[Iatrogenic colitis following immunotherapy : monocentric retrospective study at the University Hospital of Liège]. / Colites iatrogènes sur immunothérapie : étude rétrospective au CHU de Liège.

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.

La colite iatrogène sur immunothérapie est une complication souvent sous-évaluée lorsqu'elle est de bas grade et entraîne relativement peu d'hospitalisations par rapport à sa fréquence d'apparition. Une approche stricte au niveau de l'anamnèse, combinée à un bilan endo-scopique en cas de gravité, est conseillée. La mesure de la calprotectine fécale peut également s'avérer utile. Les différentes lignes de traitement sont, en cas d'utilisation adéquate, le plus souvent efficaces et les deuxièmes lignes (biothérapies) ne sont que rarement utilisées. Cependant, de récentes données conseillent une utilisation plus rapide des traitements biologiques chez les patients ayant un tableau sévère, surtout si celui-ci est confirmé au niveau endoscopique, car les corticoïdes entrainent un risque majoré de surinfection. L'objectif de ce travail est de démontrer l'efficacité des traitements non symptomatiques de 1ère et de 2ème lignes dans le cadre de colites liées aux immunothérapies sur une population de patients du CHU de Liège.

Prevalence and Natural History of Segmental Colitis Associated With Diverticulosis.

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.

Clostridium difficile colitis following geriatric hip fracture surgery: incidence, trends, and risk factors from 45,910 patients.

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.

Tyzzer disease in 19 preweaned orphaned kittens.

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.

Fecal prevalence of Clostridium innocuum DNA in healthy horses and horses with colitis.

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).

Characterization of an outbreak of equine coronavirus infection in adult horses in Switzerland.

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: Des foyers d'infection à coronavirus équin (ECoV) ont été décrits dans différentes parties du monde, y compris en Europe. L'objectif de ce rapport est de décrire les signes cliniques, le diagnostic et les conséquences du premier foyer d'ECoV documenté en Suisse, afin de sensibiliser le public à cette maladie et à ses différents aspects cliniques. L'épidémie s'est produite dans une écurie comptant 26 chevaux. Parmi ceux-ci, sept chevaux ont développé une forme clinique allant de signes légers tels que la fièvre et l'anorexie à des signes sévères de colite aiguë. Un cheval est mort en raison d'une endotoxémie sévère et d>un choc circulatoire secondaire à une entérite nécrosante aiguë sévère et à une colite. Sur les 26 chevaux, cinq ont été testés positifs à l>ECoV, dont deux poneys sans aucun signe clinique d'infection. Le faible nombre de cas positifs doit néanmoins être interprété avec prudence car les tests n'ont été effectués qu'à une seule occasion, plus d'un mois après l'apparition des signes cliniques chez le premier cas suspect. Ce rapport souligne l'importance des tests de diagnostic et de la mise en œuvre rapide de mesures de biosécurité dans une exploitation où un foyer d'ECoV est détecté. Il devrait en outre sensibiliser à la présence de signes cliniques peu spécifiques et bénins tels que la fièvre et l'anorexie chez les animaux atteints qui sont potentiellement capables de propager la maladie.

Immune checkpoint Inhibitor-Induced diarrhea and Colitis: Incidence and Management. A systematic review and Meta-analysis.

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.

Clostridium difficile colitis portends poor outcomes in lower extremity orthopaedic trauma surgery.

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.

Immunotherapy-induced Colitis: A Comprehensive Review of Epidemiology, Clinical Presentation, Diagnostic Workup, and Management Plan.

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.

Immune checkpoint inhibitor induced colitis: A nationwide population-based study.

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.

Crypts in Asymmetric Fission in Endoscopic Biopsies from German Patients With Inflammatory Bowel Disease.

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.

Immune Checkpoint Inhibitor-associated Diarrhea and Colitis: A Systematic Review and Meta-analysis of Observational Studies.

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.

Postoperative Survival in Colitis-associated Colorectal Cancer With Ulcerative Colitis in Japan: A Multicenter Analysis.

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.

Cytomegalovirus in pediatric inflammatory bowel disease patients with acute severe colitis.

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.

DSS-induced colitis is associated with adipose tissue dysfunction and disrupted hepatic lipid metabolism leading to hepatosteatosis and dyslipidemia in mice.

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.

Superiority of Higher-Volume Fresh Feces Compared to Lower-Volume Frozen Feces in Fecal Microbiota Transplantation for Recurrent Clostridioides Difficile Colitis.

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.

Epidemiology and Natural History of Elderly-onset Inflammatory Bowel Disease: Results From a Territory-wide Hong Kong IBD Registry.

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.

Post-transplant colitis after kidney transplantation: clinical, endoscopic and histological features.

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.

The risk of diarrhea and colitis in patients with lung cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

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.

Incidence and Risk of Colitis With Programmed Death 1 Versus Programmed Death Ligand 1 Inhibitors for the Treatment of Cancer.

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.