Reviewing the impact of obesity on inflammatory bowel disease and considerations for optimizing management.

PURPOSE OF REVIEW: This review examines the complex relationship between obesity and inflammatory bowel disease (IBD), encompassing their potentially shared pathogenesis, the impact of obesity on the natural history and treatment outcomes of IBD, and the management of obesity in the patient with IBD. RECENT FINDINGS: Obesity represents a state of chronic inflammation that may not only contribute to IBD pathogenesis, but also influence disease progression, complications, and response to treatment. Increased visceral adiposity may carry negative prognostic implications for disease and treatment-specific outcomes. Antiobesity medications, endoscopic bariatric therapies, and even bariatric surgery may be effective and well tolerated in selected patients with IBD. SUMMARY: The intersection of obesity and IBD presents a significant clinical challenge, with obesity influencing the natural history of IBD and potentially affecting treatment efficacy. As obesity prevalence among IBD patients rises, a tailored approach to management is crucial, taking into account the individualized risks and benefits of various treatment strategies, including lifestyle interventions, pharmacotherapy, endoscopic procedures, and bariatric surgery.

Real-World Effectiveness of Ustekinumab in Ulcerative Colitis in a United States Multicenter Cohort Consortium.

BACKGROUND: Pivotal trials have shown that ustekinumab is effective in ulcerative colitis (UC). However, the population included in these trials do not represent the cohort of patients treated in the real world. In this study, we aimed to describe the effectiveness and safety of ustekinumab in a clinical cohort of patients with UC. METHODS: We performed a multicenter retrospective cohort study and included patients with active UC starting ustekinumab. Variables collected included demographics, clinical data, and disease activity (measured using partial Mayo score [PMS] and endoscopic Mayo score) at follow-up. The primary outcomes were cumulative rates of steroid-free clinical and biochemical remission (SFCBR), defined as a PMS <2 while off steroids and a normal C-reactive protein and/or fecal calprotectin. RESULTS: A total of 245 patients met inclusion criteria. The median time of follow-up was 33 (interquartile range, 17-53) weeks, and 214 (87.3%) had previous exposure to a biologic and/or tofacitinib. Rates of SFCBR, clinical remission, and endoscopic remission at 6 and 12 months were 12.0% (n = 16 of 139), 29.0% (n = 71 of 175), and 18.0% (n = 7 of 39), and 23.8% (n = 15 of 63), 54.3% (n = 57 of 105), and 31.0% (n = 9 of 29), respectively. Non-Hispanic White race, higher baseline PMS, and the use of concomitant corticosteroids were independently associated with failure to achieve SFCBR. Of the 73 that were dose escalated, 28.4% did not respond, 49.3% experienced a benefit, and 21.6% achieved remission. CONCLUSIONS: In a population enriched with refractory UC, ustekinumab was well tolerated and induced remission in a significant number of patients. Larger studies with a longer follow-up are warranted.

Ustekinumab was shown to be efficacious and safe in a population of patients with refractory ulcerative colitis. Those patients with exposure to multiple drug classes and higher disease burden at baseline are less likely to respond.

Perinatal mental health and pregnancy-associated mortality: opportunities for change.

Perinatal mental health conditions have been associated with adverse pregnancy outcomes, including maternal death. This quality improvement project analyzed pregnancy-associated death among veterans with mental health conditions in order to identify opportunities to improve healthcare and reduce maternal deaths. Pregnancy-associated deaths among veterans using Veterans Health Administration (VHA) maternity care benefits between fiscal year 2011 and 2020 were identified from national VHA databases. Deaths among individuals with active mental health conditions underwent individual chart review using a standardized abstraction template adapted from the Centers for Disease Control and Prevention (CDC). Thirty-two pregnancy-associated deaths were identified among 39,720 paid deliveries with 81% (n = 26) occurring among individuals with an active perinatal mental health condition. In the perinatal mental health cohort, most deaths (n = 16, 62%) occurred in the late postpartum period and 42% (n = 11) were due to suicide, homicide, or overdose. Opportunities to improve care included addressing (1) racial disparities, (2) mental health effects of perinatal loss, (3) late postpartum vulnerability, (4) lack of psychotropic medication continuity, (5) mental health conditions in intimate partners, (6) child custody loss, (7) lack of patient education or stigmatizing patient education, and (8) missed opportunities for addressing reproductive health concerns in mental health contexts. Pregnancy-associated deaths related to active perinatal mental health conditions can be reduced. Mental healthcare clinicians, clinical teams, and healthcare systems have opportunities to improve care for individuals with perinatal mental health conditions.

