A tissue atlas of ulcerative colitis revealing evidence of sex-dependent differences in disease-driving inflammatory cell types and resistance to TNF inhibitor therapy.

Although literature suggests that resistance to TNF inhibitor (TNFi) therapy in patients with ulcerative colitis (UC) is partially linked to immune cell populations in the inflamed region, there is still substantial uncertainty underlying the relevant spatial context. Here, we used the highly multiplexed immunofluorescence imaging technology CODEX to create a publicly browsable tissue atlas of inflammation in 42 tissue regions from 29 patients with UC and 5 healthy individuals. We analyzed 52 biomarkers on 1,710,973 spatially resolved single cells to determine cell types, cell-cell contacts, and cellular neighborhoods. We observed that cellular functional states are associated with cellular neighborhoods. We further observed that a subset of inflammatory cell types and cellular neighborhoods are present in patients with UC with TNFi treatment, potentially indicating resistant niches. Last, we explored applying convolutional neural networks (CNNs) to our dataset with respect to patient clinical variables. We note concerns and offer guidelines for reporting CNN-based predictions in similar datasets.

Paternal Medications in Inflammatory Bowel Disease and Male Fertility and Reproductive Outcomes: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Studies evaluating reproductive outcomes among male patients with inflammatory bowel disease (IBD) are limited. We evaluated use of IBD medications and association with semen parameters, a proxy of male fertility, and adverse pregnancy outcomes (early pregnancy loss [EPL], preterm birth [PB], congenital malformations [CM]). METHODS: We searched Medline, Embase, Scopus, and Web of Science (PROSPERO CRD42020197098) from inception to April 2022 for studies reporting semen parameters and adverse pregnancy outcomes among male patients exposed to biologics, thiopurine, or methotrexate. Standardized mean difference, prevalence, and odds ratios (ORs) of outcomes were pooled and analyzed using a random effects model. RESULTS: Ten studies reporting semen parameters (268 patients with IBD) and 16 studies reporting adverse pregnancy outcomes (over 25,000 patients with IBD) were included. Biologic, thiopurine, or methotrexate use were not associated with decreased sperm count, motility, or abnormal morphology compared with nonexposed patients. The prevalence of adverse pregnancy outcomes with paternal biologic (5%), thiopurine (6%), or methotrexate (6%) exposure was comparable to nonexposed patients (5%). Biologic use was not associated with risk of EPL (OR, 1.26; I2 = 0%; P = .12), PB (OR, 1.10; I2 = 0%; P = .17), or CM (OR, 1.03; I2 = 0%; P = .69). Thiopurine use was not associated with risk of EPL (OR, 1.31; I2 = 19%; P = .17), PB (OR, 1.05; I2 = 0%; P = .20), or CM (OR, 1.07; I2 = 7%; P = .34). Methotrexate use was not associated with risk of PB (OR, 1.06; I2 = 0%; P = .62) or CM (OR, 1.03; I2 = 0%; P = .81). CONCLUSIONS: Biologic, thiopurine, or methotrexate use among male patients with IBD are not associated with impairments in fertility or with increased odds of adverse pregnancy outcomes.

Patients Report Infrequent Counseling by Physicians and Inadequate Knowledge about Inflammatory Bowel Disease and Reproductive Health Issues.

OBJECTIVE: Inflammatory bowel disease (IBD) reproductive health counseling is associated with higher knowledge, lower voluntary childlessness, greater medication adherence during pregnancy, and improved outcomes of pregnancy. Our aims were to assess counseling and knowledge about IBD and reproductive health in a tertiary care IBD patient population. STUDY DESIGN: We anonymously surveyed women and men ages 18 to 45 cared for at the Stanford IBD clinic about reproductive health and administered the CCPKnow questionnaire. STATA was used to summarize descriptive statistics and compare categorical variables using Fisher's exact test. RESULTS: Of the 100 patients (54% women) who completed the survey, only 33% reported prior reproductive health counseling. Both men and women considered not having a child due to IBD (31% women, 15% men) and most (83%) had no prior counseling. A minority of patients had an adequate (≥8/17) CCPKnow score (45% women, 17% men). The majority of women with prior pregnancy had pre-existing IBD (67%), yet many did not seek gastrointestinal (GI) care (38% preconception, 25% during pregnancy) and 33% stopped/changed medications, with 40% not discussing this with a physician. Prior counseling was significantly associated with education level (p = 0.013), biologic use (p = 0.003), and an adequate CCPKnow score (p = 0.01). Overall, 67% of people wanted more information on IBD and reproductive health. CONCLUSION: In an educated tertiary care cohort, the majority of patients had low CCPKnow scores and rates of IBD reproductive health counseling. Many patients with IBD prior to pregnancy reported no GI care preconception or during pregnancy and stopped/changed medications without consulting a physician. There is an urgent need for proactive counseling by gastroenterologists and obstetricians on IBD and reproductive health. KEY POINTS: · There is inadequate reproductive health counseling in IBD.. · Many IBD patients do not seek prenatal/perinatal GI care.. · Patients change medications without consultation.. · GIs and OBs should proactively counsel IBD patients..

Balsalazide Exposure During the Development of Fertilizing Sperm May Be Associated With Offspring Birth Defects.

