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Nevin Manimala Statistics

Body mass index and a body shape index: Individual and interactive predictors of all-cause and cardiovascular mortality risk in depression

Psychiatry Res. 2025 Dec 14;356:116907. doi: 10.1016/j.psychres.2025.116907. Online ahead of print.

ABSTRACT

OBJECTIVE: Conflicting evidence exists on the association of obesity, depression and mortality risk. This study evaluates a cohort of subjects with depression from the USA NHANES and all-cause and cardiovascular mortality risks based on baseline BMI and ABSI.

METHODS: A nationally representative cohort study was conducted using NHANES data (2005-2018), including 2854 adults with depression. Weighted Cox regression and restricted cubic spline (RCS) models were applied to assess anthropometric associations with mortality. Weighted receiver operating characteristic (ROC) curves evaluated the diagnostic value of BMI and ABSI.

RESULTS: Each 1-SD BMI increase was predictive of reduced all-cause (HR = 0.81, 95 % CI:0.67-0.98) and cardiovascular mortality (HR = 0.62, 95 % CI:0.43-0.89). Each 1-SD ABSI increase was predictive of elevated all-cause (HR = 1.27, 95 % CI:1.06-1.51) and cardiovascular mortality (HR = 1.60, 95 % CI:1.20-2.15). In these depressed individuals, BMI showed the U-shaped and ABSI the expected curvi-linear relationships with mortality as established from the studies of the NHANES cohorts. In ROC analyses, ABSI showed the best predictive performance for all-cause mortality (AUC = 0.678) and for cardiovascular mortality (AUC = 0.706). BMI Tertile 1 & ABSI Tertile 3 had the highest mortality risks (all-cause HR = 3.09, 95 % CI:1.38-6.93; cardiovascular HR = 5.45, 95 % CI:1.36-21.85). Due to the approximate statistical independence of BMI and ABSI, combining them further improved AUC values (all-cause: 0.691; cardiovascular: 0.722).

CONCLUSION: Among individuals with depression ABSI predicts mortality similar to the general population, while obesity as defined by BMI was “paradoxically” associated with lower mortality. Personalized mortality risk for an individual can be derived by combining the independent risks based on BMI and ABSI.

PMID:41420910 | DOI:10.1016/j.psychres.2025.116907

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MRA morphologic study of the vertebrobasilar artery system in patients with primary hemifacial spasm

Neuro Endocrinol Lett. 2025 Dec 16;46(6):356-365. Online ahead of print.

ABSTRACT

PURPOSE: This study assessed the efficacy of 3.0T magnetic resonance angiography (MRA) in individuals with primary hemifacial spasm (pHFS) by investigating the relationship between alterations in the morphology of the vertebrobasilar artery system and pHFS.

METHODS: A comparison was made between pHFS patients and healthy controls with respect to vertebral artery diameter, displacement rate, and other relevant parameters to explore the potential role of morphologic abnormalities in the vertebrobasilar arteries in the pathogenesis of pHFS. Independent t-tests and Wilcoxon rank-sum tests were used with statistical significance set at a p < 0.05.

RESULTS: A total of 100 pHFS patients and 150 healthy participants underwent 3.0T MRA scans for this analysis. The right vertebral artery (VA) diameter in the pHFS group was larger than the healthy control (HC) group (2.71 mm vs. 2.47 mm; p < 0.05) and the left VA deviation distance in the pHFS group was greater than the HC group (7.99 mm vs. 5.27 mm; p < 0.05). The basilar artery deviation distance in the pHFS group was greater than the HC group (7.41 mm vs. 4.78 mm; p < 0.05). The VA deviation rates in the pHFS group were significantly higher than the HC group (89% vs. 72% and 96% vs. 84.67%, respectively; p < 0.05). The VA scores on the symptomatic and non-symptomatic sides were significantly different (p < 0.05). VA migration increased with age (p = 0.034, r = 0.225).

