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Whether preoperative treatment of inflammatory bowel disease (IBD) with tumor necrosis factor inhibitors (TNFis) increases the risk of postoperative infectious complications remains controversial. The primary aim of this study was to determine whether preoperative exposure to TNFis is an independent risk factor for postoperative infectious complications within 30 days of surgery.We conducted a multicenter prospective observational study of patients with IBD undergoing intra-abdominal surgery across 17 sites from the Crohn'sColitis Foundation Clinical Research Alliance. Infectious complications were categorized as surgical site infections (SSIs) or non-SSIs. Current TNFi exposure was defined as use within 12 weeks of surgery, and serum was collected for drug-level analyses. Multivariable models for occurrence of the primary outcome, any infection, or SSI were adjusted by predefined covariates (age, sex, preoperative steroid use, and disease type), baseline variables significantly associated (P.05) with any infection or SSI separately, and TNFi exposure status. Exploratory models used TNFi exposure based on serum drug concentration.A total of 947 patients were enrolled from September 2014 through June 2017. Current TNFi exposure was reported by 382 patients. Any infection (18.1% vs 20.2%, P = .469) and SSI (12.0% vs 12.6%, P = .889) rates were similar in patients currently exposed to TNFis and those unexposed. In multivariable analysis, current TNFi exposure was not associated with any infection (odds ratio, 1.050; 95% confidence interval, 0.716-1.535) or SSI (odds ratio, 1.249; 95% confidence interval, 0.793-1.960). Detectable TNFi drug concentration was not associated with any infection or SSI.Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort.

OBJECTIVE: To discover if first-attempt failure of the American Board of Colon and Rectal Surgery (ABCRS) board examination is associated with surgical training or personal demographic characteristics. METHODS: Current colon and rectal surgery program directors in the United States were contacted via email. Deidentified records of trainees from 2011 to 2019 were requested. Analysis was performed to identify associations between individual risk factors and failure on the ABCRS board examination on the first attempt. RESULTS: Seven programs contributed data, totaling 67 trainees. The overall first-time pass rate was 88% (n = 59). Several variables demonstrated potential for association, including Colon and Rectal Surgery In-Training Examination (CARSITE) percentile (74.5 vs 68.0, P = 0.09), number of major cases in colorectal residency (245.0 vs 219.2, P = 0.16), >5 publications during colorectal residency (75.0% vs 25.0%, P = 0.19), and first-time passage of the American Board of Surgery certifying examination (92.5% vs 7.5%, P = 0.18). CONCLUSION: The ABCRS board examination is a high-stakes test, and training program factors may be predictive of failure. Although several factors showed potential for association, none reached statistical significance. Our hope is that by increasing our data set, we will identify statistically significant associations that can potentially benefit future trainees in colon and rectal surgery.

AIM Tumour necrosis factor inhibitors (TNFi) have revolutionized the management of moderate to severe ulcerative colitis (UC) since their approval for UC in 2005. However, many patients ultimately require surgery with ileal pouch-anal anastomosis (IPAA). Development of de novo Crohn's disease (CD) following IPAA is an increasingly common and devastating complication, sometimes progressing to pouch failure. The aim of this study was to evaluate the association of preoperative TNFi exposure and the development of de novo CD after IPAA. METHOD A prospective single-centre inflammatory bowel disease (IBD) registry was searched for consecutive patients with UC undergoing IPAA during a 25-year period ending July 2018. Patients with preoperative CD or IBD-unclassified were excluded. De novo CD was diagnosed upon endoscopic evidence of five or more mucosal ulcers proximal to the ileal pouch any time after surgery and/or pouch fistula occurring more than three months after ileostomy closure. RESULTS The study cohort consisted of 400 patients with a median follow-up of 44.0 (IQR 11-113) months. Sixty-two (16%) patients developed de novo CD 28.0 (IQR 6-67) months following ileostomy closure. Survival analysis of TNFi era patients revealed a significant increase in de novo CD risk in those with preoperative TNFi exposure. Multivariable proportional hazards modelling revealed two independent predictors for de novo CD development: older age was protective (HR 0.89 per 5-year increase; P = 0.009) and preoperative TNFi exposure was hazardous (HR 2.10; P = 0.011). CONCLUSION This prospective study is the first to suggest an association between preoperative TNFi exposure and the development of de novo CD.

