Background: Gallstone disease is a condition affecting the digestive system, strongly linked to inflammation and lipid metabolism. Inflammatory markers derived from high‐density lipoprotein (HDL), incorporating both immune cells and HDL‐C, play a crucial role in assessing inflammatory responses. This study aims to explore the relationship between these HDL‐related inflammatory indices and gallstone disease. Methods: The study population was derived from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 and 2021–2023 datasets. To assess the association between HDL‐related inflammatory indices and gallstone disease, weighted multivariable logistic regression and restricted cubic spline (RCS) analysis were utilized. Additionally, subgroup analysis was conducted to confirm the consistency of the results across different subpopulations. Results: Among the 16,871 participants included in the study, 11.0% were diagnosed with gallstone disease. When compared to the lowest quartile, those in the highest quartile of lymphocyte‐to‐HDL cholesterol ratio (LHR), monocyte‐to‐HDL cholesterol ratio (MHR), neutrophil‐to‐HDL cholesterol ratio (NHR), and platelet‐to‐HDL cholesterol ratio (PHR) faced an elevated risk of gallstone disease by 58.6% (OR = 1.586, 95% CI: 1.143–2.2), 67.6% (OR = 1.676, 95% CI: 1.275–2.204), 68.7% (OR = 1.687, 95% CI: 1.244–2.287), and 42.7% (OR = 1.427, 95% CI: 1.101–1.849), respectively. The correlation between HDL‐related inflammatory indices and gallstone disease was more pronounced in females, individuals without diabetes or hypertension, nonsmokers, and those who consumed alcohol. Conclusions: This research identified a positive correlation between HDL‐related inflammatory indices and gallstone disease in a nationally representative sample. These indices can be derived from routine blood tests at no additional cost, making them practical and cost‐effective tools for early risk stratification and potential large‐scale screening.

Background: Gallstones are common and have been associated with nutritional and immune status. The Prognostic Nutritional Index (PNI) reflects both nutritional and immune‐related conditions, but its association with gallstones remains unclear. This study examined this association in U.S. adults. Methods: This study analyzed data from 5060 individuals in the National Health and Nutrition Examination Survey (NHANES), with a mHean age of 48.62 years. Multivariable logistic regression was used to assess the association between PNI and gallstones. Restricted cubic spline (RCS) analysis was used to assess potential nonlinearity. Robustness was evaluated using subgroup analyses, interaction tests, and a sensitivity model with additional adjustment for fatty liver. Results: The prevalence of gallstones was 11.36%. In the fully adjusted model, each 1‐unit increase in PNI was associated with 2% lower odds of gallstones (odds ratio [OR] = 0.98, 95% confidence interval [CI] 0.96–0.99, p = 0.0185). Compared with the lowest quartile, participants in the highest quartile had lower odds of gallstones (OR = 0.72, 95% CI 0.55–0.95, p = 0.0194). RCS analysis showed an overall association between PNI and gallstone prevalence ( p for overall = 0.019), with no evidence of nonlinearity ( p for nonlinearity = 0.165). After Bonferroni correction ( α ′ ≈ 0.0015), no subgroup association remained statistically significant, and no significant interactions were detected. Conclusion: An inverse association between PNI and gallstone prevalence remained after multivariable adjustment. PNI may serve as a potential complementary immunonutritional marker associated with gallstone prevalence.

Background: Extreme temperature events and nitrogen dioxide are established risk factors for cardiovascular disease, often co‐occurring during cold spells. However, their additive interactive effects on out‐of‐hospital cardiac arrest (OHCA) in subtropical climates remain unclear. Methods: Time‐series analysis was performed using 16 769 OHCA cases in Shenzhen, China (2015–2019). Extreme temperature events were defined by apparent temperature: cold spells and heatwaves were stratified by percentile thresholds (2.5th–10th for cold, 90th–97.5th for heat) and consecutive durations (2–4 days). Quasi‐Poisson regression with distributed lag nonlinear models was applied, and additive interactions were evaluated using relative excess risk due to interaction, attributable proportion, and synergy index. Results: Cold spells were associated with a significant severity‐dependent increase in OHCA risk, with risk ratios (RRs) rising from 1.19 (95% CI, 1.13–1.26) for mildest definition (≤10th percentile for ≥2 days) to 1.50 (95% CI, 1.26–1.78) for most extreme definition (≤2.5th percentile for ≥2 days), whereas heatwaves showed no significant associations. Cold spells and nitrogen dioxide (lag 0–3 days) showed significant synergy. Under the most extreme cold spell, coexposure yielded the highest risk (RR, 1.543 [95% CI, 1.307–1.822]), with 27.7% of OHCA cases attributable to this interaction. This synergy was most pronounced for shockable rhythms (relative excess risk due to interaction up to 1.57 [95% CI, 0.34–2.79]). Conclusions: Extreme cold and nitrogen dioxide synergistically increase OHCA risk in subtropical megacities, particularly for shockable rhythms—reversible with prompt defibrillation. Integrated early‐warning systems targeting compound cold and pollution exposures are needed to reduce mortality.

Background: Somatrogon, a long-acting recombinant human growth hormone, is used in children with growth hormone deficiency. While clinical trials have shown its safety, real-world post-marketing data are limited, and uncommon or delayed adverse events (AEs) may not be fully recognized. Methods: We analyzed somatrogon-related AEs from the US FDA Adverse Event Reporting System (FAERS) (Q1 2004–Q2 2025) and the WHO global safety database via VigiAccess (up to Dec 2024). Disproportionality analyses were performed using four signal detection methods: reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). AEs were assessed at both system organ class and preferred term (PT) levels. In FAERS, time to onset was examined to characterize the temporal pattern. Results: We identified 1,001 somatrogon-related reports in FAERS and 863 in VigiAccess. Most cases occurred in pediatric patients, with slightly more reports in males. At the SOC level, most AEs involved general disorders, administration site conditions, injuries, and product issues. At the PT level, recurring signals included injection-site reactions, device-related problems, and insulin-like growth factor abnormalities. Among 168 FAERS cases with valid onset data, 79.76% occurred within 30 days, with a median onset of 0 days. Conclusion: Somatrogon’s real-world AE pattern shows early-onset injection-site reactions, device-related issues, and endocrine signals, highlighting the need for early treatment monitoring and ongoing post-marketing surveillance as its use grows globally. Key points: