Publications

INTRODUCTION: Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, often affects individuals during their peak reproductive years. Female patients with IBD face unique challenges across the reproductive years, from fertility and conception to delivery and lactation. Despite increasing awareness, knowledge gaps remain regarding optimal management during pregnancy and postpartum. This review outlines these challenges and provides a practical, evidence-based approach across reproductive stages.

AREAS COVERED: This review summarizes care for IBD in reproductive years, including preconception counseling, pregnancy management, delivery planning, surgical and perianal disease considerations, postpartum care, breastfeeding, and infant vaccination after biologic exposure.

EXPERT OPINION: Managing IBD from preconception through the postpartum period requires early planning, multidisciplinary coordination, and patient-centered care. Disease remission is the strongest predictor of maternal and fetal outcomes. Most IBD therapies, including biologics, are safe in pregnancy and lactation and should continue, except small molecules, which remain contraindicated due to teratogenic risk or limited safety data. Rotavirus and other vaccinations can generally be administered on schedule in infants exposed to biologics in utero. A proactive, treat-to-target strategy throughout pregnancy, combined with close postpartum monitoring, can prevent disease flares and support optimal outcomes for both mother and child.

BACKGROUND & AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are prescribed for type 2 diabetes mellitus (T2DM) to improve glycemic control and lower cardiovascular risk. Although the impact of GLP-1RAs on gastrointestinal motility has been characterized, their association with mucosal damage, such as in peptic ulcer disease (PUD), has received little attention.

METHODS: We conducted a nationwide retrospective study of adults with T2DM using the "All of Us" National Institutes of Health database, including a sub-group analysis of adults who were newly initiated on GLP-1RAs or insulin as second-line therapy. Our primary outcome was the odds of PUD diagnosis after time-dependent use of GLP-1RAs, adjusting for use of insulin, nonsteroidal anti-inflammatory drugs, steroids, and proton pump inhibitors and other confounders. In a subgroup analysis, we used a weighted, time-varying Cox proportional hazards model, while accounting for the competing risks of death and gastrectomy.

RESULTS: A total of 66,102 participants with T2DM were identified and included in our primary analysis. After adjusting for possible confounders, GLP-1RAs were associated with significantly lower odds of PUD diagnosis (adjusted odds ratio 0.56; 95% confidence interval, 0.45-0.71; P < .001). Our subgroup included a total of 3313 patients (1270 new GLP-1RA users; 2043 new insulin users). In this analysis, switching to a GLP-1RA as second-line therapy was associated with a significantly lower hazard of PUD compared with switching to insulin (adjusted hazard ratio [HR], 0.44; 95% confidence interval, 0.30-0.63; P < .001). The model confirmed that active use of nonsteroidal anti-inflammatory drugs (HR, 2.39) and steroids (HR, 1.84) were also associated with increased likelihood of PUD.

CONCLUSIONS: In this nationwide cohort study of patients with T2DM, GLP-1RA use was associated with 44% lower odds of PUD. In our propensity score-matched subgroup, switching to GLP-1RA as second-line therapy was associated with a 56% lower hazard of PUD vs insulin. These findings indicate an association between GLP-1RA use and reduced risk of PUD.

BACKGROUND: Cumulative data suggest that risankizumab is an effective and safe treatment for patients with Crohn's disease (CD). However, most of the data derive from randomized controlled trials or small retrospective studies with short- or mid-term follow-up. This study aimed to assess the long-term effectiveness and safety of risankizumab in a real-world cohort of patients with CD.

METHODS: This single-center, retrospective, cohort study included consecutive patients with CD treated with risankizumab from October 2022 to August 2024. A time-to-event analysis was performed for treatment failure, treatment escalation, and CD-related health care utilization. Treatment failure was defined as the need for drug discontinuation due to primary nonresponse, loss of response, or a serious adverse event or the need for IBD (inflammatory bowel disease)-related surgery. Treatment escalation was defined as the need for shortening the dose interval or intravenous reinduction due to breakthrough CD-related symptoms and/or elevated biomarkers, such as C-reactive protein and fecal calprotectin. Health care utilization was defined as CD-related emergency department visit or hospitalization. Patients were followed from start of risankizumab until drug discontinuation or the end of follow-up (October 2024).

