Nevin Manimala

Cardiovasc Diabetol. 2026 Jul 28;25(1):212. doi: 10.1186/s12933-026-03312-y.

ABSTRACT

BACKGROUND: Copeptin, a surrogate marker for vasopressin secretion, is associated with cardiovascular disease, insulin resistance and dysglycaemia. The cardioprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) may involve vasopressin modulation through fluid redistribution, but whether this effect persists long-term in high-cardiovascular-risk patients with newly detected dysglycaemia remains unknown.

METHODS: In this post-hoc analysis of the SOCOGAMI double-blind, placebo-controlled trial, 42 patients (mean age 67.5 years, 19% females) with impaired glucose tolerance or newly detected type 2 diabetes following an ACS and no heart failure were randomized to empagliflozin 25 mg/day (n = 20) or placebo (n = 22) for 7 months. Copeptin was measured during oral glucose tolerance tests (OGTT) at baseline, after 7 months on-treatment, and 3 months after treatment withdrawal. Treatment effects were assessed by repeated-measures ANOVA with treatment × time interaction and linear mixed-effects models.

RESULTS: Haematocrit, but not copeptin, showed a significant between-group difference at 7 months (p = 0.03 and p = 0.63, respectively). Both markers returned toward baseline after treatment withdrawal, but the overall treatment × time interaction was not significant for either (p = 0.72 and p = 0.64 respectively). Results were unchanged after accounting for a baseline imbalance in diuretic use (35% vs. 14%). Copeptin was not associated with the glucose-lowering effect of empagliflozin and no differential copeptin response during the OGTT across groups or visits was observed. In exploratory analyses, copeptin correlated with arterial pulse wave velocity at baseline (rs = 0.40, unadjusted p = 0.03).

CONCLUSIONS: In this post-hoc analysis, empagliflozin treatment was not associated with statistically significant sustained vasopressin secretion in post-ACS patients with newly detected dysglycaemia and preserved cardiac function. Due to the limited power and the absence of early on-treatment sampling these findings cannot exclude AVP modulation and warrant confirmation in adequately powered studies.

TRIAL REGISTRATION: EudraCT number 2015-004571-73.

PMID:42522027 | DOI:10.1186/s12933-026-03312-y

Infect Dis Poverty. 2026 Jul 28;15(1):84. doi: 10.1186/s40249-026-01484-z.

ABSTRACT

BACKGROUND: The Pradhan Mantri Ayushman Bharat Health Infrastructure Mission (PM-ABHIM) scheme, supported by the World Bank, is establishing four zonal National Institutes of Virology (NIVs) in India. It is essential to identify the zonal disease and research priorities so as to focus research at zonal levels. This study reports a zonal viral disease prioritisation exercise to support outbreak response and collaborative research. It describes zonal-prioritised viral diseases, assesses concordance and differences in zonal priority lists and, and identifies cross‑cutting research themes and preparedness gaps using an multicriteria decision analysis (MCDA)‑based consensus process.

METHODS: We conducted a cross-sectional, multi-stakeholder consultative study across four geographical zones of India in March 2024. The zonal-level consultative workshops employed a systematic consensus-building approach using the modified One Health Zoonotic Disease Prioritisation (OHZDP) tool, adapted for emerging viral diseases and applied via MCDA. We identified zonal-level stakeholders, listed 40 viral diseases and categorised them into three groups: common occurrence (Group A), limited occurrence (Group B), and rare occurrences with a chance of emergence, evolution or importation (Group C). The stakeholders from state health departments, medical colleges, research institutes and the Virus Research and Diagnostic Laboratory (VRDL) network ranked the viral diseases and research themes in each zone. Spearman rank correlation was used to assess concordance of priority rankings between zones.

RESULTS: A total of 186 participants (42-48 per zone) contributed to the four zonal workshops including collaborators from VRDL laboratories (26%), public health stakeholders from Integrated Disease Surveillance programme(IDSP) (28%), invited experts (21%), organisers (19%) and Indian Council of Medical Research (ICMR) representatives (6%). The key outcomes included the zone-specific lists of priority viral diseases in Groups A, B and C. There were zonal variations in viral disease prioritisation, reflecting local epidemiological patterns. Spearman rank correlation analysis showed moderate positive correlation between the Central and East zones (rho = 0.697, P = 0.031), whereas other pairwise comparisons were not statistically significant, which indicated both shared and distinct priority patterns within the zones. The top five priority viral diseases across zones included dengue, influenza, measles, Japanese encephalitis and hepatitis A. The research themes and subthemes were then decided for collaborative research.

