Postoperative Crohn's Disease Recurrence Risk and Optimal Biologic Timing After Temporary Diversion Following Ileocolic Resection.

BACKGROUND: Postoperative recurrence of Crohn's disease (CD) is common. While most patients undergo resection with undiverted anastomosis (UA), some individuals also have creation of an intended temporary diversion (ITD) with an ileostomy followed by ostomy takedown (OT) due to increased risk of anastomotic complications. We assessed the association of diversion with subsequent CD recurrence risk and the influence of biologic prophylaxis timing to prevent recurrence in this population. METHODS: This was a retrospective cohort study of CD patients who underwent ileocolic resection between 2009 and 2020 at a large quaternary health system. Patients were grouped by continuity status after index resection (primary anastomosis or ITD). The outcomes of the study were radiographic, endoscopic, and surgical recurrence as well as composite recurrence postoperatively (after OT in the ITD group). Propensity score-weighted matching was performed based on risk factors for diversion and recurrence. Multivariable regression and a Cox proportional hazards model adjusting for recurrence risk factors were used to assess association with outcomes. Subgroup analysis in the ITD group was performed to assess the impact of biologic timing relative to OT (no biologic, biologic before OT, after OT) on composite recurrence. RESULTS: A total of 793 CD patients were included (mean age 38 years, body mass index 23.7 kg/m2, 52% female, 23% active smoker, 50% penetrating disease). Primary anastomosis was performed in 67.5% (n = 535) and ITD in 32.5% (n = 258; 79% loop, 21% end) of patients. Diverted patients were more likely to have been males and to have had penetrating and perianal disease, prior biologic use, lower body mass index, and lower preoperative hemoglobin and albumin (all P < .01). After a median follow-up of 44 months, postoperative recurrence was identified in 83.3% patients (radiographic 40.4%, endoscopic 39.5%, surgical 13.3%). After propensity score matching and adjusting for recurrence risk factors, no significant differences were seen between continuity groups in radiographic (adjusted hazard ratio [aHR], 1.32; 95% confidence interval [CI], 0.91-1.91) or endoscopic recurrence (aHR, 1.196; 95% CI, 0.84-1.73), but an increased risk of surgical recurrence was noted in the ITD group (aHR, 1.61; 95% CI, 1.02-2.54). Most (56.1%) ITD patients started biologic prophylaxis after OT, 11.4% before OT, and 32.4% had no postoperative biologic prophylaxis. Biologic prophylaxis in ITD was associated with younger age (P < .001), perianal disease (P = .04), and prior biologic use (P < .001) but not in recurrence (P = .12). Despite higher rates of objective disease activity identified before OT, biologic exposure before OT was not associated with a significant reduction in composite post-OT recurrence compared with starting a biologic after OT (52% vs 70.7%; P = 0.09). CONCLUSIONS: Diversion of an ileocolic resection is not consistently associated with a risk of postoperative recurrence and should be performed when clinically appropriate. Patients requiring diversion at time of ileocolic resection are at high risk for recurrence, and biologic initiation prior to stoma reversal may be considered.

Diversion of an ileocolic resection is not consistently associated with a risk of postoperative recurrence and should be performed when clinically appropriate. Patients requiring diversion at time of ileocolic resection are high risk for recurrence, and biologic initiation prior to stoma reversal may be considered.

American Gastroenterological Association-Proposed Fecal Calprotectin Cutoff of 50 ug/g is Associated With Endoscopic Recurrence in a Real-World Cohort of Patients With Crohn's Disease Post-ileocolic Resection.

Background: Fecal calprotectin (FC) is a reliable predictor of active bowel inflammation in postoperative Crohn's disease (CD), but cutoffs vary between studies. Recent guidelines recommend a cutoff of <50 ug/g to avoid routine endoscopy in patients at low pretest probability for CD recurrence. We evaluated the performance of this threshold in a real-world CD cohort after ileocolic resection (ICR). Methods: In this retrospective study, patients with CD post-ICR between 2009 to 2020 with FC > 60 days but < 1 year of surgery were included from a multicenter database. Established risk factors and/or biologic prophylaxis (biologic within 90 days of surgery) defined pretest probability. Those without postoperative colonoscopy were excluded. Rates of endoscopic recurrence, defined as Rutgeerts score ≥ i2b at any time after surgery, were compared between FC < 50 versus  ≥ 50 ug/g. Student's t-test and Fisher's exact test were utilized for statistical analysis. All postoperative FCs were matched to closest colonoscopy within 1 year to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Thirty-seven patients categorized as either low-risk or high-risk and received biologic prophylaxis and had postoperative colonoscopy were included. Median time to first FC was 217 days (IQR 131-288). 15 (41%) patients had initial FC < 50 ug/g versus 22 (59%) ≥50 ug/g. Median time to first colonoscopy was 234 days (IQR 189-369). Compared to initial FC ≥ 50 ug/g, FC < 50ug/g experienced less endoscopic recurrence (0% vs. 36%, P = .005). Median time to first endoscopic recurrence in FC ≥ 50 ug/g was 145 days. There were 39 matched pairs of FC and colonoscopy. At an FC cutoff of 50 ug/g, calculated sensitivity was 90% and NPV was 93%, whereas specificity and PPV were 48% and 38%, respectively. Conclusions: In this real-world cohort, FC < 50 ug/g is a useful cutoff to exclude endoscopic recurrence in a post-ICR CD population that is at low pretest probability of recurrence.

