Tag: nevin manimala

J Transl Med. 2026 Feb 26. doi: 10.1186/s12967-026-07921-9. Online ahead of print.

ABSTRACT

BACKGROUND: Programmed cell death (PCD) plays an important role in diabetic retinopathy (DR); however, the underlying genetic mechanisms remain unclear. We used Mendelian randomization (MR) to investigate the causal relationships between PCD-related genes and DR. This study aimed to investigate the effects of PCD on the risk of DR by conducting MR analysis.

METHODS: Summary statistics from gene expression quantitative trait loci (eQTL) studies (31,684 Europeans) were analyzed. Genetic instrumental variables were selected using cis-eQTL single-nucleotide polymorphisms (SNPs; P < 5 × 10^{– 8}). Summary data-based MR (SMR) was employed to assess causal associations between PCD-related genes and DR, with three additional MR methods used for sensitivity testing. Bayesian colocalization was used to examine the shared regulatory mechanisms between PCD QTLs and DR risk loci.

RESULTS: Sensitivity and colocalization analyses revealed six genes that affected DR: cathepsin H (CTSH), NAD(P)H: quinone oxidoreductase 1 (NQO1), tribbles pseudokinase 3 (TRIB3), and phosphoglycerate mutase 5 (PGAM5), which increased DR risk, and iron-responsive element binding protein 2 (IREB2) and tumor necrosis factor (TNF), which exhibited protective effects. Multivariate MR confirmed significant causal effects for CTSH, IREB2, and PGAM5 (p < 0.050). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (including 10 STRING-derived genes) revealed that 13 genes were enriched in necroptosis, apoptosis, mitophagy, and TNF signaling pathways in DR.

CONCLUSIONS: This MR study supports the causal involvement of PCD in DR and identifies candidate genes (CTSH, IREB2, PGAM5, NQO1, TRIB3, and TNF) for therapeutic targeting or biomarker development in DR prevention or diagnosis.

PMID:41749353 | DOI:10.1186/s12967-026-07921-9

Eur J Med Res. 2026 Feb 26. doi: 10.1186/s40001-026-04029-0. Online ahead of print.

ABSTRACT

OBJECTIVES: The incidence of bladder cancer after kidney transplantation is high, but there is a lack of ideal treatment options.This study is an exploratory case series aiming to preliminarily observe the clinical manifestations and safety profile of Olaparib combined with intravesical perfusion in treating secondary bladder cancer post-kidney transplantation, so as to generate scientific hypotheses for subsequent research.

METHODS: This is a single-center preliminary study that analyzed the clinical data of 7 patients with secondary bladder cancer after kidney transplantation who received Olaparib combined with intravesical perfusion therapy. Seven patients with secondary bladder cancer after kidney transplantation were enrolled. Pathologically, 6 cases were high-grade non-muscle-invasive bladder cancer, and 1 case was small cell carcinoma complicated with high-grade non-invasive bladder cancer. Genetic testing showed 4 patients carried Homologous Recombination Repair (HRR) gene mutations, while 3 were negative. All received Olaparib combined with intravesical chemotherapy. Only descriptive follow-up was performed to monitor treatment responses, progression-free survival (PFS), and adverse events (AEs).

RESULTS: The median PFS of all patients was 15.8 months, with 15.7 months in HRR-mutated patients and 16 months in non-mutated ones. Tumor recurrence occurred in Patient 1 (20 months post-treatment) and Patient 7 (14 months post-treatment). Patient 4 discontinued Olaparib at 18 months without metastasis or recurrence during follow-up. All patients had varying drug-related AEs, but no Grade 4/5 severe events were reported, and renal allograft function remained normal throughout the study.

CONCLUSIONS: Olaparib combined with intravesical perfusion showed certain disease control effects in these 7 patients. However, limitations including small sample size, lack of a control group, and no predefined endpoints resulted in insufficient statistical power, so the findings are preliminary and hypothesis-generating.

PMID:41749345 | DOI:10.1186/s40001-026-04029-0

Liver Int. 2026 Apr;46(4):e70559. doi: 10.1111/liv.70559.

ABSTRACT

BACKGROUND: Chronic hepatitis D (CHD) causes severe chronic hepatitis. Knowledge is limited about factors correlating with ALT in treatment-naïve patients with CHD. This study analysed the pattern and determinants of ALT elevation in a large cohort of patients with CHD, including young adults, compared to propensity score-matched (PSM) patients with chronic hepatitis B (CHB).