CONCLUSIONS: These multistakeholder consultations provided a novel, replicable template for prioritising viral diseases to develop strategies for mitigating the impact of future outbreaks through collaborative research. These zonal priorities may guide similar exercises at national, regional and global levels in future.

PMID:42522023 | DOI:10.1186/s40249-026-01484-z

BMC Pediatr. 2026 Jul 25;26(1):691. doi: 10.1186/s12887-026-07370-9.

ABSTRACT

BACKGROUND: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children are mild, yet neurological complications can occur. Host immune variability is partly determined by human leukocyte antigen (HLA) polymorphisms and may influence susceptibility. This study investigates whether specific HLA-B alleles are associated with neurological involvement in pediatric coronavirus disease 2019 (COVID-19).

METHODS: This retrospective study spanned over one year, including children with confirmed SARS-CoV-2 infection. Patients were classified into two groups: patients with COVID-19 with neurological disease (neuro-COVID-19), and those with COVID-19 without neurological disease (non-neuro COVID-19). A control group of 120 healthy children was included to represent baseline allele distribution. HLA-B class I allele typing was performed using polymerase chain reaction with sequence-specific oligonucleotide probes (PCR-SSOP).

RESULTS: HLA-B49 represented the most common allele among children suffering from neurological COVID-19 (10.4%). None of the alleles reached statistical significance when compared in patients with and without neurological disease. A possible, but not statistically significant, lower frequency of the HLA-B52 allele was observed in cases with neurological manifestations (p = 0.088). However, in exploratory unadjusted analyses, HLA-B53 showed higher odds of neurological involvement when compared with children without neurological disease and healthy controls (OR = 6.29; 95% CI: 1.23-32.13; nominal p = 0.027), while HLA-B45 demonstrated a positive trend (OR = 3.75; 95% CI: 0.87-16.22; nominal p = 0.077). These allele-level findings were not corrected for multiple comparisons and should therefore be interpreted as exploratory and hypothesis-generating.

CONCLUSIONS: This study suggests a possible immunogenetic contribution to neurological complications in pediatric COVID-19, with a nominal unadjusted signal for HLA-B53. Given the small sample size, multiple-allele testing, and the absence of adjusted modelling, this finding should be considered exploratory and hypothesis-generating. Validation in larger multicenter cohorts with correction for multiple comparisons and adjustment for relevant confounders is required.

PMID:42522012 | DOI:10.1186/s12887-026-07370-9

BMC Gastroenterol. 2026 Jul 25;26(1):477. doi: 10.1186/s12876-026-05164-y.

ABSTRACT

BACKGROUND AND AIM: Autoimmune pancreatitis (AIP) is a rare chronic form of pancreatitis mediated by autoimmune mechanisms. Evidence regarding the diagnostic performance of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in AIP remains limited. This study aimed to estimate the pooled diagnostic accuracy of EUS-FNB in patients with AIP.

METHODS: PubMed, Embase, Cochrane Library, CNKI, and Wanfang Database were systematically searched to identify fully published studies evaluating EUS-FNB for tissue sampling in AIP. Pooled estimates were generated using a random-effects model. The assessed outcomes included diagnostic accuracy, sample adequacy, contribution to AIP diagnosis, and adverse events.

RESULTS: Sixteen studies, including one randomized controlled trial and four prospective studies, comprising 732 patients, were included. The overall diagnostic accuracy was 79% (73%-83%). Diagnostic accuracy was higher for the Franseen needle (83%, 75%-90%) and Fork-tip needle (90%, 80%-99%) compared with the reverse/forward‑bevel (51%, 31%-71%), with a statistically significant difference (P < 0.001). The 22G needle also demonstrated superior diagnostic accuracy (85%, 79%-91%) compared with 19G/20G needles (70%, 42%-98%) (P < 0.001). The pooled sample adequacy rate was 97% (95%-98%). EUS-FNB contributed to the diagnosis in 69% (50%-88%) of cases where diagnosis could not be established using imaging, serology, or involvement of other organs. The overall adverse event rate was 4% (1%-8%).

CONCLUSIONS: EUS-FNB demonstrates excellent histological tissue acquisition and moderate diagnostic accuracy in AIP, with a low rate of adverse events. The 22G Franseen or Fork-tip needles may be a reasonable option, though direct comparative evidence is lacking.

PMID:42522011 | DOI:10.1186/s12876-026-05164-y

BMC Ophthalmol. 2026 Jul 25;26(1):443. doi: 10.1186/s12886-026-05159-z.

ABSTRACT

PURPOSE: To assess the association between retinal fluorescence lifetimes (τm) and choriocapillaris (CC) flow deficits (FD) in intermediate age-related macular degeneration (AMD).

METHODS: Twenty-six pseudophakic eyes with intermediate, non-exudative AMD (mean age 83 ± 5 years) underwent fluorescence lifetime imaging ophthalmoscopy (FLIO) and optical coherence tomography angiography (OCTA). Fluorescence lifetimes were recorded in short- and long-wavelength channels and analyzed across ETDRS subfields. CC flow deficits were quantified using local thresholding. Associations between τm and FD were evaluated using Spearman’s rank correlation.

RESULTS: Mean τm values were consistently higher in the long-wavelength channel compared to the short-wavelength channel across all subfields. Mean CC FD increased from the outer ring (0.50 ± 0.07) to the central subfield (0.65 ± 0.11). Correlation coefficients between τm and FD ranged from – 0.07 to 0.37, with no statistically significant associations (all p > 0.05).

CONCLUSIONS: No statistically significant association was observed between fluorescence lifetimes and choriocapillaris flow deficits in this exploratory cohort. Although both biomarkers are known to be altered in AMD, the absence of evidence for a statistically significant spatial association suggests that FLIO and OCTA may reflect complementary aspects of disease pathology. Larger studies incorporating structural retinal biomarkers and longitudinal follow-up are warranted.

CLINICAL TRIAL REGISTRATION: Not applicable.

PMID:42522009 | DOI:10.1186/s12886-026-05159-z

J Transl Med. 2026 Jul 27;24(1):970. doi: 10.1186/s12967-026-08699-6.

ABSTRACT

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem disorder characterized by neuroimmune, autonomic, and gastrointestinal dysfunction. Previous studies identified coherent symptom domains involving Brain, Autonomic, Gut, and Immune manifestations and demonstrated pronounced sex-specific differences in neurocognitive-sensory and autonomic symptom organization. However, whether immune-related and gastrointestinal symptoms form distinct or integrated latent structures in women and men with ME/CFS remains unclear. In addition, the potential influence of menopausal status on these symptom domains has not been systematically investigated.

METHODS: Data from 748 adults with a medical diagnosis of ME/CFS were included in this cross-sectional analysis (608 women, 137 men, and 3 non-binary participants). Sex-stratified analyses were restricted to women and men. Symptoms were coded dichotomously. Sex-stratified analyses included cross-tabulations, Cramér’s V, tetrachoric correlations, logistic and linear regression models, exploratory factor analysis, and structural equation modeling (SEM). Additional subgroup analyses compared pre- and postmenopausal women. Model robustness was evaluated using a stratified training dataset.

RESULTS: In women, Immune (flu-like symptoms, susceptibility to infections) and Gut (gastrointestinal complaints, food intolerances) symptoms formed two distinct but related clusters, characterized by moderate within-cluster correlations (tetrachoric ρ = 0.47-0.60) and weaker cross-cluster associations (ρ = 0.30-0.35). Exploratory factor analysis (EFA) supported a two-factor solution. Consistent with this result, the alternative one-factor SEM showed comparatively poor fit (CFI = 0.913; RMSEA = 0.119), whereas the specified two-factor model was just-identified and therefore not suitable for global fit evaluation. In men, all four symptoms loaded onto a single integrated Gut/Immune factor, with within- and cross-domain tetrachoric correlations ranging from 0.43 to 0.68. SEM confirmed excellent fit for a one-factor model (CFI = 0.981; RMSEA = 0.074). Susceptibility to infections emerged as the dominant predictor in regression analyses. Among women, menopausal status selectively affected immune-related symptoms. Women classified as premenopausal reported flu-like symptoms more frequently than women classified as postmenopausal, whereas gastrointestinal symptoms and food intolerances remained stable across groups. These findings suggest differential hormonal sensitivity of immune versus gastrointestinal symptom trajectories.