Clinical Update on the Prevention and Management of Postoperative Crohn's Disease Recurrence.

PURPOSE OF REVIEW: Despite advances in therapeutics, a significant portion of patients with Crohn's disease still require surgical management. In this article, we present updates to the natural history, prognostication and postoperative monitoring, and novel therapeutics in the prevention and treatment of postoperative Crohn's disease recurrence. RECENT FINDINGS: Clinical risk factors have been associated with higher rates of postoperative recurrence (POR), and in recent studies demonstrate an increased cumulative risk with presence of additional risk factors. Additional novel clinical, histologic, and "-omic" risk factors for recurrence have recently been elucidated, including the role of the mesentery on recurrence and perioperative intraabdominal septic complications. High-risk patients benefit most from medical prophylaxis, including anti-TNF with or without immunomodulator therapy to prevent recurrence. New biologics such as vedolizumab and ustekinumab have emerging evidence in the use of prophylaxis, especially with recent REPREVIO trial data. Non-invasive disease monitoring, such as cross-sectional enterography, intestinal ultrasound, and fecal calprotectin, have been validated against ileocolonoscopy. Recent advances in the prediction, prevention, and monitoring algorithms of postoperative Crohn's disease may be leading to a reduction in postoperative recurrence. Ongoing trials will help determine optimal monitoring and management strategies for this at-risk population.

Real-World Surgical and Endoscopic Recurrence Based on Risk Profiles and Prophylaxis Utilization in Postoperative Crohn's Disease.

BACKGROUND & AIMS: Preoperative risk stratification may help guide prophylactic biologic utilization for the prevention of postoperative Crohn's disease (CD) recurrence; however, there are limited data exploring and validating proposed clinical risk factors. We aimed to explore the preoperative clinical risk profiles, quantify individual risk factors, and assess the impact of biologic prophylaxis on postoperative recurrence risk in a real-world cohort. METHODS: In this multicenter retrospective analysis, patients with CD who underwent ileocolonic resection (ICR) from 2009 to 2020 were identified. High-risk (active smoking, ≥2 prior surgeries, penetrating disease, and/or perianal disease) and low-risk (nonsmokers and age >50 y) features were used to stratify patients. We assessed the risk of endoscopic (Rutgeert score, ≥i2b) and surgical recurrence by risk strata and biologic prophylaxis (≤90 days postoperatively) with logistic and time-to-event analyses. RESULTS: A total of 1404 adult CD patients who underwent ICR were included. Of the high-risk factors, 2 or more ICRs (odds ratio [OR], 1.71; 95% CI, 1.13-2.57), active smoking (OR, 1.73; 95% CI, 1.17-2.53), penetrating disease (OR, 1.41; 95% CI, 1.02-1.94), and history of perianal disease alone (OR, 1.99; 95% CI, 1.42-2.79) were associated with surgical but not endoscopic recurrence. Surgical recurrence was lower in high-risk patients receiving prophylaxis vs not (10.2% vs 16.7%; P = .02), and endoscopic recurrence was lower in those receiving prophylaxis irrespective of risk strata (high-risk, 28.1% vs 37.4%; P = .03; and low-risk, 21.1% vs 38.3%; P = .002). CONCLUSIONS: Clinical risk factors accurately illustrate patients at risk for surgical recurrence, but have limited utility in predicting endoscopic recurrence. Biologic prophylaxis may be of benefit irrespective of risk stratification and future studies should assess this.

Change in Biologic Class Promotes Endoscopic Remission Following Endoscopic Postoperative Crohn's Disease Recurrence.

