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Fecal microbiota transplant is a promising therapy for ulcerative colitis. Parameters maximizing effectiveness and tolerability are not yet clear, and it is not known how import the transmission of donor microbes to patients is. Here (clinicaltrails.gov: NCT03006809) we have tested the effects of antibiotic pretreatment and compared two modes of maintenance dose delivery, capsules versus enema, in a randomized, pilot, open-label, 2 × 2 factorial design with 22 patients analyzed with mild to moderate UC. Clinically, the treatment was well-tolerated with favorable safety profile. Of patients who received antibiotic pretreatment, 6 of 11 experienced remission after 6 weeks of treatment, versus 2 of 11 non-pretreated patients (log odds ratio: 1.69, 95% confidence interval: −0.25 to 3.62). No significant differences were found between maintenance dosing via capsules versus enema. In exploratory analyses, microbiome turnover at both the species and strain levels was extensive and significantly more pronounced in the pretreated patients. Associations were also revealed between taxonomic turnover and changes in the composition of primary and secondary bile acids. Together these findings suggest that antibiotic pretreatment contributes to microbiome engraftment and possibly clinical effectiveness, and validate longitudinal strain tracking as a powerful way to monitor the dynamics and impact of microbiota transfer.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC. Anti-integrin therapy inhibits lymphocyte trafficking in ulcerative colitis. Here Mennillo et al. use single-cell and spatial -omics to show modulation of mononuclear phagocytes and other networks, identifying gene sets related to treatment response.

We performed a systematic review with metaanalysis of observational studies evaluating the association between 5-ASA use and colorectal cancer (CRC) or dysplasia among patients with ulcerative colitis. We conducted a search of Medline Embase Biosis, Web of Science, Cochrane Collaboration, manually reviewed the literature, and consulted with experts. Studies were included if they 1) evaluated and clearly defined exposure to 5-aminosalicylates in patients with ulcerative colitis, 2) reported CRC or dysplasia outcomes, 3) reported relative risks or odds ratio or provided data for their calculations. Quantitative analysis using a random-effects model is presented. Nine studies (3 cohort, 6 case-control) containing 334 cases of CRC, 140 cases of dysplasia, and a total of 1,932 subjects satisfied all inclusion criteria. Five studies reported CRC outcomes alone, two studies reported separate cancer and dysplasia outcomes, and two studies reported a combined outcome of CRC or dysplasia. All primary estimates are homogenous. Pooled analysis showed a protective association between use of 5-aminosalicylates and CRC (OR=0.51; 95% confidence interval (CI): 0.37-0.69) or a combined endpoint of CRC/dysplasia (OR 0.51; 95% CI: 0.38-0.69). 5-ASA use was not associated with a lower risk of dysplasia, although only two studies evaluated this outcome (OR=1.18; 95% CI: 0.41-3.43). Pooled results of observational studies support a protective association between 5-aminosalicylates and CRC or a combined endpoint of CRC/dysplasia in patients with ulcerative colitis. Additional studies analyzing the effect of 5-ASA on risk of dysplasia are needed.

Introduction: Esophageal eosinophilia (EE) is a condition that is commonly found in gastroesophageal reflux disease or eosinophilic esophagitis. Less common systemic causes of EE include various disorders including drug-induced hypersensitivity, hypereosinophilic syndromes, and various allergic/infectious etiologies. We describe a case of severe esophageal eosinophilia secondary to new-onset Bullous Pemphigoid (BP), a phenomenon that has not previously been described. Case Description: A 25 year old woman with history of end stage renal disease secondary to focal segmental glomerulosclerosis (FSGS) status post deceased donor renal transplantation with subsequent graft failure presented with malaise, dysphagia, and nausea. White blood cell count was 14 with an elevated peripheral eosinophil count of 1.19 x 10^9/L. Upper endoscopy showed white exudates throughout the esophagus (Image 1) thought to represent Candida esophagitis and Fluconazole was initiated. Esophageal biopsies returned with marked increase in intraepithelial eosinophils (peak count of >100/HPF; Image 2). She was started on high dose BID PPI for EE. One week later, she presented with a 4-day history of pruritic vesicles of bilateral coalescing into tense bullae (Image 3). Labs showed increasing peripheral eosinophilic count, now 18.72 x 10^9L. PPI and Fluconazole were stopped without improvement in skin findings. Infectious and malignancy work-up was unrevealing. Blood smear was normal, without suggestion of myeloproliferative neoplasm or lymphoproliferative disorders. Bullous pemphigoid specific immunoglobulin antibodies returned positive, and biopsies of the affected skin showed dyshidrosiform subtype of BP. She was started on IVIG and high-dose prednisone with prompt improvement in her skin lesions as well as esophageal symptoms. Discussion: Bullous pemphigoid (BP) is an acquired autoimmune disorder associated with circulating antibodies against hemidesmosomal glycoprotein; we suspect that her chronic antibody mediated renal graft rejection is what drove the development of BP. While there have been reports of esophageal involvement in bullous pemphigoid including bullae, erosions, webs, or esophagitis dissecans superficialis, eosinophilic esophagitis secondary to BP has not previously been described. In immunocompromised patients with systemic causes of esophageal eosinophilia, IVIG and systemic corticosteroids may be required to help treat the underlying process.

