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PubMed2026

Presentation, management, and outcomes of anterior inferior cerebellar artery dissecting and fusiform aneurysms: a systematic review and institutional case series.

Dissecting and fusiform aneurysms of the anterior inferior cerebellar artery (AICA) are rare and poorly characterized lesions. This study provides a comprehensive patient-level synthesis to date, combining a systematic review with institutional data to describe their clinical presentation, diagnostic workup, management strategies, and outcomes. A systematic review was conducted according to PRISMA guidelines. Studies were included if they reported on dissecting or fusiform AICA aneurysms. Individual patient data were extracted and supplemented with a single-institution case series. Outcomes, complications, and radiological evolution were analyzed descriptively. Forty-nine patients from 36 studies and 6 patients from our institution were included in this study. In the systematic review cohort, most aneurysms presented with subarachnoid hemorrhage (n = 38/49, 77.6%). Compressive cranial neuropathies, particularly including the vestibulocochlear system, were common in patients with unruptured aneurysms. Diagnosis often required digital subtraction angiography after the initial non-invasive imaging. Endovascular treatment, most commonly parent artery occlusion, was employed in 61.2% (n = 30/49) of cases. However, ischemic complications occurred in 23.3% (n = 7/30), especially in proximal (A1-A2) lesions. Bypass surgery was reported selectively for proximal aneurysms with inadequate collateral flow. As an alternative surgical approach, decompression or trapping was pursued based on aneurysm morphology or clinical context. Conservative management was typically reserved for select patients with poor-grade SAH, high procedural risk, or patient refusal of intervention. Overall, 81.4% (n = 35/43) of patients with available follow-up achieved good functional outcomes. Management of AICA dissecting and fusiform aneurysms is highly individualized. Endovascular approaches were frequently used to secure ruptured lesions or lesions considered at high risk, but periprocedural ischemic risk in perforator-rich segments remains a notable concern. Bypass procedures were reported in selected proximal aneurysms with limited collateralization. Conservative management was reserved for highly selected high-risk or anatomically inaccessible cases. Clinical trial registration: This study is not a clinical trial.

Humans↗

PubMed2026

Histopathologic, Genomic, and Clinical Characteristics of Primary Cutaneous Melanocytic Tumors With Concomitant NRAS Q61 and IDH1 R132C Mutations.

Cutaneous melanocytic tumors with concomitant NRAS Q61 and IDH1 R132C mutations have been described as intermediate-grade melanocytomas with characteristic biphasic morphology, but the malignant end of this genotype-defined spectrum remains poorly characterized. We assessed histopathologic, immunohistochemical, molecular, and clinical features of 16 primary cutaneous melanocytic tumors harboring both mutations. Following integrated review, 7 tumors were classified as melanocytoma and 9 as melanoma. Melanocytomas showed reproducible biphasic architecture with congenital nevus-like features, a biphasic HMB-45 pattern, low Ki-67, PRAME negativity, retained p16, and minimal copy number variations (CNVs). Melanomas retained partial morphologic overlap in a subset but were distinguished by higher-grade cytology, immunohistochemical features supportive of malignancy, and progression-associated genomic alterations, including TERT promoter mutation (9/9), 9p21/CDKN2A loss (4/7), and higher CNV burden. NRAS and IDH1 variant allele frequencies were strongly concordant (r = 0.83, P < 0.001), supporting their presence in the same dominant clone. Clinically, two patients presented with stage IIIB disease, but no distant metastasis or melanoma-related death occurred during a median melanoma follow-up of 3.9 years (IQR, 2.5-5.1). In exploratory analyses, moderate-to-severe atypia (RR, 6.2; 95% CI, 1.0-38.8; P = .009), Ki-67 ≥10% (RR, 4.4; 95% CI, 1.1-18.4; P = .003), lymphocytic infiltrate (RR, 2.4; 95% CI, 1.1-5.3; P = .03), absence of the typical biphasic pattern (RR, 2.4; 95% CI, 1.1-5.3; P = .03), and complete p16 loss (RR, 2.4; 95% CI, 1.1-5.3; P = .03) were associated with molecular or clinical progression to melanoma, defined as the presence of at least one of the following: TERT promoter mutation, pathogenic CDKN2A mutation, 9p21/CDKN2A loss, ≥3 genome-wide segmental CNVs, or any metastasis. These findings support the existence of NRAS/IDH1 co-mutated melanoma as the malignant counterpart of NRAS/IDH1-mutated melanocytoma within a single genotype-defined spectrum.

