Citations

Abstract Aims Significant secondary tricuspid regurgitation (STR) is associated with worse morbidity and mortality. To-date, evidence on isolated tricuspid valve surgery in STR remains controversial with uncertainty regarding management strategies. We aimed to investigate sex differences in the association of isolated tricuspid valve surgical repair/replacement (TVR) with outcomes of mortality and heart failure (HF) hospitalizations in STR. Methods and results Patients with severe STR without significant aortic valve or organic mitral valve disease, congenital heart disease, pacemakers, previous valve intervention, malignancy, or end-stage kidney/liver disease were identified. Isolated TVR was studied as a time-dependent covariate in association with mortality and HF hospitalizations. Among 2,857 patients (median age 76 years; 62% women), 143 underwent isolated TVR (58% repair; 42% replacement; 64% with low TRI-SCORE risk category) at median 56 days. Over median 1.6 (IQR 0.2-5.2) years, 1,771 patients died and 1,259 had HF hospitalization. When adjusting to age, comorbidities, left/right ventricular function, pulmonary hypertension, hemoglobin level, and dyspnea, isolated TVR was associated with lower mortality in females (HR 0.54 95% CI 0.35-0.83) but not males (HR 1.29 95% CI 0.90-1.83), p-interaction<0.01; this remained the case when restricting to groups with normal left/right ventricular function. Isolated TVR was associated with HF hospitalization without interaction with sex (HR 0.68 95% CI 0.46-0.998), p-interaction=0.51. Conclusion Isolated TVR for STR was associated with decreased HF hospitalizations in both females and males but improved survival only in females. Future studies are needed to understand differences in the natural history of TR between sexes and stratify outcomes after TR intervention by sex.

Abstract Background Online hemodiafiltration (HDF) enhances the removal of middle molecules, including large-middle molecules, through the combined action of diffusion and convection. Randomized controlled trials (RCTs) and individual participant data (IPD) meta-analyses demonstrate improved cardiovascular outcomes and, importantly, a reduction in all-cause mortality when HDF is delivered with sufficiently high convective volumes in post-dilution mode. These findings underscore that an adequate convective dose is a critical determinant of clinical benefits compared to high-flux hemodialysis (HD). However, translation into consistent clinical practice remains heterogeneous. Therefore, the Italian Society of Nephrology convened an international, multidisciplinary panel to synthesize randomized evidence comparing online post-dilution HDF with high-flux HD in adults receiving maintenance hemodialysis. Methods The critical outcomes included all-cause and cardiovascular mortality, whereas the important outcomes included selected patient-reported health domains, including physical function, patient-perceived cognitive function, pain interference, social participation, and health-related quality of life. The certainty of the evidence was appraised using the GRADE methodology. Structured guidance recommendations and best practice statements were developed through a consensus. Sensitivity analyses were performed to assess the robustness of the observed mortality effect. Results High-volume post-dilution HDF reduces all-cause mortality (hazard ratio 0.84; 95% CI 0 74–0.95; moderate-certainty evidence) and cardiovascular mortality (hazard ratio 0.78, 95% CI 0.64–0.96; moderate-certainty evidence; data from an individual participant data analysis of trials of high volume HDF versus high-flux HD). Emerging evidence suggests slower deterioration in selected patient-reported domains, including physical function, patient-perceived cognitive function, pain interference, and social participation (low-certainty evidence). Safety with on-line post-dilution HDF has been demonstrated to be similar to that of high-flux HD. Conclusions Online post-dilution HDF should be regarded as a dose-dependent therapy. We recommend its use to reduce cardiovascular mortality and suggest high-volume HDF to reduce all-cause mortality and slow deterioration in selected patient-reported health domains. Effective implementation in clinical practice requires a targeted and individualized approach with careful optimization and monitoring of convective volume, along with appropriate treatment time, blood-flow rate, supporting infrastructure, and consideration of patient preferences. This guidance provides evidence-based recommendations and best practice statements for its use.

