Citations

Background: Patients with decompensated cirrhosis experience frequent hospitalizations, yet evidence supporting remote post-discharge care remains limited. This study assessed the impact of cirrhosis-specific Remote Patient Management (CiRPM) program following hospitalization for acutely decompensated (AD) cirrhosis. Methods: Adults hospitalized for AD cirrhosis were included in a three-cohort observational study comparing CiRPM (2021-2024) with contemporary (C-control) and historical controls (H-control, 2018-2019). CiRPM enabled vital-sign and symptom transmission with 24/7 virtual nursing support. Subgroup analyses were conducted by disease etiology, CLIF-C AD score, and decompensation type. IPTW was used to adjust for confounding, and time-to-event outcomes were analyzed using Cox proportional hazards models. Results: Among 430 patients (156 CiRPM, 152 H-control, 122 C-control), mean age was 59 years, 65% had alcohol-associated liver disease (ALD), CLIF-C AD score of 56. CiRPM was associated with lower 90-day liver-related readmissions versus C-control (39% vs. 58%; HR 0.57, p =0.01) and a similar trend versus H-control (39% vs. 52%; HR 0.67, p =0.07). Associations were stronger among patients with CLIF-C AD ≥60 (HR 0.43 vs. H-control, p =0.005; HR 0.51 vs. C-control, p =0.02). Among ALD patients, fewer fluid-related readmissions (OR 0.40 and 0.37; both p <0.001) and recurrent hospitalizations (OR 0.51; p =0.001 and p =0.002) were observed in the CiRPM group. In non-ALD patients, hepatic encephalopathy readmissions were lower (OR 0.29, p =0.004; OR 0.36, p =0.02). Mortality did not differ across groups. Conclusion: CiRPM enrollment was associated with fewer liver-related hospitalizations, particularly among patients with ALD and CLIF-C AD ≥60, supporting targeted remote management as a scalable post-discharge strategy for this high-risk population.

Chimeric antigen receptor (CAR) T-cell therapy is a transformative modality for refractory hematologic malignancies; however, its adoption in Latin America and the Caribbean (LAC) is severely constrained by prohibitive manufacturing costs, limited specialized infrastructure, and fragmented regulatory frameworks. To address this translational gap, we propose a pragmatic, cost-adapted model for establishing Good Manufacturing Practice (GMP) laboratories tailored to the socioeconomic realities of LAC. This model advocates for decentralized, modular cleanroom facilities that integrate fully closed automated manufacturing platforms with risk-based quality management systems. Furthermore, we emphasize the strategic implementation of artificial intelligence (AI) and digital health tools—such as electronic batch records and predictive analytics—to optimize resource utilization and ensure stringent regulatory compliance. Essential to this framework is the cultivation of a specialized local workforce and the promotion of regional regulatory harmonization through initiatives like PAHO’s Red PARF. Ultimately, this scalable approach provides a realistic roadmap to democratize CAR T-cell therapy in LAC, fostering regional biomanufacturing autonomy and promoting equitable patient access.

Abstract Introduction: Erythromelalgia is a descriptive term for burning pain and erythema in distal extremities, often worsened by heat and improved by cold. Inherited erythromelalgia has been primarily linked to gain-of-function variants in SCN9A , encoding voltage-gated sodium channel NaV1.7. However, approximately 65% to 85% of patients with erythromelalgia do not have pathogenic SCN9A variants. Objectives: The objective of this study was to uncover and assess gene variants potentially associated with pediatric-onset erythromelalgia. Methods: With IRB approval and informed consent, probands and families with erythromelalgia underwent next-generation sequencing. A list of genes of interest was produced based on Mendelian inheritance models. Selected gene candidates were assessed using the Sequence Kernel Association Test-Optimal (SKAT-O). Results: Sixty-two probands with erythromelalgia and their relatives were included in Mendelian analysis, which identified variants in PR domain zinc finger protein 12 ( PRDM12 ) and dihydropyrimidinase-like protein 2 ( DPYSL2 ). In a targeted 12-gene rare-variant set analysis using SKAT-O, zinc finger homeobox protein 2 ( ZFHX2 ) showed evidence of association ( P = 6.9 × 10 −4 ), surpassing Bonferroni correction for 12 tests (α = 4.17 × 10 −3 ), whereas KIF1B showed only a nominal association signal ( P = 0.03) that did not survive multiple-testing correction. Conclusion: Genes associated with both increased and decreased pain sensitivity are of considerable interest for elucidating pain mechanisms and analgesic development. As rare variants in PRDM12 and DPYSL2 were identified in a pediatric erythromelalgia cohort and a gene-based rare-variant association signal for ZFHX2 was identified, replication and functional validation are needed.

