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Checkpoint inhibitor colitis is a complication that is often underestimated when it is slow-grade, and results in relatively few hospital admissions compared to its frequency of occurrence. A strict history-taking approach, combined with an endoscopic work-up in cases of severity, is recommended. The use of the fecal calprotectin may also be useful. When used appropriately, the various lines of treatment are generally effective, and second-line therapies (biotherapies) are rarely used. However, recent evidence suggests that patients with severe symptoms should be treated more rapidly with biological therapies, especially if severity is endoscopically confirmed, as corticosteroids carry a greater risk of infection. The objective of this study is to demonstrate the efficacy of non-symptomatic, first and second line therapies for immunotherapy-related colitis in a population of patients at the CHU of Liège.

Introduction: We assessed the prevalence and clinical outcomes of segmental colitis associated with diverticulosis (SCAD) in patients with newly diagnosed diverticulosis., Methods: A 3-year international, multicenter, prospective cohort study was conducted involving 2,215 patients., Results: SCAD diagnosis was posed in 44 patients (30 male patients; median age: 64.5 years; prevalence of 1.99%, 95% confidence interval, 1.45%-2.66%). Patients with SCAD types D and B showed worse symptoms, higher fecal calprotectin values, needed more steroids, and reached less likely complete remission., Discussion: Although SCAD generally had a benign outcome, types B and D were associated with more severe symptoms and worse clinical course., (Copyright © 2023 by The American College of Gastroenterology.)

Purpose: Clostridium difficile colitis is a serious complication in elderly patients undergoing surgery. The objectives of this study were: (1) to use a nationwide sample of patients to report the incidence and timing of C. difficile colitis in geriatric patients who underwent surgery for hip fractures, (2) to identify preoperative factors associated with developing C. difficile colitis and mortality., Methods: This was a retrospective evaluation of the 2016-2019 ACS Targeted Hip Fracture database merged with the ACS-NSQIP database. Patients undergoing surgery for hip fracture were included. Outcomes studied were incidence, preoperative, and postoperative risk factors for occurrence of C. difficile infection and mortality. Chi-squared tests were used to compare demographics between the patients infected (study) and not infected (control). Logistic regression models were utilized to compute the odds ratios (OR) testing for the association of independent factors on developing C. difficile infection postoperatively and mortality. A statistical threshold was set at p < 0.008., Results: The incidence of C. difficile infection within 30 days of hip fracture surgery was 0.81%. Fifty percent of infections were diagnosed within 9 days postoperatively. Preoperative and hospital-associated factors associated with development of C. difficile infection were ≥ 2 days until operation (OR 1.88 [95% CI 1.39-2.55], p < 0.001) and dependent functional status (OR 1.43 [95% CI 1.14-1.79], p = 0.002). After adjusting for multiple comorbidities, increased age, male sex, COPD, CHF, dependent functional status, and C. difficile infection were associated with increased mortality within 30 days of surgery (all p < 0.001)., Conclusion: Clostridium difficile colitis is a serious infection after hip fracture surgery in geriatric patients with an incidence of about 1%. Patients at increased risk should be targeted with preventative measures to prevent the morbidity from this complication., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Clostridium piliforme , the agent of Tyzzer disease, has traditionally not been considered a major pathogen of cats. We queried the database of the Pathology Service of the Veterinary Medical Teaching Hospital, University of California-Davis, for kittens <6-mo-old autopsied between 2000-2021 that had colitis, hepatitis, and/or myocarditis; 37 cases met the search criteria. Sections of colon, liver, and heart from these 37 cats were stained with modified Steiner; 19 of 37 (51%) cases had intraepithelial, Steiner-positive rods compatible with C. piliforme in at least one organ, confirming Tyzzer disease. The affected age range was 7-42 d (median: 17.5 d). Eighteen were orphaned kittens. Colitis was the major lesion (18 of 19) followed by random hepatitis (11 of 19). Perianal dermatitis with intraepithelial stacked rods was seen in 2 of 19. Myocarditis was not evident in any of the cases. A PCR assay for C. piliforme on 10 selected cases using formalin-fixed, paraffin-embedded (FFPE) blocks was positive or suspected in colon (5 of 10), liver (5 of 10), and heart (1 of 10). The modified Steiner stain was more sensitive in the detection of bacteria than PCR on FFPE samples. Fifteen kittens had comorbidities. A weakened immune state caused by maternal, environmental, infectious, and/or nutritional causes is speculated to have contributed to disease onset. We found that Tyzzer disease is more common than previously believed in orphaned kittens and should be considered in kittens with colitis and/or hepatitis.

This study compared the prevalence of C. innocuum DNA in the feces of healthy horses and horses with acute colitis. C. innocuum was identified in 22% (15/68) of colitis cases and 18% (12/68) of healthy horses (p = 0.416)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Outbreaks of equine coronavirus (ECoV) infections have been described in different parts of the world including Europe. The aim of this report was to describe clinical signs, diagnostic work-up and outcome of the first documented outbreak of ECoV in Switzerland in order to raise the awareness for the disease and its various clinical presentations. The outbreak occurred on a farm with 26 horses. Of these, seven horses developed clinical disease ranging from mild signs such as fever and anorexia to severe signs of acute colitis. One horse died due to severe endotoxemia and circulatory shock secondary to severe acute necrotizing enteritis and colitis. Out of the 26 horses, five horses tested positive for ECoV, including two ponies without any clinical signs of infection. The low number of positive cases should nevertheless be interpreted with caution as testing was only performed on one occasion, over a month after the onset of clinical signs in the first suspected case. This report highlights the importance of diagnostic testing and early implementation of biosecurity measures on a farm with an ECoV outbreak. It should furthermore raise the awareness for unspecific and mild clinical signs such as fever and anorexia in affected animals that are potentially able to spread the disease.