IDH1 mutations↗

PubMed2026

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n = 549) and a validation set (n = 236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60 mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60 mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans↗

PubMed2026

Cognitive behavioural therapy-based interventions on stress outcomes in pregnant women: A systematic review and meta-analysis.

BACKGROUND: Stress symptoms were the most common psychological problem in pregnancy. Cognitive behavioural therapy-based interventions are effective for antenatal depression and anxiety symptoms; but there are fewer studies for stress symptoms. OBJECTIVE: The review aims to (1) examine the effectiveness of cognitive behavioural therapy-based interventions in reducing stress outcomes (pregnancy-specific stress symptoms, generic symptoms, and objective stress) in pregnant women, and (2) identify significant moderators affecting the effectiveness of the intervention. DESIGN: Systematic review, meta-analysis, and meta-regression analysis of randomised controlled trials. METHODS: We conducted a three-step search (12 databases, 4 clinical registries, and citation searches) in English and Chinese up to July 24, 2025, by two independent reviewers. Meta-analysis, subgroup, and meta-regression analyses were performed using the R software. Quality assessment and certainty of the evidence were assessed with the Cochrane risk-of-bias tool version 2 and Grading of Recommendations, Assessment, Development, and Evaluation criteria. Publication bias was assessed using funnel plots and Egger's test. RESULTS: We included 20 randomised controlled trials involving a total of 6966 pregnant women from nine countries. Random-effects meta-analyses found that interventions significantly alleviated pregnancy-specific stress symptoms (Hedges' g = -0.84, 95% Confidence Interval, CI -1.42, -0.26, p < .01, I2 = 92.3%), reduced generic stress symptoms (g = -0.64, 95% CI -1.09, -0.20, p < .01, I2 = 87.4%) with median and large effect sizes at post-intervention. No effect was found in lowering cortisol levels (g = -0.99, 95% CI -2.58, -0.60, p = .12, I2 = 84%) at post-intervention. Subgroup and meta-regression analyses indicated that region, age of participants, use of intention-to-treat, missing data management analyses, frequency, modalities, and approaches of interventions, use of different comparators, and attrition rate were significant factors affecting the effectiveness of interventions. Subgroup analyses suggested that the intensity of intervention should be more than once per week using a blended mode among Asian populations. Multivariate meta-regression analyses indicated that both younger age (β = 0.13, p = .02) and a lower attrition rate (β = 0.03, p = .03) significantly improved the effectiveness of interventions. The overall certainty of the evidence was rated as either very low or low. CONCLUSIONS: Cognitive behavioural therapy-based interventions can supplement antenatal care to alleviate pregnancy-specific stress symptoms and generic stress symptoms, particularly in young Asian women. However, the evidence has some uncertainties. These findings should be interpreted with caution due to substantial heterogeneity. Well-designed trials on a large-scale with long-term follow-ups were needed. REGISTRATION: PROSPERO registration ID: CRD420251115913.

Humans↗

PubMed2026

PHACE syndrome: a systematic literature review and illustrative case report of a patient with severe cerebrovascular and neurodevelopmental sequelae.

BACKGROUND: PHACE syndrome is a rare neurocutaneous disorder defined by the association of large segmental infantile hemangiomas of the head and neck with malformations of the posterior fossa, cerebral and cervical arteries, heart, eyes, and ventral midline structures. Although facial hemangiomas are often the presenting feature, the cerebrovascular, neurodevelopmental, and airway manifestations are responsible for the greatest long-term morbidity. METHODS: A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Web of Science, EMBASE, and PsycINFO. After removal of duplicates and screening of 308 records, five studies meeting the inclusion criteria were retained for qualitative synthesis. We additionally present the case of a now 12-year-old girl with PHACE syndrome characterized by a left V1-distribution facial hemangioma, ocular abnormalities, multiple cerebrovascular venous and arterial malformations, neonatal intraventricular hemorrhage with hydrocephalus, and a subsequently diagnosed dural arteriovenous fistula requiring repeated embolization. RESULTS: The five included studies collectively describe epidemiology and early supportive care needs, long-term health outcomes and quality of life into adulthood, airway hemangioma prevalence and management, and the clinical spectrum of infantile hemangiomas with minimal or arrested growth (IH-MAG) as a cutaneous marker of PHACE syndrome. Across studies, cerebrovascular arteriopathy (72-91%) and facial hemangioma residua (> 90%) were the most consistent findings, while progressive arteriopathy, headaches, learning differences, and airway involvement emerged as the principal sources of long-term morbidity. The reported case illustrates an unusually severe cerebrovascular phenotype, including neonatal hemorrhagic hydrocephalus, dural venous sinus thrombosis, and a late dural arteriovenous fistula, culminating in ataxic cerebral palsy and mild intellectual disability. CONCLUSIONS: PHACE syndrome requires a multidisciplinary, lifelong follow-up strategy. The presented case underscores that cerebrovascular complications may evolve over years to decades after the initial diagnosis, reinforcing the need for long-term neuroradiological surveillance even after apparent clinical stability.

