BACKGROUND Esophageal pleural fistula (EPF) primarily arises as a complication of esophageal surgery, malignant tumors, or trauma. The high mortality rate associated with EPF underscores the critical need for early diagnosis and aggressive treatment, which often involves a multidisciplinary approach including thoracic drainage, broad-spectrum antibiotics, nutritional support, and often surgical or endoscopic intervention. Despite its clinical severity, a corresponding animal disease model for mechanistic and therapeutic research remains unavailable. AIM To establish a stable and reproducible EPF animal model using magnetic compression technology (MCT). METHODS EPF modeling surgery was successfully performed on 20 New Zealand white rabbits (weight: 2-3 kg) with our self-developed MCT device. Postoperatively, radiographic confirmation of magnet positioning was conducted within 24 hours. Fistula tract tissue samples were subjected to hematoxylin-eosin and Masson’s trichrome histochemical staining. Pathological specimens were intentionally withheld from a subset of rabbits (n = 8) to assess long-term stability; these animals were monitored for a prolonged period until postoperative day (POD) 30 before euthanasia, allowing for observation of chronic changes. RESULTS The rabbit model of EPF was successfully established. The average surgical time was 26.6 ± 4 minutes. Magnets were spontaneously excreted at 7.0 ± 0.7 days postoperatively (n = 18/20). Pleural abscesses developed in 14 rabbits (70%). All rabbits (n = 8) reached the 30-day endpoint without intervention. Data analysis revealed no significant correlation between the abscess size, surgery time, anesthesia time, magnet discharge time, and weight changes within POD 9. Gross pathology confirmed the formation of EPFs and pleural abscesses. Spontaneous healing tendencies were observed in a subset of fistulas (n = 6). Histological analysis revealed esophageal epithelial migration advancing toward the fistula lumen, whereas pleural abscess cavities contained extensive necrotic debris characterized by neutrophilic infiltration and fibrin deposition, collectively validating the model’s success. CONCLUSION The magnetic compression-derived rabbit EPF model exhibits high establishment success and prolonged viability, enabling robust pathophysiological research.

Gray-white matter contrast as an index of neurobiological alterations in anorexia nervosa.

People living with schizophrenia often experience high levels of stigma and are consistently at risk of internalizing it. Internalized stigma has a negative impact on several clinical and recovery outcomes in people with schizophrenia, but the effect of internalized stigma on important patient reported outcomes that are gaining increasing scientific and clinical relevance, such as life engagement, has not yet been extensively investigated. This study aims to investigate the relationship between several different socio-demographic, clinical, functional and medication-related variables and life engagement, with the hypothesis that internalized stigma, alongside other factors, could represent an individual predictor of reduced life engagement. Ninety-four participants diagnosed with schizophrenia were included in this cross-sectional study and were investigated with validated instruments assessing life engagement, schizophrenia symptoms severity, global clinical severity, internalized stigma, psychosocial functioning, antipsychotic-related side effects, attitude toward medications, and subjective well-being. Predictors of life engagement were assessed using a stepwise multivariate linear regression analysis. Greater global clinical severity (β = .685, p < .001), fewer years of education (β = -.240, p < .001), and greater stigma endorsement (β = .180, p = .005) emerged as individual predictors of reduced patient life engagement, explaining a large proportion of the observed variance (Adjusted R2 = .649, p = .001). Internalized stigma, among other well-recognized variables, appears to represent an individual predictor of worse patient life engagement in people living with schizophrenia. This finding should strengthen the notion that stigma, and internalized stigma in particular, represent important dimensions and treatment targets in the clinical management of schizophrenia, also in the perspective of improving patient-reported outcomes.