Introduction: Clostridium difficile is the most common cause of healthcare-associated infectious diarrhea and colitis, and carries the potential for high morbidity, particularly in frail patient populations. The purpose of this study was to utilize a large nationally representative database in order to report 1.) the incidence of CDC in patients with operative lower extremity fractures, 2.) risk factors for the development of CDC, 3.) the association of CDC with length of stay (LOS), readmission, and 30-day mortality rates., Methods: The ACS-NSQIP (2015-2019) was queried for patients who underwent surgical fixation of lower extremity fractures. A backward elimination multivariate regression model was used to identify risk factors for CDC. Chi squared and multivariate regression that controlled for preoperative variables and comorbidities were used to compare outcomes in patients with and without CDC., Results: 95,532 patients were included, 681 (0.71%) of whom developed CDC. Risk factors for CDC were advanced age, ASA class ≥ 3, smoking, dialysis, anemia, hypoalbuminemia, preoperative SIRS, preoperative wound infections, preoperative sepsis, and the use of spinal anesthesia or MAC/IV sedation. Patients with CDC had significantly increased 30-day mortality rates (10.6% vs 4.4%; OR 1.80, 95% CI 1.41-2.31), readmission (34.2% vs 7.5%; OR 5.13, 95% CI 4.36-6.05, and length of stay (7.5 days vs 5.3 days) compared to patients without CDC., Conclusion: The incidence of CDC in lower extremity orthopedic trauma patients was 0.71%. An occurrence of CDC was associated with approximately a 2.5 times increase in 30-day mortality, five times the readmission rate, and a longer hospital stay compared to patients without CDC. Mitigating the spread of c. diff through improved antibiotic stewardship and prompt treatment of CDC is paramount to decreasing the burden this infection imposes on orthopedic trauma patients and the healthcare system., Competing Interests: Declaration of Competing Interest The authors report no relevant conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of diarrhea and colitis of ICIs alone and in combination with chemotherapy or tyrosine kinase inhibitors (TKIs), histopathological findings, and management., Methods: Two separate studies, including meta-analyses, were performed. Key inclusion criteria were for Study I) phase I-IV trials, and data on diarrhea and/or colitis; for Study II) studies describing histopathologic and endoscopic findings and/or biologic treatment for ICI-induced colitis., Results: The incidence of anti-PD-1/PD-L1 antibody-induced diarrhea and colitis was 10% and 2%, respectively, with no clinically relevant differences between the compounds. The CTLA-4 inhibitor, ipilimumab, induced diarrhea and colitis in 33% and 7% of patients, respectively, whereas the incidence of diarrhea and colitis following ipilimumab combined with nivolumab was 21%-37% and 4%-8%, depending on regimen. The incidence of all-grade diarrhea following ICIs combined with chemotherapy or TKIs was high (17%-56%), whereas only 0.5% of patients developed severe (≥grade 3) colitis. The main patterns of histopathologic presentation after PD-1/CTLA-4 inhibitor mono- or combination therapy were acute and chronic active colitis and microscopic colitis-like. Infliximab and vedolizumab were equally effective against ICI-induced colitis., Conclusion: Expanding treatment options include combinations of ICIs and chemotherapy/TKI with a high incidence of diarrhea and a low incidence of colitis; thus, a potential risk of overtreatment with corticosteroids exists. We suggest a more tailored approach, particularly for the management of low-grade diarrhea. Prospective clinical trials are needed to refine management., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of a variety of malignancies including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers among others. Since their introduction, there has been significant improvement in survival and prognosis in patients with advanced malignancies. Unfortunately, improved outcomes have come at a price of significant immune-related adverse events, with those of the gastrointestinal tract being the most common. Gastrointestinal immune-related adverse events frequently present as diarrhea and colitis, the severity of which can range from mild diarrhea to fulminant colitis with intestinal perforation. Currently, management of ICI-induced colitis is primarily guided by retrospective studies and expert opinion. A significant number of ICI-induced colitis responds to high-dose corticosteroids; however, some patients require further therapy with biologics. There is limited information on the factors which may predispose patients to ICI-induced colitis. Future research elucidating these risk factors along with development of a scoring system could allow for risk-stratification of patients before initiation of ICI therapy. Such a system may help clinicians and patients keep a high index of suspicion regarding ICI-induced colitis and could hopefully reduce the incidence of severe cases. Similarly, future studies should investigate protective factors against ICI-induced colitis, which could potentially allow more patients to safely benefit from ICI therapy., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: ICIs are used in the management of several malignancies. However, they can result in immune-related adverse events, such as colitis. The aim of this study is to obtain an epidemiological survey of patients who develop immune checkpoint inhibitor (ICI)-induced colitis and identify underlying risk factors., Methods: A cohort study was performed using Explorys, a US-based population database. Our cohort included all patients in a five-year interval on an ICI. We further identified those who developed colitis after initiating an ICI. Demographic data and possible risk factors were assessed. Odds ratios were calculated and multivariable statistical analysis was performed., Results: 3.6% of patients developed ICI-induced colitis. Women [OR: 1.2; 95% CI 1.224-1.231, p <0.001], Caucasians [OR: 2.3; 2.284 - 2.299], individuals older than 65 years [OR: 1.3; 1.319 - 1.326], obese patients [OR: 3.3; 3.273 - 3.302], and those with a history of alcohol abuse [OR: 2.5; 2.485 - 2.523] were more likely to develop colitis. Patients who received Nivolumab [OR: 2.8; 2.563 - 3.022], Ipilimumab [OR: 4.9; 3.937 - 6.061], Pembrolizumab [OR 2.7; 2.463 - 2.868], and Atezolizumab [OR 2.9; 2.430 - 3.388] had an increased odds of developing colitis. The majority of cases were diagnosed in the first 6 months of therapy., Conclusions: This is the largest study to describe the epidemiology of ICI-induced colitis and it is the first to identify underlying risk factors. Ipilimumab poses the greatest risk for ICI-induced colitis. The risk of colitis should be discussed with all patients prior to initiating an ICI, as it may be a factor in choosing among ICIs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: The prevalence and significance of cytomegalovirus (CMV) colitis in pediatric acute severe colitis is unknown. The aim of this study was to determine the prevalence of CMV in colonic mucosa of children with acute severe refractory colitis and compare the clinical characteristics and outcomes of CMV positive and negative patients., Methods: In a case-control study, colonic biopsy specimens from children with severe refractory colitis were tested for CMV, and matched with non-refractory IBD controls. We characterized CMV positive patients by assessing laboratory values, concurrent medications, and need for surgery as compared with CMV negative refractory colitis patients., Results: Colonic biopsies from 96 patients were evaluated for CMV; 48 with severe refractory colitis, and 48 non-refractory controls. There was an increased prevalence of CMV in severe refractory colitis [7/48 (14.6%), P < 0.0001]; all were previously CMV negative. Viral DNA burden on immunohistochemistry was not predictive of response to antiviral therapy or need for surgery at 12 months. Lymphopenia was seen in all CMV positive patients, but this did not demonstrate statistical significance (P = 0.09). We did not see an association between azathioprine or infliximab use and the need for surgery at 12 months., Conclusions: There is an increased prevalence of CMV in colonic biopsies of pediatric patients with severe refractory colitis. Viral burden does not predict clinical outcomes or subsequent need for colectomy., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Immune checkpoint inhibitors (ICIs) have transformed the management of advanced malignancies but are associated with diarrhea and colitis. The objective of our systematic review and meta-analysis was to determine the incidence and outcomes of ICI-associated diarrhea and colitis. Bibliographic databases were searched through August 13, 2019, for observational studies of ICI therapy reporting the incidence and/or treatment of diarrhea or colitis. The primary outcome was ICI-associated diarrhea and colitis. Meta-analyses were performed with random-effects models. Twenty-five studies (N=12,661) were included. All studies had a high risk of bias in at least 1 domain. The overall incidence of diarrhea/colitis was 12.8% [95% confidence interval (CI), 8.8-18.2, I2=96.5]. The incidence was lower in patients treated with anti-programmed cell death 1/programmed death-ligand 1 (4.1%, 95% CI, 2.6-6.5) than in those treated with anti-cytotoxic T-cell lymphocyte-associated antigen 4 (20.1%, 95% CI, 15.9-25.1). The remission of diarrhea and/or colitis was higher in patients treated with corticosteroids plus biologics (88.4%, 95% CI, 79.4-93.8) than in those treated with corticosteroids alone (58.3%, 95% CI, 49.3-66.7, Q=18.7, P<0.001). ICI were permanently discontinued in 48.1% of patients (95% CI, 17.8-79.1). ICI were restarted after temporary interruption in 48.6% of patients (95% CI, 18.2-79.4) of whom 17.0% (95% CI, 6.4-30.0) experienced recurrence. Real-world incidence of ICI-associated diarrhea/colitis exceeds 10%. These events lead to permanent ICI discontinuation in just over 50% of patients, while <20% have recurrence of symptoms if ICI are resumed. Further studies are needed to identify patients who would benefit from early treatment with biologics as well as appropriate patients to resume ICI therapy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aim: We previously found in Swedish patients with inflammatory bowel disease (IBD), crypts in symmetric fission (CSF) and in asymmetric fission (CAF). This study aimed to examine CSF and CAF in a cohort of German patients with IBD., Patients and Methods: H&E-sections from 106 IBD-patients [59 ulcerative colitis (UC) and 47 Crohn colitis (CCs)] were analysed., Results: A total of 588 crypts in fission (CF) were found; 342 (58.2%) in UC and 246 (41.8%) in CCs. Out of the 505 CAFs found, 304 (60.2%) were recorded in UC, and 201(39.8%) in CCs (p=0.15272)., Conclusion: Despite that German and Swedish populations reside in disparate geographical regions with different ecological milieus, the proportions of CAF and CSF were similar, thereby suggesting that CAF and CSF develop in IBD independently of the local environmental conditions in the two regions., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Goals: To compare the clinical outcomes of different protocols for fecal microbiota transplantation (FMT) in two community hospitals with similar patient demographics., Background: FMT is commonly performed for recurrent or refractory Clostridioides difficile infection (rCDI). The clinical efficacy of FMT for this indication has been well established. However, there has been no standardization or optimization of the amount of fecal material, method of feces preparation, or route of delivery for FMT., Study: In this retrospective study, patients with rCDI received FMT using commercially available frozen fecal preparation (22.7 g) at Center A and locally prepared fresh fecal filtrate (30-50 g) at Center B. The primary outcome was defined as complete resolution of clinical symptoms related to rCDI after at least 8 weeks of follow-up., Results: Fifty patients from each center were included in the study. Clinical success after initial FMT with lower-volume frozen fecal preparation at Center A was 32/50 (64.0%) compared to 49/50 (98.0%) with higher-volume fresh fecal filtrate at Center B (p < 0.0001). Seventeen patients in Center A and 1 patient in Center B underwent at least one repeat FMT. Overall clinical success was achieved in 43/50 (86%) of patients in Center A and 50/50 (100%) in Center B (p = 0.012)., Conclusions: Our results suggest superior clinical efficacy of a larger amount of fresh fecal filtrate over a smaller amount of commercially available frozen fecal preparation. Further studies are needed to examine the effect of varying amounts of feces and the optimal protocol for FMT in patients with rCDI.

