Citations

Malignant hilar biliary obstruction (MHBO) is most commonly caused by cholangiocarcinoma or gallbladder cancer and frequently presents with obstructive jaundice, pruritus, and/or cholangitis. These symptoms impair performance status and delay the initiation of chemotherapy, making biliary drainage essential for both palliation and oncologic treatment. Endoscopic transpapillary biliary stenting via endoscopic retrograde cholangiopancreatography is the standard approach for biliary decompression. In patients with unresectable disease, either plastic or self-expandable metal stents may be used. Optimal outcomes are achieved when drainage encompasses more than 50% of functional liver volume, while atrophic segments should be avoided. When transpapillary access is not feasible or unsuccessful, alternative approaches such as percutaneous transhepatic biliary drainage or endoscopic ultrasound-guided biliary drainage may be considered. Adjunctive therapies, including photodynamic therapy and radiofrequency ablation, are being investigated to enhance local tumor control and prolong stent patency. With continued advances in stent technology, imaging modalities, and endoscopic techniques, the management of MHBO is expected to become increasingly individualized and effective.

Blood-brain barrier (BBB) disruption is a potentially deadly complication of numerous neurological diseases as diverse as cerebral malaria, dengue hemorrhagic fever, tauopathies, multiple sclerosis, schizophrenia, Parkinson’s disease, narcolepsy, and COVID-19. Neuroinflammation and immune cell infiltration are both drivers and consequences of BBB disruption. In this review, we will provide an overview of how brain-infiltrating T-cell responses engage the cellular components of the neurovascular unit (NVU), which regulates the BBB in preclinical models. This will provide context on how the immune system can contribute to vascular leakage and neuropathology in neurological diseases. We will discuss how discrete major histocompatibility complex (MHC) class I and class II molecules on NVU cell types govern T-cell entry, retention, and barrier disruption in neuroinflammatory diseases. Finally, we will summarize our current understanding of how discrete human leukocyte antigen (HLA) genes associate with specific neurological diseases characterized by neuroinflammation and BBB disruption.

Abstract Background Women with severe aortic stenosis (AS) are diagnosed later and experience poorer outcomes than men, partly because clinical approaches rely on 2D, valve-centric thresholds derived from male-predominant cohorts that underutilize information from 3D left ventricular (LV) geometry. We hypothesize that a sex-specific computational framework integrating statistical shape analysis (SSA) of pre-TAVR CT with machine learning would improve prediction of 1-year LV mass regression (LVMR). Objective To develop a computational framework leveraging 3D LV geometry and evaluate whether it improves sex-specific prediction of 1-year LVMR after TAVR. Methods We studied 339 patients with severe AS who underwent TAVR from 2013 to 2020 and had pre-TAVR CT and 1-year post-TAVR echocardiography. LV geometries were segmented into digital twins, and shape modes predictive of LVMR were extracted using SSA and partial least squares. These modes were incorporated into support vector regression models and compared with conventional echocardiographic predictors, including pre-TAVR LVEF, LVMI, and E/A ratio. Performance was assessed using RMSE and R 2 . Results After one year, 65% of patients showed positive LVMR, with median regression of approximately 10%; regression was significant overall and within each sex ( p < 0.001) and similar between sexes ( p = 0.99). Predictive shape modes differed by sex ( p < 0.01), with women showing more localized variation and men broader geometric gradients. Sex-specific shape modes outperformed general modes and clinical metrics, particularly in women (R 2 = 0.80, RMSE = 0.09 vs. R 2 = 0.59, RMSE = 0.13; clinical-only baseline R 2 = 0.16, RMSE = 0.22). In men, sex-specific modes also performed strongly (R 2 = 0.89, RMSE = 0.08). Conclusion In severe AS, 3D LV geometry predicts post-TAVR reverse remodeling more accurately than conventional metrics and may improve risk stratification, particularly in women.