Humans↗

PubMed2026

Exercise and pathologic complete response to cancer treatment: a systematic review and meta-analysis.

PURPOSE: Neoadjuvant chemotherapy (NACT) is a commonly recommended approach for treating several cancers, and improving patients' outcomes to this therapy is important. This systematic review and meta-analysis assessed the impact of exercise on pathologic complete response (pCR), a key short-term marker of treatment efficacy, in patients with solid tumors receiving NACT. METHODS: Four electronic databases were searched for randomized controlled trials with physical exercise during NACT as an intervention published until May 2025. Risk of bias was assessed using Cochrane RoB 2.0 and the TESTEX scale. A random-effect meta-analysis using the inverse variance method synthesized the results. Heterogeneity was assessed using I2 and chi2 statistics. Risk ratio estimated the effect size. RESULTS: Eight studies involving 504 patients with breast, esophageal, gastric, or rectal cancer were included in the final analysis. Exercise interventions consisted of aerobic and resistance exercise. Overall, there were no significant differences between exercise and control groups in the rate of pCR to NACT (pooled risk ratio: 1.08 (95% CI: 0.82 to 1.43) Z = 0.56, p = 0.58). However, meta-regression data from breast cancer (BC) studies (4 studies, 367 participants) suggest exercise may be associated with enhanced tumor response to NACT in HR + /HER2- subtypes (regression coefficient: 0.83 (95% CI: -0.00 to 1.67), p = 0.05). CONCLUSION: Exercise during NACT did not improve pCR across cancer types. Exploratory meta-regression findings suggest a possible benefit of exercise in BC patients with the HR + /HER2- subtype. These results should be interpreted with caution due to the small number of studies and low certainty of the evidence.

Humans↗

PubMed2026

Risk factors and management strategies for needle disengagement from the visual field in pediatric robot-assisted laparoscopic pyeloplasty.

OBJECTIVE: This study aimed to identify risk factors for suture needle disengagement from the visual field during pediatric robot-assisted laparoscopic pyeloplasty (RALP) and propose effective strategies for prevention and management. METHODS: A retrospective cohort study analyzed clinical data from 339 pediatric patients who underwent RALP for ureteropelvic junction obstruction (UPJO) at a single institution between August 2017 and December 2020. Patients were categorized based on the occurrence of needle disengagement from the visual field. Various patient demographics and surgical procedural factors were evaluated. Univariate and multivariate logistic regression, along with LASSO regression, identified independent risk and protective factors. RESULTS: Needle disengagement occurred in 38 (11.21%) of 339 cases. Multivariate logistic regression identified five independent risk factors for needle disengagement: use of a 3-mm auxiliary trocar (OR = 4.69, 95% CI: 1.98-12.53, P < 0.001), non-standard needle holder use (OR = 2.32, 95% CI: 1.04-5.18, P = 0.038), unshaped suture needles (OR = 3.16, 95% CI: 1.44-7.19, P = 0.005), simultaneous use of ≥2 intra-abdominal sutures (OR = 2.46, 95% CI: 1.15-5.48, P = 0.023), and clamping the needle shank during withdrawal (OR = 3.42, 95% CI: 1.40-8.21, P = 0.006). Conversely, sufficient assistant experience (>10 cases) was identified as a protective factor (OR = 0.39, 95% CI: 0.18-0.88, P = 0.021). CONCLUSION: Suture needle disengagement from the visual field during pediatric RALP is associated with specific technical and instrumental factors. Implementing targeted strategies-such as mandating specialized needle holders, preoperative needle shaping, a single-needle workflow, prioritizing clamping the suture thread over the needle shank during withdrawal, and ensuring adequate assistant training-has the potential to significantly reduce significantly mitigate the risk of needle loss and enhance overall surgical safety in pediatric RALP.