Background: Noninvasive tests are well validated in metabolic dysfunction–associated steatotic liver disease, but evidence in metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-associated liver disease (ALD) is limited. We evaluated noninvasive test–based clinical care pathways for fibrosis risk stratification in MetALD and ALD. Methods: This is a multinational, multicenter, cross-sectional study across 35 centers in 16 countries (2013–2025), including adults with MetALD or ALD. Fibrosis was assessed by liver biopsy and/or vibration-controlled transient elastography (VCTE). In biopsy-proven participants, we analyzed the sequential pathway (Fibrosis-4 [FIB-4] first, followed by VCTE for indeterminate FIB-4) to identify advanced fibrosis (≥F3). Diagnostic accuracy was assessed using the AUC. Results: Among 893 participants (41.3% MetALD and 58.7% ALD), the median age was 52 [43.0–61.0] years, and 79.4% were male. The estimated prevalence of advanced fibrosis was 45% (32.2% in MetALD and 54.0% in ALD). Participants with MetALD had a more dysmetabolic profile but lower fibrosis stages than ALD. Among biopsy-proven participants, FIB-4 AUC was 0.720, and VCTE AUC was 0.833. FIB-4 performed better in MetALD than ALD (AUC 0.773 vs. 0.540), while VCTE accuracy was similar across groups. In the sequential pathways, the false-negative rate for advanced fibrosis (misclassified as low risk) was 6.8% (4.9% MetALD and 11.3% ALD). Conclusions: In biopsy-proven patients, FIB-4 performance was acceptable in MetALD but substantially weaker in ALD. The standard 2-step pathway performed adequately in MetALD but missed a clinically meaningful proportion of advanced fibrosis in ALD.

Abstract: Cardiovascular disease (CVD) remains the leading cause of death worldwide. While advances in treatment have improved outcomes, the greatest gains in public health will come from primary prevention. Risk stratification is the foundation of CVD prevention. Traditional tools, such as pooled cohort equations (PCEs) and SCORE2, do not capture non-traditional risk factors and individual variability, driving efforts to refine existing approaches. We critically discuss emerging risk determinants for primary CVD prevention. Coronary artery calcium scoring can reclassify CVD risk but has limitations related to cost, access, and unvalidated improvements in clinical endpoints. Biomarkers such as apolipoprotein B and lipoprotein(a) may identify residual risk beyond LDL-C, particularly in patients with lipid discordance, but remain underused due to uncertain thresholds and the lack of prospective triallevel outcome data. Trials of colchicine in primary prevention have yielded mixed results, making the role of targeting inflammation unclear in CVD prevention. Polygenic risk scores can stratify genetic risk but face challenges in sensitivity, specificity, and generalizability. Multiomics approaches, while offering the promise of deeper phenotyping, lack established clinical applications and consensus on when their use is appropriate. Artificial intelligence may allow better prediction across cohorts but requires broader validation. Clonal hematopoiesis of indeterminate potential, a marker of inflammation and age-related CVD risk, lacks evidence supporting routine screening or intervention in younger, asymptomatic individuals. The proliferation of new risk stratification tools poses a key challenge: determining when additional data meaningfully alter clinical decisions. Until robust outcome-based evidence emerges, risk enhancers should guide, but not dictate, therapy in selected patients.

