Citations

Background Antibiotic use may alter gut microbiota, which could be associated with various diseases, including cardiovascular disease (CVD). Accordingly, further epidemiological evidence is needed to clarify the potential risk of CVD associated with antibiotic exposure. We evaluated the association between long‐term antibiotic exposure and CVD risk in South Korea. Methods and Results This nationwide retrospective cohort study used data from the Korean National Health Insurance Service database. A total of 2 159 965 individuals aged 40 to 79 years who had no history of antibiotic prescriptions from 2004 to 2005 were included and followed through December 31, 2021. Antibiotic exposure was defined as the cumulative days of antibiotic prescriptions from 2006 to 2010. The primary end point was incident CVD with 2 or more days of hospitalization from 2011 to 2021. Adjusted hazard ratios (aHR) and 95% CIs for CVD according to antibiotic exposure were estimated using multivariable Cox proportional hazards models, adjusting for a range of covariates. Longer cumulative antibiotic prescription days were associated with an increased risk of CVD. The aHRs for CVD associated with 1 to 14, 15 to 90, 91 to 180, 181 to 364, and ≥365 days of antibiotic exposure were 0.98 (95% CI, 0.96–1.01), 1.01 (95% CI, 0.99–1.03), 1.05 (95% CI, 1.03–1.08), 1.06 (95% CI, 1.04–1.09), and 1.10 (95% CI, 1.07–1.13) compared with those with no antibiotic prescriptions. Conclusions In this large population‐based cohort study of Korean adults, long‐term antibiotic exposure may be associated with a higher risk of CVD. Further research is warranted to establish causality and elucidate the underlying mechanisms for this association.

BACKGROUND: Significant disparities persist in timely, guideline-concordant breast cancer treatment across the US, impacting cancer outcomes. The influence of both patient-level and facility-level socioeconomic status (SES) on adherence to Commission on Cancer quality measures remains incompletely understood. STUDY DESIGN: We conducted a retrospective cohort study using the National Cancer Database to assess associations between patient and facility SES and concordance with timeliness of 3 Commission on Cancer breast cancer quality measures: surgery, multiagent chemotherapy, and radiotherapy, among patients diagnosed from 2018 to 2022. Multivariable logistic regression models were used to evaluate predictors of concordant care, including a composite measure of facility-level social risk. RESULTS: The analytic cohorts included 471,425 patients for surgery, 82,734 for chemotherapy, and 311,523 for radiotherapy. Black race, uninsured status, and lower educational attainment were each independently associated with lower odds of receiving guideline-concordant care across all measures. Patients treated at low-SES facilities had higher odds of receiving timely surgery (adjusted odds ratio [OR] 1.27, 95% CI 1.24 to 1.31) but lower odds of receiving timely chemotherapy (OR 0.85, 95% CI 0.79 to 0.91) and radiotherapy (OR 0.95, 95% CI 0.92 to 0.97) compared with those at other institutions. Facility type, fragmented care, and comorbidities also contributed to variation in concordance. CONCLUSIONS: Significant disparities in guideline-concordant breast cancer care persist by race, insurance, education, and facility-level social risk, highlighting intervention opportunities to improve outcomes for these already vulnerable populations. These findings highlight the importance of policy and institutional strategies that address both patient- and facility-level barriers to ensure equitable access to high-quality multidisciplinary treatment.

Abstract Minimally invasive image-guided tumor ablation techniques have been established as safe, effective methods to treat a variety of unresectable soft tissue tumors. Standard thermal ablation methods include radiofrequency ablation, microwave ablation, and cryoablation. However, newer non-thermal and/or non-invasive ablation techniques are now available as alternative options to treat soft tissue tumors, particularly those that are near critical structures or otherwise susceptible to thermal energy sink effects. The 4 types of emerging ablation techniques discussed in this review are as follows: irreversible electroporation, pulsed electric field, high-intensity focused ultrasound, and histotripsy. While the clinical trials evaluating the safety and efficacy of these ablation techniques are in their early stages, initial results are promising in the treatment of various cancers at different stages. These include potential synergistic effects when combined with chemotherapy and immunotherapy.

