Category: Nevin Manimala

BMC Med. 2026 Apr 9;24(1):217. doi: 10.1186/s12916-026-04819-7.

ABSTRACT

BACKGROUND: Stadelmaier et al. recently reported a pooled ratio of risk ratios (RRR) of 1.00 between population, intervention/exposure, comparator, outcome (PI/ECO) matched randomized controlled trials (RCTs) and cohort studies, interpreting this as evidence that randomized trials “confirm” observational findings in nutrition with “tremendous public health implications.” We hypothesized that this apparent agreement is not a validation of concordance, but an expected statistical effect arising from the pooling of null or small effect sizes with large variances rather than pairwise concordance.

METHODS: We re-analyzed the authors’ binary dataset (n = 54 pairs) using a permutation framework (B = 10,000) in which cohort studies were randomly reassigned to RCTs, breaking the original pairing (both globally and restricted within exposure-type strata) while preserving marginal distributions.

RESULTS: Under random pairing, 99.96% of permuted pooled RRRs fell within the authors’ reported confidence interval [0.91,1.10], and the observed RRR was statistically indistinguishable from the random-pairing permutation distribution (p = 0.12). A pairwise discrepancy statistic showed no improvement with matching over random pairing (p = 0.21). A precision-weighted statistic was significant (p = 0.008), but weight was highly concentrated: 4 pairs (7% of n) accounted for 54.8% of total weight, and the effective number of pairs was 9.9 (18% of n). Qualitative concordance using the authors’ prior criteria was only 13% (7/54 pairs).

CONCLUSIONS: A pooled RRR near 1.00 indicates only that cohort effect sizes are not systematically different from RCT estimates. In this dataset, an RRR near 1 is a result expected under random pairing. Pairwise agreement is not improved by PI/ECO matching for typical comparisons; the significant weighted statistic reflects alignment among a small minority of high-precision pairs, not “most” findings. Pooled RRR lacks resolution as a confirmation metric in fields with small effects and should not be interpreted as evidence of replication; otherwise, it may inappropriately influence evidence synthesis practices.

PMID:41957646 | DOI:10.1186/s12916-026-04819-7

J Nanobiotechnology. 2026 Apr 10. doi: 10.1186/s12951-026-04369-3. Online ahead of print.

ABSTRACT

BACKGROUND: Aortic dissection (AD) is a lethal condition involving vascular smooth muscle cell (VSMC) transformation and extracellular matrix degradation. While gut microbiota dysbiosis is implicated in cardiovascular diseases, its role in stress-exacerbated AD pathogenesis is unknown. This study investigates the mechanism linking chronic restraint stress (CRS) to AD progression via gut microbiota modulation.

METHODS: A β-aminopropionitrile (BAPN)-induced AD mouse model combined with CRS was utilized. Aortic dilation, mortality, and VSMC phenotype shift (assessed via α-SMA/SM22α and OPN/MMP2 expression) were evaluated. Gut microbiota composition was analyzed using 16 S rRNA sequencing. Microbiota depletion was achieved via antibiotics, and fecal microbiota transplantation (FMT) from CRS-exposed mice was performed. Serum metabolomics analysis, incorporating liquid chromatography-mass spectrometry (LC-MS), has demonstrated that outer membrane vesicles (OMVs) derived from Bacteroides vulgatus (B. vulgatus) contain high levels of the key metabolite stearic acid (SA). In vitro effects of stearic acid (SA) on AngII-induced JNK phosphorylation in VSMCs were tested, with validation using the JNK agonist anisomycin. Statistical analyses included correlation tests and appropriate comparisons (e.g., t-tests, ANOVA).

RESULTS: CRS significantly accelerated aortic dilation, increased mortality, and promoted a synthetic VSMC phenotype (decreased α-SMA/SM22α, increased OPN/MMP2) in BAPN-treated mice. 16 S sequencing revealed CRS reduced gut microbiota diversity, particularly depleting B. vulgatus, which correlated negatively with AD severity. Antibiotic-mediated microbiota ablation mitigated CRS-aggravated AD, while FMT from CRS mice exacerbated it. Metabolomics identified stearic acid (SA), a metabolite derived from OMVs of B. vulgatus, as negatively correlated with aortic diameter. SA supplementation inhibited VSMC synthetic transformation, reduced AD incidence, and suppressed JNK/MAPK pathway activation in vivo. Mechanistically, SA attenuated AngII-induced JNK phosphorylation in VSMCs in vitro, an effect reversed by the JNK agonist anisomycin.

