Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 24 appraisals
PloS one
Artificial intelligence in the diagnosis of deep vein thrombosis: A scoping review
Deep vein thrombosis (DVT) is the formation of thrombi in the deep venous system, most often in the lower extremities. Although usually not life-threatening, DVT requires timely diagnosis to prevent complications such as pulmonary embolism and post-thrombotic syndrome. The growing demand for image interpretation has generated interest in applying artificial intelligence (AI) to automated DVT detection. This scoping review analyzes the performance of artificial intelligence in diagnosing DVT using computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US). We conducted a search across seven databases from inception to May 2025 using terms related to deep vein thrombosis, artificial intelligence, and machine learning. Eligible studies were limited to those evaluating DVT diagnosis using CT, MRI, or ultrasound. Two independent reviewers selected eligible studies, and quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Eleven studies published between 2021 and 2025 met the inclusion criteria. Some of the AI algorithms included RetinaNet, Deep R-Belief Neural Networks, and Sooty Tern Optimization. US-based models were the most studied algorithms, with sensitivities and specificities ranging from 68 to 100% and 70-100%, respectively. The MRI-based model achieved sensitivities, specificities, and accuracies of 95% to 97%. One CT-based model demonstrated a sensitivity of 83%. Studies evaluated across multiple imaging datasets showed high sensitivities, specificities, and precision of 96% or higher. Future research should prioritize multicenter validation and integration of clinical factors. In addition, explainable frameworks capable of integrating multiple imaging datasets must be developed with attention to workflow efficiency and cost-effectiveness to support clinical translation. The results indicate that AI is best situated as a supplementary tool rather than a replacement for expert interpretation in DVT diagnosis.
23 June 2026
Read appraisal →Science advances
Synchronous wearable ultrasound for early detection of coronary and carotid artery comorbidity
Coronary heart disease (CHD) and carotid artery disease (CAD) often co-occur. However, conventional diagnosis typically involves separate, site-by-site examinations after symptoms appear, leading to delayed intervention. In this work, we developed a wearable ultrasound system that enables synchronous monitoring of cardiac and carotid dynamics for comorbidity assessment. The system combines dual wearable ultrasound patches, a synchronous imaging strategy, artificial intelligence-based image processing algorithms, and human circuitry models to automatically extract and analyze key cardiac-carotid metrics, such as heart rate, pulse rate, cardiac volume, cardiac output, and carotid blood pressure. By evaluating the correlation of these metrics between modeling and measurements, we showed the feasibility of differentiating among healthy participants and patients with CAD, CHD, or CAD-CHD comorbidity. This integrated approach constitutes a promising framework for supporting the proactive assessment of coronary-carotid comorbidity.
21 June 2026
Read appraisal →Lasers in medical science
Clinical dosimetry and efficacy of LED photobiomodulation for chronic lower-limb wound healing: a systematic review of randomized trials
Chronic lower-limb wounds represent a major clinical and socioeconomic burden due to delayed healing and high recurrence rates. Light-emitting diode (LED) photobiomodulation has been proposed as a noninvasive and low-cost adjunctive therapy; however, clinical evidence remains inconsistent. This systematic review aimed to synthesize evidence from randomized clinical trials investigating the efficacy of LED photobiomodulation for chronic lower-limb wound healing and to identify irradiation parameters associated with improved outcomes. A comprehensive search was conducted in PubMed, Scopus, Web of Science, and Embase up to May 2026. Six randomized clinical trials met the inclusion criteria. Wavelengths ranged from 620 to 950 nm, and energy densities varied between 2.4 and 126 J/cm². The findings suggest that LED photobiomodulation may promote wound area reduction, improve wound bed quality, and increase microcirculation, particularly in diabetic foot ulcers. However, one study using a high energy density (126 J/cm²) did not demonstrate beneficial effects, suggesting a possible dose-dependent response. The overall certainty of the evidence, assessed using the GRADE approach, was classified as very low due to inconsistency and indirectness among the included studies. Although LED photobiomodulation appears to be safe and demonstrates therapeutic potential, substantial heterogeneity in irradiation parameters, small sample sizes, and methodological limitations preclude definitive conclusions regarding its clinical efficacy. Well-designed randomized controlled trials with standardized protocols and dose-response investigations are needed to establish optimal therapeutic parameters and confirm clinical efficacy.
20 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 →Neurosurgical review
Rho-associated kinase inhibitors in cerebral cavernous malformations: a preclinical systematic review
Cerebral cavernous malformations (CCMs) are vascular abnormalities characterized by clusters of dilated capillaries. They are most associated with loss-of-function mutations in three genes (Ccm1, Ccm2, and Pdcd10/Ccm3). In capillary endothelial cells, mutations activate the Rho-associated coiled-coil-containing protein kinase (ROCK), leading to non-heme iron deposition and lesion formation, thereby contributing to CCM pathophysiology. To address this, ROCK inhibitors are being explored as potential stabilizing therapies in CCM. By reviewing the existing literature, this study aims to provide a descriptive evaluation of their effects on non-heme iron deposition and lesion formation in murine models. This systematic review followed the PRISMA 2020 guideline and was registered in PROSPERO (CRD420251048073). PubMed, Embase, Web of Science, and Scopus were searched from inception to 2 February 2026. Eligible studies included in vivo murine CCM models with mutations in the Ccm1, Ccm2, and Pdcd10/Ccm3 genes. Studies had to evaluate direct ROCK inhibitors, such as fasudil and BA-1049, or indirect modulators of the RhoA/ROCK pathway, such as statins, regardless of dosage, route, or duration, and provide molecular evidence of RhoA/ROCK pathway modulation. The primary outcome was lesion burden, and the secondary outcomes included non-heme iron deposition and ROCK activity. Systematic searches identified 389 records, of which 4 studies were included, demonstrating that fasudil, a ROCK inhibitor, consistently reduced non-heme iron deposition and lesion burden in preclinical CCM models in mice. In Ccm1+/-Msh2-/- mice, fasudil reduced non-heme iron deposition and stage 2 lesions; in Ccm2+/-Msh2-/- mice, fasudil reduced non-heme iron deposition and lesion burden. One study demonstrated that BA-1049 caused a dose-dependent reduction in non-heme iron deposition and lesion burden. Studies have shown that ROCK pathway modulation reduces non-heme iron deposition and lesion burden. Further clinical investigations involving patients with CCM are essential to verify whether these experimental benefits can be reproduced in clinical settings.