We report an association between balsalazide exposure during the development of fertilizing sperm and birth defects in offspring. Exposed offspring were approximately 8 times more likely to have a birth defect. There were no pre-existing reasons to suspect such a relationship, which should be confirmed in other data.

Biologics During Pregnancy in Women With Inflammatory Bowel Disease and Risk of Infantile Infections: A Systematic Review and Meta-Analysis.

INTRODUCTION: Biologics, such as tumor necrosis factor inhibitors, anti-integrins and anticytokines, are therapies for inflammatory bowel disease (IBD) that may increase the risk of infection. Most biologics undergo placental transfer during pregnancy and persist at detectable concentrations in exposed infants. Whether this is associated with an increased risk of infantile infections is controversial. We performed a systematic review and meta-analysis evaluating the risk of infantile infections after in utero exposure to biologics used to treat IBD. METHODS: We searched PubMed, Embase, Scopus, Web of Science, and CENTRAL from inception to June 2020 to evaluate the association of biologic therapy during pregnancy in women with IBD and risk of infantile infections. Odds ratios of outcomes were pooled and analyzed using a random effects model. RESULTS: Nine studies met the inclusion criteria comprising 8,013 women with IBD (5,212 Crohn's disease, 2,801 ulcerative colitis) who gave birth to 8,490 infants. Biologic use during pregnancy was not associated with an increased risk of all infantile infections (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.73-1.14, I2 = 30%). In a subgroup analysis for the type of infection, biologic use was associated with increased infantile upper respiratory infections (OR 1.57, 95% CI 1.02-2.40, I2 = 4%). Biologic use during pregnancy was not associated with infantile antibiotic use (OR 0.91, 95% CI 0.73-1.14, I2 = 30%) or infection-related hospitalizations (OR 1.33, 95% CI 0.95-1.86, I2 = 26%). DISCUSSION: Biologics use during pregnancy in women with IBD is not associated with the overall risk of infantile infections or serious infections requiring antibiotics or hospitalizations but is associated with an increased risk of upper respiratory infections.

Mass cytometry reveals systemic and local immune signatures that distinguish inflammatory bowel diseases.

Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis. Each disease is characterized by a diverse set of potential manifestations, which determine patients' disease phenotype. Current understanding of phenotype determinants is limited, despite increasing prevalence and healthcare costs. Diagnosis and monitoring of disease requires invasive procedures, such as endoscopy and tissue biopsy. Here we report signatures of heterogeneity between disease diagnoses and phenotypes. Using mass cytometry, we analyze leukocyte subsets, characterize their function(s), and examine gut-homing molecule expression in blood and intestinal tissue from healthy and/or IBD subjects. Some signatures persist in IBD despite remission, and many signatures are highly represented by leukocytes that express gut trafficking molecules. Moreover, distinct systemic and local immune signatures suggest patterns of cell localization in disease. Our findings highlight the importance of gut tropic leukocytes in circulation and reveal that blood-based immune signatures differentiate clinically relevant subsets of IBD.

American Society of Clinical Oncology Summit on Addressing Obesity Through Multidisciplinary Provider Collaboration: Key Findings and Recommendations for Action.

OBJECTIVE: Given the increasing evidence that obesity increases the risk of developing and dying from malignancy, the American Society of Clinical Oncology (ASCO) launched an Obesity Initiative in 2013 that was designed to increase awareness among oncology providers and the general public of the relationship between obesity and cancer and to promote research in this area. Recognizing that the type of societal change required to impact the obesity epidemic will require a broad-based effort, ASCO hosted the "Summit on Addressing Obesity through Multidisciplinary Collaboration" in 2016. METHODS: This meeting was held to review current challenges in addressing obesity within the respective health care provider communities and to identify priorities that would most benefit from a collective and cross-disciplinary approach. RESULTS: Efforts focused on four key areas: provider education and training; public education and activation; research; and policy and advocacy. Summit attendees discussed current challenges in addressing obesity within their provider communities and identified priorities that would most benefit from multidisciplinary collaboration. CONCLUSIONS: A synopsis of recommendations to facilitate future collaboration, as well as examples of ongoing cooperative efforts, provides a blueprint for multidisciplinary provider collaboration focused on obesity prevention and treatment.

White Paper AGA: An Episode-of-Care Framework for the Management of Obesity-Moving Toward High Value, High Quality Care: A Report From the American Gastroenterological Association Institute Obesity Episode of Care and Bundle Initiative Work Group.

The American Gastroenterological Association acknowledges the need for gastroenterologists to participate in and provide value-based care for both cognitive and procedural conditions. Episodes of care are designed to engage specialists in the movement toward fee for value, while facilitating improved outcomes and patient experience and a reduction in unnecessary services and overall costs. The episode of care model puts the patient at the center of all activity related to their particular diagnosis, procedure, or health care event, rather than on a physician's specific services. It encourages and incents communication, collaboration, and coordination across the full continuum of care and creates accountability for the patient's entire experience and outcome. This paper outlines a collaborative approach involving multiple stakeholders for gastrointestinal practices to assess their ability to participate in and implement an episode of care for obesity and understand the essentials of coding and billing for these services.