Abstract Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) and alveolar macrophage pneumonia (AMP) are two rare but closely related conditions within the spectrum of smoking-related interstitial pneumonias. Both share characteristic histopathologic features, including the accumulation of pigmented alveolar macrophages alongside varying degrees of interstitial inflammation and fibrosis. RB-ILD is typically a localized, bronchiolocentric process often found in smokers, whereas AMP represents a more diffuse and clinically significant disease that may arise not only from tobacco smoke but also from other causes such as occupational exposures, autoimmune diseases, and drug reactions. This review highlights the clinical presentation, imaging findings, histopathology, and treatment of both entities, emphasizing their overlapping features as well as key distinctions. We further discuss the pathogenic mechanisms driven by cigarette smoke—including oxidative stress, immune activation, and fibrosis—that underlie these diseases. A clear understanding of the similarities and differences between RB-ILD and AMP is essential for accurate diagnosis, effective management, and prognostication, particularly in patients with a history of smoking and diffuse parenchymal lung involvement.

PURPOSE Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The higher incidence and earlier onset of HCC in sub-Saharan Africa suggest a potential role for a genetic predisposition. This study evaluated the association of TERT -rs2242652-(A), a variant linked to lower HCC risk, with HCC in populations from Ghana, Nigeria, and Cameroon, compared with a population from the United States. METHODS The study included 537 patients with HCC: United States (n = 348), Ghana (n = 79), Nigeria (n = 43), and Cameroon (n = 67). The control group had 2,872 cancer-free individuals: United States (n = 2,399), Ghana (n = 323), Nigeria (n = 85), and Cameroon (n = 65). Whole-exome sequencing was conducted using germline DNA, and data for TERT -rs2242652 were analyzed. Odds ratios (ORs) and 95% CIs were calculated using unconditional logistic regression. Chi-square tests assessed protective allele frequencies. RESULTS In the US cohort, TERT -rs2242652 was significantly associated with lower HCC risk (OR, 0.75 [95% CI, 0.58 to 0.96]; P = .02), with an allele frequency of 18.8% (15.4% in HCC cases v 19.3% in controls). In the combined sub-Saharan African population, no significant association was observed, but there was a trend toward decreased HCC risk (OR, 0.80 [95% CI, 0.53 to 1.22]; P = .29), with an allele frequency of 12.2% (10.6% in HCC cases v 12.9% in controls). Separate analyses of Ghanaian, Nigerian, and Cameroonian populations showed similar nonsignificant trends. The protective allele frequency in the combined African populations was significantly lower than in the US cohort ( P < .0001). CONCLUSION In sub-Saharan African populations, there was a lower frequency of the HCC protective allele TERT -rs2242652 compared with European Americans. These findings underscore the importance of multiethnic genetic studies in understanding population differences in HCC risk and developing prevention strategies.

Abstract Malignant histiocytic neoplasms (MHNs) are rare tumors derived from the mononuclear phagocyte system (MPS), encompassing histiocytic sarcoma, Langerhans cell sarcoma, interdigitating dendritic cell sarcoma, and other high-grade MPS lineage tumors. Despite advances in understanding histiocytic neoplasms, MHNs remain diagnostically challenging and lack standardized treatment algorithms. Current classification systems differ in lineage framing and fail to address mixed or ambiguous phenotypes, contributing to diagnostic uncertainty and inconsistent care. To address these gaps, the Histiocyte Society convened an international working group of pathologists and oncologists, including World Health Organization and International Consensus Classification contributors, to harmonize nomenclature, define minimum diagnostic criteria, and develop pragmatic treatment recommendations. Using a modified Delphi process and case-based review, the group formulated &gt;40 consensus statements spanning classification, pathology, molecular testing, clinical evaluation, and therapeutic strategies. Key recommendations include the adoption of a unified MHN designation, use of a minimum immunophenotypic panel, integration of broad molecular profiling, and the documentation of previous hematopoietic malignancy. Treatment algorithms emphasize surgical resection for unifocal disease and targeted therapy or immune checkpoint inhibition for multifocal disease when actionable mutations or programmed death ligand 1 expression are present. These consensus recommendations aim to reduce diagnostic ambiguity, standardize reporting, and improve outcomes for both pediatric and adult patients. Future priorities include international registries to refine risk stratification and biomarker-driven trials exploring targeted therapy, immunotherapy, and combination approaches.