endpoint was the dose-response relationship of XXB750 vs placebo in reducing the mean 24-hour SBP from baseline to week 12. RESULTS: The study population (N = 189) had a mean age of 61 years, was 69% male, 61% White, 20% Asian, and 14% Black/African American, and had a baseline mean 24-hour ambulatory BP of 148/81 ± 11/10 mm Hg. Plasma concentrations of XXB750 dose-dependently increased in the XXB750 groups, and XXB750 dose-dependently increased plasma and urine cyclic guanosine monophosphate concentrations by week 12. However, paradoxically, there was no significant dose-dependent change from baseline in mean 24-hour SBP at week 12. In fact, none of the doses of XXB750 had a greater BP-lowering effect than placebo. Changes in ambulatory BP were not affected by the development of anti-drug antibodies. Although there were no changes from baseline in urinary sodium excretion, there were small increases in plasma renin levels in the XXB750 groups. Adverse events with XXB750 were numerically higher than with placebo. Adherence to background antihypertensive medications, assessed by drug assays in 88 patients with available plasma samples, was consistent across all treatment groups at both baseline and week 12. CONCLUSIONS: XXB750, an NPR-1 agonist, had a neutral effect on 24-hour ambulatory SBP in patients with resistant hypertension, despite showing a robust dose-response relationship for engagement of the target of pharmacologic action as indicated by increases in cyclic guanosine monophosphate levels. (An Efficacy, Safety, Tolerability and Dose Finding Study of XXB750 in Resistant Hypertension Patients; NCT05562934).
14 May 2026
Read appraisal →Journal of the American College of Cardiology
Efficacy of Tonlamarsen in Patients With Uncontrolled Hypertension: The KARDINAL Phase 2 Randomized Clinical Trial
BACKGROUND: Angiotensinogen production represents the rate-limiting step in activation of the renin-angiotensin-aldosterone system. Tonlamarsen is an investigational antisense oligonucleotide directed against hepatic angiotensinogen synthesis; its efficacy and safety among patients with hypertension are unknown. OBJECTIVES: The aim of this study was to assess the safety and efficacy of 90 mg tonlamarsen administered subcutaneously once monthly for 5 months compared with a single dose of tonlamarsen and subsequent placebo. METHODS: This randomized, placebo-controlled trial enrolled adults with office systolic blood pressure (BP) >135 mm Hg receiving 2 to 5 antihypertensive medications. Participants entered a 3-part treatment period with monthly administration of the study drug, consisting of a 4-week placebo lead-in, followed by 4-week active run-in with a single dose of tonlamarsen and subsequent randomization to 4 additional doses of tonlamarsen or matching placebo for 16 weeks. The coprimary endpoints were the between-group differences in the change from baseline to week 20 in plasma angiotensinogen and in office systolic BP. RESULTS: A total of 279 participants received placebo lead-in, 206 received 90 mg tonlamarsen during the active run-in, and 198 were randomized. The mean BP among randomized participants before and after the placebo lead-in was 147/90 and 147/89 mm Hg, respectively. Following active run-in with tonlamarsen, the mean BP was 140/87 mm Hg. Twenty weeks following the first dose of tonlamarsen, least squares (LS) mean percentage changes in plasma angiotensinogen levels were -23.0% (95% CI: -27.8% to -18.2%) with a single dose of tonlamarsen and subsequent placebo and -67.2% (95% CI: -71.9% to -62.4%) with monthly tonlamarsen administration, with a LS mean difference of -44.1% (97.5% CI: -51.9% to -36.4%; P < 0.0001). The LS mean changes in office systolic BP were -6.7 mm Hg (95% CI: -9.8 to -3.5 mm Hg) for participants following a single dose of tonlamarsen and subsequent placebo and -6.7 mm Hg (95% CI: -9.8 to -3.6 mm Hg) for participants treated with monthly tonlamarsen, with a LS mean difference of -0.1 mm Hg (95% CI: -4.5 to -4.4 mm Hg; P = 0.97). Serious adverse events were infrequent and similar between treatment groups. CONCLUSIONS: Among individuals with uncontrolled hypertension, monthly tonlamarsen administration was more effective at lowering plasma angiotensinogen compared with a single tonlamarsen dose, but there was no additional BP reduction. (A Study to Investigate Tonlamarsen for the Treatment of Adults With Uncontrolled Hypertension [KARDINAL]; NCT06864104).
14 May 2026
Read appraisal →Journal of Korean medical science
Cardiovascular Risk Stratification in Youth-Onset Type 2 Diabetes Using Machine Learning
BACKGROUND: The rising incidence of youth-onset type 2 diabetes mellitus (T2DM), along with the risk of early cardiovascular complications, is concerning. Brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (cIMT) are noninvasive markers of arterial stiffness and atherosclerosis. They serve as important markers for cardiovascular risk assessment. This study aimed to apply machine learning models to identify high-risk individuals who may benefit from early and targeted cardiovascular screening. METHODS: This retrospective study included 129 patients with youth-onset T2DM who underwent baPWV and cIMT measurements between January 2018 and July 2024. High-risk groups were defined as having values of ≥ mean + 1 standard deviation for baPWV (arterial stiffness) and cIMT (atherosclerosis). Clinical predictors were evaluated using linear, logistic regression, and machine learning analyses. Multiple machine learning models were trained using oversampling and cross-validation techniques to enhance prediction performance. RESULTS: Among the models tested, the gradient boosting model with adaptive synthetic sampling oversampling achieved the best performance in predicting both arterial stiffness (accuracy 0.81) and atherosclerosis prediction (accuracy 0.92). Age and hypertension were consistently identified as the most important factors for arterial stiffness. For atherosclerosis risk, traditional analysis identified dyslipidemia, male sex, and duration of illness as relevant factors; machine learning more clearly emphasized low-density lipoprotein cholesterol and triglyceride levels as key predictors of increased cIMT. CONCLUSION: Hypertension and age were consistent predictors of arterial stiffness, while atherosclerosis risk factors were further clarified with lipid parameters by machine learning analysis. These findings suggest that conventional and machine learning analyses offer complementary strengths. Their combined use may enable earlier to detect nuanced cardiovascular risk patterns and support early and targeted vascular screening in youth-onset T2DM.
14 May 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Metabolic, demographic, and behavioral risk factors predict brain structural variability in the general population: an analysis of the human connectome project young adults
BACKGROUND: Understanding whether commonly available metabolic, demographic, and behavioral factors can explain variability in brain structure may support the development of accessible predictive approaches. This study aims to evaluate the ability of machine learning regression models to predict brain structural measures in young, neurologically healthy adults using clinically accessible risk factors. METHODS: Data were drawn from the Human Connectome Project Young Adults dataset, including 1082 participants aged 22-37. Predictors comprised metabolic measures (systolic and diastolic blood pressure, hematocrit, body mass index, hemoglobin A1C, thyroid stimulating hormone) and demographic/behavioral variables (age, gender, race, education level, smoking history, alcohol use). Brain structural parameters from MRI included gray matter (GM) and white matter (WM) volumes, surface areas, and cortical thickness. Distance correlation (dcor) guided feature selection, followed by machine learning modeling. Model performance was evaluated using normalized mean absolute error (NMAE), normalized root-mean-squared error (NRMSE), and coefficient of determination (R²). SHAP values were used for feature interpretation. RESULTS: XGBoost consistently outperformed other algorithms, showing strong predictive accuracy for total brain segmentation, supratentorial, and total GM volumes (NMAE < 0.35, R² > 0.80). In contrast, cortical surface predictions (left superior frontal) showed moderate performance (NMAE > 0.50, R² < 0.60). SHAP analysis highlighted age, gender, education level, and diastolic and systolic blood pressure as the most influential predictors of brain structure. CONCLUSIONS: The findings highlight the methodological value of regression-based approaches for estimating brain structural variability and support their potential role as complementary tools for brain health research.
14 May 2026
Read appraisal →Journal of medical systems
VR-Based Physical Activity and Self-Management Interventions for Glycemic Control and Behavioral Outcomes in Type 2 Diabetes: A Systematic Review and Meta-Analysis
A growing body of original research has recently investigated virtual reality (VR)-based interventions for physical activity and self-management, yet yielded inconsistent results. This systematic review and meta-analysis aims to evaluate the effectiveness of VR-based physical activity and self-management interventions in improving glycemic control and modifying health-related behaviors among patients with type 2 diabetes mellitus (T2DM). A total of 10 studies involving 1,005 adults with T2DM were included, comprising 5 randomized controlled trials (RCTs), 1 non-randomized controlled trial (nRCT), and 4 self-controlled before-after studies. Of these, participants in the intervention groups received VR-based interventions, including immersive or interactive VR programs for diabetes self-management education or physical activity promotion, with most intervention durations ranging from 8 to 24 weeks. Control groups received traditional approaches, including routine care, in-person diabetes self-management programs, and content-equivalent 2D websites. The pre-post intervention analysis revealed that glycated hemoglobin (HbA1c) levels decreased significantly post-intervention (mean difference (MD) = -0.50, 95% CI: -0.92 to -0.08, p = 0.02). While VR-based physical activity and self-management interventions did not demonstrate superior efficacy to traditional intervention methods in glycemic control or behavioral outcomes, their unique advantages - including enhanced adherence, greater accessibility, and reduced spatiotemporal constraints - position them as a viable alternative for diabetes management. Nevertheless, the field requires more rigorously designed RCTs to establish efficacy and a systematic exploration of VR implementation protocols to maximize therapeutic benefits.
14 May 2026
Read appraisal →Gut
Simvastatin in the prevention of recurrent pancreatitis: a triple-blinded randomised clinical trial (the SIMBA trial)
BACKGROUND: Recurrent acute pancreatitis (RAP) or acute-on-chronic flares in chronic pancreatitis (CP) have limited preventive options beyond addressing the underlying aetiology. Statins, due to their anti-inflammatory properties, have been proposed as a potential prophylactic treatment. OBJECTIVE: We aimed to evaluate whether simvastatin could reduce the recurrence of pancreatitis. DESIGN: At 23 centres, we conducted a triple-blind, randomised, controlled, superiority trial enrolling patients with at least two episodes of RAP or CP flares in the previous 12 months. Participants were randomly assigned to receive simvastatin or placebo for 1 year. The primary endpoint was the recurrence of pancreatitis. The target sample size was 144 patients; however, an interim analysis was planned in the event of slow recruitment. RESULTS: A total of 85 patients (42.1% women) were included in the interim analysis. In the intention-to-treat analysis, no significant differences were observed regarding recurrence: 46.2% simvastatin versus 44.4% placebo; OR 1.07, 95% CI 0.43 to 2.66; p=0.88, or time to recurrence. No statistically significant differences were observed in recurrence in per-protocol analysis (35.5% simvastatin vs 41.9% placebo; OR 0.76, 95% CI 0.27 to 2.12; p=0.60). Development of diabetes mellitus was more frequent in the simvastatin group (4 vs 0 patients; OR not calculable, p=0.04). CONCLUSION: This trial, evaluating simvastatin versus placebo for the prevention of pancreatitis, did not demonstrate a reduction in recurrence rate, although results might be underpowered due to early termination. The relationship between statins in these patients and new-onset diabetes requires further investigation. TRIAL REGISTRATION NUMBER: NCT04021498.
14 May 2026
Read appraisal →Endocrine pathology
Impact of Molecular Testing on Surgical Decision-Making in Indeterminate Thyroid Nodules: A Global Meta-Analysis Across Test Generations
Thyroid nodules with indeterminate cytology represent a clinical challenge owing to uncertain malignancy risk, often leading to diagnostic surgery. Molecular testing has emerged as a promising adjunct to improve risk stratification and guide surgical decision-making. However, the clinical utility and impact of different molecular platforms remain debated. The present study evaluates the impact of molecular testing on surgical decision-making in indeterminate thyroid nodules and compares outcomes between first- and second-generation molecular platforms. A PRISMA-guided systematic review and meta-analysis identified 132 studies including 66,448 thyroid nodules, of which 30,292 (45.6%) were indeterminate (Bethesda III/IV). Pooled analyses included studies directly comparing conventional management with molecular testing or different molecular platforms. Primary outcomes were surgical resection rates and risk of malignancy (ROM), stratified by diagnostic approach and test generation. Conventional management demonstrated significantly higher surgical rates than molecular testing group (OR = 2.258, 95% CI: 1.548-3.293, p < 0.001). ROM among resected nodules was lower in the conventional management compared with the molecular testing group (OR = 0.594, 95% CI: 0.388-0.911, p = 0.017). First-generation molecular tests showed higher surgical rates and lower ROM than second-generation assays (OR = 1.709, 95% CI: 1.122-2.601, p = 0.013; OR = 0.665, 95% CI: 0.515-0.858, p = 0.002, respectively). Exclusion of non-invasive follicular thyroid neoplasm with papillary-like nuclear features attenuated differences in malignancy rates. Molecular testing significantly reduces surgical interventions in indeterminate thyroid nodules without evidence of reduced detection of clinically significant malignancy, particularly with second-generation platforms supporting more individualized and evidence-based management strategies.
14 May 2026
Read appraisal →Current nutrition reports
Digital Solutions for the Control of Lifestyle Parameters in Individuals With High Cardiometabolic Risk: a Scoping Review
BACKGROUND: Digital technologies are increasingly used to promote healthier behaviors and prevent noncommunicable diseases (NCDs). Diet and physical activity are key determinants of cardiometabolic health, where digital tools can support self-monitoring and behavior change. OBJECTIVE: This scoping review aimed to evaluate the effectiveness of digital health technologies in improving diet quality and adherence, assessing body composition, and promoting physical activity among adults at cardiometabolic risk. METHOD: A systematic search was performed in Web of Science and PubMed (2000-2025) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines and the PICo framework. Inclusion criteria focused on digital solutions for diet and exercise in adults with overweight, obesity, or metabolic complications. RESULTS: 15 studies were included (8 randomized controlled trials, 2 pilot studies, and 5 validation studies). Most intervention studies reported significant improvements in weight reduction, body mass index, or waist circumference, especially when mobile applications or wearable devices were combined with personalized feedback. Validation studies confirmed a high reliability of AI-based image analysis tools for estimating body composition compared with DXA. Improvements in dietary adherence and physical activity levels were also observed in several studies. However, heterogeneity in study design, short follow-up duration, and variability in outcome measures limited comparability across studies. Major gaps included limited long-term evidence, scarce use of AI-driven personalized interventions, insufficient reporting of measurement validity, and underrepresentation of vulnerable populations. CONCLUSION: Digital health technologies, including mobile apps, wearables, and AI-based systems, show promising potential as a complementary tool to clinician-guided care. They can enhance dietary adherence, promote self-monitoring, and support healthier lifestyles, although their long-term effectiveness remains to be confirmed. Future research should prioritize long-term randomized trials, standardized outcomes measures, validation of AI-based tools in diverse populations, and structured integration of digital interventions into clinical pathways.
14 May 2026
Read appraisal →PloS one
Efficacy and safety of the ayurvedic formulation 'Trikatu' as an add-on to standard care in dyslipidemia: Study protocol for a randomized, double-blind, placebo-controlled trial evaluating lipid parameters, and gut microbiota.
BACKGROUND: Dyslipidemia is a leading modifiable risk factor for cardiovascular disease (CVD), with early and sustained LDL-C reduction offering significant preventive benefits. However, in low- and middle-income countries, long-term adherence to statin therapy remains alarmingly low, highlighting the need for culturally acceptable and safer adjunctive options. Trikatu, a classical Ayurvedic formulation traditionally known to enhance metabolism, may offer supportive benefits in lipid regulation. This study protocol was developed to assess the efficacy and safety of Trikatu as an add-on to standard statin therapy on lipid parameters and assess changes in gut microbiota in response to the intervention and identify microbial correlates associated with favorable lipid outcomes. METHODS: This randomized, double-blind, placebo-controlled clinical trial is being conducted at AIIMS Bhubaneswar, a tertiary care center. Total 170 participants (aged 25-60 years) with moderate to high Atherosclerotic cardiovascular disease (ASCVD) risk. Dyslipidemia, as defined by the 2019 ACC/AHA Guidelines and indicated for statin therapy, will be randomized in a 1:1 ratio to receive either Trikatu (1000 mg) or matching placebo, administered orally twice daily after food for 12 weeks along with standard statin therapy (dose/intensity as per guidelines). Primary outcome includes change in fasting serum LDL-C from baseline to 12 weeks. Secondary outcomes include changes in total cholesterol, HDL-C, triglycerides, glycemic markers (fasting glucose, HbA1c, insulin, HOMA-IR), inflammatory and metabolic markers (hs-CRP, TNF-α, IL-6, adiponectin, ghrelin, ApoA1, ApoB), resting blood pressure, and gut microbiota. The proportion of participants achieving normal cholesterol levels (<200 mg/dL) will also be assessed. Drug compliance and any adverse events will also be recorded. DISCUSSION: In individuals with moderate to high ASCVD risk, achieving and sustaining optimal lipid control remains a cornerstone of cardiovascular prevention. However, poor long-term adherence to statin therapy, especially in low-resource settings, limits real-world impact. By assessing Trikatu, effects on lipid profiles, glycemic and inflammatory markers, and gut microbiota, the study aims to explore its potential to augment cardiovascular risk reduction in a holistic and culturally acceptable manner. If proven effective and safe, Trikatu could serve as a valuable complementary strategy in dyslipidemia management. CLINICAL TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI/2023/04/051942) Registered on 25/04/2023.
13 May 2026
Read appraisal →Endocrine-related cancer
Systematic review of the molecular basis for cavernous sinus invasion in somatotropinomas
Somatotropinomas are a subtype of pituitary adenomas that have a particular predilection to invade the cavernous sinus. The objective of this systematic review was to examine the evidence regarding the molecular basis for cavernous sinus invasion in somatotropinomas. This review was conducted in accordance with the 2020 PRISMA guidelines on 13 April 2025. Inclusion criteria were reports of associations between somatotropinoma molecular changes and cavernous sinus invasion in adult patients. Title/abstract screening and full-text screening were performed, with studies assessed for risk of bias using the Newcastle-Ottawa scale. A total of 43 studies were identified, encompassing 1,824 patients (724 invasive tumours). Overall, 33 studies identified molecules that were upregulated in invasive tumours and 20 studies identified molecules that were downregulated. Few studies incorporated modern proteomic or transcriptomic techniques. Risk of bias was low with a mean Newcastle-Ottawa scale score of 7.0 (±0.6). Molecules associated with invasion were related to epithelial-mesenchymal transition (E-cadherin, ESRP1, fascin-1, and MMP-9), cellular proliferation (PTTG, AIP, TCERG1, EIF2β, E2F1, Notch 2, STAT3, ARRB1, TGFB1, SMAD3, SOX9, SGK1, MAGEA6 DLL3, EGFL7, and pEGFR), hormonal signalling (GNAS, DRD5, DRD1, sst5TMD4, SSTR2, and SSTR5), and tumour angiogenesis (VEGF and Drp1). These molecular variations present a possible explanation for the proclivity of somatotropinomas for the cavernous sinus. Identified molecules represent options for novel targeted therapies or biomarkers that could inform prognostication. Modern proteomic and transcriptomic techniques and larger somatotropinoma datasets are required to further elucidate the molecular pathways responsible for cavernous sinus invasion in somatotropinomas.
13 May 2026
Read appraisal →Medical science monitor : international medical journal of experimental and clinical research
Improved Cardiac Function and Glycemic Control in Elderly Diabetic Patients Through Structured Case Management After CABG
BACKGROUND Elderly patients with both coronary heart disease (CHD) and diabetes mellitus (DM) undergoing off-pump coronary artery bypass grafting (CABG) face high risks of perioperative glucose fluctuations and impaired recovery. We evaluated the impact of a structured, multidisciplinary case management model on cardiac function and glycemic control in this population. MATERIAL AND METHODS This single-center, randomized controlled trial enrolled 168 elderly (≥65 years) patients with CHD and type 2 DM scheduled for off-pump CABG. Patients were randomized (1: 1) to a control group (CG, n=84; routine care) or an observation group (OG, n=84). The OG received routine care plus a 6-month multidisciplinary intervention including individualized cardiac rehabilitation, modified Mediterranean diet, psychological support, and intensified follow-up. The primary endpoint was 6-month left ventricular ejection fraction (LVEF); HbA1c was a key secondary endpoint. RESULTS All 168 randomized patients were analyzed. At 6 months, the observation group demonstrated significantly superior primary outcomes. LVEF was significantly higher in the OG (mean difference: 6.2%, P<0.001), and HbA1c was significantly lower (mean difference: 1.3%, P<0.001). The intervention group also showed significant improvements in secondary endpoints, including reduced left ventricular diameters (LVESD, LVEDD), an improved lipid profile (P<0.05), longer 6-minute walk test distance, and higher Diabetes-Specific Quality of Life (DSQL) and Activity of Daily Living (ADL) scores (P<0.0001). CONCLUSIONS Structured, multidisciplinary case management significantly improved cardiac function, metabolic control, and functional capacity in elderly diabetic patients after off-pump CABG, validating its efficacy for this high-risk group.
13 May 2026
Read appraisal →Stress (Amsterdam, Netherlands)
Safety and efficacy of ashwagen (a standardized withania somnifera extract) in stress and anxiety with hypertension and associated cardiometabolic risk factors: a randomized, placebo-controlled trial
Stress and anxiety are prevalent mental health conditions that often coexist with cardiovascular comorbidities, resulting in a complex interplay between psychological and physiological processes, partly mediated through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Ashwagen®, a standardized extract of Withania somnifera (Ashwagandha), has demonstrated adaptogenic and anxiolytic properties in preclinical and clinical studies. This study aimed to evaluate the safety and efficacy of Ashwagen® in managing stress and anxiety in patients with pre-existing hypertension and associated cardiometabolic risk factors. A randomized, double-blind, placebo-controlled Phase III clinical trial was conducted over 60 days in 60 patients diagnosed with stress, anxiety, and pre-existing hypertension with cardiometabolic risk profiles. Participants received either Ashwagen® (300 mg capsule) or placebo twice daily. Efficacy assessments included validated psychological scales-Hamilton Anxiety Rating Scale (HAM-A), Generalized Anxiety Disorder-7 (GAD-7), Perceived Stress Scale (PSS), Clinical Global Impression-Improvement (CGI-I), Epworth Sleepiness Scale (ESS), and Fatigue Severity Scale (FSS)-along with serum cortisol, triglycerides, LDL, and blood pressure measurements. Ashwagen® significantly reduced anxiety and stress markers compared with placebo. HAM-A, GAD-7, and PSS scores decreased by 26.94%, 50.77%, and 30.47%, respectively, in the Ashwagen® group. Cortisol levels declined by 28.99% and triglycerides by 13.00%, with favorable trends in LDL and blood pressure. No serious adverse events were reported. Ashwagen® was found to be a safe and effective adjunctive integrative intervention for stress and anxiety management in patients with pre-existing hypertension.
13 May 2026
Read appraisal →PloS one
A modular deep learning architecture for interpretable disease prediction across tabular clinical and biometric datasets
Accurate disease prediction using clinical datasets is essential for improving early diagnosis and clinical decision-support systems; however, many existing deep learning approaches are disease-specific, computationally intensive, and difficult to generalize across heterogeneous biomedical datasets. This study addresses this challenge by proposing a unified and dataset-aware deep learning framework that enables accurate and interpretable disease prediction across diverse clinical datasets. The framework adopts a modular architecture that selects appropriate models based on dataset characteristics such as feature dimensionality, sample size, and class imbalance. It integrates multiple deep learning architectures, including MLP, one-dimensional CNN, FT-Transformer, autoencoder-based classifiers, and ensemble strategies. Robust preprocessing, fold-safe feature selection, and nested cross-validation are incorporated to ensure reliable performance evaluation. The framework is evaluated on three heterogeneous benchmark datasets: the UCI Heart Disease dataset (303 samples, 13 clinical features), the PIMA Indians Diabetes dataset (768 samples, 8 metabolic features), and the Parkinson's disease voice dataset (195 recordings, 22 acoustic features). Experimental results demonstrate competitive predictive performance relative to classical baselines across the diverse tasks. The FT-Transformer + autoencoder ensemble achieved an AUC of 0.8980 (±0.0483) for heart disease prediction, while the CNN + Autoencoder ensemble obtained an AUC of 0.8451 (±0.0270) for diabetes classification. For Parkinson's disease detection, the MLP achieved an AUC of 0.7538 with perfect specificity. Overall, all models achieved AUC values comparable to ML baselines. The study contributes a scalable and interpretable deep learning framework that improves reliability, generalization, and practical applicability for multi-disease prediction in real-world healthcare environments.
13 May 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Efficacy and safety of GLP-1 receptor agonists in Parkinson's disease: a systematic review and meta-analysis of randomized clinical trials
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder with no proven disease-modifying therapies to date. Because changes in cerebral glucose metabolism and insulin resistance have been linked to PD pathophysiology, glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for diabetes, have been investigated as potential neuroprotective treatments. METHODS: This study systematically assessed the efficacy and safety of GLP-1RAs in PD through a systematic review and meta-analysis of randomized controlled trials identified in PubMed, Embase, and the Cochrane Library. The primary outcomes were motor function improvements measured by the MDS-UPDRS Part III in both on- and off-medication states at study endpoints and at intermediate timepoints of interest. Secondary outcomes included MDS-UPDRS Parts I, II, and IV, quality of life assessed by the PDQ-39, levodopa equivalent daily dose (LEDD), and the occurrence of adverse events. RESULTS: The meta-analysis found no statistically significant difference in favor of GLP-1RAs over placebo for motors and non-motors outcomes, except for PDQ-39 (MD: - 0.75; 95% CI: [- 1.34, - 0.17], P = 0.01). Regarding safety, GLP-1RAs were associated with a higher incidence of adverse events, especially gastrointestinal effects such as nausea, vomiting, and constipation. CONCLUSIONS: Overall, current evidence does not demonstrate consistent clinical benefit of using GLP-1RAs for treating motor or non-motor symptoms in PD nor support GLP-1RAs as disease-modifying therapy, underscoring the need for further research.
13 May 2026
Read appraisal →Med (New York, N.Y.)
