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Background Postoperative recurrence [POR] of Crohn’s disease following ileocolonic resection is common. The impact of immediate postoperative intra-abdominal septic complications [IASC] on endoscopic and surgical recurrence has not been elucidated. Aims To evaluate if IASC is associated with an increased risk for endoscopic and surgical POR. Methods This was a retrospective study of adult Crohn’s disease patients undergoing ileocolonic resection with primary anastomosis between 2009 and 2020. IASC was defined as anastomotic leak or intra-abdominal abscess within 90 days of the date of surgery. Multivariable logistic and Cox proportional hazard modelling were performed to assess the impact of IASC on endoscopic POR [modified Rutgeerts’ score ≥ i2b] at index postoperative ileocolonoscopy and long-term surgical recurrence. Results In 535 Crohn’s disease patients [median age 35 years, 22.1% active smokers, 35.7% one or more prior resection] had an ileocolonic resection with primary anastomosis. A minority of patients [N = 47; 8.8%] developed postoperative IASC. In total, 422 [78.9%] patients had one or more postoperative ileocolonoscopies, of whom 163 [38.6%] developed endoscopic POR. After adjusting for other risk factors for postoperative recurrence, postoperative IASC was associated with significantly greater odds (adjusted odds ratio [aOR]: 2.45 [1.23–4.97]; p = 0.01) and decreased time (adjusted hazards ratio [aHR]: 1.60 [1.04–2.45]; p = 0.03] to endoscopic POR. Furthermore, IASC was associated with increased risk (aOR: 2.3 [1.04–4.87] p = 0.03) and decreased survival-free time [aHR: 2.53 [1.31–4.87]; p = 0.006] for surgical recurrence. Conclusion IASC is associated with an increased risk for endoscopic and surgical POR of Crohn’s disease. Preoperative optimization to prevent IASC, in addition to postoperative biological prophylaxis, may help reduce the risk for endoscopic and surgical POR.

There are conflicting data assessing the impact of isolated post-operative anastomotic inflammation on future disease progression. The aim of this study was to determine the relative risk of severe disease progression in post-operative Crohn's disease (CD) patients with isolated anastomotic disease.Retrospective cohort study of adult CD patients undergoing ileocolonic resection between 2009 and 2020. Patients with a post-operative ileocolonoscopy ≤18 months from surgery and ≥1 subsequent ileocolonoscopy were included. Disease activity was assessed using the modified Rutgeerts' score (RS). Primary outcome was severe endoscopic progression, defined as i3 or i4 disease, on immediate subsequent ileocolonoscopy and during entire post-operative follow-up. Secondary outcome was surgical recurrence.One hundred and ninety-nine CD patients had an ileocolonoscopy ≤18 months from surgery, index RS of i0-i2b and ≥1 subsequent ileocolonoscopy. At index ileocolonoscopy, 34.7% had i0 disease, 16.1% i1, 24.6% i2a and 24.6% i2b. On multivariable logistic regression, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR 5.53; P 0.001) and i2a disease patients (aOR 2.63; P = 0.03). However, i2a disease did not confer increased risk compared to i0 or i1 disease (P = 0.09). Furthermore, i2b patients experienced severe endoscopic progression significantly earlier than i0 or i1 disease (aHR 4.68; P 0.001), whereas i2a disease did not differ from i0 or i1 disease (P = 0.25). Surgical recurrence was not associated with index RS i0-i2b (P = 0.86).Post-operative ileal disease recurrence, not isolated anastomotic inflammation, confers increased risk for severe endoscopic disease progression. Location of CD recurrence may impact optimal management strategies.

Pyoderma gangrenosum (PG) is a debilitating skin condition often accompanied by inflammatory bowel disease (IBD). Strikingly, ∼40% of patients that present with PG have underlying IBD, suggesting shared but unknown pathogenesis mechanisms. Impeding the development of effective treatments for PG is the absence of an animal model that exhibits features of both skin and gut manifestations. This study describes the development of the first experimental drug-induced mouse model of PG with concurrent intestinal inflammation. Topical application of pyrimidine synthesis inhibitors on wounded mouse skin generates skin ulcers enriched in neutrophil extracellular traps (NETs) and pro-inflammatory cellular as well as soluble mediators mimicking human PG. The mice also develop spontaneous intestinal inflammation demonstrated by histologic damage. Further investigations revealed increased circulating immature low-density IL-1β primed granulocytes that undergo enhanced NETosis at inflamed tissue sites supported by increase in circulatory citrullinated histone 3, a marker of aberrant NET formation. Granulocyte depletion dampens the intestinal inflammation in this model, further supporting the notion that granulocytes contribute to the skin-gut crosstalk in PG mice. We anticipate that this novel murine PG model will enable researchers to probe common disease mechanisms and identify more effective targets for treatment for PG patients with IBD.

