Citations

ABSTRACT Objective To estimate the pooled prevalence of lymphedema among adults with mucosal head and neck cancer treated with radiation therapy. Data Sources PubMed, Embase, Scopus, and Cochrane Library. Review Methods A comprehensive literature search of PubMed, Embase, Scopus, and Cochrane Library (2000–2025) identified cohort, case series, cross‐sectional, and clinical trial studies reporting lymphedema after radiotherapy for head and neck cancer. Logit‐transformed lymphedema prevalence was pooled using a DerSimonian‐Laird random‐effects model with Hartung‐Knapp‐Sidik‐Jonkman variance correction; statistical heterogeneity was evaluated using I 2 . This review was not prospectively registered. Results A total of 26 studies ( n = 3133 patients) met inclusion criteria. The pooled prevalence of lymphedema was 49% (95% CI, 36%–62%), with considerable heterogeneity (I 2 = 94%). Subgroup analyses yielded a pooled prevalence of 37% (12%–71%) for external and 45% (31%–60%) for internal lymphedema. Among studies reporting severity‐graded data, the pooled prevalence of clinically significant (grade ≥ 2) lymphedema was 32% (14%–59%). Lymphedema definitions and assessment methods varied across the included studies, most commonly employing clinical grading. Methodological quality was mixed, reflecting the predominantly retrospective, single‐arm nature of the available evidence. Overall certainty of evidence was very low. Funnel plot inspection and Egger's test suggested small‐study effects ( p = 0.06). Conclusion Lymphedema affects nearly half of patients following radiation for head and neck cancer. These findings may support routine surveillance, early identification, and timely referral for lymphedema management within survivorship care pathways. Future prospective studies should adopt standardized definitions and outcome measures to refine risk estimates and guide prevention strategies. Level of Evidence N/A.

ABSTRACT Background and Aims Autoimmune hepatitis is an immune‐mediated liver disease characterized by chronic inflammation and progressive fibrosis. Tissue‐resident memory T cells mediate organ‐specific immunity, but their role in autoimmune hepatitis remains poorly understood. We characterized tissue‐residency‐associated T‐cell populations and their cytokine profiles, assessed associations with disease severity and determined whether these signatures were reflected in peripheral blood. Methods Paired blood and liver samples were obtained from 19 patients with autoimmune hepatitis. Comparator cohorts included 20 patients with metabolic dysfunction‐associated steatotic liver disease and 20 surgical patients providing non‐inflamed adjacent non‐tumorous liver tissue. Multiparameter flow cytometry assessed tissue‐residency markers, T‐cell differentiation and cytokine production after polyclonal stimulation. Immune phenotypes were correlated with histological and clinical parameters. Results Autoimmune hepatitis was associated with compartment‐specific remodelling of T‐cell differentiation states and intrahepatic enrichment of CD8 + T cells expressing CD69, CD103 and CXCR6 relative to paired blood and comparator liver tissues. Intrahepatic CD8 + T cells exhibited an interferon‐γ‐dominant cytokine profile, whereas CD4 + T cells showed broader interferon‐γ‐, interleukin‐17A‐ and interleukin‐4‐associated responses. Despite the enrichment of tissue‐residency‐associated CD8 + T cells, cytokine‐producing CD8 + T‐cell populations with and without a tissue‐resident memory phenotype contributed comparably to the hepatic T‐cell compartment. Tissue‐residency‐associated phenotypes correlated positively with Ishak fibrosis stage, whereas the frequency of interferon‐γ‐positive intrahepatic CD8 + T cells correlated inversely with fibrosis. Conclusions Autoimmune hepatitis was characterized by intrahepatic accumulation of phenotypically distinct and functionally active CD8 + tissue‐resident memory T cells associated with fibrosis. This immune profile was not reflected in paired blood, indicating compartmentalized hepatic immune remodelling.

Cholera toxin (CTx) is a potent enterotoxin and widely used mucosal adjuvant, yet the acute host response to CTx itself, in the absence of a co-administered antigen, remains vague. In this study, we integrated physiological and metabolic phenotyping with intestinal transcriptomics, epithelial imaging, immune profiling, hepatic gene-expression analysis, and paired microbiome profiling to characterize the response to a single oral CTx exposure in mice. Within 24 h, CTx remodeled immune-cell composition in both epithelial and lamina propria compartments, with responses shaped by sex and genetic background. Recurrent changes included increased epithelial group 3 innate lymphoid cells, reduced lamina propria RORγt+ regulatory T cells, and decreased epithelial ILC1/NK cells in males of both strains. CTx also increased villus DCLK1+ tuft cells and reduced MUC2 immunoreactivity. Jejunal transcriptomics revealed induction of inflammatory defense, glycolytic, autophagy, and lipid-utilization programs together with suppression of proliferative and mitochondrial programs, consistent with coordinated stress adaptation. These local changes were accompanied by rapid restructuring of the fecal microbial community and by systemic hypometabolism, despite markedly different hypothermic responses across strains. CTx also elicited a selective hepatic stress and metabolic program, including conserved suppression of Cyp7a1 across sexes and strains. Together, these findings show that CTx alone rapidly reorganizes the intestinal immune, epithelial, metabolic, and microbial environment while suppressing whole-body metabolism. This work provides an integrated framework for understanding the acute host response to CTx and for interpreting its widespread use as a mucosal adjuvant.