RESULTS: The study population consisted of 106 patients with CD (74% receiving prior biological therapies). Patients were followed for a median of 12 [interquartile range (IQR), 6.8-18.8] months; 14 (13%) patients had treatment failure; 24 (23%) had treatment escalation; and 17 (16%) had CD-related health care utilization. Multivariable Cox proportional hazards regression analysis identified penetrating CD as associated with treatment failure [hazard ratio (HR), 5.2; 95% confidence interval (CI), 1.6-17.2; P = .007], while perianal fistulizing CD (HR, 3.3; 95% CI, 1.2-9.4; P = .023) and prior exposure to more than 2 biologics (HR, 5.8; 95% CI, 1.3-26.3; P = .022) were associated with treatment escalation.

CONCLUSION: In this real-world cohort with long-term follow-up, risankizumab was generally effective in patients with CD. Penetrating CD was associated with treatment failure, while perianal fistulizing CD and prior exposure to more than 2 biologics were associated with treatment escalation.

BACKGROUND & AIMS: Sexual and gender minority (SGM) individuals (e.g., those identifying as Lesbian, Gay, Bisexual, Transgender, Queer or Other [LGBTQ+]) are disproportionately affected by psychological distress and trauma, all recognized risk factors for disorders of gut-brain interaction (DGBIs). This suggests a potentially higher burden of DGBIs in SGM populations. However, the relationship between SGM status and DGBIs has not been well characterized in large-scale clinical datasets.

METHODS: We conducted a retrospective, cross-sectional analysis using All of Us database to identify the relationship between sexual orientation and presence of bowel DGBIs. Eligible participants were adults (≥18 years) who completed a sexual orientation survey and had gastrointestinal diagnostic data available. Participants self-identified as straight, gay or lesbian, or bisexual. Outcomes included irritable bowel syndrome (IBS), functional diarrhea, and chronic constipation, identified using ICD-10 codes. Chi-square tests and multivariable logistic regression models were used to assess associations between sexual orientation and DGBIs, stratified by gender and adjusted for demographic, socioeconomic, and psychological factors. Interaction analyses were conducted to assess whether the association between sexual orientation and DGBIs differs between men and women. Missing data were imputed using multiple imputation by chained equations (MICE) to address missing covariate data under a Missing at Random (MAR) assumption, and sensitivity analyses with pooled results were compared with complete-case analyses to support robustness.

RESULTS: Among 386,242 eligible participants, 3.58% (n=13,843) identified as gay or lesbian, and 4.09% (n=15,788) as bisexual. Gay or bisexual men had significantly higher odds of being diagnosed with IBS (aOR 1.55, 95%CI 1.36-1.76), functional diarrhea (aOR 1.82, 95%CI 1.36-2.38), chronic constipation (aOR 1.33, 95%CI 1.08-1.63), and a composite DGBI outcome of any of these diagnoses (aOR 1.49, 95%CI 1.33-1.66) compared to straight men. Among women, there were no statistically significant associations between sexual orientation and any of the DGBI diagnoses or the composite outcome. Interaction analyses demonstrated that these associations were significantly stronger among men, particularly for any DGBI, functional diarrhea, and IBS.

CONCLUSIONS: Sexual orientation was independently associated with DGBI diagnoses among men, with no significant associations observed among women. These findings underscore the importance of considering gender-specific patterns when evaluating gastrointestinal health in sexual minority populations and highlight the need for tailored, inclusive approaches to DGBI care and research.

BACKGROUND: Sexual health counseling (SHC) is a critical aspect of inflammatory bowel disease (IBD) care. Less is known about sexual health counseling in patients who identify as members of a sexual or gender minority (SGM) group.

AIMS: This study aims to characterize patient-reported sexual health counseling in SGM vs. non-SGM patients with IBD.

METHODS: We conducted an anonymous, cross-sectional survey of patients over 18 years old with IBD, currently receiving care at a large, tertiary care IBD center. Data collection included demographics, IBD history, and patient recall of SHC. Patients who self-identified as SGM were compared to non-SGM patients, with subgroup analyses by sex assigned at birth. Means were compared using t tests and percentages compared using chi-square analysis.

RESULTS: A total of 162 patients (41 SGM and 121 non-SGM) completed the survey. Both groups reported IBD impacted their sexual practices (ranging from 44% non-SGM men to 64% SGM women). SGM patients were more likely to report that their gastroenterologist asked about sexual health compared to non-SGM patients (p < .005). Importantly, 31% of respondents reported seeking SHC from their gastroenterologist (GI), placing GIs among the top sources of information regarding sexual health in this cohort.