Introduction Allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) entails prolonged recovery, serious complications, functional limitations, psychological distress, and extended isolation to prevent infection. During the peak of the COVID-19 pandemic, treatment disruptions, restricted caregiver access, and intensified isolation compounded these transplant-specific burdens. The longer-term influence of the pandemic experience on HCT recovery and survivorship remains poorly understood. Methods In this qualitative descriptive study, adults with AML who underwent allogeneic HCT from March through September 2020 participated in virtual semi-structured interviews from July 2022 through April 2023, approximately two years post-transplant. Participants were identified through the Center for International Blood and Marrow Transplant Research registry. Zoom or phone interviews were recorded, transcribed verbatim, and analyzed using inductive qualitative content analysis to describe survivorship experiences and opportunities to improve supportive care. Results A total of 25 AML survivors (ages 24-78, 56% male) were interviewed approximately two years post-transplant. Three themes were found: (1) Transplant is an arduous journey; (2) The COVID-19 pandemic shaped the transplant experience in complex and far-reaching ways; (3) Transplant demands sustained personal and relational investment throughout the transplant journey. Conclusions This study enhances our understanding of the stressors associated with transplantation during periods of heightened adversity, while also identifying opportunities to strengthen healthcare systems and supportive care services for this population. Situating these experiences within the context of a global health emergency offers a rare lens into how external stressors can exacerbate the already demanding nature of HCT survivorship. By understanding survivors’ experiences, healthcare systems can better anticipate and address the evolving needs of transplant survivors.

Background: Perinatal and early-life factors may influence non-Hodgkin lymphoma (NHL) risk, but study results have been mixed and exposure data for childhood ages are limited. Herein, we investigated associations of these exposures with risk of NHL and common subtypes. Methods: This case–control study included 2280 NHL cases and 2253 controls, enrolled from 2002 to 2014 at the Mayo Clinic Rochester. Self-reported perinatal and early-life exposures included maternal age at birth, birth order, birthweight, time breastfed, height and weight at ages 7, 12, and 18 years relative to peers, and age and weight when growth ceased. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for design variables and potential confounders. Linear trend tests were performed for ordinal variables, and heterogeneity tests were performed to evaluate whether associations varied across four NHL subtypes. Results: After multivariable adjustment, greater birth weight (OR = 1.15 for quartile 4 vs. 1; p-trend = 0.04), weight at age 7 relative to peers (compared to average, OR = 1.05 for heavy and OR = 0.87 for thin; p-trend = 0.002), and weight when growth ceased (OR = 1.30 for quartile 4 vs. 1; p-trend < 0.001) were associated with increased NHL risk. An inverse association was observed for breastfeeding duration with NHL risk (OR = 0.77 for >6 months vs. never; 95% CI 0.61–0.97). Associations did not significantly vary by major NHL subtype (p-heterogeneity > 0.05). Other perinatal and early-life exposures were not associated with NHL risk. Conclusions: Greater body weight at birth and through childhood may be associated with increased NHL risk, potentially extending the life-course perspective on adiposity and lymphomagenesis, with implications for prevention.

Left atrial (LA) myopathy plays a critical role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). This study aimed to evaluate LA function in a murine model of hypertension-induced HFpEF, with and without obesity, by analyzing left ventricular (LV) pressure signals to quantify the contribution of LA systole to total LV volume. HFpEF was induced in C57BL/6J mice using the SAUNA model, which involves uninephrectomy, chronic aldosterone infusion, and high-salt drinking water for four weeks. To model obesity-associated HFpEF, a high-fat diet (HFD) was added to the SAUNA protocol. Invasive hemodynamic measurements were obtained, and a novel method was developed to assess atrial systole using the second-order derivative of the LV pressure signal during diastolic filling. SAUNA HFpEF mice exhibited preserved LVEF, moderate hypertension, pulmonary congestion, and diastolic dysfunction as evidenced by a prolonged time constant of relaxation (Tau). In sham control mice, atrial systole accounted for 23.0 ± 2.4% of LV volume, whereas this contribution was significantly reduced to 13.9 ± 2.3% in SAUNA HFpEF mice ( P &lt; 0.01). In obese sham controls, atrial systole contributed 53.1 ± 2.2%, which was markedly decreased to 36.8 ± 3.6% in obese-SAUNA HFpEF mice ( P &lt; 0.003). This novel method enables precise quantification of LA systolic contribution to LV filling in mice and highlights the pathophysiological effects of hypertension and obesity on LA function in HFpEF.

Summary Oral ovalbumin administration prevents epicutaneously‐induced egg allergy by suppressing Tfh and B cells and IgE. This prophylactic oral ovalbumin abolishes antigen‐specific IL‐4 and IL‐13 production in skin‐draining lymph nodes.