CONCLUSIONS: Immune and gastrointestinal symptoms in ME/CFS exhibit sex-specific latent structures. Women demonstrate two partially separable but related symptom domains, whereas men show a more integrated immune-gastrointestinal architecture. Furthermore, menopausal status appears to selectively modulate immune-related symptom expression while leaving gastrointestinal symptom patterns comparatively stable. Taken together, these results provide an exploratory framework that supports the concept of sex-dependent neuroimmune-autonomic mechanisms in ME/CFS and aligns with a dynamic, hormonally modulated immune component as well as a more persistent, gut-related process. The results highlight the importance of sex- and hormone-sensitive approaches to phenotyping, mechanistic research, and therapeutic stratification in ME/CFS.

PMID:42522006 | DOI:10.1186/s12967-026-08699-6

Asia Pac J Clin Oncol. 2026 Jul 28. doi: 10.1111/ajco.70147. Online ahead of print.

ABSTRACT

AIM: Tumor heterogeneity, driven by metabolic reprogramming, challenges colorectal cancer (CRC) treatment. Methionine metabolism is crucial for tumor progression, but its role in CRC heterogeneity and the tumor immune microenvironment (TIME) requires systematic investigation.

METHODS: A systematic evaluation of 101 combinations of machine learning and statistical algorithms was conducted within a 10-fold cross-validation framework to develop and validate the optimal model, termed the methionine metabolism-related risk score (MMRS). The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) dataset served as the training cohort, while two independent Gene Expression Omnibus (GEO) cohorts (GSE39582 and GSE17536) were employed for external validation. Immune infiltration was assessed using the microenvironment cell populations-counter (MCP-counter) algorithm. Model discrimination was evaluated using time-dependent receiver operating characteristic (ROC) analysis, with the area under the curve (AUC) calculated at 1, 3, and 5 years across all cohorts.

RESULTS: Methionine metabolism-high (MMH) and metabolism-low (MML) subtypes were defined via unsupervised clustering. The MMH subtype exhibited significantly poorer overall survival and an immunosuppressive TIME. From subtype-associated differentially expressed genes (DEGs), 41 prognostic genes were identified. The optimal model (StepCox[both] + plsRcox) formed the MMRS, which effectively stratified patients into high- and low-risk groups with significantly different survival across all cohorts (all p < 0.05). Core signature genes (MID2, KIF7, GSR) were consistently selected. The high-risk group showed depleted antitumor immunity (e.g., fewer CD8+ T and NK cells) and a stroma-rich phenotype with enrichment of cancer-associated fibroblasts, underpinned by oxidative stress and alterations in energy metabolism pathways. Time-dependent ROC analysis confirmed the discriminative capacity of the MMRS, with 5-year AUCs of 0.803 (TCGA-COAD), 0.632 (GSE39582), and 0.608 (GSE17536), respectively, further supporting its prognostic accuracy across independent patient populations.

CONCLUSION: Methionine metabolism heterogeneity is a key determinant of prognosis and immune contexture in CRC. The MMRS is a prognostic signature that effectively stratifies CRC patients by risk, though its clinical utility as a predictive biomarker for treatment selection requires prospective validation.

PMID:42521983 | DOI:10.1111/ajco.70147

Forensic Sci Med Pathol. 2026 Jul 29. doi: 10.1007/s12024-026-01319-1. Online ahead of print.

ABSTRACT

S100B is a calcium-binding protein primarily found in astrocytes and Schwann cells. Accurate estimation of post-mortem interval is vital for reconstructing death timelines and guiding law enforcement. Similarly, precise determination of cause of death serves both legal and medical purposes, aiding judicial outcomes and informing public health strategies. This study aimed to assess serum S100B levels in trauma-related deaths, focusing on head and extracranial injuries, and their variation with postmortem intervals. Serum samples were collected from eighty subjects, including forty trauma cases with head and extracranial injuries and forty non-traumatic controls. Serum S100B concentrations were measured and statistically compared between trauma-related deaths and non-traumatic controls. S100B levels were also measured across different postmortem intervals (0, 6, 12, 24, 48, and 60 h). The current study showed that there was a significant increase in S100B levels in the study group (trauma-related deaths) compared to the control group, with a p-value < 0.001, and no significant differences between head and extracranial causes of death. There was also a significant elevation in S100B concentrations from 0 to 6 h postmortem (p < 0.001). After 6 h post-mortem, several S100B measurements exceeded the assay’s upper reportable limit (4000 ng/L), limiting precise quantification beyond this range. In conclusion, post-mortem serum S100B demonstrates potential as a supplementary tool for early post-mortem interval estimation and differentiating trauma-related deaths, regardless of head injury involvement. However, values beyond 12 h post-mortem exceed assay detection limits, highlighting the need for extended measurement ranges in forensic applications.