Background: There are reported variations in the intraoperative management of Crohn's disease. This consensus statement aimed to develop a standardised protocol for photographic documentation of intraoperative findings and critical procedural steps in ileocolonic Crohn's disease surgery. Methods: Colorectal surgeons with a specialist interest in minimally invasive surgery and inflammatory bowel disease were invited as committee members to develop a survey on the use of photo-documentation in Crohn's disease surgery. A 15 item survey was developed on ethical considerations and applications of photo-documentation in audit and quality control, research, and training. Results: There was strong agreement on the potential application of intraoperative photodocumentation in Crohn's disease for training, research, quality control and tertiary referrals. Reviewers agreed that intraoperative staging required photo-documentat of strictures, skip lesions, perforations, fat wrapping and mesenteric disease. The necessary steps to be photo-documented were very specific to Crohn's disease surgery, such as views of anastomosis and strictureplasties, and extent of resection(s). Conclusions: Our consensus statement identified several items for appropriate intraoperative photo-documentation in Crohn's disease surgery, to be used as an adjunct to accurate annotation of intraoperative findings and procedures.

We compared the safety and effectiveness of tumor necrosis factor α (TNF-α) antagonists vs vedolizumab vs ustekinumab in patients with Crohn's disease (CD) in a multicenter cohort (CA-IBD).We created an electronic health record-based cohort of adult patients with CD who were initiating a new biologic agent (TNF-α antagonists, ustekinumab, vedolizumab) from 5 health systems in California between 2010 and 2017. We compared the risk of serious infections (safety) and all-cause hospitalization and inflammatory bowel disease-related surgery (effectiveness) between different biologic classes using propensity score (PS) matching.As compared with TNF-α antagonists (n = 1030), 2:1 PS-matched, ustekinumab-treated patients with CD (n = 515) experienced a lower risk of serious infections (hazard ratio [HR], 0.36; 95% CI, 0.20-0.64), without any difference in the risk of hospitalization (HR, 0.99; 95% CI, 0.89-1.21) or surgery (HR, 1.08; 95% CI, 0.69-1.70). Compared with vedolizumab (n = 221), 1:1 PS-matched, ustekinumab-treated patients with CD (n = 221) experienced a lower risk of serious infections (HR, 0.20; 95% CI, 0.07-0.60), without significant differences in risk of hospitalization (HR, 0.76; 95% CI, 0.54-1.07) or surgery (HR, 1.42; 95% CI, 0.54-3.72). Compared with TNF-α antagonists (n = 442), 2:1 PS-matched, vedolizumab-treated patients with CD (n = 221) had a similar risk of serious infections (HR, 1.53; 95% CI, 0.84-2.78), hospitalization (HR, 1.32; 95% CI, 0.98-1.77), and surgery (HR, 0.63; 95% CI, 0.27-1.47). High comorbidity burden, concomitant opiate use, and prior hospitalization were associated with serious infections and hospitalization in biologic-treated patients with CD.In a multicenter cohort of biologic-treated patients with CD, ustekinumab was associated with a lower risk of serious infections compared with TNF-α antagonists and vedolizumab, without any differences in risk of hospitalization or surgery. The risk of serious infections was similar for TNF-α antagonists vs vedolizumab.

There are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients.We identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis.We compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P = .02) and had a higher burden of comorbidities (Elixhauser index,0; 37% vs 26%; P.01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05).In a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.

