RATIONALE: Follow-up of pre-licensure trial participants potentially informs a vaccine's long-term safety profile. DESIGN: This prospective study enrolled participants from the first clinical trials of ChAdOx1 nCoV-19 vaccine, many of whom subsequently received COVID-19 vaccines in the UK vaccination programme. Serious adverse events (SAEs) and adverse events of special interest (AESIs) were captured. AESI selection was based on Brighton Collaboration definitions. RESULTS: Between September 2021 and April 2022, 4470 participants enrolled (58% female, median age 50 years); 3845/4470 (86.0%) completed the study. Median follow-up was 11.77 months; total follow-up was 48,116 person-months. There were 174 SAEs and 71 AESIs (33 events recorded as both) in 195 participants, including 5 deaths. Immunology data were available for a small subset of participants; total IgG against trimeric SARS-CoV-2 spike protein tended to increase during the study. CONCLUSIONS: Although no emergent safety signals were detected, continued post-marketing surveillance remains imperative, particularly for neurological disorders. EUDRACT NUMBER: 2021-003382-36.

Previous research has explored distal extremity cooling as a strategy to enhance exercise performance. However, it remains unclear whether the intervention may aid in physiological or performance-oriented outcomes in an ecologically valid context. This study's primary purpose was to evaluate the effects of interset palm cooling (IPC) using a water cooling device during a full-body (FB), multi-set resistance training (RT) protocol on performance and perceptual measures. In a randomized crossover design, participants completed a familiarization session with 10RM testing and two randomized experimental sessions. Experimental sessions consisted of an FB RT protocol with either IPC (10-15°C) or control (CON) (22-28°C) applied for 2 min. between sets. Assessments included exercise performance (repetitions to failure, volume load, fatigue index, pre-post countermovement jump), subjective psychological markers (discomfort, session rating of perceived exertion), and physiological measures (heart rate, blood lactate, and tympanic temperature). Twelve trained females and 13 trained males completed the study. Bayesian analysis revealed low likelihood of any difference on any measured variables between conditions. The current study suggests that IPC is unlikely to enhance objective performance or improve subjective experience in hypertrophy-oriented RT.

Individuals diagnosed with psychotic disorders have reduced life expectancy, primarily attributed to cardiovascular diseases exacerbated by lifestyle habits and antipsychotic side effects. Poor diet quality, marked by low fruit and vegetable consumption and high discretionary food intake are also at play. Limited information exists on factors influencing healthy dietary habits in this population. This systematic review aims to analyze qualitative and quantitative data, from the past 20 years, on obstacles and facilitators to healthy dietary habits among individuals with psychotic disorders. PsycINFO, PubMed and Google scholar searches with these inclusion criteria were conducted: (a) peer-reviewed articles, (b) participants are adults, (c) at least 30% or more of the sample had a psychotic disorder, and (d) focus on obstacles, facilitators or interventions related to healthy dietary habits. Among 21 identified articles, 14 addressed obstacles 11 discussed facilitators and 12 proposed interventions. This review identified seven key obstacles (cost and accessibility, taste of healthy food, emotional role of food, social environment, cognitive challenges, symptoms, and medication) and four facilitators (social support, health-related motivation, improved self-perception and interventions). Notably, some factors, such as social support and neighborhood environment, emerged as both obstacles and facilitators depending on the context. Access to effective interventions, including educational resources, such as cooking and planning skills, and more research on group therapy and peer-based programs are discussed.

Acute ischemic and hemorrhagic stroke are among the leading causes of mortality and long-term disability worldwide. In addition to the results of randomized clinical trials, registry data reflecting real-world clinical practice play a key role in evaluating the quality of care. The STROKE platform of the Translational Neuroscience National Laboratory provides a comprehensive overview of the patient population treated at a Hungarian comprehensive stroke center. Our objective was to characterize the STROKE platform and summarize the findings of studies based on its data, to synthesize the main clinical and methodological conclusions, and to present its implications for quality improvement in Hungarian stroke care. The platform is based on standardized data collection of patients admitted to the Department of Neurology or Neurosurgery, University of Pécs within 24 hours due to acute ischemic stroke, transient ischemic attack, or hemorrhagic stroke. Demographic, clinical, imaging, laboratory, therapeutic, and 90-day outcome data were recorded. Outcomes were analyzed using multivariable linear and logistic regression models, propensity score matching, and comprehensive machine learning methods. Based on the platform, 77.0% of admitted patients had ischemic stroke, 16.9% transient ischemic attack, and 6.1% hemorrhagic stroke; the mean age was 72.0 ± 12.5 years. Among patients with ischemic stroke, 62.4% received recanalization therapy. The strongest independent predictors of 90-day functional outcome were neurological status at admission, premorbid functional status, extent of early ischemia, and age. The Stroke-SCORE, based on three parameters (age, premorbid status and neurological deficit), demonstrated strong predictive performance for 90-day outcome (area under the curve = 0.86). In patients undergoing reperfusion therapy, door-to-needle time <60 minutes and door-to-groin time <120 minutes were significantly associated with more favorable outcomes. After multivariable adjustment, neither anticoagulant nor antiplatelet therapy proved to be an independent adverse prognostic factor. The STROKE platform confirms that functional outcome is primarily determined by stroke severity, premorbid status, age, extent of ischemia, and timely, well-organized reperfusion care. Real-world data analyzed with advanced statistical methods substantially contribute to clinical decision-making, the reassessment of contraindications, and quality improvement in Hungarian stroke care. Orv Hetil. 2026; 167(29): 1131-1141.