Ileocolic resection for Crohn's disease traditionally does not include a high ligation of the ileocolic pedicle, and most commonly is performed with a stapled side-to-side ileocolic anastomosis. The mesentery has recently been implicated in the pathophysiology of Crohn's disease. Two techniques have been developed and are associated with reduced postoperative recurrence: the Kono-S anastomosis that excludes diseased mesentery and extended mesenteric excision that resects diseased mesentery. We aimed to assess the technical feasibility and safety of a novel combination of techniques: mesenteric excision and exclusion.This initial report is a single-center descriptive study of consecutive adults who underwent mesenteric excision and exclusion for primary or recurrent ileocolic Crohn's disease from September 2020 to June 2021. Medication exposure and endoscopic balloon dilation before surgery were recorded. Phenotype was classified using the Montreal Classification. Thirty-day outcomes were reported. A video of the mesenteric excision and exclusion including the Kono-S anastomosis is presented.Twenty-two patients with ileocolic Crohn's disease underwent mesenteric excision and exclusion: 100% had strictures, 59% had fistulas, 81% were on biologics, and 27% had previous ileocolic resection(s). Seventy-two percent underwent laparoscopic procedures, a mesenteric defect was closed in 86%, omental flaps were fashioned in 77%, and 3 patients were diverted. Median operative time was 175 minutes. Median postoperative stay was 4 days. At 30 days, there were 2 readmissions for reintervention: 1 seton placement and 1 percutaneous drainage of a sterile collection. There were no cases of intra-abdominal sepsis or anastomotic leak.Mesenteric excision and exclusion represents an innovative, progressive, and promising approach that appears to be highly feasible and safe. Further study is warranted to determine if mesenteric excision and exclusion is associated with reduced postoperative recurrence of ileocolic Crohn's disease.

Clinicians may be hesitant to prescribe biologics or immunomodulators to individuals with familial adenomatous polyposis (FAP) and comorbid inflammatory disease (CID) because of increased cancer risk. Our aim was to compare the risk of malignancy in FAP individuals with inflammatory bowel (IBD) and/or rheumatic disease that received biologics/immunomodulators to those who did not. Individuals with FAP and CID were included in the study. We compared the incidence of cancer between individuals exposed to biologics/immunomodulators compared to unexposed from the date of diagnosis of comorbid disease till last follow up or death. Hazard ratio (HR) for cancer was computed using Cox regression model and compared by exposure status to biologic/immunomodulators. 25 individuals with FAP and a comorbid inflammatory disease were identified including 9 (36%) with IBD and 16 (64%) with rheumatic disease. 14 (56%) were exposed to a biologic and or immunomodulator. Median duration of biologic/immunomodulator exposure was 48 (2-180) months. 3 (21.4%) in the exposed group compared to 1 (9.1%) in the unexposed group developed cancer with a HR for exposure of 1.92 (CI 0.2-18.5, p = 0.57). Median duration of follow up after the diagnosis of inflammatory disease was 10 (5.5-17.0) years in the exposed and 6 (3.0-15.0) years in the unexposed group. In the exposed group, 1 patient developed gastric and 2 developed colon cancer. One unexposed patient developed medullary thyroid cancer. There is a possible trend of more cancers in the group that received biologics/immunomodulators-but given the small number of patients and p-value, there may be no difference at all. This preliminary finding warrants study in a larger cohort.