Mazdutide 9 mg in Chinese adults with a body mass index ≥30 kg/m2 but without diabetes: A phase 2 randomized controlled trial
BACKGROUND: Once-weekly dual glucagon and glucagon-like peptide-1 receptor agonist mazdutide, administered at 4 and 6 mg, provides substantial weight loss in Chinese adults with overweight or obesity. This trial aimed to evaluate the efficacy and safety of mazdutide 9 mg in Chinese adults with obesity. METHODS: In this randomized, double-blind, placebo-controlled phase 2 trial (NCT01904913), participants with a body mass index (BMI) ≥30 kg/m2 and without diabetes were randomized 3:1 to receive mazdutide 9 mg or placebo for 24 weeks. The primary endpoint was the percentage change in body weight from baseline to week 24. FINDINGS: Eighty participants were randomized and received mazdutide 9 mg (n = 60) or placebo (n = 20). At week 24, the mean percentage change in weight from baseline was -12.78% with mazdutide 9 mg and 1.80% with placebo (treatment difference: -14.58% [95% confidence interval (CI) -18.00, -11.16], p < 0.0001). Weight reduction ≥5% was achieved by 81.7% of participants with mazdutide after 24-week treatment, while no participants with placebo achieved this threshold. Mazdutide treatment was associated with greater improvements in cardiometabolic risk factors vs. placebo. The most common adverse events included nausea (50.0% with mazdutide vs. 0% with placebo), diarrhea (38.3% vs. 10.0%), and vomiting (36.7% vs. 10.0%), predominantly mild to moderate in severity. CONCLUSIONS: Mazdutide 9 mg was safe and led to substantial weight reductions in Chinese adults with a BMI ≥ 30kg/m2 but without diabetes after 24-week treatment. These results support further clinical development of mazdutide 9 mg for the treatment of obesity. FUNDING: This study was sponsored by Innovent Biologics.
12 May 2026
Read appraisal →JMIR mHealth and uHealth
Efficacy and Safety of a Telemedicine System in Patients With Gestational Diabetes Mellitus (TELEGLAM): Single-Center, 2-Arm, Randomized, Open-Label, Parallel-Group Study
BACKGROUND: In the management of gestational diabetes mellitus (GDM), the usual medical treatment requires frequent visits for glucose monitoring and insulin dose adjustment, and this imposes significant physical, psychological, and economic burdens on pregnant women. As mobile health platforms become increasingly integrated into diabetes care, telemedicine may help alleviate these burdens; however, evidence evaluating its effectiveness as a replacement for routine in-person GDM care remains limited. OBJECTIVE: This study aims to evaluate the impact of telemedicine on the quality of life and costs for patients with GDM requiring insulin therapy. METHODS: This single-center, 2-arm, randomized, open-label, parallel-group study included patients with GDM who started insulin injection therapy. Participants were randomized to either the telemedicine or standard face-to-face care groups for 10 (SD 2) weeks. The telemedicine intervention used a smartphone-linked platform that enabled the automatic transfer of glucose data from connected glucose meters and facilitated real-time video consultations. Primary end points included costs and patient satisfaction. Costs were assessed using claims data, transportation calculations, and wage-based productivity losses, while patient satisfaction was evaluated through changes in the Problem Areas in Diabetes Survey and Diabetes Therapy-Related Quality of Life questionnaire scores. Secondary outcomes included glycemic control and perinatal outcomes. RESULTS: In total, 38 participants were included, with 18 assigned to the telemedicine group and 20 to the standard care group. Total costs (32,712, 95% CI 15,412-50,013 vs 59,202, 95% CI 42,603-75,800 Japanese yen; $284, 95% CI 134-435 vs $515, 95% CI 370-659, purchasing power parity [PPP]-adjusted; P=.01), direct non-health care costs (922, 95% CI -240 to 2084 vs 2561, 95% CI 1447-3676 yen; $8, 95% CI -2 to 18 vs $22, 95% CI 13 to 32 PPP-adjusted; P=.02), and indirect costs (8981, 95% CI -7119 to 25,082 vs 32,832, 95% CI 17,384-48,279 yen; $78, 95% CI -62 to 218 vs $285, 95% CI 151-420 PPP-adjusted; P=.01) reduced significantly in the telemedicine group compared with the standard care group. The improvements in the Problem Areas in Diabetes Survey (-7.6, 95% CI -13.7 to -1.4; P=.02) and Diabetes Therapy-Related Quality of Life domain 1 (10.5, 95% CI 0.9-20.1; P=.03) scores from the baseline were significantly greater in the telemedicine group than that in the standard care group. Nonetheless, glycemic control and frequency of perinatal complications were comparable between the 2 groups. Consultation time was similar across groups, suggesting no added workload for clinicians. CONCLUSIONS: In this randomized trial, mobile health-enabled telemedicine safely replaced routine in-person visits for patients with GDM requiring insulin therapy. Telemedicine significantly reduced psychological and economic burdens without compromising glycemic or perinatal outcomes, demonstrating its value as a patient-centered and cost-efficient model of care. These findings support the broader implementation of mobile-based telemedicine approaches in GDM management.
12 May 2026
Read appraisal →The aging male : the official journal of the International Society for the Study of the Aging Male
SPISE index and ensemble machine learning refine cardiovascular risk stratification in stage 0-3 CKM syndrome
BACKGROUND: While the single-point insulin sensitivity estimator (SPISE) shows promise as an insulin resistance biomarker, its association with cardiovascular disease (CVD) in early CKM stages (0-3) remains underexplored. METHODS: We analyzed 6480 participants with CKM stage 0-3 from the China Health and Retirement Longitudinal Study. CVD outcomes were assessed relative to SPISE index levels. An ensemble machine learning model was employed to predict CVD risk. RESULTS: 6480 subjects were enrolled, of whom 967 developed CVD. After stratifying participants into SPISE quartiles (Q1-Q4) and adjusting for covariates, higher quartiles were linked to a lower CVD risk. This study developed an LR+GMM (Logistic Regression + Gaussian Mixture Model) ensemble model to predict CVD risk using five strong predictors: SPISE, high-density lipoprotein cholesterol (HDL-c), diastolic blood pressure (DBP), body mass index (BMI), and glycated hemoglobin (HbA1c). The model performed well, achieving an accuracy (ACC) of 0.986 and an area under the receiver operating characteristic curve (AUC) of 0.932. CONCLUSIONS: The SPISE index is a significant inverse predictor of CVD risk in individuals with stage 0-3 CKM syndrome. The LR+GMM ensemble model, incorporating the SPISE index and four clinical metrics, demonstrated outstanding predictive performance.
12 May 2026
Read appraisal →Scientific reports
Hypnotic safety suggestions reduce cortisol awakening response and morning heart rate in daily life.
With stress being causally linked to the most frequently occurring mental and physical health problems, effective coping with acute stress is essential for promoting overall well-being and building long-term stress resilience. However, most interventions aimed at improving stress regulation require extended periods of training and practice. In a previous study, we demonstrated that the Jena Safety Anchor-a brief, hypnosis-based intervention-effectively reduced subjective stress responses in a controlled laboratory setting using the Trier Social Stress Test (TSST). The present study examined whether this effect extends to everyday life. A total of 80 participants (n = 40 female) were randomly assigned to either a hypnosis group or a control group (n = 40 per group). Over the course of two weeks, all participants collected saliva samples at home to assess their cortisol awakening response (CAR), an indicator of anticipatory stress, reflecting the body's preparation for expected demands upon waking. Additionally, all participants continuously recorded their heart rate via smartwatches during the two data collection weeks. The hypnosis group received a single guided session of the Jena Safety Anchor at the end of the first week, while the control group came to the laboratory but received no intervention. CAR was measured via three saliva samples taken within one hour after waking on specified days. Morning heart rate was measured between 6 and 9 a.m. Results revealed a significant reduction in CAR and morning heart rate in the hypnosis group during the second week, following the intervention. In contrast, no change in CAR and morning heart rate was observed in the control group. These findings show that a single session of the Jena Safety Anchor can effectively reduce physiological stress anticipation in the morning. This points to its potential as a rapid, low-effort intervention for enhancing stress coping and fostering resilience. It offers a promising approach to mental health promotion that is both time-efficient and easily integrated into everyday routines.
12 May 2026
Read appraisal →Journal of epidemiology and community health
Children's views of obesity, body size and weight: systematic review of UK qualitative evidence
BACKGROUND: Understanding views about body size and weight is key to addressing both obesity and weight stigma. The views of younger children are not well understood and may differ in important ways from those of adults and young people. This review aimed to fill this gap. METHODS: Systematic review of qualitative evidence. We searched 19 database sources in February 2025 and included qualitative studies from the UK published since 2008 reporting data on children's (4-12 years) views of obesity, body size, body shape or weight. We assessed study quality using the Critical Appraisal Skills Programme checklist and conducted a thematic synthesis of the data. RESULTS: We included 34 studies. Study quality overall was fairly high. Children reported a range of perceived impacts of body weight, including health impacts, limitations on activities, bullying and teasing, which generated negative perceptions of overweight and fear of fatness. Ideas about body shape may be influenced by family members and by media or social media content. Children identified diet and physical activity as the main influences on body weight. There may be differences in views between girls and boys at older ages, although both are concerned about weight. We found very little data on differences relating to ethnicity or socioeconomic status. Children with overweight or obesity reported a pervasive experience of negative attitudes and bullying, which could be a barrier to participating in activities. CONCLUSION: Children, including very young children, generally hold very negative views of overweight and obesity. Overweight is seen to be linked with unhealthiness, limited agency and with being bullied. These links may influence how children understand messages about weight and health. PROSPERO REGISTRATION NUMBER: CRD42025650306.
12 May 2026
Read appraisal →Endocrine pathology
Lineage Classification of Pituitary Neuroendocrine Tumors From Whole-Slide Images Using Attention-Guided Graph Representation Learning
Pituitary neuroendocrine tumors (PitNETs) are common sellar neoplasms and represent a major component of routine pituitary pathology. In the 2022 World Health Organization (WHO) Classification, transcription factor-defined lineage assignment is central to diagnosis. However, lineage-related morphologic information on routine hematoxylin and eosin (H&E)-stained whole-slide images (WSIs) has not been systematically characterized. We developed an attention-guided graph neural network to predict PitNET lineage directly from H&E-stained WSIs and to identify regions prioritized for classification. Consecutive patients who underwent surgical resection for PitNETs at Beijing Tiantan Hospital between 2021 and 2025 were included. In the internal hold-out set, the five fold-specific models achieved a mean F1-score of 92.78% and a mean balanced accuracy of 94.84%. In a temporally independent validation cohort, the final model achieved an F1-score of 87.64% and a balanced accuracy of 89.48%. Performance varied across lineages and histomorphologic subtypes, and the most common error pattern was misassignment of PIT-1 and T-PIT tumors to SF-1. Attention maps predominantly highlighted tumor-rich regions. Quantitative cell-level morphometry supported lineage-associated patterns, including larger cell and nuclear sizes in PIT-1 tumors, more elongated nuclei in SF-1 tumors, and higher cellular density with reduced intercellular spacing in T-PIT tumors. In six cases with multiple synchronous PitNETs of distinct lineages, patch-level prediction maps corresponded closely to transcription factor immunohistochemistry. In a small exploratory subset with available DNA methylation data, methylation classifier results were concordant with model predictions in 11 of 15 cases and with routine histopathologic diagnoses in 8 of 15 cases. These findings indicate that routine H&E-stained WSIs contain learnable morphologic information related to PitNET lineage. Attention-guided spatial modeling provides an interpretable framework for characterizing lineage-associated patterns in PitNETs.
12 May 2026
Read appraisal →Journal of global health
Folate and global health review series, part 3: syntheses on cardiovascular, cerebrovascular, and metabolic diseases.
BACKGROUND: Cardiovascular and metabolic diseases account for an increasing share of morbidity and mortality globally. Folic acid supplementation has been linked to a lowered risk of stroke and some metabolic indicators due to its involvement in homocysteine and one-carbon metabolism and its role in the production of nitric oxide; however, the evidence on these associations is inconclusive. METHODS: We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and the Database of Abstracts of Reviews of Effects from inception to February 2024 for systematic reviews and meta-analyses investigating the associations of folate (dietary intake, supplementation, or blood concentrations) with any cardiometabolic outcome. We performed screening, data abstraction, and risk of bias assessment in duplicate, and assessed the credibility of the evidence using predefined criteria. RESULTS: We identified 113 unique associations from 49 reviews. The included syntheses mostly had low risk of bias of and provided pooled risk estimates from intervention trials or prospective cohorts. A larger volume of evidence was available for composite cardiovascular outcomes, coronary heart disease, and stroke compared to other outcomes. No association reached a convincing or highly suggestive level of credibility. Six directional associations and five null associations met the criteria for a suggestive level of credibility. Three dose-response relationships, all at suggestive levels of credibility, supported an association between higher dietary folate intake and a reduced risk of coronary heart disease and stroke. CONCLUSION: The available evidence on the association between folate status and cardiometabolic outcomes primarily focuses on secondary prevention of cardiometabolic diseases and substantially underrepresents low- and middle-income countries. More large-scale studies are warranted to validate a relationship between folate status and cardiometabolic events or indicators. Overall, the evidence landscape around folate and cardiometabolic diseases appears to be limited both in volume and scope. REGISTRATION: PROSPERO: CRD42021265041.
12 May 2026
Read appraisal →European journal of clinical pharmacology
Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors on lipid profiles in patients with chronic kidney disease: a systematic review and meta-analysis
BACKGROUND: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel oral agents for treating anemia in chronic kidney disease (CKD), with potential effects on lipid modulation. We aimed to systematically evaluate the effects of HIF-PHIs on lipid profiles and cardiovascular outcomes in CKD patients. MATERIALS AND METHODS: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase (Ovid) were searched for randomized controlled trials comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in dialysis-dependent (DD) or nondialysis-dependent (NDD) CKD patients. Primary outcomes included changes in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). Secondary outcomes included cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and all-cause mortality. RESULTS: A total of 20 trials involving 12,155 patients were analyzed in this review. Roxadustat significantly reduced LDL-C (mean difference [MD], -16.07 mg/dL; 95% CI, -17.92 to -14.21; 14 randomized controlled trials [RCTs], 10,510 patients), total cholesterol (MD, -25.25 mg/dL; 95% CI, -29.70 to -20.81; 10 RCTs, 5,538 patients), triglycerides (MD, -19.70 mg/dL; 95% CI, -30.78 to -8.61; 9 RCTs, 4,616 patients), but also decreased HDL-C (MD, -4.91 mg/dL; 95% CI, -6.80 to -3.02; 9 RCTs, 5,132 patients). Desidustat significantly reduced LDL-C and total cholesterol, but showed no significant effects on triglycerides or HDL-C, whereas molidustat showed no significant lipid-lowering effects. Overall, treatment with HIF-PHIs was not associated with significant differences in cardiovascular death (RR, 1.00; 95% CI, 0.84 to 1.18; 10 RCTs, 9,371 patients), myocardial infarction (RR, 1.12; 95% CI, 0.90 to 1.38; 15 RCTs, 11,265 patients), stroke (RR, 1.18; 95% CI, 0.86 to 1.61; 14 RCTs, 11,136 patients), or all-cause mortality (RR, 1.06; 95% CI, 0.96 to 1.17; 19 RCTs, 11,903 patients), compared with ESAs or placebo. CONCLUSION: Roxadustat showed the most substantial lipid-lowering effects, while desidustat showed significant reductions in LDL-C and total cholesterol but no significant effects on triglycerides or HDL-C, and molidustat showed no significant effects. Despite these changes in lipid profiles, no significant differences in cardiovascular outcomes were observed for these three HIF-PHIs, compared with ESAs or placebo.
11 May 2026
Read appraisal →Biomaterials science
Hydrogel-based wearable and implantable biosensors in health monitoring.
Hydrogel-based wearable and implantable biosensors have quickly established themselves as a paradigm-shifting platform for continuous health monitoring. They effectively reconcile the mechanical and chemical discrepancies between conventional rigid electronics and delicate biological tissues. This success is largely attributed to the hydrogel material's inherent advantages: high water content, a precisely tunable elastic modulus, and versatile functional chemistry. Collectively, these features provide structural, biological, and processing benefits that facilitate truly seamless bioelectronic integration. This Review systematically summarizes the latest advancements in hydrogel biosensors, placing emphasis on their distinctive material attributes. These include the synergistic ionic-electronic conduction, sensitive stimuli responsiveness, advanced antifouling surface chemistry, and exceptional tissue-mimicking compliance. We further delve into the fundamental physical and chemical sensing mechanisms, supported by representative applications spanning from the non-invasive, real-time analysis of sweat, tears, saliva, and interstitial fluids to the more complex domains of subcutaneous, cardiac, and neural implants. Finally, we candidly address the crucial hurdles that remain, such as long-term hydration stability, signal fidelity drift, and adverse immune responses. Concurrently, we highlight pioneering strategies to overcome these issues, including the adoption of zwitterionic designs for enhanced biocompatibility, nanocomposite reinforcement for mechanical robustness, and the utilization of transient biodegradability. By critically elucidating the intricate relationships governing hydrogel structure, chemistry, and bioelectronic function, this Review aims to chart the research trajectory toward the next generation of durable, self-healing, and fully biointegrated sensing systems.
11 May 2026
Read appraisal →Journal of medical Internet research
AI in Clinical Decision Support Systems: Promising Applications and Strategies for Managing Data Challenges
The translation of big data analytics and artificial intelligence (AI) into clinical decision support systems (CDSSs) has advanced from proof of concept to real-world clinical practice. AI-informed CDSSs show measurable improvements in diagnostic accuracy, risk stratification, resource use, and patient outcomes compared to traditional models, offering the potential to assist clinicians in managing symptom complexity and uncertainty in health care delivery. Despite this potential, access to large amounts of high-quality and granular data remains one of the most significant bottlenecks to AI-enabled CDSSs. We argue that as health care systems increasingly adopt data-driven decision support, addressing the challenges of data accessibility and protection is essential to realizing the full potential of AI in clinical medicine. We use selected case examples of AI-informed CDSSs in oncology, organ transplantation, diabetic retinopathy, epilepsy, spinal cord injury, rare disease diagnosis, and emergency medicine to illustrate opportunities and challenges related to AI's potential to improve patient outcomes. We discuss public and semipublic, medical institutional and commercial, and government and national data sources that are currently available for the development of CDSSs and highlight the practical and ethical constraints associated with these data. We consider alternative data resources and ways in which health care systems can strengthen data ecosystems to increase AI-driven CDSS efficacy and implementation to improve patient outcomes.
11 May 2026
Read appraisal →Journal of medical Internet research
Effects of Stand-Alone Digital Lifestyle Interventions on Weight-Related Outcomes in Adults With Overweight or Obesity: Systematic Review and Meta-Analysis of Randomized Controlled Trials
BACKGROUND: Obesity is a major global health concern, and scalable digital solutions are urgently needed. While digital lifestyle interventions (DLSIs) have shown promise, prior meta-analyses often included hybrid formats with human support, limiting insights into the effectiveness of fully digital interventions. OBJECTIVE: This study aimed to evaluate the independent effects of standalone DLSIs-defined as interventions delivered exclusively via digital platforms without in-person or adjunctive support-on anthropometric and dietary outcomes in adults with overweight or obesity. METHODS: We searched MEDLINE, Embase, PsycINFO, Web of Science, and the Cochrane Library from inception through March 4, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating stand-alone DLSIs in adults with overweight or obesity. Interventions were included if they targeted diet or physical activity exclusively through digital platforms. We included fully automated, asynchronous, or one-to-many synchronous systems without individualized support. Studies involving hybrid interventions, including one-to-one synchronous human interaction, nonadult populations, or non-RCT designs, were excluded. Two independent reviewers performed study selection and data extraction. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool (Cochrane Bias Methods Group). Meta-analysis used a random-effects model with the Hartung-Knapp-Sidik-Jonkman method, and heterogeneity was assessed using I2 statistics. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: A total of 19 RCTs involving 3556 participants were included. Stand-alone DLSIs significantly improved anthropometric outcomes compared to controls (standardized mean difference 0.26, 95% CI 0.14-0.38; 95% prediction interval [PI] -0.16 to 0.68; P<.001; 19 studies; n=3556; I2=56.1%), corresponding to an additional weight loss ranging from 2.62 kg to 6.55 kg, depending on the baseline body weight. Significant improvements were also found in dietary outcomes (standardized mean difference 0.26, 95% CI 0.04-0.48; 95% PI -0.29 to 0.81; P=.008; 8 studies; n=1365; I2=57.5%). Subgroup analyses for anthropometric outcomes revealed significant differences only by control group type (P<.001), with waitlist controls showing the largest effect. For dietary outcomes, no significant subgroup differences were found (P>.05). While most studies showed a low risk of bias, substantial statistical heterogeneity was observed in some outcomes. Consequently, the certainty of evidence for both outcomes was rated as moderate. CONCLUSIONS: This review is innovative as it is the first to isolate the pure efficacy of stand-alone DLSIs by excluding synchronous human support. Our findings provide moderate-certainty evidence that these tools are effective for weight management and dietary improvement without human intervention. While stand-alone DLSIs offer a highly scalable, cost-effective first-step intervention, the PIs included zero, and substantial heterogeneity was observed, suggesting that benefits may vary across settings. Future research should identify user characteristics that maximize engagement with unguided digital tools.
11 May 2026
Read appraisal →Journal of physiology and biochemistry
Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis
Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12). Chronic exercise (12-36 weeks) showed significant increases in healthy (SMD 0.57; 95%CI 0.33-0.82) and diseased populations (SMD 1.51; 95%CI 0.87-2.16). Resistance exercise thrice weekly demonstrated the highest effect (SMD 1.60; 95%CI 0.81-2.38). Most studies had high risk of bias, with quality of evidence ranging from very low to moderate. Exercise significantly increases s-Klotho levels, with acute and subacute aerobic sessions benefiting healthy and diseased populations, while chronic resistance exercise elicited greater responses in diseased populations. Despite promising findings, low methodological quality suggests cautious interpretation.
10 May 2026
Read appraisal →Lancet (London, England)
Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial
BACKGROUND: Alcohol use disorder accounts for 5% of deaths worldwide annually, and there is an urgent need for new therapeutic interventions. Preclinical and initial human studies indicate that the GLP-1 receptor agonist semaglutide might reduce alcohol drinking. This study evaluated the efficacy of semaglutide once-weekly in treatment-seeking patients with alcohol use disorder and comorbid obesity. METHODS: In a 26-week, single-centre, randomised, double-blinded, placebo-controlled trial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were assigned (1:1) to receive once-weekly semaglutide (2·4 mg subcutaneously) or placebo (saline subcutaneously), in addition to standard cognitive behavioural therapy. The primary endpoint was a reduction in the number of heavy drinking days assessed after 26 weeks of intervention, analysed with an ANCOVA model. Analysis adhered to the intention-to-treat principle, and missing outcome data were addressed using multiple imputations. Safety was assessed in all treated patients. The trial is registered at ClinicalTrials.govNCT05895643, and is complete. FINDINGS: From June 10, 2023, to Feb 4, 2025, 108 participants (53 women and 55 men) were enrolled, with 54 participants in each of the semaglutide and placebo treatment groups, and all were included in the data analysis. Overall, 88 participants (81%) completed the full intervention. Semaglutide was associated with a reduction in heavy drinking days (-41·1 percentage points from baseline, 95% CI -48·7 to -33·5) compared with placebo (-26·4, -34·1 to -18·6; estimated treatment difference -13·7 percentage points, -22·0 to -5·4; p=0·0015), and had substantial effects on multiple secondary alcohol-related and somatic outcomes. Adverse events were transient, generally mild to moderate gastrointestinal effects, and occurred more frequently in the semaglutide group. INTERPRETATION: Semaglutide showed robust therapeutic effects in treatment-seeking participants with obesity and alcohol use disorder and this trial supports previous preclinical and clinical findings suggesting GLP-1 receptor agonists as a potential novel treatment target for alcohol use disorder. FUNDING: The Research Foundation, Mental Health Services (Capital Region of Denmark), the Novo Nordisk Foundation, the Novavi Foundation, the Hartmann Foundation, and the Augustinus Foundation.
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 →Journal of diabetes science and technology
Adherence Monitor for Measurement of Removable Cast Walker Wear-Time: Multiple Sensors and Predictive Analytics Improve Accuracy
BACKGROUND: Treatment of diabetes and its complications is a primary health care expense. Up to 25% of people with diabetes will develop diabetic foot ulcers (DFUs). Removable cast walker (RCW) boots commonly prescribed for DFU treatment, promote healing, and provide offloading and wound protection. Patient RCW removal for hygiene and wound care can lead to decreased adherence and treatment effectiveness. This study evaluated a new system for wear-time adherence measurement using multiple sensor types. METHODS: An electronic wear-time monitor was developed, which included internal and external temperature sensors, an accelerometer, and capacitive proximity foot and ankle sensors. Time-stamped and date-stamped data were saved once per minute for up to 22 days. Ten healthy volunteer subjects were recruited to wear an RCW for two weeks while keeping a diary of don/doff times. Sensor data were then compared with volunteers' wear diaries using confusion matrix predictive analytics. RESULTS: Algorithms were developed for data processing. Correlation coefficients between algorithms and diaries were calculated for individual and multiple sensor combinations. Differential temperature and accelerometer algorithms were significantly better at predicting subject wear-time than individual temperature sensor algorithms (P = .009, P = .001, respectively). Foot proximity had significantly better correlation with subject diaries than temperature (P = .024), and acceleration algorithms (P = .005). Multi-sensor analysis showed high correlation (.96) with wear-time from subject diaries. CONCLUSIONS: Removable cast walker wear-time can be accurately determined using an electronic data recorder and multiple sensors. Wear-time measurement accuracy can be improved using algorithms that operate on data from multiple sensors that use a variety of sensor technologies.