Humans↗

PubMed2026

Diagnostic performance of machine learning models versus established risk stratification for intracranial aneurysm rupture: a systematic review and bivariate meta-analysis.

BACKGROUND: Machine learning (ML) models have been proposed to improve the discrimination of intracranial aneurysm rupture status beyond established clinical risk stratification tools. However, reported performance is heterogeneous and the relative contribution of model architecture and feature dominance remains unclear. METHODS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-diagnostic test accuracy systematic review and diagnostic meta-analysis of studies evaluating ML models for intracranial aneurysm rupture discrimination. PubMed, Embase and CENTRAL were searched to February 2026. Sensitivity and specificity were pooled using a bivariate random-effects model, with summary receiver operating characteristic curves generated across training, internal testing and external validation datasets. Models were compared with regression-based approaches and Population, Hypertension, Age, Size of aneurysm, Earlier subarachnoid haemorrhage, Site of aneurysm (PHASES) scores. Subgroup and meta-regression analyses explored associations between algorithm family and feature domain. RESULTS: Sixty-two retrospective cohorts (29 709 patients 209 models) met the inclusion criteria. In training datasets, pooled sensitivity and specificity for ML were 0.81 (95% CI 0.75 to 0.85) and 0.83 (0.80-0.86), with an area under the curve (AUC) of 0.878, exceeding PHASES (AUC 0.667). In testing datasets, ML retained higher discrimination (AUC 0.837) than regression models (0.806) and PHASES (0.646). In external validation, sensitivity was preserved (0.82), but specificity declined (0.66). Deep learning demonstrated the highest AUCs (training and testing). Incorporation of haemodynamic or radiomic features improved pooled discrimination relative to morphology alone. Evidence of small-study effects and mostly unclear Prediction Model Risk Of Bias Assessment Tool ratings were observed. CONCLUSIONS: ML approaches demonstrate higher pooled discrimination for aneurysm rupture status than conventional risk scores in retrospective datasets, but reduced external validation specificity and heterogeneity limit confidence for clinical translation. Prospective, externally validated, calibrated models are required before integration into routine cerebrovascular risk stratification.

Humans↗

PubMed2026

A Dynamic Nomogram to Predict Metabolic Dysfunction-Associated Fatty Liver Disease in Patients with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) involves multiple metabolic disorders. This study aimed to identify high-risk populations for metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with MetS and to establish a dynamic predictive nomogram. METHODS: A total of 627 patients with MetS from six regions in Zhejiang Province were enrolled and categorized into MAFLD and non-MAFLD groups, then randomly assigned to training and validation sets at a ratio of 7:3. Independent predictors of MAFLD were identified using least absolute shrinkage and selection operator regression and multivariable logistic regression analyses. These predictors were then used to construct a dynamic nomogram. RESULTS: A total of 627 patients with MetS were included in the final analysis, of whom 77.0% (483/627) were diagnosed with MAFLD. Multivariable logistic regression analysis identified body mass index (BMI), waist circumference (WC), total cholesterol (TC), alanine aminotransferase (ALT), MetS-defined dysglycemia, and education level as independent risk factors for MAFLD. MetS-defined dysglycemia showed the highest odds ratio (OR) for MAFLD development [OR = 1.87, 95% confidence interval (CI): 1.07-3.29]. Although the number of MetS components and the metabolic syndrome score were significantly associated with MAFLD in univariate analysis, they were not independently associated with MAFLD in the multivariate model. A dynamic nomogram for predicting MAFLD risk in patients with MetS was developed and internally validated. The area under the receiver operating characteristic curve was 0.834 (95% CI: 0.787-0.880) in the training set and 0.839 (95% CI: 0.771-0.899) in the validation set, indicating strong predictive performance. Bootstrap internal validation demonstrated good agreement between predicted and observed outcomes in calibration curves. Decision curve analysis further indicated favorable clinical applicability of the nomogram. CONCLUSION: BMI, WC, TC, ALT, MetS-defined dysglycemia, and education level are independent risk factors for MAFLD. A dynamic nomogram for predicting MAFLD risk in patients with MetS was successfully developed and validated.

Humans↗

PubMed2025

Global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD: a systematic review and meta-analysis.