The management of hospitalized patients with acute, severe ulcerative colitis involves close coordination among a multidisciplinary team. For patients not improving on intravenous corticosteroids, surgical consultation should be sought. The remaining hospital course requires frequent communications between the gastroenterologist managing the medical aspects of care, and the colorectal surgeon involved in planning for potential surgery, to optimize patient outcomes. This comanagement includes joint decision-making around the timing of surgery, minimizing medications associated with postoperative morbidity, addressing nutritional and psychosocial aspects of the patient's condition, and planning for a coordinated postoperative course. In this review, we highlight these aspects of care and the need for coordination and communication between gastroenterologists and surgeons in the management of acute severe colitis.

Despite significant development in the pharmacological treatment of inflammatory bowel diseases (IBD) along with the evolution of therapeutic targets and treatment strategies, a significant subset of patients still requires surgery during the course of the disease. As IBD patients are frequently exposed to biologics at the time of abdominal and perianal surgery, it is crucial to identify any potential impact of biological agents in the perioperative period. Even though detectable serum concentrations of biologics do not seem to increase postoperative complications after abdominal procedures in IBD, there is increasing evidence on the role of therapeutic drug monitoring (TDM) in the perioperative setting. This review aims to provide a comprehensive summary of published studies reporting the association of drug concentrations and postoperative outcomes, postoperative recurrence (POR) after an ileocolonic resection for Crohn’s disease (CD), colectomy rates in ulcerative colitis (UC), and perianal fistulizing CD outcomes in patients treated with biologics. Current data suggest that serum concentrations of biologics are not associated with an increased risk in postoperative complications following abdominal procedures in IBD. Moreover, higher concentrations of anti-TNF agents are associated with a reduction in colectomy rates in UC. Finally, higher serum drug concentrations are associated with reduced rates of POR after ileocolonic resections and increased rates of perianal fistula healing in CD. TDM is being increasingly used to guide clinical decision making with favorable outcomes in many clinical scenarios. However, given the lack of high quality data deriving mostly from retrospective studies, the evidence supporting the systematic application of TDM in the perioperative setting is still inconclusive.

Introduction Due to concerns over wound healing, hemorrhoidectomy in patients with Crohn’s disease (CD) remains controversial. We sought to ascertain safety and efficacy of excisional hemorrhoidectomy in CD. Methods A retrospective review of all adult CD patients undergoing excisional hemorrhoidectomy between January 1, 1995, and January 1, 2019, at 2 IBD referral centers was performed. Data collected included patient demographics, clinical characteristics of CD (anorectal symptoms; prior nonoperative hemorrhoidal therapy; presence of other perianal disease; and activity, duration, and anatomic location of CD), and postoperative complications including bleeding, wound healing, and need for further therapy or surgical intervention after surgery. Results A total of 36 adult patients with Crohn’s disease with symptomatic hemorrhoidal disease were included. The study cohort included 16 males (44%), and median age was 49 (range, 21 to 77) years. Predominant symptoms included pain (n = 16; 44%), prolapse (n = 8; 22%), and bleeding (n = 12; 33%). Sixteen patients (44%) had nonoperative therapy before surgery. Twenty-four patients (67%) had other perianal disease. At the time of hemorrhoidectomy, 9 patients (25%) were exposed to corticosteroids, 8 patients (25%) to immunomodulators, and 9 patients (25%) to biologics. During a median follow-up time of 31.5 (range, 1 to 255) months after hemorrhoidectomy, 4 patients (11%) had complications (1 developed a stricture, 1 developed a perianal abscess/fistula, 1 had a nonhealing wound, and 1 had hemorrhoidal recurrence). Conclusion Our data suggest that excisional hemorrhoidectomy may be performed safely in CD patients who have failed nonoperative hemorrhoidal therapy without concern for de novo perianal disease or need for proctectomy. Hemorrhoidal disease is common in patients with Crohn’s disease. This study sought to understand the outcomes of surgically treating hemorrhoids in patients with Crohn’s disease.

