Dietary Interventions for the Treatment of Inflammatory Bowel Diseases: An Updated Systematic Review and Meta-analysis.

BACKGROUND & AIMS: This study aimed (1) to systematically review controlled trials of solid food diets for the treatment of inflammatory bowel disease (IBD); and (2) to grade the overall quality of evidence. METHODS: Systematic review of prospective controlled trials of solid food diets for the induction or maintenance of remission in IBD. Two authors independently performed study selection, data extraction, and assessment of certainty of evidence. Meta-analyses were performed on studies with quantitative data on response, remission, and relapse. RESULTS: There were 27 studies for meta-analysis. For induction of remission in Crohn's disease (CD), low refined carbohydrate diet and symptoms-guided diet outperformed controls, but studies had serious imprecision and very low certainty of evidence. The Mediterranean diet was similar to the Specific Carbohydrate Diet (low certainty of evidence), and partial enteral nutrition (PEN) was similar to exclusive enteral nutrition (very low certainty of evidence). PEN reduced risk of relapse (very low certainty of evidence), whereas reduction of red meat or refined carbohydrates did not (low certainty of evidence). For ulcerative colitis, diets were similar to controls (very low and low certainty of evidence). CONCLUSIONS: Among the most robust dietary trials in IBD currently available, certainty of evidence remains very low or low. Nonetheless, emerging data suggest potential benefit with PEN for induction and maintenance of remission in CD. Reduction of red meat and refined carbohydrates might not reduce risk of CD relapse. As more dietary studies become available, the certainty of evidence could improve, thus allowing for more meaningful recommendations for patients.

Acute Liver Failure Guidelines.

Acute liver failure (ALF) is a rare, acute, potentially reversible condition resulting in severe liver impairment and rapid clinical deterioration in patients without preexisting liver disease. Due to the rarity of this condition, published studies are limited by the use of retrospective or prospective cohorts and lack of randomized controlled trials. Current guidelines represent the suggested approach to the identification, treatment, and management of ALF and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence was reviewed using the Grading of Recommendations, Assessment, Development and Evaluation process to develop recommendations. When no robust evidence was available, expert opinions were summarized using Key Concepts. Considering the variety of clinical presentations of ALF, individualization of care should be applied in specific clinical scenarios.

American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease.

This guideline presents an update to the 2013 American College of Gastroenterology Guideline on the Diagnosis and Management of Celiac Disease with updated recommendations for the evaluation and management of patients with celiac disease (CD). CD is defined as a permanent immune-mediated response to gluten present in wheat, barley, and rye. CD has a wide spectrum of clinical manifestations that resemble a multisystemic disorder rather than an isolated intestinal disease, and is characterized by small bowel injury and the presence of specific antibodies. Detection of CD-specific antibodies (e.g., tissue transglutaminase) in the serum is very helpful for the initial screening of patients with suspicion of CD. Intestinal biopsy is required in most patients to confirm the diagnosis. A nonbiopsy strategy for the diagnosis of CD in selected children is suggested and discussed in detail. Current treatment for CD requires strict adherence to a gluten-free diet (GFD) and lifelong medical follow-up. Most patients have excellent clinical response to a GFD. Nonresponsive CD is defined by persistent or recurrent symptoms despite being on a GFD. These patients require a systematic workup to rule out specific conditions that may cause persistent or recurrent symptoms, especially unintentional gluten contamination. Refractory CD is a rare cause of nonresponsive CD often associated with poor prognosis.

ACG Clinical Guideline: Diagnosis and Management of Biliary Strictures.