Although the treatment of ischemic heart disease is becoming increasingly mature, the role of neuropeptide Y (NPY) in the pathophysiology after reperfusion still remains remains unanswered. In our study, we used a mouse model of myocardial ischemia/reperfusion (I/R) injury and demonstrated significant upregulation of NPY and its receptor NPYR1 after reperfusion. Over-expression of NPYR1exacerbates cardiac remodeling, manifested as worsening myocardial fibrosis (p < 0.01) and impaired left ventricular ejection fraction. On the contrary, NPYR1 knockdown weakened fibrosis response and improved cardiac function recovery. These findings were confirmed in HL-1 cell line subjected to hypoxia/reoxygenation model, where fibrotic markers of cardiomyocyte were similarly influenced by NPYR1 modulation. Our research findings indicate that NPY/NPYR1 signaling plays a pivotal role in maladaptive cardiac remodeling post I/R injury and is a promising therapeutic target for alleviating excessive fibrosis.

BACKGROUND: Cytoreductive nephrectomy (CN) combined with thrombectomy remains controversial for metastatic renal cell carcinoma with venous tumor thrombus (mRCC-VTT), and optimal patient selection remains undefined. METHODS: We retrospectively analyzed 238 patients with RCC-VTT treated at a single center between February 2006 and December 2023. Patients were stratified as non-metastatic surgical (nmRCC-VTT-S, n = 135), metastatic surgical (mRCC-VTT-S, n = 53), or metastatic non-surgical (mRCC-VTT-NS, n = 50). Inverse probability of treatment weighting (IPTW) was used to reduce measured confounding. Perioperative outcomes, OS, PFS, subgroup heterogeneity, and 3-month landmark sensitivity analyses were evaluated. RESULTS: After IPTW adjustment, perioperative outcomes were comparable between metastatic and non-metastatic surgical cohorts (all P > 0.05). In the metastatic cohort, surgery was associated with longer OS than non-surgical management (P = 0.027), and this association remained significant in the 3-month landmark analysis after re-estimating IPTW (P = 0.018). PFS showed no significant difference after primary IPTW adjustment (P = 0.517) and showed only a non-significant favorable trend after landmark IPTW adjustment (P = 0.064). Mayo level modified the association between surgery and OS (P for interaction < 0.001) and PFS (P for interaction = 0.034). For OS, surgery was associated with longer survival in Mayo 0-II thrombi (HR 0.56, P = 0.045), whereas patients with Mayo III-IV thrombi had worse outcomes after surgery (HR 6.22, P = 0.016). CONCLUSIONS: CN combined with thrombectomy appeared feasible and was associated with improved OS in selected patients with mRCC-VTT, particularly those with low-level thrombi. Mayo level should inform surgical decision-making, and systemic therapy-first strategies should be considered for high-level thrombi.

BACKGROUND: In patients with structural heart disease (SHD) and moderately impaired left ventricular ejection fraction (LVEF > 35%), data on outcomes after ventricular tachycardia (VT) ablation remain limited. This analysis focuses on VT recurrence after ablation in patients presenting with sustained VT and LVEF > 35% within a secondary-prevention population. OBJECTIVE: To evaluate procedural outcomes and long-term VT recurrence after catheter ablation in SHD patients with LVEF > 35%. METHODS: We analyzed 219 consecutive patients with SHD and LVEF > 35% undergoing VT ablation, including 89 with ischemic cardiomyopathy (ICM) and 130 with non-ischemic cardiomyopathy (NICM). Procedural characteristics, complications, and VT recurrence during follow-up were compared between groups. RESULTS: ICM patients were older, more frequently hypertensive, and had slightly lower LVEF than NICM patients. Ablation was predominantly endocardial in ICM, whereas combined endocardial-epicardial ablation was required in 28% of NICM patients (p < 0.001). Acute VT non-inducibility was achieved more frequently in ICM than in NICM (93% vs 67%; p < 0.001). Procedural complications were infrequent and comparable between groups (6% overall; p = 0.342). During follow-up, VT recurred in 35% of patients, more frequently in NICM than ICM (42% vs 25%; p = 0.004). Cardiomyopathy type emerged as the only independent predictor of VT recurrence (HR 2.312, CI 1.3-4.0, p = 0.004), while acute non-inducibility was associated with a lower recurrence risk. CONCLUSION: VT ablation in SHD patients with LVEF > 35% was associated with acceptable safety and moderate arrhythmia control. Outcomes were more favorable in ICM than in NICM, reflecting the heterogeneity of arrhythmic risk in this secondary prevention population.