BACKGROUND: The presence of diabetes increases the risk of adverse outcomes of patients with non-alcoholic fatty liver disease (NAFLD) even in those with lean or non-obese NAFLD. However, the epidemiological data regarding the prevalence of diabetes and prediabetes in lean or non-obese NAFLD populations remain limited. We assessed the global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD. METHODS: Published studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science databases from the inception of the databases to October 2024. The pooled global prevalence of diabetes or prediabetes in patients with NAFLD was evaluated using random-effects meta-analysis. Subgroup meta-analysis and meta-regression were used to investigate potential sources of heterogeneity. RESULTS: A total of 54 studies involving 146,714 patients with non-obese or lean NAFLD were included. The pooled global prevalence of diabetes among patients with lean or non-obese NAFLD was 15.6% (95% CI 10.8%-22.7%). Studies from South America reported the highest prevalence (41.3%, CI 39.1%-43.5%). Meta-regression models showed that geographic region and mean age (p < 0.05) were associated with the were associated with the prevalence of diabetes, jointly accounting for 51.61% of the heterogeneity. The global prevalence of prediabetes among patients with lean or non-obese NAFLD was 22.9% (95% CI 12.5%-41.9%) with the highest prevalence reported in studies from Europe (34.4%, CI 23.0%-51.4%). Meta-regression models showed that geographic region and country (p < 0.05) were associated with the prevalence of prediabetes, jointly accounting for 73.65% of the heterogeneity. CONCLUSION: The pooled global prevalence of diabetes and prediabetes were 15.6% and 22.9% in lean or non-obese patients with NAFLD, respectively. These findings suggest the importance of diabetes screening in these patients.

Humans↗

PubMed2026

[Efficacy and safety of thoracic paravertebral block combined with thoracic nerve block for acute herpes zoster neuralgia involving upper thoracic dermatomes in middle-aged and elderly patients].

To investigate the clinical efficacy and safety of ultrasound-guided thoracic paravertebral block (TPVB) combined with pectoral nerve block (Pecs) in the treatment of acute herpetic neuralgia (AHN) involving the upper thoracic segments in middle-aged and elderly patients, a prospective study was conducted. A total of 70 middle-aged and elderly patients with upper thoracic AHN who visited the Department of Pain Medicine at Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, from June to December 2023, were enrolled and randomly divided into a control group and an experimental group using a random number table, with 35 patients in each group. The control group received TPVB once weekly for a total of 3 sessions, while the experimental group received TPVB combined with Pecs block using the same regimen. Outcome measures included the Visual Analogue Scale (VAS) for pain, Pittsburgh Sleep Quality Index (PSQI), 7-item Generalized Anxiety Disorder Scale (GAD-7), 9-item Patient Health Questionnaire (PHQ-9), treatment satisfaction score, incidence of postherpetic neuralgia (PHN), rescue analgesia, and adverse events. Assessments were conducted at 1, 4, 8, and 12 weeks post-treatment, and between-group differences were compared. Ultimately, 33 patients in the experimental group and 31 in the control group completed the follow-up and were included in the final analysis. The results showed that both groups demonstrated significant improvements in VAS scores, PSQI, GAD-7, PHQ-9, and satisfaction scores compared with baseline (all P<0.05). Compared with the control group, the experimental group exhibited significantly lower VAS scores and higher satisfaction scores at 1, 4, and 8 weeks post-treatment (P<0.05), as well as significantly lower PSQI, GAD-7, and PHQ-9 scores at 4 and 8 weeks (P<0.05). There were no statistically significant differences between the two groups in the incidence of PHN, rescue analgesia, or adverse events (all P>0.05). This study demonstrates that compared with TPVB alone, the combination of TPVB and Pecs block provides better pain relief, improves sleep quality, and alleviates anxiety and depression in middle-aged and elderly patients with upper thoracic AHN, with a favorable safety profile.

Humans↗

PubMed2026

Beyond predictive performance: A systematic review and critical methodological appraisal of AI/ML and conventional modelling strategies in breast, colorectal, and pancreatic Cancer.