Background/aim: The aim of the study was to analyze the postoperative survival of colitis-associated colorectal cancer (CAC) with ulcerative colitis (UC), and the risk factors affecting it., Patients and Methods: A questionnaire including postoperative survival was sent to 88 hospitals that reported CAC patients in the literature up until January, 2006 and to members of the Research Group of Intractable Inflammatory Bowel Disease., Results: The 5-year postoperative overall survival (OS) of 170 CAC patients was 74.2% which was similar to sporadic colorectal cancer in Japan (72.1%). Pathologic TNM stage, histological type, type of surgical procedure (proctocolectomy, segmental resection), and preoperative cancer surveillance were statistically significant factors for OS. By Cox regression analysis, pathologic TNM stage and proctocolectomy were statistically significant prognostic factors for OS., Conclusion: In CAC with UC, the postoperative OS was similar to sporadic colorectal cancer. Pathologic TNM stage and proctocolectomy were confirmed as important prognostic factors., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Elderly-onset inflammatory bowel disease [IBD], defined as age ≥60 at diagnosis, is increasing worldwide. We aimed to compare clinical characteristics and natural history of elderly-onset IBD patients with those of adult-onset IBD patients., Methods: Patients with a confirmed diagnosis of IBD from 1981 to 2016 were identified from a territory-wide Hong Kong IBD registry involving 13 hospitals. Demographics, comorbidities, clinical features, and outcomes of elderly-onset IBD patients were compared with those of adult-onset IBD patients., Results: A total of 2413 patients were identified, of whom 270 [11.2%] had elderly-onset IBD. Median follow-up duration was 111 months (interquartile range [IQR]: 68-165 months). Ratio of ulcerative colitis [UC]: Crohn's disease [CD] was higher in elderly-onset IBD than in adult-onset IBD patients [3.82:1 vs 1.39:1; p <0.001]. Elderly-onset CD had less perianal involvement [5.4% vs 25.4%; p <0.001] than adult-onset CD. Elderly-onset IBD patients had significantly lower cumulative use of immunomodulators [p = 0.001] and biologics [p = 0.04]. Elderly-onset IBD was associated with higher risks of: cytomegalovirus colitis (odds ratio [OR]: 3.07; 95% confidence interval [CI] 1.92-4.89; p <0.001); herpes zoster [OR: 2.42; 95% CI 1.22-4.80; p = 0.12]; and all cancer development [hazard ratio: 2.97; 95% CI 1.84-4.79; p <0.001]. They also had increased number of overall hospitalisations [OR: 1.14; 95% CI 1.09-1.20; p <0.001], infections-related hospitalisation [OR: 1.87; 95% CI 1.47-2.38; p <0.001], and IBD-related hospitalisation [OR: 1.09; 95% CI 1.04- 1.15; p = 0.001] compared with adult-onset IBD patients., Conclusions: Elderly-onset IBD was associated with increased risk of infections and cancer development, and increased infection- and IBD-related hospitalisations. Specific therapeutic strategies to target this special population are needed., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Considering high prevalence of non-alcoholic fatty liver diseases (NAFLD) in patients with inflammatory bowel disease (IBD), this study aimed to elucidate molecular mechanisms for how intestinal inflammatory conditions are causally linked to hepatic steatosis and dyslipidemia. Both younger and older mice treated with acute or chronic dextran sodium sulfate (DSS) developed colitis, which was evidenced by weight loss, colon length shortening, and elevated disease activity index and inflammation score. They also showed decreased expression of intestinal barrier function-related proteins and elevated plasma lipopolysaccharide level, indicating DSS-induced barrier dysfunction and thereby increased permeability. Interestingly, they displayed phenotypes of hepatic fat accumulation and abnormal blood lipid profiles. This DSS-induced colitis-associated lipid metabolic dysfunction was due to overall disruption of metabolic processes including fatty acid oxidation, lipogenesis, lipolysis, reverse cholesterol transport, bile acid synthesis, and white adipose tissue browning and brown adipose tissue thermogenesis, most of which are mediated by key regulators of energy homeostasis such as FGF21, adiponectin, and irisin, via SIRT1/PGC-1α- and LXRα-dependent pathways. Our study suggests a potential molecular mechanism underlying the comorbidity of NAFLD and IBD, which could provide a key to understanding how the two diseases are pathogenically linked and discovering critical therapeutic targets for their treatment.

Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for the increased risk of gastrointestinal complications in kidney transplant recipients. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. This study evaluated the incidence of post-transplant gastrointestinal complications during screening colonoscopy. Kidney transplant recipients undergoing a colonoscopy for any reasons in the period 2014-2018 were included. Among the 134 patients completing the colonoscopy, 74 patients (56%) had an abnormal finding: an adenoma was found in 25 patients (18.6%), while 19 patients (14.1%) had colitis. Mycophenolic acid/related colitis was the most common colitis (6%), while 7 patients (5.2%) developed a de novo inflammatory bowel disease. Patients with post-transplant colitis were younger and with shorter time from transplant compared to patients without colitis. In conclusions, immunosuppression may predispose kidney transplant recipients to an increased risk of post-transplant colitis. Diagnostic colonoscopy should be encouraged in all transplant patients with refractory diarrhea and gastrointestinal symptoms to allow a prompt diagnosis and a timely treatment, finally improving the quality of life and long-term outcomes of affected patients.