A biliary stricture is an abnormal narrowing in the ductal drainage system of the liver that can result in clinically and physiologically relevant obstruction to the flow of bile. The most common and ominous etiology is malignancy, underscoring the importance of a high index of suspicion in the evaluation of this condition. The goals of care in patients with a biliary stricture are confirming or excluding malignancy (diagnosis) and reestablishing flow of bile to the duodenum (drainage); the approach to diagnosis and drainage varies according to anatomic location (extrahepatic vs perihilar). For extrahepatic strictures, endoscopic ultrasound-guided tissue acquisition is highly accurate and has become the diagnostic mainstay. In contrast, the diagnosis of perihilar strictures remains a challenge. Similarly, the drainage of extrahepatic strictures tends to be more straightforward and safer and less controversial than that of perihilar strictures. Recent evidence has provided some clarity in multiple important areas pertaining to biliary strictures, whereas several remaining controversies require additional research. The goal of this guideline is to provide practicing clinicians with the most evidence-based guidance on the approach to patients with extrahepatic and perihilar strictures, focusing on diagnosis and drainage.

Pneumococcal Vaccination Recommendation and Completion Rates Among Patients With Inflammatory Bowel Disease and Barriers to Vaccination.

BACKGROUND: Guidelines for inflammatory bowel disease (IBD) patients receiving immunosuppression encouraged both the pneumococcal polysaccharide vaccine (PPSV23) and the pneumococcal conjugate vaccine (PCV13). We aimed to evaluate which pneumococcal vaccines are recommended and administered, and to understand provider and IBD patient knowledge regarding pneumococcal vaccinations. METHODS: We performed a retrospective, cross-sectional analysis of 357 adult IBD patients on immunosuppression in our health care system. Patient demographics and clinical characteristics were collected. The primary outcome was rate of documented vaccinations recommended by providers; the secondary outcome was rate of receipt of the vaccines. We identified factors associated with receipt of any pneumococcal vaccine through multivariable logistic regression. We also performed provider and IBD patient surveys to understand provider and patient knowledge regarding pneumococcal vaccines. We used χ 2 and Fisher exact tests to assess survey responses. RESULTS: Fifty seven percent of IBD patients had any pneumococcal vaccination recommended and 35% had recommendations for both PPSV23 and PCV13. Forty percent received any pneumococcal vaccine and 18% received both vaccines. In multivariable analyses, increasing age (adjusted odds ratio: 1.03, 95% CI: 1.01-1.05) was associated with receipt of any pneumococcal vaccine, after adjusting for gender, race, insurance, disease activity, and time seen in our gastroenterology clinics. In the survey study, on average, 59% of providers correctly answered questions regarding pneumococcal vaccination indications. CONCLUSION: In our health care system, while recommendation for any pneumococcal vaccination was >50%, receipt of both PPSV23 and PCV13 was low. Simplified vaccine regimens (ie, PCV20) will likely improve vaccination rates.

Vitamin D for the treatment of inflammatory bowel disease.

