Characteristics of Immune Checkpoint Inhibitor-Associated Gastritis: Report from a Major Tertiary Care Center.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have increased our ability to treat an ever-expanding number of cancers. We describe a case series of 25 patients who were diagnosed with gastritis following ICI therapy. MATERIALS AND METHODS: This was a retrospective study involving 1712 patients treated for malignancy with immunotherapy at Cleveland Clinic from January 2011 to June 2019 (IRB 18-1225). We searched electronic medical records using ICD-10 codes for gastritis diagnosis confirmed on endoscopy and histology within 3 months of ICI therapy. Patients with upper gastrointestinal tract malignancy or documented Helicobacter pylori-associated gastritis were excluded. RESULTS: Twenty-five patients were found to meet the criteria for diagnosis of gastritis. Of these 25 patients, most common malignancies were non-small cell lung cancer (52%) and melanoma (24%). Median number of infusions preceding symptoms was 4 (1-30) and time to symptom onset 2 (0.5-12) weeks after last infusion. Symptoms experienced were nausea (80%), vomiting (52%), abdominal pain (72%), and melena (44%). Common endoscopic findings were erythema (88%), edema (52%), and friability (48%). The most common diagnosis of pathology was chronic active gastritis in 24% of patients. Ninety-six percent received acid suppression treatment and 36% of patients also received steroids with an initial median dose of prednisone 75 (20-80) mg. Within 2 months, 64% had documented complete resolution of symptoms and 52% were able to resume immunotherapy. CONCLUSION: Patients presenting with nausea, vomiting, abdominal pain, or melena following immunotherapy should be assessed for gastritis and if other causes are excluded, may require treatment as consideration for complication of immunotherapy.

Patients and physicians' attitudes change on fecal microbiota transplantation for inflammatory bowel disease over the past 3 years.

BACKGROUND: In the past 3 years, increasing data and experience has become available regarding fecal microbiota transplantation (FMT) for the treatment of inflammatory bowel disease (IBD). However, how this increase in knowledge has impacted the attitudes of patients and physicians is largely unknown. This study aimed to investigate the change of patients' and physicians' attitudes towards FMT for IBD treatment. METHODS: Questionnaires for patient and physician attitude on FMT for IBD were pilot-tested and developed. Patients and physicians from the same groups completed the questionnaires in 2016 and 2019, separately. The attitudes towards efficacy, adverse events, and methodological features of FMT in 2016 were compared with those in 2019. RESULTS: A total of 1,255 questionnaires from 486 patients and 769 physicians were collected. Over the 3 years, an increased number of patients had heard of FMT and had similarly positive opinions towards using FMT for IBD therapy. Additionally, patients retained the tendency to overestimate the efficacy. The physicians' perceptions became closer to the findings reported in recent studies in 2019 compared with 2016. However, only a minority of patients and physicians understood the frequency required of FMT courses for induction of clinical remission. In particular, both patients and physicians underestimated the risk of mild adverse events and IBD flare. CONCLUSIONS: Patients are receptive towards FMT as therapy for IBD but opportunity remains to improve understanding of benefit and potential risks. Physicians also demonstrated knowledge gaps in use of this therapy. Aligning patient preference and physician knowledge gap will lead to better education and facilitate the development of decision-making guidelines.

The role of the transition clinic from pediatric to adult inflammatory bowel disease care.

PURPOSE OF REVIEW: The transition of patients from pediatric to adult centered care represents not only the means to transfer medical care to a group of providers who specialize in adult care but also is part of the process of the transfer of healthcare responsibility from the family to a patient. The intent of this review is to provide a summary of some of the important studies published in the past 2 years that advance this knowledge. RECENT FINDINGS: Progress has been made in the recognition of the process of transition, including developing tools to assess transition readiness, improving routes of communication along with patient education. Other studies provided information on patients' preferences for information seeking, types of family interactions, and factors that improved transition success. SUMMARY: In general, reported clinics and programs did demonstrate improvements in adherence, clinic retention, and even quality of life. Further studies should focus on clinical outcomes of transition programs and risk assessment for transitioning patients.

Challenges in Transitional Care in Inflammatory Bowel Disease: A Review of the Current Literature in Transition Readiness and Outcomes.

Transitional care for patients with IBD focuses on efforts to successfully transfer care from pediatric to adult providers while encouraging the assumption of health care responsibility. As 25% of patients will be diagnosed with IBD before the age of 18 years, many will undergo this process. Efforts to enhance this process have included transition clinics and other means to improve patient comfort with transition and develop the skill of health care self-management. Currently, most pediatric practitioners provide transition care with informal education and emphasize independence without formal programs. A variety of tools to assess transition readiness have been developed. Given the varied disease process, often varied and subjective outcomes, and lack of studies such as randomized controlled trials, further data are necessary to determine the best avenue to transition and assess outcomes. Critically relevant to providing adequate care to transitioning patients includes understanding the development of self-management skills and the developmental processes relevant to young adults with IBD. Transition represents an area for quality improvement, and although progress has been made in recognition and promotion of transition practices, future directions in research will allow improved understanding of the evidence-based practices and needs of these individuals to further enhance their care.