BACKGROUND: Predictive modelling for cancer risk, treatment-related complications, and survival is central to precision oncology. Conventional logistic regression (LR) and Cox proportional hazards (CoxPH) regression remain widely used but are limited when modelling nonlinear interactions, high-dimensional imaging features, and multimodal clinical-metabolic predictors. Artificial intelligence (AI) and machine learning (ML) methods offer expanded capability through automated feature extraction, ensemble learning, and flexible survival modelling, but the evidence on when AI/ML adds value over conventional models across cancer sites and predictive tasks remains fragmented. OBJECTIVE: To systematically evaluate the methodological performance, validation strategies, and translational limitations of AI/ML models compared with conventional statistical models in published predictive-modelling studies for breast, colorectal, or pancreatic cancer. METHODS: PubMed, Scopus, and Web of Science were searched for studies published between January 2019 and March 2025. Two reviewers independently conducted title-and-abstract screening, full-text eligibility assessment, and PROBAST risk-of-bias assessment. Sixty-five studies (n = 907,567 participants) were narratively synthesised by cancer site, predictive task, model family, comparator, validation strategy, predictor modality, and calibration or explainability reporting. RESULTS: The 65 studies comprised breast cancer (n = 35), colorectal cancer (n = 21), and pancreatic cancer (n = 9). AI/ML superiority over LR and CoxPH was task- and data-dependent. CNN- and U-Net-based models predominated in imaging and body-composition tasks, tree-based ensembles consistently outperformed LR for tabular perioperative complication prediction, and CoxPH remained competitive, and in the largest pancreatic risk study, superior to XGBoost (C-index 0.802 vs 0.723) in well-structured datasets. PROBAST analysis-domain risk was moderate in 54 of 65 studies (83%), driven by limited external validation, sparse calibration reporting (11/65), and few decision-curve analyses (7/65). CONCLUSION: AI/ML adds the most methodological value in imaging-derived feature extraction and nonlinear perioperative prediction, while conventional regression remains preferable in large, structured datasets with linear predictors. Clinical translation requires standardised body-composition definitions, external validation, calibration assessment, decision-curve analysis, and explainability, in line with TRIPOD+AI and CLAIM standards.

Humans↗

PubMed2026

Effects of an actuated ankle exoskeleton on walking stability in healthy adults: a controlled laboratory study.

BACKGROUND: Ankle exoskeletons are widely used to reduce the metabolic cost of walking, yet their effects on walking stability during unperturbed gait remain insufficiently understood. Walking stability can be characterized using complementary measures that capture stride-to-stride variability, global temporal organization, and local dynamic stability. Understanding how walking with an actuated ankle exoskeleton system influences these different aspects of gait stability is essential for the safe design and control of wearable robotic devices. METHODS: Eighteen healthy adults walked on a treadmill at a constant speed (1.1 m/s) with and without an actuated bilateral ankle exoskeleton in a randomized crossover design. Spatiotemporal variability was quantified using coefficients of variation (CoV) of stride length, step width, and stance ratio. Global gait stability was assessed using detrended fluctuation analysis of stride time. Local dynamic stability was evaluated using maximum Lyapunov exponent calculated for the trunk, hip, upper leg, lower leg, and foot. Paired-samples two-sided t-tests were used to compare conditions. RESULTS: Walking with the ankle exoskeleton resulted in increased stride-to-stride spatiotemporal variability, reflected by higher CoV values for stride length (p < 0.001) and stance ratio (p = 0.005), while mean stride length and step width remained unchanged. Mean stance ratio was reduced in the exoskeleton condition (p < 0.001). Global gait stability did not differ between conditions, indicating preserved long-range temporal gait organization. Local dynamic stability increased at the lower leg (p < 0.001) and foot (p = 0.019) when walking with the exoskeleton. CONCLUSIONS: Walking with the actuated ankle exoskeleton alters gait control across multiple levels during steady walking. While stride-to-stride variability in stride length and stance ratio increased, global gait stability remained unchanged. Local dynamic stability was increased at the lower leg and foot, suggesting segment-specific effects of ankle-level assistance close to the assisted joint. However, these findings should be interpreted as the combined effect of wearing the exoskeleton and receiving active assistance, rather than the isolated effect of plantarflexion assistance. These results provide insight for the design and control of ankle exoskeletons with respect to stability-related effects during walking.

Humans↗

PubMed2026

Efficacy and Safety of Ultra-Low Starting Dose Febuxostat Titration in Male Patients With Primary Gout.