ObjectiveTo develop and validate tools for measuring inpatient gastroenterology (GI) consultation quality on oncologic patients.MethodsA total of 145 inpatient GI consults were analyzed using electronic health records in this cross-sectional study. Essential Consult Elements on oncologic-hospitalized patients (EE-COH) and Hospitalized Oncologic Patients Enhanced Quality of Consult Assessment Tool (HOPE-QCAT) were used for grading. Interrater reliability was assessed.ResultsBoth EE-COH and HOPE-QCAT showed near-perfect interrater reliability across most measures in the validation cohort. On application of these measures for quality assessment, basic evaluation by the requesting hospitalist was partially complete in 24.8%, the request for GI consultation was inappropriate in 18.6%, while the rationale for recommended studies from the GI consultant was provided in 55.7% of cases suggesting key areas for quality improvement.ConclusionWe developed highly reliable quality measures for inpatient GI consults on oncology patients. The EE-COH and HOPE-QCAT tools can be utilized in future studies of inpatient GI consult quality and to form the basis for interventions to improve communication between consultants and hospitalists. Such tools could be adapted for inpatient quality assessment across other specialties and settings.

Uncertainty exists regarding safety and efficacy of dual biological therapy (DBT) in inflammatory bowel disease. We present four cases of DBT in Crohn’s disease. Three patients had refractory disease non-responsive to biological monotherapy or combination therapy with immunomodulators. One patient had concomitant ankylosing spondylitis. DBT was implemented by combining vedolizumab with an anti tumour necrosis antibody or with ustekinumab. DBT was well-tolerated, though two patients did experience self-limited infections. The efficacy of DBT remains unproven but it appears promising as three of the four patients achieved clinical remission. Our case series contributes insight into the safety of DBT that incorporates vedolizumab for future efficacy studies.

Background Lynch syndrome is the most common cause of hereditary colorectal cancer (CRC) and confers increased risk of other cancers. Identification of patients improves morbidity and mortality. Screening tumors for absent mismatch repair (MMR) protein expression by immunohistochemistry (IHC) is a recommended approach. Despite guidelines advocating universal screening, significant variation in clinical practice exists. Aims/Methods A retrospective study of two different IHC-based Lynch syndrome screening protocols at an urban, university hospital was performed. Outcomes from a “selective” screening strategy utilized from August 2007–July 2010 on CRC tumors from patients with high-risk features were compared with a “universal” strategy of screening all CRC tumors from July 2010–August 2013. Positively screened patients were referred for genetic counseling and offered germline testing. Results A total of 392 patients with CRC were screened: 107 selectively and 285 universally. The prevalence of Lynch syndrome was 3.1 %, with no difference by strategy. There was a trend ( p  = 0.06) toward fewer universally screened patients agreeing to genetic counseling compared with those selectively screened. Selective criteria failed to identify one of eight cases of Lynch syndrome from the universal group, though the universal strategy screened 166 additional tumors to find this additional patient. Conclusions Selective screening for Lynch syndrome has similar outcomes as universal screening in terms of identifying Lynch syndrome, despite screening far fewer patients. In addition, fewer eligible patients in our study agreed to undergo genetic counseling and germline testing than in prior studies. These lower rates may better reflect uptake of these services in clinical practice.