Background Individuals with schizophrenia spectrum disorders are at increased risk of cardiometabolic complications, largely due to antipsychotic-associated metabolic effects. Effective management strategies remain limited. Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown metabolic benefits in the general population, but its role in this population remains unclear. Objective To evaluate the efficacy and safety of semaglutide compared with placebo in individuals with schizophrenia spectrum disorders receiving antipsychotic therapy and experiencing metabolic abnormalities. Design Systematic review and meta-analysis of randomized controlled trials. Data Sources and Methods: A systematic review and meta-analysis was conducted following PRISMA guidelines. PubMed, Cochrane Library, Embase, and ScienceDirect were searched from inception to February 2026. Randomized controlled trials comparing semaglutide with placebo were included. The longest follow-up time point from each study was used for pooled analysis. Mean differences (MD) and odds ratios (OR) with 95% confidence intervals (CIs) were calculated using RevMan 5.4. The certainty of evidence for critical outcomes was assessed using the GRADE framework. Results Three randomized controlled trials (n = 258) were included. Semaglutide was associated with reductions in body weight (MD: -11.01 kg), BMI (MD: -3.63 kg/m 2 ), and waist circumference (MD: -6.33 cm). Improvements were also observed in body composition. No significant differences were found in lipid or glycemic parameters except HbA1c which showed a significant reduction. Psychiatric outcomes remained unchanged. Gastrointestinal adverse particularly nausea and vomiting events were more frequent with semaglutide. Conclusion Semaglutide appears to improve anthropometric outcomes without worsening psychiatric symptoms in individuals receiving antipsychotic therapy. However, evidence is limited, and larger, long-term trials are required. According to the GRADE framework, the certainty of evidence ranged from moderate for key anthropometric and safety outcomes to low or very low for several metabolic and psychiatric outcomes, highlighting the need for larger, long-term randomized trials.

ABSTRACT Background and Aim Significant health disparities persist in alcohol‐associated liver disease (ALD), largely driven by social determinants of health (SDOH). However, the influence of neighbourhood‐level SDOH on ALD outcomes remains underexplored. In this study, we aimed to evaluate how neighbourhood‐level SDOH are associated with disease burden, comorbid conditions, and mortality in individuals with ALD. Methods We conducted a retrospective cohort study of patients with ALD in the Banner Health System, representing hospitals across Arizona, California, Nevada, Wyoming and Colorado, from January 2012 to October 2024 using ICD codes. Neighbourhood‐level SDOH were quantified using the Social Deprivation Index (SDI). Patients were stratified into quartiles based on SDI score, with Quartile 4 representing the most socioeconomically disadvantaged neighbourhoods. Primary outcomes included incidence of mortality, cirrhosis, major adverse liver outcome (MALO), Type 2 diabetes mellitus, any cancer, and major adverse cardiovascular events (MACE). A multivariable competing risk analysis was performed adjusting for age, sex, race/ethnicity, insurance type, primary language, smoking status, Type 2 diabetes mellitus, hypertension, hyperlipidemia, aspirin use, statin use, alcohol use disorder and a composite mental‐health/substance‐use disorder variable encompassing depression, anxiety disorders, post‐traumatic stress disorder, bipolar disorder, schizophrenia, and non‐alcohol substance use disorders. Results Among 11,394 patients with ALD and available SDI data, 6747 had ≥ 365 days of follow‐up. The average age was 51 years and 65.6% were female; 68.8% were non‐Hispanic White, 19.7% Hispanic, 5.9% Native American/Alaskan Native (NA), 3.2% Black, and 0.4% Asian/Pacific Islanders. Patients residing in the most disadvantaged neighbourhoods (Quartile 4) were significantly younger, more likely to be female, had a higher median BMI, and more frequently reported a non‐English primary language compared with those in the least disadvantaged areas (Quartile 1). Patients in the most deprived neighbourhoods were more likely to be Hispanic, Black, or Native American/Alaska Native and to be uninsured or on Medicaid, whereas those in the least disadvantaged neighbourhoods predominantly had private insurance. Individuals in Quartile 4 had increased mortality (adjusted hazard ratio [aHR]: 1.48, 95% Confidence Interval [CI]: 1.09–2.01) compared with individuals in Quartile 1. Conclusions In this large and demographically diverse ALD cohort, residing in socioeconomically disadvantaged neighbourhoods was associated with increased risk of mortality. These findings support the need for contextually tailored clinical interventions and broader treatment strategies that target upstream sociocultural and environmental factors that are associated with health outcomes. Addressing neighbourhood‐level SDOH through community engagement, policy reform, and cross‐sector partnerships to improve collaborative care efforts is needed to reduce health disparities in ALD.