Vedolizumab in the treatment of Crohn's disease of the pouch.

BACKGROUND: Our recent study showed the efficacy and safety of vedolizumab in the treatment of chronic antibiotic-refractory pouchitis. However, there are no published studies on its efficacy and safety in Crohn's disease (CD) of the pouch. The aim of this study was to assess the efficacy and safety of vedolizumab in those patients. METHODS: This case series included all eligible patients with CD of the pouch from our prospectively maintained, IRB-approved Pouchitis Registry from 2015 to 2017. Disease activity in pouch patients can be monitored using the modified Pouchitis Disease Activity Index (mPDAI). mPDAI is the 18-point pouchitis disease activity index consisting of three principal component scores: symptom (range, 0-6 points), endoscopy, (range 0-6 points), and histology (range, 2-6 points). Pre- and post- treatment (minimum 6 months) pouchoscopy and clinical visits were used to calculate mPDAI. RESULTS: A total of 12 patients were included in this study, who had restorative proctocolectomy with ileal pouch anal anastomosis for medically refractory ulcerative colitis (UC). The mean age at the time of pre-colectomy diagnosis of UC was 25.0 ± 11.5 years. The mean current age was 41.0 ± 12.1 years, nine (75.0%) were female, three (25.0%) had smoked and eight (66.7%) had used anti-tumor necrosis factor agents prior to vedolizumab use. The mean duration of vedolizumab use was 1.0 ± 6.4 years. There was a significant reduction in mPDAI symptom subscores after vedolizumab therapy (3.50 ± 1.93 vs 5.08 ± 0.79, P = 0.015). The pre- and post-treatment mean endoscopy subscores were 1.25 ± 1.36 and 0.91 ± 1.50 in the afferent limb (P = 0.583); 2.58 ± 1.68 and 2.27 ± 2.05 (P = 0.701) in the pouch body; and 2.67 ± 1.93 and 2.09 ± 2.12 (P = 0.511) in the cuff, respectively. None of the patients experienced side effects throughout the vedolizumab therapy. CONCLUSION: The findings of our study suggests that vedolizumab appears to be effective and safe in reducing the symptoms in patients with CD of the pouch.

Women's health issues after ileal pouch surgery.

: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with ulcerative colitis and familial polyposis who require colectomy. This surgical intervention allows for resection of colon, while offering intestinal continuity with fecal continence, discontinuation of most medications related to ulcerative colitis and reduction in the risk of colitis-associated neoplasia. As a proportion of these patients are women of childbearing age, it is important to understand the impact on reproductive health and function. Although limited data exist, restorative proctocolectomy/IPAA does not seem to adversely affect menstrual function. In general, sexual function is reported to improve postsurgery with the ability to achieve orgasm unaltered. However, dyspareunia is commonly reported post restoratively. Of concern, there are data to suggest that fertility is decreased post-IPAA. The reasons stated are pelvic adhesions and obstruction of fallopian tubes. Laparoscopic approach may improve fertility outcomes by reducing postoperative adhesions as compared with the open approach. Once achieved, pregnancy in patients with IPAA is characterized by a transient increase in stool frequency that resolves postdelivery. Whether vaginal delivery or cesarean section is preferred route of delivery in these patients is still controversial. But commonly cesarean section is advocated for patients' post-IPAA to prevent anal sphincter injury and long-term effects on pouch function. All of these issues should be included in the discussion with women who are contemplating IPAA, so they are well aware of them before deciding on the best management plan.

Trends in hospitalizations of children with inflammatory bowel disease within the United States from 2000 to 2009.

BACKGROUND: The incidence and prevalence of pediatric inflammatory bowel disease (IBD) seems to be increasing in North America and Europe. Our objective was to evaluate hospitalization rates in children with IBD in the United States during the decade 2000 to 2009. METHODS: We analyzed cases with a discharge diagnosis of Crohn disease (CD) and ulcerative colitis (UC) within the Healthcare Cost and Utilization Project Kids' Inpatient Database, Agency for Healthcare Research and Quality. RESULTS: We identified 61,779 pediatric discharges with a diagnosis of IBD (CD, 39,451 cases; UC, 22,328 cases). The number of hospitalized children with IBD increased from 11,928 to 19,568 (incidence, 43.5-71.5 cases per 10,000 discharges per year; P < 0.001). For CD, the number increased from 7757 to 12,441 (incidence, 28.3-45.0; P < 0.001) and for UC, 4171 to 7127 (15.2-26.0; P < 0.001). Overall, there was a significant increasing trend for pediatric hospitalizations with IBD, CD, and UC (P < 0.001). In addition, there was an increase in IBD-related complications and comorbid disease burden (P < 0.01). CONCLUSION: There was a significant increase in the number and incidence of hospitalized children with IBD in the United States from 2000 to 2009.