9 June 2026
Read appraisal →The New England journal of medicine
Ultrasound-Facilitated, Catheter-Directed Fibrinolysis for Acute Pulmonary Embolism
BACKGROUND: Whether anticoagulation alone is an adequate treatment for acute, intermediate-risk pulmonary embolism is uncertain. METHODS: We conducted a multinational, adaptive-design trial with blinded outcome adjudication. Patients with intermediate-risk pulmonary embolism (with a ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter of ≥1.0 and an elevated troponin level) were eligible if they had at least two indicators of cardiorespiratory distress (systolic blood pressure of ≤110 mm Hg, a heart rate of ≥100 beats per minute, or a respiratory rate of >20 breaths per minute). Patients were randomly assigned to undergo ultrasound-facilitated, catheter-directed fibrinolysis with alteplase plus anticoagulation (the intervention group) or anticoagulation alone (the control group) according to prespecified treatment protocols. The primary outcome was a composite of pulmonary embolism-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days. RESULTS: The intention-to-treat population comprised 544 patients: 273 in the intervention group and 271 in the control group. The mean (±SD) age was 58.2±13.5 years, and 42.6% of the patients were women. A primary-outcome event occurred in 11 patients (4.0%; 95% confidence interval [CI], 2.3 to 7.1) in the intervention group and 28 (10.3%; 95% CI, 7.2 to 14.5) in the control group (relative risk, 0.39; 95% CI, 0.20 to 0.77; P = 0.005). The effect was driven primarily by a lower risk of cardiorespiratory decompensation or collapse in the intervention group. Major bleeding occurred within 7 days after randomization in 11 patients (4.1%) in the intervention group and 6 (2.2%) in the control group (P = 0.32); major bleeding occurred within 30 days in 11 patients (4.1%) and 8 patients (3.0%), respectively (P = 0.64). No substantial between-group differences in the incidence of other serious adverse events were observed up to 30 days after randomization; no intracranial hemorrhage occurred. CONCLUSIONS: In patients with acute, intermediate-risk pulmonary embolism, ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation led to a lower risk of the composite of pulmonary embolism-related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days than anticoagulation alone. (Funded by Boston Scientific; HI-PEITHO ClinicalTrials.gov number, NCT04790370.).
29 May 2026
Read appraisal →Autoimmunity
IgA Vasculitis with necrotizing arteritis: a multicenter retrospective study from the French Vasculitis Study Group and systematic review of the literature
IgA vasculitis (IgAV) primarily affects small vessels, but rare cases with necrotizing arteritis (NA) raise questions about overlap with polyarteritis nodosa (PAN). To characterize IgAV with necrotizing arteritis (IgAV-NA) and compare its phenotype with classical IgAV and PAN. We performed a multicenter retrospective study combined with a systematic literature review (1990-2025). Patients fulfilled EULAR/PRINTO/PRES IgAV criteria, had pathological or imaging evidence of NA in small or medium arteries, and were ANCA-negative. Thirty patients were included (7 from databases, 23 from the literature). NA was confirmed by biopsy (n = 16) or vascular imaging (n = 14). Clinical features, treatments, remission, and mortality were compared with 257 adult IgAV and 196 PAN patients. Median age was 54.5 years. IgAV-NA was characterized by severe manifestations, including gastrointestinal bleeding, perforation, surgical abdomen, neuropathy, pancreatitis, and livedo. Compared with classical IgAV, IgAV-NA showed significantly higher rates of multi-organ involvement and mortality. Compared with PAN, IgAV-NA shared vascular complications but had less fever and neuropathy. Despite arterial involvement, patients did not fulfil PAN criteria. IgAV-NA represents a rare, severe IgAV phenotype with life-threatening complications rather than an IgAV-PAN overlap. Severe or atypical IgAV presentations should prompt vascular imaging and intensified immunosuppression.