CONCLUSION: The results imply a potential association between morphologic irregularities in the vertebrobasilar arteries and pHFS. Limitations of the study included substantial missing data for displacement measurements (64%-67%), age differences between groups, and selection bias from the surgical population.

PMID:41420884

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Mediation Mendelian Randomization Analysis of the Effect of Immune Cells on Autism Spectrum Disorder Mediated by Inflammatory Factors

Neuro Endocrinol Lett. 2025 Dec 16;46(6):315-322. Online ahead of print.

ABSTRACT

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that impairs communication. Increasing research indicates that maternal immune activation (MIA) is one of the most important environmental factors that increase the risk of autism spectrum disorder (ASD) in offspring. Maternal immune activation produces elevated cytokine levels that cross the placental barrier and disrupt fetal neurodevelopment, increasing ASD risk. However, the specific causal pathways and mediating mechanisms remain unclear, limiting our understanding.

METHODS: This mediation Mendelian randomization study examined causal pathways linking immune cell traits (exposures) and inflammatory factors (mediators) to ASD risk.The research merged immune data (731 phenotypes + 48 cytokines) and ASD data from a cohort comprising 18,382 cases and 27,969 controls. Various MR approaches were used to reduce potential biases, along with thorough descriptions of statistical procedures and instrumental variable selection.

RESULTS: The study’s findings propose potential causal relationships among cytokines representing inflammatory factors, immune cells, and ASD through mediation Mendelian randomization. Reverse MR was then employed to investigate the possibility of reverse causality. CD8+ T cell %leukocyte (OR = 1.099, 95% CI: 1.039-1.163, p = 0.001), CCR2+ CD62L+ myeloid dendritic cells (OR = 0.933, p = 0.029), and CD45+ immature myeloid-derived suppressor cells (OR = 1.056, p = 0.001) showed evidence of causal association with ASD risk.Furthermore, reduced Artemin levels and elevated FLT3L and 2B4 levels were significantly linked to ASD risk, indicating that abnormalities in immunomodulatory factors may play a crucial role in the pathogenesis of ASD. Additionally, ASD occurrence may result in alterations in Natural Killer cell receptor 2B4 levels.

CONCLUSION: This mediation Mendelian randomization study provides evidence that immune dysfunction is associated with ASD pathophysiology through inflammatory mediators, requiring functional validation before clinical application.Cytokines act as mediators in the pathogenesis of ASD, providing a theoretical basis for understanding its immunoinflammatory pathogenesis and offering insight into treatment.

PMID:41420879

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Characterization of gut microbiomes in rural Honduras reveals uncharacterized species and associations with human genetic variation

Cell Rep. 2025 Dec 18;45(1):116724. doi: 10.1016/j.celrep.2025.116724. Online ahead of print.

ABSTRACT

The gut microbiome is integral to human health, yet research data to date have emphasized industrialized populations. Here, we performed large-scale shotgun metagenomic sequencing on 1,893 individuals from rural Honduras, providing the most comprehensive microbiome dataset from Central America. We identify a distinct microbial composition enriched in Prevotella species. Longitudinal analysis in 301 individuals reveals microbiome instability, with shifts in taxonomic diversity and metabolic potential, including changes associated with severe acute respiratory syndrome coronavirus 2 infection. Additionally, we characterize the gut virome and eukaryotic microbiome, identifying uncharacterized viral taxa and a high prevalence of Blastocystis species in individuals with greater microbial diversity. Finally, by integrating host genomic data, we uncover significant host-microbiome associations, highlighting the influence of human genetic variation on microbial composition. These findings expand our understanding of microbiome diversity in non-industrialized populations, underscoring the need for global microbiome research.

PMID:41420859 | DOI:10.1016/j.celrep.2025.116724

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Association of race and survival in patients treated with apalutamide: Pooled analysis of two phase 3 trials

Cancer. 2026 Jan 1;132(1):e70236. doi: 10.1002/cncr.70236.