Colitis is a major immune-related adverse event associated with programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors, but the risk of colitis with PD-1 versus PD-L1 inhibitors is not well characterized. We performed a meta-analysis for the incidence of all grade and grade 3-4 colitis with PD-1 inhibitor (nivolumab, pembrolizumab, and cemiplimab) or PD-L1 inhibitor (atezolizumab, avelumab, and durvalumab) monotherapy using a fixed effects model. We also conducted subgroup meta-analyses of non-small cell lung cancer (NSCLC) or urothelial carcinoma (UC) trials, and a network meta-analysis of randomized trials comparing PD-1 or PD-L1 inhibitors with docetaxel for NSCLC. We also analyzed the Food and Drug Administration Adverse Event Reporting System database to estimate the reporting odds ratio of each medication. PD-1 inhibitors were associated with a higher incidence of all grade and grade 3-4 colitis compared with PD-L1 inhibitors in the analysis of all cancer types [1.49% vs. 0.83%, relative risk; 1.80, 95% confidence interval (CI); 1.22-2.67 for all grade colitis, and 0.85% vs. 0.34%, relative risk; 2.52, 95% CI; 1.46-4.37 for grade 3-4 colitis]. The meta-analyses of NSCLC and UC trials, and the network meta-analysis of NSCLC trials were also suggestive of a higher risk of colitis with PD-1 versus PD-L1 inhibitors. The reporting odds ratio of colitis with PD-1 versus PD-L1 inhibitors was 1.80 (95% CI; 1.53-2.14). In this meta-analysis of clinical trials exploring PD-1 and PD-L1 inhibitors in solid tumors, PD-1 inhibitors were associated with a higher risk of colitis.

Background: The risk of lymphoma in patients with inflammatory bowel disease (IBD) treated with anti-TNF agents remains unclear., Aim: To assess the comparative risk of lymphoma with anti-TNF agents and/or thiopurines in IBD METHODS: We searched PubMed, EMBASE and Cochrane Library to identify studies that evaluated lymphoproliferative disorders associated with anti-TNF agents with or without thiopurines. The risk of lymphoma was assessed through four comparator groups: combination therapy (anti-TNF plus thiopurine), anti-TNF monotherapy, thiopurine monotherapy and control group. Pooled incidence rate ratios (IRR) were estimated through Poisson-normal models., Results: Four observational studies comprising 261 689 patients were included. As compared with patients unexposed to anti-TNF and thiopurines, those exposed to anti-TNF monotherapy, thiopurine monotherapy or combination therapy had pooled IRR (per 1000 patient-years) of lymphoma of 1.52 (95% CI: 1.06-2.19; P = 0.023), 2.23 (95% CI: 1.79-2.79; P < 0.001) and 3.71 (95% CI: 2.30-6.00; P ≤ 0.01), respectively. The risk of lymphoma associated with combination therapy was higher than with thiopurines or anti-TNF alone with pooled IRR of 1.70 (95% CI: 1.03-2.81; P = 0.039) and 2.49 (95% CI: 1.39-4.47; P = 0.002), respectively. The risk did not differ between anti-TNF monotherapy and thiopurine monotherapy with pooled IRR of 0.72 (95% CI: 0.48-1.07; P = 0.107). All observational studies were of high quality according to the Newcastle-Ottawa scale., Conclusions: There is an increased risk of lymphoma in IBD patients treated with anti-TNF agents, either alone or when combined with thiopurines., (© 2020 John Wiley & Sons Ltd.)

Background: Immune checkpoint inhibitors (icis), including inhibitors of PD-1, PD-L1, and ctla-4, are relatively novel therapies for lung cancer, although their use might be limited by gastrointestinal toxicity. The aim of the present study was to determine the risk of diarrhea and colitis associated with icis in lung cancer and the rates of discontinuation because of those toxicities., Methods: Electronic databases were searched for prospective trials reporting the risk of diarrhea and colitis in patients with lung cancer treated with PD-1, PD-L1, and ctla-4 inhibitors. The incidences of diarrhea and colitis and their grades were assessed clinically using standardized reporting criteria. Pooled incidence and weighted relative risk estimates for diarrhea and colitis with 95% confidence intervals (cis) were estimated using a random effects model. The incidence of discontinuations for gi toxicity was also calculated., Results: Twenty-seven studies were included: sixteen studies with PD-1 inhibitors, nine studies with PD-L1 inhibitors, and four studies combining PD-based strategies with ctla-4 inhibitors. The incidence of all-grade diarrhea was 9.1% (95% ci: 7.8% to 10.5%) for anti-PD-1 therapy and 11.0% (95% ci: 7.5% to 14.5%) for anti-PD-L1 therapy. The incidence of all-grade colitis was 0.9% (95% ci: 0.4% to 1.3%) for anti-PD-1 therapy and 0.4% (95% ci: 0.0% to 0.8%) for anti-PD-L1 therapy. The relative risk for all-grade diarrhea was higher with combination anti-PD-1 and anti-ctla-4 than with anti-PD-1 monotherapy (relative risk: 1.61; 95% ci: 1.14 to 2.29). Anti-PD-1 therapy was discontinued in 4.1% of patients with diarrhea (95% ci: 0.7% to 7.4%) and in 35.7% of those with colitis (95% ci: 0.0% to 81.1%); combination therapy was discontinued in 10.1% of patients with diarrhea (95% ci: 4.8% to 15.4%) and in 39.9% of those with colitis (95% ci: 3.9% to 75.9%)., Conclusions: Diarrhea is a relatively frequently encountered gi toxicity when ici therapy is used in lung cancer treatment. Colitis is less frequently encountered, although when it does occur, it often results in therapy discontinuation., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none., (2020 Multimed Inc.)

Background: Ileal pouch-anal anastomosis is a common surgical procedure in patients with an initial diagnosis of ulcerative colitis or indeterminate colitis. Tobacco smoking has been associated with protection from onset of ulcerative colitis. Smoking has been reported to be both a protective factor and a risk factor for the development of pouchitis., Aim: To examine the influence of smoking on the risk of pouchitis., Methods: We identified 15 studies evaluating smoking as a risk factor for developing pouchitis in ulcerative colitis or indeterminate colitis patients with a history of ileal pouch-anal anastomosis in a systematic search performed from inception through May 4, 2020. A meta-analysis was then performed using a random-effects model to generate risk ratios (RR) and 95% confidence intervals (CI)., Results: A history of smoking compared with never smoking was not associated with an increased risk of developing pouchitis (RR = 0.94, 95% CI 0.76-1.18, I 2  = 73.7%). There was also no significant risk of pouchitis when comparing current smokers vs nonsmokers (RR = 0.93, 95% CI 0.70-1.24, I 2  = 78.5%) and former smokers vs nonsmokers (RR = 0.96, 95% CI 0.74-1.23, I 2  = 78.5%)., Conclusions: Smoking, past or present, is not associated with an increased risk for the development of pouchitis in patients with ulcerative colitis or indeterminate colitis., (© 2020 John Wiley & Sons Ltd.)