Objective The primary lateral sclerosis ( PLS ) consensus diagnostic criteria and functional rating scale ( PLSFRS ) were recently established to facilitate and optimize future PLS clinical trials. We examined the trajectory of the PLSFRS and other functional outcome measures and biomarkers in the PLS Natural History Study ( PLS NHS ) to understand their performance in this prospective cohort. Methods The PLS NHS is a prospective, longitudinal, multicenter study of people living with PLS in different diagnostic categories: early (disease duration <2 years); probable (2–4 years); and definite PLS (4–15 years). PLSFRS scores and other functional outcome measures were collected at baseline, 3‐, 6‐, 9‐, and 12‐month follow‐up visits. Baseline characteristics were compared between the groups. The slopes of the PLSFRS and other functional outcome measures over 12 months were examined in the overall cohort and subgroups using linear mixed‐effect models. The associations between baseline characteristics and the rate of PLSFRS decline were analyzed with linear regression models. Results A total of 76 participants were included: early (n = 6); probable (n = 26); and definite (n = 44) PLS . Baseline PLSFRS total scores were highest in the early PLS group, followed by the probable and definite PLS groups. In the overall cohort, the PLSFRS total score declined by 0.33 points/month (95% confidence interval [0.27–0.39], adjusted p < 0.05). The rate of decline was steepest in the early PLS group, followed by the probable and definite PLS groups. Baseline neurofilament light chain level was associated with the rate of PLSFRS decline over 1 year ( p = 0.001). Interpretation In PLS, the rate of functional decline, as measured by the PLSFRS total score, is faster during the early phase of the disease. Neurofilament light might serve as a prognostic biomarker in PLS. ANN NEUROL 2026;99:418–428

Abstract Hepatocellular carcinoma (HCC) mortality is increasing globally, partly due to the growing prevalence of nonviral liver diseases. Genome‐wide association studies (GWAS) have identified genetic variants associated with HCC development. Leveraging GWAS summary statistics and linkage disequilibrium score regression (LDSR), we investigated disease co‐development with hepatitis C virus‐negative (HCV‐negative) HCC to provide unique insights into HCC etiology and prioritize relationships for further causal inquiry. We utilized the LDSR statistical framework to estimate the genetic correlation and heritability between HCV‐negative HCC with 901 epidemiologic, behavioral, and clinical traits from the United Kingdom Biobank (UKBB). First, we set the threshold for observed scale heritability of each trait at 0.02 to ensure reliable inferences with adequate study power. Next, we observed significant positive genetic correlations between HCV‐negative HCC and blood‐based biomarkers of liver injury (ALT, GGT) and allostatic load (including glycated hemoglobin, blood pressure, and total albumin). We also identified a positive genetic correlation between HCV‐negative HCC and diseases associated with metabolic dysfunction‐associated steatotic liver disease (MASLD), including diabetes, hypertension, chronic ischemic heart disease, and others. Taken together, our results help to identify polygenic and pleiotropic signals related to different phenotypic traits associated with HCC and support further exploration of the predictive power of blood‐based biomarkers identified in this study for inferring HCC development among HCV‐negative individuals.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