BACKGROUND: Vitamin D possesses immunomodulatory properties and has been implicated in the pathogenesis and severity of inflammatory bowel disease (IBD). Animal studies and emerging epidemiological evidence have demonstrated an association between vitamin D deficiency and worse disease activity. However, the role of vitamin D for the treatment of IBD is unclear. OBJECTIVES: To evaluate the benefits and harms of vitamin D supplementation as a treatment for IBD. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was Jun 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people of all ages with active or inactive IBD comparing any dose of vitamin D with another dose of vitamin D, another intervention, placebo, or no intervention. We defined doses as: vitamin D (all doses), any-treatment-dose vitamin D (greater than 400 IU/day), high-treatment-dose vitamin D (greater than 1000 IU/day), low-treatment-dose vitamin D (400 IU/day to 1000 IU/day), and supplemental-dose vitamin D (less than 400 IU/day). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. clinical response for people with active disease, 2. clinical relapse for people in remission, 3. quality of life, and 4. withdrawals due to adverse events. Our secondary outcomes were 5. disease activity at end of study, 6. normalisation of vitamin D levels at end of study, and 7. total serious adverse events. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included 22 RCTs with 1874 participants. Study duration ranged from four to 52 weeks. Ten studies enroled people with Crohn's disease (CD), five enroled people with ulcerative colitis (UC), and seven enroled people with CD and people with UC. Seventeen studies included adults, three included children, and two included both. Four studies enroled people with active disease, six enroled people in remission, and 12 enroled both. We assessed each study for risk of bias across seven individual domains. Five studies were at low risk of bias across all seven domains. Ten studies were at unclear risk of bias in at least one domain but with no areas of high risk of bias. Seven studies were at high risk of bias for blinding of participants and assessors. Vitamin D (all doses) versus placebo or no treatment Thirteen studies compared vitamin D against placebo or no treatment. We could not draw any conclusions on clinical response for UC as the certainty of the evidence was very low (risk ratio (RR) 4.00, 95% confidence interval (CI) 1.51 to 10.57; 1 study, 60 participants). There were no data on CD. There may be fewer clinical relapses for IBD when using vitamin D compared to placebo or no treatment (RR 0.57, 95% CI 0.34 to 0.96; 3 studies, 310 participants). The certainty of the evidence was low. We could not draw any conclusions on quality of life for IBD (standardised mean difference (SMD) -0.13, 95% CI -3.10 to 2.83 (the SMD value indicates a negligent decrease in quality of life, and the corresponding CIs indicate that the effect can range from a large decrease to a large increase in quality of life); 2 studies, 243 participants) or withdrawals due to adverse events for IBD (RR 1.97, 95% CI 0.18 to 21.27; 12 studies, 1251 participants; note 11 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 12). The certainty of the evidence was very low. High-treatment-dose vitamin D versus low-treatment-dose vitamin D Five studies compared high treatment vitamin D doses against low treatment vitamin D doses. There were no data on clinical response. There may be no difference in clinical relapse for CD (RR 0.48, 95% CI 0.23 to 1.01; 1 study, 34 participants). The certainty of the evidence was low. We could not draw any conclusions on withdrawals due to adverse events for IBD as the certainty of the evidence was very low (RR 0.89, 95% CI 0.06 to 13.08; 3 studies, 104 participants; note 2 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 3). The data on quality of life and disease activity could not be meta-analysed, were of very low certainty, and no conclusions could be drawn. Any-treatment-dose vitamin D versus supplemental-dose vitamin D Four studies compared treatment doses of vitamin D against supplemental doses. There were no data on clinical response and relapse. There were no data on quality of life that could be meta-analysed. We could not draw any conclusions on withdrawals due to adverse events for IBD as the certainty of the evidence was very low (RR 3.09, 95% CI 0.13 to 73.17; 4 studies, 233 participants; note 3 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 4). AUTHORS' CONCLUSIONS: There may be fewer clinical relapses when comparing vitamin D with placebo, but we cannot draw any conclusions on differences in clinical response, quality of life, or withdrawals, due to very low-certainty evidence. When comparing high and low doses of vitamin D, there were no data for clinical response, but there may be no difference in relapse for CD. We cannot draw conclusions on the other outcomes due to very low certainty evidence. Finally, comparing vitamin D (all doses) to supplemental-dose vitamin D, there were no data on clinical relapse or response, and we could not draw conclusions on other outcomes due to very low certainty evidence or missing data. It is difficult to make any clear recommendations for future research on the basis of the findings of this review. Future studies must be clear on the baseline populations, the purpose of vitamin D treatment, and, therefore, study an appropriate dosing strategy. Stakeholders in the field may wish to reach consensus on such issues prior to new studies.

Avoidant Restrictive Food Intake Disorder Prevalent Among Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) alter their dietary behaviors to reduce disease-related symptoms, avoid feared food triggers, and control inflammation. This study aimed to estimate the prevalence of avoidant/restrictive food intake disorder (ARFID), evaluate risk factors, and examine the association with risk of malnutrition in patients with IBD. METHODS: This cross-sectional study recruited adult patients with IBD from an ambulatory clinic. ARFID risk was measured using the Nine-Item ARFID Screen. Nutritional risk was measured with the Patient Generated-Subjective Global Assessment. Logistic regression models were used to evaluate the association between clinical characteristics and a positive ARFID risk screen. Patient demographics, disease characteristics, and medical history were abstracted from medical records. RESULTS: Of the 161 participants (Crohn's disease, 45.3%; ulcerative colitis, 51.6%; IBD-unclassified, 3.1%), 28 (17%) had a positive ARFID risk score (≥24). Most participants (92%) reported avoiding 1 or more foods while having active symptoms, and 74% continued to avoid 1 or more foods even in the absence of symptoms. Active symptoms (odds ratio, 5.35; 95% confidence interval, 1.91-15.01) and inflammation (odds ratio, 3.31; 95% confidence interval, 1.06-10.29) were significantly associated with positive ARFID risk. Patients with a positive ARFID risk screen were significantly more likely to be at risk for malnutrition (60.7% vs 15.8%; P < .01). CONCLUSIONS: Avoidant eating behaviors are common in IBD patients, even when in clinical remission. Patients who exhibit active symptoms and/or inflammation should be screened for ARFID risk, with referrals to registered dietitians to help monitor and address disordered eating behaviors and malnutrition risk.