GOALS: Assess the outcomes of various therapeutic regimens to treat initial endoscopic postoperative recurrence despite biologic prophylaxis. BACKGROUND: Postoperative biologic prophylaxis reduces postoperative Crohn's disease (CD) recurrence rates. Optimal treatment strategies for endoscopic recurrence have not been elucidated. STUDY: Retrospective cohort study of adult CD patients who underwent ileocolonic resection between 2009 and 2020. Patients with endoscopic postoperative recurrence despite prophylactic biologic therapy and ≥1 subsequent colonoscopy were included. Treatment changes after recurrence were categorized as (1) therapy optimization or continuation or (2) new biologic class. The primary outcome was composite endoscopic or surgical recurrence at the time of or prior to subsequent follow-up colonoscopy. RESULTS: Eighty-one CD patients with endoscopic recurrence (54.3% i2b, 22.2% i3, and 23.5% i4) despite biologic prophylaxis (86.4% anti-tumor necrosis factor, 8.6% vedolizumab, 4.9% ustekinumab) were included. Most patients received therapy optimization or continuation (76.3%, n=61) following recurrence compared to being started on a new biologic class. Sixty patients (N=48 therapy optimization; N=12 new biologic class) experienced composite recurrence (78.3% endoscopic, 21.7% surgical). On multivariable modeling, initiation of a new biologic class was associated with reduced risk for composite recurrence compared to therapy optimization or continuation (aOR: 0.26; P=0.04). Additionally, initiation of a new biologic class was associated with endoscopic improvement when adjusting for endoscopic severity at the time of recurrence (aOR: 3.4; P=0.05). On sensitivity analysis, a new biologic class was associated or trended with improved rates of endoscopic healing and composite recurrence when directly compared to therapy optimization or continuation. CONCLUSION: In patients with CD who experience endoscopic recurrence despite biologic prophylaxis, changing the mechanism of biologic action may promote endoscopic improvement.

Prostate Cancer Progression Relies on the Mitotic Kinase Citron Kinase.

Prostate cancer remains the second leading cause of cancer death in men in Western cultures. A deeper understanding of the mechanisms by which prostate cancer cells divide to support tumor growth could help devise strategies to overcome treatment resistance and improve survival. Here, we identified that the mitotic AGC family protein kinase citron kinase (CIT) is a pivotal regulator of prostate cancer growth that mediates prostate cancer cell interphase progression. Increased CIT expression correlated with prostate cancer growth induction and aggressive prostate cancer progression, and CIT was overexpressed in prostate cancer compared with benign prostate tissue. CIT overexpression was controlled by an E2F2-Skp2-p27 signaling axis and conferred resistance to androgen-targeted treatment strategies. The effects of CIT relied entirely on its kinase activity. Conversely, CIT silencing inhibited the growth of cell lines and xenografts representing different stages of prostate cancer progression and treatment resistance but did not affect benign epithelial prostate cells or nonprostatic normal cells, indicating a potential therapeutic window for CIT inhibition. CIT kinase activity was identified as druggable and was potently inhibited by the multikinase inhibitor OTS-167, which decreased the proliferation of treatment-resistant prostate cancer cells and patient-derived organoids. Isolation of the in vivo CIT substrates identified proteins involved in diverse cellular functions ranging from proliferation to alternative splicing events that are enriched in treatment-resistant prostate cancer. These findings provide insights into the regulation of aggressive prostate cancer cell behavior by CIT and identify CIT as a functionally diverse and druggable driver of prostate cancer progression. SIGNIFICANCE: The poorly characterized protein kinase citron kinase is a therapeutic target in prostate cancer that drives tumor growth by regulating diverse substrates, which control several hallmarks of aggressive prostate cancer progression. See related commentary by Mishra et al., p. 4008.

Suboptimal Guideline Adherence and Biomarker Underutilization in Monitoring of Post-operative Crohn's Disease.

BACKGROUND: Crohn's disease recurrence after ileocecal resection is common. Guidelines suggest colonoscopy within 6-12 months of surgery to assess for post-operative recurrence, but use of adjunctive monitoring is not protocolized. We aimed to describe the state of monitoring in post-operative Crohn's. METHODS: We conducted a retrospective study of patients with Crohn's after ileocolic resection with ≥ 1-year follow-up. Patients were stratified into high and low risk based on guidelines. Post-operative biomarker (C-reactive protein, fecal calprotectin), cross-sectional imaging, and colonoscopy use were assessed. Biomarker, radiographic, and endoscopic post-operative recurrence were defined as elevated CRP/calprotectin, active inflammation on imaging, and Rutgeerts ≥ i2b, respectively. Data were stratified by surgery year to assess changes in practice patterns over time. P-values were calculated using Wilcoxon test and Fisher exact test. RESULTS: Of 901 patients, 53% were female and 78% high risk. Median follow-up time was 60 m for LR and 50 m for high risk. Postoperatively, 18% low and 38% high risk had CRPs, 5% low and 10% high risk had calprotectins, and half of low and high risk had cross-sectional imaging. 29% low and 38% high risk had colonoscopy by 1 year. Compared to pre-2015, time to first radiography (584 days vs. 398 days) and colonoscopy (421 days vs. 296 days) were significantly shorter for high-risk post-2015 (P < 0.001). Probability of colonoscopy within 1 year increased over time (0.48, 2011 vs. 0.92, 2019). CONCLUSION: Post-operative colonoscopy completion by 1 year is low. The use of CRP and imaging are common, whereas calprotectin is infrequently utilized. Practice patterns are shifting toward earlier monitoring.