Background: Data on gastrointestinal toxicities related antiangiogenesis cancer therapy is very limited. We aim to describe the clinical, endoscopic, and histologic features and outcomes of antiangiogenesis-associated colitis and diarrhea (ACD) at a tertiary-care cancer center., Patients and Methods: We performed a retrospective study of cancer patients who received antiangiogenesis therapy (AAT) and underwent endoscopy for ACD symptoms during 2000-2018., Results: A total of 12,045 patients received AAT during the study period. Of these, 552 patients underwent lower gastrointestinal tract endoscopic evaluation after AAT. Among them, we identified 41 patients who developed ACD. The median time from AAT initiation to ACD onset was 20 weeks. Most patients received bevacizumab (83%). The median duration of ACD symptoms was 6 days. On endoscopy, 7 patients (17%) had mucosal ulceration, and 16 (39%) had nonulcerative inflammation. Active histologic inflammation was evident in 8 patients (20%). Thirteen patients (32%) received treatment for ACD: antibiotics in 5 (12%) and antimotility agents in 11 (27%). Sixteen patients (39%) were hospitalized for ACD, and 2 were admitted to the intensive care unit. One colonic perforation (2%) related to underlying malignancy was reported after colonoscopy. Patients with enterocolitis symptoms had more frequent abnormal endoscopic findings (P = .024) and less frequently received antimotility agents (P = .011) compared to those with diarrhea only. Abnormal endoscopic findings were associated with more hospitalizations (P = .063) compared to normal group., Conclusion: ACD is a rare adverse event of AAT and is usually mild. Despite its rarity, complications of ACD can be serious, requiring intensive care unit and surgery. Colonic perforation occurred after routine endoscopy after AAT in 2% of our cohort., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to study clinical, imaging findings, response patterns, and immune-related adverse events in classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma (NHL) patients treated with immune checkpoint inhibitors (ICIs)., Methods: A retrospective search was performed to identify patients with relapsed/refractory cHL and NHL treated with ICIs from 2015 to 2019. Clinical and laboratory data were collected. Imaging studies were reviewed for treatment response and immune-related adverse events., Results: Ten patients with relapsed/refractory cHL (median age, 41 years) and 14 patients with relapsed/refractory NHL (median age, 61 years) were identified. Overall response rate was 70% for cHL patients. None of the NHL patients demonstrated complete or partial response. One case of hyperprogression and one case with atypical response were radiologically detected in cHL patients. Hypothyroidism requiring treatment occurred in 2 (20%) of 10 cHL patients, one of which had imaging correlate. Of 14 NHL patients, 1 (7%) had radiologic evidence of pneumonitis and 1 (7%) had colitis., Conclusions: This single-institution observational study demonstrated that overall response rate was higher in patients with cHL undergoing ICI. Immune checkpoint inhibitor therapy has unique response patterns and toxicities in both cHL and NHL patients that radiologists should keep in mind.

Background: The programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) axis plays a central role in suppressing antitumor immunity; axis dysregulation can be used by cancer cells to evade the immune system. Tislelizumab, an investigational monoclonal antibody with high affinity and binding specificity for PD-1, was engineered to minimize binding to FcγR on macrophages to limit antibody-dependent phagocytosis, a potential mechanism of resistance to anti-PD-1 therapy. The aim of this phase IA/IB study was to investigate the safety/tolerability, antitumor effects and optimal dose and schedule of tislelizumab in patients with advanced solid tumors., Methods: Patients (aged ≥18 years) enrolled in phase IA received intravenous tislelizumab 0.5, 2, 5 or 10 mg/kg every 2 weeks; 2 or 5 mg/kg administered every 2 weeks or every 3 weeks; or 200 mg every 3 weeks; patients in phase IB received 5 mg/kg every 3 weeks. Primary objectives were to assess tislelizumab's safety/tolerability profile by adverse event (AE) monitoring and antitumor activity using RECIST V.1.1. PD-L1 expression was assessed retrospectively with the VENTANA PD-L1 (SP263) Assay., Results: Between May 2015 and October 2017, 451 patients (n=116, IA; n=335, IB) were enrolled. Fatigue (28%), nausea (25%) and decreased appetite (20%) were the most commonly reported AEs. Most AEs were grade 1-2 severity; anemia (4.9%) was the most common grade 3-4 AE. Treatment-related AEs led to discontinuation in 5.3% of patients. Grade 5 AEs were reported in 14 patients; 2 were considered related to tislelizumab. Pneumonitis (2%) and colitis (1%) were the most common serious tislelizumab-related AEs. As of May 2019, 18% of patients achieved a confirmed objective response in phase IA and 12% in phase IB; median follow-up duration was 13.6 and 7.6 months, respectively. Pharmacokinetics, safety and antitumor activity obtained from both phase IA and IB determined the tislelizumab recommended dose; ultimately, tislelizumab 200 mg intravenous every 3 weeks was the dose and schedule recommended to be taken into subsequent clinical trials., Conclusions: Tislelizumab monotherapy demonstrated an acceptable safety/tolerability profile. Durable responses were observed in heavily pretreated patients with advanced solid tumors, supporting the evaluation of tislelizumab 200 mg every 3 weeks, as monotherapy and in combination therapy, for the treatment of solid tumors and hematological malignancies., Trial Registration Number: NCT02407990., Competing Interests: Competing interests: JD has served in a consulting or advisory role for Amgen, BeiGene, Bionomics, Eisai, Eli Lilly and Novartis, and their institution has received research funding from Bionomics, GlaxoSmithKline, Novartis and Roche. SD has received personal fees from Roche; C-CL has served in a consulting or advisory role for Novartis and has received travel, accommodations and expenses from BeiGene; BK has received grants and personal fees from AstraZeneca and MSD Oncology, grants from Ono Pharmaceutical and personal fees from Genexin; MJ's institution has received research funding from BeiGene, Merck Sharp & Dohme, Pfizer and Bristol-Myers Squibb; BM has served in a consultancy or advisory role for Novartis; LH has received grants from Astellas; MF has received honoraria from AstraZeneca, Merck Sharp & Dohme, Lilly, Takeda and Novartis, serves in a consulting or advisory role for AstraZeneca, Merck Sharp & Dohme and has received research funding from BeiGene and AstraZeneca. AH is employed by, has a leadership role in and has stock or other ownership in, Tasman Healthcare/Tasman Oncology Research. SS has received grants from Merck, Britsol-Meyers Squibb, Amgen, Endocyte, AstraZeneca and Roche; PB has received personal fees from Roche; LL, C-YW, JW, VP and YZ are employees of BeiGene; MM serves in a consulting or advisory role for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis and Roche, and has received travel, accommodations and expenses from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme and Roche., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: Diarrhea and colitis are among the most commonly encountered immune-mediated adverse events among patients receiving antiprogrammed cell death protein/ligand-1 (PD-1/L1) as well as anticytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies. With growing indications and widespread use of immune checkpoint inhibitors, it is imperative to summarize the current body of evidence concerning the incidence, pathogenesis, risk factors, diagnostic challenges, and treatment options currently available for the management of immune-mediated diarrhea and colitis. Additionally, with emerging evidence analyzing the resumption of immune checkpoint inhibitors, it is pivotal to summarize our current understanding and future challenges., Recent Findings: Immune-mediated diarrhea and colitis can potentially be a viable surrogate marker for improved survival as it is validated further in large-scale studies. Early endoscopic evaluation can aid in the identification of patients at risk of developing steroid refractory immune-mediated colitis, and hence can be chosen to receive early add-on therapy with infliximab, vedolizumab or fecal microbiota transplantation, an emerging treatment option for immune-mediated diarrhea and colitis. Resuming immune checkpoint inhibitors carries a manageable risk of recurrent diarrhea and colitis, with most cases being mild and effectively managed with immunosuppressive therapy., Summary: As our understanding of immune-mediated diarrhea and colitis grows, it is likely that this clinicopathologic entity will represent more than just an adverse event. With a growing number of treatment options, the management algorithms for immune-mediated diarrhea/colitis are likely to evolve in the future.

Objective: We aimed to share our observations on the demographics, clinical characteristics, and outcomes of lymphonodular hyperplasia (LNH) in children., Subjects and Methods: The study included children on whom colonoscopy was performed between January 2015 and May 2018 (n = 361). Demographics, treatment modalities, and outcomes of the patients with LNH were recorded., Results: LNH was found in 66 patients (18.3%; mean age 8.6 ± 5.96 years, 59.1% male). We found that the etiologic factors were food hypersensitivity (FH) in 25 (37.8%), nonspecific colitis in 12 (18.2%), irritable bowel syndrome in 10 (15.2%), familial Mediter-ranean fever in 7 (10.6%), primary immunodeficiency in 4 (6.1%), and intestinal dysmotility, oxyuriasis, Crohn's disease, and giardiasis in 1 (1.5%) patient. Additionally, in the genetic analysis of patients with idiopathic LNH (n = 4), we detected heterozygote MEFV mutations in all. Cow's milk and egg (25%) were the most common allergens in patients with FH. Symptoms of all patients (n = 25) improved after an elimination diet., Conclusions: LNH is a common finding in pediatric colonoscopies with a variety of etiologies ranging from FH and familial Mediterranean fever to immunodeficiency., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Crohn's disease (CD) is an inflammatory bowel disease that can involve any region of the gastrointestinal tract. First described in 1932 as terminal ileitis or regional enteritis, it predominately involves the ileum with or without colonic involvement. Isolated colonic CD was first described in 1960 and since then the phenotypic classification of CD has evolved to stratify patients into isolated ileal, ileocolonic, or isolated colonic involvement. In the current review we evaluate the published literature regarding differences in epidemiology, natural history, pathogenesis, response to therapy, and disease monitoring, when stratified by disease location. Based on the available evidence consideration could be given to a new classification for CD, which splits it into ileum dominant (isolated ileal and ileocolonic) and isolated colonic disease. This may allow for a more optimized approach to clinical care and scientific research for CD., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have declared that no competing interests exist.