Background Withdrawal of life-sustaining treatments (WLST) is a leading cause of death in patients with severe acquired brain injuries (ABI). These decisions often occur under conditions of prognostic uncertainty and time-critical therapeutic windows and may be shaped by a complex interplay of factors. Elucidating these influences is essential to ensure that WLST decisions are made in an informed, unbiased, and transparent manner, and in alignment with wishes of the patients as well as their surrogate decision makers. Objective Conduct a scoping review of literature to identify, elaborate and analyze the various factors that influence decisions to WLST in adult patients with ABI. This review aims to provide a comprehensive understanding of current practices. Methods This scoping review, conducted according to PRISMA-ScR guidelines, examined literature on WLST in adult ABI, in whom brain death had not been declared. The search was conducted in PubMed and Web of Science, up to August 2024. Studies were screened by title/abstract and full text, with data systematically extracted. Only original, peer-reviewed articles focusing on WLST in adult severe ABI patients were included. N = 2,963 independent papers were initially found, of which N = 2,881 were excluded. A final count of N = 81 independent papers were included. Results Demographic factors (age, sex, race, socioeconomic status, etc.; n = 50), prognosis and clinical factors ( n = 59), family preferences ( n = 28), physician-related factors and institutional context ( n = 31), formal medical directive ( n = 13), ethical/legal frameworks ( n = 13), geographical differences ( n = 9) and religious beliefs ( n = 5) all played pivotal roles in WLST decisions. Older age consistently emerged as a determinant for WLST, as well as poor prognosis and white race. Conclusion WLST decisions are most often made for older adults, with age consistently identified as a key predictor, independent of the clinical severity of ABI. Additional factors such as race, socioeconomic status, advance directives, and variations in healthcare provider attitudes and institutional policies further contribute to disparities in WLST practices. Understanding these intersecting influences is essential to recognizing potential biases and promoting more equitable, patient-centered end-of-life decision-making.

Tendinopathy is a common musculoskeletal condition associated with persistent pain and functional limitation. Although vitamin D deficiency has been widely implicated in musculoskeletal disorders, its association with clinical outcomes in tendinopathy remains incompletely understood. This study investigated the association between serum vitamin D levels, clinical severity of tendinopathy, and the effects of vitamin D supplementation. This retrospective observational study included 350 patients with tendinopathy treated at a tertiary referral center between 2023 and 2025. Patients were classified into a vitamin D supplementation group (n = 221), receiving 50,000IU weekly for 4weeks followed by 2000IU daily for 8weeks, and a nonsupplemented group (n = 129). Pain intensity (VAS), functional status (0-100 scale), disease duration, chronicity, and ultrasonographic inflammation severity were evaluated. Patients with serum vitamin D levels below 20ng/mL exhibited significantly higher pain scores (7.3 ± 1.2 vs. 5.7 ± 1.3, p < 0.001), longer disease duration (8.2 vs. 4.1months, p < 0.001), and a higher prevalence of chronic tendinopathy (79.6% vs. 24.0%, p < 0.001). Following supplementation, serum vitamin D levels increased from 14.2 to 38.4ng/mL (p < 0.001), accompanied by significant reductions in pain and improvements in functional status compared with the nonsupplemented group (p < 0.001). Severe vitamin D deficiency (< 10ng/mL) was independently associated with a sevenfold increased likelihood of severe and chronic tendinopathy (OR: 7.2, p < 0.001). Vitamin D deficiency is strongly associated with greater clinical severity and chronicity of tendinopathy. Vitamin D supplementation is associated with meaningful improvements in pain and functional outcomes, suggesting that vitamin D status represents a clinically relevant and potentially modifiable factor in tendinopathy management. Clinical trial registration Clinical trial number: not applicable. This study was a retrospective observational study and was, therefore, not registered as a clinical trial.