CONCLUSIONS: CRS exacerbates the pathogenesis of AD by disrupting the gut microbiota, particularly by reducing the abundance of B. vulgatus and the levels of SA, which is a metabolite encapsulated in the OMVs of B. vulgatus. This leads to unchecked JNK/MAPK signaling, driving detrimental VSMC transformation. Restoration of SA inhibits this pathway and mitigates AD progression. Targeting the gut microbiota-B. vulgatus-SA axis presents a novel therapeutic strategy for stress-aggravated AD.

PMID:41957631 | DOI:10.1186/s12951-026-04369-3

Cardiovasc Diabetol. 2026 Apr 9. doi: 10.1186/s12933-026-03159-3. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatic metabolic burden is an integral component of cardiometabolic risk. However, the association of hepatic metabolic burden assessed by the fatty liver index (FLI) with all-cause mortality in cardiovascular-kidney-metabolic (CKM) syndrome has not been well described when individuals are stratified by glucose metabolism status. Therefore, this study aimed to evaluate the association between FLI and all-cause mortality across different glucose metabolism states in adults with CKM syndrome.

METHODS: Data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Adults with CKM syndrome according to the AHA/ADA framework were included and categorized by glucose metabolism status as normoglycemia, prediabetes, or diabetes. Hepatic metabolic burden was assessed using FLI. Weighted multivariable Cox proportional hazards models and restricted cubic spline (RCS) analyses were applied to examine the associations between FLI and all-cause mortality across glucose metabolism status. Additionally, joint analyses with combined FLI (FLI ≥ 60 vs. <60) and glycemic categories and multiple sensitivity analyses were performed.

RESULTS: Among 19,107 participants with CKM syndrome (weighted N = 105,007,226), 2482 deaths occurred over a median follow-up of 9.42 years. No robust independent association was observed between FLI and all-cause mortality among individuals with normoglycemia or prediabetes after multivariable adjustment. In contrast, among individuals with diabetes, multivariable Cox regression and RCS analysis indicated that higher FLI was significantly associated with increased mortality risk and demonstrated a J-shaped nonlinear dose-response relationship. Joint analyses further showed that elevated FLI was associated with progressively higher death risk in the presence of impaired glucose metabolism, with the highest risk observed among individuals with diabetes and FLI ≥ 60. Multiple sensitivity analyses confirmed that the main analysis results were robust.

CONCLUSIONS: Within the CKM syndrome spectrum, elevated FLI was associated with a higher risk of all-cause mortality among individuals with diabetes, with a J-shaped association, whereas the association between FLI and all-cause mortality was not significant among individuals with normoglycemia or prediabetes. These findings suggest that the relationship between FLI and mortality in CKM populations may vary according to glycemic status and highlight the importance of considering glycemic context when interpreting liver-related metabolic markers.

PMID:41957630 | DOI:10.1186/s12933-026-03159-3

BMC Med Educ. 2026 Apr 9. doi: 10.1186/s12909-026-09141-7. Online ahead of print.

ABSTRACT

BACKGROUND: Large language models (LLMs) such as ChatGPT have garnered growing attention for their potential to support medical education, including specialty areas like cardiology. However, the accuracy, guideline adherence, and pedagogical usefulness of these AI-generated materials remain incompletely characterized.

OBJECTIVE: This study aimed to evaluate the factual accuracy, guideline alignment, and teaching utility of ChatGPT-generated responses on 15 core cardiology topics.

METHODS: Fifteen high-yield cardiology subjects (e.g., acute coronary syndrome, heart failure, valvular disease, arrhythmias) were identified based on standard medical curricula. Each topic was queried with 10 standardized prompts (150 total). Two cardiologists independently rated each ChatGPT response across five domains (factual accuracy, completeness, clarity/readability, guideline alignment, and teaching utility) using a 5-point rubric. Representative examples of higher- and lower-performing responses were also reviewed qualitatively to illustrate recurrent strengths and common error patterns. Inter-rater reliability was assessed via Cohen’s kappa (κ), and descriptive statistics summarized performance by domain and by topic. All prompts were entered using the free web version of ChatGPT (OpenAI; GPT-4o) under standardized default settings during October-November 2024.