METHODS: We identified 2382 treatment-naïve HBsAg+ adults with CHD (HDV RNA positive) and 1553 with CHB attending a liver center in Mongolia during 2015-2023. The correlation between ALT levels, virological, biochemical, and fibrosis parameters was assessed using Spearman coefficient (rho). Logistic regression analysis was used to identify determinants of elevated ALT in 1371 PSM pairs with CHD and CHB matched on age, sex, metabolic factors, and date of initial test.

RESULTS: In CHD, 78.5% of patients had ALT elevation, with the highest prevalence in the 18-20 years group (n = 219, 84.5%). This age group displayed 8.2-adjusted odds ratio (aOR) for elevated ALT, 2.7-aOR for elevated GGT, and 4.5-aOR of cirrhosis than matched CHB group (all p < 0.05). In CHD, ALT correlated weakly with HDV RNA (rho = 0.23) and liver stiffness (rho = 0.37), moderately with GGT (rho = 0.48), while showed no correlation with HBV DNA or HBsAg. Independent factors for elevated ALT were age < 30 years, elevated GGT and HDV RNA levels.

CONCLUSIONS: In this large cohort of Asian patients, an earlier and more severe inflammatory process could be demonstrated in CHD compared to CHB regardless of liver cirrhosis. Longitudinal studies are warranted to risk-stratify and prioritise patients for therapies.

PMID:41749331 | DOI:10.1111/liv.70559

Knee Surg Relat Res. 2026 Feb 26;38(1):9. doi: 10.1186/s43019-026-00308-6.

ABSTRACT

PURPOSE: Patellofemoral (PF) complications are a common cause of dissatisfaction and revision following total knee arthroplasty (TKA), often linked to altered kinematics and implant design. “Patella-friendly” femoral components with a wider, funnel-shaped trochlear groove may better restore native patellar motion. This study evaluated PF kinematics both before and after TKA performed using kinematic alignment, investigating the role of implant design and quadriceps loading.

METHODS: In total, 12 paired fresh-frozen cadaveric lower limbs were tested before and after TKA. Within each pair, one limb received a traditional medial pivot femoral component, while the contralateral limb received a “patella-friendly” medial pivot femoral component. Native and implanted knees were tested by flexing the knee under the action of an external load applied through the quadriceps tendon, varying its magnitudes (20, 160, 280N) and directions in the frontal (neutral,±6°, ±12°) and sagittal plane (neutral, +5° anterior). Motion was captured using an eight-camera optoelectronic system.

RESULTS: In the reference condition (20N, neutral direction), neither design showed statistical differences versus native (p > 0.05). However, the patella excursion in varus-valgus rotation was much higher in the specimens implanted with the traditional femoral component design (35.1° versus 14.6° native) than with the patella-friendly (20.5°). Differences between the designs emerged mainly with quadriceps load variations, especially frontal direction changes, which significantly affected patellar motion in both native and implanted knees (p < 0.05). Overall, the patella-friendly design better reproduced native kinematics under most conditions. However, with extreme medial loading (12°), three out of six specimens implanted with the patella-friendly femoral component were untestable owing to instability, and others exhibited high lateral displacement and trochlear dysplasia. In contrast, all traditional design implants remained stable, though with greater deviation from native kinematics.

CONCLUSIONS: This study provides foundational insights into PF biomechanics before and after TKA with kinematic alignment. By analyzing the interplay between implant geometry and quadriceps loading direction, it emphasizes the importance of selecting femoral components on the basis of individual patient anatomy. Our findings suggest that patella-friendly femoral components-although capable of better reproducing native motion in some cases-may not be suitable for patients with medially directed quadriceps forces or severely varus morphotypes.

PMID:41749321 | DOI:10.1186/s43019-026-00308-6

Diabetes Obes Metab. 2026 Feb 26. doi: 10.1111/dom.70576. Online ahead of print.

ABSTRACT

BACKGROUND: We examined the association between visit-to-visit HbA1c variability and risk of mortality, acute myocardial infarction (AMI), stroke, lower extremity amputation (LEA), neuropathy, and nephropathy.

