Citations

Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are immune-mediated disorders of the gastrointestinal (GI) tract that, despite involving different tissues, are increasingly recognized to coexist. Epidemiologic studies demonstrate a bidirectional association, with patients affected by one condition showing a higher-than-expected prevalence of the other, suggesting shared susceptibility rather than incidental overlap. Genetic and epigenetic data support partial convergence in immune regulatory pathways, while epithelial barrier dysfunction and antigen-driven immune activation emerge as common upstream features. Overlapping cytokine networks, including IL-4, IL-13, and IL-23 signaling, contribute to chronic inflammation in both diseases, although differences in tissue environment and immune dominance give rise to distinct inflammatory phenotypes and clinical behavior. Clinical outcomes in patients with dual diagnoses appear heterogeneous, with available data suggesting neither uniformly worsened nor clearly protective disease courses, underscoring the complexity of shared immune mechanisms operating within different anatomic contexts. Beyond inflammatory activity, coexistence of EoE and IBD poses important nutritional and quality-of-life challenges, as overlapping dietary restrictions and chronic symptoms increase the risk of malnutrition, micronutrient deficiencies, and psychosocial burden. Current therapies remain disease-specific, with strong evidence supporting proton pump inhibitors, swallowed topical steroids, dietary therapy, and dupilumab in EoE, and biologics and small molecules targeting TNF-α, IL-12/23, IL-23, integrins, and JAK–STAT signaling in IBD, while evidence guiding treatment in patients with dual diagnosis remains limited. Together, current evidence supports a framework of shared immune machinery with tissue-specific expression that explains coexistence while preserving the distinct identities of EoE and IBD. By integrating emerging genetic, immunologic, and clinical evidence, this review aims to provide a framework for understanding and managing patients with coexisting EoE and IBD.

Abstract Purpose This study evaluates associations with suicidal ideation (SI) of impact of work on personal relationships (IWPR), self-valuation (SV), and imposter phenomenon and compares the SI point prevalence in physicians vs other workers. Method This study used American Medical Association Physician Professional Data to sample US physicians across different specialties between November 2020-March 2021. Of 7360 survey respondents, 6497 (88.3%) completed the SI question. A probability-based sample included 2508 nonphysician individuals from the US population employed at the time of survey administration, with 2501 workers (99.7%) completing the SI item. Logistic regression was used to evaluate the associations of occupational distress factors, including IWPR, SV, imposter phenomenon, and other factors, with SI before and after adjusting for depression and compare the risk of SI among physicians with other US workers. Results The study included 6497 physicians and 2501 workers in other fields. Adjusting for sex, age, relationship status, parenting status, and depression, each 1-point higher IWPR score (range, 0-10) was associated with 10% increased SI odds (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.05-1.15). Adjusting for the same variables, each 1-point higher SV score (range, 0-10) was associated with 10% lower SI odds (OR, 0.90; 95% CI, 0.85-0.95). The association between imposter phenomenon scores (range, 4-20) and SI was not statistically significant (OR, 1.03; 95% CI, 0.99-1.08). The unadjusted 1-year SI point prevalence was 6.6% (95% CI, 6.0%-7.4%) in physicians vs 5.6% (95% CI, 4.7%-6.6%) among workers in other fields (P = .09). In a multivariable model, workers in other fields with a bachelor’s or master’s degree had lower SI odds compared with physicians (OR, 0.64; 95% CI, 0.46-0.87). Conclusions IWPR and low SV are associated with SI among physicians, independent of depression. Development and evaluation of interventions designed to mitigate these factors in physicians may be warranted.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues. It is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths from leukemias in the United States. 1 The NCCN Guidelines Panel for AML convenes annually to update recommendations for the diagnosis and treatment of AML in adults. These recommendations are based on a review of recently published clinical trials that have led to significant improvements in treatment or have yielded new information regarding biologic factors that may have prognostic importance. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding the monitoring and management of measurable (minimal) residual disease.

Abstract Hematoxylin and eosin (H&E) slides are routinely available in cancer care, but molecular profiling often requires additional tissue processing and turnaround time. We introduce HistoMethyl, a DNA methylation-aware pathology foundation model that aligns whole-slide histopathology with matched genome-scale methylation beta-value profiles during pre-training while requiring only an H&E slide at inference. We evaluated HistoMethyl across four task groups: gene mutation prediction, morphology-associated classification, overall survival prediction, and direct DNA methylation beta-value recovery. Evaluation spanned TCGA cross-validation, a disease-held-out lower-grade glioma cohort, and external cohort validation in CPTAC glioblastoma and SurGen rectal adenocarcinoma, totaling 14 cancer cohorts and 81 gene mutation tasks. The best-performing configuration improved mean mutation AUROC by 5.03 percentage points. By converting DNA methylation supervision into an H&E-only representation, His-toMethyl could support an early molecular triage layer that helps prioritize cases for confirmatory sequencing, methylation profiling, immunohistochemistry, and molecular tumor board review. These image-only predictions are intended to accelerate downstream molecular testing and tissue allocation while leaving final diagnosis and treatment selection anchored in validated molecular assays.