RESULTS: Clarity/readability (4.4 ± 0.5) was the highest-scoring domain overall, while factual accuracy (3.7 ± 0.6) showed moderate performance. Guideline alignment varied across the 15 topics, ranging from 4.2 in stable angina to 3.0 in complex pericardial diseases. Heart failure with reduced ejection fraction (HFrEF) also had lower guideline concordance (3.1 ± 0.6). Illustrative examples indicated that lower scores were most often driven by omission of newer therapies, incomplete discussion of advanced procedural indications, and overly generic explanations in more complex subspecialty topics. Cohen’s kappa values (0.78-0.85) indicated substantial inter-rater agreement.

DISCUSSION: ChatGPT provided coherent explanations suitable for introductory learning across most cardiology topics, but gaps were evident in rapidly evolving areas like advanced heart failure and congenital anomalies. These findings underscore ChatGPT’s value as a supplementary educational tool while highlighting the need for careful expert oversight in verifying content accuracy and currency. Strategies for safely integrating AI-generated materials into medical education are discussed.

CONCLUSIONS: While ChatGPT can aid cardiology instruction through clear, concise overviews, reliance on it as a primary source risks propagation of incomplete or outdated information. Ongoing refinement of LLMs, coupled with consistent expert review, will be crucial for leveraging AI effectively in cardiology education.

PMID:41957617 | DOI:10.1186/s12909-026-09141-7

Respir Res. 2026 Apr 9. doi: 10.1186/s12931-026-03648-9. Online ahead of print.

NO ABSTRACT

PMID:41957608 | DOI:10.1186/s12931-026-03648-9

BMC Med. 2026 Apr 9;24(1):218. doi: 10.1186/s12916-026-04820-0.

ABSTRACT

We respond to the Matters Arising article by Calkins et al. commenting on our meta-epidemiological study “Evaluating agreement between individual nutrition randomised controlled trials and cohort studies”. We appreciate the opportunity to respond to the points raised and to clarify the methods and interpretation of our work.

PMID:41957603 | DOI:10.1186/s12916-026-04820-0

BMC Infect Dis. 2026 Apr 9. doi: 10.1186/s12879-026-13207-8. Online ahead of print.

ABSTRACT

BACKGROUND: Bacillary dysentery remains a common intestinal infectious disease in China. With economic development and improvements in sanitation, the incidence rate of bacillary dysentery has changed substantially across counties in Shaanxi Province. This study aims to elucidate its epidemiological characteristics and spatio-temporal dynamics to inform prevention and control strategies.

METHODS: Surveillance data of confirmed bacillary dysentery cases in Shaanxi Province from 2005 to 2024 were obtained from the China Information System for Disease Control and Prevention. We analyzed epidemiological features across temporal, regional, and population distributions. Long-term incidence trends were assessed using Joinpoint regression, while spatial autocorrelation and spatio-temporal scan statistics were employed to identify clustering patterns at the county level.

RESULTS: A total of 156,656 cases of bacillary dysentery were reported in Shaanxi Province from 2005 to 2024. The reported incidence decreased from 65.30 per 100,000 in 2005 to 3.33 per 100,000 in 2024. A unimodal seasonal pattern was observed, with 76.09% of cases occurring between May and October. Children under five years of age were the most susceptible group, particularly infants under one. The incidence was higher in males than in females. The majority of cases were farmers (27.08%), home-care children (22.35%), and students (17.71%). Joinpoint regression revealed a significant overall decreasing trend (Average Annual Percent Change, AAPC = -15.0%; 95% CI: -18.4%, -11.4%; p < 0.001). Geographically, high-incidence counties were primarily located in the northern and central-western regions before 2014. After 2015, the number of high-incidence counties markedly decreased. By 2024, the incidence in 84.07% (95/113) of counties had fallen below 5 per 100,000. Global spatial autocorrelation analysis indicated significant clustered distributions annually. Local spatial autocorrelation identified 174 “High-High” clusters. Spatio-temporal scan statistics showed that primary clusters were located in the northern and central-western regions before 2010, shifting to the central region thereafter.

CONCLUSIONS: Both the incidence and the spatial clustering of bacillary dysentery have decreased significantly in Shaanxi Province. However, targeted interventions during the summer and autumn seasons, focusing on children under five and populations in the central region, remain crucial for future control efforts.