METHODS: We conducted a retrospective cohort study of adults with type 2 diabetes managed at specialist outpatient clinics between 2009 and 2017. HbA1c variability was assessed using intra-individual visit-to-visit coefficient of variation (COV), variation independent of mean (VIM), and HbA1c Variability Score (HVS). Diabetes-related outcomes were identified using diagnosis and service codes. Cox proportional hazards and weighted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: The cohort comprised 18 293 patients (mean age: 63.8 ± 13.1 years; 55.1% male). Compared to those in the lowest quartiles of HbA1c variability, patients in the highest quartile had higher HRs for mortality (COV: HR = 2.03, 95% CI: 1.43-2.88; VIM: HR = 2.70, 95% CI: 1.61-4.53; HVS: HR = 2.32, 95% CI: 1.49-3.62), and nephropathy (COV: HR = 1.34, 95% CI: 1.14-1.56; VIM: HR = 1.31, 95% CI: 1.14-1.52; HVS: HR = 1.20, 95% CI: 1.04-1.39), with statistically significant tests for linear trend. No significant associations were observed between HbA1c variability and AMI (HR = 0.88, 95% CI: 0.51-1.52), stroke (HR = 1.19, 95% CI: 0.92-1.56), neuropathy (HR = 1.01, 95% CI: 0.80-1.28), or LEA (HR = 1.00, 95% CI: 0.65-1.55).

CONCLUSION: Higher HbA1c variability was associated with significantly increased risk of mortality and nephropathy, but not significantly associated with the risk of AMI, stroke, neuropathy, or LEA.

PMID:41749305 | DOI:10.1111/dom.70576

Trials. 2026 Feb 26. doi: 10.1186/s13063-026-09518-5. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Cancer-related lymphedema (CRLE), a chronic complication of cancer treatment, affects 39-73% of patients post-lymph node dissection, impacting physical health, social participation, and finances. Prophylactic immediate lymphatic reconstruction (ILR) via lymphaticovenous anastomosis (LVA) has shown potential in reducing CRLE incidence by two-thirds following axillary and inguinal node dissection. However, rigorous phase III studies with long-term follow-up are still needed to confirm these promising results. This study aims to evaluate the efficacy, safety, and long-term outcomes of ILR in preventing CRLE in a prospective, controlled trial setting.

METHODS/DESIGNS: A phase III randomized controlled trial will evaluate an intervention in adult patients undergoing axillary or groin node dissection for cutaneous malignancy. Block randomization will stratify participants by upper or lower extremities. Primary outcomes include lymphedema incidence and quality-of-life measures. Statistical analyses will compare lymphedema rates and quality-of-life outcomes between intervention and control groups.

OBJECTIVES: The primary endpoint is to assess the impact of prophylactic LVA on the presence or absence of lymphedema post axillary or groin lymphadenectomy and participant quality of life. The secondary endpoint is the incidence of complications related to nodal dissection.

SIGNIFICANCE: CRLE, a common complication of cancer surgery and radiotherapy, severely impacts patients’ lives and healthcare resources. Reducing its incidence by two-thirds would significantly improve outcomes for cancer survivors and decrease treatment demands. This underscores the need for advanced research in prevention and early intervention strategies to mitigate lymphedema’s burden on patients and healthcare systems.

TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05136079 2021-11-02.

PMID:41749241 | DOI:10.1186/s13063-026-09518-5

Eur J Med Res. 2026 Feb 26. doi: 10.1186/s40001-026-04040-5. Online ahead of print.

ABSTRACT

BACKGROUND: Fibroblast activation protein inhibitor (FAPI)-PET is a novel imaging modality that targets FAP. The purpose of this study was to conduct a meta-analysis and synthesize the available data about the sensitivity and specificity of FAPI-PET in assessing cardiac fibroblast activation and predicting left ventricular function in patients with cardiovascular disease (CVD).

METHODS: We searched the PubMed, Web of Science, and Embase databases from the time the databases were created until December 19, 2025. The diagnostic performance of FAPI-PET was meta-analyzed with Python (version 3.12). Data management and numerical computations were carried out with pandas and NumPy; meta-analytic calculations and statistical tests were implemented using SciPy; and all figures (forest plots, subgroup analyses, Deeks’funnel plot, SROC curve, and leave-one-out sensitivity analyses) were produced using Matplotlib.