Background and Aims It is unclear whether pre-pouch ileitis heralds an aggressive inflammatory pouch disease in patients with ileal pouch-anal anastomosis [IPAA]. We compared outcomes of patients with pouchitis and concomitant pre-pouch ileitis with those with pouchitis alone. Methods Patients undergoing IPAA surgery for inflammatory bowel disease, who subsequently developed pouchitis with concomitant pre-pouch ileitis [pre-pouch ileitis group], were matched by year of IPAA surgery and preoperative diagnosis [ulcerative colitis or inflammatory bowel disease-unclassified] with patients who developed pouchitis alone [pouchitis group]. Primary outcomes were development of Crohn’s disease [CD]-like complications [non-anastomotic strictures or perianal disease >6 months after ileostomy closure] and pouch failure. Secondary outcomes were need for surgical/endoscopic interventions and immunosuppressive therapy. Log-rank testing was used to compare outcome-free survival, and Cox regression was performed to identify predictors of outcomes. Results There were 66 patients in each group. CD-like complications and pouch failure developed in 36.4% and 7.6% patients in the pre-pouch ileitis group and 10.6% and 1.5% in pouchitis group, respectively. CD-like complications-free survival [log-rank p = 0.0002] and pouch failure-free survival [log-rank p = 0.046] were significantly lower in the pre-pouch ileitis group. The pre-pouch ileitis group had a higher risk of requiring surgical/endoscopic interventions [log-rank p = 0.0005] and immunosuppressive therapy [log-rank p Conclusions Pre-pouch ileitis is associated with a higher risk of complicated disease and pouch failure than pouchitis. It should be considered a feature of CD.

A mysterious feature of Crohn’s disease (CD) is the extra-intestinal manifestation of “creeping fat” (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria., Graphical Abstract, Highlights • Gut bacterial translocation to mesenteric adipose tissue (MAT) naturally occurs • MAT from Crohn’s disease (CD) harbors a bacterial consortium defined by C. innocuum • These bacteria in CD promote restructuring of MAT and formation of “creeping fat” • Creeping fat expansion and fibrosis prevent systemic translocation of gut bacteria, Ha et al. provide evidence that, in humans with inflammatory bowel disease, the phenomenon known as “creeping fat” is a protective response where mesenteric adipose tissue migrates (or “creeps”) to sites of gut barrier dysfunction to prevent systemic dissemination of potentially harmful bacterial antigens that have translocated across the barrier from the gut lumen.

ispartof: DISEASES OF THE COLON & RECTUM vol:63 issue:7 pages:870-873 ispartof: location:United States status: published

The management of IBD has been highly affected in the context of the COVID-19 pandemic, with restriction of hospitalisations and unprecedented redeployment of health care resources. Hospital admissions of IBD patients should be limited to reduce the risks of coronavirus transmission. However, delaying hospitalisation of IBD patients with severe or complicated disease may increase the risk of poor outcomes. Delaying surgery in some cases may increase the risk of disease progression, postoperative morbidity, and disease complications. IBD patients who are infected with SARS-CoV-2 may have a higher risk of poor outcomes than the general population, potentially related to concomitant medications, especially corticosteroids. There is no evidence today that IBD patients with COVID-19 have worse outcomes if they receive immunosuppressant medications including thiopurines, biologics, and novel small molecules. This article summarises recommendations by the international membership of IOIBD regarding hospitalisations of IBD patients, either for active or complicated IBD or for severe COVID-19, and for management of IBD patients according to SARS-CoV-2 infectious status.