9 May 2026
Read appraisal →Journal of diabetes science and technology
Explainable Machine-Learning Models to Predict Weekly Risk of Hyperglycemia, Hypoglycemia, and Glycemic Variability in Patients With Type 1 Diabetes Based on Continuous Glucose Monitoring
BACKGROUND AND OBJECTIVE: The aim of this study was to develop and validate explainable prediction models based on continuous glucose monitoring (CGM) and baseline data to identify a week-to-week risk of CGM key metrics (hyperglycemia, hypoglycemia, glycemic variability). By having a weekly prediction of CGM key metrics, it is possible for the patient or health care personnel to take immediate preemptive action. METHODS: We analyzed, trained, and internally tested three prediction models (Logistic regression, XGBoost, and TabNet) using CGM data from 187 type 1 diabetes patients with long-term CGM monitoring. A binary classification approach combined with feature engineering deployed on the CGM signals was used to predict hyperglycemia, hypoglycemia, and glycemic variability based on consensus targets (time above range ≥5%, time below range ≥4%, coefficient of variation ≥36%). The models were validated in two independent cohorts with a total of 223 additional patients of varying ages. RESULTS: A total of 46 593 weeks of CGM data were included in the analysis. For the best model (XGBoost), the area under the receiver operating characteristic curve (ROC-AUC) was 0.9 [95% confidence interval (CI) = 0.89-0.91], 0.89 [95% CI = 0.88-0.9], and 0.8 [95% CI = 0.79-0.81] for predicting hyperglycemia, hypoglycemia, and glycemic variability in the interval validation, respectively. The validation test showed good generalizability of the models with ROC-AUC of 0.88 to 0.95, 0.84 to 0.89, and 0.80 to 0.82 for predicting the glycemic outcomes. CONCLUSION: Prediction models based on real-world CGM data can be used to predict the risk of unstable glycemic control in the forthcoming week. The models showed good performance in both internal and external validation cohorts.
9 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 →Journal of the American Society of Nephrology : JASN
Streamlining the Histopathologic Workflow in Diabetic Kidney Disease with Artificial Intelligence
KEY POINTS: Artificial intelligence models effectively generalized across studies and animal models and reduced translational gaps when applied to human biopsies. Artificial intelligence assistance reduced study evaluation turnaround times by up to 90% versus manual whole slide imaging scoring, matching expert-level performance. Self-supervised learning captured diabetic kidney disease-relevant features and mitigated expert-specific bias. BACKGROUND: Assessment of pathology end points in animal models of diabetic kidney disease is time-consuming and prone to expert bias. In addition, the sparsity of human kidney biopsy data hinders the development of translational models from animals to humans. METHODS: We developed an artificial intelligence (AI)-driven workflow to streamline histopathologic assessments in animal models of diabetic nephropathy. Our approach ( 1 ) detected glomeruli in whole slide images, ( 2 ) enabled fast expert scoring through an annotation tool, and ( 3 ) automated scoring. By leveraging unlabeled preclinical data for self-supervised learning, we enhanced AI scoring performance, reduced expert bias, and enabled the translation of AI scoring from animal models to human biopsies. To translate AI models from preclinical studies to human biopsies, we introduced a method that adjusted the feature extractor to human-specific features during inference without the need for annotated examples. RESULTS: Our annotation tool streamlined glomerular scoring, reducing turnaround time by 80%. Supervised AI models outperformed expert agreement and further reduced turnaround time by 90%, demonstrating generalization across studies involving both the same and different animal models. Without supervision, the self-supervised model achieved a κ value of 0.78, effectively identifying glomerular changes without guidance. Incorporating self-supervised learning into supervised training improved performance to κ=0.84 and reduced bias compared with individual experts ( P < 0.001). Our translational approach achieved a κ value of 0.63 on human glomeruli, although the model was trained exclusively on mouse glomeruli scores, reducing the translational gap by 45%. CONCLUSIONS: In this study, we accelerated and enhanced pathology readouts in a real-life pharmaceutical industry setting. We show that AI-assisted scoring reduced pathologists' workload and expedited study assessments. Self-supervised learning captured intrinsic properties of kidney morphology without expert annotation and reduced expert bias and translational discrepancies, greatly facilitating translational activities in drug development for patients with diabetic kidney disease.
5 May 2026
Read appraisal →Science advances
Augmenting ultrasound for continuous glucose monitoring via a wearable acoustically readable microneedle patch
Continuous glucose monitoring (CGM) represents substantial advancement, yet poses a challenge in wearable health care development. Current enzymatic CGM faces limitations in stability, cost, and durability. We introduce an enzyme-free, wearable acoustically readable microneedle patch (ARMPatch) composed of glucose-responsive hydrogel. Positioned between a standard ultrasound probe and the skin, ARMPatch acts as an acoustic interface enabling CGM using conventional ultrasound. Its hydrogel microneedles minimally penetrate the epidermis, allowing interstitial fluid to trigger variable swelling of the microneedles in response to glucose fluctuations. ARMPatch delivers stable and selective glucose readings for up to 56 days. Glucose variations with millimolar resolution are obtained via ultrasound within a response time of 30 to 60 minutes. In vivo CGM in animal models for 7 days reveals a reversible correlation between microneedle swelling and glucose variations. Acting as "accessory" for standard ultrasound probes, this approach offers a minimally invasive, cost-effective, and long-lasting solution to non-enzymatic CGM, expanding the utility of ultrasound in wearable biosensing.
5 May 2026
Read appraisal →Journal of advanced research
Flexible wearable medical devices: from material innovations and data processing to intelligent healthcare applications
BACKGROUND: Flexible wearable medical devices drive healthcare transformation via non-invasive, real-time physiological monitoring and personalized management. Traditional rigid devices lack long-term comfort, while chronic disease care and telemedicine demand reliable, patient-centered solutions. Advances in materials (carbon nanomaterials, liquid metals, hydrogels) enable stretchable, biocompatible substrates adapting to bodily movements. Innovative sensing (PPG, EEG, sweat-based detection) tracks blood pressure, glucose, and neural signals accurately. Key challenges include insufficient sensor flexibility, lagging supervision, data security issues, and large-scale production difficulties, requiring interdisciplinary collaboration. AIM OF REVIEW: This review integrates cutting-edge advances in flexible wearable medical devices, covering material innovations, sensing breakthroughs, power management, and AI-driven data analysis. It evaluates strategies to enhance biocompatibility of carbon composites, liquid metals, and hydrogels, analyzing improvements in device sensitivity, biocompatibility, and real-world applicability. It critically discusses machine learning's role and limitations in chronic disease management, telemedicine, and sports optimization. Key unresolved challenges include lagging regulations, privacy risks in multi-source data fusion, mismatched sensing development, and large-scale production difficulties. The aim is to provide a scalable, secure, and clinically translatable roadmap for future research. KEY SCIENTIFIC CONCEPTS OF REVIEW: Core technologies involve carbon nanomaterials (e.g., graphene), liquid metals (structurally optimized for balanced conductivity and flexibility), and hydrogels (preferred as flexible substrates for mimicking natural soft tissues' mechanics and biocompatibility). Sensing technologies (PPG, EEG, sweat-based detection) enable non-invasive, real-time monitoring of vital parameters like blood pressure, glucose, and neural signals. AI decodes complex physiological data for predictive diagnosis, while IoT/5G integration advances telemedicine. Current limitations include poor sensor flexibility, lagging regulations, and large-scale production hurdles, contrasting with trends like advanced sensing, new materials, and hybrid diagnostic-therapeutic systems-highlighting flexible wearables' potential in intelligent healthcare.
5 May 2026
Read appraisal →Microvascular research
OPU-NET-DADENA: Optimized deep learning ensemble with u-net segmentation for early detection of diabetic retinopathy
One of the most significant microvascular complications of diabetes mellitus (DM) is diabetic retinopathy (DR). In the early stages, patients with DR may not exhibit any noticeable symptoms. It is a diabetic disorder that damages retinal blood vessels in the eyes. At first, there are no symptoms or sporadic visual issues. When it worsens, it affects both eyes and can lead to partial or total blindness. A person who already has DM is therefore constantly at a higher risk of developing the condition. Early identification can prevent the possibility of total and irreversible blindness. Therefore, needs an efficient and early diagnosis system. So, this paper proposes a new deep-learning methodology in a specific Deep Siamese DenseNet for early detection of DR. The proposed method is accomplished through various steps, such as Data Collection, Preprocessing, Augmentation, Segmentation, Feature Extraction, Feature Selection, and Detection. An adaptive histogram equalization approach named Contrast Limited Adaptive Histogram Equalization (CLAHE) is used to preprocess input images, which reduces amplification of noise. Then, the segmentation is done by the Optimized U-NETs. Next, features of the contrasted retinal images are extracted by residual attention EfficientNet (RA-EfficientNet). Then, the optimal features are selected by a hybrid Reptile Search Algorithm (RORS). Finally, the deep learning methodology includes DarkNet, DenseNet 201, and NasNetMobile used to detect diabetic retinopathy at an early stage. The model is implemented in MATLAB and evaluated using accuracy, precision, F-score, specificity, sensitivity, MCC, NPV, FPR, and FNR. The proposed approach achieves 99.33% accuracy and 98.32% precision, outperforming previous methods that reported accuracies of 95-97% and precisions of 94-96%, demonstrating its effectiveness for reliable early detection of DR.
5 May 2026
Read appraisal →Journal of diabetes science and technology
Diabetes-Technology and Waste: The Future is Now.
The downside of the success story of diabetes technology is the amount of waste generated by manufacturing and using such medical products. Quantitative surveys performed in the United States and Germany document how many pounds of plastic waste, batteries, and electronic parts are piling up per patient with diabetes each year; however, the actual environmental burden of diabetes care has not been assessed yet. Given the highly probable further increase in usage of diabetes technology devices, what are the options to change the situation? Ideally, one would avoid generating waste by optimizing the design of the products (Eco-Design); however, this approach faces a number of complex regulatory and economic hurdles. The issue of waste management is becoming increasingly important as the use of wearable devices increases. Stewardship of the environment will require all stakeholders to address waste management.
4 May 2026
Read appraisal →Environmental science. Processes & impacts
Machine learning-driven QSAR models for the prediction of metabolic mechanisms and thyroid hormone-disrupting effects of emerging pollutants in the human body: a case study of bisphenol analogues
Research on theoretical prediction methods for elucidating the reaction mechanisms and thyroid hormone-disrupting effects of emerging pollutants in the human body faces significant challenges. The application of in silico methods utilizing machine learning is increasingly recognized as an effective strategy to determine the mechanisms of reactions catalyzed by human cytochrome P450 enzymes (CYPs) and to predict the adverse effects of emerging pollutants. Bisphenol analogues (BPs) represent one of the most important endocrine disruptors. These compounds can cause serious effects on the ecological environment and human health. Herein, density functional theory (DFT) calculations was employed to investigate the reaction mechanisms of the O-addition and H-abstraction of 20 BPs by human CYPs. A machine-learning-integrated quantitative structure-activity relationship (ML-QSAR) framework was established to predict the energy barriers of three types of reactions. Moreover, binding affinities were calculated between BPs (including their metabolites) and TRβ-LBD to evaluate their thyroid hormone-disrupting effects. The binding affinity data of BPs to TRβ-LBD were used as a training set to develop a ML-QSAR model for efficient prediction of potentially hazardous BPs. A ML-QSAR model with an R2 of 0.869 was established to predict their thyroid hormone-disrupting effects. The study enhances our understanding of CYP catalytic mechanisms involving BPs and provides a reference for the future design of environmentally friendly BPs. The predictive model developed for thyroid hormone-disrupting effects can aid in identifying the adverse effects of emerging BPs, supporting more effective management of toxic compounds.
4 May 2026
Read appraisal →Journal of diabetes science and technology
Plantar Thermogram Analysis Using Deep Learning for Diabetic Foot Risk Classification
AIMS: Thermography is a noninvasive method to identify patients at risk of diabetic foot ulcers. In this study, we employed thermography and deep learning to stratify patients with diabetes at risk of developing foot ulcers. METHODS: We prospectively recorded clinical data and plantar thermograms for adult patients with diabetes who underwent diabetic foot screening. A total of 153 thermal images were analyzed using a deep learning algorithm to determine the risk of diabetic foot ulcers. The neural network was trained using a balanced dataset consisting of 98 thermal images (49 normal and 49 abnormal), with 80% allocated for training and 20% for validation. The trained model was then validated on a separate testing dataset consisting of 55 thermal images (42 normal and 13 abnormal). The neural network was trained to prioritize higher sensitivity in identifying at-risk feet for screening purposes. RESULTS: Participants had a mean age of 63.1 ± 12.6 years (52.3% female), and 62.1% had been diagnosed with diabetes for more than 10 years. The average body mass index was 27.5 ± 5.6 kg/m2. Of the thermal images, 91 were classified as category 0 and 62 as categories 1 to 3, according to the diabetic foot risk classification system of the International Working Group on the Diabetic Foot. Using five-fold cross-validation, the neural network model achieved an overall accuracy of 71.8 ± 4.9%, a sensitivity of 81.2 ± 10.0%, and a specificity of 64.0 ± 7.4%. Additionally, the Matthews correlation coefficient was 0.46 ± 0.08%Conclusions:These results suggest that thermography combined with deep learning could be developed for screening purposes to stratify patients at risk of developing diabetic foot ulcers.
4 May 2026
Read appraisal →Cytopathology : official journal of the British Society for Clinical Cytology
Application of Artificial Intelligence-Based Transfer Learning Models to the Bethesda System for Thyroid Cytopathology
BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) provides a standardised framework for thyroid fine needle aspiration cytology (FNAC). Deep learning approaches, particularly transfer learning, have shown potential for cytology but are rarely applied to TBSRTC categorisation. AIMS AND OBJECTIVES: To evaluate the performance of an ensemble soft voting transfer learning model in categorising thyroid cytology smears according to TBSRTC. MATERIALS AND METHODS: A retrospective study of 94 thyroid FNAC cases with 949 representative images was conducted. Six transfer learning models (Xception, ResNet50V2, DenseNet121, MobileNetV2, InceptionV3, EfficientNetB3) were combined using ensemble soft voting with a weighted average. Model performance was assessed using sensitivity, specificity, precision (PPV), negative predictive value (NPV), F1 score and area under the receiver operating characteristic curve (AUCROC). RESULTS: DenseNet121 achieved the highest overall sensitivity (0.91) and specificity (0.98) among all single models. The weighted ensemble model achieved an F1 score of 0.867, marginally below DenseNet121 but with superior precision (0.882) and NPV (0.968). AUCROC was highest in DenseNet 121 (0.99) followed by the weighted ensemble (0.98). CONCLUSION: This is the first study to apply ensemble transfer learning to TBSRTC categorisation. The approach demonstrated strong predictive accuracy, particularly for benign and malignant categories. Larger datasets, ideally with whole-slide imaging, are needed to further validate these findings.
4 May 2026
Read appraisal →FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Lysosomal Membrane Proteins: Key Regulators of Glucose Metabolism and Its Associated Diseases
Glucose homeostasis, which is critical for maintaining energy supply and health, involves glycogen metabolism, glycolysis, and gluconeogenesis. Lysosomal membrane proteins (LMPs) play core roles in regulating these processes. However, no focused systematic review of the topic has been reported. This review provides an in-depth analysis of the central roles of LMPs in glucose metabolism, focusing on the regulation of glucose homeostasis and their potential effects on metabolic diseases through the regulation of autophagy, signaling networks, specialized transporter functions, and other relevant mechanisms. In general, LMPs play core roles in lysosomal biosynthesis, and an in-depth study of their relationship with glucose metabolism could significantly highlight the important contribution of lysosomes in the development of related diseases.
3 May 2026
Read appraisal →Journal of chemical information and modeling
Generative AI Uncovers Novel Chrebp/Txnip Axis Inhibitors with Potential Anti-inflammatory Activity
Type 2 diabetes is driven in part by metabolic inflammation, where activation of the Chrebp/Txnip axis promotes NLRP3 inflammasome assembly, leading to pancreatic β-cell dysfunction and pro-inflammatory cytokine release. Despite the therapeutic relevance of this pathway, the Chrebp-14-3-3 (regulatory-protein client) protein-protein interaction (PPI) remains largely underexplored, with only a limited number of small-molecule modulators reported to date. To address this gap, we developed an artificial intelligence-driven generative design framework for de novo discovery of selective PPI-targeting compounds. A conditional recurrent neural network (cRNN), implemented as a quantitative structure-property relationship-guided generative network (QSPR-GEN), was pretrained on a large, chemically diverse corpus to learn general SMILES syntax and structural priors, and subsequently fine-tuned on a curated, target-focused data set of approximately 5900 compounds, achieving high scaffold uniqueness (94.6%). Selectivity-oriented physicochemical descriptors were incorporated as conditional inputs to bias generation away from promiscuous chemotypes, while maintaining anchoring to a known active seed. Structure-based refinement was further applied by focusing on the noncanonical α-helical epitope unique to the Chrebp regulatory-protein interface, establishing a dual-layered strategy for selective PPI modulation. The integrated pipeline, combining virtual screening, molecular dynamics simulations, and MM/PBSA free-energy calculations, prioritized lead candidates with favorable binding energetics and pharmacokinetic profiles. In THP-1 macrophages under metabolic stress, the top candidate T7 markedly suppressed Txnip and NLRP3 expression, reduced IL-1β secretion, and attenuated pyroptotic cell death, outperforming a reference inhibitor. Collectively, this study presents a robust computational framework for the inverse design of challenging PPIs and demonstrates its utility through the identification and experimental validation of mechanistically precise lead compounds, exemplified by T2 and T7.
2 May 2026
Read appraisal →Molecular neurobiology
Establishing a Diagnostic Model Based on Plasma CDR1as and Alpha-Synuclein for Mild Cognitive Impairment in Type 2 Diabetes
Emerging evidence implicates cerebellar degeneration-related protein 1 antisense transcript (CDR1as) and alpha-synuclein (α-Syn) in diabetes and cognitive decline, suggesting their potential to serve as biomarkers. This study aimed to evaluate their diagnostic efficacy for type 2 diabetes mellitus-associated mild cognitive impairment (T2DM-MCI) and establish a corresponding diagnostic model using machine learning. T2DM-MCI-associated differentially expressed genes were identified from the hippocampus using the Gene Expression Omnibus and predictive databases. The study involved 529 T2DM patients in two phases (training set = 408, test set = 121). Levels of plasma CDR1as, α-Syn, Aβ1-40/1-42, and ApoE genotype were detected. Three diagnostic models were identified using least absolute shrinkage and selection operator (LASSO) and logistic regression. Their performance was assessed using the area under the curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI). The best-performing model was selected from nine machine learning algorithms. Personalized risk assessment was achieved with the SHapley Additive exPlanations (SHAP). Bio-informatics analysis identified CDR1as and α-Syn as potential biomarkers. Their inclusion in multi-modal panels markedly improved diagnostic accuracy. The Random Forest (RF) model outperformed eight other machine learning classifiers (AUC = 0.975, 95% CI: 0.946-0.999) with the lowest Brier score (0.054). When evaluated on a test set, the RF model maintained robust performance (AUC = 0.901, accuracy = 0.850). An online diagnostic tool was established ( https://www.xsmartanalysis.com/model/list/predict/model/html?mid=6734&symbol=816GyBh9ag1Wr9367341 ). The study preliminarily identified CDR1as and α-Syn as promising biomarkers for T2DM-MCI. Integrating these markers with conventional blood tests showed potential clinical utility for improving diagnostic precision.
2 May 2026
Read appraisal →Bone research
A phase 2 trial of burosumab for treatment of fibroblast growth factor-23-mediated hypophosphatemia in children and adults with fibrous dysplasia
Fibrous dysplasia (FD) is a rare disorder associated with fractures and deformities. FD lesions produce excess phosphaturic hormone fibroblast growth factor 23 (FGF23), leading to hyperphosphaturia in most patients, and hypophosphatemia in those with high FD burden. Skeletal complications are associated with both low-normophosphatemia and frank hypophosphatemia. Burosumab is approved for other forms of FGF23 excess, but there is little evidence to inform use in FD. A phase 2 study investigated the safety and efficacy of burosumab in patients with FD. The primary endpoint was the proportion of participants achieving phosphate levels within the mid to upper part of the normal range (age and sex-adjusted Z-score -1 to +2). 12 participants (7 children, 5 adults) received burosumab for 48 weeks. Median phosphate Z-score increased from -2.88 (1.65) to 0.22 (1.37), meeting the target in 100% of participants. Alkaline phosphatase levels were elevated at baseline in 8 participants [median 846 U/L (464)] and declined by 49% at week 48, representing a median decline of -364 (244.5) U/L. PROMIS questionnaires showed trends toward improvements in all domains in children; adult scores showed no identifiable trends. Two children experienced transformational mobility gains, including advancement from full-time wheelchair use to independent ambulation. Lesion biopsies showed no changes in cellularity or composition, and 18F-NaF PET/CT scans showed no changes in tracer uptake, suggesting burosumab did not adversely impact lesional activity. Adverse events were mild, and none resulted in treatment withdrawal. Burosumab treatment in patients with FD was well-tolerated, restored phosphate homeostasis, and reduced alkaline phosphatase levels. Burosumab has the potential to lead to functional improvements and ambulation gains in severely affected patients and is a valuable tool to reduce the impact of FD-related disability.
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 →The Cochrane database of systematic reviews
Cognitive behavioural therapeutics for insomnia symptoms in the perimenopause through to the early postmenopausal period
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Primary Objective i) To assess the effects of cognitive behavioural therapy for insomnia (CBT-I) and cognitive behavioural therapy for menopausal symptoms (CBT-M) on sleep disturbances in women in perimenopause through to the early postmenopausal period. Secondary Objectives i) To assess the effects of CBT-I and CBT-M on vasomotor symptoms in women in perimenopause through to the early postmenopausal period. ii) To assess the impact of socioeconomic status on the effectiveness of CBT-I and CBT-M, in order to determine the interventions' impact on health equality.
28 Apr 2026
Read appraisal →BMJ paediatrics open
Metabolically obese normal weight phenotype in children and adolescents aged 3 to 18 years: a systematic review
BACKGROUND: Children with normal Body Mass Index (BMI) may still exhibit adverse metabolic profile-termed as the metabolically obese normal weight (MONW) phenotype, placing them at increased risk of long-term cardiometabolic complications. OBJECTIVE: To systematically synthesise the evidence of the MONW phenotype in children and adolescents aged 3-18 years, and to identify early-life determinants. METHODS: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and searched PubMed/ MEDical Literature Analysis and Retrieval System On-Line (MEDLINE), Scopus, Web of Science (WoS), Google Scholar, Embase and Cochrane Library for studies from 2000 to January 2026. Observational studies of children and adolescents aged 3-18 years with normal BMI and at least one metabolic abnormality were included. Two reviewers independently screened the studies, extracted data and assessed risk of bias. Searches were conducted between March 2025 and January 2026, and 11 studies met the predefined inclusion and exclusion criteria. RESULTS: The reported prevalence of MONW ranged from 10.6% to 56.2%, varying by diagnostic criteria and population. Children with MONW consistently showed higher visceral adiposity, insulin resistance (IR), dyslipidaemia, hypertension, impaired glucose metabolism and elevated markers of low-grade inflammation despite having normal BMI. Early-life determinants included extremes of birth weight, rapid infant weight gain, adverse maternal metabolic status, unhealthy dietary patterns and sedentary behaviour. Overall risk of bias across studies was judged to be low to moderate, with the main concerns relating to residual confounding and use of heterogeneous MONW definitions. CONCLUSIONS: MONW represents a clinically relevant but under-recognised paediatric phenotype. Reliance on BMI alone may delay identification of vulnerable children. Early risk stratification integrating metabolic proofing and central adiposity measures may enable timely prevention of long-term metabolic disease. Harmonised operational definitions of MONW and robust longitudinal life-course studies are required to inform evidence-based screening thresholds and preventive interventions.
27 Apr 2026
Read appraisal →ACS sensors
Self-Correction of pH-Induced Signal Variations in Methylene Blue-Labeled Aptamer Electrochemical Biosensors: Wearable Cortisol Detection in Sweat
Common electrochemical aptamer-based (E-AB) biosensors employing methylene blue (MB) redox reporters suffer from significant pH-induced signal variations. Consequently, dynamic pH fluctuations in biofluids, such as in sweat, can greatly distort the measured signal and lead to inaccurate target quantification. Here, we introduce a self-correction strategy that enables accurate analyte quantification by compensating for pH-induced signal variations in MB-based aptasensors using the Nernstian shift of the MB peak potential. The highly reproducible reversible pH dependence of the MB peak potential enables real-time monitoring of the sample pH that provides a continuously synchronized built-in compensation of the pH interference, thereby eliminating the need for external pH sensors or additional measurement steps. This precise yet simple and effective self-correction of pH effects ensures that the Square Wave Voltammetry (SWV) signal reliably reflects real-time analyte variations, as demonstrated using a cortisol MB-labeled E-AB biosensor in both in vitro and on-body settings. In vitro measurements in artificial sweat across pH 5.5-7.5 showed excellent correlation with real-time pH and cortisol changes, confirming the reliability of the peak potential-based correction. On-body measurements using an epidermal wearable patch showed cortisol changes in sweat that would have been missed without this signal-correction method. This approach is broadly applicable to other MB-labeled E-AB biosensors and biofluids, providing a robust strategy for continuous on-body monitoring.