ABSTRACT

BACKGROUND: Clinical studies have shown that outcomes of patients with prostate cancer could vary depending on race. In this study, the authors sought to determine if the treatment effect of apalutamide, an androgen receptor pathway inhibitor (ARPI), on overall survival (OS) varies depending on the race of the patient.

METHODS: This pooled analysis includes individual patient data from two phase 3 trials, TITAN and SPARTAN, which randomized patients to androgen deprivation therapy (ADT) ± apalutamide in metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer, respectively. Race was self-identified and categorized as Asian, Black, White, and Others categories. The authors applied a stratified (stratification for the trial) multivariable Cox proportional hazards regression model to determine heterogeneity of treatment effect on OS after adjustment for age, performance status, body mass index, T- and N-stage, Gleason score, comorbidities, and exposure to statins and metformin.

RESULTS: Overall, 2190 patients were included: 16.9% patients were Asian, 3.7% were Black, 67.4% were White, and 12.0% were from the Others category. The authors did not find any significant heterogeneity of treatment effect from apalutamide on OS across racial groups (interaction-p = .46). Among ADT plus apalutamide-treated patients, there was no association of race with OS (hazard ratio for Asian, 0.77 [95% CI, 0.56-1.06]; Black, 0.82 [95% CI, 0.49-1.37]; and Others, 1.00 [95% CI, 0.75-1.34], all compared to White).

CONCLUSIONS: In this study, the authors did not find any evidence of difference in the treatment effect of apalutamide on OS across patients of different races, although interpretation remains limited by poor representation of racial minorities. Among apalutamide-treated patients, there was no association of race with OS.

PMID:41420831 | DOI:10.1002/cncr.70236

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Incidence of ventral hernia surgery after laparoscopic bariatric surgery in Sweden: a registry-based study 2009-2019

Hernia. 2025 Dec 20;30(1):43. doi: 10.1007/s10029-025-03547-w.

ABSTRACT

PURPOSE: The incidence of trocar site hernia (TSH) after bariatric surgery is unclear. This study aims to describe the cumulative incidence of ventral hernia surgery after laparoscopic bariatric surgery in total and by laparoscopic method (LRYGB; Roux-en-Y Gastric Bypass and LSG; Sleeve Gastrectomy).

METHODS: This was a register based observational study on patients subjected to laparoscopic bariatric surgery (LRYGB or LSG) in Sweden 2009-2019. The Scandinavian Obesity Surgery Registry (SOReg) was linked to the Swedish National Patient Register (NPR) to obtain instances of ventral hernia surgery. Nearby codes were used as proxies for TSH surgery, since a specific procedure code for TSH surgery is lacking.

RESULTS: In 64 124 patients, mean follow-up was 67 ± 36 months, LRYGB (n = 52 020) 74 ± 34 months and LSG (n = 12 104) 34 ± 22 months. Mean time between bariatric- and ventral hernia surgery was 36 ± 28 months (range 0-129). The five-year cumulative incidence of surgery for ventral hernia was 2.9% (CI 2.8-3.1). The probability of having hernia surgery was significantly higher for LRYGB compared to LSG (Breslow test, p < 0.001), still significant with differences in follow-up time accounted for (p < 0.001).

CONCLUSION: The incidence of surgery for ventral hernia after laparoscopic bariatric surgery is not negligible in this material covering over a decade of bariatric procedures. Ventral hernia surgery was more common after gastric bypass than after sleeve gastrectomy.

PMID:41420786 | DOI:10.1007/s10029-025-03547-w

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Efficacy of PCSK9 Inhibitors on Clinical Outcomes in Patients with Established Atherosclerotic Cardiovascular Disease: A Network Meta-analysis

Am J Cardiovasc Drugs. 2025 Dec 20. doi: 10.1007/s40256-025-00778-1. Online ahead of print.