The host receptor for severe acute respiratory syndrome coronavirus 2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small bowel (SB). Our aim was to identify factors influencing intestinal ACE2 expression in Crohn's disease (CD), ulcerative colitis (UC), and non-inflammatory bowel disease (IBD) controls.Using bulk RNA sequencing or microarray transcriptomics from tissue samples (4 SB and 2 colonic cohorts; n = 495; n = 387 UC; n = 94 non-IBD), we analyzed the relationship between ACE2 with demographics and disease activity and prognosis. We examined the outcome of anti-tumor necrosis factor and anti-interleukin-12/interleukin-23 treatment on SB and colonic ACE2 expression in 3 clinical trials. Univariate and multivariate regression models were fitted.ACE2 levels were consistently reduced in SB CD and elevated in colonic UC compared with non-IBD controls. Elevated SB ACE2 was also associated with demographic features (age and elevated body mass index) associated with poor coronavirus disease 2019 outcomes. Within CD, SB ACE2 was reduced in patients subsequently developing complicated disease. Within UC, colonic ACE2 was elevated in active disease and in patients subsequently requiring anti-tumor necrosis factor rescue therapy. SB and colonic ACE2 expression in active CD and UC were restored by anti-cytokine therapy, most notably in responders.Reduced SB but elevated colonic ACE2 levels in IBD are associated with inflammation and severe disease, but normalized after anti-cytokine therapy, suggesting compartmentalization of ACE2-related biology in SB and colonic inflammation. The restoration of ACE2 expression with anti-cytokine therapy might be important in the context of severe acute respiratory syndrome coronavirus 2 infection and potentially explain reports of reduced morbidity from coronavirus disease 2019 in IBD patients treated with anti-cytokines.

Background Although biologic agents have revolutionized the medical management of severe ulcerative colitis (UC), there is considerable controversy regarding adverse effects of vedolizumab on surgical outcomes. We evaluated 30-day postoperative morbidity in UC patients undergoing abdominal colectomy (AC) treated with vedolizumab before surgery. Methods From 2007 to 2017, 285 patients were enrolled in prospectively maintained database evaluating the role of clinical, serologic markers with clinical phenotypes in UC. The patients treated with vedolizumab within 12 weeks of AC was queried, then matched 1:3:3 into 3 preoperative treatment groups based on age, gender and surgical treatment of UC; ileal pouch-anal anastomosis (IPAA) with ileostomy vs total colectomy with end stoma: a) vedolizumab (n = 25); b) anti-tumor necrosis factor (anti-TNF) (n = 74); and c) no biologics (n = 54). Thirty-day postoperative complications among patient groups were compared. Results The 3 patient groups were well-matched in other characteristics including disease duration, disease extent, medication history and preoperative serological data. There were no significant differences in the overall incidence of postoperative complications among patients treated preoperatively with vedolizumab, anti-TNFs, or no biologics (44% vs. 45% vs. 37%; p = 0.67). Although there was no significant difference between patient cohorts in infectious complications (p = 0.20), postoperative ileus (POI) was significantly more common among the vedolizumab group (n = 9; 36%) compared to anti-TNF (n = 12; 16%) or no biologics (n = 5; 9%) (p = 0.01). Multivariable analysis showed that vedolizumab treatment prior to surgery was an independent risk factor for POI (OR: 5.16, 95% CI; 1.71–15.52; p = .004). Conclusion Although preoperative vedolizumab exposure did not influence the rate of overall 30-day postoperative complications, vedolizumab tends to increase incidence of POI.

Initial reports of transanal ileal pouch-anal anastomosis (taIPAA) suggest safety and feasibility compared with transabdominal IPAA. The purpose of this study was to evaluate differences in technique and results of taIPAA in three centers performing taIPAA across two continents. Prospective IPAA registries from three institutions in the US and Europe were queried for patients undergoing taIPAA. Demographic, preoperative, intraoperative, and postoperative data were compiled into a single database and evaluated. Sixty-two patients (median age 38 years; range 16–68 years, 43 (69%) male) underwent taIPAA in the three centers (USA 24, UK 23, Italy 15). Most patients had had a subtotal colectomy before taIPAA [n = 55 (89%)]. Median surgical time was 266 min (range 180–576 min) and blood loss 100 ml (range 10–500 ml). Technical variations across the three institutions included proctectomy plane of dissection (intramesorectal or total mesorectal excision plane), specimen extraction site (future ileostomy site vs. anus), ileo-anal anastomosis technique (stapled vs. hand sewn) and use of fluorescence angiography. Despite technical differences, anastomotic leak rates (5/62; 8%) and overall complications (18/62; 29%) were acceptable across the three centers. This is the first collaborative report showing safety and feasibility of taIPAA. Despite technical variations, outcomes are similar across centers. A large multi-institutional, international IPAA collaborative is needed to compare technical factors and outcomes.