26 Apr 2026
Read appraisal →Journal of ethnopharmacology
Tianjing Zelan formula improves polycystic ovary syndrome by regulating steroid biosynthesis and arachidonic acid metabolism
ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a set of symptoms related to menstrual irregularities that can cause infertility in women of reproductive age. Unfortunately, there are currently no authorized treatment medications for PCOS. The Tianjing Zelan (TJZL) formula, a herbal formulation developed from the ancient Chinese medical classic Beiji Qianjin Yaofang in Tang Dynasty, is employed in the clinical management of menstrual irregularities and amenorrhea. However, its clinical characteristics and mechanism have not been systematically evaluated. AIM OF THE STUDY: To reveal the clinical characteristics and mechanisms of TJZL in treating PCOS. MATERIALS AND METHODS: A multicenter and single-arm clinical trial, and two PCOS models were used to evaluate the effectiveness of TJZL. The chemical constituents of TJZL were analyzed by UHPLC-QTOF-MS/MS. In addition, a combination of untargeted metabolomics and transcriptomics was used to reveal the complex therapeutic mechanisms of TJZL on PCOS. Subsequently, a metabolite-gene network analysis was performed to reveal potential differentially expressed genes associated with metabolites in PCOS patients. Key targets and pathways were further validated using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry in PCOS mice. Finally, molecular docking analysis was employed to explore the potential active ingredients of TJZL. RESULTS: Clinical trials provided evidence that TJZL significantly improved the menstrual cycle, sex hormone levels, and hyperandrogenic phenotypes, and reduced insulin resistance in PCOS patients. TJZL significantly improved the fertility, estrous cycle, ovarian morphology, sex hormone levels, and oral glucose tolerance in PCOS model. Transcriptomic and metabolomics results show that TJZL has a significant regulatory effect on metabolites and gene expression profiles in pathways such as steroid synthesis, arachidonic acid metabolism, and fatty acid metabolism. Utilizing metabolite-gene association analysis, We further verified that TJZL significantly improved the expression of genes and proteins related to the ovarian steroidogenesis and arachidonic acid metabolism pathways, including CYP17A1, CYP19A1, HSD17B3 and PTGS2. Furthermore, molecular docking results showed that berberine, rosmarinic acid and glycyrrhizinic acid in TJZL had strong affinity with PTGS2 in arachidonic acid metabolism, and hesperidin, naringin and liquiritin have strong affinity with CYP19A1 in steroid synthesis. CONCLUSION: TJZL exerts beneficial therapeutic effects on PCOS in both clinical and laboratory studies. TJZL improves PCOS by regulating multiple endogenous metabolites and correcting abnormal steroid synthesis and arachidonic acid metabolism in the ovaries. Our research provides a promising therapeutic agent for PCOS patients.
25 Apr 2026
Read appraisal →Renal failure
Dapagliflozin improves hemoglobin and anemia in chronic kidney disease: a systematic review and meta-analysis
Anemia becomes increasingly prevalent as kidney function declines. Current treatments carry multiple safety risks. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), dapagliflozin, have emerged as background anemia modulator, a promising alternative, showing protective effects against anemia. This study synthesizes evidence on dapagliflozin's potential to improve anemia in chronic kidney disease (CKD) patients. A systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, including eight studies identified from six databases. Risk of bias was assessed using tools appropriate for each study design (RoB 2, NOS, JBI). Data were pooled using a random-effects model with RevMan 5.4. The primary analysis for hemoglobin demonstrated significant increase (MD = 4.37; 95% CI = 0.71-8.03; p = 0.02) and remained significant in the sensitivity analysis (MD = 4.11; 95% CI = 0.19-8.04; p = 0.04). A sensitivity analysis for hematocrit revealed a highly significant increase (MD = 2.15; 95% CI = 1.86-2.44; p < 0.00001). In the sensitivity analysis for adverse events dapagliflozin significantly reduced the overall risk (RR = 0.77; 95% CI = 0.59-0.99; p = 0.04). This finding was associated with significantly lower mortality (RR = 0.67; p = 0.02), while no significant differences were observed for cardiovascular (p = 0.22) or genitourinary events (p = 0.70). Dapagliflozin is associated with clinically meaningful improvements in hemoglobin and anemia outcomes in CKD. These findings suggest a potential erythropoietic benefit beyond glycemic control, although dedicated anemia-focused trials are needed to confirm clinical applicability.
25 Apr 2026
Read appraisal →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 →Journal of medicinal chemistry
The Discovery of RGH-706, a Highly Efficacious MCH1 Receptor Antagonist, for the Treatment of Obesity and Insatiable Hunger
The discovery and characterization of a novel 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole derivative MCH1 receptor antagonist (37) is disclosed. Starting from our previously investigated pyrazino[1,2-a]indole series and utilizing a scaffold hopping strategy, pyrimidine- and 1,4-diazepine-fused indole derivatives were designed and synthesized. Among these, only the prototype molecule containing the 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole scaffold emerged as a chemically stable and potent MCHR1 antagonist. Previous SAR knowledge coupled with an ex vivo occupancy assay helped us to optimize this advanced lead to our candidate (37). The high MCHR1 potency and excellent receptor occupancy profile of 37 translated into statistically significant body weight loss after 14 days in a DIO mice study, supporting the potential use of this compound as a weight loss agent. Compound 37 (RGH-706) has successfully completed a phase I (SAD & MAD) clinical study in the indication of obesity, followed by an exploratory Phase II study in patients with Prader-Willi Syndrome (PWS).
25 Apr 2026
Read appraisal →Nutricion hospitalaria
Refeeding syndrome ‒ What we know and what remains to be explored.
Background: refeeding syndrome (RS) is a serious metabolic complication that occurs upon reintroducing nutrition to malnourished individuals. Although formally recognized for more than 70 years, significant gaps in its understanding remain. Objective: to conduct a narrative review on the current state of knowledge regarding RS, its recent advances, existing gaps, and future perspectives. Methods: an integrative review was conducted using articles published between 2000 and 2024 from international databases, following a systematic methodology of literature search, selection, and analysis. Results: the main pathophysiological mechanisms of RS, its multisystemic clinical manifestations, current diagnostic criteria, and risk-based therapeutic strategies were identified. Despite advances in biomarkers and personalized nutrition, challenges remain in early diagnosis, prevention, and treatment, especially in vulnerable populations. Conclusions: RS continues to pose a complex clinical challenge that requires standardized protocols, identification of reliable biomarkers, and increased clinical research, particularly in underrepresented regions such as Latin America. Prevention, based on a multidisciplinary approach, is important to reducing its impact. Introducción: el síndrome de realimentación (SR) es una complicación metabólica grave que ocurre tras reintroducir la nutrición en personas desnutridas. Aunque formalmente reconocido desde hace más de 70 años, aún existen importantes lagunas en su comprensión. Objetivo: realizar una revisión narrativa sobre el estado actual del conocimiento del SR, sus avances recientes, las brechas existentes y las perspectivas futuras. Métodos: se realizó una revisión integrativa de artículos publicados entre 2000 y 2024 en bases de datos internacionales, siguiendo una metodología sistemática de búsqueda, selección y análisis de la literatura. Resultados: se identificaron los principales mecanismos fisiopatológicos del SR, sus manifestaciones clínicas multisistémicas, los criterios diagnósticos actuales y las estrategias terapéuticas basadas en el riesgo. A pesar de los avances en términos de biomarcadores y nutrición personalizada, persisten desafíos en el diagnóstico precoz, la prevención y el tratamiento, especialmente en las poblaciones vulnerables. Conclusiones: el SR sigue siendo un reto clínico complejo que exige protocolos estandarizados, identificación de biomarcadores fiables y una mayor investigación clínica, especialmente en regiones poco estudiadas como América Latina. La prevención basada en un enfoque multidisciplinario es clave para reducir su impacto.
25 Apr 2026
Read appraisal →BMJ open diabetes research & care
Sex differences in glycemic outcomes: a systematic review and meta-analysis of diabetes treatments
UNLABELLED: Sex differences in glycemic outcomes following insulin therapy remain underexplored despite biological and psychosocial factors that may influence individual responses. This systematic review examines sex-specific differences in glycemic control to guide personalized diabetes care and promote health equity. We searched PubMed, Scopus, Cochrane Library, and Google Scholar (August 2014-December 2025) for randomized and observational studies involving adults of both sexes on insulin. Twenty-four studies were included, with certainty of evidence assessed using GRADE. In type 1 diabetes, women showed no significant difference in achieving HbA1c <7% (RR 1.05, 95% CI 0.91 to 1.22; very low certainty) and toward higher time-in-range (SMD 0.78, -0.01 to 1.57; moderate certainty). In type 2 diabetes, men were more likely to achieve HbA1c targets (RR 0.86, 95% CI 0.72 to 1.03; low certainty), while women required higher weight-adjusted insulin doses (SMD 0.55, 0.23 to 0.86; very low certainty). Hypoglycemia risk showed opposing trends in inpatient (RR 0.78, 95% CI 0.33 to 1.83; very low certainty) versus outpatient settings (RR 1.08, 95% CI 0.61 to 1.89; low certainty) with substantial heterogeneity (I2>70%). These findings suggest that sex-related differences in glycemic outcomes vary by diabetes type and treatment context. Given the low certainty and heterogeneity of current evidence, results should be interpreted as hypothesis-generating. This review supports the consideration of biological sex within a broader, individualized diabetes management framework and highlights the need for future sex-stratified analyses with rigorous control of lifestyle and physiological factors. INTRODUCTION: Sex differences in glycemic outcomes following the same insulin therapy in diabetes remain underexplored. Numerous factors, encompassing both biological and psychosocial aspects, could potentially influence individual responses to insulin therapy. This systematic review examines sex-specific differences in glycemic control to guide personalized diabetes care and promote health equity. METHODS: PubMed, Scopus, Cochrane Library, and Google Scholar were searched (August 1, 2014-December 31, 2025) for randomized and observational studies. Eligible studies included adults of both sexes on insulin reporting sex-specific data for predefined outcomes. Data on glycated hemoglobin (HbA1c), blood glucose metrics, hypoglycemia, and insulin dose were extracted. Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: Twenty-four studies were included. In type 1 diabetes, women showed no significant difference in achieving HbA1c <7% (risk ratio (RR) 1.05, 95% CI 0.91 to 1.22; very low certainty) and toward higher time-in-range (standardized mean difference (SMD) 0.78, -0.01 to 1.57; moderate certainty). In type 2 diabetes, men were more likely to achieve HbA1c targets (RR 0.86, 95% CI 0.72 to 1.03; low certainty), whereas women required higher weight-adjusted insulin doses (SMD 0.55, 0.23 to 0.86; very low certainty). Hypoglycemia risk showed opposing trends in inpatient (RR 0.78, 95% CI 0.33 to 1.83; very low certainty) versus outpatient settings (RR 1.08, 95% CI 0.61 to 1.89; low certainty), with substantial heterogeneity (I2 >70%). CONCLUSION: Sex-related differences in glycemic outcomes under insulin therapy were observed, with patterns varying by diabetes type, treatment context, and outcome. Given the low certainty and heterogeneity of the evidence, these findings should be interpreted as hypothesis-generating rather than directive for clinical practice. The results support consideration of biological sex as one component within a broader, individualized diabetes management framework. Future studies should prioritize sex-stratified analyses with rigorous control of polypharmacy, body composition, and lifestyle factors to determine whether sex-specific insulin strategies provide meaningful clinical benefit. PROSPERO REGISTRATION NUMBER: CRD420251144696.
25 Apr 2026
Read appraisal →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 New England journal of medicine
Transdermal Estradiol Patches in Locally Advanced Prostate Cancer
BACKGROUND: Transdermal estradiol (tE2) is an alternative to luteinizing hormone-releasing hormone (LHRH) agonists as androgen-deprivation therapy in patients with prostate cancer. With tE2, testosterone is suppressed, and the side effects of estrogen depletion due to LHRH agonists and the thromboembolic side effects of oral estrogen are mitigated. METHODS: In this phase 3, noninferiority, randomized trial, we assigned men with locally advanced (M0 and N0 or N+) prostate cancer to receive tE2 patches (100 μg of estradiol every 24 hours) or LHRH agonists. The primary outcome was 3-year metastasis-free survival. The noninferiority margin was 4 percentage points; this corresponded to a target hazard ratio of 1.31, as derived from the observed 3-year metastasis-free survival in the LHRH agonist group. Secondary outcomes included castrate levels of testosterone (<1.7 nmol per liter), overall survival, and safety. RESULTS: Between 2007 and 2022, we recruited 1360 patients at 75 U.K. centers. The median age of the patients was 72 years (interquartile range, 68 to 77); 85% had a T3 tumor stage and 65% an N0 nodal stage. Observed 3-year metastasis-free survival was 87.1% with tE2 and 85.9% with LHRH agonists (hazard ratio for confirmed metastasis or death, 0.96; upper limit of the one-sided 95% confidence interval [CI], 1.11, which met the criterion for noninferiority). Among patients continuing the assigned treatment, castrate levels of testosterone were sustained during the first year after randomization in 85% in each group. Observed 5-year overall survival was 81.1% with tE2 and 79.2% with LHRH agonists (hazard ratio for death, 0.90; 95% CI, 0.75 to 1.07). During treatment, hot flashes occurred in 44% of the patients who received tE2 and 89% of those who received LHRH agonists (grade ≥2 events, 8% and 37%, respectively) and gynecomastia in 85% and 42% (grade ≥2 events, 37% and 9%). CONCLUSIONS: In patients with locally advanced prostate cancer, tE2 was noninferior to LHRH agonists for 3-year metastasis-free survival, with a lower incidence of hot flashes but a higher incidence of gynecomastia. (Funded by Cancer Research U.K. and the U.K. Research Institute Medical Research Council; PATCH ClinicalTrials.gov number, NCT00303784; STAMPEDE-1 ClinicalTrials.gov number, NCT00268476.).
24 Apr 2026
Read appraisal →Journal of medical economics
Cost-effectiveness of tirzepatide versus semaglutide for patients with obesity or overweight in the US: evidence from the SURMOUNT-5 head-to-head phase-3 trial
PURPOSE: This study evaluated the cost-effectiveness (from the United States [US] societal perspective) of tirzepatide at its maximum-tolerated-dose (MTD) compared to semaglutide (MTD), both administered adjunct to a reduced-calorie diet and increased physical activity. The analysis focused on individuals with obesity (body mass index [BMI] ≥ 30 kg/m2), or overweight (BMI ≥27 to <30 kg/m2 + ≥1 obesity-related complication), using data from the head-to-head Phase-3 SURMOUNT-5 trial (patients without type 2 diabetes [T2D]). PATIENTS AND METHODS: This patient-level simulation modeling study assessed the cost and long-term clinical outcomes of tirzepatide (MTD) versus semaglutide (MTD), using data from the SURMOUNT-5 trial population. The modeled population were at risk of developing obesity-related complications including cardiovascular disease (CVD) and obstructive sleep apnea (OSA), amongst others. These outcomes were modeled using cardiometabolic parameters including weight, systolic blood pressure, high-density lipoprotein, glycated hemoglobin (HbA1c) and total cholesterol, by assessing their impact on healthcare and wider societal costs, quality of life, and mortality. Incremental cost-effectiveness ratios (ICERs; cost/quality-adjusted life year [QALY]) and incremental net health benefit (iNHBs) were calculated, and uncertainty was assessed through sensitivity and scenario analyses. RESULTS: Tirzepatide (MTD) was estimated to be less costly and more efficacious compared to semaglutide (MTD) with per patient cost savings of $41,688, 0.506 QALYs gained and positive iNHB of 0.784, indicating a net health benefit for tirzepatide. The model predicted that per 1,000 patients, 70 fewer patients will develop T2D, 10 fewer will develop CVD with tirzepatide (MTD) and patients spend 3.07 more years living with moderate/severe OSA when treated with semaglutide (MTD). CONCLUSION: Based on this simulation model, using head-to-head SURMOUNT-5 trial data, tirzepatide (MTD) had lower total costs and higher QALYs compared to semaglutide (MTD). This supports that tirzepatide (MTD) is a cost-effective treatment option for individuals with obesity or overweight compared to semaglutide (MTD). This study focused on evaluating the cost-effectiveness of two weight management drugs, tirzepatide and semaglutide, for adults in the US who are overweight or have obesity. Using data from the SURMOUNT-5 trial, the analysis showed that tirzepatide was more effective and less costly, providing better weight loss and health benefits compared to semaglutide.The findings revealed that for every 1,000 individuals treated with tirzepatide, there were 70 fewer cases of type 2 diabetes and 10 fewer cases of heart disease compared to those treated with semaglutide. Additionally, patients on semaglutide experienced a longer duration living with moderate or severe sleep apnea. The study highlighted that tirzepatide led to greater improvements in reducing weight and returning blood sugar levels to normal. Over a lifetime, tirzepatide was found to save $41,688 per patient and provide an additional 0.5 quality-adjusted life years (QALYs; a measure that helps compare how much different treatments improve both length and quality of life), emphasizing its advantages both financially and health-wise.Tirzepatide also demonstrated a reduction in absenteeism (when people are not at work because of illness or health problems) and presenteeism (when people are at work but not fully productive because they are unwell), meaning fewer days lost from work compared to semaglutide, thus highlighting productivity benefits. Overall, the research supports that tirzepatide offered a more cost-effective and beneficial treatment option for weight management in the US healthcare context compared to semaglutide.
24 Apr 2026
Read appraisal →JMIR medical informatics
Modeling Diabetes Risk and Progression With Public Health Data: Ontology-Guided, Simulation-Capable Digital Twin Study
BACKGROUND: Digital twins (DTs) offer a paradigm for health care by enabling data-driven, simulation-capable representations of individual health trajectories. However, DT development remains limited by the scarcity of standardized, temporally structured, and multidomain data suitable for modeling chronic disease progression. Most existing DT studies rely on narrowly scoped or proprietary datasets, restricting generalizability. Public health datasets, such as the Midlife in the United States study, provide rich biopsychosocial information but are underused due to structural complexity and lack of semantic integration frameworks. OBJECTIVE: This study aimed to develop and evaluate an ontology-guided, agent-orchestrated framework for constructing offline, simulation-capable, and progression-aware DTs from public health datasets. Using diabetes as a case study, the framework integrates agent-based orchestration, medical ontologies, and large language model (LLM)-assisted semantic reasoning with machine learning to support explainable feature structuring, risk prediction, and predictive "what-if" progression analysis. METHODS: A 6-stage DT framework was developed and applied to Midlife in the United States wave 2 (baseline) and wave 3 (follow-up) data. Ontology- and LLM-assisted feature selection identified predictors across biological, behavioral, psychosocial, and socioeconomic domains. Cleaned and harmonized data were used to train predictive models (random forest, eXtreme gradient boosting, and logistic regression) to estimate diabetes onset at follow-up. A state-transition simulator was implemented to model between-wave progression dynamics, quantify transitions across low-, medium-, and high-risk states, and evaluate predictive "what-if" scenarios such as weight reduction and lifestyle improvement. Model performance was assessed using accuracy, F1 score, area under the receiver operating characteristic curve (AUC), and calibration metrics. RESULTS: From 9976 candidate variables, ontology- and LLM-guided selection retained the top 200 relevant predictors spanning biological, behavioral, psychosocial, and socioeconomic domains. Predictive modeling achieved strong discrimination, with random forest (AUC=0.82, accuracy=0.76) and eXtreme gradient boosting (AUC=0.81, accuracy=0.75) outperforming logistic regression (AUC=0.78). The state-transition simulator reproduced realistic progression patterns: 33.9% (1414/4174) of participants changed risk states between waves, and the high-risk group increased from 10.8% (451/4174) to 32.2% (1344/4174). Next-state prediction accuracy reached 92.5%. Predictive "what-if" analyses showed that with a simulated 10% weight reduction, model-estimated diabetes cases decreased by 98 (from 576 to 478). A placebo test (0% weight change) produced less than 0.3% difference in risk distribution, confirming model stability. CONCLUSIONS: This study presents a foundational, ontology-guided, and agent-orchestrated framework for constructing offline, simulation-capable, and progression-aware DTs from public datasets. By combining semantic reasoning, multidomain predictors, and predictive "what-if" progression simulation, the framework transforms static population data into longitudinal, interpretable representations of individual health trajectories. The proof-of-concept application to diabetes demonstrates that public health data can support robust and explainable DT models for exploratory risk analysis and hypothesis generation, without implying causal intervention effects or direct clinical decision support.
24 Apr 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Secukinumab in Moderate-to-Severe Graves Orbitopathy: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study
CONTEXT: Interleukin (IL)-17, a key proinflammatory cytokine, drives inflammation and fibrosis in Graves orbitopathy (GO), and elevated IL-17 and Th17 cells correlate with disease activity and severity. OBJECTIVE: The ORBIT study aimed to evaluate the efficacy and safety of secukinumab, an IL-17A inhibitor, in individuals with active, moderate-to-severe GO. METHODS: A randomized, double-blind, placebo-controlled, parallel-group, multicenter trial was conducted. Adults with active, moderate-to-severe, non-sight-threatening GO randomly (1:1) received secukinumab 300 mg or placebo subcutaneously over a 16-week double-blind treatment period, followed by an additional 16-week open-label treatment phase for proptosis nonresponders. Safety parameters, thyroid-related hormones, and autoantibodies were also assessed. The primary end point was overall response of reduced Clinical Activity Score (CAS) of 2 or more points and a reduction of 2 mm or greater in proptosis from baseline without worsening in the fellow eye at week 16. RESULTS: Twenty-eight adult GO patients with a CAS of 4 or greater were enrolled (secukinumab, n = 14; placebo, n = 14). None in either the secukinumab or placebo group achieved an overall response at weeks 16 and 32, respectively, when all patients received open-label secukinumab. No clinically meaningful changes were observed in ophthalmic symptoms and signs, proptosis, lid aperture, eye muscle motility, CAS, and health-related quality of life either at week 16 or week 32. No meaningful effect on serum levels of thyroid-related hormones and antibodies was observed. Secukinumab was well tolerated, with mostly mild adverse events. Neither treatment-induced study discontinuation nor new safety signals were registered. CONCLUSION: Secukinumab did not show clinical efficacy vs placebo when treating patients with active, moderate-to-severe GO.
24 Apr 2026
Read appraisal →European journal of preventive cardiology
Aerobic exercise and cardiovascular outcomes in patients with diabetes undergoing percutaneous coronary intervention: a nationwide population-based study
AIMS: We investigated the impact of aerobic exercise on clinical outcomes in patients with diabetes undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: We analyzed a nationwide prospective population database from the Korean National Health Insurance System. We included 8225 patients with diabetes who had undergone PCI and documented their aerobic exercise habits before and after the procedure (mean interval: 2.0 years). The patients were categorized into four groups: persistent non-exercisers, new exercisers, exercise discontinuers, and exercise maintainers. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction, revascularization, and heart failure. We assessed the risk of clinical events using inverse probability-weighted Cox proportional hazards models. During a mean follow-up of 4.9 years, exercise maintainers, discontinuers, and new exercisers were associated with a significantly lower risk of MACE compared to non-exercisers. The lowest risk was observed in exercise maintainers (maintainers: aHR, 0.78; 95% CI: 0.71-0.86; discontinuers: aHR, 0.88; 95% CI: 0.79-0.98; new exercisers: aHR, 0.89; 95% CI: 0.80-1.00). A J-curve relationship between the amount of aerobic exercise and adverse clinical outcomes was observed, with the lowest risk identified at 1000-1499 MET-min/week. Benefits diminished with exercise intensity ≥1500 MET-min/week. CONCLUSION: Aerobic exercise maintenance after PCI was associated with a reduced risk of cardiovascular events in patients with diabetes, with a moderate amount of exercise providing maximal benefit. Therefore, aerobic exercise is advisable for patients with diabetes undergoing PCI, and the optimal exercise dosage warrants further research. LAY SUMMARY: This large-scale prospective population study, based on the Korean National Health Insurance System, demonstrated that maintaining aerobic exercise in patients with diabetes undergoing percutaneous coronary intervention is significantly associated with a lower risk of cardiovascular events.A J-curve relationship was observed between the amount of aerobic exercise and clinical outcomes, with the lowest risk observed at 1000-1499 MET-min/week for both new exercisers and the entire study population.However, exercising beyond 1500 MET-min/week offers diminishing returns, highlighting the need for balanced exercise intensity.
24 Apr 2026
Read appraisal →ACS applied materials & interfaces
Flexible, Scalable SERS Substrate with High Sensitivity and Stability for On-Site Detection and Wearable Applications
A key challenge in the commercialization of surface-enhanced Raman scattering (SERS) technology is the scalable and controllable preparation of substrates that simultaneously achieve high sensitivity, uniform signal distribution, excellent reproducibility, and long-term stability. In this study, we report a flexible SERS substrate based on a porous, high-surface-energy nanofilm, designed to serve as a spatially confined template for the uniform growth of silver nanoparticles (AgNPs). This substrate exhibits outstanding SERS performance with an enhancement factor (EF) of 2.05 × 1010 and a detection limit (DL) as low as 1.74 × 10-15 M for rhodamine 6G (R6G). The preparation process is mild, highly reproducible (RSD = 8.53% over 60 consecutive batches), and scalable to 25 cm2 areas. Moreover, the substrate maintains its SERS activity for over three months within a vacuum bag at room temperature. Owing to its excellent adhesion and good flexibility, the substrate can adhere effectively to complex surfaces. The substrate was successfully applied to sensitive in situ detection of trace thiram residues on grape surfaces, achieving a detection limit (DL) of 8.51 × 10-10 g cm-2. Additionally, a wearable sensor was developed based on the substrate and used for the noninvasive monitoring of uric acid levels in human sweat, with a DL of 2.95 × 10-7 M. This work provides a practical strategy for constructing high-performance, scalable, and flexible SERS substrates, advancing their potential for real-time, on-site analysis.
23 Apr 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
An Interpretable Machine-Learning Model for Predicting Occult Central Lymph Node Metastasis in Papillary Thyroid Cancer
CONTEXT: Accurate preoperative prediction of occult lymph node metastasis (OLNM) in clinically lymph node negative (cN0) papillary thyroid carcinoma (PTC) is critical for optimizing therapeutic strategy, particularly for thermal ablation and active surveillance. OBJECTIVE: The aim of this study was to develop an interpretable machine-learning (ML) model to predict the risk of OLNM in cN0 PTC patients. METHODS: This retrospective study analyzed data of 961 cN0 PTC patients (August 2018-August 2023). Multivariable logistic regression identified independent risk factors for OLNM in cN0 PTC. The cohort was randomly divided into the training and test sets, and a subset of patients with tumors sized 1 cm or less was further extracted from the test set for internal validation. Eight ML models incorporating clinical, ultrasonographic, and molecular features were developed and evaluated. Shapley Additive exPlanations (SHAP) enhanced interpretability. RESULTS: RET fusion positivity and BRAF mutation positivity were identified as independent molecular risk factors for OLNM in cN0 PTC, alongside 6 clinical and ultrasonographic variables. Nine predictors were incorporated into the predictive model. The random forest (RF) model achieved optimal performance with an area under the curve (AUC) of 0.906 in the training set and 0.733 in the test set, along with the lowest Brier scores of 0.135 and 0.212, respectively. Analysis of tumors sized 1 cm or less internally validated the model's robustness with an AUC of 0.719. SHAP analysis identified size, age, and clustered punctate echogenic foci as the top predictors. CONCLUSION: This is the first study to identify RET fusion positivity as an independent OLNM risk factor in cN0 PTC. The developed RF model demonstrates moderate predictive performance for OLNM risk and provides a framework for integrating clinical, sonographic, and molecular data, and is deployed as a web calculator (https://predictingoccultlymphnodemetastasis.shinyapps.io/web3/).
