Updates on the management of inflammatory bowel disease from periconception to pregnancy and lactation.

Inflammatory bowel disease (IBD) affects reproductive planning due to psychological effects and mechanical problems related to surgery. Children of people with IBD have an increased risk of about 10% if one parent has IBD and up to 33% if both parents have IBD. The fertility of people with IBD is similar to the general population, but fertility might be reduced in individuals with active IBD, ileal pouch-anal anastomosis, or perianal Crohn's disease. Flaring disease during pregnancy increases complications, such as preterm birth. Thus, disease management with appropriate medications can optimise outcomes. As most medications have minimal fetal risks, people with IBD should be informed about the risks of stopping medications and the importance of maintaining remission. A period of disease remission is advisable before pregnancy and could reduce the risks for both the pregnant person and the fetus. Flexible endoscopy, intestinal ultrasound, and gadolinium-free magnetic resonance enterography are safe during pregnancy. We provide state-of-the-art knowledge on the basis of the latest evidence to ensure successful pregnancy outcomes in controlled IBD.

White Paper: American Gastroenterological Association Position Statement: The Future of IBD Care in the United States-Removing Barriers and Embracing Opportunities.

Despite incredible growth in systems of care and rapidly expanding therapeutic options for people with inflammatory bowel disease, there are significant barriers that prevent patients from benefiting from these advances. These barriers include restrictions in the form of prior authorization, step therapy, and prescription drug coverage. Furthermore, inadequate use of multidisciplinary care and inflammatory bowel disease specialists limits patient access to high-quality care, particularly for medically vulnerable populations. However, there are opportunities to improve access to high-quality, patient-centered care. This position statement outlines the policy and advocacy goals that the American Gastroenterological Association will prioritize for collaborative efforts with patients, providers, and payors.

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..

Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Biologics are used routinely in pregnant women with inflammatory bowel disease (IBD), but large-scale data reporting adverse pregnancy outcomes among biologic users are lacking. We sought to estimate the prevalence of adverse pregnancy outcomes in women with IBD on biologic therapies. METHODS: We searched major databases from inception to June 2020 for studies estimating the prevalence of adverse pregnancy outcomes in IBD when using biologics (anti-tumor necrosis factor [TNF], anti-integrins, and anticytokines). Prevalence and relative risk (RR) were pooled using a random-effects model. RESULTS: Forty-eight studies were included in the meta-analysis comprising 6963 patients. Biologic therapy in IBD pregnancies was associated with a pooled prevalence of 8% (95% CI, 6%-10%; I2 = 87.4%) for early pregnancy loss, 9% (95% CI, 7%-11%; I2 = 89.9%) for preterm birth, 0% (95% CI, 0%-0%; I2 = 0%) for stillbirth, 8% (95% CI, 5%-10%; I2 = 87.0%) for low birth weight, and 1% (95% CI, 1%-2%; I2 = 78.3%) for congenital malformations. These rates are comparable with those published in the general population. In subgroup analyses of a small number of studies, the prevalence of early pregnancy loss and preterm birth were higher in vedolizumab vs anti-TNF users. Meta-regression did not show an association of disease activity or concomitant thiopurine on adverse outcomes. Continued TNF inhibitor use during the third trimester was not associated with risk of preterm birth (RR, 1.41; 95% CI, 0.77-2.60; I2 = 0%), low birth weight (RR, 1.32; 95% CI, 0.80-2.18; I2 = 0%), or congenital malformations (RR, 1.28; 95% CI, 0.47-3.49; I2 = 0%). CONCLUSIONS: Adverse pregnancy outcomes among pregnant IBD women using biologics are comparable with that of the general population. PROSPERO protocol #CRD42019135721.

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.

Correlation-Based Uncertainty in Loaded Reverberation Chambers.

When reverberation chambers are loaded to increase the coherence bandwidth for modulated-signal measurements, a secondary effect is decreased spatial uniformity. We show that an appropriate choice of stirring sequence, consisting of a combination of mode-stirring mechanisms such as paddle and antenna-platform stirring, can mitigate the potential for increased uncertainty. We develop a new mode-stirring sample correlation model for uncertainty due to the stirring sequence. In a comparison with an empirical uncertainty analysis, the model is found to have an agreement within 2.5%. Our analysis is demonstrated for four loading cases in each of three reverberation chambers. The model is used to determine an optimal stirring sequence for a given chamber setup directly from correlations associated with each stirring mechanism. The model can also be understood in terms of the entropy of a measurement and it is shown that maximizing the entropy corresponds to a minimized uncertainty. The method presented here not only provides insight into sources of uncertainty but also allows users to determine an optimal mode-stirring sequence with minimized uncertainty for a given chamber setup.