The majority of colorectal cancers (CRC) harbor somatic mutations and epigenetic modifications in the tumor tissue, and some of these mutations can be detected in plasma as circulating tumor DNA (ctDNA). Precancerous colorectal lesions also contain many of these same mutations. This study examined plasma for ctDNA from patients undergoing a screening or diagnostic colonoscopy to determine the sensitivity and specificity of the ctDNA panel for detecting CRC and precancerous lesions. Two hundred patients without a history of nonskin cancer had blood drawn before a colonoscopy. Plasma ctDNA was measured with a 96 mutation panel for nine cancer driver genes. The ctDNA results were correlated with the findings at colonoscopy. Of the 200 patients, 176 (88%) had wild‐type DNA, 12 (6%) had mutations detected, and 12 (6%) had indeterminate results. Colonoscopy was normal in 80% of the patients and 20% were found to have polyps. No CRC was found in this study, precluding a determination of true‐positive rate for CRC detection. Our ctDNA panel was positive in 13.2% of patients with colonic polyps found at colonoscopy, while 4.7% of patients with normal colonoscopy also had ctDNA detected, which may represent ctDNA released from a benign process, an occult tumor, or an acquired somatic mutation from clonal hematopoiesis.

Traditionally, surgical interventions for colonic Crohn's disease (CD) have been limited to total abdominal colectomy and ileorectal anastomosis, or total proctocolectomy with end ileostomy if there is rectal involvement. However, improved understandings of the biology of CD, as well as the development of biologic therapies, have enabled more limited resections. Here, we review the indications for, and limitations of, specific procedures aiming to preserve intestinal continuity in colonic CD.

Background and Aims Heterogeneity in Crohn’s disease [CD] provides a challenge for the development of effective therapies. Our goal was to define a unique molecular signature for severe, refractory CD to enable precision therapy approaches to disease treatment and to facilitate earlier intervention in complicated disease. Methods We analysed clinical metadata, genetics, and transcriptomics from uninvolved ileal tissue from CD patients who underwent a single small bowel resection. We determined transcriptional risk scores, cellular signatures, and mechanistic pathways that define patient subsets in refractory CD. Results Within refractory CD, we found three CD patient subgroups [CD1, CD2, and CD3]. Compared with CD1, CD3 was enriched for subjects with increased disease recurrence after first surgery [OR = 6.78, p = 0.04], enhanced occurrence of second surgery [OR = 5.07, p = 0.016], and presence of perianal CD [OR = 3.61, p = 0.036]. The proportion of patients with recurrence-free survival was smaller in CD3 than in CD1 (p = 0.02, median survival time [months] in CD1 = 10 and CD3 = 6). Overlaying differential gene expression between CD1 and CD3 on CD subgroup-associated genetic polymorphisms identified 174 genes representing both genetic and biological differences between the CD subgroups. Pathway analyses using this unique gene signature indicated eukaryotic initiation factor 2 [eIF2] and cyclic adenosine monophosphate [cAMP] signalling to be dominant pathways associated with CD3. Furthermore, the severe, refractory subset, CD3, was associated with a higher transcriptional risk score and enriched with eosinophil and natural killer T [NKT] cell gene signatures. Conclusion We characterized a subset of severe, refractory CD patients who may need more aggressive treatment after first resection and who are likely to benefit from targeted therapy based on their genotype and tissue gene expression signature.

