B cells, which are critical for intestinal homeostasis, remain understudied in ulcerative colitis (UC). In this study, we recruited three cohorts of patients with UC (primary cohort, n = 145; validation cohort 1, n = 664; and validation cohort 2, n = 143) to comprehensively define the landscape of B cells during UC-associated intestinal inflammation. Using single-cell RNA sequencing, single-cell IgH gene sequencing and protein-level validation, we mapped the compositional, transcriptional and clonotypic landscape of mucosal and circulating B cells. We found major perturbations within the mucosal B cell compartment, including an expansion of naive B cells and IgG + plasma cells with curtailed diversity and maturation. Furthermore, we isolated an auto-reactive plasma cell clone targeting integrin αvβ6 from inflamed UC intestines. We also identified a subset of intestinal CXCL13-expressing TFH-like T peripheral helper cells that were associated with the pathogenic B cell response. Finally, across all three cohorts, we confirmed that changes in intestinal humoral immunity are reflected in circulation by the expansion of gut-homing plasmablasts that correlates with disease activity and predicts disease complications. Our data demonstrate a highly dysregulated B cell response in UC and highlight a potential role of B cells in disease pathogenesis.UC is a chronic inflammatory bowel disease (IBD) characterized by relapsing episodes of inflammation of the colonic mucosa 1 . In healthy individuals, intestinal B cell responses are dominated by the homeostatic generation of IgA-producing plasma cells (PCs) that promote under exclusive licence to Springer Nature America, Inc. 2022Reprints and permissions information is available at www.nature.com/reprints.

These data demonstrate that NPT is valuable for both MS2s and MS4s: MS2s benefited from the social and cognitive congruence afforded by near-peer teachers, whereas MS4s used this experience to build and enhance their skills as educators. These results support the continued involvement of MS4s in this second-year course, as well as broadening the scope of and opportunities for student teaching at our medical school and beyond. Near-peer teaching is recognised as an effective method for teaching and learning within medical education.

Our objective was to establish nomograms for fetal eye measurements from 12 weeks' gestation by using transvaginal and transabdominal high-resolution ultrasound techniques. A prospective cross-sectional study was performed on 450 normal singleton pregnancies between 12 and 37 weeks' gestation. Vitreous and lens circumferences were measured by transvaginal ultrasonography until 17 weeks, and by abdominal ultrasound between 18 and 37 weeks' gestation. Regression analyses were used to create nomograms, and several transformations were done to obtain linearity. Eye measurements of 12 fetuses at risk for ocular disturbances were plotted on the constructed nomograms. Linear relationships were fitted between vitreous (r2 = 0.79) and lens (r2 = 0.88) circumferences and gestational age. In addition, there was a significant correlation between these measurements and the biparietal diameter. Data of the fetuses at risk showed that disturbances in ocular growth were associated mainly with abnormal cerebral development. These normative data may be helpful in the prenatal diagnosis of suspected congenital syndromes that include, among their manifestations, ocular growth disturbances such as microphthalmos and anophthalmos.

Background and Aims The medical management of inflammatory bowel disease (IBD) has become increasingly targeted with the identification of specific immune mediators involved its pathogenesis. IL-23 is an inflammatory cytokine involved in both innate and adaptive immunity that has been identified as a therapeutic target in Crohn’s disease (CD) and ulcerative colitis (UC) through its upstream inhibition of the T helper 17 (Th17) pathway. We sought to review available data on the efficacy of IL-23 inhibitors in the treatment of IBD and the potential for clinical and molecular predictors of response to facilitate a personalized medicine approach with these agents. Methods We reviewed and summarized available clinical trial data on the use of the IL-23 inhibitors risankizumab, brazikumab, mirikizumab and guselkumab in the treatment of IBD, as well as the evidence from studies of these agents in IBD and other immune-mediated conditions that might inform prediction of response to IL-23 inhibition. Results Early clinical trials have demonstrated promising results following both induction and maintenance therapy with IL-23 inhibitors in CD and UC. Pre-and post-treatment levels of IL-22 and post-treatment levels of IL-17 have been identified as potential molecular predictors of response to therapy in several studies. No significant clinical predictors of response have been identified thus far. Conclusions IL-23 antagonism is a promising therapeutic approach in IBD. Further exploration of molecular and clinical predictors of response may identify patients most likely to benefit from these medications.

Background Inflammatory bowel disease (IBD) commonly affects women during childbearing years and often requires antepartum therapy. Data regarding effects of biologic exposure on delivery outcomes are limited. We explored whether peripartum biologic exposure impacts wound healing following cesarean section (C-section) and vaginal delivery (VD) in IBD patients. Methods Pregnancy and IBD data from the IBD Preconception and Pregnancy Planning (I-PrePP) Clinic database were collected and analyzed. Primary outcome was frequency of postpartum wound infection in women receiving peripartum biologics, defined as exposure in the third trimester and up to 2 weeks postdelivery relative to nonexposed patients. Secondary outcomes included effect of peripartum biologic timing and IBD phenotype on wound healing. Descriptive statistics summarized data using frequency for categorical variables and median for continuous variables. Univariate analyses tested associations when appropriate. Results Of 100 deliveries (interquartile range, 30–35; median, 33 years old), 58 were C-sections and 42 VDs. Peripartum biologic exposure occurred in 72% (42 of 58) and 57% (24 of 42), respectively. Median time from last dose to delivery was 6 (interquartile range, 4–8) weeks; 21 (32%) received biologics within 72 hours following delivery. Seven infections occurred following C-section among 5 unique CD patients. Peripartum biologic exposure was not associated with infection (4 of 66 [6%] exposed vs 3 of 34 [8.8%] nonexposed; P = .68), nor was disease activity (P = 1.0). Crohn’s disease (P = 0.02), internal penetrating phenotype (P < .001), prior IBD surgery (P = .03), and prior postpartum infection (P = .04) were associated with infection. Conclusions Peripartum biologic exposure does not impair postpartum wound healing; however, patients with more complicated disease phenotypes require close monitoring.