Background: When a water pipe breaks, contaminants can enter the drinking water system and cause waterborne illnesses such as acute gastrointestinal illness. In May 2010, a major water pipe broke near Boston, MA, and a boil water order was issued to nearly two million residents., Methods: Using a case-crossover study design, we examined the association between the water pipe break and subsequent emergency department visits for acute gastrointestinal illness. We identified cases of illness according to ICD-9-CM diagnosis codes and selected control dates 2 weeks before and after each case. We estimated the risk of visiting the emergency department during the 0-3 and 4-7 days after the water pipe break using conditional logistic regression models., Results: Our analysis included 5,726 emergency department visits for acute gastrointestinal illness from 3 April 2010 to 5 June 2010. Overall, there was a 1.3-fold increased odds for visiting the emergency department for acute gastrointestinal illness during the 0-3 days after the water pipe break (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.1, 1.4) compared with referent dates selected 2 weeks before and after. During the 4-7 days after the break, the association diminished overall (OR = 1.1; 95% CI = 0.96, 1.2). However, in communities over 12 miles from the break, the 4- to 7-day association was elevated (OR = 1.4; 95% CI = 1.1, 1.8)., Conclusions: This study suggests that a major water pipe break was associated with emergency department visits for acute gastrointestinal illness, particularly during the 0-3 days after the break, when a boil water order was in effect.

Introduction: Clostridium difficile infection (CDI) has been attracting attention lately as the most common hospital acquired infection. Patients with neutropenia because of malignancy seem to be at an increased risk for developing CDI. There is currently limited data that assesses the national burden and outcomes of CDI in Febrile Neutropenia (FN)., Methods: We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of FN with or without CDI (ICD-9 codes 288.00, 288.03,780.60, and 008.45) as primary or secondary diagnosis during the period from 2008 to 2014. All analyses were performed with SAS, version 9.4 (SAS Institute)., Results: From 2008 to 2014 there were total 19422 discharges of FN patients with CDI. There was a rising incidence of CDI in patients with FN from 4.11% (in 2008) to 5.83% (in 2014). The In-hospital mortality showed a decreasing trend from 7.79% (in 2008) to 5.32% (in 2014), likely because of improvements in diagnostics and treatment. The overall mortality (6.37% vs. 4.61%), length of stay >5 days (76.45% vs. 50.98%), hospital charges >50,000 dollars (64.43% vs. 40.29%), colectomy and colostomy (0.35% vs. 0.15%), and discharge to skilled nursing facility (10.47% vs. 6.43%) was significantly more in FN patients with CDI versus without CDI over 7 years (2008 to 2014). Age above 65 years, Hispanic race, hematological malignancies, urban hospital settings, and sepsis were significant predictors of mortality in febrile neutropenia patients with CDI., Discussion: Despite the significant decrease in mortality, the incidence of CDI is rising in hospitalized FN patients with underlying hematological malignancies. Risk factor modification, with the best possible empiric antibiotic regimen is imperative for reducing mortality and health care costs in this cohort.

In physiological conditions, the gut is heavily infiltrated with various subsets of inflammatory cells, whose activity is tightly controlled by counter-regulatory mechanisms. Defects in such mechanisms can favour the development of chronic intestinal disorders, such as Crohn's disease (CD) and ulcerative colitis (UC), the principal forms of inflammatory bowel diseases (IBD) in humans, as well as systemic disorders. Over the last years, the frequency of intestinal and systemic immune-inflammatory disorders has increased in previously low incidence areas, likely due to the Westernization of lifestyles, including dietary habits. The Western diet is characterized by high consumption of proteins, saturated fats and sweets, as well as by a broad use of food additives (e.g., emulsifiers, bulking agents), which are used to preserve and enhance food quality. Accumulating evidence suggests that food additives can perturb gut homeostasis, thereby contributing to promote tissue-damaging inflammatory responses. For instance, mice given the emulsifiers carboxymethylcellulose and polysorbate 80 develop dysbiosis with overgrowth of mucus-degrading bacteria. Such an effect triggers colitis in animals deficient in either interleukin-10, a cytokine exerting anti-inflammatory and regulatory functions, or Toll-like receptor 5, a receptor recognizing the bacterial flagellin. Similarly, the polysaccharide maltodextrin induces endoplasmic reticulum stress in intestinal goblet cells, thereby impairing mucus release and increasing host susceptibility to colitis. In this review, we report and discuss the current knowledge about the impact of food additives on gut homeostasis and their potential contribution to the development of inflammatory disorders., Competing Interests: the authors declare no conflict of interest.

Background: The immune reconstitution inflammatory syndrome (IRIS) in HIV-infected infants and young children is relatively understudied in regions endemic for HIV and TB. We aimed to describe incidence, clinical features and risk factors of pediatric IRIS in Sub-Saharan Africa and India., Methods and Findings: We conducted an observational multi-centred prospective clinical study from December 2010 to September 2013 in children <72 months of age recruited from public antiretroviral programs. The main diagnostic criterion for IRIS was a new or worsening inflammatory event after initiating antiretroviral therapy (ART). Among 198 participants, median age 1.15 (0.48; 2.21) years, 38 children (18.8%) developed 45 episodes of IRIS. Five participants (13.2%) had two IRIS events and one (2.6%) had 3 events. Main causes of IRIS were BCG (n = 21; 46.7%), tuberculosis (n = 10; 22.2%) and dermatological, (n = 8, 17.8%). Four TB IRIS cases had severe morbidity including 1 fatality. Cytomegalovirus colitis and cryptococcal meningitis IRIS were also severe. BCG IRIS resolved without pharmacological intervention. On multivariate logistic regression, the most important baseline associations with IRIS were high HIV viral load (likelihood ratio [LR] 10.629; p = 0.0011), recruitment at 1 site (Stellenbosch University) (LR 4.01; p = 0.0452) and CD4 depletion (LR 3.4; p = 0.0654). Significantly more non-IRIS infectious and inflammatory events between days 4 and 17 of ART initiation were noted in cases versus controls (35% versus 15.2%: p = 0.0007)., Conclusions: IRIS occurs commonly in HIV-infected children initiating ART and occasionally has severe morbidity. The incidence may be underestimated. Predictive, diagnostic and prognostic biomarkers are needed., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The literature related to eosinophilic gastritis (EG), gastroenteritis (EGE), and colitis (EC) is limited. We aimed to characterize rates of diagnosis, clinical features, and initial treatments for patients with EG, EGE, and EC., Methods: In this retrospective study, data were collected from 6 centers in the Consortium of Eosinophilic Gastrointestinal Researchers from 2005 to 2016. We analyzed demographics, time trends in diagnosis, medical history, presenting symptoms, disease overlap, and initial treatment patterns/responses., Results: Of 373 subjects (317 children and 56 adults), 38% had EG, 33% EGE, and 29% EC. Rates of diagnosis of all diseases increased over time. There was no male predominance, and the majority of subjects had atopy. Presenting symptoms were similar between diseases with nausea/vomiting and abdominal pain, the most common. One hundred fifty-four subjects (41%) had eosinophilic inflammation outside of their primary disease location with the esophagus the second most common gastrointestinal (GI) segment involved. Multisite inflammation was more common in children than in adults (68% vs 37%; P < 0.001). Initial treatment patterns varied highly between centers. One hundred-nine subjects (29%) had follow-up within 6 months, and the majority had clinical, endoscopic, and histologic improvements., Conclusions: In this cohort, EG, EGE, and EC were diagnosed more frequently over time, and inflammation of GI segments outside the primary disease site co-occurrence of atopy was common with a lack of male predominance. Symptoms were similar between diseases, and initial treatment strategies were highly variable. Future investigation should assess the cause of the increased prevalence of eosinophilic GI disorders and prospectively assess outcomes to establish treatment algorithms.

