Citations

Background. Liver transplant recipients face high risks of cardiometabolic events after transplant, driven by posttransplant weight gain, diabetes, hypertension, as well as immunosuppression-related side effects. Glucagon-like peptide-1 receptor agonists (GLP1RAs) improve metabolic and cardiorenal outcomes in nontransplant populations, but their role in liver transplant recipients remains understudied. Methods. This retrospective cohort study used TriNetX data (January 2010–December 2023) to compare outcomes in liver transplant recipients prescribed GLP1RAs (semaglutide, dulaglutide, liraglutide) within 1-mo posttransplant (n = 546) versus nonusers (n = 37 153). Propensity score matching (1:1) balanced demographics, comorbidities, and medications (n = 541 per group). Outcomes included mortality, hospitalizations, cardiovascular/renal/respiratory events, and graft outcomes. Results. Over a mean follow-up 838.5 d (SD 291.9) in the GLP1RA cohort and 884.3 d (SD 313.7) in the non-GLP1RA group, GLP1RA use was associated with a 43% lower all-cause mortality (7.0% versus 12.9%; hazard ratio [HR], 0.566; 95% confidence interval [CI], 0.381-0.841) and 39% fewer hospitalizations (60.4% versus 74.5%; HR, 0.613; 95% CI, 0.530-0.710). Acute heart failure (HR, 0.386; 95% CI, 0.285-0.524), renal failure/dialysis (HR, 0.489; 95% CI, 0.413-0.579), and respiratory failure (HR, 0.484; 95% CI, 354-0.662) risks were significantly reduced. No differences were observed in graft failure/rejection, myocardial infarction, stroke, atrial fibrillation/flutter, ventricular tachycardia, or ischemic optic neuropathy. Conclusions. Early GLP1RA initiation in liver transplant recipients was associated with reduced mortality, hospitalizations, respiratory, and cardiorenal complications without compromising graft safety. These findings support GLP1RAs as a promising adjunct therapy, warranting prospective trials to confirm benefits in this high-risk population.

Abstract Left atrial enlargement is a well-recognized marker of adverse cardiovascular outcomes, but its impact on early morbidity and mortality after valve replacement remains uncertain. We retrospectively reviewed 422 patients who underwent aortic and/or mitral valve replacement (MVR) for rheumatic heart disease at X between 2004 and 2022. Preoperative left atrial diameter index (LADI) was measured, and patients were classified as normal (<2.3 cm/m2) or abnormal (≥2.3 cm/m2). Clinical, operative, and postoperative outcomes were compared. The primary endpoint was 30-day all-cause mortality; secondary endpoints included postoperative atrial fibrillation (POAF), neurological events, renal impairment, re-exploration for bleeding, and intraoperative pacing wire requirement. Nearly half of patients (48.8%) had abnormal LADI. Patients with enlarged atria were more often female, had smaller body size, and were significantly more likely to undergo MVR (42.7% versus 18.1%, p < 0.001). Abnormal LADI was strongly associated with POAF (16.0% versus 7.4%, p = 0.006) and intraoperative pacing wire insertion (38.3% versus 23.5%, p = 0.001). Multivariate analysis confirmed severe LADI as an independent predictor of POAF (OR 3.91, p = 0.001) and pacing requirements (OR 2.31, p = 0.004). No significant differences were observed in 30-day mortality, stroke/transient ischemic attack, renal dysfunction, or bleeding complications. Preoperative LADI is an independent predictor of postoperative arrhythmic complications and pacing needs after valve replacement, but not early mortality. Incorporating LADI into preoperative risk assessment may improve rhythm surveillance and perioperative planning. Future prospective studies should evaluate its long-term prognostic value and role in reverse remodeling after surgery.