RESULTS: There were 13 studies involving 256 patients, including 166 males with CVD. The age of the patients ranged from 23.0 to 76.1 years. The CVD patient-level pooled sensitivity, specificity and area under the curve (AUC) of FAPI-PET in evaluating cardiac fibroblast activation were 0.91, 0.75 and 0.9358, respectively. The pooled sensitivity and specificity of FAPI-PET in evaluating cardiac fibroblast activation in CAD patients were 0.96 and 0.82, respectively; those in non-CAD patients were 0.89 and 0.58, respectively. Multiple semiquantitative FAPI-PET uptake metrics were significantly correlated with LVEF. Among them, FAP volume (Pearson) demonstrated the best random effects pooled correlation estimate (-0.73), with substantial heterogeneity (I² = 0%; τ² = 0.0000, p = 0.41).

CONCLUSIONS: FAPI-PET has high sensitivity, specificity and AUC in evaluating cardiac fibroblast activation in CVD. It has significant predictive value for LV function and can be used successfully for the early detection and assessment of activated fibroblasts.

REGISTRATION: PROSPERO; No.: CRD42024561672; URL: https://www.crd.york.ac.uk/prospero.

PMID:41749239 | DOI:10.1186/s40001-026-04040-5

BMC Med Inform Decis Mak. 2026 Feb 26. doi: 10.1186/s12911-026-03389-1. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular disease constitutes the most formidable public health challenge in China, accounting for 48.98% and 47.35% of mortality in rural and urban populations, respectively, affecting approximately 330 million individuals. Existing risk stratification models predominantly derive from Western populations, with the Framingham Risk Equation systematically overestimating cardiovascular risk by 276% in Chinese men and 102% in Chinese women, underscoring the critical imperative for population-specific predictive instruments. Although machine learning methodologies demonstrate considerable promise in cardiovascular risk prognostication, their inherent “black-box” characteristics substantially impede clinical translational implementation.

OBJECTIVE: Leveraging longitudinal cohort data from the China Health and Retirement Longitudinal Study (CHARLS) and integrating machine learning with explainable artificial intelligence techniques, we sought to develop and validate a cardiovascular disease long-term risk prediction model tailored to the Chinese middle-aged and elderly population, achieving optimal synthesis of predictive accuracy and clinical interpretability through quantitative risk factor contribution analysis.

METHODS: We incorporated four waves of CHARLS surveillance data spanning 2011-2020, with 8,080 participants aged ≥ 45 years completing 9-year follow-up after rigorous inclusion criteria application. Recursive feature elimination was employed to identify optimal predictors from 90 candidate variables. We systematically evaluated 12 machine learning algorithms encompassing linear, non-linear, ensemble learning, and deep learning methodologies, utilizing stratified random 7:3 partitioning for training and validation cohorts. SHAP (SHapley Additive exPlanations) methodology facilitated comprehensive global and local interpretability analyses, with decision curve analysis assessing clinical net benefit.

RESULTS: Among 5,699 training cohort participants, 1,248 (21.9%) experienced cardiovascular events during follow-up. Recursive feature elimination identified 18 pivotal predictive factors spanning lipid metabolism, anthropometric parameters, renal function, and glucose homeostasis domains. The gradient boosting machine demonstrated superior comprehensive performance, achieving validation cohort AUC of 0.798 (95% CI: 0.776-0.820), specificity of 98%, and positive predictive value of 78%. SHAP analysis revealed waist circumference, triglycerides, and hypertension history as the three predominant predictive factors, with mean absolute SHAP values significantly exceeding other variables. Individual risk attribution analysis demonstrated substantial heterogeneity: extremely high-risk specimens (predicted probability 0.991) exhibited synergistic multi-factorial risk amplification, with standardized waist circumference contributing + 0.0778 SHAP value and triglycerides (477 mg/dL) contributing + 0.0729; conversely, low-risk specimens (predicted probability – 0.0393) demonstrated triglycerides (45.1 mg/dL) providing the maximal singular protective contribution of -0.166. Decision curve analysis confirmed positive net benefit across the 0-0.95 threshold probability spectrum, systematically surpassing conventional strategies.

CONCLUSIONS: The gradient boosting machine model achieved superior discrimination (AUC 0.798, 95% CI 0.785-0.825) compared to Framingham (0.638) and China-PAR (0.654) scores for 9-year cardiovascular disease prediction in Chinese adults aged ≥ 45 years. Waist circumference, triglycerides, and hypertension emerged as principal predictive features, though SHAP-derived importance reflects statistical contribution rather than causal effects. Decision curve analysis demonstrated clinical utility across threshold probabilities 0.05-0.95, enabling flexible deployment from population screening (98.3% sensitivity) to targeted intervention (98.7% specificity). External validation in independent cohorts is essential to establish generalizability before clinical implementation.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:41749231 | DOI:10.1186/s12911-026-03389-1

World J Surg Oncol. 2026 Feb 27. doi: 10.1186/s12957-026-04198-6. Online ahead of print.

