Publications by Year: 2026

BACKGROUND: Temporary mechanical circulatory support (t-MCS) is increasingly used in fulminant myocarditis (FM), yet long-term outcomes and risk factors remain poorly defined.

METHODS: From the FULLMOON international cohort (419 adults with suspected FM across 36 centers in 15 countries), 295 patients treated with venoarterial extracorporeal membrane oxygenation (V-A ECMO) and/or Impella were analyzed. The primary endpoint was mortality at 1 year, heart transplantation (HTx), or left-ventricular assist device (LVAD). Multivariate Cox regression identified predictors of adverse outcomes. A propensity score-weighted analysis assessed outcomes based on timing of endomyocardial biopsy (EMB): early (≤ 2 days), delayed (> 2 days), or none.

RESULTS: The median age was 39 years (IQR 28-60), and 55% were female. Myocarditis was confirmed in 204 (69%) of the patients via histology or cardiac MRI. Histological data were available for 151 (51%) of the cohort. One-year mortality was 36%, while 44% died or had an HTx or LVAD. Predictors of worse outcomes were giant cell myocarditis, older age, cardiac arrest at ECMO initiation, and delayed EMB. Delayed EMB was consistently associated with higher mortality, HTx, or LVAD compared to early (HR = 1.55; 95% CI 1.23-1.96; p < 0.01) or no EMB (HR = 1.59; 95% CI 1.26-2.01; p < 0.01). However, event-free survival did not differ significantly between early EMB and no EMB (HR = 1.03; 95% CI 0.80-1.32; p = 0.85).

CONCLUSIONS: Despite a relatively young cohort, FM requiring t-MCS is associated with a high 1-year mortality rate. Timely recognition and early referral to specialized ECMO centers before cardiac arrest are critical.

BACKGROUND: Timing for anticoagulation (AC) initiation in atrial fibrillation (AF) after ischemic stroke (IS) remains uncertain. Previous large studies mostly represented high-income countries, with limited representation of severe stroke and low rates of primary outcomes. We aimed to compare AC initiation at different timeframes in a broader and more diverse population.

METHODS: We searched Medline, Embase, Cochrane, and Clinical Trials for trials and observational studies comparing early versus late AC initiation in AF after IS. The study groups were 0-4, 5-14, and ≥ 15 days. Primary endpoints were recurrent IS only and intracranial hemorrhage (ICH). Secondary endpoints included systemic embolism, all-cause mortality, and major bleeding. Sensitivity analysis focused on studies using direct oral anticoagulants and timing categories consistent with our classification.

RESULTS: Our meta-analysis included 20 studies with 25,884 patients. Mean NIHSS was 6.14, with at least 3204 severe strokes. IS was similar between groups, but the 0-4 days strategy ranked first (P-score = 0.92). Sensitivity analysis showed reduced recurrent IS in the 0-4 days group versus the ≥ 15 days group (RR, 0.28; 95% CI, 0.12-0.65; P < 0.01). ICH had no difference across all periods, 0-4 days versus 5-14 days (RR, 1.13; 95% CI, 0.58-2.18; P = 0.14); ≥ 15 days versus 5-14 days (RR, 0.91; 95% CI, 0.50 to 1.65; P = 0.75); and 0-4 days versus ≥ 15 days (RR, 0.87; 95% CI, 0.49-1.55; P = 0.63). No differences were observed in all secondary outcomes.

CONCLUSION: Initiating AC 0-4 days after IS appears safe and may reduce the risk of recurrent stroke without increasing ICH, even in a more diverse population with higher-bleeding risk.

BACKGROUND: Cardiovascular disease remains the leading cause of morbidity and mortality in the United States. JACC Cardiovascular Statistics 2026 reports the most up-to-date data on cardiovascular health in the United States. The report covers major cardiovascular risk factors (hypertension, diabetes, obesity, cholesterol, and cigarette smoking) and conditions that collectively account for most cardiovascular deaths and disability: coronary heart disease, acute myocardial infarction, heart failure, peripheral artery disease, and stroke.

OBJECTIVES: JACC Cardiovascular Statistics was developed to provide a clear, comprehensive, and accessible snapshot of cardiovascular health in the United States. An annual synthesis of contemporary cardiovascular statistics is needed to inform patients, clinicians, researchers, public health professionals, policymakers, and the public.