PMID:41957594 | DOI:10.1186/s12879-026-13207-8

BMC Anesthesiol. 2026 Apr 10. doi: 10.1186/s12871-026-03800-4. Online ahead of print.

NO ABSTRACT

PMID:41957567 | DOI:10.1186/s12871-026-03800-4

BMC Cardiovasc Disord. 2026 Apr 9. doi: 10.1186/s12872-026-05837-2. Online ahead of print.

ABSTRACT

BACKGROUND: Pregnant women with mechanical heart valves (MHVs) require continuous anticoagulation; however, first-trimester exposure to warfarin raises concerns regarding fetal safety. Data on long-term pediatric outcomes after low-dose warfarin exposure remain limited. This study aimed to evaluate long-term growth, neurodevelopmental, cardiac, and endocrine outcomes in children antenatally exposed to low-dose warfarin combined with enoxaparin, compared with enoxaparin alone.

METHODS: This single-center observational cohort study reports long-term pediatric follow-up outcomes of 32 children born to 30 women with MHVs who were enrolled at one participating center of the multicenter KYBELE study. Maternal data regarding anticoagulant therapy during pregnancy were obtained retrospectively from medical records, while pediatric data were collected through prospective clinical evaluations. Children underwent standardized assessments including physical examination, growth evaluation, Denver II developmental screening, skeletal radiography review, hearing and vision testing, electrocardiography, echocardiography, and thyroid and abdominal ultrasonography. Based on first-trimester anticoagulation regimen, children were classified as enoxaparin only (n = 12), enoxaparin plus warfarin 2.5 mg/day (n = 8), or enoxaparin plus warfarin 4 mg/day (n = 12).

RESULTS: The median age at last follow-up was 61.5 months (range 9-168). No child had growth parameters below the 3rd percentile. The overall rate of prematurity was 19%. Although higher in children receiving enoxaparin plus warfarin (2.5 mg or 4 mg/day) compared with those receiving enoxaparin alone, the difference was not statistically significant (p = 0.6). Developmental delay on Denver II screening was identified in 2 of 32 children (p = 0.7), with no significant differences among groups. All children had normal hearing, vision, and thyroid function tests. Minor neonatal echocardiographic findings (e.g., patent ductus arteriosus or patent foramen ovale) were observed in 10 children (31%) and largely resolved during follow-up, with no child requiring cardiac intervention. No skeletal dysplasia or features suggestive of warfarin embryopathy were identified.

CONCLUSIONS: In this single-center follow-up cohort of live-born children, first-trimester exposure to low-dose warfarin combined with enoxaparin was not associated with signals of major long-term adverse outcomes in growth, neurodevelopment, cardiac status, or thyroid function compared with enoxaparin alone. These findings support cautious use of low-dose warfarin when maternal indications exist, while underscoring the need for larger multicenter studies.

PMID:41957566 | DOI:10.1186/s12872-026-05837-2

Ann Afr Med. 2026 Apr 9. doi: 10.4103/aam.aam_791_25. Online ahead of print.

ABSTRACT

BACKGROUND: Jigsaw technique, one type of cooperative learning, was proposed by Aronson et al. in the 1970s, wherein students work in small groups with a fixed set of learning objectives to reach a common goal. This study aimed to evaluate the effectiveness as well as the perception of the jigsaw technique as a teaching-learning method in teaching surgery to Phase II MBBS students.

MATERIALS AND METHODS: A quasi-experimental mixed methodology study was conducted on Phase II MBBS students attending surgery. Five contact sessions were held, of 1 h each, on different topics. Assessment was done by a pre- and posttest consisting of prevalidated multiple-choice questions. Feedbacks were taken at the end of the fifth contact session by a prevalidated questionnaire.

RESULTS: All five sessions of the jigsaw technique showed statistically significant improvements in posttest scores (P < 0.001). The responses for “strongly agree” and “agree” were consistently the highest across all 10 feedback items. Students found the jigsaw technique helpful for understanding, retention, summarization, and engagement.

CONCLUSION: The jigsaw technique is effective and helps in understanding, retention, and summarization of topics in surgery. It can be introduced in Phase II as a reinforcement tool in teaching-learning surgery.

PMID:41957540 | DOI:10.4103/aam.aam_791_25