Précis: Glaucoma patients with significant visual field defects show poorer driving performance, higher collision risks, and a greater likelihood of driving cessation. They face difficulties with lane maintenance, slower hazard responses, and self-regulation while driving. Purpose: Glaucoma is a chronic, progressive optic neuropathy associated with visual field (VF) defects, which in advanced disease has been shown to affect patients’ activities of daily living. This systematic review qualitatively analyzes existing literature that explores the impact of glaucomatous VF loss on the driving performance of glaucoma patients, the extent of driving limitation and cessation, as well as the risk of motor vehicle collisions (MVCs). Methods: A literature search of MEDLINE and Embase (via Ovid), PubMed, Cochrane Library, and Web of Science databases was performed for studies published from 2003 to 2023, with the terms “glaucoma,” “visual field defect/disorder,” and “driving,” followed by selective vetting based on inclusion criteria. Within studies, data pertaining to study design, subject demographics, VF defect characteristics, driving performance and related outcomes were extracted. Results: Initial search yielded 835 studies, with 20 studies selected. Three more studies were included through hand-searching, with a total of 23 studies included for final review. Moderate to severe VF defects resulted in poorer driving performance, with slower response times to road hazards, decreased ability for lane maintenance, and increased difficulty driving at night. Patients with more severe VF defects and with bilateral glaucoma were more likely to limit or cease driving compared with those with milder and unilateral glaucoma. A greater severity of VF loss was associated with a higher risk of MVCs. Conclusion: More severe glaucomatous VF and bilateral glaucoma is associated with worse driving performances and a higher risk of MVCs, in both simulator and real-world settings.

Abstract Background Despite advances in diagnosis and management, the interstitial lung disease (ILD) lexicon is plagued by ambiguous and inconsistent terminology that complicates communication and impedes knowledge generation. The objective of this Fleischner Society Consensus Statement was to produce standardized terminology for ILD multidisciplinary diagnoses and major phenotypes. Methods Interviews with 10 experts were used to identify ILD clinical diagnoses and major phenotypes. The preferred terms for each entity and potential alternatives were identified, alongside the rationale for the preferred term. Entities with more than one potential term were the subject of an online modified Delphi survey posed to the 29 committee members, aiming to achieve consensus. Committee members rated their agreement with the initially preferred term—5 (strongly agree), 4 (agree), 3 (neutral/unsure), 2 (disagree), and 1 (strongly disagree)—with the option to provide additional comments. Median score ≥4 and interquartile range ≤1 were considered consensus agreement. Terms not reaching agreement were discussed by video conference, followed by an additional survey that incorporated feedback. Results From the 60 initial terms, there were two root terms that required upfront consensus before survey initiation (ILD and interstitial pneumonia) and another eight terms that had no alternative suggested by the committee or in the literature. Agreement was met by 47/50 terms (94%) in Round 1 of the survey. The three terms (6%) that did not reach agreement met agreement in Round 2. Conclusions This document provides standardized recommended terms for ILD multidisciplinary diagnoses and major phenotypes that will facilitate communication among clinicians, researchers, patients, and other stakeholders.

Abstract Aging increases the vulnerability of kidneys to injury and impairs their regenerative capacity. SIRT3 expression declines with aging and is associated with multiple age‐related pathologies. The expression profile and functional role of SIRT3 in renal aging remain unclear. Here, SIRT3 expression in aging kidneys is assessed and analyzed for its promoter methylation patterns using methylation‐specific PCR (MSP). It is found that aging exacerbates UUO‐induced renal fibrosis, associated with downregulated SIRT3 expression. Mechanistically, age‐related SIRT3 downregulation is mediated by hypermethylation of its promoter region. SIRT3 knockout exacerbated renal fibrosis in young mice subjected to UUO, whereas SIRT3 overexpression attenuated fibrosis in aged UUO mice. Integration of RNA‐seq and immunoprecipitation‐mass spectrometry (IP‐MS) analyses revealed that SIRT3 deficiency leads to hyperacetylation of GSK3β at lysine 15 (K15). This K15 hyperacetylation inhibited GSK3β activity, consequently stabilizing its substrate β‐catenin. Furthermore, self‐assembled PEG‐PCL‐PEG micelles are designed and synthesized to encapsulate hydrophobic honokiol (HKL). These micelles significantly enhanced the aqueous solubility and oral bioavailability of free HKL, maintained stable blood concentrations, and ultimately improved its anti‐fibrotic efficacy. These findings propose novel therapeutic strategies for managing renal fibrosis in the aging population and provide a foundation for developing new drugs and combination therapies.