28 May 2026
Read appraisal →Journal of ethnopharmacology
Therapeutic potential of pharmacological components of Salvia miltiorrhiza against atherosclerosis: A preclinical systematic review and meta-analysis
ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis (AS) severely threatens global health, while current therapies exhibit limitations. Recognized as a 'superior-grade' herb in the Shennong Ben Cao Jing, Salvia miltiorrhiza Bunge (Danshen) has been shown in modern studies to protect against cardiovascular diseases. AIM OF THE STUDY: The aim of this study was to investigate the therapeutic potential and protective mechanism of pharmacological components of Salvia miltiorrhiza against AS. MATERIALS AND METHODS: Relevant animal studies were collected from 8 databases, namely, PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang Data, VIP, and SinoMed. Risk of bias of the included studies was evaluated using the SYRCLE's tool. Statistical analysis was performed using R 4.2.0 and Python 3.14.2 software. Machine learning model was trained to predict optimal intervention parameters and was subsequently validated. RESULTS: A total of 64 studies were included. The pharmacological components of Salvia miltiorrhiza ameliorated atherosclerotic plaque formation and stability, and modulated various biomarkers, including lipid profiles, inflammatory cytokines, oxidative stress indicators, endothelial function markers, as well as matrix metalloproteinases. Machine learning identified an optimal Tanshinone IIA regimen against AS, which was defined as a single dose of 33.18 mg/kg dose over 84 days and demonstrated predictive robustness in validation. CONCLUSIONS: The pharmacological components of Salvia miltiorrhiza attenuate AS by regulating lipid metabolism, anti-inflammatory and antioxidant actions, improving endothelial function, modulating of vascular smooth muscle cells, remodeling extracellular matrix, and regulating programmed cell death. These findings provide translational insights that pave the way for subsequent preclinical and early-clinical studies, pending systematic validation through more rigorous research.
24 May 2026
Read appraisal →Lancet (London, England)
Ticagrelor with aspirin dual antiplatelet therapy combined with intravenous thrombolysis in patients with ischaemic stroke in China (TAPIS): a multicentre, double-blind, randomised controlled trial
BACKGROUND: Evidence supporting the early addition of antiplatelet therapy to intravenous thrombolysis in patients with acute ischaemic stroke remains inconclusive. We aimed to investigate the efficacy and safety of early oral dual antiplatelet therapy (DAPT), started within 6 h of onset, as an adjunct to intravenous thrombolysis. METHODS: TAPIS was a randomised, double-blind, placebo-controlled trial done in 60 hospitals across China. We enrolled patients treated with intravenous thrombolysis for ischaemic stroke, with a National Institutes of Health Stroke Scale score of 4-10. We randomly assigned (1:1) patients to receive oral aspirin plus ticagrelor (DAPT group) or corresponding placebo within 6 h of stroke onset, either before, during, or after receiving thrombolysis. Ticagrelor or placebo was continued for days 2-7 in each group, with open-label aspirin administered for days 2-90. Patients, clinicians, and investigators were masked to the group assignment. The primary efficacy outcome was an excellent functional outcome (modified Rankin Scale score 0-1) at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage within 36 h. This trial was registered with ClinicalTrials.gov (NCT06316570) and is completed. FINDINGS: Between April 3, 2024, and Sept 30, 2025, we randomly assigned 1382 patients to the early DAPT (n=690 [49·9%]) or placebo (n=692 [50·1%]) groups. The median age was 65·6 years (IQR 58·3-72·0), 991 (71·7%) were men, and 391 (28·3%) were women. At 90 days, 474 (68·7%) patients in the early DAPT group and 429 (62·0%) in the placebo group achieved excellent functional outcomes (risk ratio 1·11 [95% CI 1·03-1·20; p=0·0089). Symptomatic intracranial haemorrhage within 36 h occurred in six (0·9%) patients in the early DAPT group versus five (0·7%) in the control group (risk ratio 1·20 [95% CI 0·37-3·93; p=0.76). INTERPRETATION: Among patients treated with intravenous thrombolysis for moderate ischaemic stroke, initiation of oral DAPT within 6 h of onset improved the likelihood of excellent functional outcomes at 90 days. Although no significant between-group difference in symptomatic intracranial haemorrhage was detected, wide CIs precluded exclusion of a small increased risk. FUNDING: National Natural Science Foundation of China, Capital's Funds for Health Improvement and Research, Noncommunicable Chronic Diseases-National Science and Technology Major Project, Beijing Municipal Science & Technology Commission, and the New Cornerstone Science Foundation.
18 May 2026
Read appraisal →PloS one
D-dimer and lower limb ultrasound as prognostic factors for recurrent deep venous thrombosis and pulmonary embolism: A systematic review and meta-analysis
Venous thromboembolic disease is a chronic, recurrent condition. The optimal duration of anticoagulation therapy remains uncertain. We aim to evaluate D-dimer and lower limb ultrasonography as prognostic tools for the recurrence of venous thromboembolism. A search was conducted on May 28, 2022, in the Medline, Embase, and Cochrane databases. Inclusion criteria encompassed cohort studies, case-control studies, and clinical trials. Two reviewers independently screened all records and analyzed studies for inclusion/exclusion criteria, as well as risk of bias, using a structured framework (PROSPERO ID: CRD42022341082). The initial search yielded 4652 titles and abstracts. After removing 777 duplicates and reviewing 3875 titles and abstracts, 48 articles providing information on D-dimer and/or lower limb ultrasonography as prognostic factors were finally included. Very low-certainty evidence suggests that both residual vein thrombosis (RVT) at anticoagulation discontinuation and a positive post-treatment D-dimer are significantly associated with an increased risk of recurrent venous thromboembolism (VTE). For RVT, the pooled analysis showed a two-fold increase in risk (OR 2.00, 95% CI 1.02 to 3.94; I² = 85.7) while for positive D-dimer, the risk was similarly elevated (OR, 2.48; 95% CI, 1.85-3.33; I² = 56.0). In conclusion, very low-quality evidence suggests that abnormal D-dimer and RVT are associated with recurrent VTE; however, this association is inconsistent due to significant heterogeneity and wide prediction intervals. These biomarkers should be interpreted with caution as isolated predictors in clinical practice.