BACKGROUND: Since gout is a common metabolic arthritis caused by urate crystal deposition, urate-lowering therapy (ULT) is clearly indicated, but the initiation of ULT frequently causes paradoxical acute flares that in turn impair patient adherence. OBJECTIVE: This study sought to assess the effectiveness and safety of an ultra-low-dose initiation strategy for febuxostat (10 mg/day) compared to the standard starting dose (20 mg/day) in reducing initiation-related flares while maintaining long-term urate control. METHODS: 120 male patients with primary gout presenting with acute arthritis were randomly assigned to initiate febuxostat at 10 mg/day (Group A) or 20 mg/day (Group B), with protocol-mandated biweekly titration. The primary outcomes were gout flare frequency over 24 weeks (assessed using Poisson regression), serum uric acid (SUA) target attainment, and the incidence of adverse events. RESULTS: Although both groups achieved comparable target SUA levels by week 24, Group A demonstrated a significantly lower overall flare incidence (36.7% vs. 70.0%; p < 0.001), along with a greater percentage of flare-free patients (70.0% vs. 46.7%; p = 0.016). Multivariable Poisson regression revealed that Group B had an approximately twofold higher risk of flares compared to Group A (Incidence Rate Ratio = 1.95; p = 0.012), with obese patients deriving the most pronounced benefit from the ultra-low-dose approach. To avert one additional flare, the calculated number needed to treat was 4.3. Additionally, the occurrence of clinically significant liver injury (ALT/AST > 3× ULN) was low in both groups, with 3.3% in Group A and 1.7% in Group B. Multivariable regression analysis confirmed that LDL-C is an independent predictor of ALT (β = 12.90, p = 0.009), while febuxostat dosage was not linked to hepatotoxicity. CONCLUSION: Initiating febuxostat at a dose of 10 mg/day with gradual titration demonstrates a superior safety profile by effectively reducing early acute flares without compromising long-term urate control, which is particularly advantageous for high-risk cohorts, including obese patients.

Humans↗

PubMed2026

An Assessment of Reliability Estimation Methods for Binomial Health Care Quality Measures.

We evaluated the performance of commonly used methods for estimating the reliability of binomial health care quality measures using simulated datasets spanning a range of performance score means and variances, numbers of entities, and patient sample sizes. For each simulation, reliability was estimated for all selected methods and compared with the known true reliability derived from the simulation parameters, with methods assessed on their accuracy and precision. Logistic regression with reliability estimated on the outcome scale demonstrated the highest accuracy and precision among all methods evaluated. The widely used Adams beta-binomial method performed poorly, although a modification recommended by Nieser and Harris substantially improved its performance. These approaches are applicable only to binomial measures. Among methods that can be applied to both binomial and continuous measures, permutation resampling of the Spearman rank correlation coefficient was the most accurate and precise, outperforming other commonly used approaches. Overall, for binomial quality measures, logistic regression on the outcome scale is the preferred method for reliability estimation, followed closely by the modified beta-binomial approach, while for non-binomial measures, permutation-based Spearman rank correlation appears to be the most suitable method.

Reproducibility of Results↗

PubMed2026

A STORM-based protocol for nanoscale imaging and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber.

Stochastic Optical Reconstruction Microscopy (STORM) enables nanoscale mapping of molecular components beyond the diffraction limit; however, its reproducible implementation in hydrophobic polymer matrices remains challenging because fluorescence-labeling specificity, fluorophore photoswitching, three-dimensional localization, chromatic registration, and quantitative image analysis must be carefully controlled. This protocol presents a standardized experimental workflow for dual-color labeling, astigmatism-based three-dimensional STORM acquisition, and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber (NR). The workflow covers sample pretreatment, Cy5 NHS ester labeling of protein-associated primary amines, DiI labeling of phospholipid-rich domains, STORM imaging-buffer preparation, three-dimensional single-molecule localization, dual-channel registration, generation of standardized xy projections, aggregate-size analysis, and projected lateral spatial correlation assessment. Reproducibility is supported by defined acquisition and localization criteria, three independent sample preparations with at least five fields of view analyzed per condition, and unlabeled, single-color, dye-only matrix, and processing-associated Cy5 controls. Mean lateral localization precisions of 11.8 ± 2.3 nm for Cy5 and 13.5 ± 2.9 nm for DiI were obtained, while two-dimensional Fourier ring correlation analysis of the xy projections yielded effective lateral image resolutions of approximately 25 and 28 nm, respectively. Image-based particle segmentation and localization-coordinate-based density-based spatial clustering of applications with noise (DBSCAN) were applied to standardized xy projections as complementary quantitative approaches. Application of the protocol to untreated, centrifuged, and protease-treated NR samples demonstrated treatment-associated changes in the detected abundance and projected size distributions of protein- and phospholipid-associated aggregates, together with a non-monotonic change in their projected lateral spatial correlation. These observations describe alterations in nanoscale organization but do not, by themselves, establish stable protein-phospholipid complex formation. Unlike previous studies that primarily demonstrated the feasibility of STORM imaging in rubber materials, the principal contribution of this work is an end-to-end, step-by-step protocol incorporating defined controls, three-dimensional localization, image-quality metrics, chromatic-registration procedures, and complementary quantitative-analysis pipelines for non-expert users. The workflow may be adaptable to other hydrophobic polymers and soft-material systems after appropriate optimization and validation.