Introduction: Fecal microbiota transplant (FMT) is increasingly being explored as a potential therapy for ulcerative colitis (UC). Optimal frequency, duration, and mode of delivery have not yet been defined. Studies of FMT in UC using repeated therapy via enema demonstrated good results although this mode of delivery may be burdensome for long term therapy. Recent data in recurrent clostridium difficile infection (rCDI) indicate that FMT delivered by capsule (cap-FMT) may be equally efficacious to delivery by colonoscopy. However, cap-FMT has not yet been studied for management of UC. We aimed to investigate the tolerability of cap-FMT in UC patients as a maintenance regimen following FMT via colonoscopic infusion. Methods: We performed an open-label, prospective trial of FMT in patients with endoscopically and histologically confirmed UC. As an optional extension arm, patients were given a maintenance regimen of 10 FMT capsules once a week for 6 weeks. All participants received FMT by colonoscopy on two separate occasions, 1 month apart, prior to entering this arm of the study. Concomitant therapies were allowed to continue. The primary outcome was a composite safety endpoint (NIH grade > 2 adverse event or escalation of therapy). Secondary outcome was decrease in modified Mayo score. Results: 15 patients enrolled to receive cap-FMT. Two patients were excluded due to lack of follow-up data. Of the 13 patients who completed follow-up, 3 experienced minor adverse events including diarrhea and constipation, resulting in 2 patients discontinuing cap-FMT (one after 3 weeks of cap-FMT; one after 4 weeks of cap-FMT). No patients experienced serious adverse events or required escalation of UC therapy. There was no significant improvement in mean Modified Mayo Score from initiation of capsule-FMT and at completion of the 6 weeks in the 11 patients who did complete the course (2.82 vs. 2.18, p=0.35). Conclusion: While cap-FMT has been reported in UC patients for treatment of rCDI, this is the first report of cap-FMT for treatment of UC. Cap-FMT was overall well tolerated in our study with no serious adverse events in our cohort. Modified Mayo score did not significantly decrease after initiation of cap-FMT possibly because the group who entered the extension arm of capsule therapy already had well controlled disease following colonoscopic administration of FMT. Future studies should focus on comparing efficacy of enema delivery to cap-FMT considering patient convenience.

Serrated polyps of the colorectum are a histologically and genetically heterogeneous group of lesions, which include classic hyperplasic polyps, sessile serrated adenomas (SSAs), and traditional serrated adenomas. Accumulating evidence suggests that they may have different malignancy potentials. This study sought to determine the association between the presence of large serrated colorectal polyps and synchronous advanced colorectal neoplasia. Among 4,714 asymptomatic subjects who underwent screening colonoscopy, cases of advanced colorectal neoplasia (tubular adenoma > or =1 cm, adenoma with any villous histology, adenoma with carcinoma in situ / high-grade dysplasia, or invasive adenocarcinoma) were compared with controls without advanced neoplasia with respect to candidate predictors, including age, sex, family history of colorectal cancer, body mass index, the presence and number of small tubular adenomas (<1 cm), the presence of multiple small serrated polyps (<1 cm), and the presence of large serrated polyps (> or =1 cm). Independent predictors of advanced neoplasia were determined by multivariate logistic regression analysis. Among 467 cases and 4,247 controls, independent predictors of advanced colorectal neoplasia were increasing age (odds ratio (OR)=4.51; 95% confidence interval (CI), 1.43-14.3; P=0.01 for subjects > or =80 years vs. 50-54 years of age); non-advanced tubular adenomas (OR=2.33; 95% CI 1.37-3.96, P=0.0017 for 3 or more); and large serrated polyps (OR=3.24; 95% CI 2.05-5.13, P<0.0001). In total, 109 subjects (2.3% of the study population) had large serrated polyps. Right- and left-sided large serrated polyps had a similar association with advanced colorectal neoplasia (OR=3.38 vs. 2.66, P=0.62). Large serrated polyps are strongly and independently associated with synchronous advanced colorectal neoplasia. Our results suggest that large serrated polyps may be a marker for advanced colorectal neoplasia. Further studies are needed to determine whether the association with advanced neoplasia differs among subsets of serrated polyps, particularly SSAs and classic hyperplastic polyps.

Whether or not 5-aminosalicylates can prevent colorectal cancer among patients with colitis remains an open question. The observational studies examining this question have provided conflicting results, but none of these studies have been of sufficient quality to provide a definitive answer one way or another.