23 Apr 2026
Read appraisal →PloS one
A hybrid CNN-XLSTM-GRU deep learning model with autoencoder-based feature selection for hypothyroidism diagnosis.
Hypothyroidism, caused by reduced thyroid-hormone production, is often difficult to diagnose because its symptoms are non-specific and overlap with other disorders. We developed FusionNet-CXG, a hybrid deep-learning model that couples CNN, eXtended LSTM, and GRU components for hypothyroidism prediction. Experiments were performed on a public dataset (3,772 records; 30 features). Class imbalance was mitigated using SMOTE-NC, and performance was estimated using 10 repetitions of 5-fold stratified cross-validation, yielding 50 fold-level evaluations to obtain stable results. Across folds, FusionNet-CXG achieved 0.9394 mean accuracy, F1 = 0.906, and AUC-ROC = 0.94, and it exceeded CNN+LSTM and CNN + BiLSTM baselines under the same protocol. The results indicate that combining local feature extraction with recurrent modelling is effective for this task. To support interpretability, SHAP was used to quantify feature influence on the predictions. Future work will focus on external validation using more diverse real-world cohorts and incorporating temporal clinical data to improve clinical relevance.
23 Apr 2026
Read appraisal →The Analyst
Recent progress in wearable electrochemical sensors based on MXene-conductive hydrogels
MXene-based conductive hydrogels (MCHs) have emerged as highly promising materials for next-generation wearable electrochemical sensors, owing to their exceptional electrical conductivity, mechanical flexibility, and biocompatibility. This review provides a comprehensive and up-to-date overview of recent advances in the development of wearable sensors that incorporate Ti3C2Tx MXene hydrogels for the detection of a wide range of analytes in various biofluids. Diverse hydrogel matrices have been integrated with MXenes to fabricate highly sensitive platforms capable of monitoring key biomarkers such as glucose, dopamine, uric acid, lactate, norepinephrine, sodium, creatinine, and pH. These sensors have been successfully deployed at various locations in the body, including the forearm, chest, wrist, and head, using flexible formats such as skin patches, microfluidic devices, pantyliners, wearable caps, and attachable body accessories. Notably, several configurations demonstrate ultralow detection limits, reaching the nanomolar level, enabling real-time, noninvasive analysis of sweat, urine, and other physiological fluids. The wide range of functional additives and customizable design approaches underscores the modularity and tunability of MCH-based systems for specific applications. This review critically evaluates the design principles, sensing mechanisms, performance metrics, and practical limitations of current MCH-based wearable platforms, providing insights that can guide future innovations in smart wearable healthcare technologies.
23 Apr 2026
Read appraisal →Annals of medicine
Comparative evaluation of oxidative stress biomarkers F2-isoprostanes and 8-OHdG in Parkinson's disease and Type 2 Diabetes Mellitus: a systematic review and meta-analysis of human studies
BACKGROUND: Oxidative stress is central to type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). However, the utility of biomarkers for lipid peroxidation (F2-isoprostanes) and DNA damage (8-OHdG) in the comorbidity of PD and T2DM remains unclear. METHODS: We conducted a systematic review and meta-analysis of 54 unique studies of human subjects aged ≥ 50 years (n = 7,521: 3,522 with T2DM, 722 with PD, and 3,277 controls), measuring biomarkers in serum, plasma, or leukocytes. Mixed-effects models quantified standardized differences (Hedges' g) across subgroups. RESULTS: In T2DM, F2-isoprostanes (g = 1.60, 95% CI: 0.95-2.25) and 8-OHdG (g = 2.64, 95% CI: 2.13-3.14) were markedly elevated (p < 0.001). Stronger effects were observed in younger cohorts and serum/plasma samples, with complications like nephropathy exhibiting extreme oxidative stress (g = 5.24). In PD, 8-OHdG was moderately elevated (g = 0.78, 95% CI: 0.18-1.39; p = 0.011), particularly in randomized controlled trials and plasma samples, whereas F2-isoprostanes were not significantly elevated (g = 0.47, 95% CI: -0.43-1.38). High heterogeneity in T2DM (I2 > 90%) reflected methodological variability. CONCLUSION: Distinct profiles - both markers elevated in T2DM but only 8-OHdG in PD - underscore 8-OHdG's potential in PD-T2DM comorbidity. Future research should focus on standardized assays, multi-compartmental or multi-modal sampling, and longitudinal studies to clarify mechanisms and therapeutic targets.
21 Apr 2026
Read appraisal →BMJ open
Cost-effectiveness of osteoporotic fracture risk assessment in people with intellectual disabilities: a UK NHS modelling study
OBJECTIVES: We compared the cost-effectiveness of alternative fracture risk assessment strategies for people with intellectual disabilities (ID) aged ≥40 years from a UK National Health Services perspective over a lifetime horizon. DESIGN: Cost-effectiveness analysis using a lifetime decision-analytical model. SETTING: UK primary care, with data from literature and national databases. PARTICIPANTS: People with ID. INTERVENTIONS: Three strategies were assessed: (S1) Risk assessment using the UK QFracture score; (S2) use of IDFracture (a fracture risk prediction tool specifically developed for adults with ID); and (S3) conducting a one-time dual-energy X-ray absorptiometry (DXA) scan in all. S1 and S2 were followed by DXA scan for those at risk. At-risk individuals received treatment according to UK practice (bisphosphonates plus vitamin D and calcium for osteoporosis, and vitamin D and calcium alone for osteopenia). PRIMARY OUTCOME MEASURES: Direct healthcare costs and quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: In the base case, S2 (ICER: -£2568/QALY) was dominant (ie, less costly and more effective) and S3 (ICER: £1678/QALY) was cost-effective relative to S1 for major osteoporotic fracture (MOF). For hip fracture, S2 (ICER: £32 116/QALY) and S3 (ICER: £49 536/QALY) were not cost-effective relative to S1 under the National Institute for Health and Care Excellence-recommended cost-effectiveness thresholds. Findings from the sensitivity analyses were predominantly consistent with the base-case results. Subgroup analyses showed that age-specific and gender-specific strategies could be used. CONCLUSION: For people with ID aged ≥40 years, a proactive approach to risk assessment for MOF is not only clinically beneficial, but also cost-effective.
20 Apr 2026
Read appraisal →Global health action
Lifestyle interventions to prevent gestational and type 2 diabetes among migrant women from low- and middle-income countries: a systematic review.
Migrant women from low- and middle-income countries (LMICs) living in high-income settings experience disproportionately high risk of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM). This review aimed to identify and synthesise culturally adapted lifestyle interventions for preventing or managing GDM and T2DM among migrant women from LMICs, focusing on intervention components, cultural adaptation strategies, and behavioural and metabolic outcomes. Five databases (PubMed, Embase, Scopus, CINAHL, Cochrane Central) were searched using Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 guidelines. Eligible studies included experimental designs involving lifestyle interventions delivered to migrant women from LMICs in high-income countries, reporting outcomes related to GDM or T2DM targeting behaviour change. Data were synthesised narratively; study quality was appraised using RoB2 for RCTs and a structured narrative approach for non-randomised designs. Certainty of evidence was evaluated using GRADE. Eight studies met the inclusion criteria. Sample sizes ranged from 28 to 641 participants. Intervention duration varied from 6 weeks to 12 months. Most interventions incorporated atleast one culturally tailored component, such as bilingual delivery, culturally adapted dietary education, or community-based engagement. Improvements were reported across dietary behaviours, physical activity, glycaemic measures, or diabetes-related knowledge; however, effect sizes were modest and inconsistent. Interventions combining dietary modification, physical activity, and culturally adapted delivery demonstrated greater improvements than exercise-only or digital-only programmes. Overall certainty of evidence ranged from low to moderate. Culturally adapted, multi-component lifestyle interventions show promise for improving behavioural and metabolic outcomes among migrant women from LMICs; however, the evidence base remains limited. Main findings: Culturally adapted, multi-component lifestyle interventions show modest but inconsistent improvements in behavioural and metabolic outcomes among migrant women from low- and middle-income countries with overall low-to-moderate certainty of evidence.Added knowledge: This review highlights cultural adaptation as a key feature of intervention effectiveness and identifies important evidence gaps, including limited high-quality studies and challenges in comparing heterogeneous interventions.Global health impact for policy and action: Policies should prioritise scalable, culturally responsive interventions – such as bilingual and community-based approaches – to reduce diabetes disparities and improve maternal health outcomes in migrant populations.
19 Apr 2026
Read appraisal →Medical science monitor : international medical journal of experimental and clinical research
Use of Deep Learning Models in the Diagnosis of Proptosis Through Orbital Magnetic Resonance Imaging
BACKGROUND Proptosis is a common manifestation of orbital disease; however, current diagnostic tools, such as the Hertel exophthalmometer and manual radiological measurements, have limited reproducibility and are observer-dependent. More objective, automated approaches are needed. In this single-center retrospective study, orbital magnetic resonance imaging (MRI) examinations from 521 participants (261 with proptosis, 260 controls) were analyzed. Proptosis was defined on MRI using interzygomatic line-based distance criteria. Three-dimensional convolutional neural network models based on DenseNet121, DenseNet169, DenseNet264, and ResNet50 architectures were trained on volumetric orbital MRI data. MATERIAL AND METHODS Data were divided into training, validation, and test sets, and 5-fold cross-validation with early stopping was used to optimize and validate model performance. Diagnostic performance was assessed using accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS DenseNet121 achieved the best overall performance, with mean accuracy of 95.0%, AUC of 0.986, sensitivity of 92.7%, and specificity of 96.9% across 5-fold cross-validation. CONCLUSIONS To the best of our knowledge, prior artificial intelligence studies in orbital imaging have primarily focused on CT-based measurements, radiomics approaches, or thyroid-associated orbitopathy assessment rather than end-to-end 3-dimensional deep learning analysis of orbital MRI volumes. In this context, the present study explores a volumetric MRI-based deep learning framework for automated proptosis detection, emphasizing patient-level classification and explainable model interpretation.
19 Apr 2026
Read appraisal →Inflammation research : official journal of the European Histamine Research Society ... [et al.]
The calcium-sensing receptor in sepsis and septic shock, mechanistic pathways and translational perspectives: a systematic review.
BACKGROUND: Sepsis and septic shock are major causes of mortality in critically ill patients. They are linked to widespread metabolic and immune dysregulation, including alterations in calcium and phosphate homeostasis. The calcium-sensing receptor (CaSR) not only plays a role in mineral balance, but also modulates key immune pathways and may contribute to the pathogenesis of sepsis. METHODS: A systematic literature review was conducted according to PRISMA 2020 guidelines. Four databases (PubMed, EMBASE, Cochrane Library, and Google Scholar) were searched for studies published since 1990. To be eligible for inclusion, articles had to be original research, reviews, or clinical trials involving adult models (mammalian or human). Full-text availability was required. Risk of bias was assessed for all studies included. RESULTS: Sixty-six articles met the inclusion criteria: 49 original studies and 17 reviews. No randomized controlled trials or meta-analyses were identified. Most studies relied on in vitro or in vivo models. CaSR was consistently reported to be upregulated or activated following exposure to bacterial and inflammatory stimuli in immune cells, including monocytes and lymphocytes. CaSR activation promotes proinflammatory cytokine release, notably IL-1β via the NOD like receptor family 3 (NLRP3) inflammasome although results in intestinal epithelial models remain inconsistent. In non-septic models, CaSR activation was associated with tissue and organ injury, including renal and cardiac damage, as well as vasoplegia related to endothelial dysfunction. Preclinical models of pneumonia and endotoxemia suggest that CaSR antagonists may effectively mitigate inflammation and organ injury. CONCLUSION: This systematic review identifies the CaSR as an amplifier of the host inflammatory response across both septic and non-septic preclinical models The lack of robust clinical data underscores the need for translational studies assessing CaSR expression or activity in patients with sepsis or septic shock, alongside in vivo validation of CaSR inhibition as a therapeutic strategy.
19 Apr 2026
Read appraisal →BMJ open
'It's not just diabetes': implementation enablers and barriers of an indigenous-focused virtual diabetes care clinic using the Consolidated Framework for Implementation Research (CFIR) - a qualitative assessment.
INTRODUCTION: Indigenous peoples living with diabetes face unique challenges accessing comprehensive specialty diabetes care. A small diabetes virtual care clinic oriented towards Indigenous individuals, and those in rural and remote communities, has provided care to over 400 individuals. OBJECTIVES: We characterised the distinguishing features of care provided at this clinic and used the Consolidated Framework for Implementation Research 2.0 (CFIR) to explore the enablers and barriers to implementing this model of care, from the perspective of the clinic's staff and providers. RESEARCH METHODS AND DESIGN: Guided by CFIR, we conducted eight semi-structured interviews with six clinic staff members. Deductive thematic analysis was used to identify relevant enablers and barriers. RESULTS: The aspirational features of care were cultural safety, comprehensiveness and virtual delivery. The implementation of this model of care was enabled by an internal culture of relational care; a nimble, resourceful, pragmatic and client-centred approach to virtual delivery; wayfinding and resources from key external organisations; community engagement and a small team of motivated and independent providers. Key barriers included the lack of physical interactions and uncertain or limited resources and funding. CONCLUSION: The identified enablers and barriers to implementing an Indigenous-focused virtual diabetes care clinic have implications for future interventions to improve rural Indigenous chronic disease care, and for governments and adjacent organisations tasked with meeting Canada's Truth and Reconciliation Commission's calls to action in healthcare. Further research examining the effectiveness of virtual diabetes care at this clinic is ongoing.
19 Apr 2026
Read appraisal →Journal of the International Society of Sports Nutrition
Effects of eight weeks of eicosapentaenoic acid and medium-chain triacylglycerol structured lipid intake on EPA/AA ratio and muscle performance in young men
BACKGROUND: Structured triglycerides (STGs), in which eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are esterified with medium-chain triglycerides (MCTs), have demonstrated greater bioavailability and potential benefits in improving endurance and reducing post-exercise strength loss compared with physical mixtures (PMs) of EPA and MCTs. However, it remains unclear whether STGs have superior effects on blood EPA levels and muscular endurance and fatigue. This study compared the effects of 8-week STG and PM intake on blood EPA levels, muscular endurance, and fatigue following resistance exercise. METHODS: Twenty-eight healthy young men were randomly assigned to an STG group (n = 15) or a PM group (n = 13) in a double-blind, parallel-group, active comparator trial. Participants consumed 4,560 mg/day of the test oil (600 mg EPA, 260 mg DHA) for 8 weeks. After the intervention, the participants performed four sets of leg extensions to exhaustion at 40% of their body weight. Muscular endurance was assessed by the number of repetitions, and fatigue was evaluated by changes in maximal voluntary contraction, range of motion, thigh circumference, muscle thickness, echo intensity, and jump performance. RESULTS: The STG group showed a significantly greater increase in the serum EPA/arachidonic acid (AA) ratio compared with the PM group. However, no significant differences were found between groups in repetition counts or fatigue-related measures. CONCLUSION: Eight weeks of STG supplementation improved the blood EPA/AA ratio more than a PM, but did not yield superior effects on muscle endurance or fatigue.
18 Apr 2026
Read appraisal →Neuron
Spatial and single-cell transcriptomic atlas of human suprachiasmatic nucleus
The suprachiasmatic nucleus (SCN) is considered the master pacemaker of the circadian clock in mammals, but our current knowledge of the SCN is mostly based on rodent studies. Here, we report a comprehensive molecular and cellular atlas for the adult human SCN by spatial transcriptomics, single-nucleus RNA sequencing, and deep-learning-based histological analysis. We identified seven human SCN neuron subtypes with specific transcriptomes and spatial distributions. Comparison of humans, mice, and non-human primates revealed the conserved functional segregation within the SCN regulated by LIM homeobox 1 (LHX1) and RAR-related orphan receptor B (RORB). Furthermore, our results suggested that the human SCN has undergone marked reorganization of its neuropeptide signaling network. Finally, integrative analysis of human SCN transcriptomes and genome-wide association studies (GWASs) identified arginine vasopressin (AVP)/neuromedin S (NMS) subtype as the potential neuronal correlate for morningness chronotype. Thus, our spatial and single-cell transcriptomic atlas of the human SCN provided a basis for the understanding of neural and molecular mechanisms of the human circadian clock.
18 Apr 2026
Read appraisal →Breast cancer research and treatment
Oral selective estrogen receptor degraders in hormone receptor-positive, HER2-negative advanced breast cancer: a systematic review and meta-analysis
PURPOSE: The development of endocrine resistance is frequent in hormone receptor-positive, HER2-negative advanced breast cancer (HR + /HER2-ABC), particularly after CDK4/6 inhibitor exposure. Next-generation oral selective estrogen receptor degraders (SERDs) have been developed to improve estrogen receptor blockade; however, randomized trials have yielded heterogeneous results with uncertain clinical benefit. METHODS: A PRISMA 2020 compliant systematic review and meta-analysis with PROSPERO registration was conducted. PubMed, Embase, and Cochrane CENTRAL were searched through October 2025 for phase II-III randomized trials comparing oral SERDs with standard endocrine therapy (ET) in HR + /HER2-ABC after prior ET. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Treatment effects were pooled using random effects models with prespecified subgroup analyses by ESR1 mutation status and key clinical characteristics. RESULTS: Six randomized trials, including 2808 patients, were analyzed. Oral SERDs improved PFS versus standard ET in the overall population (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.70 to 0.89). ORR was higher with oral SERDs (odds ratio [OR] 1.67; 95% CI 1.23 to 2.28), corresponding to absolute response rates of approximately 21% versus 14%. An OS improvement was observed (HR 0.72; 95% CI 0.57 to 0.90), although follow-up was limited. Benefit was concentrated in ESR1-mutated tumors (PFS, HR 0.57; 95% CI 0.48 to 0.67) with no significant PFS advantage in ESR1 wild-type disease. Gastrointestinal adverse events were more frequent with oral SERDs compared with the control ET. CONCLUSIONS: Pooled randomized evidence supports a clinically meaningful benefit of oral SERDs over standard ET after endocrine progression in HR + /HER2-ABC, with the strongest and most consistent efficacy observed in ESR1-mutated disease.
18 Apr 2026
Read appraisal →Journal of the American College of Surgeons
Predictive Model for Mild Autonomous Cortisol Secretion in Patients Evaluated in Artificial Intelligence-Driven Adrenal Incidentaloma Clinic
BACKGROUND: Mild autonomous cortisol secretion (MACS) is present in approximately 20% to 50% of adrenal incidentalomas. These patients do not exhibit the clinical manifestations of overt Cushing's syndrome, and differentiation from nonfunctional adrenal incidentalomas (NFAI) is typically made after a low-dose dexamethasone suppression test. The objective of this study was to develop predictive models to distinguish MACS from NFAI using clinical and radiological parameters. STUDY DESIGN: This retrospective study included patients evaluated in an adrenal incidentaloma clinic between February 2022 and August 2024 who were diagnosed with either NFAI or MACS. Demographic characteristics, medical and medication history, and radiological features were collected. Patients were randomly divided into training and test cohorts in a 3:1 ratio. Predictive models for MACS were developed using Least Absolute Shrinkage and Selection Operator (LASSO) regression and random forest (RF) algorithms. RESULTS: A total of 397 patients were included, with 297 allocated to the training set and the remaining 100 to the test set. The mean age was 62.3 years, and 55% of participants (n = 220) were women. MACS was present in 34% of the study population (n = 136). The most influential predictive factors of MACS were BMI, Posterior Adiposity Index, and the number of antihypertensive medications. The LASSO and RF models achieved discrimination with area under the curve values of 0.686 and 0.736, respectively. At Youden Index thresholds balancing sensitivity and selectivity, the LASSO model had 58.8% sensitivity, 75.8% specificity, and 70% accuracy, whereas the RF model had 64.7% sensitivity, 75.8% specificity, and 72% accuracy. CONCLUSIONS: Predictive models incorporating clinical and radiological characteristics offer a promising approach for distinguishing MACS from NFAI in patients with adrenal incidentalomas.
17 Apr 2026
Read appraisal →BMJ open
mHealth-based Healthy Lifestyle Promotion (MYLIFE) for metabolic syndrome risk reduction in Chinese employed adults: protocol for a cluster-randomised controlled trial
INTRODUCTION: Metabolic syndrome (MetS) poses a significant public health challenge among employed adults. Lifestyle modifications have been shown to be effective in preventing the onset and progression of MetS in employed adults, and the widespread adoption of mobile and wearable technologies introduces an appealing approach to mHealth lifestyle interventions. When widely implementing smartphone-based interventions for employed adults, enhancing equitable access and promoting wearable device use for those with MetS is a more cost-effective way to reduce health disparities, particularly in resource-limited settings. However, relevant evidence is currently lacking. OBJECTIVE: This study aims to design an mHealth-based Healthy Lifestyle Promotion (MYLIFE) trial, a three-arm randomised controlled trial (RCT), to evaluate the effectiveness of a smartphone-based lifestyle intervention and a combined smartphone-based lifestyle intervention with intensive intervention for MetS individuals using wearable devices, in reducing MetS risk among employed adults. METHODS AND ANALYSIS: This is a three-arm, parallel, single-blind, cluster RCT with a 12-week intervention and a total follow-up of 1 year. The trial will recruit 120 workplaces from the Chinese Cohort of Working Adults in a 1:1:1 ratio to either a control group or one of two intervention groups. Within these workplaces, a total of at least 348 eligible participants will be enrolled. The regular mHealth group will receive smartphone-based intervention. The intensive mHealth group will receive smartphone-based intervention for all participants, and an additional wearable device-intensive intervention for those with MetS. The primary outcome is the Chinese MetS Z score at 12 weeks. Secondary outcomes include MetS Z score, prevalence of MetS, specific MetS components, questionnaire-based indicators, and clinical outcomes at 12 weeks and 1 years. The main analysis will follow the intention-to-treat principle, using mixed-effects models to assess between-group differences in outcomes. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of the West China School of Public Health and the West China Fourth Hospital, Sichuan University (Gwll2025024). The findings will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2500101904.
17 Apr 2026
Read appraisal →PloS one
Ultra-processed food consumption and the risk of overweight and obesity in adolescents: A systematic review and meta-analysis
INTRODUCTION: Overweight and obesity during early life increase the risk of premature morbidity and mortality. Adolescent obesity raises the likelihood of developing cardiovascular risk factors, including prediabetes, type 2 diabetes, dyslipidemia, hypertension, liver disease, and metabolic syndrome. Sedentary lifestyles and unhealthy diets are major contributors, with one of the fastest-growing unhealthy eating patterns being the consumption of ultra-processed foods (UPFs). No systematic review and meta-analysis has specifically examined the association between UPF consumption and overweight/obesity in adolescents. OBJECTIVE: To systematically review and conduct a meta-analysis of available evidence on the association between UPF consumption and overweight or obesity among adolescents. METHODS: We searched PubMed, ScienceDirect, HINARI, Google, and Google Scholar for primary studies reporting UPF consumption and overweight/obesity outcomes in adolescents, without restrictions on language or study period. Study quality was assessed using the Newcastle-Ottawa Scale. Heterogeneity was evaluated using Cochrane's Q test and the I² statistic. Publication bias and small-study effects were assessed using Egger's regression test (p < 0.05). A random-effects model estimated pooled associations. RESULTS: Twenty-three studies involving 155,000 adolescents were included. Adolescents with higher UPF consumption had 63% greater odds of overweight or obesity compared with those with lower intake (OR = 1.63; 95% CI: 1.36-1.95). CONCLUSION: High UPF consumption is associated with an increased risk of overweight and obesity among adolescents. Public health strategies targeting reduced UPF intake and promotion of healthier diets should be prioritized to prevent adolescent overweight/obesity and associated health risks.
16 Apr 2026
Read appraisal →The Journal of clinical investigation
Disrupted neurovascular-endocrine coupling in type 1 diabetes with impaired awareness of hypoglycemia
BACKGROUNDRecurrent hypoglycemia in type 1 diabetes (T1D) may culminate in impaired awareness of hypoglycemia (IAH). While neuroimaging studies identified affected brain regions, more complex perspectives integrating vascular dynamics with endocrine profile are needed.METHODSHere, 26 healthy adults, 30 T1D patients with normal hypoglycemia awareness (NAH), and 25 T1D patients with IAH underwent a hyperinsulinemic stepped clamp (euglycemia → hypoglycemia 50 mg/dL) combined with pseudo-continuous arterial spin-labeling MRI. Cerebral blood flow (CBF) and sympathetic vasomotor range (0.02-0.05 Hz) CBF oscillations were modeled against serially sampled plasma cortisol, epinephrine, norepinephrine, and glucagon.RESULTSIn healthy individuals treated as controls, hypoglycemia evoked robust thalamo-striatal and salience-interoceptive CBF increases (mean Cohen's d across significant clusters = 0.93) and suppression of vasomotor oscillations (d = 0.71). T1D retained CBF response but failed to attenuate oscillations (dT1D>controls = 0.43). IAH further blunted hypoglycemia-associated CBF increase, especially in thalamus, striatum, and insula (dNAH>IAH = 0.51). Hormone-CBF coupling differed quantitatively: cortisol/epinephrine-CBF correlations were positive in controls (r = 0.37/0.26), negative in NAH (-0.16/-0.40), and strongly positive in IAH (0.42/0.46).CONCLUSIONThus, our findings indicate that T1D disrupts dynamic, sympathetic modulation of CBF, whereas IAH additionally impairs perfusion reserve and shows maladaptive catecholamine-dependent CBF regulation, suggesting a qualitatively distinct neurovascular phenotype.TRIAL REGISTRATIONClinicalTrials.gov: NCT02747680 and NCT02866435.FUNDINGNIH (P41-EB-015894, P30-NS-076408, R01-DK-099137, R56-DK-099137, and DP1 AG093028); National Center for Advancing Translational Sciences of the NIH (KL2-TR-000113 and UL1-TR-000114); DP1 AG093028; Charles University, Czech Republic (Cooperatio Program, research area NEUR), Brain Dynamics (grant number CZ.02.01.01/00/22_008/0004643); General University Hospital in Prague (MH CZ-DRO-VFN64165).