Background Endoscopic postoperative recurrence (POR) of Crohn’s Disease (CD) following ileocolonic resection (ICR) is common; however, optimal treatment strategies of identified POR are unknown. We assessed the role of biologic therapy to treat endoscopic POR in a real-world cohort. Methods Retrospective cohort study of adult CD patients who underwent ICR from 2009–2020 at a tertiary center. Patients with endoscopic POR detected on postoperative colonoscopy and a subsequent follow-up colonoscopy were included. Patients were categorized by biologic therapy at time of POR and further sub-grouped by therapy modification after POR detection (no change, therapy optimization, or change in biologic class). Therapy optimization included: starting or modifying immunomodulator therapy, corticosteroids, or budesonide. POR was defined by Rutgeerts’ ≥ i2b. Results 203 CD patients (49.8% female, 15.4% > 1 prior ICR, 49.0% pre-operative biologic exposure) were included. Of these, 137 (67%) patients were not on biologic therapy at POR detection: 43% subsequently started a biologic, 23% optimized therapy, and 34% had no change. 66 (33%) patients were on anti-TNF at POR identification: 24% subsequently changed biologic class, 48% optimized anti-TNF, and 27% had no change (Figure 1). There was no difference in median time from ICR to POR detection (483 days, p=0.08) or inter-colonoscopy interval (483 days, p=0.25) between groups. In patients not on biologics at POR detection, those who started a biologic saw a 21% increase in subsequent endoscopic remission compared to those who optimized therapy (49.2% vs 28.1%, p=0.09) and a 12% increase compared to those who received no change (49.2% vs 37%). In patients not on biologics with severe POR (i3/i4, n=62), there was significantly higher remission rate by starting biologic therapy compared to optimizing existing therapy (53.3% vs 16.7%) or no change (53.3% vs 35.7%), p=0.04. In individuals receiving anti-TNF at time of POR, there was a 25% increase in endoscopic remission in patients who switched biologic class compared to those who optimized therapy (56.2% vs 31.2%) and a 34% increase compared to those with no change (56.2% vs 22.2%), p=0.1. Furthermore, significantly higher rates of improved Rutgeerts’ score were observed in switching biologic class compared to therapy optimization (68.8% vs 43.8%) or no change (68.8% vs 27.8%), p=0.04. Conclusion After endoscopic POR detection following ICR, initiating biologic therapy in individuals not previously receiving it, and changing mechanism of action in those already receiving anti-TNF, may improve clinical outcomes compared to alternative management strategies. If confirmed, these findings may inform optimal management strategies for endoscopic POR.

BACKGROUND: Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for treatment of small bowel fibrostenotic Crohn’s disease (CD). AIM: To perform a systematic review summarizing evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL, and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported. RESULTS: Eleven studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomized controlled trial (RCT) each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumor necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 27.6% (95% CI: 18.4%−39.3%) and 18.5% (95% CI: 8.3–36.2%), respectively over a median follow up of 23 months (range 5.5–105.8), and 21.8 months (range 5–47). Risk of repeat endoscopic balloon dilation (EBD) in those with intralesional therapy was 58.3% (95% CI: 36.6–77.3%) over a median follow up of 21.8 months (range 5–47). CONCLUSIONS: TNF antagonists are the preferred therapy for patients with stricturing small bowel CD. Data is lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery.

INTRODUCTION: The efficacy and safety profile of ustekinumab (UST) in Crohn’s disease (CD) is favorable, however, data in elderly patients is lacking. We aimed to assess the safety and efficacy of UST in elderly CD. METHODS: We performed a retrospective cohort study of CD patients classified as elderly (age≥65 years at UST initiation) or nonelderly (0.05 all). While nearly 90% patients in both groups experienced clinical response to UST, compared to nonelderly, elderly patients were less likely to achieve complete clinical remission (28.2% vs. 52.6%, p=0.01). On regression modeling, age was not associated with clinical outcomes (p>0.05 all). Mucosal healing was achieved in 26% elderly and 30% nonelderly patients (p=0.74). There were no significant differences in infusion reactions (2.6% vs. 6.4%, p=0.77), infection (5.2% vs. 7.7%, p=0.7) or post-surgical complications (p=0.99) by age category. CONCLUSION: UST is safe and effective in elderly CD. Although limited by sample size and retrospective design, such real-world data can inform biologic positioning in this IBD population.