METHODS: This report synthesizes data from multiple national sources, including population-based surveys, clinical registries, administrative datasets, and vital statistics. For each risk factor and condition, we evaluated trends in disease epidemiology, quality of care, and morbidity and mortality. Data are presented overall and, where available, stratified by age, sex, race and ethnicity, socioeconomic status, and geography. Findings are presented using a standardized, visually accessible framework.

RESULTS: Cardiovascular risk factors-hypertension, diabetes, obesity, cholesterol, and cigarette smoking-remain prevalent among U.S. adults, with persistent gaps in prevention and treatment. Across cardiovascular conditions-coronary heart disease, acute myocardial infarction, heart failure, peripheral artery disease, and stroke-long-term gains in mortality are slowing or reversing, with ongoing gaps in quality of care and persistent health disparities.

CONCLUSIONS: JACC Cardiovascular Statistics 2026 provides a comprehensive snapshot of cardiovascular health in the United States, serving as an annual benchmark to guide clinical practice, inform health policy, and promote accountability in efforts to improve cardiovascular health and outcomes for all.

Tissue stiffening is central to disease progression and aggressiveness in pancreatic adenocarcinoma (PDAC). Here we report how the biomechanical characteristics of the cell culture conditions impact the amount, as well as the cargo, of extracellular vesicles (EVs) produced by pancreatic cancer cells. Cells grown on softer matrices (0.5 kPa) release upwards of 40 times more EVs than those grown on stiffer surfaces (8 kPa) and their cargo is more enriched in protein-coding RNAs related with mitochondrial and cytoskeleton pathways. Moreover, cells grown in a 3D conformation release more EVs than those grown in 2D, with the repeat RNA content being maintained across all different cell culture conditions. Our study provides evidence to support that the mechanical microenvironment of cells influences EV generation, with distinct consequences for coding and non-coding RNA packaged within the EVs.

OBJECTIVE: To identify perceived benefits, concerns, and challenges to adolescents with cancer accessing online patient portals.

STUDY DESIGN: Semi-structured, qualitative interviews with 48 dyads of adolescents with cancer (12-17 years) and their parents. Interviews explored parental and adolescent experiences, motivations, and concerns to accessing the portal. Three team members analyzed interview transcripts using thematic analysis.

RESULTS: Most adolescents (41/48, 85%) and parents (42/48, 87.5%) believed that adolescents should have access to their electronic health information (EHI), but that access should depend on certain factors, such as the adolescent's age, maturity level, or ability to understand portal content. Although most parents reported having accessed the portal (42/48, 88%), only 12 adolescents (25%) had previously accessed the portal. We identified seven themes related to both real-life and hypothetical benefits and concerns of adolescent portal access: promoting communication between adolescents, caregivers, and clinicians; providing reassurance to adolescents; supporting adolescent engagement and responsibility; supporting adolescent knowledge and understanding; creating confusion or misunderstanding; creating worry or fear; and potential for misuse.

CONCLUSION: In our qualitative study, most adolescents with cancer and their parents believed that teens should have access to their EHI but expressed a diversity of opinions on when and under what circumstances teens should have access. Both parents and teens recognized that portals had the potential to both alleviate and contribute to anxiety and worries related to cancer care and prognosis. Our study found novel areas of concern relating to the potential for portal use to negatively impact adolescent mental health.

Patients with sickle cell disease (SCD) commonly receive red blood cell (RBC) transfusions and can become RBC alloimmunized. This study was designed to investigate if RBC alloimmunization before hematopoietic cell transplant (HCT) was associated with post-HCT outcomes and transfusion support using the multicenter Sickle cell Transplant Advocacy and Research (STAR) retrospective registry. From a cohort of 229 pediatric patients with SCD who underwent human leukocyte antigen (HLA)-matched related donor HCT with myeloablative or reduced intensity conditioning, 40 patients (17%) were RBC alloimmunized pre-HCT. The RBC alloimmunized group had a significantly higher incidence of grade III-IV acute graft-versus-host disease (GVHD) (15% vs. 3.7%, p = 0.013), which remained significant (OR 4.22, 95% CI, 1.19, 14.3; p = 0.027) when controlling for pre-HCT RBC transfusion burden and conditioning intensity. Graft failure occurred in 10% of RBC alloimmunized patients compared with 2.6% of non-alloimmunized patients, p = 0.052. Patients with RBC alloimmunization had lower 5-year severe GVHD-free, rejection-free survival (69% vs. 88%, p = 0.004), which remained significant when controlling for age. Post-HCT patients received a median 3 RBC units (IQR 2, 6) and 11 platelet transfusions (IQR 7, 19). Pre-HCT RBC alloimmunization was associated with a greater requirement for post-HCT platelet transfusions, but not post-HCT RBC units transfused. We postulate that the observed associations of pre-HCT RBC alloimmunization with severe acute GVHD and post-HCT platelet transfusion burden are due to inherent immunologic characteristics that render patients at increased risk of developing multiple immune-mediated complications.