PMID:42521978 | DOI:10.1007/s12024-026-01319-1

J Thromb Thrombolysis. 2026 Jul 28. doi: 10.1007/s11239-026-03376-3. Online ahead of print.

ABSTRACT

A growing proportion of patients admitted to the intensive care unit (ICU) receive chronic oral anticoagulation with direct oral anticoagulants (DOACs) or warfarin. The comparative safety of continuing DOACs versus warfarin during critical illness remains uncertain. We evaluated bleeding and clinical outcomes among ICU patients who continued the same oral anticoagulant during the early ICU course. We conducted a retrospective cohort study of adult ICU admissions across Mayo Clinic sites from 2012 to 2023. Eligible patients were taking a DOAC or warfarin at ICU admission and continued the same anticoagulant during the first three ICU calendar days. The primary outcome was major bleeding during the index hospitalization. Secondary outcomes included ICU and hospital mortality, ICU- and hospital-free days, bleeding subtypes, and need for procedural interventions. Among 6,258 eligible ICU admissions, 2,410 patients continued the same oral anticoagulant during the first three ICU calendar days, including 1,074 continuing DOAC therapy and 1,336 continuing warfarin therapy. In the multivariable analysis, there was no statistically significant difference in major bleeding events, (aOR 1.34, 95% CI 0.89-2.02; p = 0.161) between the DOACs and warfarin groups, respectively. Gastrointestinal bleeding (GI) was more frequent among patients continuing warfarin and remained significant after adjustment (adjusted OR 3.90, 95% CI 1.91-7.94; p < 0.001). Hospital mortality was lower with warfarin use than DOACs (5.6% vs 11.6%; p < 0.001; aOR 0.47, 95% CI 0.33-0.68). Among ICU patients selected to continue their baseline oral anticoagulant, continued DOAC therapy was not associated with higher adjusted odds of major bleeding and was associated with lower GI bleeding events than warfarin, but this bleeding advantage did not translate into lower mortality. This discordance suggests that the mortality in this population is driven largely by illness severity, comorbidity, unmeasured confounding and other non-bleeding related pathways.

PMID:42521975 | DOI:10.1007/s11239-026-03376-3

Environ Sci Pollut Res Int. 2026 Jul 28. doi: 10.1007/s11356-026-38083-2. Online ahead of print.

ABSTRACT

Air pollution remains an environmental health risk, with particulate matter (PM_2.5) disproportionately affecting vulnerable communities. Allegheny County, Pennsylvania, a high-PM_2.5 region, requires assessment of exposure variability and risk. This study evaluated spatial and seasonal variation in PM_2.5-equivalent concentrations using community monitoring from 290 homes across Allegheny County (2016-2021). Particle counts (> 0.5 µm) from the ROCIS Low-Cost Monitoring Project were converted to estimated PM_2.5-equivalent mass concentrations, and census tracts were classified by environmental justice (EJ) status and proximity to industrial sources using GIS. Generalized estimating equation (GEE) models assessed spatial and seasonal patterns, and noncancer risks were estimated using hazard quotients (HQs). Overall, 33.8% of the study sites (n = 290) exceeded the WHO 2021 24-h guideline (15 µg/m³) and the 66.6% EPA annual reference (9 µg/m³), based on 3-week site medians-screening-level comparisons rather than regulatory determinations. Compared to the WHO 2021 24-h guideline, median (mean ± SD) PM_2.5 concentrations were highest in Sewickley-median 19.3 µg/m³, range = 6.1-22.8 µg/m³ (16.1 ± 8.8 µg/m³), with GEE estimated at 62% above the Etna baseline, though this rests on only three homes and should be read as exploratory. Winter concentrations were significantly elevated (p < 0.001), with the combined cold season (winter and fall) exceeding the warm season (p < 0.05). Although EJ differences were not statistically significant, 42% of municipalities had HQ ≥ 1, indicating potential noncancer risks. These results highlight fine-scale pollution variability not captured by regulatory monitors and underscore the need for spatially resolved assessments to guide public health interventions.

PMID:42521969 | DOI:10.1007/s11356-026-38083-2