Postoperative Crohn's disease (CD) surveillance relies on endoscopic monitoring. The role of cross-sectional imaging is less clear. We evaluated the concordance of cross-sectional enterography with endoscopic recurrence and the predictive ability of radiography for future CD postoperative recurrence.We performed a multi-institution retrospective cohort study of postoperative adult patients with CD who underwent ileocolonoscopy and cross-sectional enterography within 90 days of each other following ileocecal resection. Imaging studies were interpreted by blinded, expert CD radiologists. Patients were categorized by presence of endoscopic postoperative recurrence (E+) (modified Rutgeerts' score ≥i2b) or radiographic disease activity (R+) and grouped by concordance status.A total of 216 patients with CD with paired ileocolonoscopy and imaging were included. A majority (54.2%) exhibited concordance (34.7% E+/R+; 19.4% E-/R-) between studies. The plurality (41.7%; n = 90) were E-/R+ discordant. Imaging was highly sensitive (89.3%), with low specificity (31.8%), in detecting endoscopic postoperative recurrence. Intestinal wall thickening, luminal narrowing, mural hyper-enhancement, and length of disease on imaging were associated with endoscopic recurrence (all Plt; .01). Radiographic disease severity was associated with increasing Rutgeerts' score (Plt; .001). E-/R+ patients experienced more rapid subsequent endoscopic recurrence (hazard ratio, 4.16; P = .033) and increased rates of subsequent endoscopic (43.8% vs 22.7%) and surgical recurrence (20% vs 9.5%) than E-/R- patients (median follow-up, 4.5 years).Cross-sectional imaging is highly sensitive, but poorly specific, in detecting endoscopic disease activity and postoperative recurrence. Advanced radiographic disease correlates with endoscopic severity. Patients with radiographic activity in the absence of endoscopic recurrence may be at increased risk for future recurrence, and closer monitoring should be considered.

Mechanical and inflammatory complications of pelvic pouch surgery have been well described but there has been limited recognition of problems such as fecal incontinence, anal skin irritation and metabolic changes that may develop after surgery. Reported rates of daytime and nighttime fecal incontinence rates are 29% and 47% respectively. We discuss strategies for managing fecal incontinence and associated anal skin irritation that can develop. Metabolic consequences of pelvic pouch surgery are also increasingly being recognized. Patients with IPAA who are doing well with no evidence of pouch inflammation have low rates of nutrient deficiencies but should be monitored for vitamin B12, vitamin D and zinc deficiencies. In contrast, patients with IPAA who develop pouchitis, diarrhea, and/or rectal bleeding are more susceptible to nutrient deficiencies and should have a broader assessment of nutrient status. In additions, there appears to be an increased risk of bone loss among patients with IPAA and thus these patients should undergo appropriate risk screening and testing. Finally, patients with IPAA have physiologic changes that predispose to formation of calcium oxalate and uric acid renal stones.

Scientific research into the effects and mechanisms of acupuncture for gastrointestinal diseases including inflammatory bowel disease has been rapidly growing in the past several decades. In this review, we discuss the history, theory, and methodology of acupuncture and review potentially beneficial mechanisms of action of acupuncture for managing inflammatory bowel disease. Acupuncture has been shown to decrease disease activity and inflammation via increase of vagal activity in inflammatory bowel disease. Acupuncture has demonstrated beneficial roles in the regulation of gut dysbiosis, intestinal barrier function, visceral hypersensitivity, gut motor dysfunction, depression/anxiety, and pain, all of which are factors that can significantly impact quality of life in patients with inflammatory bowel disease. A number of clinical trials have been performed to investigate the therapeutic effects of acupuncture in ulcerative colitis and Crohn's disease. Although the data from these trials are promising, more studies are needed given the heterogeneous and multifactorial aspects of inflammatory bowel disease. There is also an important need to standardize acupuncture methodology, study designs, and outcome measurements.

The presentation of an upper gastrointestinal bleed secondary to an accessory splenic artery is a rare circumstance described only in 2 previous case reports. This report is the first to describe an upper gastrointestinal bleed consequent of a submucosal accessory splenic artery arising from the left phrenic artery, requiring multiple endoscopies and endovascular embolization. Vascular anatomic variants can pose a challenge to treatment, especially when they are unknown. This case adds to the limited number of case reports involving accessory splenic arteries.