16 Apr 2026
Read appraisal →Clinical cancer research : an official journal of the American Association for Cancer Research
A Multicenter Phase II Randomized Controlled Trial Comparing 177Lu-Dotatate/Capecitabine Combination Treatment with 177Lu-Dotatate Monotherapy in Patients with Neuroendocrine Tumors
PURPOSE: Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-[DOTA0,Tyr3]octreotate (177Lu-Dotatate) is an effective and safe treatment for patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP NET). Whereas 177Lu-Dotatate prolongs progression-free survival (PFS) and preserves quality of life (QoL), objective response rates (ORR) remain limited. Capecitabine, as a radiosensitizer, could increase efficacy without increasing 177Lu-Dotatate activity. This phase II randomized controlled trial investigated the additional cytotoxic or radiosensitizing effect of capecitabine in combination with 177Lu-Dotatate. PATIENTS AND METHODS: Patients with advanced somatostatin receptor-positive GEP NET or bronchopulmonary NET were scheduled to receive four cycles of 7.4 GBq 177Lu-Dotatate and capecitabine or 177Lu-Dotatate alone. Capecitabine (1,650 mg/m2/day) was administered for 2 weeks from the start of each PRRT cycle. Primary endpoints were ORR, PFS, and median overall survival (OS). Secondary endpoints included biochemical response, adverse events, and QoL. RESULTS: A total of 111 of the 200 predefined patients were randomized for 177Lu-Dotatate/capecitabine (n = 50) or 177Lu-Dotatate (n = 61). According to the intention-to-treat analysis, the ORR was 32% for the 177Lu-Dotatate/capecitabine group versus 46% for the 177Lu-Dotatate group (P = 0.348). Treatment with 177Lu-Dotatate/capecitabine did not prolong median PFS (45.7 vs. 31.7 months, P = 0.629) or median OS (75.8 vs. 61.4 months, P = 0.530). Quality-adjusted life years (QALY) were lower in the 177Lu-Dotatate/capecitabine group (1.30 ± 0.48 vs. 1.47 ± 0.48, P = 0.014). CONCLUSIONS: In this prematurely closed phase II study, 177Lu-Dotatate/capecitabine did not improve ORR or prolong PFS and OS in patients with advanced NET compared with 177Lu-Dotatate alone and was associated with reduced QALY.
16 Apr 2026
Read appraisal →Human fertility (Cambridge, England)
The global evaluation of the effects of antioxidants on seminal outcomes in infertile men: a systematic review and meta-analysis
The aim of the current review is to summarise information from publications on the impact of antioxidants on seminal outcomes in infertile men. A systematic search was performed in the five valid databases (Scopus, PubMed, Medline, Embase, and Web of Science) utilizing two sets of keywords up to September 2025, according to the PRISMA approach. Of the 11749 papers identified, 101 papers were included in this review, for a total of 11889 infertile men. Sperm concentration, normal sperm morphology, progressive sperm motility, and total sperm motility, were considerably higher in experimental groups compared with control groups. Both sperm concentration (106 mL-1) and total motility (%) were higher in experimental groups compared to control groups with an overall pooled standardised mean difference (SMD) of 2.33 (95% CI: 1.73, 2.94) for sperm concentration and SMD of 1.62 (95% CI: 1.20, 2.04) for total motility (%). Subgroup analysis demonstrated that duration of treatments of more than 6 months were more effective than those of less than 3 months. Based on the findings of this review, no definitive recommendation can be made regarding the use of antioxidants as a therapy for male infertility, and further research is necessary.
16 Apr 2026
Read appraisal →The Journal of clinical investigation
Carriage of rare APOB variants predisposes to severe steatotic liver disease and hepatocellular carcinoma
BACKGROUNDMetabolic dysfunction-associated steatotic liver disease (MASLD) has a substantial inherited component. Rare variants in apolipoprotein B gene (APOB) have been implicated in susceptibility to liver steatosis, but their role in disease progression and outcomes is unclear.METHODSWe investigated APOB rare variants in a case-control cohort of people with advanced MASLD versus healthy controls (n = 510 and 261, respectively), a family-based study (n = 43 and literature meta-analysis), the Million Veteran Program (MVP) cohort (n = 94,885), and the UK Biobank (UKBB) (n = 417,657).RESULTSIn the clinical cohort, APOB variants were enriched in people with advanced MASLD (OR 13.8, 95% CI: 2.7-70.7, P = 0.002) and associated with lower circulating lipids, but higher MASLD activity and fibrosis (P < 0.05). In the family study, APOB variants segregated with hepatic steatosis and fibrosis (P < 0.05). Cross-ancestry meta-analysis of the study cohorts yielded pooled ORs for cirrhosis and hepatocellular carcinoma (HCC) of 1.82, 95% CI: 1.33-2.49 and 3.53, 95% CI: 2.09-5.98, respectively. Variants affecting specifically ApoB100 had a 3-fold greater effect on hepatic lipid metabolism compared with those impairing also ApoB48 and were specifically protective against coronary artery disease (P < 0.05). The variants affected cirrhosis risk similarly, but ApoB48/100 had a larger effect on HCC (P < 0.05).CONCLUSIONSRare APOB variants predispose individuals to advanced MASLD and HCC, with distinct contributions from disrupted VLDL and chylomicrons secretion. These findings highlight the interplay between hepatic and intestinal lipid handling, suggesting that APOB genotyping may enhance MASLD risk stratification and patient identification.FUNDINGEuropean Union, Italian Ministry of Health, Swedish Research Council, Veterans Health Administration, NIH.
16 Apr 2026
Read appraisal →Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
SERS-based deep learning approach for early detection of gestational diabetes mellitus
Early and precise diagnosis of gestational diabetes mellitus (GDM) is crucial for improving maternal and neonatal outcomes and reducing the risk of adverse pregnancy events. However, current clinical screening methods for GDM still exhibit limitations in detection speed, sensitivity and convenience, making it difficult to meet the clinical demand for rapid early-pregnancy screening. To address this, we propose a novel strategy for early GDM diagnosis based on surface-enhanced Raman spectroscopy (SERS) combined with deep learning, aiming to achieve rapid and accurate early screening. Characteristic SERS spectra of serum were obtained using a substrate based on silver nanoparticles (Ag NPs). A fused PCA-CNN model integrating principal component analysis (PCA) for dimensionality reduction and a one-dimensional convolutional neural network (1D-CNN) for feature learning was developed. The PCA-CNN model effectively extracts potential biomarker features from serum SERS spectra, achieving a diagnostic accuracy of 93.7%, with sensitivity and specificity of 0.95 and 0.93, respectively. Moreover, the entire detection process can be completed within 30 min, requires about 2.5 μL of serum per sample, and involves minimal preprocessing, highlighting both efficiency and practicality. This study provides a novel method for early GDM screening that combines high diagnostic performance with clinical applicability, offering promising technical support for early intervention and clinical management of GDM.
16 Apr 2026
Read appraisal →Open heart
Chronotype-aligned exercise timing in middle-aged adults at cardiometabolic risk: a randomised controlled trial
OBJECTIVE: To investigate whether aligning exercise timing with chronotype enhances cardiometabolic and sleep-related benefits in sedentary adults with cardiovascular risk factors. METHODS: In this 12-week randomised controlled trial conducted in Lahore, Pakistan (January-June 2025), 150 sedentary adults (aged 40-60) with at least one cardiovascular risk factor were recruited and categorised as morning-type or evening-type using the Morningness-Eveningness Questionnaire and validated by 48 hour core body temperature monitoring. Participants were randomised into a chronotype-aligned exercise (CAE) group exercising at their preferred time, or a chronotype-misaligned exercise (CME) group exercising at their non-preferred time. Moderate-intensity aerobic training (5 sessions/week, 40 min/session) was supervised. Primary outcomes included systolic and diastolic blood pressure (BP) and heart rate variability (RMSSD); secondary outcomes included peak oxygen consumption (VO₂ peak), low density lipoprotein (LDL), fasting glucose and sleep quality (PSQI), assessed pre- and post-intervention. RESULTS: Of 150 randomised participants, 134 completed the study (CAE: n=64; CME: n=70). CAE led to significantly greater improvements in systolic BP (-10.8 vs -5.5 mm Hg, p=0.002), diastolic BP, RMSSD, VO₂ peak, LDL, fasting glucose and PSQI scores compared with CME. Repeated measures analysis of variance (ANOVA) revealed significant group×time interactions across all outcomes (eg, systolic BP: η²=0.095, p=0.005). The reduction in systolic BP in the CAE group was substantial and significantly greater than in the CME group. CONCLUSION: Aligning exercise timing with individual chronotype significantly enhances cardiometabolic and sleep-related outcomes in at-risk adults. Chronotype-based exercise prescriptions may offer a cost-effective, personalised approach to improving cardiovascular health.
16 Apr 2026
Read appraisal →African journal of reproductive health
The therapeutic potential of exosomes derived from mesenchymal stem cells for premature ovarian failure: A systematic review
This review evaluates mesenchymal stem cell-derived exosomes (MSC-Exos) for treating premature ovarian failure (POF). A comprehensive search was conducted across five databases, including PubMed, Embase, and Web of Science (WoS), yielding 17 English-language studies published between 2016 and 2025. Studies primarily using animal and in vitro models assessed the therapeutic effects and mechanisms of MSC-Exos from diverse sources. MSC-Exos significantly elevated estrogen levels, reduced follicle-stimulating hormone (FSH), increased antral follicle counts, and restored estrous cyclicity. Specifically, BMSC-Exos activated the PI3K/AKT pathway via miRNAs to suppress granulosa cell apoptosis; hUCMSC-Exos mitigated cellular senescence and autophagy; ADSC-Exos promoted follicular development through SMAD and SIRT1/FOXO1; PMSC-Exos attenuated ROS damage by improving mitochondrial function; AFSC-Exos together with MenSC-Exos enhanced oocyte maturation via the P53 pathway. Notably, perinatal exosomes showed 18-32% greater efficacy in functional recovery than adult-tissue counterparts with fewer doses. MSC-Exos present a promising therapeutic strategy for POF by targeting apoptosis, autophagy, angiogenesis, and oxidative stress. Perinatal-derived exosomes offer superior potential due to their non-invasive collection and minimal ethical concerns. Nonetheless, challenges pertaining to heterogeneity, long-term safety, and standardized manufacturing necessitate resolution through multicenter clinical trials to advance clinical applicability.. Cette revue évalue l’utilisation d’exosomes dérivés de cellules souches mésenchymateuses (MSC-Exos) pour le traitement de l’insuffisance ovarienne prématurée (IOP). Une recherche exhaustive a été menée dans cinq bases de données, notamment PubMed, Embase et Web of Science (WoS), et a permis d’identifier 17 études publiées en anglais entre 2016 et 2025. Les études, reposant principalement sur des modèles animaux et in vitro, ont examiné les effets thérapeutiques et les mécanismes d’action des MSC-Exos issus de différentes sources. Les MSC-Exos ont significativement augmenté les taux d’œstrogènes, réduit l’hormone folliculostimulante (FSH), accru le nombre de follicules antraux et rétabli la cyclicité œstrale. Plus précisément, les exosomes dérivés de cellules souches mésenchymateuses de la moelle osseuse (BMSC-Exos) ont activé la voie PI3K/AKT via des miARN afin de supprimer l’apoptose des cellules de la granulosa ; les exosomes dérivés de cellules souches mésenchymateuses du cordon ombilical humain (hUCMSC-Exos) ont atténué la sénescence cellulaire et modulé l’autophagie ; les exosomes dérivés de cellules souches mésenchymateuses du tissu adipeux (ADSC-Exos) ont favorisé le développement folliculaire via les voies SMAD et SIRT1/FOXO1 ; les exosomes dérivés de cellules souches mésenchymateuses placentaires (PMSC-Exos) ont réduit les dommages liés aux espèces réactives de l’oxygène (ROS) en améliorant la fonction mitochondriale ; les exosomes dérivés de cellules souches du liquide amniotique (AFSC-Exos), associés aux exosomes dérivés de cellules souches mésenchymateuses menstruelles (MenSC-Exos), ont amélioré la maturation ovocytaire via la voie P53. Il est à noter que les exosomes d’origine périnatale ont montré une efficacité de récupération fonctionnelle supérieure de 18 à 32 % à celle des exosomes issus de tissus adultes, et ce avec un nombre de doses plus faible. Les MSC-Exos constituent une stratégie thérapeutique prometteuse pour l’IOP en ciblant l’apoptose, l’autophagie, l’angiogenèse et le stress oxydatif. Les exosomes d’origine périnatale offrent un potentiel supérieur grâce à un prélèvement non invasif et à des préoccupations éthiques limitées. Néanmoins, des défis liés à l’hétérogénéité, à la sécurité à long terme et à la standardisation de la fabrication doivent être résolus au moyen d’essais cliniques multicentriques afin de favoriser une application clinique. Cette revue évalue l’utilisation d’exosomes dérivés de cellules souches mésenchymateuses (MSC-Exos) pour le traitement de l’insuffisance ovarienne prématurée (IOP). Une recherche exhaustive a été menée dans cinq bases de données, notamment PubMed, Embase et Web of Science (WoS), et a permis d’identifier 17 études publiées en anglais entre 2016 et 2025. Les études, reposant principalement sur des modèles animaux et in vitro, ont examiné les effets thérapeutiques et les mécanismes d’action des MSC-Exos issus de différentes sources. Les MSC-Exos ont significativement augmenté les taux d’œstrogènes, réduit l’hormone folliculostimulante (FSH), accru le nombre de follicules antraux et rétabli la cyclicité œstrale. Plus précisément, les exosomes dérivés de cellules souches mésenchymateuses de la moelle osseuse (BMSC-Exos) ont activé la voie PI3K/AKT via des miARN afin de supprimer l’apoptose des cellules de la granulosa ; les exosomes dérivés de cellules souches mésenchymateuses du cordon ombilical humain (hUCMSC-Exos) ont atténué la sénescence cellulaire et modulé l’autophagie ; les exosomes dérivés de cellules souches mésenchymateuses du tissu adipeux (ADSC-Exos) ont favorisé le développement folliculaire via les voies SMAD et SIRT1/FOXO1 ; les exosomes dérivés de cellules souches mésenchymateuses placentaires (PMSC-Exos) ont réduit les dommages liés aux espèces réactives de l’oxygène (ROS) en améliorant la fonction mitochondriale ; les exosomes dérivés de cellules souches du liquide amniotique (AFSC-Exos), associés aux exosomes dérivés de cellules souches mésenchymateuses menstruelles (MenSC-Exos), ont amélioré la maturation ovocytaire via la voie P53. Il est à noter que les exosomes d’origine périnatale ont montré une efficacité de récupération fonctionnelle supérieure de 18 à 32 % à celle des exosomes issus de tissus adultes, et ce avec un nombre de doses plus faible. Les MSC-Exos constituent une stratégie thérapeutique prometteuse pour l’IOP en ciblant l’apoptose, l’autophagie, l’angiogenèse et le stress oxydatif. Les exosomes d’origine périnatale offrent un potentiel supérieur grâce à un prélèvement non invasif et à des préoccupations éthiques limitées. Néanmoins, des défis liés à l’hétérogénéité, à la sécurité à long terme et à la standardisation de la fabrication doivent être résolus au moyen d’essais cliniques multicentriques afin de favoriser une application clinique.
15 Apr 2026
Read appraisal →Food & function
Metabolic and inflammatory effects of oleuropein and olive leaf extract: a systematic review and meta-analysis
Background: Olive leaves, a by-product of olive oil production, are rich in oleuropein, a phenolic compound with antioxidant and anti-inflammatory properties. This systematic review and meta-analysis evaluated the effects of olive leaf extract (OLE) and oleuropein on glucose metabolism, lipid profile, and inflammatory markers in randomized clinical trials (RCTs). Methods: The review was registered in PROSPERO (CRD42022375615) and followed PRISMA guidelines. PubMed, Scopus, and Web of Science were searched up to January 2026 without restrictions. Eligible studies were RCTs in adults comparing OLE or oleuropein with placebo or control. Study selection, data extraction, and risk of bias (RoB 2) assessment were performed independently by two reviewers; certainty of evidence was assessed with GRADE. Meta-analyses were conducted when at least two trials reported suitable data. Results: Eleven RCTs were included (4 short-term and 7 continuous-intake trials). Short-term crossover studies showed heterogeneous effects on postprandial glycemia and insulin responses, precluding meta-analysis. In continuous-intake, parallel-design RCTs, pooled analyses demonstrated no statistically or clinically significant effects on glycemic or lipid outcomes. Evidence regarding inflammatory markers was scarce and of low certainty. Conclusion: The current evidence does not support clinical recommendations for OLE supplementation aimed at health benefits. Data from methodologically consistent and robust trials indicate no statistically significant metabolic or inflammatory effects under usual human consumption patterns, whereas evidence from other study designs remains inconclusive. Further high-quality RCTs are required to clarify potential metabolic benefits.
15 Apr 2026
Read appraisal →Analytical chemistry
Dual-Signal Amplification Strategy for Synchronous Monitoring of Stress Hormones and Metabolic Indicators
The synchronous monitoring of stress hormones and metabolic indicators is crucial for long-term health management, yet it remains a significant challenge for wearable sensors, primarily due to the ultralow abundance of biomarkers in sweat and the vulnerability of weak electrochemical signals to interference. Herein, we report a wearable electrochemical sensor based on a dual-signal amplification strategy for the synchronous and highly sensitive detection of cortisol, glucose (Glu), and uric acid (UA). The CuFe-PBA/CC substrate provides a platform featuring high surface area, electrocatalytic activity, and dual signal amplification capabilities, which are the primary sources of high sensitivity. The MIP layer enhances the effective concentration of target substances near active sites through a local enrichment effect. Combined with the substrate's high catalytic activity, this amplifies the electrochemical signal specific to the target. It synergizes with an exogenous redox probe ([Fe(CN)6]3-/4-) to establish a dual-amplification pathway, which enhances the current output to the milliampere level and substantially improves the signal-to-noise ratio. To ensure the optimal performance of the sensor, the preparation parameters were optimized via the integration of machine learning. This integrated sensing system exhibits high selectivity, superior sensitivity (with detection limits of 44.78 fM for cortisol, 0.064 μM for Glu, and 0.089 μM for UA), and excellent stability (retaining 88% of the initial signal after 100 cycles of mechanical deformation). Furthermore, we fabricated the sensor into a watch-like form factor, integrated it with high-precision wearable electronic modules, and achieved real-time wireless detection of sweat cortisol, Glu, and UA in ex vivo sweat monitoring experiments. This work provides a novel solution for objective stress assessment and metabolic status monitoring, holding promise for advancing long-term health management applications.
15 Apr 2026
Read appraisal →Food & function
Regular black tea kombucha consumption is associated with improved insulin resistance and increased ADIPOQ expression in adults with obesity: a pre-post clinical trial
Kombucha is a fermented beverage obtained by a Symbiotic Culture of Bacteria and Yeast (SCOBY). Although in vitro and animal studies suggest that kombucha has anti-inflammatory and anti-obesogenic properties, no clinical trials have confirmed that. In this pre-post clinical intervention study, we aimed to evaluate whether regular black tea kombucha consumption would impact metabolic, inflammatory, and oxidative stress markers; body weight and composition; and obesity-associated genes in individuals with and without obesity. This study follows the Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) guidelines. Individuals with normal weight (Group 1; n = 20) and with obesity (Group 2; n = 16) received 200 mL of black tea kombucha for 8 consecutive weeks. Blood and subcutaneous adipose tissue (SAT) were collected at the baseline (T0) and after 8 weeks of intervention (T8). Most inflammatory (hs-CRP, IFN-γ, TNF-α, and IL-4, IL-6, IL-8, IL-10, and IL-12p70) and oxidative stress markers (FRAP, MDA, and NO) showed significant changes over time following the intervention. However, interaction analyses revealed that responses to kombucha consumption differed between groups for only a limited number of variables: body weight, conicity index, HOMA-IR, and hs-CRP. An upregulation of the gene ADIPOQ in the SAT (p = 0.0481) was also observed, alongside a positive correlation between the BMI and PPARγ (r = 0.58; p = 0.030), and between HOMA-IR and both NFκB (r = 0.73; p = 0.002) and SREBF1 (r = 0.66; p = 0.010). In conclusion, metabolic and inflammatory pathways may respond differently to kombucha consumption depending on the obesity status. The results are mainly attributed to the high number and diversity of phenolic compounds identified in the black tea kombucha, which confer a high antioxidant capacity to the beverage.
15 Apr 2026
Read appraisal →Neurology
Type 1 Diabetes and Incident Dementia: An Analysis in the All of Us Cohort
BACKGROUND AND OBJECTIVES: Although diabetes mellitus (DM) is a well-established determinant of dementia risk, most studies have evaluated type 2 DM (T2DM) or any DM. The influence of type 1 DM (T1DM) on dementia risk remains unclear. We evaluated associations of T1DM and T2DM, separately, with incident dementia using linked electronic health records (EHRs). METHODS: This prospective cohort study used previously collected survey and EHR data from the All of Us (AoU) cohort, a convenience sample of US adults. Eligible participants were 50 years or older and completed baseline surveys. Enrollment began in 2017, with data available through October 2023, along with records before enrollment. Mean follow-up from baseline was 2.4 years. We developed an algorithm to distinguish DM type based on count of T1DM encounters. This algorithm was validated against 2 reference measures: self-reported diabetes type and C-peptide values. Using AoU data, we classified participants as having no DM, T1DM, or T2DM. We ascertained incident dementia using ICD-9, ICD-10, and Systematized Nomenclature of Medicine codes in participants' EHRs. We estimated hazard ratios (HRs) and 95% CIs for the association of diabetes type with incident dementia using Cox proportional hazards models. RESULTS: Among 283,772 participants (mean [SD] age 64.62 [8.96] years; 56.7% women), 60.3% identified as non-Hispanic White and 13.3% as Hispanic/Latino. Optimal DM classification algorithm cutoffs varied by reference standard: self-reported diabetes: ≥1 T1DM EHR encounter (sensitivity: 0.59; specificity: 0.90) and C-peptide: ≥3 T1DM EHR encounters (sensitivity: 0.76; specificity: 0.79). Defining T1DM as having ≥1 T1DM encounter, 5,442 participants had T1DM. Compared with those without DM, participants with T1DM had higher dementia incidence (sociodemographic-adjusted HR 2.82; 95% CI 2.28-3.48) and those with T2DM also had elevated risk (sociodemographic-adjusted HR 2.08; 95% CI 2.87-2.31). Results were similar across sex, race, and ethnicity strata. DISCUSSION: In AoU, DM was associated with elevated dementia risk, with the highest risk among those with T1DM. These findings highlight the need to better understand mechanisms tying T1DM to dementia.
14 Apr 2026
Read appraisal →Cardiovascular toxicology
A Real-World Disproportionality Analysis of Drug-Induced Heart Failure: Integrating FAERS Database and AHA Statement
Heart failure (HF), the advanced stage of diverse cardiac conditions, poses a significant public health challenge. This study analyzes adverse event (AE) signals associated with HF within the FDA Adverse Event Reporting System (FAERS) database, offering critical insights to guide rational medication use in clinical settings. Adverse event reports (AERs) associated with HF in the FAERS database, spanning from the first quarter of 2004 to the fourth quarter of 2024, were analyzed. The potential HF risk of drugs was assessed using the disproportionality analysis, with findings juxtaposed against the American Heart Association (AHA) drug list. Drug-induced HF cases showed equivalent distribution between male and female, and high rates of rehospitalization and mortality. Prominent hypoglycemic drugs associated with HF included rosiglitazone, pioglitazone, and saxagliptin. Combination therapies, such as metformin/saxagliptin and metformin/rosiglitazone, also demonstrated elevated risks. In the context of pulmonary hypertension, drugs like macitentan, selexipag, and epoprostenol were particularly notable. Analysis against the AHA drug list confirmed stronger signal strength and frequency among Class A drugs, validating our results. Furthermore, drugs not flagged as positively signaling in the AHA registry, such as amiodarone, aliskiren, and testosterone, merit closer scrutiny due to their potential for adverse reactions. Our analysis of the FAERS database has identified medications associated with potential HF risks, providing valuable evidence to inform clinical decision-making and promote the safe use of medications.
13 Apr 2026
Read appraisal →Scientific reports
Effect of glucose on medium chain triglyceride induced ketosis in healthy adults in a randomized, double-blind, controlled study
Although medium-chain triglycerides (MCT) stimulate and carbohydrates inhibit ketone body synthesis, their quantitative interaction in humans is not well defined. This randomised, controlled, double-blind crossover study investigated how increasing glucose doses affects C8-MCT-induced ketone body synthesis after overnight fasting. Eleven healthy young woman (22.5 ± 1.9 years) received a constant dose of tricaprylin (99% C8; 0.2 g/kg bodyweight) combined with increasing glucose doses (0.2-0.6 g/kg bodyweight). In additional interventions, both C8-MCT and glucose were increased in parallel. Plasma β-hydroxybutyrate (βHB), glucose, and insulin were measured for up to 300 min post-dose. Indirect calorimetry in a subset and side effects were monitored. C8-MCT significantly increased βHB concentrations at low and medium glucose doses compared with control, but not at highest glucose dose. When both substrates were increased equally (1:1 ratio), ketone body synthesis increased. βHB was negative correlated with increasing glucose dosing at constant C8-MCT dosing, while parallel increases in both substrates showed a positive moderate correlation between βHB and C8-MCT doses. No dose-dependent side effects occurred. Overall, ketone body synthesis declines with rising glucose intake. It remains unclear whether a C8-MCT: glucose ratio of 1:3 represents a metabolic cut-off or whether glucose intake becomes excessive due to linear effects.Trial registration This study was prospectively registered in the German Clinical Trials Register (DRKS ID DRKS00035373 https//www.bfarm.de/EN/BfArM/Tasks/GermanClinicalTrialsRegister/_node.html ).