BACKGROUND: Psoriasis and depression frequently coexist, creating a complex, bidirectional relationship that complicates treatment. This study, integrating clinical assessments with transcriptomic and metabolomic analyses, hypothesizes that TYK2 (tyrosine kinase 2) inhibitors possess a dual therapeutic potential to simultaneously address both dermatological manifestations of psoriasis and the frequently accompanied depressive symptoms.

METHODS: In a cohort of 298 psoriasis patients evaluated using the Hospital Anxiety and Depression Scale (HADS), participants were categorized into a TYK2 inhibitor group, a Janus kinase (JAK) inhibitor group, and a non-JAK pool (comprising interleukin [IL]-23 biologics, IL-17 biologics, and other treatments) to avoid overlapping JAK pathway inhibition. Statistical analysis was conducted using generalized linear models (GENMOD), with adjustments for the following covariates: age, sex, Psoriasis Area and Severity Index (PASI), body surface area (BSA), prior systemic or biologic therapy within 12 months, disease duration, and phototherapy history.

RESULTS: For HADS-D scores, the TYK2 inhibitor group showed significantly lower values compared with the non-JAK pool (β = 1.23, 95% confidence interval [CI]: 0.37-2.10). However, no significant differences were observed when compared with the IL-23 biologics group (β = 0.67, 95% CI: -0.76-2.10) or the JAK inhibitor group (β = 0.84, 95% CI: -1.54-3.21). Transcriptomic analysis of peripheral blood revealed significant downregulation of genes related to the IL-6 receptor, long-term depression pathways, and Th17 cell differentiation, while pathways associated with neuronal activity were upregulated. Metabolomic profiling highlighted a decrease in kynurenic acid, which is known for its pro-inflammatory and depressive effects, and an increase in 1H-indole-3-propanoic acid, an anti-inflammatory metabolite with neuroprotective properties. It is important to note that these findings are based on exploratory omics analyses, for which false discovery rate (FDR) control was applied.

CONCLUSIONS: These findings provide a hypothesis that TYK2 inhibitors disrupt the persistent "peripheral inflammation-central depression" cycle by targeting the IL-23/Th17 axis and modulating the IL-6/tryptophan metabolic hub. This innovative, multi-targeted approach represents a possibility for treating psoriasis with comorbid depression, offering not only clinical improvements in both skin and mood symptoms but also enhanced patient adherence to treatment regimens.

Objective The aim of this study was to examine whether the intake of folate, vitamin B6, and vitamin B12 before and after disease diagnosis impacts the risk of death among individuals with Parkinson's disease (PD). The impact of folate, vitamin B6, and B12 intake on mortality in individuals with PD is unknown. Methods The study population comprised 1521 participants of two large prospective cohorts who were newly diagnosed with PD during follow-up. Participants responded to repeated dietary assessments using validated food frequency questionnaires, covering up to 30 years before to more than 10 years after PD diagnosis. We estimated the hazard ratio (HR) and 95% confidence interval (CI) of death according to quartiles of the cumulative average intake of B vitamins before and after disease diagnosis. We also examined PD-specific mortality and alternative exposure definitions. Results We documented 1005 deaths during 15 years of follow-up. A higher cumulative average intake of B vitamins before disease diagnosis was associated with a lower risk of death among patients with PD. The multivariable-adjusted HR (95% CI) of death comparing top to bottom quartiles of intakes was 0.78 (0.62-0.99) for folate, 0.76 (0.62-0.93) for B6, and 0.86 (0.69-1.09) for B12. These estimates were stronger in analyses restricting to intakes from supplemental sources and in those considering intakes reported up to 12 years before diagnosis. The intake of these B vitamins after PD diagnosis was not associated with the risk of death. Conclusions Higher intake of B vitamins before disease diagnosis, particularly folate and vitamin B6, may decrease the risk of death in individuals with PD. Postdiagnosis intake did not appear to impact survival.