UNLABELLED: In patients with atrioventricular (AV) block and left ventricular ejection fraction (LVEF) of > 50%, dual-chamber pacemaker (DCPM) implantation remains the standard of care. However, in this population the relationship between other baseline echocardiographic parameters and the development of post-pacing cardiomyopathy (PPCMP) remains poorly defined. OBJECTIVE: To identify preimplant echocardiographic parameters associated with the development of PPCMP in patients with normal LVEF undergoing DCPM implantation for AV block. METHODS: Among 140 consecutive patients who underwent DCPM implant for AV block between January 1st 2016 and December 31st, 2019, data from 111 patients with available follow-up through December 31, 2024, was retrospectively analyzed. PPCMP was defined as a 10% reduction in LVEF and/or absolute LVEF < 50% with an average ventricular pacing burden of ≥ 20%. RESULTS: Of 140 patients, 111 with complete data were included (mean age: 76 ± 10 years; 55% male and 88% white). Preimplant LVEF was 61 ± 4% with echocardiogram performed 2(0-26) days before DCPM implant. Over a mean follow-up of 4 ± 2.3 years, 46 patients (41%) developed PPCMP (LVEF%: 45[35-50] vs 62[58-64]; p < 0.001). Preimplant left atrial (LA) dimension (cm; 4.3[3.8-4.5] vs 3.8[3.5-4.3]; p = 0.03) and LA dimension index (mL/m; 38 ± 12 vs 32 ± 11; p = 0.008) were larger in patients who developed PPCMP. Among PPCMP patients, LVEF reduction correlated inversely with mitral annular septal and lateral E/e' ratios (r = -0.33, p = 0.03 and r = -0.34, p = 0.04, respectively), early diastolic mitral inflow velocity (r = -0.34, p = 0.02) and LA size (r = -0.35, p = 0.01). Larger LA size also correlated with higher E/e' ratios (r = 0.4, p < 0.02) but not with history of AF, HTN, obesity and mitral valve disease. In multivariable regression analyses, each 1-cm increase in LA size was associated with a 5.54-fold higher hazard of first heart failure (HF) admission (Cox, p = 0.0008) and a ~125% increase in total HF admissions (Poisson, p = 0.006) during the study period. CONCLUSION: Among patients with normal LV systolic function undergoing DCPM for AV block, pre-existing LV diastolic dysfunction, reflected by larger LA size, elevated E/e' ratios, and higher early diastolic mitral inflow velocity, is strongly associated with development of PPCMP. Preimplant recognition of these parameters may help identify patients who would benefit from upfront biventricular or conduction system pacing to mitigate the risk of PPCMP.

Ventricular fibrillation (VF) is the primary arrhythmia causing sudden cardiac death. While typically linked to structural heart disease, a significant subset of VF episodes-especially in younger individuals-is triggered by focal ectopy from the His-Purkinje system (HPS). The HPS possesses distinct electrophysiological properties that make it inherently susceptible to arrhythmogenesis. It serves a dual role, acting as both a primary source of initiating premature ventricular complexes through abnormal automaticity and triggered activity (early and delayed afterdepolarizations), and as a critical substrate maintaining VF via micro-re-entrant circuits. This narrative review comprehensively synthesizes current knowledge on Purkinje-triggered VF, from its epidemiology and clinical setting to its underlying pathophysiological and ionic mechanisms of arrhythmia initiation and perpetuation. Finally, we critically evaluate contemporary diagnostic and management strategies, contrasting conventional focal trigger-based ablation with evolving substrate-based approaches such as Purkinje "de-networking."

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a chronic autoinflammatory condition marked by recurring, painful sores in the mouth. It is often confused with Behcet's disease (BD), a rare systemic vasculitis that also presents with oral ulcers. Despite overlapping symptoms, BD has broader systemic implications, making an accurate diagnosis critical. This study aims to identify unique serum proteins that could reliably distinguish idiopathic RAS from BD. METHODS: We reanalyzed our previous mass spectrometry dataset comprising blood samples from 12 BD patients, 12 individuals with idiopathic RAS, and 21 healthy controls. Differentially expressed proteins (DEPs) related to RAS were identified and examined through Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathway enrichment. A protein-protein interaction (PPI) network was created to explore functional connections among the DEPs. Validation of three RAS-related proteins was carried out using enzyme-linked immunosorbent assay (ELISA) in a separate cohort of 26 RAS patients, 26 BD patients, and 30 healthy individuals. Their diagnostic utility was then evaluated receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 99 proteins showed differential expression in RAS samples but not in BD cases when compared to healthy controls-85 were upregulated, and 14 were downregulated. Enrichment analyses indicated these proteins are primarily involved in metabolic and infection-related pathways, particularly influencing keratinocyte differentiation and oxidative stress responses. PPI network analysis highlighted key metabolic and keratinocyte-related proteins as central hubs, suggesting a role in RAS pathology. ELISA validation confirmed significantly elevated levels of ANXA2, ENO1, and S100A7 in RAS patients compared to both BD patients and healthy subjects. CONCLUSION: Our findings identify a set of RAS-related serum proteins with potential diagnostic value. These serum proteins may enhance the clinical differentiation of RAS from BD, aiding in more accurate and timely patient care.