12 Apr 2026
Read appraisal →PloS one
Exploring barriers and enablers to diabetes self-care practice in Ethiopia, 2025: A qualitative systematic review
INTRODUCTION: Diabetes mellitus is a growing public health concern in Ethiopia, with increasing prevalence and a high proportion of undiagnosed cases. Effective self-care is crucial for managing diabetes; however, many patients face challenges ranging from personal beliefs to systemic and sociocultural constraints. Although multiple qualitative studies have explored these challenges, a synthesized, context-specific understanding that incorporates broader social and health system factors remains limited. This review aimed to synthesize qualitative evidence on barriers and facilitators of diabetes self-care practice in Ethiopia. METHODS: A qualitative systematic review was conducted in accordance with PRISMA 2020 and PRISMA-QS guidelines. A comprehensive search of PubMed/MEDLINE, Scopus, CINAHL, Web of Science, and Google Scholar was performed using relevant keywords and Medical Subject Headings. Eligible studies included primary qualitative and mixed-methods studies with extractable qualitative findings that explored diabetes self-care barriers and facilitators among patients, caregivers, or healthcare providers in Ethiopia. Purely quantitative studies, reviews, editorials, and studies conducted outside Ethiopia were excluded. Thematic synthesis was employed to integrate findings, and the GRADE-CERQual approach was used to assess confidence in the review findings. RESULTS: Eleven studies were included, comprising qualitative and mixed-methods designs conducted across diverse urban and semi-urban healthcare settings in Ethiopia. Study participants included adults with type 1 and type 2 diabetes, as well as healthcare professionals and caregivers. Six major barriers to diabetes self-care were identified: health system limitations, individual-level challenges, socioeconomic constraints, behavioral and lifestyle factors, cultural and social norms, and lack of social support. Key facilitators included strong family and social support, health education and counseling, patient motivation and skills, culturally aligned practices, and signs of health system readiness. CONCLUSION AND RECOMMENDATION: Diabetes self-care in Ethiopia is shaped by interconnected individual, cultural, and systemic factors. While substantial barriers persist, important enablers, particularly family involvement and supportive healthcare interactions, offer opportunities for improvement. Interventions should be culturally sensitive, community-centered, and supported by strengthened health systems. Policy efforts should prioritize integration of diabetes care into primary healthcare services, capacity building of healthcare providers, and incorporation of patients' lived experiences into care planning. Prospero registration number CRD420251033692.
11 Apr 2026
Read appraisal →Psychological medicine
Interventions to prevent antipsychotic-induced weight gain and metabolic complications in individuals with a first-episode psychosis and minimal antipsychotic exposure: a systematic review and meta-analysis
BACKGROUND: Rapid weight gain commonly occurs following the onset of first-episode psychosis (FEP), leading to cardiometabolic disease. Most weight gain in FEP occurs in the first 3 months of treatment, offering a critical window for prevention. Despite this, most studies aiming to prevent antipsychotic-induced weight gain include people with chronic illness or people who have had lengthy exposure to antipsychotic medication. We aimed to synthesize and analyze the literature on interventions aimed at preventing antipsychotic-induced weight gain. METHODS: We conducted a systematic review in PsycInfo, MEDLINE, CINAHL, and EMBASE of studies that examined the effectiveness of interventions in preventing antipsychotic-induced weight gain in FEP. We examined their effect on weight gain and a range of cardiometabolic markers. RESULTS: We screened 2,092 articles, 13 of which were eligible. Behavioral interventions, all three of which consisted of a multidisciplinary team approach, resulted in a mean of 3.05 kg less weight gain than treatment-as-usual (95% CI 1.36 kg to 4.73 kg). Pharmacological interventions displayed marked clinical and statistical heterogeneity, with each of the seven trials in adults using a different pharmacological intervention. Few studies collected comprehensive data on metabolic health. Only two pharmacological studies, and five studies in total, have been published since 2010. CONCLUSIONS: Despite the importance of preventing weight gain in FEP, there have been few recent studies investigating this topic. Our results indicate that multidisciplinary team interventions are effective in preventing weight gain in FEP and should be offered to all patients.
11 Apr 2026
Read appraisal →PloS one
Prevalence and determinants of inadequately controlled diabetes in Qatar's public primary care settings: A cross-sectional study
BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasing worldwide, causing serious morbidity and mortality. Proper management and control of T2DM are essential in slowing and reducing complications. Measuring the adequacy of diabetic control, therefore is one of the ways of evaluating the success of health care system and the individuals in addressing disease morbidity and mortality. This study was proposed to assess the extent of uncontrolled T2DM in ambulatory adults managed in the public primary care settings of Qatar over five years. In addition, it aimed to predict the risk of uncontrolled disease based on age, sex, nationality and comorbidity. METHODS: A cross sectional review of Electronic Health Records of 84,512 adult individuals with T2DM having at least one HbA1c blood test result per year during the 5 years study period (1st January 2018, to 31st December 2022) was analyzed. The term "inadequately controlled" T2DM was used to define an individual with HbA1c measurements of 7% or higher. RESULTS: The yearly prevalence of inadequately controlled T2DM remained stable at a high rate (53%) during the last three years of observations. Aging increases the probability of having inadequately controlled T2DM, but this was attributed to comorbidities. Adjusting for those comorbidities will show that younger ages are the ones at higher risk of being uncontrolled. Additionally, the study reported that hypertension and dyslipidemia are the most frequently prevalent comorbidities, nevertheless retinopathy, although less frequent, was the most important predictor for inadequately controlled T2DM. CONCLUSIONS: The study highlights the significant healthcare challenge posed by T2DM in Qatar due to its high prevalence and associated complications. Males, South Asian ethnic background and Qatari locals have the highest probability of being inadequately controlled. Overall, the study emphasizes the need for targeted interventions to address the challenges of controlling diabetes, particularly among high-risk groups identified in the study.
10 Apr 2026
Read appraisal →Annals of medicine
Comparison of VCV and PCV-VG modes on diaphragmatic function in diabetic patients undergoing laparoscopic colorectal surgery: a prospective randomized controlled study
BACKGROUND: Diabetic patients are prone to induce diaphragmatic weakness, which can lead to postoperative pulmonary complications (PPCs). The optimal mechanical ventilation mode may potentially improve postoperative diaphragmatic function. This study evaluates the effects of two ventilation modes under driving pressure-guided ventilation strategy on diaphragmatic function, as assessed by diaphragm thickening fraction (DTF) and diaphragm excursion (DE), in diabetic patients following laparoscopic colorectal surgery. METHODS: Eighty patients diagnosed with Type II diabetes scheduled for elective laparoscopic colorectal surgery, were randomly allocated to either the pressure-controlled volume-guaranteed ventilation (PCV-VG) group (Group P) or the volume-controlled ventilation (VCV) group (Group V) during surgery. The primary outcome was diaphragmatic function assessed during both tidal breathing and maximal inspiratory effort after surgery. Secondary outcomes included intraoperative mechanical power, PPCs, and other complications. RESULTS: A total of eighty patients were included in the final analysis. The averaged area under the curve (AUC) for mechanical power during ventilation was significantly lower in Group P than in Group V (p = 0.002). PCV-VG significantly improved both DE and DTF within the first two days post-surgery (AUCDEtidal: p = 0.088, AUCDTFtidal: p = 0.004, AUCDEmax: p = 0.029, AUCDTFmax: p = 0.017). Postoperative diaphragmatic weakness was less frequent in Group P than in Group V (p = 0.019). However, there was no difference in the incidence of PPCs between the two groups (p = 0.155). CONCLUSION: PCV-VG mode can reduce intraoperative mechanical power, better preserve postoperative diaphragmatic function. However, these improvements did not translate into clinical benefits, as evidenced by the lack of reduction in the incidence of PPCs.
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 →PloS one
MaxGRNet: A multi-axis vision transformer with improved generalization for eye disease classification using explainable AI with insertion-deletion operations on fundus images
Eye diseases, including diabetic retinopathy (DR), glaucoma, and cataracts, represent a major global health concern and can lead to severe visual impairment or blindness if not identified in a timely manner. This study proposes a novel eye disease classification framework based on a multi-axis vision transformer (MaxViT) applied to color fundus images with Explainable Artificial Intelligence (XAI) techniques to enhance model transparency. The proposed architecture integrates transformer-based attention mechanisms with Global Response Normalization (GRN)-based multi-layer perceptron (MLP) layers to capture complex spatial and contextual relationships within fundus images effectively. The model was evaluated on a publicly available eye disease classification dataset using a five-fold cross-validation strategy to assess its robustness and generalization. The experimental results show that the proposed approach consistently outperforms conventional Convolutional Neural Networks (CNNs) and Vision Transformer (ViT) variants, including ResNet50, Swin-T, MaxViT-T, and ViT-B16. The model achieved a macro-averaged test accuracy, precision, and recall values of 96.75%, 96.70%, and 96.80%, respectively, with paired statistical t-tests confirming that these improvements were statistically significant. Rigorous preprocessing techniques were employed to improve data consistency, and XAI-based visual explanations provided insights into the model's decision-making process, supporting interpretability in ophthalmic image analysis. Overall, the proposed MaxViT-based framework is robust and computationally feasible for research-oriented evaluation approaches for automated fundus image classification, highlighting the potential of advanced transformer architectures for future decision-support and research-oriented ophthalmic applications.
10 Apr 2026
Read appraisal →Proceedings of the National Academy of Sciences of the United States of America
Reconstruction of human metabolic models with large language models
Genome-scale metabolic models (GEMs) have become essential tools for understanding human metabolism. Here, we introduce Human2, a consensus human GEM with enhanced precision and biological relevance, which leverages large language models (LLMs) and GitHub Action checks to streamline automated, efficient, and collaborative curation. Human2 supports the reconstruction of tissue- and organ-specific models tailored to sex- and age-specific human groups. By integrating transcriptomic, proteomic, and kinetic data, we reveal distinct metabolic features across these groups, such as significant differences in arachidonic acid and leukotriene metabolism. The specific models were integrated into a dynamic whole-body framework, marking an enzyme-constrained dynamic model that simulates interorgan metabolite exchanges under varying nutritional states, from feeding to fasting. Our work highlights the transformative role of LLMs in GEM reconstruction and introduces a whole-body dynamic simulation that integrates kinetic data, offering a powerful resource for multiscale human metabolism modeling.
10 Apr 2026
Read appraisal →Cell metabolism
Blood-flow restriction resistance training improves skeletal muscle mitochondrial capacity and cardiovascular risk factors in type 2 diabetes.
Impaired muscle strength and mitochondrial functionality are hallmarks of type 2 diabetes (T2D). Conventional combined resistance/endurance exercise training has limited efficacy to simultaneously improve muscle function and metabolism. We examined whether low-load blood-flow restriction training (BFRT) increases both muscle strength and mitochondrial oxidative capacity in T2D. Over 12 weeks, BFRT and conventional resistance training (CREST) similarly improved muscle strength despite lower workload in BFRT. Uniquely, BFRT enhanced muscle and adipose tissue oxidative capacity and increased muscle mitochondrial content. Transcriptomic profiling revealed more pronounced changes, particularly in angiogenesis-linked pathways, upon BFRT. BFRT also preferentially led to reductions in visceral adipose tissue volume and waist circumference, whereas CREST more effectively decreased subcutaneous adipose tissue volume. Both interventions lowered resting heart rate and diastolic blood pressure. These findings position BFRT as a promising low-load exercising strategy to simultaneously improve mitochondrial oxidative capacity, muscle strength, and body composition in individuals with T2D.
9 Apr 2026
Read appraisal →European thyroid journal
Promise and pitfalls of AI chatbots in complex decision-making for thyroid nodules and papillary thyroid cancer
INTRODUCTION: Artificial intelligence (AI) chatbots are increasingly used in medicine, but their reliability in scenarios with multiple management options is unclear. Indeterminate thyroid nodules and low- and low-to-intermediate-risk papillary thyroid carcinoma (PTC) represent such cases. METHODS: In a nationwide web-based survey, 201 members of the Hellenic Endocrine Society evaluated 12 clinical vignettes on indeterminate thyroid nodules and low- and low-to-intermediate-risk PTC. Their responses were compared with those generated by four conversational AI models (ChatGPT, Gemini, Copilot, and DeepSeek) at two time points, 11 months apart. DeepSeek was assessed only at the second time point. Chatbot outputs were assessed for agreement with endocrinologists' predominant answers, concordance with the most guideline-consistent options (American and European Thyroid Association recommendations), temporal stability, and inter-model agreement. RESULTS: Alignment between chatbots and endocrinologists' predominant responses was limited, reaching at most 25% across scenarios. In contrast, concordance with the most guideline-consistent options was higher, up to 83% (10/12 scenarios), depending on the model and time point. Across 12 scenarios, ChatGPT, Gemini, and Copilot changed their responses in 4, 7, and 5 scenarios, respectively, with some updates moving closer to, and others further from, guideline-based answers. Inter-model agreement ranged from 33 to 67%, indicating substantial variability among chatbots. CONCLUSION: AI chatbots show evolving but inconsistent performance in complex thyroid management scenarios. While guideline concordance can be relatively high, substantial variability across models, limited temporal reproducibility, and poor alignment with clinical practice highlight the need for ongoing longitudinal evaluation before safe integration into clinical decision-making.
9 Apr 2026
Read appraisal →The New England journal of medicine
Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease
BACKGROUND: Despite guideline recommendations, evidence from randomized trials evaluating the appropriate low-density lipoprotein (LDL) cholesterol target for secondary prevention in patients with atherosclerotic cardiovascular disease remains limited. METHODS: In this open-label superiority trial conducted in South Korea, we randomly assigned patients with atherosclerotic cardiovascular disease in a 1:1 ratio to a target LDL cholesterol level of less than 55 mg per deciliter (1.4 mmol per liter) (intensive-targeting group) or less than 70 mg per deciliter (1.8 mmol per liter) (conventional-targeting group). The primary end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina at 3 years. Safety was also assessed. RESULTS: Of 3048 patients who underwent randomization, 1526 were assigned to the intensive-targeting group and 1522 to the conventional-targeting group. The median follow-up was 3.0 years. The median LDL cholesterol level during the trial was 56 mg per deciliter (1.4 mmol per liter) in the intensive-targeting group and 66 mg per deciliter (1.7 mmol per liter) in the conventional-targeting group. A primary end-point event occurred in 100 patients (Kaplan-Meier estimate of cumulative incidence, 6.6%) in the intensive-targeting group and in 147 patients (Kaplan-Meier estimate of cumulative incidence, 9.7%) in the conventional-targeting group (hazard ratio, 0.67; 95% confidence interval, 0.52 to 0.86; P = 0.002). The incidence of prespecified safety end points was similar in the two trial groups, except for a lower incidence of creatinine elevation in the intensive-targeting group. CONCLUSIONS: Among patients with atherosclerotic cardiovascular disease, targeting an LDL cholesterol level of less than 55 mg per deciliter resulted in a lower risk of cardiovascular events at 3 years than targeting a level of less than 70 mg per deciliter. (Funded by the Cardiovascular Research Center and Yuhan; Ez-PAVE ClinicalTrials.gov number, NCT04626973.).
9 Apr 2026
Read appraisal →Translational vision science & technology
OptiDON-Guard: An Ensemble Model for Identification of Dysthyroid Optic Neuropathy Using Optical Coherence Tomography Angiography
PURPOSE: To explore the value of machine learning models based on optical coherence tomography angiography (OCTA) in identifying dysthyroid optic neuropathy (DON). METHODS: A retrospective, dual-center, cross-sectional study was conducted involving 346 thyroid eye disease patients (with/without DON) from two institutions. Participants underwent ophthalmic examinations, including OCTA scans centered on the macula and optic nerve head. The OCTA data from Center 1 were split into a training set and an internal validation set, while the data from Center 2 served as an external test set. Features were extracted from OCTA images, and a wrapper-based feature selection strategy identified the optimal subset. A two-tiered stacking modeling framework was used, incorporating baseline model construction, data augmentation using pseudo-labeling, and ensemble integration. Model performance (area under the curve [AUC], accuracy, sensitivity, specificity, precision) was evaluated alongside receiver operating characteristic, calibration, and decision curve analyses. Additionally, the SHapley Additive exPlanation method was used to interpret feature contributions. RESULTS: The ensemble model, OptiDON-Guard, demonstrated superior performance to individual models on both internal validation and external test sets. In the internal validation set, it achieved an AUC of 0.872, accuracy of 0.943, sensitivity of 0.667, specificity of 0.979, and precision of 0.943. In the external test set, it maintained strong performance with an AUC of 0.854, accuracy of 0.816, sensitivity of 0.767, specificity of 0.842, and precision of 0.854. CONCLUSIONS: The OptiDON-Guard is a reliable, interpretable, and clinically applicable tool for identifying DON. TRANSLATIONAL RELEVANCE: The OptiDON-Guard offers a valuable clinical tool to enhance the diagnostic precision of DON.
9 Apr 2026
Read appraisal →Archives of endocrinology and metabolism
Cushing's syndrome: a systematic review of psychiatric and cognitive symptoms in case studies
OBJECTIVE: Cushing's syndrome, characterized by chronic hypercortisolism, is associated with various health risks, including psychiatric symptoms and cognitive impairments. This systematic review of case studies aimed to map and categorize these symptoms. MATERIALS AND METHODS: We hypothesized that a broader range of psychiatric and cognitive manifestations would be observed beyond anxiety, depression, and memory impairment. The review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024433186). We conducted searches in PsycINFO, Embase, PubMed, and Scopus, identifying 273 potentially relevant studies. After screening, 66 studies were included, comprising 74 cases (81% female; mean age 35.7 years, range 13-81). RESULTS: revealed that 93% of cases presented psychiatric complaints, including depression (39.2%), psychosis/schizophrenic symptoms (35.1%), suicidal ideation/attempts (20.3%), anxiety (17.5%), panic attacks (2.7%), and post-traumatic stress disorder (1.4%). Cognitive complaints were reported in 32% of cases, primarily as general cognitive complaints (18.9%), memory impairment (9.5%), and attentional deficits (5.4%). An overlap of psychiatric and cognitive symptoms was observed in 26% of cases. CONCLUSION: This review underscores the clinical relevance of symptoms such as mania, psychosis, and suicidal behavior in Cushing's syndrome, which are often underreported. Individualized clinical assessment informed by these case studies is crucial for comprehensive management that extends beyond the typical focus on depression and memory. Moreover, greater awareness of the full spectrum of neuropsychiatric manifestations in hypercortisolism is needed.
8 Apr 2026
Read appraisal →Journal of the American Heart Association
Blood Pressure Parameters and Risk of Cognitive Decline and Dementia in Type 2 Diabetes: Results From the ADVANCE Trial
BACKGROUND: Blood pressure (BP) variability and cumulative BP load are significantly associated with cardiovascular disease risk beyond mean systolic BP, but less is known regarding their associations with cognitive decline/dementia and whether these associations differ by cognitive function at baseline or by sex. The aims of this study were to determine associations of different BP parameters with cognitive decline/dementia in patients with type 2 diabetes and explore differences by mild cognitive impairment at baseline and sex. METHODS: Using data from the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) study, BP parameters were calculated from an 18-month exposure window comprising measurements at 3, 4, 6, 12, and 18 months, after randomization. Logistic regression was used to estimate the odds ratio (OR) per SD higher and 95% CI for the associations of BP parameters with the composite outcome of cognitive decline (≥3 points from baseline on the Mini-Mental State Examination) or clinical diagnosis of dementia. RESULTS: Of the 11 140 ADVANCE participants, 9586 patients had 5 complete BP measurements within the 18-month exposure window. After a mean follow-up of 3.5 years, 1674 (17.5%) participants were diagnosed with cognitive decline and/or dementia. Overall, variability and baseline pulse pressure (PP), but not BP load, were associated with higher odds of cognitive decline/dementia (OR: variability in systolic BP, 1.11 [95% CI, 1.05-1.17]; diastolic BP, 1.11 [95% CI, 1.05-1.17]; PP, 1.05 [95% CI, 1.00-1.11]; mean arterial pressure, 1.13 [95% CI, 1.07-1.19]; and baseline PP, 1.19 [95% CI, 1.13-1.25]). There were no differences by mild cognitive impairment at baseline or sex. CONCLUSIONS: Higher BP variability and baseline PP, but not mean BP or BP load, were associated with higher odds of cognitive decline/dementia in patients with type 2 diabetes. BP variability and PP may be important therapeutic markers for the preservation of brain health. REGISTRATION: URL: https://clinicaltrials.gov; Unique Identifier: NCT00145925.
8 Apr 2026
Read appraisal →JMIR research protocols
Remote Management of Patients With Diabetic Macular Edema Receiving Long-Term Intravitreal Anti-Vascular Endothelial Growth Factor Therapy (RE-SHINE Study): Protocol for a Real-World Study
BACKGROUND: Long-term intravitreal anti-vascular endothelial growth factor therapy is the gold standard for treating diabetic macular edema (DME). However, poor treatment adherence in real-world settings often leads to suboptimal visual outcomes. Evidence-based remote management strategies are required to bridge the gap between clinical protocols and patient self-management. OBJECTIVE: This study aims to describe a remote management program based on the Behavior Change Wheel model designed to increase treatment adherence and improve disease outcomes for patients with DME receiving long-term anti-vascular endothelial growth factor therapy, and to report the study protocol. METHODS: The RE-SHINE study was structured into three phases: theoretical modeling, digital platform development, and a validation cohort study. The intervention included a smartphone-based app providing personalized health education, self-monitoring of vision (Amsler grid), injection reminders, and direct communication with health care providers. The efficacy of the remote management model was tested in a real-world cohort study. Participants were assessed at baseline and at each follow-up visit over 12 months. The primary outcome measure was best-corrected visual acuity, and secondary outcome measures included central retinal thickness and treatment adherence (injection rate and follow-up frequency). RESULTS: A total of 1006 patients with DME underwent initial screening, and 958 (95.2%) patients met the inclusion criteria, with only 7 patients declining follow-up. We anticipate that the remote management system will be both feasible and acceptable for patients with DME. It is hypothesized that the intervention group would demonstrate significantly higher levels of treatment adherence and better visual preservation compared to the retrospective control group. In addition, we intend to assess the impact of the digital intervention on patient-reported outcomes, encompassing quality of life and self-efficacy. Participant recruitment began in September 2023 and was completed by the time of submission. The data analysis is yet to begin. The results are expected to be published in 2026. CONCLUSIONS: A Behavior Change Wheel-based remote management approach could be a scalable and sustainable method to enhance adherence in patients requiring long-term intravitreal therapy. If proven effective, this model could be integrated into routine ophthalmic care to mitigate the risk of vision loss due to undertreatment in DME.
7 Apr 2026
Read appraisal →PloS one
Advanced microfluidic and 3D cell culture platforms for modeling vascularization in diabetic foot ulcers: A systematic review of translational challenges and perspectives
The healing process of diabetic foot ulcers (DFUs) presents a slow pattern with an increased risk of infections, ischemia, and thrombosis correlated with high levels of reactive oxygen species production. Vascular injury is one of the factors contributing to the difficulty of wound healing in diabetic patients. Although the understanding of the pathophysiology of DFUs has significantly increased in recent years, associated treatments still have a high level of failure, leading to high morbidity rates, mortality, and amputations. Three-dimensional (3D) cell culture platforms offer a new approach to investigating and treating these wounds, as they can reproduce one or more physiological systems in a relevant microenvironment. This systematic review describes the advancements, challenges, and future implications of advanced 3D culture models in vascularization, encompassing pathophysiological understanding, treatment, and prognostic perspectives. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This work was registered under PROSPERO protocol number CRD42022336473. The eligibility criteria addressed studies related to chronic DFUs that analyzed vascularization during the healing process. The selected study designs involved 3D cultures and organ-on-a- chip (OoC) platforms, utilizing either primary or secondary human cell lines. Studies published more than 10 years ago or using only animal cells in 2D culture environments were excluded. The search was conducted in PubMed, LILACS, Embase, MEDLINE, IEEE, the BSV regional portal, ScienceDirect, Scopus, CINAHL, EBSCO, and Web of Science. A total of 2,539 relevant studies were identified as of June 1, 2025. After screening, only seven met the inclusion criteria. These studies reflect a growing interest in using hydrogel scaffolds and microfluidic systems to replicate diabetic skin environments; however, the field remains in an early stage of development. OoC platforms, in particular, stand out for their ability to recreate dynamic, tissue-like conditions and vascular function. While some promising attempts have been made to combine hydrogels with these technologies, the evidence is still limited and inconclusive for chronic wound modeling. This review underscores both the potential and the urgent need for more robust and translational research in this area-especially toward building personalized, clinically relevant models to support future drug testing and therapeutic innovation.
7 Apr 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
A community based participatory research approach to evaluate barriers and facilitators for behavioral weight loss intervention implementation in a predominantly black community.
PURPOSE: Breast cancer survivors with overweight or obesity have worse breast cancer specific survival and outcomes as compared to those with average weight by Yung and Ligibel (Clin Adv Hematol Oncol 14:790-797, 2016) and Druesne-Pecollo et al. (Breast Cancer Res Treat 135:647-654, 2012). Our pilot Group-basEd Telehealth behavioral Weight Los (GET-WEL) Program showed that fewer Black breast cancer survivors (BBCS) enrolled and lost less weight than White breast cancer survivors by Allison et al. (Obesity Science and Practice 10:e70023, 2024). This study is aimed at using a community-based participatory research approach to assess barriers and facilitators of implementing a behavioral weight loss intervention among BBCS. METHODS: Eight BBCS from a predominantly Black community were invited to participate in semi-structured interviews that were voice recorded, transcribed, coded, and analyzed via comparative thematic analysis. RESULTS: Thematic analyses revealed multiple barriers within participants. These included lack of affordable healthy food access, safety concerns with regards to outdoor activities, lack of affordable fitness center memberships, time constraints related to competing work/life obligations, and steep learning curves with technology use. Most BBCS preferred an integrated community-based coach to guide their weight loss interventions via a combination of both virtual and in-person sessions. CONCLUSION: Our results indicate that a multimodal approach including nutrition education, reducing physical activity barriers, limiting time constraints by implementing both in-person and virtual platforms, and assisting with technology courses, is necessary to improve the equitable implementation of weight loss interventions. BBCS recommended utilizing established community facilities and leveraging known community members such as nutrition counselors and physical trainers to increase successful implementation.