aims: We assessed the diagnostic accuracy of the SVEAT score in predicting 30-day major adverse cardiac events (MACE) in comparison with the well-established HEART and TIMI scores. background: Acute chest pain (ACP) is a common symptom in emergency departments. Various risk stratification tools have been developed to assess patients presenting with ACP. The Simple Vascular Event Assessment Tool (SVEAT) is the most recent scoring system introduced, based on five variables: Symptoms of chest pain, history of Vascular disease, ECG, Age, and Troponin-I. objective: We assessed the diagnostic accuracy of the SVEAT score in predicting 30-day major adverse cardiac events (MACE) in comparison with the well-established HEART and TIMI scores. method: Following PRISMA guidelines, a systematic literature search was conducted across five databases until June 22, 2024. Four studies comprising 1,520 patients were included in this meta-analysis. The predictive accuracy of the SVEAT, HEART, and TIMI scores for 30-day MACE was assessed by the area under the receiver operating characteristic curve (AUC). Heterogeneity was evaluated using the I² statistic, with values over 75% indicating significant heterogeneity. Indirect comparisons among the scores were performed using the Z-test. result: Pooled AUC for the SVEAT score was 0.92 (95% CI: 0.86-0.98), indicating superior predictive accuracy compared to the HEART (AUC: 0.86, 95% CI: 0.81-0.92) and TIMI (AUC: 0.82, 95% CI: 0.69-0.96) scores. However, significant heterogeneity (I² = 90.6%) was observed across studies, potentially due to variations in patient demographics, clinical settings, and outcome definitions. Despite the higher AUC, indirect Z-test comparisons revealed no statistically significant differences between the scoring systems. conclusion: SVEAT score demonstrates potential as an accurate tool for predicting 30-day MACE in patients with ACP. other: N/A

ABSTRACT Background Infection enteritis is associated with the development of irritable bowel syndrome (IBS) and functional dyspepsia. Aim This study aimed to examine the long‐term risk of IBS and functional dyspepsia, and associated health care utilisation following infection enteritis. Methods We conducted a retrospective cohort study using TriNetX U.S. Network. Adults with infection enteritis were identified and matched to controls, balancing demographics and comorbidities. Primary outcomes were the risk of incident IBS and functional dyspepsia diagnoses at 1, 5, and 10 years. Secondary outcomes were rates of IBS‐ and functional dyspepsia‐related medications, endoscopy, abdominal imaging, and hospitalizations. Pathogen‐specific and multivariate analyses were performed to assess variations in IBS risk. Results After matching, 202,244 patients were identified in each study cohort. At 1 year of follow‐up, the infection enteritis cohort had higher rates of IBS (RR = 2.35; 95% CI: 2.14–2.59), functional dyspepsia (RR = 2.02; 95% CI: 1.84–2.22), use of IBS‐related medications (RR = 1.29; 95% CI: 1.26–1.31), functional dyspepsia‐related medications (RR = 1.56; 95% CI: 1.55–1.59), abdominal imaging (RR = 2.42; 95% CI: 2.29–2.54), and Oesophagogastroduodenoscopy/colonoscopy (RR = 1.57; 95% CI: 1.50–1.65). These risks remained significantly higher in the IE cohort at 5 and 10 years. Salmonella/Shigella (RR = 6.48), and Giardia lamblia (RR = 5.05) had the highest risk of developing incident IBS. Conclusion Infection enteritis was associated with increased risk of IBS and functional dyspepsia, rates of related medication use, and greater healthcare utilisation.

Abstract Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare central nervous system tumors. Our understanding of the clinical course, prognostic factors, and optimal treatment strategies remains limited. Histologic, molecular, and clinical data were collected and analyzed for 25 patients with DLGNT reviewed at St. Jude Children’s Research Hospital. The median age at diagnosis was 6 years (11 months-20 years). Nineteen (72%) patients were male. The disease was localized at diagnosis in 12 (48.0%) patients, with most tumors localized in the spinal cord. BRAF fusion was present in 22 (95.6%) of 23 patients who had material for testing. Of 18 patients who had tissue for DNA methylation profiling, 3 (16.7%) matched to DLGNT MC-1, 3 (16.7%) to DLGNT MC-2, and 12 (66.7%) did not match to a DLGNT subclass. Median follow-up was 63 months. Twenty-four (96.0%) patients received adjuvant therapy after initial diagnosis or at progression. Thirty-five cytotoxic chemotherapy and 24 single-agent targeted therapy regimens were used in 22 and 13 patients, respectively. With targeted therapy, 3 (12%) patients had partial responses. Eleven (44.0%) received radiotherapy. Median progression-free survival (PFS) after a patient’s first chemotherapy, targeted therapy, or radiotherapy regimen was 44 months (1-77), 11 months (4-39), and 16.5 months (9-23), respectively. The 5-year PFS was 18.7%±9.2, while the 5-year overall survival (OS) was 82.4%±9.2. The 5-year OS was lower in patients older than 9 years at diagnosis (60.0%±21.9 vs 91.7%±8.0, p = 0.02). Ki67 &gt;4% was associated with worse PFS (0%±0 vs 24.6%±11.9 at 5 years, p = 0.03). Initial disease dissemination (localized vs. disseminated) and 1q gain status do not influence PFS or OS. PFS for DLGNT remains poor across all treatment modalities, including targeted therapies, despite the high frequency of BRAF fusions. Due to its rarity, establishing optimal therapeutic strategies for DLGNT requires additional treatment and outcome data and prospective multi-institutional trials.