BACKGROUND: Large language models are increasingly applied in medical education and clinical decision support. However, comparative evaluations of their performance on pediatric content-spanning multiple subspecialties and question complexities-remain limited. This study sought to assess the performance of two advanced large language models, DeepSeek-R1 and GPT-4o, using a comprehensive set of Pediatrician Licensing Exam practice questions. METHODS: We administered 280 expert-validated pediatric questions covering 11 subspecialties and three levels of clinical complexity (A1: direct, A2: simple cases, A3: complex cases) to DeepSeek-R1 and GPT-4o. Each model was tested twice, with a 4-week interval. Performance metrics, including per-run accuracy, consistent accuracy (correct in both runs), aggregate accuracy (correct in either run), and inter-run consistency, were compared using chi-square tests and Bonferroni correction. RESULTS: DeepSeek-R1 outperformed GPT-4o in both runs (1 run: 90.7% vs. 81.8%, P=0.003; 2 run: 86.8% vs. 79.3%, P = 0.02). It also showed higher aggregate accuracy (92.5% vs. 85.7%, P=0.01) and consistent accuracy (85.0% vs. 75.4%, P = 0.01). Performance declined with increasing question complexity for both models, with DeepSeek-R1 demonstrating numerically higher accuracy across all question types. For consistent accuracy, DeepSeek-R1 achieved 89.2% vs. 79.2% on A1 questions (P=0.05), 83.8% vs. 71.6% on A2 questions (P=0.11), and 80.2% vs. 73.3% on A3 questions (P=0.36). At the subspecialty level, DeepSeek-R1 showed more uniform performance, achieving >90% consistent accuracy in four subspecialties: Neonatology (94.7%), Infectious Diseases (93.8%), Nephrology (91.9%), and Cardiovascular diseases (90%). In comparison, GPT-4o reached >90% consistent accuracy in three subspecialties-Genetics (100%), Infectious Diseases (100%), and Cardiovascular diseases (90%)-with greater variability across other domains. CONCLUSION: DeepSeek-R1 demonstrated higher accuracy than GPT-4o on pediatric questions. The observed variability across different runs warrants attention, particularly in contexts that require highly consistent and reproducible performance.

BACKGROUND: Postinfarction cardiac repair is orchestrated by macrophages that undergo sequential polarization from proinflammatory M1 to reparative M2 states. These macrophage subsets regulate inflammation resolution, angiogenesis, and fibrotic remodeling in the infarcted myocardium. Tumor-associated macrophages (TAMs) in breast cancer share transcriptional features with cardiac M2 macrophages, providing an opportunity for cross-disease comparison of shared immune programs. Understanding the molecular programs common to reparative macrophages across pathological contexts may identify candidate regulatory nodes for future therapeutic investigation. METHODS: Single-cell RNA sequencing data were obtained from GEO: GSE136088 (murine post-AMI cardiac macrophages), GSE176078 and GSE167036 (human primary breast cancer). Analyses included quality control, UMAP/t-SNE dimensionality reduction, graph-based clustering, diffusion pseudotime trajectory reconstruction, ligand-receptor communication analysis, principal component analysis, and cross-dataset correlation analysis. All analyses were performed in Python using scanpy with cross-species ortholog mapping in R (biomaRt, 14,892 one-to-one mouse-human orthologs) with downstream analyses in Python (scanpy). RESULTS: Post-QC datasets (GSE136088: ~14,900 cells; GSE176078: 100,064 cells; and GSE167036: 49,141 cells) were analyzed. UMAP and t-SNE resolved multiple macrophage and immune subpopulations across all three datasets. Diffusion pseudotime analysis reconstructed a sequential activation trajectory with an M1/M2 fate bifurcation. A 7-gene coexpression module (Spp1, Mif, Tgfb1, Arg1, Il10, Tnf, and Mrc1) was identified in cardiac macrophages and showed partially conserved expression patterns in breast cancer macrophage populations (GSE176078: Pearson r = 0.72; GSE167036: 6 of 7 genes detected, ARG1 not detected). Ligand-receptor communication analysis identified MIF-ACKR3, SPP1-CD44, and TGFB1-TGFBR2 as shared ligand-receptor pairs mediating macrophage-stromal communication in both cardiac and tumor microenvironments. Cross-dataset Pearson correlation of the 7-gene module between cardiac macrophages and breast cancer macrophage populations reached = 0.72 (GSE176078) and = -0.07 (GSE167036, n.s.). CONCLUSION: This single-cell transcriptomic analysis characterizes macrophage polarization programs in postinfarction cardiac repair and evaluates their partial conservation in breast cancer. The identified 7-gene module showed moderate cross-dataset correlation with GSE176078 ( = 0.72) but was not replicated in GSE167036, where M2-polarized macrophages were not detected. The MIF-ACKR3 signaling axis represents a computationally derived hypothesis for future experimental validation. These findings highlight both shared features and context-dependent differences in macrophage polarization across disease states, underscoring the need for functional studies in paired cardiac and tumor models.