16 May 2026
Read appraisal →PloS one
Machine learning-based model for predicting recanalization in isolated distal deep vein thrombosis and analysis of predictors
BACKGROUND: Isolated distal deep vein thrombosis (IDDVT) is common, yet tools for predicting poor recanalization remain limited. We aimed to develop and compare machine learning models for predicting poor recanalization in patients with IDDVT and to identify the most informative predictors. METHODS: A total of 1600 patients with IDDVT were retrospectively enrolled. The dataset was randomly divided into a development set (n = 1280) and an independent test set (n = 320) using stratified sampling. Six predictive models were developed and compared: logistic regression (LR), support vector machine (SVM), random forest (RF), multilayer perceptron (MLP), extreme gradient boosting (XGBoost), and a Voting Ensemble. Model training and hyperparameter tuning were performed in the development set using five-fold stratified cross-validation, and optimal classification thresholds were determined using the Youden index. Model performance was evaluated by discrimination, calibration, and classification metrics, with 95% confidence intervals estimated by bootstrap resampling (10,000 iterations). SHAP analysis was applied to interpret the final model. RESULTS: In the independent test set, all models showed acceptable to strong discrimination, with AUC values ranging from 0.808 to 0.908. XGBoost achieved the best overall performance, with an optimal threshold of 0.183, an AUC of 0.908 (95% CI, 0.855-0.952), a Brier score of 0.077 (95% CI, 0.058-0.096), an accuracy of 0.900 (95% CI, 0.866-0.931), a precision of 0.650 (95% CI, 0.529-0.767), a recall of 0.803 (95% CI, 0.686-0.906), an F1-score of 0.717 (95% CI, 0.615-0.806), and a specificity of 0.918 (95% CI, 0.884-0.950). The calibration intercept and slope of the XGBoost model were 0.149 (95% CI, -0.192 to 0.454) and 1.410 (95% CI, 1.098-1.809), respectively, indicating acceptable overall calibration. SHAP analysis identified D-dimer rate, provoking-factor-related variables, anticoagulant use, and age group as the most influential predictors. CONCLUSION: Among six candidate models, XGBoost showed the best overall performance for predicting poor recanalization in patients with IDDVT. This study establishes an interpretable machine learning-based prediction framework focused specifically on poor recanalization in IDDVT and highlights the contribution of dynamic laboratory information, particularly D-dimer rate. The model may support early risk stratification and individualized follow-up planning, but external validation is required before routine clinical implementation.
13 May 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Night-time compression with a Mobiderm® auto-adjustable arm-sleeve in addition to daytime compression was superior to daytime compression alone for maintenance therapy of upper limb lymphedema in breast cancer patients in a randomized controlled trial: LYMphoNIGHT study.
PURPOSE: To assess the benefit of night-time compression in addition to daytime compression on arm excess volume after 3 months of maintenance treatment in patients with secondary upper limb breast cancer-related lymphedema (BCRL). METHODS: This multicenter, controlled, randomized study was carried out in six centers in France and Turkey. Women with upper limb BCRL who had undergone the intensive phase of decongestive lymphedema therapy (DLT) were randomized into two groups: the Control group wore a daytime compression sleeve without any night compression for 3 months and the MOBIDERM Autofit (MobA) group used a night-time compression sleeve in addition to the daytime compression. The primary outcome was the change in arm excess volume between day 0 (D0) and D90. The main secondary endpoints were: quality of life (QoL), sleep quality, skin thickness and suppleness, satisfaction, compliance, and safety. RESULTS: Fifty-six patients were recruited (mean (± SD) age: 61.4 ± 12.3 years). Between D0 and D90, the mean excess volume decreased by 29.2% in the MobA group and increased by 10.7% in the Control group (p = 0.001). Only 3.6% of patients in the MobA group presented with treatment failure vs. 23.1% in the Control group. At D90, patients in the MobA group had a significantly greater improvement in QoL (p < 0.05), sleep quality (p = 0.018), skin suppleness (p = 0.01) reduced skin thickness (p = 0.025) compared with the Control group. CONCLUSION: MOBIDERM Autofit used in addition to daytime compression for 3 months during the maintenance phase after DLT was superior to daytime compression alone for the reduction of arm excess volume. Registered on ClinicalTrials.gov (NCT04203069; 17/12/2019).