Low sociodemographic index (SDI) countries bear a disproportionate burden of aneurysmal subarachnoid hemorrhage (SAH) yet remain underrepresented in medical research. A retrospective multicenter cohort of 1145 patients from tertiary centers in Brazil and the USA (2012-2024). Demographics, clinical severity (WFNS, modified Fisher scale, mFs), treatment modality, and outcomes were compared. Primary outcomes were in-hospital mortality and poor functional outcome (mRS > 2); secondary outcome was hospital length of stay (LOS). Multiple imputation was used for missing at random (MAR)-type missingness; adjusted models incorporated Bonferroni correction. Mean age was 54.5 ± 14.4years; 73.9% female. Racial/ethnic distribution was 49.6% White, 23.5% Black, 19.5% multiracial, 1.7% Asian, 5.6% other, and 0.2% Native American. Hypertension and smoking were more prevalent among American patients, Black and White individuals, respectively. Brazilian patients underwent microsurgery more often (61.9% vs. 92% endovascular in the USA) and had markedly longer time to treatment (77.7 vs. 4.3h; p < 0.0001).In-hospital mortality was higher in Brazil (23.4% vs. 13.4%; OR 1.98; p < 0.0001) and remained significant after adjustment. LOS was shorter in the USA (-5.4days; p = 0.0021). Black Brazilians had worse outcomes (OR 2.3; p = 0.0028), while White patients trended toward lower mortality overall (OR 0.7; p = 0.0350). Rehabilitation access differed sharply (39.8% vs. 0.8%). Poor long-term outcome was more common in Brazil (53.2% vs. 38.8%; p < 0.0001). Although USA patients had more vascular comorbidities, Brazilian hospitals experienced substantially higher mortality and long-term disability. These differences were consistent with disparities in care delivery and resource availability-reflected by longer treatment delays, differing treatment modalities, and limited access to post-acute rehabilitation-beyond measured patient-level risk, while also underscoring the importance of primary care-based prevention in high-income settings.

Objective The function of hypoxia-inducible factor-2α (HIF-2α) in ulcerative colitis pathogenesis is subject to ongoing debate, with conflicting reports indicating either disease-promoting or beneficial roles. This investigation was designed to define the precise contribution of T lymphocyte-restricted HIF-2α to UC development. Methods We immunohistochemically stained colonic biopsy tissues from human UC donors and healthy controls. A Lck-Cre-mediated Cre-loxP mediated HIF-2α conditional knockout mouse (HIF-2^ΔT/NKT) was generated and subjected to DSS-induced colitis induction. For mechanistic experiments, primary CD4 + T cells were transduced with lentiviral vectors harboring HIF-2-directed shRNA or cDNA. Protein-Protein interactions, signal transduction and cellular phenotype were assessed by Co-IP, qPCR array, multi-parametric flow cytometry, immunoblotting and histology. Results Immunohistochemistry demonstrated increased HIF-2α expression in colonic tissues from UC patients, but its expression levels in lymphocyte subtypes were inversely correlated with the clinical disease severity. Mice with T/NKT cell specific HIF-2 deletion were more susceptible to DSS colitis, associated with abrogated polarization of T helper cells towards the Th2 lineage. This led to upregulation of Il4 and Gata3 transcription, as well as increased production of IL-4 cytokine. Molecularly, HIF-2α bound directly to the proteolytically cleaved form of Notch1 intracellular domain (NICD), leading to a decrease in NICD-induced transcriptional activity. Consistent with this mode of action, forced HIF-2α expression in CD4 + T cells abrogatedJagged1-induced Th2 commitment in vitro . In contrast, HIF-2α deficiency enhanced Notch pathway signaling, promoted Th2 polarization and exacerbated colonic inflammation in vivo . Conclusion Our results establish a non-redundant protective function for T cell-intrinsic HIF-2α in ulcerative colitis. The protein directly engages Notch1-NICD to restrain Notch signal transduction, ultimately limiting pathological Th2 cell differentiation and ameliorating intestinal inflammation. These data reconcile prior contradictory findings by revealing a crucial cellular context-dependent mechanism.

Background/Objectives: Isolated methylmalonic acidemia (iMMA) is a rare autosomal recessive metabolic disorder caused by defects in methylmalonyl-CoA mutase (MCM) activity or in the biosynthesis of its cofactor, adenosylcobalamin. Mutations in five genes—MMUT, MMAA, MMAB, MMADHC, and MCEE—are known to underlie this condition. This study aimed to characterize the clinical features and molecular spectrum of iMMA in Malaysian patients of diverse ethnic backgrounds. Material and Methods: Patients with biochemical evidence suggestive of iMMA, including elevated propionylcarnitine (C3), increased C3/C2 ratio, and raised urine methylmalonic acid levels in the absence of hyperhomocysteinemia, were selected for genetic testing. Sanger sequencing was performed to identify pathogenic variants in the MMUT, MMAA, MMAB, MMADHC, or MCEE genes. Results: The cohort consisted predominantly of Iban patients (n = 5), with the remaining cases comprising one Malay and one Thai–Malay individual. Age at diagnosis ranged from Day 1 of life to 6 years. All 7 patients were confirmed to have iMMA through molecular analysis. A total of seven pathogenic or likely pathogenic variants were identified, including two novel MMUT variants (c.246_250delinsGA and c.1358G&gt;C), four known MMUT variants (c.560C&gt;G, c.693C&gt;G, c.982C&gt;T, c.1106G&gt;A), and one known MMAB variant (c.644+1G&gt;A). Clinical presentation and disease severity varied across cases, reflecting underlying genotypic heterogeneity. Conclusions: This study highlights the molecular diversity and clinical variability of iMMA in Malaysia. Our findings reinforce the importance of integrating metabolic screening with molecular diagnostics to identify disease-causing variants and guide patient management strategies effectively.