ABSTRACT

AIMS: Residual cardiovascular risk remains substantial in patients with atherosclerotic cardiovascular disease (ASCVD) despite high-intensity statin therapy. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), including monoclonal antibodies and small-interfering RNA agents, offer additional risk reduction, yet comparative evidence across individual regimens remains limited.

METHODS AND RESULTS: We conducted a systematic review and network meta-analysis of randomized controlled trials evaluating approved PCSK9i dosages in patients with ASCVD. The primary outcome was major adverse cardiovascular events (MACE); the secondary outcomes included myocardial infarction, stroke, coronary revascularization, cardiovascular mortality, and all-cause death. A total of eight trials involving 49,847 patients were included. Evolocumab (140 mg every 2 weeks or 420 mg monthly) and alirocumab 150 mg every 2 weeks significantly reduced MACE compared with placebo (risk ratios (RR): 0.78, 95% confidence intervals (CI): 0.66-0.93 and RR: 0.47, 95% CI 0.25-0.86, respectively). Evolocumab was also associated with reductions in myocardial infarction, stroke, and revascularization. Alirocumab 150 mg demonstrated the most pronounced effect on revascularization and was superior to both evolocumab and the lower alirocumab dose in this outcome. No regimen significantly reduced cardiovascular or all-cause mortality.

CONCLUSIONS: These findings suggest that PCSK9 inhibitors are effective in ASCVD, with generally similar efficacy across agents; however, regimens achieving lower and sustained low-density lipoprotein cholesterol levels may confer greater benefit, in line with the concept that “the lower, the better.”

TRIAL REGISTRATION: PROSPERO identifier no. CRD420251022108.

PMID:41420785 | DOI:10.1007/s40256-025-00778-1

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Effect of OTX-101 0.09% ciclosporin solution on clinical signs of dry eye disease in patients with moderate-to-severe corneal damage: a post-hoc analysis of randomized clinical trials

Graefes Arch Clin Exp Ophthalmol. 2025 Dec 20. doi: 10.1007/s00417-025-07054-7. Online ahead of print.

ABSTRACT

PURPOSE: This post-hoc analysis of two OTX-101 clinical trials assessed the efficacy of 0.09% ciclosporin in treating dry eye disease (DED) patients with moderate-to-severe corneal damage.

METHODS: The criteria for moderate-to-severe corneal damage were defined as a CFS total score (5 zones) of ≥ 6 or single zone ≥ 2 at baseline (modified NEI scale). 516 patients (49% of the intention-to-treat population) met these criteria at baseline. Changes in ocular surface damage (cornea and conjunctiva) and aqueous tear deficiency from baseline were determined through corneal fluorescein staining (CSF), Lissamine green staining (LGS) and Schirmer’s test without anesthesia (ST).

RESULTS: After 12 weeks of treatment with OTX-101 versus (vs.) vehicle, outcomes improved across six parameters: (I) Central CFS mean change from baseline was -0.48 vs. -0.36, p = 0.0144. (II) Total CFS corneal staining change from baseline was -2.30 vs. -1.61 p = 0.0004. (III) Improvement ≥ 50% in total CFS from baseline was 44.8% vs. 33.4% p = 0. 0010. (IV) Conjunctival damage as measured by LGS mean change from baseline was -1.61 vs. -0.99, p = 0.0006. (V) Tear production as measured by ST as percentage of eyes with ≥ 10 mm increase from baseline was 18.2% vs. 8.3% p = 0.0003, and (VI) ST mean change from baseline was +2.94 vs. +0.28 p = 0.0008.

CONCLUSION: Administration of OTX-101 0.09% leads to statistically significant improvement across six parameters in ocular surface staining and tear production in DED patients with moderate to severe corneal damage.

PMID:41420783 | DOI:10.1007/s00417-025-07054-7

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Accuracy of frameless stereotactic brain biopsy: a retrospective cohort study with MRI-only and MRI-CT fusion navigation

Acta Neurochir (Wien). 2025 Dec 20. doi: 10.1007/s00701-025-06720-3. Online ahead of print.

