Low-Dose Aspirin Use Does Not Increase Disease Activity in Pregnant Patients with Inflammatory Bowel Disease.

BACKGROUND: The adverse effects of non-steroidal anti-inflammatory (NSAID) drugs on the gastrointestinal system are well recognized, but the effect of NSAID use on disease activity patients with inflammatory bowel disease (IBD) remains unresolved. Low-dose aspirin (LDA) is recommended for all pregnant patients with risk factors for developing preeclampsia, including autoimmune conditions. As recognition of risk factors for preeclampsia improves, the preventative use of LDA is likely to increase. AIMS: To investigate if LDA use for prevention of preeclampsia increases the risk of disease activity in pregnant women with IBD. METHODS: Single-center retrospective cohort study of pregnant patients with IBD who delivered from 2012 to 2020, comparing those with and without LDA use. Primary outcome was odds of clinical IBD activity in patients in remission at time of conception. Secondary outcomes were rate of elevated inflammatory biomarkers, defined as C-reactive protein > 5 ug/mL or fecal calprotectin > 250 ug/g, and rate of preeclampsia. Univariate analyses tested for associations. RESULTS: Patients taking LDA were older (p = 0.003) and more likely to have chronic hypertension (p = 0.002), to have undergone in vitro fertilization (p < 0.001), and to be on biologics (p = 0.03). Among patients in remission at conception, there was no difference in clinical disease activity or biomarker elevation during pregnancy based on LDA use (OR 1.27, 95% CI [0.55-2.94], p = 0.6). Rates of preeclampsia were similar between groups. CONCLUSION: LDA use for preeclampsia prevention did not increase the incidence of disease activity in pregnant patients with IBD.

Personalised Medicine with IL-23 Blockers: Myth or Reality?

BACKGROUND AND AIMS: The medical management of inflammatory bowel disease [IBD] has become increasingly targeted, through the identification of specific immune mediators involved in its pathogenesis. IL-23 is an inflammatory cytokine involved in both innate and adaptive immunity, which 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 personalised medicine approach with these agents. METHODS: We reviewed and summarised 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 which 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.

Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity.

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 αvß6 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.

Peripartum Exposure to Biologic Therapy Does Not Impact Postpartum Wound Healing in Women With IBD.

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.

No prior studies have explored risk of postpartum wound infection in women receiving biologics in the peripartum period. We found no significant increase in risk of postpartum wound infection; however, internal penetrating Crohn's phenotype may be an important risk factor.

Near-peer teaching programme for medical students.

BACKGROUND: Near-peer teaching (NPT) is increasingly recognised as an effective method for teaching and learning within medical education. We describe a student-as-teacher programme developed for fourth-year students (MS4s) helping to deliver the second-year Respiratory Pathophysiology course at our medical school. METHODS: Twelve MS4s were paired with faculty members to co-teach one or two small group case-based sessions for second-year students (MS2s). Beforehand, MS4s attended an orientation session and workshop, reviewing skills and strategies for teaching effectively. Following each teaching session co-taught by MS4s, both MS4s and MS2s completed multiple-choice surveys evaluating the MS4's teaching skills and the experience overall. MS4s also wrote reflection essays describing their experiences. Faculty member co-teachers completed a 12-question feedback form for MS4s during the session. RESULTS: We received 114 post-session MS2 surveys, 13 post-session MS4 surveys and 13 post-session faculty staff evaluations. The majority of MS2s reported that MS4s enhanced their understanding of the material, and considered the quality of MS4 teaching to be 'good' or 'outstanding'. Nearly all of the MS4s enjoyed their experiences and believed that the programme improved their teaching skills. Time management was the most common challenge cited by both MS4s and faculty member co-teachers. DISCUSSION: 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.

The relationship between developmental assets and food security in adolescents from a low-income community.

PURPOSE: To explore the association between developmental assets (characteristics, experiences, and relationships that shape healthy development) and food insecurity among adolescents from a low-income urban community. METHODS: This mixed-methods study occurred in two phases. In phase 1, using a census approach, 2,350 6th to 12th graders from the public school district completed an anonymous survey that included the developmental assets profile (DAP), the youth self-report form of the Core Food Security Module, and demographic questions. Logistic and multinomial regression analyses determined independent associations between developmental assets and food security adjusting for demographics. In phase 2, 20 adult key informant interviews and four semistructured student focus groups were performed to explain findings from phase 1. RESULTS: On average, DAP scores were consistent with national norms. Food insecurity was prevalent; 14.9% reported low food security and 8.6% very low food security (VLFS). Logistic regression revealed that higher DAP was associated with lower odds of food insecurity (odds ratio [OR], .96; 95% confidence interval [CI], .95-.97); family assets drove this association (OR, .93; 95% CI, .91-.95). In multinomial regression modeling, these associations persisted, and paradoxically, higher community assets were also associated with VLFS (ORVLFS, 1.08; 95% CI, 1.04-1.13). Qualitative analyses suggested that greater need among VLFS youth led to increased connections to community resources despite barriers to access such as stigma, home instability, and cultural differences. CONCLUSION: Food insecurity is a pervasive problem among adolescents from low-income communities and is associated with lower developmental assets, particularly family assets. The fact that community assets were higher among VLFS youth underscores the importance of community-level resources in struggling areas.