Subjective sleep quality predict clinical pain severity more strongly than polysomnographic parameters: Machine learning findings from a cross-sectional study.

Clinical characteristics and severity of primary ciliary dyskinesia caused by large homozygous deletion including exons 1-4 of DRC1: A multicenter retrospective cohort study.

Vitamin D Levels in SARS-CoV-2: Do Current Adequacy Thresholds Reflect Clinical Risk? Insights from a Large Turkish Cohort.

Biomarking MELAS with neurofilament light chain and circulating cell free mitochondrial DNA.

A critical concern of newborn screening (NBS) for very-long chain acyl-CoA dehydrogenase deficiency (VLCADD) is the difficulty of predicting clinical outcomes. To address this, we investigated neonatal C18:2-carnitine concentrations as a possible predictor of VLCADD phenotype. To investigate the impact of sex, gestational age (GA) at birth, sampling day and birth weight on C18:2-carnitine, we analyzed NBS-dried blood spots (DBS) from Dutch newborns born between 2018 and 2020 (n = 209.785). After normalization for resulting confounders, C18:2-carnitine concentrations were investigated in NBS-DBS (n = 15) and neonatal plasma (n = 35) of Dutch VLCADD-patients, and in German NBS-DBS (n = 6) and correlated with clinical severity and diagnostic assays. Results showed that C18:2-carnitine concentrations were affected by GA, sampling day, birth weight and, to a lesser extent, by sex. High C18:2-carnitine, normalized for GA, sampling day and birth weight, reliably identified all VLCADD-patients with (expected) severe phenotypes. The differentiating C18:2-carnitine was identified as linoleylcarnitine. In conclusion, this study shows that neonatal C18:2-carnitine concentrations can serve to predict disease severity directly after positive NBS for VLCADD. Patients with high C18:2-carnitine concentrations can be considered "severe" and require strict dietary treatment and close monitoring. Patients with low C18:2-carnitine concentrations can be identified as "mild" and only need preventive dietary measures.

Evaluation of blood-brain barrier integrity and clinical characteristics in autoimmune glial fibrillary acidic protein astrocytopathy.

Sennoside A alleviates fungal keratitis by modulating inflammation and immune responses through the caspase-1/GSDMD pathway.

Hemophilia A and hemophilia B are rare genetic disorders characterized by low plasma levels of coagulation factor VIII or factor IX, resulting in a bleeding tendency with a clinical severity proportional to the degree of the clotting factor deficiency. Although rare, hemophilia patients can paradoxically experience thrombotic events that complicate the clinical picture and the management by physicians operating at hemophilia treatment centers. Such thromboembolic complications, which can involve either the arterial or the venous districts, recognize various causes, including aging (due to the progress of care during the last three decades) and inherited and acquired (treatment-related) risk factors. These determinants often interact with each other to increase patients' susceptibility to thrombosis. In this narrative review, we summarize the current knowledge on the mechanisms, clinical presentation, and management of thrombotic complications in hemophilia patients.

Asymmetric Valve Reconstruction Surgery for Severe Chronic Lower Extremity Venous Insufficiency Caused by Post-Thrombotic Syndrome.

Beyond survival: Early markers of poor outcome in pediatric trauma.

Changing landscape of pediatric influenza in Northern Mexico: A comparative clinical and virological study.

Multi-omics dissection of Parkinson's patients in subgroups associated with motor and cognitive severity.