What's New in the Postoperative Management of Crohn's Disease?

Patients with Crohn's disease (CD) often require surgical resection due to complications, such as strictures and abscesses, or disease refractory to medical therapy. To understand the evolving management of patients with CD after surgery, we outline the risk factors for postoperative recurrence, advances in postoperative endoscopic evaluation and characterization of recurrence, noninvasive methods of assessing postoperative recurrence, use of postoperative prophylactic medical therapy including newer biologics, and novel surgical methods to reduce postoperative recurrence. The Rutgeerts score (RS) was developed to predict progression of disease based on endoscopic appearance postoperatively and to guide medical therapy. However, this scoring system groups ileal and anastomotic lesions into the same category. A modified RS was developed to separate lesions isolated to the anastomosis and those in the neo-terminal ileum to further understand the role of anastomotic lesions in CD progression. Additional scoring systems have also been evaluated to better understand these differences. In addition, noninvasive diagnostic methods, such as small bowel ultrasound, have high sensitivity and specificity for the detection of postoperative recurrence and are being evaluated as independent methods of assessment. Studies have also shown a reduction in endoscopic recurrence with postoperative anti-TNFα therapy. However, preoperative exposure to anti-TNFα therapy may impact postoperative response to these medications, and therefore, determining optimal postoperative prophylaxis strategy for biologic-experienced patients requires further exploration. Lastly, new surgical modalities to reduce postoperative recurrence are currently being investigated with preliminary data suggesting that an antimesenteric functional end-to-end anastomosis (Kono-S) may decrease postoperative recurrence.

Thiopurine Monotherapy Is Effective in Maintenance of Mild-Moderate Inflammatory Bowel Disease.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are complex, inflammatory bowel diseases (IBD) with debilitating complications. While severe IBD typically requires biologic agents, the optimal therapy for mild-moderate IBD is less clear. AIMS: To assess the efficacy of thiopurine monotherapy for maintenance of mild-moderate IBD and clinical variables associated with treatment outcome. METHODS: This retrospective study included adults with mild-moderate IBD who were started on thiopurines without biologic therapy. The primary outcome was therapy failure, defined by disease progression based on clinical, endoscopic, and radiologic criteria. Clinical variables were extracted at time of thiopurine initiation. Univariable and multivariable Cox proportional hazards models were used to examine the independent contribution of the clinical variables on treatment response. RESULTS: From 230 CD patients, 64 (72%) were free of treatment failure with mean follow-up of 3.3 years. In our multivariable model, thiopurine failure was associated with concomitant systemic steroid administration (aHR 2.43, p = 0.001), whereas protective factors included concomitant oral 5-aminosalicylic acid (5-ASA) therapy (aHR 0.54, p = 0.02) and non-fistulizing, non-stricturing disease (aHR 0.57, p = 0.047). From 173 UC patients, 50 (71%) were free from treatment failure with mean follow-up of 3.3 years. On multivariable analysis, concomitant oral steroids were associated with thiopurine failure (aHR 2.71, p = 0.001). Only 13 (4%) discontinued thiopurines from adverse effects. CONCLUSIONS: In mild-moderate uncomplicated IBD, thiopurine monotherapy was associated with longitudinal maintenance of remission and may represent a lower-cost, convenient, and effective alternative to biologics. Multiple clinical variables were predictive of treatment response.

ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections.

Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not the only, approach to clinical scenarios.

Rates of inflammatory bowel disease in Hispanics comparable to non-Hispanic Whites: results of a cohort study.

PURPOSE: Previous studies have suggested that inflammatory bowel disease (IBD) occurs at higher rates among non-Hispanic Whites (NHWs) compared to other ethnicities; however, Hispanics as the largest minority in the United States remain underrepresented in IBD research and we hypothesize that they have similar rates of IBD. We examined the epidemiology, demographics, clinical presentation, and treatment of IBD in a predominantly Hispanic cohort in Los Angeles (LA) County. METHODS: This was a retrospective cohort study based at Olive View-UCLA Medical Center, one of the three major safety-net hospitals in LA County. Electronic medical records from 2015 to 2018 were queried, and biopsy-proven cases of IBD (n = 170) were identified. Outcomes included the incidence and prevalence of IBD, disease distribution, treatment, and IBD-related surgery. RESULTS: The incidence of IBD among Hispanics was 175 (95% confidence interval [CI] 127-240) and 113 (95% CI 62-200) for NHWs per 100,000 person-years. Prevalence of IBD per 100,000 people was 418 (95% CI 341-512) for Hispanics and 557 (95% CI 431-739) for NHWs. Notably, the proportion of Hispanic IBD patients with a history of smoking was 21.5% vs 50.8% in NHWs (p = 0.011). There were no significant differences between the two groups with regard to Montreal classification, pharmacotherapy, or IBD-related surgery. CONCLUSIONS: In one of the largest US studies of Hispanics with IBD, and the only one to have both clinical and histopathologic confirmation as inclusion criteria, we found the incidence and prevalence of IBD among Hispanics to be higher than previously recognized and comparable to NHWs. Additionally, Hispanic IBD patients had lower rates of smoking compared to NHWs.

Stopping Mesalamine Therapy in Patients With Crohn's Disease Starting Biologic Therapy Does Not Increase Risk of Adverse Outcomes.

BACKGROUND & AIMS: Little is known about the effects of discontinuing mesalamine therapy for patients with Crohn's disease (CD) who initiate therapy with an anti-tumor necrosis factor (anti-TNF) agent. We analyzed data from 2 national population cohorts to compare outcomes of patients with CD already on mesalamine therapy who started treatment with an anti-TNF agent and then either stopped or continued mesalamine. METHODS: The primary outcome was any adverse clinical event, defined as a composite of new corticosteroid use or CD-related hospitalization or surgery. We collected data from the Truven MarketScan (IBM, Armonk, NY) health claims database in the United States and the Danish health registers. Our analysis included patients with CD who started anti-TNF therapy after at least 90 days of oral mesalamine therapy. Patients were classified as stopping mesalamine if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors, and health care utilization. Adjusted hazard ratios with 95% CIs were calculated, comparing stopping mesalamine with continuing mesalamine. RESULTS: A total of 3178 patients with CD were included in our final analysis (2960 in the United States and 218 in Denmark). Stopping mesalamine after initiating anti-TNF therapy was not associated with an increased risk of adverse clinical events in the US cohort (adjusted hazard ratio, 0.89; 95% CI, 0.77-1.03; P = .13) or in the Danish cohort (adjusted hazard ratio, 1.13; 95% CI, 0.68-1.87; P = .63). Similar results were obtained from sensitivity analyses of concomitant immunomodulator use and duration of mesalamine treatment before initiation of anti-TNF therapy. CONCLUSIONS: In a retrospective analysis of 2 national databases, we found that stopping mesalamine therapy for patients with CD who were starting anti-TNF therapy did not increase their risk of adverse clinical events. These results should be validated in a prospective study.

Levels of Vitamin D Are Low After Crohn's Disease Is Established But Not Before.