Rubber↗

PubMed2026

Transcutaneous vagus nerve stimulation influences sleep quality and insomnia: A systematic review and meta-analysis.

Impairments in sleep quality, timing, or duration disrupt normal sleep patterns. This systematic review and meta-analysis investigated the effects of transcutaneous vagus nerve stimulation (tVNS) protocols on sleep outcomes. Thirteen randomized controlled trials with parallel or crossover designs that applied tVNS intervention and assessed sleep quality (Pittsburgh Sleep Quality Index) and insomnia severity (Athens Insomnia Scale and Insomnia Severity Index) were included. Effect sizes were calculated by comparing changes between the active tVNS and control groups. Moderator analyses examined whether stimulation of different targeted regions influences sleep outcomes. Meta-regression analyses examined potential relationships between the effects of tVNS protocols on sleep quality and demographic characteristics and multiple tVNS parameters, respectively. The random-effects meta-analysis indicated that tVNS protocols influenced better sleep quality and lower insomnia severity. Moderator variable analysis revealed that tVNS targeting the concha region induced better sleep quality. Meta-regression analysis revealed that better sleep quality was associated with lower ages of participants. These findings suggest that tVNS protocols, particularly those targeting the concha, were associated with favorable changes in sleep quality and insomnia severity, with age potentially moderating the treatment response.

Humans↗

PubMed2026

Optimized AAV5-RPGR ORF15 Gene Therapy Rescues Photoreceptor Structure and Function in X-Linked Retinitis Pigmentosa Mouse Model.

PURPOSE: To develop and evaluate an rAAV5-based gene therapy vector expressing an optimized human RPGR ORF15 transgene (rAAV5-RPGR) for the treatment of X-linked retinitis pigmentosa caused by RPGR mutations, addressing the challenges of cloning the unstable wild-type ORF15 sequence. DESIGN: This was a prospective experimental study. SUBJECTS: This was an animal study. METHODS: An optimized RPGR ORF15 sequence was designed to eliminate problematic secondary structures and cryptic splice sites. In vitro expression was validated in HEK 293T and photoreceptor-like 661 W cells. A complete Rpgr knockout mouse model (Rpgr-knockout [KO]) was generated and characterized phenotypically. Therapeutic efficacy was assessed in Rpgr-KO mice via subretinal injection of rAAV5-RPGR at low (1 × 10⁹ vg/eye), medium (3 × 10⁹ vg/eye), or high (1 × 10¹⁰ vg/eye) doses. Structural and functional outcomes were evaluated at 12- and 14-month postinjection. Short-term safety was assessed in rabbits 1 month after subretinal injection. MAIN OUTCOME MEASURES: Level of RPGR protein expression and Protein isoform profile (elimination of truncated isoforms), Cellular localization of transgene expression and Dose-dependence of expression, outer nuclear layer thickness, and electroretinography parameters. RESULTS: (1) The optimized vector increased RPGR protein expression 3.3-fold in vitro compared to wild-type and eliminated truncated isoforms. (2) Subretinal delivery of rAAV5-RPGR in mice demonstrated dose-dependent transgene expression localized correctly to photoreceptor inner segments. (3) In Rpgr-KO mice, high-dose treatment significantly preserved outer nuclear layer thickness at the injection site (42% greater than controls at 14 months, P < .01) and central retina (P < .05), reduced aberrant rhodopsin mislocalization (P < .01), and partially restored retinal function. ERG showed significantly improved scotopic a-wave (≥100 vs <90 µV in controls at 10 cd·s/m²) and photopic b-wave amplitudes (49-66 vs 31-46 µV at 30 cd·s/m²) in treated mice. (4) No vector-related toxicity was observed in rabbits. CONCLUSIONS: rAAV5-RPGR mediated efficiently, targeted expression of optimized RPGR-ORF15, significantly preserved photoreceptor structure and function in a severe X-linked retinitis pigmentosa mouse model, and demonstrated a favorable safety profile. This study provides preclinical proof-of-concept for RPGR-targeted gene replacement therapy.

Animals↗