Risankizumab to treat moderately to severely active Crohn's disease in adults: an evaluation of trials and data.

INTRODUCTION: Risankizumab is a humanized monoclonal antibody that selectively inhibits interleukin (IL)-23. It is approved for the treatment of moderate-to-severe plaque psoriasis, psoriatic arthritis, and more recently moderate-to-severe Crohn's disease (CD). AREAS COVERED: After examining the current landscape of CD management including therapies which are currently approved and those in late stages of development, we will review the interleukin pathway and discuss the specific mechanism of targeted IL-23 inhibition, summarize available clinical trial data on efficacy and safety of Risankizumab, consider future positioning of Risankizumab in the therapeutic armamentarium, and ultimately discuss future needs for the field. EXPERT OPINION: Risankizumab represents the first and only targeted IL-23 inhibitor approved for the treatment of CD, providing a promising addition to the therapeutic armamentarium for CD, with a favorable safety profile and demonstrated efficacy in both biologic-naïve and exposed populations. It is possible that the targeted nature of Risankizumab may enhance efficacy and safety over combined IL-12/23 inhibition, with trials underway attempting to shed light on that hypothesis.

Effectiveness and Safety of Antiobesity Medications in Patients With Obesity and Inflammatory Bowel Disease.

INTRODUCTION: Limited data exist evaluating antiobesity medications (AOM) in patients with inflammatory bowel disease (IBD). METHODS: We performed a case-control study evaluating the effectiveness and safety of AOM in patients with IBD with obesity, matched to non-IBD controls. RESULTS: After 12 months, the case (n = 36) and control (n = 36) groups achieved similar percent total body weight loss of -6.9 ± 8.3 and -8.1 ± 7.0 (P = 0.30), respectively. Side effect profiles were similar between groups. Seven patients experienced an IBD flare, all managed medically. DISCUSSION: AOM use in patients with IBD demonstrated similar effectiveness and safety when compared with that observed in the non-IBD population.

Exploring the impact of water on the morphology and crystallinity of xylan hydrate nanotiles.

There has been a resurgence of studies on xylan particles describing various properties and exploring new applications. The aim of this study was to analyze xylan hydrate crystals in the wet state and after air-drying using state-of-art imaging techniques in order to assess the impact of water on both crystallinity and particle morphology. Xylan from esparto grass (Stipa tenacissima) was crystallized and formed convex platelets, termed 'nanotiles'. Fully hydrated xylan crystals were examined in a layer of vitreous ice by cryogenic electron microscopy. Selected area electron diffraction of the xylan hydrate crystals revealed an oriented crystalline core, unlike the dried crystals that showed no orientation. The surface topographies and thickness of wet and air-dried xylan nanotiles were observed using atomic force microscopy imaging in both liquid and in air. X-ray diffraction was used to assess the crystallinity of xylan nanotiles after drying to varying levels. Air-dried crystals gave diffraction maxima corresponding to xylan hydrate, while wet crystals gave diffraction maxima corresponding to xylan dihydrate. This study offers new insight into xylan hydrate particles, focusing on the role of water on their crystallinity, ultrastructure, and orientation of the crystalline layers.

Size-controlled synthesis of xylan micro / nanoparticles by self-assembly of alkali-extracted xylan.

Valorization of underutilized biobased feedstocks like hetero-polysaccharides is critical for the development of the biorefinery concept. Towards this goal, highly uniform xylan micro/nanoparticles with a particle size ranging from 400 nm to 2.5 µm in diameter were synthesized by a facile self-assembly method in aqueous solutions. Initial concentration of the insoluble xylan suspension was utilized to control the particle size. The method utilized supersaturated aqueous suspensions formed at standard autoclaving conditions without any other chemical treatments to create the resulting particles as solutions cooled to room temperature. Processing parameters of the xylan micro/nanoparticles were systematically studied and correlated with both the morphology and size of xylan particles. By adjusting the crowding of the supersaturated solutions, highly uniform dispersions of xylan particles were synthesized of defined size. The xylan micro/nanoparticles prepared by self-assembly have a quasi-hexagonal shape, like a tile, and depending upon solution concentrations xylan nanoparticles with a thickness of <100 nm were achieved at high concentrations. Based on the usefulness of polysaccharide nanoparticles, like cellulose nanocrystals, these particles have potential for unique structures for hydrogels, aerogels, drug delivery, and photonic materials. This study highlights the formation of a diffraction grating film for visible light with these size-controlled particles.