Background And Aims The host receptor for severe acute respiratory syndrome coronavirus 2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small bowel (SB). Our aim was to identify factors influencing intestinal ACE2 expression in Crohn's disease (CD), ulcerative colitis (UC), and non–inflammatory bowel disease (IBD) controls. Methods Using bulk RNA sequencing or microarray transcriptomics from tissue samples (4 SB and 2 colonic cohorts; n = 495; n = 387 UC; n = 94 non-IBD), we analyzed the relationship between ACE2 with demographics and disease activity and prognosis. We examined the outcome of anti–tumor necrosis factor and anti–interleukin-12/interleukin-23 treatment on SB and colonic ACE2 expression in 3 clinical trials. Univariate and multivariate regression models were fitted. Results ACE2 levels were consistently reduced in SB CD and elevated in colonic UC compared with non-IBD controls. Elevated SB ACE2 was also associated with demographic features (age and elevated body mass index) associated with poor coronavirus disease 2019 outcomes. Within CD, SB ACE2 was reduced in patients subsequently developing complicated disease. Within UC, colonic ACE2 was elevated in active disease and in patients subsequently requiring anti–tumor necrosis factor rescue therapy. SB and colonic ACE2 expression in active CD and UC were restored by anti-cytokine therapy, most notably in responders. Conclusions Reduced SB but elevated colonic ACE2 levels in IBD are associated with inflammation and severe disease, but normalized after anti-cytokine therapy, suggesting compartmentalization of ACE2-related biology in SB and colonic inflammation. The restoration of ACE2 expression with anti-cytokine therapy might be important in the context of severe acute respiratory syndrome coronavirus 2 infection and potentially explain reports of reduced morbidity from coronavirus disease 2019 in IBD patients treated with anti-cytokines.

BACKGROUND Patients with inflammatory bowel disease-unclassified (IBDU) undergoing ileal pouch-anal anastomosis (IPAA) are at the risk of developing Crohn's disease (CD) after surgical procedure. In these patients, a clinically centered set of preoperative risk factors has not been prospectively defined. We report a single-center analysis of clinical factors associated with the development of CD after IPAA. METHODS Consecutive IBDU patients undergoing IPAA were identified. The diagnosis of IBDU was based on the presence of atypical disease distribution, presence of granulomas on endoscopic biopsy, and/or perianal disease. The diagnosis of CD after IPAA included the presence of afferent limb inflammation on pouchoscopy in the absence of nonsteroidal anti-inflammatory drug use and/or the development of pouch fistulizing disease more than 3 months after ileostomy closure. RESULTS Of the 149 study patients, 33 (22%) were diagnosed with CD after IPAA at a median of 37 months (interquartile range, 11-83 mo) after ileostomy closure. CD was diagnosed by mucosal inflammation above the pouch (n = 23; 70%), pouch fistulizing disease (n = 4; 12%), anorectal septic complications (n = 2; 6%), or the presence of ≥2 of the above complications (n = 4; 12%). The sole clinical predictor for the development of CD after IPAA was younger age at disease onset even after controlling for relevant clinical factors in a multivariate analysis. The odds of developing CD increased by 4% for each year that IBDU was diagnosed at a younger age. CONCLUSIONS Younger age at disease onset is the only clinical factor associated with the development of CD after IPAA for IBDU. Patients with IBDU undergoing IPAA with young age at disease onset should be counseled about the potentially higher risk of developing CD.

The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) is the only global organization devoted to the study of and management of the inflammatory bowel diseases (IBDs), namely, Crohn?s disease and ulcerative colitis. Membership is composed of physician-scientists who have established expertise in these diseases. The organization hosts an annual meeting and a number of working groups addressing issues of the epidemiology of IBD, diet and nutrition, and the development and use of treatments for IBD. There are currently 89 members of IOIBD representing 26 different countries. The organization has taken particular interest in the coronavirus disease-2019 (COVID-19) pandemic and how it may affect the IBD patient population. This document summarizes the results of 2 recent virtual meetings of the group and subsequent expert guidance for patients and providers.