Background Postoperative Crohn’s disease (CD) surveillance relies on endoscopic monitoring. The role of cross-sectional imaging in post-operative CD surveillance is less clear. We aimed to evaluate radiographic characteristics, endoscopic concordance, and the predictive ability of imaging for postoperative recurrence (POR). Methods Multi-institution retrospective cohort study of adult CD patients who underwent ileocolonic resection (ICR) between 2009–2020. Patients with a CT or MR enterography within 90 days of a postoperative surveillance colonoscopy were included. Imaging studies were interpreted by blinded expert CD radiologists. Endoscopic activity was assessed by Rutgeerts’ scoring (POR ≥ i2b). Patients were categorized by presence of endoscopic POR (E+ or E-) or radiographic disease activity (R+ or R-) and grouped by endoscopic and radiographic concordance. Results 201 CD patients (57.7% female, mean age 31 years, 81.2% stricturing CD, 17.9% >1 prior ICR, 22.5%) with paired colonoscopy and imaging were included. Median time from ICR to paired endoscopy was 23.2 months. Imaging was highly sensitive for detecting POR (84.2%), but poorly specific (32.8%). The plurality (41.8%, N=84) were discordant E-/R+, 32.8% concordant positive (E+/R+), 20.4% concordant negative (E-/R-), and 5% discordant E+/R-. In patients with endoscopic POR, imaging detected intestinal wall thickening (86.8%; p=0.004) and hyper-enhancement (84.2%; p=0.003) at higher rates and corresponded with endoscopic severity (Figure 1). Multiple correspondence analysis showed association between severe endoscopic (i3/i4) disease and advanced radiographic disease. The majority (58.3 %) of E+/R- patients (N=12) had a Rutgeerts’ score of i2b. Majority of E-/R+ (N=84) had minimal/mild radiographic disease (81%). Differences in characteristics between the E-/R+ and E+/R+ was most pronounced in length of disease >10 cm (26.1%, 45.3%). Subsequent colonoscopies were performed in 74 E-/R+ (i0=28, i1=12, i2a=34) and 35 E-/R- (i0=20, i1=9, i2a=6) patients with 18 E-/R+ (24.3%; i0=8, i1=3, i2a=7) and 4 E-/R- (11.4%; i0=1, i1=2, i2a=1) patients developing POR (p=0.09). However, survival analysis between E-/R+ and E-/R- showed no difference to time to subsequent POR (p=0.24) (Figure 2). Imaging features at time of paired negative endoscopy did not predict subsequent endoscopic POR. Conclusion Cross-sectional imaging is highly sensitive to detect endoscopic POR; advanced radiographic disease correlates with increased endoscopic severity. Patients with no endoscopic recurrence in the presence of radiographic activity may require increased surveillance, though larger study cohorts are needed. Imaging compliments, but should not supplant, endoscopic POR surveillance paradigms.

Background Hypertrophy of visceral adipose tissue (VAT) is a hallmark of Crohn disease (CD). The VAT produces a wide range of adipokines, biologically active factors that contribute to metabolic disorders in addition to CD pathogenesis. The study aim was to concomitantly evaluate serum adipokine profiles and VAT volumes as predictors of disease outcomes and treatment course in newly diagnosed pediatric patients with CD. Methods Pediatric patients ages 6 to 20 years were enrolled, and their clinical data and anthropometric measurements were obtained. Adipokine levels were measured at 0, 6, and 12 months after CD diagnosis and baseline in control patients (CP). The VAT volumes were measured by magnetic resonance imaging or computed tomography imaging within 3 months of diagnosis. Results One hundred four patients undergoing colonoscopy were prospectively enrolled: 36 diagnosed with CD and 68 CP. The serum adipokine resistin and plasminogen activator inhibitor (PAI)-1 levels were significantly higher in patients with CD at diagnosis than in CP. The VAT volume was similar between CD and CP. Baseline resistin levels at the time of diagnosis in patients with CD who were escalated to biologics was significantly higher than in those not treated using biologic therapy by 12 months (29.8 ng/mL vs 13.8 ng/mL; P = 0.004). A resistin level of ≥29.8 ng/mL at the time of diagnosis predicted escalation to biologic therapy in the first year after diagnosis with a specificity of 95% (sensitivity = 53%; area under the curve = 0.82; P = 0.015 for model with log-scale). There was a significantly greater reduction in resistin (P = 0.002) and PAI-1 (P = 0.010) at the 12-month follow-up in patients on biologics compared with patients who were not treated using biologics. Conclusions Serum resistin levels at diagnosis of pediatric CD predict the escalation to biologic therapy at 12 months, independent of VAT volumes. Resistin and PAI-1 levels significantly improved in patients with CD after treatment using biologics compared with those not on biologics. These results suggest the utility of resistin as a predictive biomarker in pediatric CD.