Assessing Racial Disparities in Access, Use, and Outcomes for Pregnant and Postpartum Veterans and Their Infants in Veterans Health Administration.

Objective: Limited population-based data examines racial disparities among pregnant and postpartum Veterans. Our objective was to determine whether Black/white racial disparities in health care access, use, and Veteran and infant outcomes are present among pregnant and postpartum Veterans and their infants using Veterans Health Administration (VA) care. Methods: The VA National Veteran Pregnancy and Maternity Care Survey included all Veterans with a VA paid live birth between June 2018 and December 2019. Participants could complete the survey online or by telephone. The independent variable was self-reported race. Outcomes included timely initiation of prenatal care, perceived access to timely prenatal care, attendance at a postpartum check-up, receipt of needed mental health care, cesarean section, postpartum rehospitalization, low birthweight, preterm birth, admission to a neonatal intensive care unit, and breastfeeding. Nonresponse weighted general linear models with a log-link were used to examine associations of race with outcomes. Cox regression was used to examine the association of race with duration of breastfeeding. Models adjusted for age, ethnicity, urban versus rural residence, and parity. Results: The analytic sample consisted of 1,220 Veterans (Black n = 916; white n = 304) representing 3,439 weighted responses (Black n = 1,027; white n = 2,412). No racial disparities were detected for health care access or use. Black Veterans were more likely than white Veterans to have a postpartum rehospitalization (RR 1.67, 95% CI: 1.04-2.68) and a low-birthweight infant (RR 1.67, 95% CI: 1.20-2.33). Conclusion: While no racial disparities were detected for health care access and use, we identified disparities in postpartum rehospitalization and low birthweight, underscoring that access is not sufficient for ensuring health equity.

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Improving the Maternity Care Safety Net: Establishing Maternal Mortality Surveillance for Non-Obstetric Providers and Institutions.

The siloed nature of maternity care has been noted as a system-level factor negatively impacting maternal outcomes. Veterans Health Administration (VA) provides multi-specialty healthcare before, during, and after pregnancy but purchases obstetric care from community providers. VA providers may be unaware of perinatal complications, while community-based maternity care providers may be unaware of upstream factors affecting the pregnancy. To optimize maternal outcomes, the VA has initiated a system-level surveillance and review process designed to improve non-obstetric care for veterans experiencing a pregnancy. This quality improvement project aimed to describe the VA-based maternal mortality review process and to report maternal mortality (pregnancy-related death up to 42 days postpartum) and pregnancy-associated mortality (death from any cause up to 1 year postpartum) among veterans who use VA maternity care benefits. Pregnancies and pregnancy-associated deaths between fiscal year (FY) 2011-2020 were identified from national VA databases. All deaths underwent individual chart review and abstraction that focused on multi-specialty care received at the VA in the year prior to pregnancy until the time of death. Thirty-two pregnancy-associated deaths were confirmed among 39,720 pregnancies (PAMR = 80.6 per 100,000 live births). Fifty percent of deaths occurred among individuals who had experienced adverse social determinants of health. Mental health conditions affected 81%. Half (n = 16, 50%) of all deaths occurred in the late postpartum period (43-365 days postpartum) after maternity care had ended. More than half of these late postpartum deaths (n = 9, 56.2%) were related to suicide, homicide, or overdose. Integration of care delivered during the perinatal period (pregnancy through postpartum) from primary, mental health, emergency, and specialty care providers may be enhanced through a system-based approach to pregnancy-associated death surveillance and review. This quality improvement project has implications for all healthcare settings where coordination between obstetric and non-obstetric providers is needed.

Gynecologist Supply Deserts Across the VA and in the Community.