11 May 2026
Read appraisal →AJNR. American journal of neuroradiology
Comparative Analysis of Artificial Intelligence-Based Quantification versus Visual Rating of Enlarged Perivascular Spaces in the Multi-Ethnic Study of Atherosclerosis Cohort
BACKGROUND AND PURPOSE: Enlarged perivascular spaces (PVS) are fluid-filled spaces surrounding small cerebral vessels. Current PVS research has been limited by the absence of efficient and scalable quantification tools. We compared visual ratings versus artificial intelligence (AI)-based quantification in identifying associations of PVS with vascular risk factors and cognitive performance. MATERIALS AND METHODS: This cross-sectional study included 235 participants from the Multi-Ethnic Study of Atherosclerosis who had undergone brain MRI and had available both visual ratings and AI-derived PVS quantification. Visual ratings were performed by an expert neuroradiologist (K.D.H.) using a semiquantitative scale. AI-derived counts were based on a fully automated deep learning algorithm. Visual and AI-derived counts were grouped into 4 a priori-defined anatomic locations: basal ganglia, frontoparietal cerebrum, midbrain, and cerebellum. The relationships of PVS counts with demographic characteristics, vascular risk factors, and global and domain-specific cognitive scores were examined using ordinal logistic regression (for ordinal categoric outcomes) and linear regression (for continuous outcomes) models. RESULTS: Mean age (SD) was 72.1 (6.8) years; 95 (40%) participants were men; and 126 (54%) self-reported as black. Means (SD) of AI-derived regional PVS counts were 63.7 (24.6) for basal ganglia, 414.9 (167.5) for frontoparietal cerebrum, and 9.8 (4.4) for midbrain. On visual ratings, the most prevalent count category for each region was 11-20 for basal ganglia (40%), 21-40 (31%) for frontoparietal cerebrum, and 1-5 (83%) for midbrain. For basal ganglia PVS, while both methods were associated with older age and white race/ethnicity, AI-derived counts exhibited additional associations with higher systolic blood pressure (β, 0.20; 95% CI, 0.05-0.36) and diabetes (unstandardized β coefficient [β], 11.51; 95% CI, 3.48-19.55), as well as poorer global cognition (β, -0.012; 95% CI, -0.023 to -0.0004), delayed memory (β, -0.005; 95% CI, -0.010 to -0.0005), and attention/processing speed (β, -0.005; 95% CI, -0.009 to -0.001) cognitive performance. CONCLUSIONS: In this cross-sectional study, AI-derived PVS quantification was more sensitive in detecting associations with vascular risk factors and cognitive outcomes than traditional visual ratings. AI-based quantification may aid in the analysis of large-scale epidemiologic data, advancing PVS research.
11 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 →Neurology
Association of MRI-Visible Perivascular Spaces With Longitudinal Cognitive Decline Over a Decade
BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (SVD) is the most common vascular contributor to dementia. SVD markers often coexist, contributing to difficulty assessing their independent contributions to cognitive domains. MRI-visible perivascular spaces (PVSs) are an emerging SVD marker visualized by MRI. We previously showed that basal ganglia PVSs cross-sectionally contribute to worse cognition, independent of other SVD markers. To further characterize the clinical relevance of PVS, we studied its role as a unique SVD marker of longitudinal cognitive decline. METHODS: Participants without stroke or dementia were included in the Vanderbilt Memory and Aging Project, a longitudinal observational cohort study based in Nashville, TN. Participants completed 3T MRI at study entry to measure SVD burden (PVS volume fraction, white matter hyperintensities volume, lacune counts, and cerebral microbleeds counts). PVS volumes were segmented using a deep learning algorithm. Participants underwent comprehensive serial neuropsychological testing over an 11-year follow-up period (mean follow-up = 4.9 ± 3.1 years). Each SVD marker was related to longitudinal neuropsychological performances using a linear mixed-effects model adjusting for age, sex, race/ethnicity, education, baseline cognitive status, apolipoprotein E-ε4 presence, Framingham Stroke Risk Profile, and intracranial volume. Head-to-head comparisons simultaneously tested multiple statistically significant SVD markers. RESULTS: Among participants (n = 750, age 68 ± 9 years, 52% female), higher basal ganglia PVS burden at baseline was associated with worse longitudinal performances in Boston Naming Test (β = -29.63; 95% CI -56.66 to -2.60), Animal Naming (β = -33.09; 95% CI -65.66 to -0.51), Wechsler Adult Intelligence Scale IV Coding (β = -86.36; 95% CI -150.9 to -21.82), executive function composite (β = -9.51; 95% CI -14.33 to -4.68), Hooper Visual Organization Test (β = -26.06; 95% CI -50.53 to -1.59), and episodic memory composite (β = -7.05; 95% CI -11.9 to -2.21). In head-to-head comparisons, basal ganglia PVS remained independent associations with executive function composite (β = -7.47; 95% CI -12.84 to -2.10) and Hooper Visual Organization Test (β = -22.11; 95% CI -42.38 to -1.85). DISCUSSION: Basal ganglia PVS burden independently contributes to worse longitudinal executive function and visuospatial skills independent of other SVD markers, highlighting PVS as an emerging marker of domain-specific cognitive decline in aging. Although causation cannot be established, findings further support PVS as a vascular contributor to deep brain structure damage underlying cognitive decline over time.