Determination of serum antibodies to Clostridium difficile toxin B in patients with inflammatory bowel disease.

Clostridium difficile infection has increased in prevalence among patients with inflammatory bowel disease (IBD). Serum antibodies against C. difficile toxins have been detected in susceptible populations and may be protective; however, such antibodies have not been previously characterized in IBD patients. This study measured immunoglobulin G antibody levels to C. difficile toxin B in serum from IBD patients in remission and IBD patients in relapse. IBD patients demonstrated significantly higher antibody levels than non-IBD patients. In addition, a higher proportion of IBD patients in remission had positive antibody levels compared to IBD patients in relapse. Further characterization of antibody responses may elucidate understanding of susceptibility to C. difficile infection among IBD patients.

Transitional care in inflammatory bowel disease.

Transitional care is an organized effort to provide pediatric patients with the tools and resources they need to assume personal responsibility for their medical care while facilitating their transfer from a pediatrician to an adult practitioner. Since inflammatory bowel disease (IBD) is usually chronic and up to 25% of IBD patients are diagnosed before the age of 18 years, transitional care is an important consideration for adolescent and young adult patients. The importance of transitional care for chronic diseases that begin in childhood has been recognized in a number of published recommendations. However, most of these recommendations arise from intuitive reasoning, as physicians lack information regarding the need for transitional care, optimal delivery protocols, and the efficacy of transition programs. Even fewer studies have been published regarding transitional care in IBD. Current guidelines stress the importance of providing patients with educational resources to help them develop the skills they need to manage their care as independent adults, introducing the concept of transfer to adult care in advance of the actual transfer, and developing routes of communication to facilitate the transfer from pediatric to adult care providers. Future studies should aim to elucidate which programs are effective and how they should be implemented.

Antisense inhibition of ICAM-1 expression as therapy provides insight into basic inflammatory pathways through early experiences in IBD.

BACKGROUND: Alicaforsen (ISIS 2302), an antisense to intercellular adhesion molecule-1 (ICAM-1) (CD54), was designed to inhibit ICAM-1 expression. ICAM-1 seems to play a role in cell-mediated inflammation, specifically cell trafficking. For this reason, it may be useful in a variety of immune-mediated diseases, including inflammatory bowel disease. OBJECTIVE: To evaluate the use of alicaforsen in clinical trials to understand its efficacy and side effects, as well as assess for evidence that may offer insight into disease pathways. METHODS: We evaluate all of the available, published trials, with a focus on the prospective, randomized trials. RESULTS/CONCLUSIONS: Systemic treatment for Crohn's disease has not revealed significant effect. Topical enemas for ulcerative colitis have demonstrated some effect in secondary outcomes, and initial studies in pouchitis are promising. In general, the compound has been well tolerated and safe.

Gastric function in children with cystic fibrosis: effect of diet on gastric lipase levels and fat digestion.

The effect of diet, usual (44 +/- 4% energy as fat), high-fat (49 +/- 4% energy as fat), and moderate-fat (33 +/- 2% energy as fat), on gastric function (lipase and pepsin activities, pH, emptying rate) and intragastric digestion of fat were assessed in six children with cystic fibrosis. Fasting and postprandial activity of digestive enzymes, gastric pH, and gastric volume measured before, during, and after 120 min of feeding did not differ significantly as a function of fat intake. Postprandial gastric lipase output (units per kilogram of body weight) during usual, moderate-fat, and high-fat diets was close to or higher than (38.8 +/- 7.2, 44.9 +/- 8.6, and 54.8 +/- 5.5 U/kg per 20 min) gastric lipase output of premature infants (22.5 +/- 6.4 to 28.3 +/- 6.6 U/kg per 20 min) or of healthy adults (5.4 +/- 0.4 U/kg per 15 min) fed a high-fat diet. Postprandial pepsin output was higher (4749 +/- 797, 6117 +/- 925, and 5444 +/- 819 U/kg per 20 min) than in premature infants (597 +/- 77 to 743 +/- 97 U/kg per 20 min) or healthy adults (781 +/- 56 U/kg per 15 min). Eighty minutes after feeding gastric lipolysis reached 20 to 36%. This study shows that gastric lipase activity is high in cystic fibrosis patients maintained on diets providing 32% to 49% energy as fat, and that gastric lipase level did not increase over the ranges of dietary fat intake tested.