White Paper AGA: POWER - Practice Guide on Obesity and Weight Management, Education, and Resources.

The epidemic of obesity continues at alarming rates, with a high burden to our economy and society. The American Gastroenterological Association understands the importance of embracing obesity as a chronic, relapsing disease and supports a multidisciplinary approach to the management of obesity. Because gastrointestinal disorders resulting from obesity are more frequent and often present sooner than type 2 diabetes mellitus and cardiovascular disease, gastroenterologists have an opportunity to address obesity and provide an effective therapy early. Patients who are overweight or obese already fill gastroenterology clinics with gastroesophageal reflux disease and its associated risks of Barrett's esophagus and esophageal cancer, gallstone disease, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, and colon cancer. Obesity is a major modifiable cause of diseases of the digestive tract that frequently goes unaddressed. As internists, specialists in digestive disorders, and endoscopists, gastroenterologists are in a unique position to play an important role in the multidisciplinary treatment of obesity. This American Gastroenterological Association paper was developed with content contribution from Society of American Gastrointestinal and Endoscopic Surgeons, The Obesity Society, Academy of Nutrition and Dietetics, and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, endorsed with input by American Society for Gastrointestinal Endoscopy, American Society for Metabolic and Bariatric Surgery, American Association for the Study of Liver Diseases, and Obesity Medicine Association, and describes POWER: Practice Guide on Obesity and Weight Management, Education and Resources. Its objective is to provide physicians with a comprehensive, multidisciplinary process to guide and personalize innovative obesity care for safe and effective weight management.

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.

Gastroenterology Clinic Follow-Up Reduces Gastroenterology-Specific Readmissions Among Patients With Severe Ulcerative Colitis.

BACKGROUND AND AIMS: Readmission within 30 days occurs in up to 18% of admitted patients with ulcerative colitis (UC). The importance of postdischarge follow-up with a gastroenterologist as well as the optimal follow-up interval is unknown. METHODS: We conducted a retrospective cohort study of patients with UC who were admitted to Stanford University Hospital between 2010 and 2020. We included adult patients with UC who were admitted for a UC flare. Patients with a colectomy during hospitalization or with Clostridium difficile infection at the index hospitalization were excluded. The primary outcome was time to readmission for a gastroenterology (GI) indication, and the primary predictor (time dependent) was follow-up with a GI provider. Patients were followed for 180 days after discharge. Data were analyzed using a Cox proportional hazards model. RESULTS: Of the 223 patients hospitalized with UC during the study period, 25% (n = 57) were readmitted within 180 days, with 13.9% occurring within 30 days. Early follow-up (within 7 days) was observed in 29% (n = 65) of patients, while 30-day follow-up was seen in 68.7% (n = 153), and follow-up within 180 days was seen in 198 (89%) patients. In the adjusted Cox proportional hazards model, GI follow-up was associated with fewer readmissions (hazard ratio, 0.42; 95% confidence interval, 0.22-0.81; P = .009). Early follow-up was strongly associated with a reduced risk of readmission (hazard ratio, 0.24; 95% 95% confidence interval, 0.09-0.69; P = .008). Follow-up in 7 days was associated with fewer readmissions (P < .0001). CONCLUSIONS: Outpatient GI follow-up after UC hospitalization reduces readmissions, with the greatest reduction occurring among patients followed up within 1 week of discharge.

In recently discharged ulcerative colitis patients, time to follow-up with a gastroenterologist was tightly related to the risk of readmission. Follow-up within 1 week offered the best protection. Efforts to improve postdischarge coordination are likely to improve quality.

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.

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.

Dynamic Spectrum Access Algorithms Based on Survival Analysis.

In this study, we design and implement two algorithms for dynamic spectrum access that are based on survival analysis. They use a non-parametric estimate of the cumulative hazard function to predict the remaining idle time available for secondary transmission subject to the constraint of a preset probability of successful completion. In addition to theoretical performance analysis of the algorithms, we evaluate them using data collected from a long term evolution band to model primary user activity to demonstrate their effectiveness in real-world scenarios, even at fine time scales. The algorithms are run in different configurations, i.e., they are trained and run on a few combinations of data sets. Our results show that as long as the cumulative hazard functions are fairly similar across datasets, the algorithms can be trained on one dataset and run on that of another without any significant degradation of performance. The algorithms achieve fairly high white space utilization and have a measured probability of interference that is at or below the preset threshold.

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.

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.