Background Pyoderma gangrenosum (PG) is a severe extraintestinal manifestation of inflammatory bowel disease (IBD). Objective To better characterize PG features and management among an IBD cohort. Methods Subjects with PG were identified using a large database at a tertiary center. Patient demographics and clinical characteristics were summarized using descriptive statistics. Results Eighty patients with an episode(s) of PG were identified, yielding an overall prevalence of 1.9%. Overall, 93% of patients with PG had some degree of colonic inflammation. Thirty-one (39%) patients required hospitalization for PG. Underlying bowel disease was active at the time of PG episode(s) in 52 (65%) patients. The PG location was variable, with the lower extremity being the most common. Most patients (71.3%) required multiple therapies to achieve PG healing. Conclusions We describe one of the largest case series of PG among patients with IBD. The variety of treatment strategies used highlights the lack of clear guidelines in managing this complex group of patients.

Many Crohn’s disease (CD) patients develop intestinal strictures, which are difficult to prevent and treat. Cationic steroid antimicrobial 13 (CSA13) shares cationic nature and antimicrobial function with antimicrobial peptide cathelicidin. As many functions of cathelicidin are mediated through formyl peptide receptor-like 1 (FPRL1), we hypothesize that CSA13 mediates anti-fibrogenic effects via FPRL1. Human intestinal biopsies were used in clinical data analysis. Chronic trinitrobenzene sulfonic acid (TNBS) colitis-associated intestinal fibrosis mouse model with the administration of CSA13 was used. Colonic FPRL1 mRNA expression was positively correlated with the histology scores of inflammatory bowel disease patients. In CD patients, colonic FPRL1 mRNA was positively correlated with intestinal stricture. CSA13 administration ameliorated intestinal fibrosis without influencing intestinal microbiota. Inhibition of FPRL1, but not suppression of intestinal microbiota, reversed these protective effects of CSA13. Metabolomic analysis indicated increased fecal mevalonate levels in the TNBS-treated mice, which were reduced by the CSA13 administration. CSA13 inhibited colonic HMG-CoA reductase activity in an FPRL1-dependent manner. Mevalonate reversed the anti-fibrogenic effect of CSA13. The increased colonic FPRL1 expression is associated with severe mucosal disease activity and intestinal stricture. CSA13 inhibits intestinal fibrosis via FPRL1-dependent modulation of HMG-CoA reductase pathway.

Patients with inflammatory bowel disease (IBD), namely ulcerative colitis (UC) and Crohn's disease (CD), have worse outcomes with Clostridium difficile infection (CDI), including increased readmissions, colectomy, and death. Oral vancomycin is recommended for the treatment of severe CDI, while metronidazole is the standard of care for nonsevere infection. We aimed to assess treatment outcomes of CDI in IBD. We conducted a retrospective observational study of inpatients with CDI and IBD from January 2006 through December 2010. CDI severity was assessed using published criteria. Outcomes included readmission for CDI within 30 days and 12 weeks, length of stay, colectomy, and death. A total of 114 patients met inclusion criteria (UC, 62; CD, 52). Thirty-day readmissions were more common among UC than CD patients (24.2% versus 9.6%; P = 0.04). Same-admission colectomy occurred in 27.4% of UC patients and 0% of CD patients ( P < 0.01). Severe CDI was more common among UC than CD patients (32.2% versus 19.4%; P = 0.12) but not statistically significant. Two patients died from CDI-associated complications (UC, 1; CD, 1). Patients with UC and nonsevere CDI had fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen compared to those treated with metronidazole (30-day readmissions, 31.0% versus 0% [ P = 0.04]; length of stay, 13.62 days versus 6.38 days [ P = 0.02]). Patients with UC and nonsevere CDI have fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen relative to those treated with metronidazole alone. Patients with ulcerative colitis and CDI should be treated with vancomycin.

The significance of ulcers confined to the anastomotic line in Crohn’s disease patients remains unclear.