Background and Aims Crohn’s disease (CD) is a chronic illness that affects both the pediatric and adult populations with an increasing worldwide prevalence. We aim to identify a large, single-center cohort of patients with CD using natural language processing (NLP) in combination with codified data and extract surgical rates and medication usage from the electronic medical record (EMR). Methods Patients with CD were identified from the entire Cleveland Clinic EMR using ICD codes and CD-specific terms identified by NLP to fit a logistic regression model. Cohorts were developed for pediatric-onset (younger than 18 years) and adult-onset (18 years and older) CD. Surgeries were identified using current procedural terminology (CPT) codes and NLP. Crohn’s disease–related medications were extracted using physician orders in the EMR. Results Patients with pediatric-onset (n = 2060) and adult-onset (n = 4973) CD were identified from 2000 to 2017 with a positive predictive value of 98.5%. Rate of CD-related abdominal surgery over time was significantly higher in adult-onset compared with pediatric-onset CD (10-year surgery rate 49.9% vs 37.7%, respectively; P < 0.001). Treatment with biologics was significantly higher in pediatric vs adult-onset CD cohorts (63.6% vs 49.2%; P < 0.001). The overall rate of CD-related abdominal surgery was significantly higher in those who received Conclusion We used a combination of codified and NLP data to establish the largest, North American, single-center EMR cohort of pediatric- and adult-onset CD patients and determined that biologics are associated with lower rates of surgery over time, potentially altering the natural history of the disease.

Annals of the rheumatic diseases 76(5), 906-913 (2017). doi:10.1136/annrheumdis-2016-210324, Published by BMJ Publ. Group, London

Pyoderma gangrenosum (PG) is a debilitating skin condition characterized by deep, pus-filled, non-healing ulcers packed with neutrophils and is a common extraintestinal manifestation of inflammatory bowel disease (IBD). Strikingly, ~40% of people with an initial presentation of PG go on to be also diagnosed with IBD, suggesting that both diseases have common factors driving their pathogenesis. The molecular and cellular mechanisms of PG and IBD co-development are currently unknown, hampering the development of effective treatment strategies for individuals affected by both diseases. Prior studies of individuals with PG demonstrate an enrichment of circulating immature low-density neutrophils (LDGs) that are sensitized to undergo NETosis, a specialized form of cell death. NETosis induces inflammation and, when dysregulated, can promote chronic cycles of inflammation. We hypothesize that LDGs mediate NETosis-driven inflammation in both PG and IBD, but the LDGs from individuals that develop both diseases are functionally distinct. In this translational study, blood samples are collected from healthy subjects or individuals with only PG, only Crohn’s disease, only ulcerative colitis, or individuals with both PG and IBD for the analysis of neutrophil populations, neutrophil function, as well as circulating markers of inflammation and NETosis. Preliminary data from 45 subjects demonstrate an enrichment of circulatory LDGs (CD45+ CD15+ CD66b+ CD10+ CD16+ cells from the low density fraction) in individuals with inflammatory disease as compared to healthy subjects (19.2% +/- 2.81%, n=41 vs. 9.9% +/- 2.9%, n=4; p=0.04). This is correlated with increased NETosis in vitro, however differences in the responsiveness of LDGs to priming signals, such as IL-1β, TNFα, and IL-6, are emerging between disease sub-groups. There is considerable variation in the levels of LDGs within disease sub-groups and analyses are underway to determine whether this variation correlates with subject reported disease activity, inflammatory markers (serum C-reactive protein), or circulating markers of NETosis (serum citrullinated histone 3). These preliminary findings point to the presence of a unique population of cells potentially contributing to inflammatory cross-talk between the skin and gut. Further analysis of these potentially disease driving cells may result in more effective care of IBD patients with extraintestinal manifestations, such as PG, through more mechanistically targeted therapeutic approaches, as well as potential biomarker discovery that predicts which PG patients are more likely to develop IBD leading to earlier intervention and better disease outcomes.