BACKGROUND: Individuals with hypertension are at risk to reduced quality of life (QoL). Explainable machine learning (ML) can be used for domain-specific risk stratification and prioritization of modifiable determinants of low QoL. OBJECTIVE: To train ML classifier algorithms for QoL risk stratification in hypertension, where meaningful determinants were explored through Shapley additive explanations (SHAP). METHODS: Data from hypertensive individuals (n = 534) completed WHOQOL BREF, Quick Physical Activity Rating, Morisky Medication Adherence Scale 8, and standardized questionnaires for acceptance and knowledge were analyzed utilizing Decision Tree, Gradient Boosting, XGBoost, AdaBoost, Random Forest, and Naive Bayes ML classifiers. The trained ML algorithms were evaluated using stratified 10-fold cross-validation, where the stability was examined using rank-based metrics. SHAP were applied to the gradient boosting, as the most stable model. RESULTS: For physical QoL, Random Forest (AUC 0.850; sensitivity 0.835; specificity 0.738) and Gradient Boosting (AUC 0.850; sensitivity 0.801; specificity 0.764) showed good reduced QoL identification. For psychological domain, best classifications were obtained from Gradient Boosting performed best (AUC 0.833; sensitivity 0.818; specificity 0.651) and XGBoost (AUC 0.831; sensitivity 0.824; specificity 0.660), with the former observed as the most stable SHAP analysis identified acceptance and medication adherence as the dominant shared drivers of risk across both QoL domains. Physical QoL risk was further influenced by physical activity-related factors, whereas Psychological QoL risk showed additional contributions from age and educational attainment. CONCLUSION: Ensemble tree-based classifiers, particularly Gradient Boosting, had the most optimal performance in discriminating reduced and good QoL. Acceptance and medication adherence are the most influential shared drivers of risk, while physical activity, age, and educational attainment contributed to domain-specific heterogeneity.

BACKGROUND: Coronary heart disease is a leading cause of death worldwide, making early risk identification essential. This study compares the predictive performance of FINDRISC and the Framingham model in the Kharameh Cohort. METHODS: This prospective cohort study included 9,469 participants aged 40-70 years from the Kharameh cohort (a branch of the PERSIAN study) who were free of CHD at baseline and were followed for 6 years to identify incident CHD events. Data on FINDRISC components, as well as laboratory and demographic variables, were collected at enrollment. Logistic regression models were developed using the total FINDRISC score and its individual items, and their predictive performance was compared with the Framingham non‑laboratory risk score using 10‑fold cross‑validation and metrics including AUC‑ROC, sensitivity, and specificity. RESULTS: During a six‑year follow‑up of 9,469 participants (mean age 51.6 years, 55.6% female), 540 incident CHD events (5.7%) were identified. The total FINDRISC score was significantly higher in individuals who developed CHD (11.35 vs. 9.59, P<0.001). However, the total FINDRISC score alone showed weak discriminatory power (AUC=58.6%, 95% CI: 55.9-61.3%). An item-based FINDRISC model demonstrated improved performance (AUC=71%, 95% CI: 68.9-73%), and further enhancement with gender, systolic blood pressure, and total cholesterol yielded the highest predictive accuracy (AUC=75.2%, 95% CI: 73%-77%). The non‑laboratory Framingham risk score (AUC=73.3%, 95% CI: 71.4-75.1%) showed similar discriminatory performance compared with the enhanced item‑based FINDRISC models. CONCLUSION: The enhanced item-based FINDRISC model, incorporating gender and systolic blood pressure showed comparable performance to the Framingham non-laboratory model, providing a simple, accessible screening tool for the Iranian population.

BACKGROUND: Sodium-glucose transporter 2 (SGLT2) inhibitors have shown significant cardiovascular benefits in heart failure (HF) patients with diabetes mellitus or chronic kidney disease. However, their safety and efficacy in non-diabetic patients without HF presenting with acute myocardial infarction (AMI) remain understudied. METHODS: Databases including MEDLINE, Scopus, Cochrane Library, and ClinicalTrials.gov were queried through August 2025 to identify randomized controlled trials (RCTs). Data were pooled using a random-effects model using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). RESULTS: Five RCTs involving 9,135 patients (SGLT2i: 4,581 and placebo: 4,554) were included. On pooled analysis, SGLT2 inhibitors were associated with significantly reduced first HF hospitalization (RR: 0.74, p=0.02), improved LVEF (MD: 2.08; p=0.002), and reduced NT-proBNP levels (MD: 12.81; p < 0.0001). No significant differences were noted in all-cause mortality and the composite of first HF hospitalization with all-cause mortality. CONCLUSION: In non-diabetic patients without HF, SGLT2 inhibitors significantly reduce the first HF hospitalization and improve LVEF following AMI. The findings of this meta-analysis suggest that future research should evaluate the cardiovascular benefits of SGLT2 inhibitors in this patient population.