28 Apr 2026
Read appraisal →Renal failure
Factors influencing patency after percutaneous transluminal angioplasty for autogenous arteriovenous fistulae: a systematic review and meta-analysis
This systematic review and meta-analysis identified factors influencing patency after percutaneous transluminal angioplasty (PTA) for autogenous arteriovenous fistulae (AVF) in hemodialysis patients. Literature through July 2025 was searched for observational and randomized trials. Two reviewers independently performed study selection, quality assessment (Newcastle-Ottawa Scale/Cochrane tool), and data extraction. Meta-analyses used fixed-/random-effects models in R (per I2 statistic), with sensitivity and publication bias analyses. Fifty-two studies (n = 6,407) were included, 45 of high quality. For primary patency, independent risk factors were diabetes (OR = 1.02, 95% CI 1.01-1.02), lesion length >2 cm (OR = 2.87, 1.38-5.96), previous intervention (OR = 3.13, 1.69-5.79), failed AVF history (OR = 1.69, 1.22-2.35), brachiocephalic configuration (vs. radiocephalic, OR = 1.73, 1.33-2.26), vascular calcification, and multiple comorbidities. High post-PTA flow was protective, and drug-coated balloons outperformed conventional angioplasty. Secondary patency was compromised by diabetes (OR = 1.05, 95% CI 1.02-1.08), longer lesions (OR = 1.01, 95% CI 1.01-1.02), and residual stenosis (OR = 1.02, 95% CI 1.01-1.04), with procedural success protective. Intimal hyperplasia strongly predicted failure. Restenosis risk was elevated by diabetes (OR = 1.72, 95% CI 1.28-2.31) and hypertension (OR = 1.59, 95% CI 1.04-2.44), while medical therapy with nitrates (OR = 0.20, 95% CI 0.05-0.79) and higher albumin were protective. Conventional biomarkers had limited value. Long-term AVF patency after PTA depends on anatomical, historical, and pathological factors, emphasizing the need to target modifiable procedural and hemodynamic variables in clinical practice.
25 Apr 2026
Read appraisal →European heart journal
Predictors of recurrent venous thromboembolism and bleeding in patients with cancer: a meta-analysis
BACKGROUND AND AIMS: Patients with cancer and venous thromboembolism (VTE) have a high risk of recurrent VTE and anticoagulant-related bleeding. This study aimed to identify prognostic factors for these complications. METHODS: A systematic review was performed for randomized trials and cohort studies evaluating prognostic factors for recurrent VTE or anticoagulant-related bleeding in adult patients with cancer and VTE. Adjusted hazard ratios (aHRs) for factors were pooled using random-effects meta-analysis. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: Thirty-three studies (n = 96 753) were included in the meta-analyses. Factors with high certainty of association with increased risk of recurrent VTE included a previous history of VTE [aHR 1.50 (95% CI 1.08-2.09)], Eastern Cooperative Oncology Group (ECOG) performance status >0 [1.81 (1.34-2.46)] or >1 [2.44 (1.55-3.84)], advanced cancer [1.38 (1.15-1.65)], and specific cancer sites including lung [1.78 (1.29-2.46)], hepatobiliary [2.37 (1.70-3.30)], pancreas [3.20 (2.06-4.96)], and genitourinary [1.38 (1.14-1.67)]. Conversely, recent surgery [aHR 0.56 (95% CI 0.40-0.76)] and breast cancer [0.43 (0.23-0.81)] had a high certainty of association with a decreased risk. Factors with a high certainty of association with an increased risk of anticoagulant-related bleeding included a history of bleeding [aHR 2.41 (95% CI 1.50-3.88)], ECOG performance status ≥2 [2.10 (1.48-2.99)], advanced cancer [1.60 (1.29-1.97)], and cancers of the brain [2.25 (1.64-3.09)], gastrointestinal system [1.74 (1.44-2.11)], genitourinary system [1.90 (1.48-2.45)], and prostate [1.72 (1.26-2.34)]. CONCLUSIONS: The prognostic factors identified in this meta-analysis should be considered as part of risk stratification frameworks for anticoagulation management in patients with cancer and VTE.
24 Apr 2026
Read appraisal →Journal of neurointerventional surgery
Intravascular lithotripsy in calcified carotid stenosis: technical and clinical outcomes
INTRODUCTION: Carotid artery stenosis (CAS) is a major cause of stroke, disability, and mortality worldwide. While medical therapy and revascularization remain the cornerstones of management, both surgical and endovascular approaches can be limited by complex anatomy and heavily calcified plaques, which increase procedural risk. Intravascular lithotripsy (IVL), originally developed for coronary and peripheral interventions, has recently emerged as a potential strategy for plaque modification in CAS. By delivering localized shockwave pulses, IVL fractures vascular calcium, facilitating safer angioplasty and stent deployment. However, its use in CAS remains off-label and poorly described. METHODS: A systematic search of PubMed, Google Scholar, and Embase was conducted in September 2025 in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included patients with CAS undergoing IVL with reported procedural success and/or clinical outcomes. Risk of bias was assessed using the Joanna Briggs Institute (JBI) appraisal tools. RESULTS: Fifteen studies comprising 120 patients were included. The mean age ranged from 50 to 82 years, and the degree of stenosis from 70%-95%. Technical success was reported in 100% of cases. Across the pooled cohort, 101 of 120 patients (84.2%) achieved residual stenosis ≤30%. Seven patients (5.8%) experienced ipsilateral stroke or transient ischemic attack within 30 days. CONCLUSION: IVL for CAS is an emerging therapy demonstrating consistent technical feasibility and favorable short-term safety across published studies. These findings suggest that IVL may benefit patients with complex calcified plaques at high risk for standard revascularization; however, randomized controlled trials are needed to confirm its role in clinical practice.