Background The significance of serrated lesions in inflammatory bowel disease (IBD) remains unclear. We aim to characterize synchronous and metachronous lesions in IBD patients with an index serrated polyp and compare them to sporadic subjects with SSP. Methods Serrated lesions in patients with IBD were identified from a pathology database and, after review, were reclassified as hyperplastic (HP), sessile serrated (SSPs), or serrated polyps unclassifiable (SPU). Results One hundred thirty-four IBD patients were found to have 147 serrated polyps at index colonoscopy. SSPs were more likely to be located in the right colon: SSP (76.0%), SPU (41.7%) and HP (27.8%); P = 0.002. Synchronous multifocal visible dysplasia occurred more frequently in the SSP or SPU groups (44.5% and 66%) compared to the HP group (12%); P = 0.031. Among 13 IBD patients with index SSP followed over a median of 6 years, 61.5% developed metachronous visible dysplasia or additional SSPs. Larger index SSP size was associated with higher risk of developing subsequent visible dysplasia with a 10% increase for every 1 mm increase in size (HR = 1.1; P = 0.028), but was not associated with developing subsequent SSP (P = 0.50). The risk of subsequent SSP or visible dysplasia was no different between the IBD and non-IBD groups, but there was a trend suggesting SSP may be a marker of increased early risk of metachronous visible dysplasia in IBD patients. Conclusions IBD patients with an index SSP and SPU have a heightened risk of synchronous multifocal visible dysplasia. Additionally, IBD patients with SSP may be at risk of early metachronous visible dysplasia.

Background & Aims Most patients with Crohn's disease (CD) eventually require an intestinal resection. However, CD frequently recurs after resection. We performed a randomized trial to compare the ability of infliximab vs placebo to prevent CD recurrence. Methods We evaluated the efficacy of infliximab in preventing postoperative recurrence of CD in 297 patients at 104 sites worldwide from November 2010 through May 2012. All study patients had undergone ileocolonic resection within 45 days before randomization. Patients were randomly assigned (1:1) to groups given infliximab (5 mg/kg) or placebo every 8 weeks for 200 weeks. The primary end point was clinical recurrence, defined as a composite outcome consisting of a CD Activity Index score >200 and a ≥70-point increase from baseline, and endoscopic recurrence (Rutgeerts score ≥i2, determined by a central reader) or development of a new or re-draining fistula or abscess, before or at week 76. Endoscopic recurrence was a major secondary end point. Results A smaller proportion of patients in the infliximab group had a clinical recurrence before or at week 76 compared with the placebo group, but this difference was not statistically significant (12.9% vs 20.0%; absolute risk reduction [ARR] with infliximab, 7.1%; 95% confidence interval: -1.3% to 15.5%; P =.097). A significantly smaller proportion of patients in the infliximab group had endoscopic recurrence compared with the placebo group (30.6% vs 60.0%; ARR with infliximab, 29.4%; 95% confidence interval: 18.6% to 40.2%; P

Crohn’s Disease is a relapsing and remitting disease involving chronic intestinal inflammation that is often characterized by hypertrophy of visceral adipose tissue (VAT). While an increased ratio of VAT to subcutaneous fat (SQF) has previously been identified as a predictor of worse outcomes in Crohn’s Disease, bowel-proximal fat regions have also been hypothesized to play a role in inflammatory response. However, there has been no detailed study of VAT and SQF regions on MRI to determine their potential utility in assessing Crohn’s Disease severity or guiding therapy. In this paper we present a fully-automated algorithm to segment and quantitatively characterize VAT and SQF via routinely acquired diagnostic bowel MRIs. Our automated segmentation scheme for VAT and SQF regions involved a combination of morphological processing and connected component analysis, and demonstrated DICE overlap scores of 0.86±0.05 and 0.91±0.04 respectively, when compared against expert annotations. Additionally, VAT regions proximal to the bowel wall (on diagnostic bowel MRIs) demonstrated a statistically significantly, higher expression of four unique radiomic features in pediatric patients with moderately active Crohn’s Disease. These features were also able to accurately cluster patients who required aggressive biologic therapy within a year of diagnosis from those who did not, with 87.5% accuracy. Our findings indicate that quantitative radiomic characterization of visceral fat regions on bowel MRIs may be highly relevant for guiding therapeutic interventions in Crohn’s Disease.