6 Apr 2026
Read appraisal →Journal of ethnopharmacology
Evaluation of the association of pseudoaldosteronism with licorice-containing herbal medicine using the Japanese adverse drug event report (JADER) database
ETHNOPHARMACOLOGICAL RELEVANCE: Herbal medicine in Japan is known as Kampo preparation, a traditional medicine that combines multiple medicinal herbs and is widely used in medical practice. Pseudoaldosteronism is an issue associated with herbal medicines that contain licorice. However, the relationship between licorice intake and pseudoaldosteronism is not fully understood and is debatable. AIM OF THE STUDY: This study evaluates the association between herbal medicine preparations containing licorice and pseudoaldosteronism using data from the Japanese Adverse Drug Reaction Reporting System (JADER) database. MATERIALS AND METHODS: The JADER database contained 961,171 reports published between April 2004 and December 2024. The association between herbal medicines and pseudoaldosteronism was evaluated using the pharmacovigilance index as the reporting odds ratio (ROR) and logistic regression models. RESULTS: There were 537 cases of pseudoaldosteronism (PT code: 10037113). The reporting ratio of pseudoaldosteronism was higher in the licorice-containing herbal medicines group than in the overall herbal medicines group. The RORs of the top 20 herbal medicines with the highest number of pseudoaldosteronism reports, all of which contained licorice, exceeded one, and a signal was detected. The risk of pseudoaldosteronism increased with increasing licorice intake. According to the receiver operating characteristic (ROC) curve for pseudoaldosteronism (area under the curve (AUC) = 0.71, sensitivity = 0.8493, 1-specificity = 0.5530), the cutoff value was 1.125 g/day. CONCLUSIONS: This study is the first to clarify the association between licorice intake from herbal medicines and pseudoaldosteronism using Japan's spontaneous adverse event-reporting database. These findings will be useful and informative for medical professionals considering treatments with herbal medicines.
6 Apr 2026
Read appraisal →Chinese medical journal
Efficacy and safety of topical finasteride spray solution in the treatment of Chinese men with androgenetic alopecia: A phase III, multicenter, randomized, double-blind, placebo-controlled study
BACKGROUND: Topical finasteride is a novel treatment for men with androgenetic alopecia (AGA). This study aimed to evaluate the efficacy and safety of topical finasteride spray solution in Chinese men with AGA. METHODS: This randomized, double-blind, placebo-controlled, phase III trial enrolled 270 individuals with AGA from 16 sites across China between December 2021 and March 2023. The participants were randomized at a ratio of 2:1 to receive either topical finasteride or placebo treatment once daily for 24 weeks. The primary endpoint was the change from baseline in target area (0.903 cm 2 area) hair count at week 24. The secondary endpoints were change from baseline in target area hair count at week 12, target area terminal hair count at weeks 12 and 24, target area terminal hair width at week 24, and target area hair width at week 24; an improvement of vertex hair growth assessed by the investigator at week 24; and the patient-assessed scores on the Male Hair Growth Questionnaire at week 24. RESULTS: A total of 270 individuals were enrolled and randomized, and 251 completed the study (165 in topical finasteride group, 86 in placebo group). Compared with the placebo group, in the topical finasteride group, the change from baseline in target area hair count was significantly higher at week 24 ( P <0.05), although it was only numerically higher at week 12 ( P = 0.0688). Significant differences favoring topical finasteride over placebo were observed for change from baseline in target area terminal hair count at weeks 12 ( P <0.05) and 24 ( P <0.01). The improvement of vertex hair growth assessed by the investigator was significantly greater in the topical finasteride group vs. the placebo group at week 24 ( P <0.01). Topical finasteride was generally safe and well-tolerated. CONCLUSIONS: In Chinese men with AGA, topical finasteride spray solution increased hair growth and showed good safety and tolerability profile during a 24-week treatment period. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05135468.
5 Apr 2026
Read appraisal →PloS one
Utilizing the transformer mechanism to predict cervical lymph node metastasis in patients with papillary thyroid carcinoma
RATIONALE AND OBJECTIVE: The status of cervical lymph node metastasis(LNM) in Papillary thyroid carcinoma(PTC) can affect the patient's treatment plan and prognosis. This study aims to develop and validate the application value of Vision transformer (ViT) model in preoperatively predicting cervical LNM in PTC. MATERIALS AND METHODS: A total of 540 PTC patients were retrospectively reviewed from two hospitals from April 20,2022 to August 20,2023.The ViT model is built based on the two-dimensional rectangular ultrasound image of the primary thyroid tumor, and at the same time, to compare its performance, a deep learning model of the traditional Convolutional neural network (CNN) framework, a ultrasound radiomics combined model(Clinical-Rad model), and clinical model are built. RESULTS: The ViT model demonstrated an AUC of 0.807 (95% CI: 0.709-0.905) in the internal validation cohort and 0.809 (95% CI: 0.720-0.900) in the external validation cohort. The ViT model's AUC ranged from 0.807-0.814 across all cohorts, significantly exceeding the clinical model (AUC: 0.595-0.669, P<0.001). While the AUC of the ViT model in the training cohort was slightly lower than that of the combined ultrasound radiomics model (0.814 vs 0.828, P=0.491), it showed significantly higher AUC values in the internal (0.807 vs 0.718, P=0.049) and external validation cohorts (0.809 vs 0.691, P<0.001). Compared to the clinical and combined radiomics models, the ViT model exhibited stable and superior predictive performance for PTC cervical lymph node metastasis.In the internal validation cohort, Doctor C's net reclassification improvement (NRI) with the ViT model was 0.106 (P=0.022), and the integrated discrimination improvement (IDI) was 0.106 (P=0.023). Doctor D showed NRI and IDI values of 0.113 (P=0.022) and 0.106 (P=0.024), respectively. In the external validation cohort, Doctor C's NRI and IDI were 0.090 (P=0.024) and 0.106 (P=0.024), while Doctor D had values of 0.011 (P=0.013) and 0.106 (P=0.013). The ViT model enhanced the diagnostic capabilities of both Doctor C, with less clinical experience, and Doctor D, with extensive experience. CONCLUSION: The deep learning model based on the Transformer mechanism shows good performance in predicting LNM in PTC patients, which is superior to the clinical model, Clinical-Rad model, and traditional CNN model.
5 Apr 2026
Read appraisal →BMJ open
Synthetic data-augmented machine learning for 30-day readmission prediction in patients with chronic conditions: a retrospective real-world study
OBJECTIVES: To develop and evaluate an explainable machine learning framework enhanced with synthetic data generation to predict unplanned 30-day hospital readmissions among patients with chronic obstructive pulmonary disease (COPD), heart failure (HF) and type 2 diabetes mellitus (T2DM), and to identify key clinical and social predictors of readmission. DESIGN: A retrospective cohort study using electronic health record data incorporating both structured variables and information extracted from unstructured clinical notes. Synthetic data were generated using advanced resampling and deep learning-based techniques to address outcome imbalance and improve model training. SETTING: Intensive care unit and general ward admissions at a single tertiary academic medical centre included in the MIMIC-IV (Medical Information Mart for Intensive Care IV) database. PARTICIPANTS: Adult patients (≥18 years) were admitted with a primary diagnosis of COPD (n=14 050), HF (n=7097) or T2DM (n=12 735) between 2008 and 2019, with complete 30-day follow-up and no in-hospital mortality during the index admission. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was unplanned all-cause hospital readmission within 30-days of discharge. Predictors were drawn from six domains, including demographics, comorbidities, clinical acuity, therapies, behavioural factors and care continuity. Predictive performance was evaluated using multiple machine learning methods and fivefold cross-validation, with model interpretability assessed using established goal and local explanation approaches. RESULTS: Ensemble-based machine learning models demonstrated the strongest predictive performance across all three disease cohorts. Key predictors of readmission included higher illness severity, greater comorbidity burden, medication non-adherence, gaps in preventive care and limited social support. Models incorporating synthetic data augmentation showed improved discrimination compared with models trained on original data alone. CONCLUSIONS: An explainable synthetic-data driven framework incorporating clinical, behavioural and social data can support prediction of 30-day readmissions among patients with common chronic conditions using routinely available electronic health record data.
5 Apr 2026
Read appraisal →Medicine
Neuroendocrine neoplasms diagnosed in the setting of inflammatory bowel disease: A systematic review and proposed management algorithm
BACKGROUND: Patients with inflammatory bowel disease (IBD) are at higher risk of developing malignancies, including neuroendocrine neoplasms, but the specifics of that are not well known. We reviewed the existing literature to map the evidence surrounding this phenomenon. METHODS: Following PRISMA 2020 guidelines, we searched PubMed from inception to September 2024 for patients with gastrointestinal neuroendocrine neoplasms (NENs) and either Crohn disease (CD) or ulcerative colitis (UC). Eligible studies included case reports, case series, and larger retrospective IBD cohorts. We extracted demographic and clinical data including tumor grade, location, metastatic status, and mode of detection. Comparative analyses between UC and CD were performed using Fisher exact test, chi-square test, and independent t-tests. RESULTS: We identified 67 case studies with data available for a total of 108 patients (61.1% male), ranging from 14 to 87 years of age. The median duration from IBD diagnosis to NEN detection was 13 years. Fifty-five (50.9%) patients had CD and 53 (49.1%) had UC. UC patients were older at NEN diagnosis (mean 49 vs 40 years, P = .004) and had a higher metastatic rate (39.6% vs 18.2%, P = .019). Most NENs were low-grade (69.4%), while 20.4% were high-grade and 8.3% were mixed. The most common tumor locations were the rectum (29.6%) and appendix (27.8%), with rectal and colonic NENs more prevalent in UC and small bowel or appendiceal NENs more common in CD. At diagnosis, 71.3% of patients had localized disease. For high-grade NENs, 86.4% of cases were metastatic, compared to 9.3% for low-grade tumors. Only 10.2% of NENs were detected via endoscopic surveillance. CONCLUSIONS: NENs in IBD show distinct patterns by IBD type, with significant differences in tumor location, grade, and metastatic rates between UC and CD. These hypothesis-generating observations suggest heightened vigilance after approximately 10 years of IBD or around age 44, focusing on rectal lesions in UC and small bowel/appendiceal lesions in CD. Validation in prospective, population-based studies is needed before these findings can inform clinical practice.
4 Apr 2026
Read appraisal →Journal of telemedicine and telecare
Telemedicine and digital health for chronic conditions in pediatrics: A systematic review
BackgroundThe prevalence of chronic diseases in children and adolescents has significantly increased. The COVID-19 pandemic accelerated telemedicine adoption, leading to improved healthcare access and outcomes. Despite its benefits, telemedicine is still not fully integrated into standard care. Previous reviews have been limited in scope. This systematic review aims to provide a comprehensive overview of recent trials on web or app-based telemedicine for chronically ill children and adolescents, identifying interventions and outcomes for future healthcare strategies.MethodsA comprehensive search was conducted on PubMed on November 21, 2023, and updated on January 9, 2025. Results were filtered to include prospective intervention studies involving children and adolescents with chronic conditions and limited to publications from 2017 onwards. A total of 8699 results were retrieved, and 1506 titles were screened for eligibility, resulting in 116 studies included in the review.ResultsThese studies covered 45 different conditions, with the highest numbers for diabetes, asthma, and obesity. Telemedicine interventions varied, including gamification, video meetings, integrated devices, psychological components, symptom tracking, and educational content. Most studies reported high feasibility and patient satisfaction. Clinical outcomes improved in some cases, and none were worse than standard care. The heterogeneity limited direct comparisons and meta-analysis, and small sample sizes in many studies affected the generalizability and statistical significance of the findings.ConclusionsOur study highlights the potential of telemedicine in managing chronic illnesses among children, emphasizing the need for standardized methodologies, larger sample sizes, and continued investment in infrastructure and equitable policies to fully realize its benefits in improving accessibility, convenience, cost savings, and overall health outcomes.
4 Apr 2026
Read appraisal →Physiological reviews
An umbrella review of systematic reviews of the impact of wrist-worn wearables on health outcomes
We conducted an umbrella review to synthesize the evidence on the effectiveness of interventions incorporating wrist-worn wearables' feedback on diverse health outcomes including health promotion (i.e., health behaviors and disease risk perception) morbidity, mortality, functioning, and other health-related metrics in humans. We searched in MEDLINE, Web of Science, Embase, and Cochrane Library until March 18, 2025, for eligible systematic reviews. After screening 9,487 citations, we identified 39 systematic reviews, which included 98 original studies (1 observational study, 95 randomized controlled trials, and 1 pre-post study). The reviews primarily focused on adult populations, individuals with cardiometabolic conditions, and cancer survivors. The original interventional studies mainly included Fitbit (40.2%), Polar (12.4%), and ActiGraph (10.3%) devices. Over 80% of the clinical trials involved complex behavioral interventions with wearable-based feedback, and the control groups varied. Most systematic reviews were rated as low confidence, with common flaws including inadequate consideration for risk-of-bias and heterogeneity. Interventions incorporating wrist-worn activity trackers increased physical activity in diverse populations. The effect of interventions incorporating wrist-wearables' feedback on cardiometabolic risk markers, quality of life, depression/anxiety, and pain was limited and remained inconsistent. Our findings rely on existing systematic reviews, which may vary in quality, review methodologies, and comprehensiveness. There is also potential for missing more recent evidence not yet captured in these reviews. These limitations should be considered when interpreting our results. Acknowledging these caveats, wrist-worn wearables seem to increase physical activity and may have additional benefits that require further study.
4 Apr 2026
Read appraisal →Journal of diabetes investigation
A machine learning approach to predicting severe diabetes distress in adults with type 1 diabetes mellitus.
BACKGROUND: Diabetes distress is common in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to construct and validate prediction models for diabetes distress in adults with T1DM using continuous glucose monitoring (CGM) metrics. METHODS: The CGM metrics were collected from 259 adults with T1DM. Severe diabetes distress was defined as 40 points on the Problem Areas in Diabetes scale. Prediction models were developed based on ten machine learning algorithms: random forest (RF), support vector machine (SVM), Naive Bayes (NB), Neural Network (NN), k-nearest neighbor (k-NN), XGBoost (XGB), SGDClassifier (SGDC), XGB_limitet_depth (CGB_ld), L1LogisticRegression (L1), and LightGBM. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score. RESULTS: Among the ten models, accuracy in the NN model was the highest (NN: 0.744, L1: 0.731, NB: 0.718, SVM: 0.692, SGDC: 0.654, RF: 0.628, k-NN: 0.628, LightGBM: 0.615, XGBoost: 0.564, and XGB_ld: 0.564). The NN model achieved the highest AUC of 0.728 (95% confidence interval: 0.608-0.845). CONCLUSIONS: This study developed a predictive model for severe diabetes distress using machine learning, incorporating both demographic and CGM metrics in adults with type 1 diabetes mellitus. The NN model demonstrated potential as a practical tool to assist clinicians in identifying individuals at risk of severe diabetes distress.
4 Apr 2026
Read appraisal →Journal of advanced research
Machine learning ensemble meets clinical practice: developing a real-world risk prediction model for metabolic syndrome using super learner and scorecard approaches
INTRODUCTION: Metabolic syndrome (MetS) refers to a cluster of metabolic abnormalities that significantly increase the risk of developing cardiovascular diseases (CVDs). Traditional binary definitions of MetS fall short in capturing its severity spectrum, limiting personalized risk stratification. OBJECTIVES: We aimed to develop a super learner model and multilevel risk scorecard to improve MetS risk prediction and support early cardiovascular risk identification. METHODS: This study included a total of 460,256 health examination records from Zhejiang, China (2018-2023), with 344,925 used for model development and 115,331 used for external validation. A super learner model combining multiple machine learning algorithms was constructed to predict MetS risk. Key predictors identified through feature selection were used to develop a logistic regression-based MetS risk scorecard, stratifying individuals into five risk levels for practical and interpretable applications. RESULTS: The super learner model achieved area under the receiver operating characteristics (AUCs) of 0.816 (95 % confidence interval [CI]: 0.814-0.817) and 0.810 (95 % CI: 0.808-0.813) in the development and external validation cohorts, respectively. The risk scorecard, which incorporates ten predictors, demonstrated comparable performance, with AUCs of 0.793 (95 % CI: 0.791-0.794) and 0.788 (95 % CI: 0.785-0.791) in the respective cohorts. Based on the risk scorecard, individuals were stratified into five categories: very low, low, normal, high, and very high risk levels. CONCLUSION: The super learner model provides a highly accurate tool for MetS risk prediction, whereas the risk scorecard offers a practical and interpretable solution for clinical and personal use. These models enable precise risk assessment to guide prevention and improve outcomes.
4 Apr 2026
Read appraisal →Clinical nutrition ESPEN
Artificial intelligence in clinical nutrition. A narrative review.
The rapid integration of Artificial Intelligence (AI) into healthcare, particularly clinical nutrition, holds transformative potential for enhanced diagnostics, risk prediction, and personalized therapeutic support. However, many clinicians lack sufficient understanding of AI principles, capabilities, and limitations, which may hinder adoption, lead to inappropriate use, or result in missed opportunities to enhance patient care. This narrative review aims to provide an accessible overview of foundational AI concepts, such as machine learning, deep learning, and large language models, and their practical applications in clinical nutrition. While AI offers immense promise in advancing nutritional care, its successful implementation requires clinicians to be adequately prepared to engage with these technologies. Education programs tailored to healthcare professionals, interdisciplinary collaboration between AI experts and clinicians, and robust ethical oversight are critical to ensure responsible and effective integration. By equipping clinicians with the necessary knowledge and tools, AI can serve as a powerful ally in delivering personalized and patient-centered nutritional care while maintaining human expertise at the forefront of decision-making.
2 Apr 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 →Gut Microbes
Machine-learning assisted discovery unveils novel interplay between gut microbiota and host metabolic disturbance in diabetic kidney disease
Diabetic kidney disease (DKD) is a serious healthcare dilemma. Nonetheless, the interplay between the functional capacity of gut microbiota and their host remains elusive for DKD. This study aims to elucidate the functional capability of gut microbiota to affect kidney function of DKD patients. A total of 990 subjects were enrolled consisting of a control group (n = 455), a type 2 diabetes mellitus group (DM, n = 204), a DKD group (n = 182) and a chronic kidney disease group (CKD, n = 149). Full-length sequencing of 16S rRNA genes from stool DNA was conducted. Three findings are pinpointed. Firstly, new types of microbiota biomarkers have been created using a machine-learning (ML) method, namely relative abundance of a microbe, presence or absence of a microbe, and the hierarchy ratio between two different taxonomies. Four different panels of features were selected to be analyzed: (i) DM vs. Control, (ii) DKD vs. DM, (iii) DKD vs. CKD, and (iv) CKD vs. Control. These had accuracy rates between 0.72 and 0.78 and areas under curve between 0.79 and 0.86. Secondly, 13 gut microbiota biomarkers, which are strongly correlated with anthropometric, metabolic and/or renal indexes, concomitantly identified by the ML algorithm and the differential abundance method were highly discriminatory. Finally, the predicted functional capability of a DKD-specific biomarker, Gemmiger spp. is enriched in carbohydrate metabolism and branched-chain amino acid (BCAA) biosynthesis. Coincidentally, the circulating levels of various BCAAs (L-valine, L-leucine and L-isoleucine) and their precursor, L-glutamate, are significantly increased in DM and DKD patients, which suggests that, when hyperglycemia is present, there has been alterations in various interconnected pathways associated with glycolysis, pyruvate fermentation and BCAA biosynthesis. Our findings demonstrate that there is a link involving the gut-kidney axis in DKD patients. Furthermore, our findings highlight specific gut bacteria that can acts as useful biomarkers; these could have mechanistic and diagnostic implications.
1 Dec 2025
Read appraisal →JAMA
An AI-Powered Lifestyle Intervention vs Human Coaching in the Diabetes Prevention Program: A Randomized Clinical Trial
IMPORTANCE: Prediabetes is common, yet evidence-based lifestyle interventions are underutilized. OBJECTIVE: To determine whether referral to an exclusively artificial intelligence (AI)-led lifestyle intervention based on the Diabetes Prevention Program (DPP) is noninferior to referral to a human-led DPP in achieving recommended thresholds for weight loss, hemoglobin A1c (HbA1c) reduction, and weekly physical activity among adults with prediabetes and overweight or obesity. DESIGN, SETTING, AND PARTICIPANTS: This phase 3, parallel-group, pragmatic, noninferiority randomized clinical trial was conducted from October 11, 2021, to December 16, 2024 (last follow-up) at 2 US clinical sites in Baltimore, Maryland, and Reading, Pennsylvania. Adults 18 years or older with prediabetes and overweight or obesity were enrolled. INTERVENTIONS: Participants were randomized in a 1:1 ratio to receive either a referral to an AI-powered DPP lifestyle intervention delivered via a mobile app and Bluetooth-enabled digital scale or a referral to a human coach-led DPP lifestyle intervention delivered remotely. Both interventions were delivered independently of the study team over a 12-month period. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of maintaining an HbA1c less than 6.5% throughout the study and achievement of at least 5% weight loss, at least 4% weight loss plus at least 150 minutes of weekly physical activity (assessed with actigraphy), or an absolute reduction in HbA1c of at least 0.2 percentage points at 12 months. Noninferiority of referral to the AI-led DPP compared with referral to the human-led DPP was prespecified to be determined if the 1-sided 95% CI lower boundary of the risk difference did not cross -15%. RESULTS: A total of 368 participants were included (median [IQR] age, 58 [50-65] years; 71% were female, 27% were Black, 6% were Hispanic, and 61% were White; median [IQR] BMI, 32.3 [28.5-37.1]). After referral, 171 of 183 participants (93.4%) initiated the AI-led DPP and 153 of 185 (82.7%) initiated the human-led DPP. The primary outcome was achieved by 58 of 183 participants (31.7%) in the AI-led DPP group and 59 of 185 (31.9%) in the human-led DPP group (risk difference, -0.2% [1-sided 95% CI, -8.2%]), meeting the criterion for noninferiority. Findings were consistent across individual components of the composite end point and in sensitivity analyses. CONCLUSIONS AND RELEVANCE: Among adults with prediabetes and overweight or obesity, referral to a fully automated AI-led DPP was noninferior to referral to a human-led DPP in achieving a composite outcome based on weight reduction, physical activity, and HbA1c. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05056376.
1 Dec 2025
Read appraisal →Nat Commun
Proteome atlas for mechanistic discovery and risk prediction of diabetic retinopathy
Proteomics offers an unprecedented opportunity to characterize and predict diabetic retinopathy (DR) with minimal invasiveness. Here we examine this in 10,873 individuals with (pre)diabetes from two ethnically distinct cohorts. By simultaneous profiling of ~3000 proteins, we identify 668 associations with mechanistically plausible directionality that constitute a comprehensive DR proteomic landscape with linkages to retinal tomographic structure and genetic predisposition, pointing to established and novel biological pathways conferring DR risk. Integrating DR proteomic profile markedly improves predictive performance beyond clinical and genetic predictors, with plexin B2, growth differentiation factor 15, and renin emerging as top proteins validated across cohorts and linked to retinal microvascular degeneration in Guangzhou Diabetic Eye Study (GDES) based on SS-OCTA. A parsimonious panel of these three proteins alone achieves comparable performance in predicting DR development and progression, while renin is confirmed as a causal promoter through genetic analyses. Our findings highlight the potential of large-scale proteomics in elucidating DR pathogenesis and advancing biomarker discovery, with broad implications for early detection and intervention.
1 Oct 2025
Read appraisal →Cardiovasc Diabetol
Association of estimated glucose disposition rate with aging acceleration and mortality risk in individuals with cardiovascular-kidney-metabolic syndrome: evidence from two large national population-based studies
OBJECTIVE: This study investigated the relationship between estimated glucose disposal rate (eGDR), aging acceleration (AgeAccel), and mortality in adults diagnosed with cardiovascular-kidney-metabolic (CKM) stages 1 to 4. METHODS: The study utilized data from 4,826 adults with CKM syndrome stages 1 to 4, collected from the National Health and Nutrition Examination Survey (NHANES) conducted during the 2005-2010 survey cycles. The assessment of AgeAccel was performed using two complementary measures: phenotypic AgeAccel (PhenoAgeAccel) and biological AgeAccel (BioAgeAccel). Survey-weighted logistic regression and Cox proportional hazards models were used to assess the associations of eGDR with AgeAccel and mortality risk, respectively. To assess the prognostic value of eGDR for mortality risk, we implemented a suite of nine distinct machine learning models. Additionally, a nomogram was developed to enhance the clinical applicability of our findings. Furthermore, we performed causal mediation analysis to quantify the proportion of the total effect of eGDR on mortality that was mediated through AgeAccel. To ensure the robustness of the results, we replicated our primary analyses using data from the nationally representative China Health and Retirement Longitudinal Study (CHARLS) cohort. RESULTS: Our analysis included 4,826 NHANES participants, among whom we documented 831 all-cause mortality events and 208 cardiovascular disease (CVD)-specific deaths during follow-up. In multivariable-adjusted Cox regression models, each unit increase in eGDR was significantly associated with a 10% reduction in all-cause mortality risk (Hazard ratio [HR] = 0.90, 95% Confidence interval [CI] 0.86-0.93) and a 13% decrease in CVD mortality risk (HR = 0.87, 95% CI 0.81-0.93). Additionally, eGDR showed a negative association with AgeAccel, including both BioAgeAccel (odds ratio [OR] = 0.85, 95% CI 0.82-0.87) and PhenoAgeAccel (OR = 0.78, 95% CI 0.75-0.80). For predicting all-cause mortality from eGDR, the K-Nearest Neighbors (KNN) showed superior discrimination (Area Under the Curve [AUC]: 0.926), exceeding the performance of other machine learning algorithms in a comparative evaluation. Mediation analysis revealed that the protective effect of higher eGDR was partially explained by slower PhenoAgeAccel, with mediation effects accounting for 23.53% and 15.73% of the total impact on all-cause and CVD mortality, respectively. CONCLUSIONS: In the CKM population, lower eGDR levels may be associated with both AgeAccel and an increased risk of mortality, with AgeAccel potentially mediating the relationship between eGDR and mortality. These findings suggested that eGDR could serve as a potential predictor and intervention target for delaying aging and reducing mortality risk.
1 Oct 2025
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