e15598 Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of gastrointestinal (GI) malignancies. Emerging evidence suggests that gut microbiome composition plays a critical role in modulating the efficacy of immunotherapy. Antibiotics, by disrupting intestinal microbial diversity, may attenuate antitumor immune responses and compromise ICI outcomes. We evaluated time-dependent clinical outcomes associated with antibiotic exposure using real-world data. Methods: We conducted a retrospective cohort study using a large federated real-world database (2015-2025). Adults (18–89 years) with gastrointestinal or hepatobiliary malignancies (including colorectal, gastric, esophageal, and liver cancers) treated with ICI, receiving systemic antibiotics, were compared with matched controls without antibiotic exposure. Cohorts were balanced using 1:1 Propensity score matching for demographics, comorbidities, and treatment variables. The primary outcome was all-cause mortality at 30 days of ICI initiation; the secondary outcomes were hospitalization secondary to infectious and organ-related complications, overall survival at 1 and 3 years. Pre-specified subgroup analyses were performed in older adults ( > / = 65 years). Effect estimates were reported as risk ratios( RR), hazard ratios (HR), and absolute risk differences. Survival was analyzed using Kaplan–Meier curves and Cox proportional hazards models. Results: Within 30 days, antibiotic exposure was associated with significantly increased risks of Clostridioides difficile infection (RR 2.39), pneumonia (RR 2.93), acute kidney injury (RR 1.40), acute respiratory failure (RR 2.11), and neutropenia (RR 1.18) (all p < 0.05). Absolute risk differences translated to a number needed to harm (NNH) of approximately 38 for pneumonia, 143 for acute kidney injury, and ~140 for C. difficile infection. One-month mortality was modestly higher in the antibiotic group (5.4% vs 4.5%; HR 1.22; p = 0.014). However, no significant differences in mortality were observed at 6 months, 1 year, or 3 years, and survival curves converged over time. In the subgroup analysis of adults ≥65 years, early adverse event patterns were preserved, while long-term mortality remained unchanged. One-year hospital admission rates did not differ significantly between groups. Conclusions: Antibiotic exposure is associated with substantial early infectious and organ-related harm and a small increase in short-term mortality, without improvement in long-term survival, including among older adults. These findings highlight a critical opportunity for risk-adapted antibiotic stewardship and careful reassessment of empiric antibiotic use. Key words: ICI- Immune checkpoint inhibitors, RR- Risk ratio, HR- Hazard Ratio, NNH- Number Needed to Harm.

8075 Background: The role of definitive local thoracic therapy in metastatic non–small cell lung cancer (NSCLC) remains controversial. While stereotactic body radiation therapy (SBRT) is increasingly utilized, comparative survival outcomes with surgical resection in real-world populations remain limited. We evaluated survival and pulmonary outcomes associated with surgery versus SBRT in patients with stage IV NSCLC. Methods: We conducted a retrospective cohort study using the TriNetX Research Network including adults (≥18 years) with stage IV NSCLC treated between January 2013 and December 2023 who underwent definitive local thoracic therapy with either surgical resection or SBRT. Patients with small cell lung cancer, prior lung cancer diagnoses, prior thoracic radiation, or incomplete survival data were excluded. Propensity score matching (1:1) was performed to balance demographics, comorbidities, smoking history, and exposure to systemic therapy including chemotherapy and immunotherapy within 6 months of index treatment. Primary outcomes included landmark 1-year all-cause mortality and overall survival. Secondary outcomes included pneumonia and respiratory failure. Kaplan–Meier analysis and Cox proportional hazards regression were performed. Results: After matching, 1,934 patients were included (967 per cohort). At 1 year, surgical resection was associated with significantly lower mortality compared with SBRT (17.5% vs 31.4%; RR 0.56, 95% CI 0.47–0.66; p < 0.001), corresponding to an absolute risk reduction of 13.9% and an estimated number needed to treat of approximately 7. Kaplan–Meier analysis demonstrated superior survival in the surgical cohort (log-rank p < 0.001). Surgical resection remained associated with significantly improved long-term survival, with a 64% lower hazard of death (HR 0.36, 95% CI 0.30–0.44; p < 0.001) and prolonged median survival (3,942 vs 1,182 days). Pulmonary outcomes favored surgery. Pneumonia incidence was significantly lower in the surgical cohort at both 1 year (12.9% vs 29.3%; RR 0.44; p < 0.001) and 3 years (5.9% vs 14.2%; RR 0.42; p < 0.001). Rates of respiratory failure did not differ significantly between treatment groups. Conclusions: In this large real-world propensity-matched study, surgical resection was associated with significantly improved survival compared with SBRT in carefully selected patients with stage IV NSCLC. Surgery was additionally associated with lower long-term pulmonary infectious complications without increased respiratory failure risk. These findings suggest a potential role for aggressive local therapy in selected metastatic patients and support prospective trials to refine patient selection strategies.