ABSTRACT

Triple therapy of hepatic arterial infusion chemotherapy (HAIC) combined with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) achieves satisfactory clinical efficacy in advanced hepatocellular carcinoma (HCC). However, the optimal therapeutic strategy to improve prognosis in this patient population remains controversial. The objective of this retrospective study was to evaluate the efficacy and safety of HAIC-based therapy, either sequentially (SE) or concurrently (Con) combined with targeted immunotherapy, in patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC. This retrospective study analyzed 235 patients with advanced HCC who received FOLFOX-based HAIC in combination with ICIs and TKIs either concurrently or sequentially at the Affiliated Hospital of North Sichuan Medical College from January 2020 to December 2024. Propensity score matching (PSM) was performed at a 1:1 ratio to eliminate potential imbalances in confounding factors. Patients were categorized into the sequential group (SE) and concurrent group (Con) based on whether the interval between the completion of HAIC and the initiation of systemic therapy exceeded three weeks. Following PSM, each group contained 85 patients. Statistical comparisons of Overall Survival (OS) (via Kaplan-Meier and log-rank tests) revealed a significantly longer median survival in the Con group (14.5 months) versus the SE group (11.2 months, P < 0.01). Furthermore, the median Progression-Free survival (PFS) in the Con group (7.9 months) was also longer than that in the SE group (6.2 months). Treatment responses and adverse events (AEs) profiles were documented. Upon analysis according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), the objective response rate (ORR) of the SE regimen was lower than that of the Con regimen. The Con group had a generally higher AE incidence, with significantly higher rates of hyperbilirubinemia (44.7% vs. 24.7%, p = 0.04 < 0.05) and anemia (43.5% vs. 16.5%, p = 0.005 < 0.05) than the SE group. No grade 5 severe and life-threatening AEs were reported in either group.

PMID:41749226 | DOI:10.1186/s12957-026-04198-6

BMC Nurs. 2026 Feb 26. doi: 10.1186/s12912-026-04470-w. Online ahead of print.

ABSTRACT

INTRODUCTION: The triage system is a process that is used to prioritise patient-care based on the urgency of their medical need. The triage system helps to expedite the delivery of time-critical treatment for patients with life-threatening conditions, to ensure that all patients are appropriately prioritised according to their medical urgency, improve patient flow, and improve patient satisfaction. However, based on our knowledge there’s no developed tool that assesses Clinical Triage Readiness and Practice among midwives, particularly in our context.

AIM: This study aims to primarily develop the clinical triage readiness and practice assessment tool for midwives, and second, to use the scale to identify and describe factors influencing clinical triage readiness and practices among midwives in resource-constrained district hospitals in Mpumalanga Province.

METHODS: A quantitative, cross-sectional, and descriptive research design underpinned this study. A stratified random sampling approach was used to select participants from a population of 300 midwives working in the maternity units. Data were collected using a self-developed questionnaire, and only 150 questionnaires were returned filled. The data were organised and analysed using the Statistical Package for Social Sciences (SPSS) version 29.0 computer software. Exploratory factor analysis using principal component analysis was conducted to determine the underlying dimensional structure of the instrument, followed by Cronbach’s alpha to assess the internal consistency of each extracted dimension. Logistic regression analysis was used to identify factors influencing triage practices.

RESULTS: The factor analysis illuminates that clinical triage readiness and practices can be assessed by six factors. Among the factors are knowledge and usefulness, organisational and policy readiness for triage, midwives’ skills and teamwork, patient-related challenges, and resource and infrastructure constraints. The study further yields that knowledge and usefulness, and organizational support/staff well-being are positively associated with good practice.

CONLUSION: This study developed the clinical triage readiness and practice assessment tool to assess factors influencing clinical triage readiness and practices among midwives in maternity units. The tool demonstrated acceptable reliability and a clear multidimensional structure, capturing individual, organisational, patient-related, and health system influences on triage. The study underscored that knowledge and usefulness, organisational support and staff well-being is positively associated with good practice. Therefore, theses findings advocates for an clinical environment that supports the psychological well-being of midwives to enhance quality triage practice.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:41749222 | DOI:10.1186/s12912-026-04470-w