BACKGROUND: The Veterans Health Administration (VA) refers patients to community providers for specialty services not available on-site. However, community-level specialist shortages may impede access to care. OBJECTIVE: Compare gynecologist supply in veterans' county of residence versus at their VA site. DESIGN: We identified women veteran VA patients from fiscal year (FY) 2017 administrative data and assessed availability of a VA gynecologist within 50 miles (hereafter called "local") of veterans' VA homesites (per national VA organizational survey data). For the same cohort, we then assessed community-level gynecologist availability; counties with < 2 gynecologists/10,000 women (per the Area Health Resource File) were "inadequate-supply" counties. We examined the proportion of women veterans with local VA gynecologist availability in counties with inadequate versus adequate gynecologist supply, stratified by individual and VA homesite characteristics. Chi-square tests assessed statistical differences. PARTICIPANTS: All women veteran FY2017 VA primary care users nationally. MAIN MEASURES: Availability of a VA gynecologist within 50 miles of a veteran's VA homesite; county-level "inadequate-supply" of gynecologists. KEY RESULTS: Among 407,482 women, 9% were in gynecologist supply deserts (i.e., lacking local VA gynecologist and living in an inadequate-supply county). The sub-populations with the highest proportions in gynecologist supply deserts were rural residents (24%), those who got their primary care at non-VAMC satellite clinics (13%), those who got their care at a site without a women's clinic (13%), and those with American Indian or Alaska Native (12%), or white (12%) race. Among those in inadequate-supply counties, 59.9% had gynecologists at their local VA; however, 40.1% lacked a local VA gynecologist. CONCLUSIONS: Most veterans living in inadequate-supply counties had local VA gynecology care, reflecting VA's critical role as a safety net provider. However, for those in gynecologist supply deserts, expanded transportation options, modified staffing models, or tele-gynecology hubs may offer solutions to extend VA gynecology capacity.

Sexual Health Assessment Is Vital to Whole Health Models of Care.

Sexual health is the state of well-being regarding sexuality. Sexual health is highly valued and associated with overall health. Overall health and well-being are more than the absence of disease or dysfunction. Health care systems adopting whole health models of care need to incorporate a holistic assessment of sexual health. This includes assessing patients' sexual orientation and gender identity (SOGI). If health systems, including but not limited to the Veterans Health Administration (VHA), incorporate sexual health into whole health they could enhance preventive care, promote healthy sexual functioning, and optimize overall health and well-being. Assessing sexual health can give providers important information about a patient's health, well-being, and health goals. Sexual concerns or dysfunction may also signal undiagnosed health conditions. Additionally, collecting SOGI information as part of a sexual health assessment would allow providers to address problems that drive disparities for lesbian, gay, bisexual, transgender, queer, and similar minority (LGBTQ+) populations. Health care providers do not routinely assess sexual health in clinical practice. One barrier is a gap in communication between patients and providers. Providers cite beliefs that patients will bring up sexual concerns themselves or might be offended by discussing sexual health. Patients often report an expectation that providers will bring up sexual health and being comfortable discussing sexual health with their providers. Within the VHA, the lack of a sexual health template within the electronic health record (EHR) adds an additional barrier. The VHA's transition toward whole health and updates to its EHR provide unique opportunities to integrate sexual health assessment into routine care. We highlight system modifications to address this within the VHA. These examples may be helpful for other health care systems interested in moving toward whole health. It will be vital for health care systems integrating a whole health approach to develop both practical and educational interventions to address the communication gap. These interventions will need to target both providers and patients in health care systems that transition to a whole health model of care, not just the VHA. Both the communication gap between providers and patients, and the lack of support within some EHR systems for sexual health assessment are barriers to assessing sexual health in primary care clinics. Routine sexual health assessment would benefit patient well-being and present an opportunity to address health disparities for LGBTQ+ populations. Health care systems (ie, both the VHA and other systems) can overcome these barriers by implementing educational interventions and updating their EHRs and back-end data structures. VHA's expertise in developing and implementing health education interventions and EHR-based quality improvements may help inform interventions beyond VHA.

Prevalence and Impact of Obesity in a Population-Based Cohort of Patients With Crohn's Disease.

BACKGROUND: Obesity is on the rise within the inflammatory bowel disease population. The impact obesity has on the natural history of Crohn's disease (CD) is not well-understood. We aimed to describe the prevalence of obesity in a population-based cohort of newly diagnosed patients with CD, and the impact obesity had on disease phenotype and outcomes of corticosteroid use, hospitalization, intestinal resection, and development of fistulizing or penetrating disease. MATERIALS AND METHODS: A chart review was performed on Olmsted County, Minnesota residents diagnosed with CD between 1970 and 2010. Data were collected on demographics, body mass index, CD location and behavior, CD-related hospitalizations, corticosteroid use, and intestinal resection. The proportion of individuals considered obese at the time of CD diagnosis was evaluated over time, and CD-associated complications were assessed with Kaplan-Meier survival analysis. RESULTS: We identified 334 individuals diagnosed with CD between 1970 and 2010, of whom 156 (46.7%) were either overweight (27.8%) or obese (18.9%) at the time of diagnosis. The proportion of patients considered obese at the time of their diagnosis of CD increased 2-3 fold over the course of the study period. However, obesity did not have a significant impact on the future risk of corticosteroid use, hospitalization, intestinal resection, or development of penetrating and stricturing complications. CONCLUSIONS: Obesity is on the rise in patients with CD, although in this cohort, there did not appear to be any negative association with future CD-related outcomes. Further prospective studies, ideally including obesity measures such as visceral adipose tissue assessment, are warranted to understand the implications of the rising prevalence of obesity on CD outcomes.

