Indolent T-cell lymphoproliferative disorders of the gastrointestinal tract are rare clonal T-cell diseases that more commonly occur in the intestines and have a protracted clinical course. Different immunophenotypic subsets have been described, but the molecular pathogenesis and cell of origin of these lymphocytic proliferations is poorly understood. Hence, we performed targeted next-generation sequencing and comprehensive immunophenotypic analysis of 10 indolent T-cell lymphoproliferative disorders of the gastrointestinal tract, which comprised CD4+ (n=4), CD8+ (n=4), CD4+/CD8+ (n=1) and CD4-/CD8-(n=1) cases. Genetic alterations, including recurrent mutations and novel rearrangements, were identified in 8/10 (80%) lymphoproliferative disorders. The CD4+, CD4+/CD8+, and CD4-/CD8-cases harbored frequent alterations of the JAK-STAT pathway genes (5/6, 82%); STAT3 mutations (n=3), SOCS1 deletion (n=1) and STAT3-JAK2 rearrangement (n=1), and 4/6 (67%) had concomitant mutations in epigenetic modifier genes (TET2, DNMT3A, KMT2D). Conversely, 2/4 (50%) of the CD8+ cases exhibited structural alterations involving the 3' untranslated region of the IL2 gene. Longitudinal genetic analysis revealed stable mutational profiles in 4/5 (80%) cases and acquisition of mutations in one case were a harbinger of disease transformation. The CD4+ and CD4+/CD8+ lymphoproliferative disorders displayed heterogeneous Th1 (T-bet+), Th2 (GATA3+) or hybrid Th1/Th2 (T-bet+/GATA3+) profiles, while the majority of CD8+ disorders and the CD4-/CD8-disease showed a type-2 polarized (GATA3+) effector T-cell (Tc2) phenotype. Additionally, CD103 expression was noted in 2/4 CD8+ cases. Our findings provide insights into the pathogenetic bases of indolent T-cell lymphoproliferative disorders of the 4 gastrointestinal tract and confirm the heterogeneous nature of these diseases.Detection of shared and distinct genetic alterations of the JAK-STAT pathway in certain immunophenotypic subsets warrants further mechanistic studies to determine whether therapeutic targeting of this signaling cascade is efficacious for a proportion of patients with these recalcitrant diseases.

Recognizing the limited quality of current studies in the area of DFT testing and outcomes, available data suggest that DFT testing at the time of ICD implantation does not appear to predict total mortality and ventricular arrhythmias during follow-up. Large randomized controlled trials, adequately powered to detect clinical outcomes, are warranted.

Objective:To identify, categorize, and evaluate the quality of literature, and to provide evidence-based guidelines on virtual surgical education within the cognitive and curricula, psychomotor, and faculty development and mentorship domains.Summary of Background Data:During the coronavirus disease 2019 pandemic, utilizing virtual learning modalities is expanding rapidly. Although the innovative methods must be considered to bridge the surgical education gap, a framework is needed to avoid expansion of virtual education without proper supporting evidence in some areas.Methods:The Association for Surgical Education formed an ad-hoc research group to evaluate the quality and methodology of the current literature on virtual education and to build evidence-based guidelines by utilizing the SiGN methodology. We identified patient/problem–intervention–comparison–outcome-style questions, conducted systematic literature reviews using PubMed, EMBASE, and Education Resources information Center databases. Then we formulated evidence-based recommendations, assessed the quality of evidence using Grading of Recommendations, Assessment, Development, and Evaluation, Newcastle-Ottawa Scale for Education, and Kirkpatrick ratings, and conducted Delphi consensus to validate the recommendations.Results:Eleven patient/problem–intervention–comparison–outcome-style questions were designed by the expert committees. After screening 4723 articles by the review committee, 241 articles met inclusion criteria for full article reviews, and 166 studies were included and categorized into 3 domains: cognition and curricula (n = 92), psychomotor, (n = 119), and faculty development and mentorship (n = 119). Sixteen evidence-based recommendations were formulated and validated by an external expert panel.Conclusion:The evidence-based guidelines developed using SiGN methodology, provide a set of recommendations for surgical training societies, training programs, and educators on utilizing virtual surgical education and highlights the area of needs for further investigation.