Citations

Abstract Background Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) have emerged as a vital component in the management of heart failure (HF), demonstrating significant improvements in cardiac function. However, their impact on outcomes in patients with acute myocardial infarction (AMI) remains poorly characterized. This study aimed to evaluate the long-term outcomes of SGLT2-Is among patients with AMI. Methods We conducted a retrospective cohort study using data from the TriNetX Banner Health Network platform in the United States, including patients aged ≥18 years with AMI identified through ICD-10 codes. Patients were categorized into two cohorts based on SGLT2-I use. Propensity score matching (PSM) was performed to balance baseline demographics, comorbidities (e.g., hypertension, diabetes, chronic kidney disease, heart failure, and hyperlipidemia), and medication use (e.g., heart failure therapies, antiplatelet agents, anticoagulants). Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated for the following cardiovascular outcomes: acute HF hospitalizations, stroke, all-cause hospitalizations, recurrent AMI, cardiac arrest, and new-onset atrial fibrillation (AF). Kaplan-Meier analysis was completed to estimate survival probability from all-cause hospitalizations. Results After PSM, 2,440 patients were analyzed (1,220 SGLT2-I users; 1,220 non-users). Both cohorts had similar characteristics without any residual imbalance: mean age 67.7 years in the SGLT2-I group vs. 67.5 years in non-users, and both groups included 85.2% White and 33.6% female patients. Mean follow-up duration was 608 days for SGLT2-I users and 1,013.5 days for non-users. SGLT2-I use was associated with significantly lower rates of all-cause hospitalizations (RR: 0.712; 95% CI: 0.652–0.777), HF-related hospitalizations (RR: 0.878; 95% CI: 0.781–0.987), recurrent AMI (RR: 0.821; 95% CI: 0.703–0.959), and cardiac arrest (RR: 0.500; 95% CI: 0.345–0.725). No significant differences were observed in stroke (RR: 0.909; 95% CI: 0.702–1.178) or new-onset AF (RR: 0.889; 95% CI: 0.782–1.010) between the cohorts. Conclusions SGLT2-Is are associated with improved cardiovascular outcomes in patients with AMI, including reductions in all-cause and HF-related hospitalizations, recurrent AMI, and cardiac arrest. While these findings are hypothesis-generating, they emphasize the need for prospective clinical trials to confirm these results.Kaplan-Meier Analysis.

ObjectiveThe objective is to provide evidence‐based and expert guidance for the screening, treatment, and management of lupus nephritis.MethodsThe Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations. The Voting Panel achieved a consensus ≥70% on the direction (for or against) and strength (strong or conditional) of each recommendation.ResultsWe present 28 graded recommendations (7 strong, 21 conditional) and 13 ungraded, consensus‐based good practice statements for the screening and management of lupus nephritis. Our recommendations focus on the unifying principle that lupus nephritis therapy is continuous and ongoing, rather than consisting of discrete induction/initial and maintenance/subsequent therapies. Therapy should include pulse glucocorticoids followed by oral glucocorticoid taper and two additional immunosuppressive agents for 3–5 years for those achieving complete renal response.ConclusionThis guideline provides direction for clinicians regarding screening and treatment decisions for management of lupus nephritis. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each individual patient.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy marked by increased left ventricular wall thickness, leading in some cases to left ventricular outflow tract (LVOT) obstruction, heart failure, and arrhythmias. Mavacamten, a selective allosteric inhibitor of cardiac myosin, has demonstrated benefits in improving hemodynamics and reducing LVOT obstruction. However, its impact on arrhythmic burden remains unclear, with reports of early atrial fibrillation (AF) risk contrasting with long-term reductions in arrhythmias. This study assesses the temporal patterns of Holter-detected arrhythmias in HCM patients treated with mavacamten. Methods: This retrospective study included HCM patients from three Mayo Clinic sites. Baseline demographic, clinical, and echocardiographic data were collected. Holter monitoring was performed at baseline, short-term (<6 months), and long-term (>6 months) follow-up. Arrhythmic events, including premature atrial contractions (PACs), premature ventricular contractions (PVCs), and supraventricular tachycardia (SVT), were analyzed using standardized rates per 24 h. Statistical comparisons utilized the Wilcoxon signed-rank test. Results: Twenty-seven patients (56% female, median age 66 years) were included. PACs, PVCs, and SVT duration transiently but not significantly increased at short-term follow-up but returned to baseline at long-term follow-up. No sustained or high-risk ventricular arrhythmias were observed. Conclusions: Mavacamten is associated with transient arrhythmic fluctuations early in treatment, followed by stabilization. These findings support its long-term electrophysiological safety and underscore the need for early rhythm monitoring. Further research should explore its role in arrhythmic risk stratification in HCM patients.