Vulvar Crohn's Disease: Clinical Features and Outcomes.

INTRODUCTION: Vulvar involvement is a rare complication of Crohn's disease (CD). The optimal treatment of vulvar CD is unknown. METHODS: We conducted a 25-year retrospective cohort study of vulvar CD from 3 referral centers. Clinical features and outcomes were studied. RESULTS: Fifty patients were identified. The most common vulvar symptoms were pain (74%), edema (60%), ulcerations (46%), nodules (36%), and abscess (34%). Medical management leading to symptomatic improvement varied, and 5 patients ultimately required surgery. DISCUSSION: Vulvar CD manifests with a broad spectrum of symptoms. Aggressive medical management was frequently effective, although surgery was required in 10% of cases.

Prevalence and Impact of Obesity on Disease-specific Outcomes in a Population-based Cohort of Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: There remains a historical misconception that inflammatory bowel disease [IBD] patients are underweight. However, recent data suggest rates of obesity in IBD parallel to those of the general population. The impact obesity has on the natural history of IBD is unclear. We aimed to determine obesity rates at the time of IBD diagnosis in a population-based cohort of ulcerative colitis [UC] patients. METHODS: Chart review was performed on patients diagnosed with UC over 1970-2010. Data were collected on demographics, body mass index [BMI], disease characteristics, IBD-specific hospitalisations, intestinal resection, and corticosteroid use. The proportion of patients who were obese at the time of their diagnosis was evaluated over time, and survival free of IBD-related complications was assessed using Kaplan-Meier survival analysis. RESULTS: A total of 417 adults were diagnosed with UC over 1970-2010, 55.4% of whom were classified as either overweight [34.8%] or obese [20.6%]. The prevalence of obesity increased 2-3-fold over the 40-year study period. Obese patients had a 72% increased risk of hospitalisation (hazard ratio [HR],1.72; 95% confidence interval [CI], 1.10-2.71; p = 0.018) when compared with normal weight patients. Additionally, with each incremental increase in BMI by 1 kg/m2, the risk of hospitalisation increased by 5% [HR,1.05; 95% CI, 1.01-1.08; p = 0.008] and risk of corticosteroid use increased by 2.6% [HR,1.026; 95% CI, 1.00-1.05; p = 0.05]. CONCLUSIONS: The prevalence of obesity in the UC population is increasing and may have negative prognostic implications, specifically regarding risk of future hospitalisation and corticosteroid use. Additional prospective studies are necessary to more clearly define these associations.

Obesity in inflammatory bowel disease: A review of its role in the pathogenesis, natural history, and treatment of IBD.

In contrast to previous perceptions that inflammatory bowel disease (IBD) patients are generally malnourished and underweight, there is mounting evidence to suggest that rates of obesity in IBD now mirror that of the general population. IBD is an immune-mediated condition that appears to develop in individuals who have not only a genetic predisposition to immune dysregulation but also likely exposure to various environmental factors which further potentiate this risk. With the surge in obesity alongside the rising incidence of IBD, particularly in developing nations, the role that obesity may play, not only in the pathogenesis but also in the natural history of disease has become a topic of growing interest. Currently available data exploring obesity's impact on the natural history of IBD are largely conflicting, potentially limited by the use of body mass index as a surrogate measure of obesity at varying time points throughout the disease course. While there are pharmacokinetic data to suggest possible detrimental effects that obesity may have on the response to medical therapy, results in this realm are also inconsistent. Moreover, not only is it unclear whether weight loss improves IBD outcomes, little is known about the safety and efficacy of available weight-loss strategies in this population. For these reasons, it becomes increasingly important to further understand the nature of any interaction between obesity and IBD.