BACKGROUND & AIMS: Low serum levels of vitamin D have been associated with Crohn's disease (CD). However, it is unclear whether low vitamin D levels cause CD or CD reduces serum vitamin D. METHODS: United States military personnel with CD (n = 240) and randomly selected individuals without CD (controls, n = 240) were matched by age, sex, race, military branch, and geography. We measured 25-hydroxyvitamin D in sera 8-3 years (pre-2) and 3 years to 3 months before diagnosis (pre-1) and 3 months before through 21 months after diagnosis (pre-0). We genotyped VDR and GC vitamin D related polymorphisms. We used conditional logistic regression, including adjustments for smoking, season, enlistment status, and deployment, to estimate relative odds of CD according to vitamin D levels and interactions between genetic factors and levels of vitamin D. RESULTS: Levels of vitamin D before diagnosis were not associated with CD in pre-2 (P trend = .65) or pre-1 samples (P trend = .84). However, we found an inverse correlation between CD and highest tertile of vitamin D level in post-diagnosis samples (P trend = .01; odds ratio, 0.51; 95% CI, 0.30-0.86). Interactions were not detected between vitamin D levels and VDR or GC polymorphisms. We observed an association between VDR Taq1 polymorphism and CD (independent of vitamin D) (P = .02). CONCLUSIONS: In serum samples from military personnel with CD and matched controls, we found no evidence for an association between CD and vitamin D levels up to 8 years before diagnosis. However, we observed an inverse-association between post-diagnosis vitamin D levels and CD. These findings suggest that low vitamin D does not contribute to development of CD-instead, CD leads to low vitamin D.

Trends in EMR for nonmalignant colorectal polyps in the United States.

BACKGROUND AND AIMS: Although most large nonpedunculated colorectal lesions can be safely and efficaciously removed using EMR, the use of colectomy for benign colorectal lesions appears to be increasing. The reason(s) is unclear. We aimed to determine the use and adverse events of EMR in the United States. METHODS: We used Optum's de-identified Clinformatics Data Mart Database (2003-2016), a database from a large national insurance provider, to identify all colonoscopies performed with either EMR or simple polypectomy on adult patients from January 1, 2011 to December 31, 2015. We measured time trends, regional variation, and adverse event rates. We assessed risk factors for adverse events using multivariate logistic regression. RESULTS: The rate of EMR use in the US increased from 1.62% of all colonoscopies in 2011 to 2.48% of colonoscopies in 2015 (P < .001). There were, however, significant regional differences in the use of EMRs, from 2.4% of colonoscopies in the western United States to 2.0% of colonoscopies in the southern United States. Between 2011 and 2015, we found stable rates of perforation, GI bleeding (GIB), infections, and cardiac adverse events and decreasing rates of admissions after EMR. In our multivariate model, EMR was an independent risk factor for adverse events, albeit the rates of adverse events were low (1.35% GIB, .22% perforation). CONCLUSIONS: Use of EMR is rising in the United States, although there is significant regional variation. The rates of adverse events after EMR and polypectomies were low and stable, confirming the continued safety of EMR procedures. A better understanding of the regional barriers and facilitators may improve the use of EMR as the standard management for benign colorectal lesions throughout the United States.

Cytomegalovirus infection is associated with worse outcomes in inflammatory bowel disease hospitalizations nationwide.

BACKGROUND: Cytomegalovirus (CMV) infection may complicate ulcerative colitis (UC) or Crohn's disease (CD) hospitalizations. Studies examining this relationship are often single-center examining short time periods. AIMS: To quantify the prevalence of CMV and its impact on outcomes among UC and CD hospitalizations over time using nationwide administrative databases. METHODS: The National Inpatient Sample and Nationwide Readmissions Database were analyzed to calculate CMV prevalence per 1000 UC and CD hospitalizations between 1998 and 2014. Univariable and multivariable logistic and linear regression were used to assess CMV's association with outcomes. Separate analyses examined effects from the introduction of anti-TNF therapy in UC in 2005, CD anatomic extent, and Clostridioides difficile infection. RESULTS: Among UC, from 1998 to 2014, the prevalence of CMV infection rose from 1.4 to 6.3 per 1000 UC hospitalizations (p < 0.001), although this increase was not statistically significant for the years 2006 to 2014 (p = 0.07). Among CD, prevalence rose from 0.3 to 1.8 per 1000 CD hospitalizations (p < 0.001) from 1998 to 2014. CMV was independently associated with increased inpatient mortality (UC: odds ratio (OR) 2.3, 95% confidence interval (CI) 1.2-4.5; CD: OR 4.6, CI 1.5-13.7), colectomy in UC (OR 2.5, CI 1.9-3.3), and higher length of stay and costs. CONCLUSION: CMV infection's prevalence among UC and CD hospitalizations is rising over time, but may have slowed after 2005 in UC. CMV is independently associated with increased inpatient mortality, length of stay, and hospital charges in UC and CD and with colectomy in UC.

