Cytokine Release Syndrome-Associated Colitis: Insights From a Case of Rituximab-Induced Pancolitis.

Rituximab (RTX), a widely used monoclonal antibody for hematologic malignancies and rheumatologic disorders, is known for infusion-related reactions. However, its potential to induce colitis is often overlooked. We present an 85-year-old woman with chronic lymphocytic leukemia experiencing severe adverse effects during her fourth RTX infusion, including abdominal pain, hypotension, and bright red blood per rectum. Computed tomography of the abdomen and pelvis with contrast revealed pancolonic mural wall thickening without perforation. Prompt treatment with vasopressors and intravenous fluids led to symptom resolution within 24 hours. We highlighted the importance of recognizing RTX-induced colitis and discussed and depicted immunological dysregulation mechanisms involved.

Endoscopic Ultrasound-guided Jejunocolostomy for Management of Refractory Severe Obesity in a Post-gastric Bypass Patient.

Obesity is a complex disease process, which often requires multifactorial, patient-tailored strategies for effective management. Treatment options include lifestyle optimization, pharmacotherapy, endobariatrics, and bariatric metabolic endoscopy. Obesity-based interventions can be challenging in patient populations with severe obesity, particularly post-gastric bypass. We report the case of a non-surgical patient with a failed remote open gastric bypass, who underwent an endoscopic small bowel diversion procedure, resulting in partial caloric diversion, via the creation of an EUS-guided jejunocolostomy (EUS-JC). The procedure is an extension of prior reported EUS-guided and magnet-based small bowel bypass procedures, in this case, for the purposes of weight loss (Kahaleh et al., 1; Jonica et al. Gastrointest Endosc. 97(5):927-933, 2; Machytka et al. Gastrointest Endosc. 86(5):904-912, 3;). The procedure was performed without peri-procedural complications, with effective weight loss during follow-up. Endoscopic bariatric interventions that target the small bowel, such as EUS-JC, offer promising tools for obesity management and should be studied further. Numerous factors including lifestyle, psychosocial, genetic, behavioral, and secondary disease processes contribute to obesity. Severe obesity (defined as a BMI > 50 kg/m2) is associated with increased morbidity and mortality with a significantly reduced response to treatment (Flegal et al. JAMA. 309(1):71-82, 4;). Weight regain can be noted in up to 50% of patients post-RYGB. In populations with severe obesity, there is an associated 5-year surgical failure rate of 18% (Magro et al. Obesity Surg. 18(6):648-51, 5;). These patients may not be surgical candidates for revision or can develop post-revision chronic protein-caloric malnutrition (Shin et al. Obes Surg. 29(3):811-818, 6;). Lifestyle, modification, pharmacotherapy, or endoscopic transoral reduction (TORe) can be effective generally; however, in patients with severe obesity, the total desired excess body weight loss may not likely be accomplished solely by these strategies. An endoscopic small bowel intervention that diverts a portion of caloric intake from small bowel absorption can potentially promote weight loss similar to a surgical lengthening of the Roux limb (Shah et al. Obes Surg. 33(1):293-302, 7; Hamed et al. Annal Surg. 274(2):271-280, 8;), in the sense that there is a reduction in the total small bowel surface area for absorption. Roux limb distalization can be effective for weight regain for post bypass patients. The EUS-JC technique aims to work similarly by reducing the total small bowel surface area utilized for absorption. Since this patient was deemed a non-surgical candidate, an EUS-guided jejunocolostomy was offered. Prior to the procedure, the patient established longitudinal care with our bariatric nutritionist and obesity medicine services. Extensive pre-bariatric labs were screened to rule out confounders for recurrent severe obesity. Intra-procedure, the patient received one dose of 500 mg intravenous levofloxacin. Post-procedure, loperamide was prescribed every 8 h as needed for post-procedure diarrhea. Within 2 weeks, the patient was no longer taking anti-diarrheals. The post-procedure diet consisted of a liquid diet for 2 days before advancement to a low-residue diet for 1 month, and then a regular diet.

Mycobacterium avium subspecies paratuberculosis (MAP) and Crohn's disease: the debate continues.

Crohn's disease (CD) in humans and Johne's disease (JD) in ruminants share numerous clinical and pathologic similarities. As Mycobacteria avium subspecies paratuberculosis (MAP) is known to fulfill Koch's postulates as the cause of JD, there has been considerable debate over the past century about whether MAP also plays a role in CD. With recent advances in MAP identification techniques, we can now demonstrate a higher presence of MAP in CD patients compared to the general population. However, it remains unclear if MAP is playing a bystander role or is directly pathogenic in these patients. Studies have shown that there may be an immune response targeting MAP in these patients, which may underlie a pathologic role in CD. Clinical studies have yielded conflicting results as to whether anti-MAP therapy improves clinical outcomes in CD, leading to the lack of its inclusion within evidence-based clinical guidelines. Additionally, many of these studies have been small case series, with only a few randomized controlled trials published to date. In this article, we will discuss the historical context of MAP in CD, review clinical and laboratory data surrounding detection of MAP and possible pathogenesis in human disease, and suggest future directions which may finally provide some clarity to this debate.

Phenotype and Natural History of Inflammatory Bowel Disease in Patients With Concomitant Eosinophilic Esophagitis.

BACKGROUND: The co-occurrence of autoimmune diseases is well recognized. Though studies have suggested that eosinophilic esophagitis (EoE) is more common in patients with inflammatory bowel diseases (IBD), whether co-occurrence of EoE modifies natural history of IBD is unknown. METHODS: This was a retrospective case-control study at a referral center. Cases consisted of patients with IBD and EoE, with both diseases diagnosed using established criteria. Controls comprised patients with IBD without concomitant EoE. Two controls were selected per case and were matched for duration of IBD. Relevant covariates regarding disease presentation and natural history were extracted from the medical record and compared between the 2 groups. RESULTS: A total of 95 IBD-EoE cases and 190 IBD controls were included in our study. The IBD-EoE group was diagnosed with IBD at a younger age than those with IBD alone (22.3 years vs 29.0 years; P < 0.001) and were more likely to be male (80.0% vs 45.8%; P < 0.001). There were no differences in medical or surgical therapy for IBD between the 2 groups. Among those with IBD-EoE, patients for whom IBD was diagnosed first presented more commonly with dysphagia (50.8% vs 26.9%; P = 0.04) and endoscopically had evidence of esophageal rings (50.0% vs 23.1%; P = 0.02) when compared with those where EoE was diagnosed first. CONCLUSION: Patients with concurrent IBD-EoE are diagnosed at a younger age and more likely to be males but have similar natural history as those without EoE. There were differences in EoE phenotype based on whether the EoE or IBD was diagnosed first.

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.

BACKGROUND: Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). METHOD: V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. RESULTS: Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. CONCLUSION: The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.