17 Apr 2026
Read appraisal →The New England journal of medicine
Asundexian for Secondary Stroke Prevention
BACKGROUND: Patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA) are at risk for recurrent stroke. Low factor XI levels are associated with a reduced risk of ischemic stroke. Asundexian inhibits activated factor XI. Whether the addition of asundexian to antiplatelet therapy would be superior to antiplatelet therapy alone for the secondary prevention of ischemic stroke is unclear. METHODS: In this phase 3, double-blind trial, we randomly assigned patients within 72 hours after the onset of a noncardioembolic ischemic stroke or high-risk TIA to receive asundexian (50 mg once daily) or placebo, in addition to planned dual or single antiplatelet therapy. Patients had at least one of the following: a nonlacunar infarct on imaging, a history of atherosclerosis, or evidence of atherosclerotic plaque at any location on cerebrovascular imaging. The primary efficacy outcome was ischemic stroke. The composite of death from cardiovascular causes, myocardial infarction, or stroke was a key secondary outcome. The primary safety outcome was major bleeding. RESULTS: Among 12,327 patients who underwent randomization (6162 to the asundexian group and 6165 to the placebo group), the incidence of ischemic stroke was lower in the asundexian group than in the placebo group (6.2% vs. 8.4%; cause-specific hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.84; P<0.001). The incidence of the composite of death from cardiovascular causes, myocardial infarction, or stroke was lower in the asundexian group than in the placebo group. The incidence of major bleeding was similar in the asundexian group and the placebo group (1.9% and 1.7%, respectively; cause-specific hazard ratio, 1.10; 95% CI, 0.85 to 1.44). The incidence of adverse events was 69.3% in the asundexian group and 70.1% in the placebo group; the incidence of serious adverse events was 19.2% and 19.5%, respectively. CONCLUSIONS: Among patients with noncardioembolic ischemic stroke or high-risk TIA treated with antiplatelet therapy, asundexian at a daily dose of 50 mg resulted in lower risks of ischemic stroke and major cardiovascular events than placebo, without a higher risk of major bleeding. (Funded by Bayer; OCEANIC-STROKE ClinicalTrials.gov number, NCT05686070.).
16 Apr 2026
Read appraisal →International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
Effects of locally applied water-filtered infrared a irradiation adjunctive to iloprost and carbon dioxide hand baths in patients with systemic sclerosis and severe Raynaud's phenomenon - a randomized controlled trial
BACKGROUND: Almost all patients with systemic sclerosis (SSc) experience Raynaud's phenomenon (RP) with risk of digital ulcers (DU). In severe RP, intravenous iloprost is standard, yet additive hyperthermic therapy may enhance vasodilation and microcirculation. However, whether more intensive or alternative hyperthermic modalities offer benefits beyond commonly used CO2 hand baths remains unclear. METHODS: In this randomized, controlled trial, all patients received a baseline therapy of iloprost plus CO2 hand baths. The intervention group (IG) received additional water-filtered infrared-A (wIRA; 2 × 30 min/day, 8 days), while the control group (CG) received baseline therapy alone. The primary endpoint was the difference in RP-associated pain (VAS 0-100 mm) after treatment. Secondary outcomes included changes in RP duration, frequency, and intensity, Health Assessment Questionnaire (HAQ), serum interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). RESULTS: Of 46 randomized patients, 38 (IG = 19, CG = 19) completed the study. Pain decreased from 70.4 ± 27.8 to 56.7 ± 21.4 mm with wIRA and from 73.9 ± 27.5 to 65.3 ± 26.8 mm in controls. Multivariable ANCOVA showed a mean difference of -14.7, 95% CI [-28.8;-0.7], p = 0.041 in favor of wIRA. RP duration improved more in the wIRA group (day 23: β = -3.8, 95% CI [-7.4;-0.2], p = 0.041), while RP frequency, intensity, HAQ, IL-6, and VEGF showed no significant differences (all p > 0.05). No adverse events occurred. CONCLUSIONS: Adjunctive wIRA during iloprost therapy was safe and yielded modest, short-term improvements in pain and RP duration. These exploratory effects warrant confirmation in larger controlled trials.
15 Apr 2026
Read appraisal →Blood advances
RNA interference therapy targeting coagulation factor XI: a first-in-human trial of RBD4059 (vortosiran)
Inhibiting coagulation factor XI (FXI) activity has emerged as a promising strategy to prevent intravascular thrombosis. Here, we describe the first-in-human trial with an N-acetylgalactosamine-conjugated small interfering RNA (siRNA), RBD4059, targeting FXI. In this phase 1 single ascending dose study (NCT05653037), healthy volunteers were randomized to receive either active drug or placebo (6 + 2), administered subcutaneously, in 4 consecutive dose cohorts ranging from 50 mg to 600 mg. The primary end point was safety and tolerability up to day 169 after dose. Secondary end points included pharmacokinetic and pharmacodynamic (PD) parameters. Single ascending doses of RBD4059 were well tolerated, and no apparent safety concerns were identified. RBD4059 was associated with a dose-dependent and durable suppression of FXI activity up to >90%. Modeling of the available PD data supports clinical dosing schemes of 3 to 6 months to achieve a robust antithrombotic effect. Altogether, these observations support further clinical development of RBD4059 to provide an siRNA-based therapeutic option targeting FXI for patients inadequately treated with or contraindicated for current available thrombosis prophylaxis. This trial was registered at www.clinicaltrials.gov as #NCT05653037.
15 Apr 2026
Read appraisal →Blood advances
Neutrophil CD14 is a driver and a therapeutic target for deep vein thrombosis.