ABSTRACT Background Concomitant atrial fibrillation (AF) and gastrointestinal (GI) bleeding present a clinical challenge due to recurrent bleeding risk associated with anticoagulation for AF‐associated stroke prevention. Left atrial appendage occlusion (LAAO) offers an alternative stroke prevention strategy, but its impact on recurrent GI bleeding remains unknown. Methods This retrospective, multicenter cohort study used the TriNetX database to identify adults with AF on oral anticoagulation and a history of GI bleeding. Patients were stratified by treatment with or without LAAO. 1:1 propensity score matching (PSM) was employed. The primary outcome was recurrent GI bleeding. Cox regression analysis was used to generate hazard ratios (HRs) with 95% confidence intervals (CIs). Odds ratios (ORs) were used to evaluate effect sizes between groups. Kaplan–Meier curves were used for time‐to‐event analyses. Results After PSM, 9259 patients were compared in each group. Odds of recurrent GI bleeding were consistently lower in patients undergoing LAAO than without LAAO across all follow‐up intervals: at 3 months (OR 0.84; 95% CI 0.78–0.91), 6 months, 1 year, 3 years, and 5 years (OR 0.87; 95% CI 0.82–0.92). Kaplan–Meier analysis demonstrated significantly lower risk of recurrent GI bleeding with LAAO (HR 0.80; 95% CI 0.76–0.84; p < 0.01). Conclusion In patients with AF and prior GI bleeding, LAAO was associated with a significantly lower risk of recurrent GI bleeding at short‐term and long‐term time intervals.

Abstract Background Oxidative phosphorylation (OXPHOS) is a central function and a key indicator of mitochondrial fitness, yet studies in human tissue remain limited. Inclusion body myositis (IBM) is a progressive myopathy that lies at the intersection of aging, inflammation and mitochondrial dysfunction. We aimed to perform a comprehensive profiling of mitochondrial respiration in muscle tissue from patients with IBM. Methods A wide battery of complementary tests from RNA level to high-resolution respirometry on permeabilized muscle fibers was performed. The relationship between respiration, mitochondrial content, mitochondrial DNA (mtDNA) abnormalities and mitophagy was examined, along with the correlation with various clinical parameters to determine the clinical significance of the findings. Results The study included a total of 67 patients with IBM and 45 controls. IBM muscle tissue exhibited reduced maximal respiration per tissue weight in State 3 (high substrates, high ADP) and uncoupled state with decreased coupling efficiency and higher leak control ratios. When adjusting for citrate synthase reflecting mitochondrial content, males had decreased State 3 intrinsic respiration, whereas females had greater intrinsic respiration in leak states. Complex II control ratio strongly correlated with disease duration and severity only in females. IBM was associated with decreased RNA and protein expression of OXPHOS complexes. Complex I activity was decreased mainly in females. IBM samples exhibited lower maximal H 2 O 2 emission, accompanied by a higher total antioxidant capacity that correlated with disease duration in females. In IBM, there was decreased mtDNA content, and impaired mitophagy, both of which strongly correlated with respirometry measures and markers of disease severity, indicating these pathways are likely interconnected and of clinical significance. Conclusion IBM is characterized by multilevel impairments in mitochondrial coupling efficiency, revealing several potential therapeutic targets to improve mitochondrial fitness, while accounting for sex-specific differences.