CONCLUSION: Most study participants reported that IBD has impacted their sexual practices. SHC rates were low in all study groups despite GI providers being a primary source of information. Clearer recommendations on aspects of SHC could improve quality of care for both SGM and non-SGM patients with IBD.

Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the sinonasal cavity affecting millions worldwide. Its complex pathophysiology remains poorly understood, with emerging evidence implicating interactions between diverse immune and epithelial cells in disease progression. We applied single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to both dissociated and intact human tissues from individuals with CRS with and without nasal polyps and compared them with controls. We revealed mechanisms of macrophage-eosinophil recruitment, CD4+ and CD8+ T cell dysregulation, and mast cell enrichment. We identified key immune-epithelial interactions in tissue remodeling, particularly involving basal progenitor and tuft cells. A distinct basal cell trajectory was implicated in nasal polyp formation. Orthogonal validation with spatial transcriptomics from >100 individuals with CRS revealed conserved tissue remodeling features. Our study provides insights into CRS pathophysiology, highlighting immune-epithelial interactions as potential therapeutic targets in chronic inflammation, also serving as a resource for dissecting immune disease mechanisms.

Smartphones are ubiquitous in daily life, with many people now using them while sitting on the toilet. Despite anecdotal evidence that length of time spent on the toilet is a risk factor for hemorrhoids, a multivariate analysis of smartphone use has not been performed. This study examines the correlation between smartphone use on the toilet and prevalence of hemorrhoids. A cross-sectional study was conducted among adult patients undergoing screening colonoscopy at Beth Israel Deaconess Medical Center. Participants completed survey questions regarding their smartphone habits while using the toilet, Rome IV questionnaires, and additional behaviors including straining, fiber intake and levels of physical activity. Presence of hemorrhoids were evaluated endoscopically and independently rated by two blinded endoscopists. Categorical variables were analyzed using chi-square tests and linear variables with regression analysis. A total of 125 adult participants completed the survey and 43% had hemorrhoids visualized on colonoscopy. Participants who used smartphones on the toilet were younger than non-users (mean ages 55.4 vs. 62.1, p = 0.001). Of all respondents, 66% used smartphones while on the toilet. Participants who used smartphones on the toilet spent significantly more time there than those who did not, with 37.3% of smartphone users spending more than five minutes per visit on the toilet, compared to 7.1% of non-smartphone users (p = 0.006). Furthermore, in a multivariate logistic regression, smartphone use on the toilet was associated with a 46% increased risk of hemorrhoids (p = 0.044) after adjusting for age, sex, BMI, exercise activity, straining and fiber intake. The most common activity performed while on the toilet was reading "news" (54.3%), followed by "social media" (44.4%). The study suggests that prolonged engagement with smartphones while using the toilet may be associated with an increased prevalence of hemorrhoids.

BACKGROUND: There are limited data regarding therapeutic drug monitoring (TDM) of non-anti-tumor necrosis factor therapy in inflammatory bowel disease (IBD). This study aimed to evaluate the efficacy of proactive TDM in IBD patients treated with intravenous (iv) vedolizumab (VDZ).

METHODS: This single-center retrospective cohort study included consecutive IBD patients treated with maintenance iv VDZ therapy undergoing TDM from November 2016 to March 2023. Patients were followed through June 2023 and were divided in to 2 groups: those who had at least 1 proactive TDM vs those who underwent only reactive TDM. A survival analysis was performed to evaluate drug persistence, defined as no need for drug discontinuation due to loss of response, serious adverse event, or an IBD-related surgery.

RESULTS: The study population consisted of 94 patients (proactive TDM, n = 72) with IBD (ulcerative colitis, n = 53). Patients undergoing at least 1 proactive TDM compared with patients having only reactive TDM demonstrated a higher cumulative probability of drug persistence (Log-rank P < .001). In multivariable Cox proportional hazard regression analysis, at least 1 proactive TDM was the only factor associated with drug persistence (hazard ratio, 14.3; 95% confidence interval [CI], 3.8-50; P < .001). A ROC analysis identified a VDZ concentration of 12.5 µg/mL as the optimal drug concentration threshold associated with drug persistence (area under the ROC curve: 0.691; 95% CI, 0.517-0.865; P = .049).

CONCLUSION: In this single-center retrospective study reflecting real-life clinical practice, proactive TDM was associated with increased drug persistence in patients with IBD treated with iv VDZ.