Fecal Microbiota Transplantation for Chronic Liver Diseases: Current Understanding and Future Direction.

Chronic liver disease is a major cause of morbidity and mortality worldwide. Even though effective treatments are now available for most chronic viral hepatitis, treatment options for other causes of chronic liver disease remain inadequate. Recent research has revealed a previously unappreciated role that the human intestinal microbiome plays in mediating the development and progression of chronic liver diseases. The recent remarkable success of fecal microbiota transplantation (FMT) in treating Clostridioides difficile demonstrates that the intestinal microbiota can be manipulated to obtain favorable therapeutic benefits and that FMT may become an important component of a total therapeutic approach to effectively treat hepatic disorders.

Reduction in Hospitalizations for Esophageal Reflux in a Decade with Minimal Increases in Other Functional and Motor Disorders.

BACKGROUND: Functional and motility disorders (FMDs) are common conditions that cause significant morbidity and economic loss. A comprehensive analysis of these disorders and their impact has not been done in an inpatient setting. AIMS: We seek to evaluate adult hospitalization trends for FMDs in the USA. METHODS: The National Inpatient Sample between 2005 and 2014 was analyzed. Poisson regression was used to assess hospitalization trends for FMDs referenced to non-FMD hospitalizations. Linear regression was used to assess cost per hospitalization and length of stay (LOS). All models were adjusted for age, sex, primary insurance, and Charlson comorbidity index. RESULTS: Hospitalizations with FMDs as the primary diagnosis fell by an adjusted 2.46%/year over the study period (p < 0.001). The entirety of this reduction was explained by falling admissions for gastroesophageal reflux (adjusted reduction of 7.04%/year, p < 0.001). The hospitalization rate for all other FMDs (excluding gastroesophageal reflux) minimally increased by 0.75%/year (p = 0.001). Total cost of care for FMD hospitalizations remained relatively stable ($3.17 billion in 2014), while increasing for all other hospitalizations. Mean LOS for FMD hospitalization increased by an adjusted 0.025 days/year, but decreased by 0.038 days/year for all other hospitalizations (p < 0.001). CONCLUSIONS: The hospitalization rate for gastroesophageal reflux fell between 2005 and 2014, but remained relatively stable to increase for all other FMDs. These trends may be due to increased proton pump inhibitor use, better patient/provider education, emphasis on outpatient management, and/or coding bias.

Probiotics for induction of remission in Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, in which the pathogenesis is believed to be partly influenced by the gut microbiome. Probiotics can be used to manipulate the microbiome and have therefore been considered as a potential therapy for CD. There is some evidence that probiotics benefit other gastrointestinal conditions, such as irritable bowel syndrome and ulcerative colitis, but their efficacy in CD is unclear. This is the first update of a Cochrane Review previously published in 2008. OBJECTIVES: To assess the efficacy and safety of probiotics for the induction of remission in CD. SEARCH METHODS: The following electronic databases were searched: MEDLINE (from inception to 6 July 2020), Embase (from inception to 6 July 2020), the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane IBD Review Group Specialised Trials Register, World Health Organization (WHO) International Clinical Trials Registry, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared probiotics with placebo or any other non-probiotic intervention for the induction of remission in CD were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the methodological quality of included studies. The primary outcome was clinical remission. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes. MAIN RESULTS: There were two studies that met criteria for inclusion. One study from Germany had 11 adult participants with mild-to-moderate CD, who were treated with a one-week course of corticosteroids and antibiotics (ciprofloxacin 500 mg twice daily and metronidazole 250 mg three times a day), followed by randomised assignment to Lactobacillus rhamnosus strain GG (two billion colony-forming units per day) or corn starch placebo. The other study from the United Kingdom (UK) had 35 adult participants with active CD (CDAI score of 150 to 450) randomised to receive a synbiotic treatment (comprised of freeze-dried Bifidobacterium longum and a commercial product) or placebo. The overall risk of bias was low in one study, whereas the other study had unclear risk of bias in relation to random sequence generation, allocation concealment, and blinding. There was no evidence of a difference between the use of probiotics and placebo for the induction of remission in CD (RR 1.06; 95% CI 0.65 to 1.71; 2 studies, 46 participants) after six months. There was no difference in adverse events between probiotics and placebo (RR 2.55; 95% CI 0.11 to 58.60; 2 studies, 46 participants). The evidence for both outcomes was of very low certainty due to risk of bias and imprecision. AUTHORS' CONCLUSIONS: The available evidence is very uncertain about the efficacy or safety of probiotics, when compared with placebo, for induction of remission in Crohn's disease. There is a lack of well-designed RCTs in this area and further research is needed.