Neutrophilic dermatoses, including pyoderma gangrenosum (PG) and Sweet syndrome (SS), are inflammatory disorders characterized by neutrophilic infiltration without infection. Conventional therapies are often inadequate. We aim to evaluate the efficacy and safety of JAK inhibitors (JAK-I) in the treatment of PG and SS. The study was registered (PROSPERO-CRD420251113331), and a relevant search was conducted on PubMed/MEDLINE, Scopus, Web of Science, and Embase until July 27, 2025. Included studies were English language reports describing PG or SS treated with any JAK-I or cases of JAK-I-associated SS. Reviews, animal studies, and reports with insufficient clinical data were excluded. Four reviewers independently screened records. Data extraction included demographics, comorbidities, treatment regimens, outcomes, and adverse events. Risk of bias was assessed using the National Heart, Lung, and Blood Institute and Murad et al. tools through discussion-based consensus. Due to heterogeneous outcome definitions and small sample sizes, only descriptive synthesis was performed. Fifty-four reports, including 70 patients (59 PG, 5 SS) treated with JAK-I and 6 JAK-I-associated SS, were included. Across 43 PG studies, five JAK-Is-tofacitinib, upadacitinib, baricitinib, abrocitinib, and ruxolitinib-produced 33 complete and 26 partial responses. Twenty-six patients (44.1%) received monotherapy. Most patients (51/59; 86.4%) had at least one comorbidity. Adverse events occurred in 6 (10.1%), including anemia, hypertension, renal dysfunction, fatigue, and acneiform eruption. Among 11 SS reports, all 5 treated patients achieved complete resolution with baricitinib, ruxolitinib, or filgotinib. Six additional cases described ruxolitinib-associated SS, generally improving with corticosteroids or drug withdrawal. Most studies were rated good quality. Evidence is limited to small cases with heterogeneous outcome definitions, variable dosing, and inconsistent follow-up. JAK-Is are associated with clinical improvement in PG and selected SS cases and may serve as useful adjunct therapies, though caution is needed in patients with hematologic malignancies. Larger controlled studies are needed.

CTNNA3 encodes T-catenin, an intercalated disc (ICD) protein essential for cardiomyocyte coupling. Human omics studies have shown reduced CTNNA3 expression, ICD ultrastructural disruption, and dilated cardiomyopathy (DCM)-associated hyperphosphorylation of T-catenin. Direct RNA-level evidence linking biallelic CTNNA3 variants to human cardiomyopathy has been lacking. Clinical exome sequencing was performed in a 21-year-old man with DCM, severe left ventricular systolic dysfunction (LVEF 20%), and atrial fibrillation (AF). The identified homozygous variant (NM_013266.4 : c.1733 - 1G > C) was assessed with multiple splicing prediction tools and functionally validated via a minigene hybrid assay in HEK293 cells. Splicing predictors indicated loss of the canonical acceptor site. The minigene assay confirmed three aberrant transcripts: out-of-frame exon 13 skipping with a premature stop codon, a 24-nucleotide in-frame deletion, and partial intron retention, resulting in a possibly nonfunctional protein. Under guideline-directed medical therapy, LVEF normalized, but a persistent arrhythmic phenotype remained, with recurrent AF, frequent ventricular ectopic beats, and nonsustained ventricular tachycardia. We report a recessive form of DCM associated with a homozygous canonical splice-site variant in CTNNA3, encoding the ICD protein T-catenin. Our results are consistent with human omics studies. Altogether, these data provide evidence that biallelic CTNNA3 splice-disrupting variants can cause human cardiomyopathy driven by ICD dysfunction. The dissociation between ventricular recovery and persistent arrhythmia highlights the complex phenotypic spectrum of CTNNA3-related disease.