ABSTRACT

PURPOSE: Stereotactic-guided biopsy remains the gold standard for diagnosing intracranial lesions not amenable to surgical resection. Frameless techniques, such as the VarioGuide® system (Brainlab AG, Munich, Germany), offer a minimally invasive alternative, typically using MRI-based navigation. However, MRI-based navigation may be affected by geometric distortions that impair targeting precision. CT imaging provides superior geometric fidelity. This retrospective analysis evaluates the accuracy of frameless stereotactic biopsies in clinical routine. Patients were grouped based on the imaging modality used for neuronavigation-either MRI-only or MRI-CT fusion-allowing secondary comparison between both approaches.

METHODS: In this retrospective cohort study, 99 patients who underwent frameless stereotactic biopsy between February 2022 and September 2024 were analysed. Patients were grouped by neuronavigation modality: CT-MRI fusion-based (n = 18) and MRI-only (n = 81). Accuracy was assessed by measuring entry and target deviations using postoperative CT. Lesion volume, depth, procedure duration, and complication rates were also evaluated.

RESULTS: Entry and targeting accuracy was comparable between groups (entry deviation: 5.2 ± 3.9 mm vs. 5.4 ± 3.0 mm, p = 0.84; target deviation: 4.2 ± 3.0 mm vs. 4.4 ± 2.7 mm, p = 0.85). Lesion volume and target depth showed no significant differences. No statistically significant differences in complication rates were observed between groups (27.8% vs. 11.1%, p = 0.14).

CONCLUSION: MRI-only and CT-MRI fusion-based frameless stereotactic biopsies showed no statistically significant difference in targeting accuracy. While CT-based registration may theoretically reduce distortion-related errors, this was not reflected in our data. The choice of imaging modality should therefore be guided by clinical context and imaging availability. Further prospective studies are needed to clarify the value of CT integration in specific clinical scenarios.

PMID:41420774 | DOI:10.1007/s00701-025-06720-3

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Adverse events associated with the subconjunctival Ex-Press® Glaucoma Filtration Device: a ten-year review of the MAUDE database

Int Ophthalmol. 2025 Dec 20;46(1):44. doi: 10.1007/s10792-025-03886-8.

ABSTRACT

PURPOSE: To analyze adverse events related to the Ex-Press® Glaucoma Filtration Device reported in the FDA’s MAUDE database over a 10-year period.

STUDY DESIGN: A retrospective case series.

METHODS: We retrospectively reviewed 533 unique adverse event reports submitted between January 1, 2015, and November 8, 2024. Data collected included patient demographics, reporter details, device model, event type (injury vs. malfunction), problem codes, and device availability for manufacturer evaluation. Descriptive statistics summarized patterns of device and patient problems.

RESULTS: The median patient age was 72 years (range 20-94), with sex reported in 2.3% of cases. The P-50 PL model accounted for 98% of reports, followed by the P-200 PL (2%). Devices were available for evaluation in 36.8% of cases, but only 19.3% were evaluated. Reports were 61% injuries and 39% malfunctions. A total of 440 device-related and 457 patient-related problems were identified. The most common device problems were displacement (31.4%) and flow obstruction (26.8%). Among patient problems, increased intraocular pressure (27.6%) and iris contact (22.3%) were most frequent. Injuries predominated in 2015-2016 (73.7%), shifting to malfunctions from 2020 to 2024 (76.9%).

CONCLUSIONS: Adverse events involving the Ex-Press® device primarily include injuries and malfunctions, with device displacement and flow obstruction being most common. The observed shift likely reflects changes in device use and surveillance rather than true safety changes. Despite limitations of passive reporting, these findings offer valuable real-world insights that complement clinical trial data and highlight the utility of the FDA’s MAUDE database as a tool for post-market surveillance. This approach can be replicated for other ophthalmic devices to enhance long-term safety monitoring and inform clinical decision-making.

PMID:41420769 | DOI:10.1007/s10792-025-03886-8