The global burden of hepatocellular carcinoma (HCC) continues to rise, driven by increasing metabolic risk factors such as nonalcoholic fatty liver disease, obesity, and type II diabetes. Patients with advanced HCC have limited therapeutic options and a dismal prognosis. While recent advancements in combination therapies—including immune checkpoint blockade (ICB) with anti-PD-1/PD-L1 and anti-CTLA-4 agents and anti-angiogenics—have improved survival for some, up to 80% of patients fail to respond, underscoring an unmet need for new strategies. Emerging data indicate a strong association between increased tumor-infiltrating lymphocytes (TILs) and better responses in ICB-treated HCC, suggesting TIL enhancement as a promising approach. However, HCC’s inherent low immunogenicity and immunosuppressive tumor microenvironment (TME) limit the efficacy of current TIL-promoting strategies. Here, we demonstrate that low-dose intratumoral immunotherapy using the trivalent MMR vaccine—composed of live attenuated measles, mumps, and rubella viruses—modulates TME immune infiltration, increases cytotoxic T cell frequency, and delays tumor growth in multiple murine HCC models. Importantly, intratumoral or systemic MMR administration in combination with dual ICB (anti-mPD-1/anti-mCTLA-4) significantly prolongs survival, promoting tumor-specific and memory immune responses in both subcutaneous and orthotopic HCC models. These findings reveal a unique mechanism of vaccine-induced anti-tumor activity, highlighting MMR as a viable, globally accessible option for enhancing immune responses in advanced HCC therapy. Citation Format: Mulu Z. Tesfay,Aleksandra Cios,Khandoker U. Randal S. Shelton,Bahaa Mustafa,Camila C. Simoes,Steven Post,Thomas Kelly,Moaven Moaven,Lewis R. Roberts,Mitesh J. Borad,Martin J. Cannon,Alexei Basnakian,Nagalo Bolni. Live attenuated MMR vaccines modulate tumor immune cell infiltration and synergize with standard of care to prolong survival in preclinical HCC models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 945.

Background Severe alcohol-associated hepatitis (sAH) is a life-threatening condition with high mortality, where corticosteroid use is the only treatment that has shown short-term benefits. Pentoxifylline, an anti-tumour necrosis factor-alpha agent, has been proposed for its potential to improve outcomes, especially in patients with acute kidney injury (AKI). We aimed to evaluate the impact of pentoxifylline on mortality in patients with sAH and AKI in a well-characterised global cohort. Methods We conducted a retrospective, registry-based study including patients meeting the National Institute on Alcohol Abuse and Alcoholism clinical criteria for sAH and AKI. Mortality was the primary endpoint, with liver transplantation as a competing risk. Statistical analysis included Cox regression and Kaplan-Meier survival estimates. Results We included 525 patients from 20 centres across eight countries. The median age was 48 years, with 26.1% females, and 76.9% had a history of cirrhosis. Multivariable Cox regression models showed that pentoxifylline use was not associated with survival (HR 1.20, 95% CI 0.85 to 1.69, p=0.291). Factors associated with mortality included age (HR 1.23, 95% CI 1.10 to 1.36, p<0.001), Model for End-Stage Liver Disease score at admission (HR 1.06, 95% CI 1.04 to 1.08, p<0.001) and renal replacement therapy use (HR 1.39, 95% CI 1.05 to 1.84, p=0.019). The main causes of death were multiple organ failure (42%), infections (10%), oesophageal varices bleeding (7%) and renal failure (6%). Conclusion Pentoxifylline showed no significant benefit on mortality in patients with sAH and AKI. Further studies are needed to refine treatment strategies for this high-risk group.