PURPOSE OF REVIEW: Sarcoidosis is associated with an increasing global burden, driven by rising prevalence, severe organ involvement, treatment-related morbidity, and substantial impairment in quality of life (QoL). Despite advances in diagnostics and therapeutics, important barriers continue to limit timely, equitable, and patient-centered care. This review highlights three common challenges in sarcoidosis management and outlines pragmatic approaches to address them, using a patient-centered framework that emphasizes whether patients feel better, function better, and are able to thrive. RECENT FINDINGS: Recent evidence confirms persistent delays in diagnosis, limited access to sarcoidosis expertise, and inequities in referral to specialized care. Growing data indicates that chronic glucocorticoid use contributes substantially to long-term morbidity, supporting glucocorticoid stewardship and earlier use of steroid-sparing therapies. In parallel, patient-reported manifestations, such as fatigue, cognitive dysfunction, dysautonomia, and small fiber neuropathy-related symptoms, are increasingly recognized as major determinants of functional impairment and health-related QoL inadequately captured by traditional objective disease markers. Recent expert recommendations emphasize practical, implementable strategies applicable across both specialist and nonspecialist settings. SUMMARY: Improving sarcoidosis care requires a pragmatic, holistic approach that prioritizes timely diagnosis, equitable access to expertise, minimization of glucocorticoid-related harm, and systematic assessment of patient-reported outcomes. Collectively, these strategies support a patient-centered framework that evaluates treatment success not only by disease control but also by whether patients feel better, function better, and are able to thrive in the context of optimal health, meaningful social connection and contribution. This approach aligns care with patient priorities and supports individualized, shared decision-making.

Nutrition plays a pivotal role in determining the health outcomes of people living with human immunodeficiency virus (PLHIV), particularly those undergoing antiretroviral therapy. This narrative review explores the bidirectional relationship between HIV and nutritional status, highlighting both undernutrition and overnutrition as significant concerns. Evidence suggests that deviations from recommended dietary allowances negatively impact CD4 counts, body mass index, hemoglobin levels, and overall quality of life (QoL). Multiple studies reveal a growing prevalence of obesity among PLHIV, particularly among males, raising concerns about comorbidities such as cardiovascular disease and diabetes. Conversely, undernutrition remains a persistent issue in resource-limited settings and is associated with increased mortality and opportunistic infections. Socioeconomic factors, food insecurity, education, and behavioral practices strongly influence dietary habits and nutritional outcomes. In addition, studies from diverse geographic regions underscore the role of nutrition in modulating QoL, with mental health, social support, and education emerging as key determinants. A comprehensive, context-sensitive approach to nutrition is vital for optimizing HIV care and long-term management.

BACKGROUND Aorto-aortic extra-anatomical bypass is a specialized surgical intervention primarily used to manage complex vascular complications, including stent graft infections after endovascular aortic repair. Stent graft infection is a rare but severe complication associated with high morbidity and mortality, which requires prompt treatment to prevent life-threatening sequelae such as pseudoaneurysm formation, aortic rupture, or fistula formation. CASE REPORT We describe 2 young male patients who developed infected thoracic aortic stent grafts after aortic arch debranching and endovascular repair. The first patient, a 37-year-old man with a history of traumatic aortic isthmus transection managed via tube interposition grafting 10 years earlier, presented with a proximal anastomotic pseudoaneurysm; he subsequently underwent arch debranching and endovascular stent grafting. He was later readmitted with systemic infection and mediastinal hematomas indicative of graft infection. The second patient, a 34-year-old man with Behçet disease and an aortic arch aneurysm, presented with an infected mediastinal hematoma involving the aortic stent graft after arch debranching and stent grafting. Both patients underwent stent graft explantation and extra-anatomical ascending-to-descending aorto-aortic bypass under peripheral cardiopulmonary bypass with deep hypothermic circulatory arrest. Both patients survived the complex aortic procedure and remained clinically stable at 38 and 17 months of follow-up (after the most recent procedure), respectively. One patient required additional wound management for a surgical site infection; the other underwent delayed repair of an ascending aortic pseudoaneurysm. CONCLUSIONS This case series demonstrates the feasibility of aorto-aortic extra-anatomical bypass as a potentially life-saving intervention for aortic endograft infection when perioperative management is optimized.

BACKGROUND: Pulmonary sequestration (PS) is a congenital lung malformation, which is defined by an anomalous arterial supply from systemic circulation and an absence of communication with the tracheobronchial tree. It is further divided into intralobar and extralobar PS. Pulmonary sequestrations are usually treated surgically, especially if they are symptomatic. Malignant tumors are rarely found within such malformations, mainly adenocarcinomas. We report a case of a malignant melanoma found in a patient operated for intralobar pulmonary sequestration, which is, to the best of our knowledge, the first reported case of a malignant melanoma occurring within a pulmonary sequestration. CASE PRESENTATION: We present a case of an 84-year-old male patient who underwent surgical treatment for a symptomatic pulmonary sequestration. The patient was first diagnosed with an intralobar PS two years prior to the surgery by a multislice computed tomography (MSCT) scan. It was located in the left lower lung lobe and had an anomalous arterial supply from an artery arising from the thoracic aorta. Two years later, the patient presented twice to the emergency department with hemoptysis and was thereafter referred to the thoracic surgeon. Another MSCT scan conducted before the surgery showed a newly formed solid lesion within the previously described PS. The thoracic surgeon therefore performed a left lower lobectomy and lymphadenectomy via thoracotomy. Histopathological analysis discovered two melanomas in the specimen, measuring 6 × 5 × 4 cm and 1.7 × 1.7 × 1.5 cm. The patient was referred to an oncologist. A positron emission tomography/computed tomography (PET/CT) scan, along with other diagnostic procedures, didn't show any other signs of malignant disease elsewhere in the body. Several other skin lesions were excised and biopsied, but none have turned out to be melanomas. A year after surgery, the disease disseminated. CONCLUSIONS: Although the origin of the melanoma in this case could not be definitively established, this report demonstrates that pulmonary sequestration may harbor malignant neoplasm and highlights the diagnostic challenges in distinguishing primary pulmonary melanoma from metastatic melanoma. The appearance of a new solid lesion within a pulmonary sequestration necessitates careful evaluation and consideration of surgical resection.