Eosinophilic colitis is a rare entity characterized by the presence of a high eosinophilic infiltrate into the colonic wall in symptomatic patients, more often presenting with abdominal pain or diarrhea. These characteristics distinguish eosinophilic colitis from primary colonic eosinophilia, in which patients are asymptomatic. Primary colonic eosinophilia does not need any therapy, while eosinophilic colitis requires a strict treatment, similar to that of the more codified chronic intestinal inflammatory diseases. To date the lack of codified guidelines regarding the diagnostic criteria and the eosinophil threshold values for each colonic segment are the main diagnostic challenge for eosinophilic colitis. In addition, eosinophilic colitis is a diagnosis of exclusion, once all other causes of colonic eosinophilia (food allergens, infections, drugs, etc.) have been excluded. Several treatment options are available for eosinophilic colitis, although the evidence for most of them is limited to case reports and small case series. We examine the epidemiology, etiology, pathophysiology, diagnostic criteria and therapeutic options of eosinophilic colitis reporting recent evidence from the current literature., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Immune checkpoint inhibitors (ICI) significantly improve overall survival (OS) in patients with advanced melanoma, but immune-related colitis may occur and warrant anti-tumor necrosis factor α (TNFα) treatment in severe forms. A nationwide, multicenter retrospective survey was conducted to assess both, the real-life incidence of grade 3/4 ICI-induced colitis treated with anti-TNFα, in patients with advanced melanoma, and the consequence of this therapeutic strategy on disease outcome. All patients with advanced melanoma treated with anti-TNFα agents for severe ICI-related colitis in the participating centers were included. Relative incidence was calculated according to the total number of patients treated with ICI in network centers during the period of inclusion. The possible impact of anti-TNFα treatment on disease outcome was evaluated through comparison of objective response rate, progression-free survival, and OS with pivotal literature data. Twenty-seven patients from 13 tertiary referral centers were included. Overall, severe ICI-related colitis treated with anti-TNFα occurred in 1% of patients with advanced melanoma, mostly with ipilimumab. Infliximab was successfully used in all patients but 1, mostly after 1 infusion. OS and progression-free survival of 12 and 3 months, respectively, were observed in these patients, along with an objective response rate of 41% at 12 months. This survey shows a low real-life incidence of severe colitis requiring anti-TNFα. Response rates to immunotherapy and survival data do not appear to significantly differ from those observed in pivotal studies. Severe ICI-induced colitis requiring anti-TNFα treatment appears to be a rare event in advanced melanoma, and infliximab does not seem to adversely affect disease outcome.

Background: To support families managing the complex requirements of home parenteral nutrition (HPN) in pediatric patients, health professionals need information about HPN indications and complications. Nationally representative information is limited., Methods: A retrospective cohort analysis of the Truven Health MarketScan Commercial Claims and Encounters Database was performed and identified 683 patients aged ≤18 years receiving HPN during dates of service from January 2013 through September 2015. Baseline diagnoses were measured in the 30 days before the first observed HPN claim (preindex). Indications for older (aged 13-18 years) and younger (aged ≤12 years) children were compared. Hospital and emergency department (ED) utilization rates were measured for 30 postindex days., Results: Gastrointestinal diagnoses and/or symptoms affected more than three-quarters of patients. Short bowel syndrome was more common in younger than in older patients (24% vs 7%, respectively), and colitis was less common (13% vs 33%; both P < .01). Cancer was common in both age groups (22%-23%). Additional diagnoses indicating complex medical conditions were observed in a minority of patients: sepsis (9%), convulsions/epilepsy (7%), encephalopathy (3%), and immune deficiency (3%). From the preindex to postindex periods, rates of inpatient hospitalization declined from 78% to 41%, but hospital ED visits increased from 10% to 14%. In both periods, >95% of hospital and ED use was disease related., Conclusion: In a nationally representative sample of commercially insured pediatric patients treated with HPN, complex medical conditions were common. Findings highlight the importance of American Society for Parenteral and Enteral Nutrition recommendations for team-based care., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Background: Drug toxicity is a common and even serious problem in the gastrointestinal tract that is thought to be caused by a broad spectrum of agents. Although withdrawal of the causative agent would cure the disease knowledge is scarce and mostly derives from case reports and series., Aim: To investigate potential triggers of drug-induced colitis (DiC)., Methods: We conducted a retrospective, observational case control study. Patients were assigned to DiC or one of two age- and gender-matched control groups (non-inflammatory controls and inflammatory colitis of another cause) based on histopathological findings. Histopathology was reassessed in a subset of patients (28 DiC with atherosclerosis, DiC without atherosclerosis and ischaemic colitis each) for validation purposes. Medical history was collected from the electronic database and patient records. Statistical analysis included chi-squared test, t -test, logistic and multivariate regression models., Results: Drug-induced colitis was detected in 211 endoscopically sampled biopsy specimens of the colon mucosa (7% of all screened colonoscopic biopsy samples); a total of 633 patients were included equally matched throughout the three groups (291 males, mean age: 62.1 ± 16.1 years). In the univariate analysis, DiC was associated with diuretics, dihydropyridines, glycosides, ASS, platelet aggregation inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), statins and fibrates, and with atherosclerosis, particularly coronary heart disease, and hyperlipoproteinaemia. Echocardiographic parameters did not show substantial differences. In the multivariate analysis only fibrates [odds ratio (OR) = 9.1], NSAIDs (OR = 6.7) and atherosclerosis (OR = 2.1) proved to be associated with DiC. Both DiC reassessment groups presented milder inflammation than ischaemic colitis. The DiC patients with atherosclerosis exhibited histological features from both DiC without atherosclerosis and ischaemic colitis., Conclusion: Several drugs indicated for the treatment of cardiovascular and related diseases are associated with DiC. Atherosclerosis and microcirculatory disturbances seem to play an important pathogenetic role., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest.

Mucohaemorrhagic diarrhea associated with Brachyspira hampsonii infection has emerged as a production-limiting disease in western Canada. This pathogen was first described in North America in 2010, and reports of its detection occurred concurrently in western Canada and the United States. Since that time, Brachyspira hampsonii has been detected in Europe, both in pigs and in waterfowl. The origin of B. hampsonii and the timing and reasons for its emergence are unknown. We conducted a retrospective study of historic, archived cases of porcine colitis to determine when B. hampsonii was first evident in western Canada. A total of 206 samples from 114 cases submitted from 57 different farms or productions systems in 1984 and 1999-2009 were screened using real-time PCR assays targeting B. hampsonii genomovars I and II, and Brachyspira hyodysenteriae (the traditional agent of swine dysentery). In most cases, positive real-time PCR results were confirmed by amplification and sequencing of additional gene targets. A total of 9, 7 and 5 samples tested positive for B. hampsonii (I), B. hampsonii (II) or B. hyodysenteriae respectively. The results of this study push the date of first appearance of B. hampsonii in pigs in western Canada back to 2002 (B. hampsonii (I)) and 2006 (B. hampsonii (II)), which is up to 7 years before the new species were first identified in fresh samples., (© 2018 Blackwell Verlag GmbH.)

Immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1) have recently revolutionized anti-cancer therapy and are nowadays used in different metastatic cancers. These treatments may induce immune-related adverse events which frequently involve the digestive tract and, to a less extent the liver. The tissular injuries, which are still poorly characterized from a morphological and physiopathological point of view, may lead on one side to the interruption of a life-saving treatment and on the other side to the development of severe complications, if not death. Therefore, it is crucial to diagnose as early as possible and treat these digestive and hepatic adverse effects in an optimal way. This article aims to describe the clinical and pathological presentations of digestive and hepatic adverse events induced by these immunotherapies., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The aim of the current study was to enhance the awareness of phlebosclerotic colitis (PC) through our clinical experience.A retrospective review of 25 patients who were diagnosed as PC in our 2 affiliated hospitals from January 2013 to October 2017 was conducted.The patients were found at a mean age of 63.5 years, range 47 to 87years. The majority of patients were male (23 cases). Only 4 patients (16%, 4/25) had the history about long-term use of Chinese herbs and medical liquor. The most common symptoms were abdominal pain (40%) and intestinal obstruction (16%), followed by diarrhea (12%), and gastrointestinal bleeding (12%), etc. Three cases (12%) had no symptoms. The varying degrees of calcifications along the colon and mesenteric venous were found in all of their computed tomography (CT) images. The lesions mainly located in transverse and ascending colon (60%, 15/25). The terminal ileum, the whole colon and rectum involvement were also been found. Fourteen patients had the examination of colonoscopy which all presented characteristic dark purple-colored endoscopic findings. Conservative treatment with close follow-up was preferred in our group. Three cases had the surgery of colectomy due to the repeatedly intestinal obstruction, perforation.The PC was a very rare but characteristic entity with unclear etiopathogenesis. Examination of abdomen CT and colonoscopy could help you to make clinical diagnosis.

Background: Immunotherapies in cancer treatment have a long history going all the way back to the very beginning of the field, and recent advances are extremely promising. These therapies are becoming a larger part in many patients' oncology treatment as the number of approaches, individual medicines, and indications increase. Furthermore, these novel therapies have different side effect profiles from those traditional chemotherapies which have, until recently, typified the oncologist's approach to treatment together with surgery and radiation., Methods: An electronic literature search was conducted in May and June 2017 and March 2018 with the PubMed and Ebscohost databases. Articles were chosen for their relevance to the drugs in question, cancer physiology, or historic significance., Conclusions: Checkpoint inhibitors are becoming very common and possess autoimmune side effects such as pneumonitis, hypothyroidism, and colitis. These may present at any time the patient is on the medications but are more common several weeks to several months from beginning therapy. Chimeric antigen receptor T-cell therapies are powerful but have strong side effects such as cytokine release syndrome. Neoantigens are currently in the early stages of clinical trials and may become an exciting avenue for personalized cancer treatment but are not yet typical., Competing Interests: Conflict of interest: none declared., (© Copyright 2018 by the American Board of Family Medicine.)

Colitis is one of major adverse event induced by immune checkpoint inhibitor(ICPi), especially in the treatment with anti- CTLA-4 antibody. Colitis can occur anytime during ICPi therapy. The most common symptom is diarrhea. Other symptoms are abdominal pain, hematochezia, weight loss, fever and vomiting. To diagnose ICPi-induced colitis, it is important to deny infectious enterocolitis and tumor-related symptoms. Sigmoidoscopy or colonoscopy with biopsy are useful for proper diagnosis and evaluation of the severity. Patients with ulcer lesion tend to show resistance to steroid therapy. Diarrhea is an important symptom to evaluate the severity of colitis. American Society of Clinical Oncology and European Society for Medical Oncology published clinical guidelines for immune related adverse events including colitis. If patient has CTCAE Grade 2 or more severe diarrhea, both guidelines recommend stop ICPi and start corticosteroid therapy. As colitis can progress rapidly and induce perforation, the initiation of steroid therapy should not be hesitated. Some patients are resistant to steroid therapy, in which case infliximab, anti-TNF-a antibody, is recommended. ICPi-induced colitis is different from conventional adverse event induced by cytotoxic agents in terms of management with coticosteroid. Therefore, consultation to gastroenterologist is essential for proper diagnosis and corticosteroid initiation without delay.

Study Design: A retrospective study of prospectively collected data., Objective: The aim of this study was to utilize a large national database with post-hospitalization follow-up data [National Surgical Quality Improvement Program (NSQIP)] to determine the incidence, risk factors, timing, and clinical impact of Clostridium difficile colitis in spine surgery patients., Summary of Background Data: Recent literature has suggested an increased incidence of C. difficile infections. However, there has been a lack of large cohort studies defining the incidence and impact of C. difficile colitis in patients undergoing spine surgery., Methods: Patients who underwent spine surgical procedures in the 2015 NSQIP database were identified. The primary outcome was a diagnosis of C. difficile colitis within the 30-day postoperative period. Independent risk factors for development of C. difficile colitis were identified using multivariate regression. Postoperative length of stay and rate of 30-day readmission were compared between patients who did and did not develop C. difficile colitis., Results: A total of 23,981 patients who underwent spine surgical procedures were identified. The incidence of C. difficile colitis was approximately 0.11% [95% confidence interval (95% CI), 0.07-0.16]. Of the cases that developed C. difficile colitis, 70% were diagnosed postdischarge and 88% had not had a pre-existing infection diagnosed. Independent risk factors for the development of C. difficile colitis were combined anterior/posterior lumbar fusion procedures [odds ratio (OR) = 12.29, 95% CI = 2.22-68.13, P = 0.010], greater age (most notably ≥76 years old, OR = 10.31, 95% CI = 3.06-34.76, P < 0.001), hypoalbuminemia (OR = 6.40, 95% CI = 2.49-16.43, P < 0.001), and anemia (OR = 2.39, 95% CI = 1.13-5.05, P = 0.023). The development of C. difficile colitis was associated with greater length of stay (2.2 vs. 12.5 days; P < 0.001) and increased 30-day readmission (OR = 8.21, 95% CI = 3.14-21.45, P < 0.001)., Conclusion: C. difficile was diagnosed in 0.11% of patients undergoing spine surgery. The majority of these cases occurred after discharge and in patients not having prior infection diagnoses. High-risk patients should be monitored and targeted with preventative interventions accordingly., Level of Evidence: 3.

Chronic abdominal and pelvic pain are common debilitating clinical conditions experienced by millions of patients around the globe. The origin of such pain commonly arises from the intestine and bladder, which share common primary roles (the collection, storage, and expulsion of waste). These visceral organs are located in close proximity to one another and also share common innervation from spinal afferent pathways. Chronic abdominal pain, constipation, or diarrhea are primary symptoms for patients with irritable bowel syndrome or inflammatory bowel disease. Chronic pelvic pain and urinary urgency and frequency are primary symptoms experienced by patients with lower urinary tract disorders such as interstitial cystitis/painful bladder syndrome. It is becoming clear that these symptoms and clinical entities do not occur in isolation, with considerable overlap in symptom profiles across patient cohorts. Here we review recent clinical and experimental evidence documenting the existence of "cross-organ sensitization" between the colon and bladder. In such circumstances, colonic inflammation may result in profound changes to the sensory pathways innervating the bladder, resulting in severe bladder dysfunction.