Neutrophil-mediated persistent inflammation and neutrophil extracellular trap formation (NETosis) are critical in the pathogenesis of deep vein thrombosis (DVT). Identifying the mechanisms controlling these proinflammatory and prothrombotic functions is critical for designing and developing new therapeutics for DVT. However, how neutrophils acquire these phenotypes during the early stages of DVT remains poorly understood. Here, multiomic analyses (RNA sequencing, proteomics, and flow cytometry) of bone-marrow neutrophils 3 hours after DVT, revealed consistent overexpression of CD14. Concurrently, mice with DVT exhibited significantly elevated plasma granulocyte colony-stimulating factor (G-CSF) and neutrophil hyperactivation. Mechanistic studies using a geometric deep learning model (DeepPBS) and chromatin immunoprecipitation revealed that elevated G-CSF drives CD14 overexpression by upregulating the transcription factor C/EBPα (leucine zipper CCAAT-enhancer binding protein α). Importantly, neutrophil-specific CD14 knockdown using a novel lentiviral short hairpin RNA approach significantly improved DVT outcomes by lowering thrombus burden, thrombosis incidence, and intrathrombus neutrophil and citrullinated histone H3 accumulation. Studies in G-CSF stimulated primary human neutrophils revealed that CD14 inhibition reduces markers of inflammation and NETosis (activated gasdermin D, citrullinated histone H3, and S100A8/A9), while increasing apoptosis, thus demonstrating translational relevance. Collectively, our study uncovers an essential role of neutrophil CD14 in DVT pathogenesis and establishes it as a promising therapeutic target for DVT.
14 Apr 2026
Read appraisal →Heart (British Cardiac Society)
Subclinical atherosclerosis in women after pre-eclampsia: a systematic review and meta-analysis
BACKGROUND: Women with pre-eclampsia are at increased risk of later-life cardiovascular disease (CVD). Despite suggestions that women affected by pre-eclampsia should undergo routine CVD screening, uniform recommendations are lacking. Subclinical atherosclerosis provides a window of opportunity to identify and treat those at risk of CVD. Coronary artery calcium scoring (CAC), carotid intima-media thickness (CIMT) and ankle brachial index (ABI) are effective methods of detecting subclinical atherosclerosis. This systematic review sought to explore associations between timing of measurement and presence of subclinical atherosclerosis in women with a history of pre-eclampsia. METHODS: We searched the MEDLINE, EMBASE and CINAHL databases for all studies which reported subclinical atherosclerosis in women with a history of pre-eclampsia. Common and random effects models were used to examine the associations between pre-eclampsia and subclinical atherosclerosis. RESULTS: 35 case-control studies comprising 20 235 women were included in the final analysis. 3376 had a history of pre-eclampsia. Among the 26 studies assessing CIMT, pre-eclampsia was associated with increased CIMT (standardised mean difference 0.63 (95% CI 0.32, 0.93)). This difference was present during pregnancy (0.65 (95% CI 0.33, 0.98)) and persisted for 12 months post partum (0.84 (95% CI 0.20, 1.47)) and beyond (0.50 (95% CI 0.01, 0.99)). Pooled analysis of the eight CAC studies also demonstrated that the odds of having subclinical atherosclerosis were 1.57 (95% CI 1.39, 1.77) times higher in women with a history of pre-eclampsia. CONCLUSIONS: Among women with a history of pre-eclampsia, subclinical atherosclerosis can be seen during pregnancy and persists long term. Our review supports the importance of early follow-up in patients who have had pre-eclampsia.
12 Apr 2026
Read appraisal →PloS one
Voxel-wise deep learning segmentation of hydroxyapatite and iodine in spectral photon-counting CT: A quantitative phantom study
Accurate non-invasive identification of hydroxyapatite (HA) deposits is important for diagnosing calcific musculoskeletal disease and quantifying vascular calcification, but conventional and dual-energy CT often struggle to distinguish HA from iodinated contrast because of overlapping attenuation, noise, and beam-hardening artifacts. Spectral photon-counting CT (SPCCT) offers improved energy resolution and spatial fidelity, yet most deep-learning approaches in spectral CT focus on continuous density regression or anatomical segmentation rather than direct voxel-wise material labeling. We developed SPFF-UNet, a spectral-preserving 3D segmentation model for direct classification of HA and iodine concentrations from five-bin SPCCT volumes without material-decomposition preprocessing. A cylindrical phantom containing twelve materials was scanned at 0.1 mm isotropic resolution, including five HA concentrations, three iodine concentrations, three soft-tissue equivalents, and water. SPFF-UNet integrates spectral squeeze-excitation, EnergyFiLM, and FourierGate to preserve and exploit multi-energy information throughout the network. The model was trained for thirteen-class voxel-wise segmentation and compared with five established 3D architectures under matched training conditions. SPFF-UNet achieved the best macro-averaged performance on a held-out phantom scan (Dice 0.72 ± 0.01, IoU 0.59 ± 0.01, sensitivity 0.73 ± 0.01, precision 0.71 ± 0.01), outperforming the strongest comparator, ResUNet++ (Dice 0.66 ± 0.02, IoU 0.46 ± 0.02, sensitivity 0.67 ± 0.02, precision 0.61 ± 0.03). Performance gains were concentrated in mid/low-contrast HA and low-concentration iodine, with reduced slice-wise variability and fewer HA-iodine misclassifications. These results suggest that preserving spectral information and applying targeted spectral modulation can improve concentration-aware voxel classification from SPCCT. This phantom-based proof-of-concept provides a basis for future in vivo validation.
11 Apr 2026
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