BACKGROUND: Tobacco use is a major risk factor for ischemic heart disease (IHD), substantially increasing the likelihood of myocardial infarction, stroke, and premature mortality. This study examined U.S. trends in IHD mortality with documented tobacco use disorder from 1999 to 2023. METHODS: CDC mortality data for adults aged ≥ 25 years with IHD (ICD-10 codes: I20-I25) and documented tobacco use (ICD-10 code: F17) listed as contributing causes of death were analyzed. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated. Joinpoint regression was used to estimate annual percent change (APC) and average annual percent change (AAPC). RESULTS: From 1999 to 2023, 1,497,919 deaths were reported. The AAMR rose from 3.90 to 32.37 (AAPC: 10.71; p < 0.01). Males had a higher AAMR (39.68; AAPC: 10.72) than females (14.05; AAPC: 10.77). Non-Hispanic (NH) Whites had the highest AAMR (26.86), followed by American Indians (25.43), NH Blacks (19.77), and Hispanics (10.38). The Midwest had the highest regional AAMR (32.96). Most deaths occurred in inpatient facilities (27.9%). Adults aged ≥ 65 years had the highest mortality rate (CMR: 92.16). Rural areas exceeded urban (35.73 vs. 22.95). CONCLUSION: IHD mortality with documented tobacco use has risen sharply, disproportionately affecting older adults, males, rural areas, the Midwest, and NH Whites.

BACKGROUND: Infective endocarditis (IE) complicated by aortic root abscess, fistulation and multivalve involvement is rare but carries high mortality. Fistulation from the left ventricular outflow tract (LVOT) to the right atrium (RA) represents an exceptionally uncommon sequela due to extensive perivalvular tissue destruction. Early surgical intervention remains crucial, but postoperative outcomes vary widely depending on host factors, organism control and the feasibility of durable reconstruction. CASE PRESENTATION: We report two cases of severe aortic valve endocarditis with aortic root abscess and acquired LVOT-RA fistula. The first patient had native-valve Streptococcus mitis endocarditis and underwent aortic and tricuspid valve replacement with double CardioCel patch repair of the fistula. He recovered after transient renal and hepatic dysfunction and completed six weeks of intravenous ceftriaxone. The second patient had prosthetic aortic valve endocarditis with aortomitral curtain destruction, pseudoaneurysm, severe malnutrition, and tricuspid involvement. He underwent redo sternotomy, aortomitral curtain reconstruction, double patch fistula repair, and triple bioprosthetic valve replacement. Although the initial repair was technically satisfactory, he later developed severe mitral paravalvular regurgitation with recurrent Staphylococcus haemolyticus bacteremia and died after deterioration with sepsis and multiorgan dysfunction. CONCLUSION: These cases illustrate the range of outcomes after complex endocarditis surgery. Patch-based reconstruction may be appropriate when radical debridement leaves sufficient tissue for secure prosthetic seating, whereas extensive prosthetic infection, malnutrition, recurrent bacteremia, and tissue friability increase the risk of late mechanical failure.

BACKGROUND: DOX, an anthracycline antibiotic, is extensively utilized in the treatment of various solid tumors and hematological malignancies but is constrained by its cumulative cardiotoxicity. PDA has emerged as a promising drug delivery platform owing to its superior biocompatibility, pH-responsive drug release capability, and multifunctional surface properties.The FH peptide, which specifically targets Tenascin-C overexpressed in DOX-injured myocardium, offers a promising strategy to enhance cardiac-specific drug accumulation. METHODS: In vitro experiments were performed using primary neonatal mouse cardiomyocytes. Cardioprotective efficacy was evaluated in an acute DOX-induced myocardial injury mouse model, and antitumor activity was assessed in a 4T1 tumor-bearing mouse model. RESULTS: Our comprehensive analysis, including spectroscopic methods and physicochemical characterization, confirmed the successful integration of Dex and FH onto the PDA platform. Both in vitro and in vivo studies demonstrated that PDA-Dex/FH effectively treats DOX-induced cardiotoxicity, with FH incorporation enhancing cardiac targeting while preserving DOX's antitumor efficacy. CONCLUSIONS: we demonstrated that, under the experimental conditions of this study, PDA-Dex/FH not only markedly mitigates myocardial injury with enhanced cardiac accumulation but also retains the chemotherapeutic efficacy of doxorubicin, thereby.