Epidemiology and implications of concurrent diagnosis of eosinophilic oesophagitis and IBD based on a prospective population-based analysis.

OBJECTIVE: Eosinophilic oesophagitis (EoO) and IBD are immune-mediated diseases of the gastrointestinal tract with possible overlapping pathogenic mechanisms. Our aim was to define the epidemiology and clinical implications of concurrent EoO and IBD diagnoses. DESIGN: We conducted a prospective cohort analysis using the Truven MarketScan database (2009-2016) to estimate the incidence and prevalence of EoO in patients with Crohn's disease (CD) or UC and vice versa. Cox proportional hazards and Kaplan-Meier methods were used to estimate the risk of EoO-related or IBD-related complications among patients with concurrent diagnoses. RESULTS: Among 134 013 536 individuals, the incidence of EoO, CD and UC were 23.1, 51.2 and 55.2 per 100 000 person-years, respectively. The risk of EoO was higher among patients with CD (incidence rate ratio [IRR] 5.4, p<0.01; prevalence ratio (PR) 7.8, p<0.01) or UC (IRR 3.5, p<0.01; PR 5.0, p<0.01), while the risk of IBD was higher among patients with EoO (CD: IRR 5.7, p<0.01; PR 7.6, p<0.01; UC: IRR 3.4, p<0.01; PR 4.9, p<0.01) versus individuals without either diagnosis. Concurrent diagnosis of EoO and IBD was associated with greater composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.09, p=0.01; UC: aHR 1.10, p=0.04) but lower composite risk of EoO-related complications (aHR 0.59; p<0.01). CONCLUSION: Based on a population-based prospective cohort analysis, the risk of EoO is significantly higher among patients with IBD and vice versa. Concurrent diagnoses might modify the risk of IBD-related and EoO-related complications. Studies defining the mechanisms underlying these observations are needed.

Stopping 5-aminosalicylates in patients with ulcerative colitis starting biologic therapy does not increase the risk of adverse clinical outcomes: analysis of two nationwide population-based cohorts.

OBJECTIVE: The benefit of continuing 5-aminosalicylate (5-ASA) in patients with ulcerative colitis (UC) who initiate anti-tumour necrosis factor-alpha (anti-TNF) biologics is unknown. We aimed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA. DESIGN: Our primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, UC-related hospitalisation or surgery. We used two national databases: the United States (US) Truven MarketScan health claims database and the Danish health registers. Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included. Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors and healthcare utilisation. Adjusted HRs (aHR) with 95% CI are reported comparing stopping 5-ASA with continuing 5-ASA. RESULTS: A total of 3589 patients with UC were included (2890 US and 699 Denmark). Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort (aHR 1.04; 95% CI 0.90 to 1.21, p=0.57) nor in the Danish cohort (aHR 1.09; 95% CI 0.80 to 1.49, p=0.60). Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF. CONCLUSION: In two national databases, stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events. These results should be validated in a prospective clinical trial.