Background: Alcohol-associated hepatitis (AH) is a severe inflammatory liver condition driven by dysregulated immune responses. CD8 T cells accumulate in the liver during AH, yet their functional role remains poorly defined. Methods: A murine NIAAA chronic-binge model with lipopolysaccharide (LPS) challenge was used. Single-cell RNA sequencing of liver and blood immune cells defined CD8 T cell subsets, followed by pathway analysis and reanalysis of human AH datasets. Spatial relationships were validated by immunohistochemistry of human AH liver tissue with CD8 T RM and liver sinusoidal endothelial cell (LSEC) co-staining. LSEC–CD8 T cell interactions were examined using in vitro co-culture, and signaling pathways were assessed by bulk RNA sequencing and phospho-protein analyses. IL15 function was evaluated by in vivo neutralization. Results: Single-cell RNA sequencing in the murine AH model revealed a distinct population of CD8 tissue-resident memory T cells (T RM ) with heightened activation and proinflammatory cytokine production. Analysis of human AH liver single-cell RNA sequencing data, along with immunohistochemistry validation, supported CD8 T RM enrichment in diseased tissue. IL15 emerged as a prominent pathway linked to T RM activation, and IL15 blockade reduced T RM abundance and attenuated EtOH/ lipopolysaccharide-induced liver injury. Mechanistically, LSECs not only provided a structural niche for T RM retention but also amplified IL15 signalling. In vitro, coculture experiments demonstrated that LSECs intensified activation in pre-stimulated CD8 T cells in a stimulus-dependent manner: under IL15 stimulation, LSECs boosted effector function without inducing cell death, whereas under T-cell receptor stimulation, LSECs drove hyperactivation and activation-induced cell death. Bulk RNA-seq and phospho-protein analysis identified the PI3K-AKT pathway as a shared pathway enhanced by LSEC coculture in activated CD8 T cells. These findings define a context-dependent mechanism in which LSECs promote IL15-driven signaling through AKT pathway amplification, promoting T RM persistence and inflammatory activity in AH. Conclusions: IL15-associated signaling within the hepatic microenvironment, shaped by LSEC-CD8 T-cell interactions, promotes activation and persistence of CD8 T RM cells in AH. Targeting the IL15-LSEC-AKT axis may disrupt pathogenic T RM niches and represent a promising therapeutic strategy for severe AH.

Breast size changes are common, but the underlying cause may be challenging to diagnose and requires a structured approach combining patient history, physical examination, and multimodality imaging to differentiate benign from malignant causes and improve patient outcomes.

Background and Objective: This study aimed to characterize clinical characteristics and visual outcomes of patients with hemorrhagic choroidal detachments. Patients and Methods: Single-center retrospective case series of patients with hemorrhagic choroidal detachments from January 1, 2003, to December 31, 2020 at Mayo Clinic. Patients were categorized as appositional or non-appositional based on ultra-sonography. Results: Among 39 cases with hemorrhagic choroidal detachments, 15 (38%) were appositional and 24 (62%) were non-appositional. There was a significant difference between the appositional and non-appositional groups in mean initial logMAR visual acuity (VA) (2.8 [ SD = 0.20] vs 2.2 [ SD = 0.78], P < .001). However, no difference was observed in final logMAR VA (1.9 [ SD = 1.2] vs 1.5 [ SD = 1.1], P = .30). Comparison between surgical ( N = 9) versus non-surgical ( N = 5) hemorrhagic appositional choroidal detachments cases revealed no differences in outcomes. Comparison between anticoagulated ( N = 21) versus nonanticoagulated ( N = 18) patients with hemorrhagic choroidal detachments also revealed no differences in outcomes. Conclusion: Patients with appositional and nonappositional hemorrhagic choroidal detachments did not differ significantly with regards to visual outcome. Surgical intervention was not associated with improved final vision in this cohort.

Abstract The minichromosome maintenance 2-7 (MCM2-7) proteins form a hexameric protein complex that is the structural core of replicative helicase, which is essential for accurate DNA replication. While their role in replication is well-established, the biological functions of excess chromatin-bound MCM2-7 proteins remain unclear. Here, we identify a transcriptional regulatory function of MCM2-7 through its interaction with nuclear factor κB (NF-κB) p65. We demonstrate that MCM2-7 proteins and NF-κB p65 reciprocally recruit each other to target gene promoters. Consequently, MCM2-7 proteins facilitate the localization of RNA Pol II to NF-κB target gene promoters and along the gene body, thereby promoting transcription of NF-κB target genes. These findings reveal MCM2-7 proteins promote NF-κB target gene transcription by facilitating p65 and RNA Pol II recruitment, offering a potential avenue for fine-tuning NF-κB target gene transcription.