Anastomotic Configuration and Temporary Diverting Ileostomy Do Not Increase Risk of Anastomotic Stricture in Postoperative Crohn's Disease.

INTRODUCTION: Surgical management of Crohn's disease (CD) is common. Postoperative complications include anastomotic stricturing (AS). The natural history and risk factors for AS have not been elucidated. METHODS: A retrospective cohort study of patients with CD who underwent ileocolonic resection (ICR) with ≥1 postoperative ileocolonoscopy between 2009 and 2020. Postoperative ileocolonoscopies with corresponding cross-sectional imaging were evaluated for evidence of AS without neoterminal ileal extension. Severity of AS and endoscopic intervention at time of detection were collected. Primary outcome was development of AS. Secondary outcome was time to AS detection. RESULTS: A total of 602 adult patients with CD underwent ICR with postoperative ileocolonoscopy. Of these, 426 had primary anastomosis, and 136 had temporary diversion at time of ICR. Anastomotic configuration consisted of 308 side-to-side, 148 end-to-side, and 136 end-to-end. One hundred ten (18.3%) patients developed AS with median time of 3.2 years to AS detection. AS severity at time of detection was associated with need for repeat surgical resection for AS. On multivariable Cox proportional hazard regression, anastomotic configuration and temporary diversion were not associated with risk of or time to AS. Preoperative stricturing disease was associated with decreased time to AS (adjusted hazard ratio 1.8; P = 0.049). Endoscopic ileal recurrence before AS was not associated with subsequent AS detection. DISCUSSION: AS is a relatively common postoperative CD complication. Patients with previous stricturing disease behavior are at increased risk of AS. Anastomotic configuration, temporary diversion, and ileal CD recurrence do not increase risk of AS. Early detection and intervention for AS may help prevent progression to repeat ICR.

The impact of the COVID-19 pandemic on Clostridioides difficile infection and utilization of fecal microbiota transplantation.

Previous research has demonstrated that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains cell entry through the angiotensin-converting enzyme 2 receptor, which is abundantly found throughout the gastrointestinal (GI) tract, resulting in a wide array of GI manifestations of coronavirus disease 2019 (COVID-19). By gaining entry into the intestinal epithelial and stromal cells, SARS-CoV-2 has been observed to cause intestinal inflammation and gut dysbiosis. Alterations in gut microbiota are known to be involved in the pathophysiology of Clostridioides difficile infection (CDI). During the initial stages of the COVID-19 pandemic, rates of CDI were similar to historical data despite the increased use of antibiotics. This may be due to increased emphasis on hygiene and protective equipment and reduced C. difficile testing as diarrhea was presumed to be COVID-19 related. Studies also demonstrated additional risk factors for CDI in COVID-19 patients, including length of hospitalization and new abdominal pain during admission. Although not associated with increased mortality, CDI was associated with increased length of hospital stay among patients admitted with COVID-19. Due to fecal viral shedding and concern of oral-fecal transmission of SARS-CoV-2, increased safety regulations were introduced to fecal microbiota transplantation (FMT) leading to reduced rates of this procedure during the COVID-19 pandemic. FMT for recurrent CDI during the COVID-19 pandemic remained highly effective without any reports of SARS-CoV-2 transmission. In addition, limited data show that FMT may be effective in treating COVID-19 and restoring healthy gut microbiota. The goal of this article is to review the impact that the COVID-19 pandemic has had on hospital-acquired CDI and the utilization of FMT.

Early Initiation of Antitumor Necrosis Factor Therapy Reduces Postoperative Recurrence of Crohn's Disease Following Ileocecal Resection.

BACKGROUND: Postoperative recurrence (POR) of Crohn's disease (CD) is common after surgical resection. We aimed to compare biologic type and timing for preventing POR in adult CD patients after ileocecal resection (ICR). METHODS: We performed a retrospective cohort study of CD patients who underwent an ICR at 2 medical centers. Recurrence was defined by endoscopy (≥ i2b Rutgeerts score) or radiography (active inflammation in neoterminal ileum) and stratified by type and timing of postoperative prophylactic biologic within 12 weeks following an ICR (none, tumor necrosis factor antagonists [anti-TNF], vedolizumab, and ustekinumab). RESULTS: We identified 1037 patients with CD who underwent an ICR. Of 278 (26%) who received postoperative prophylaxis, 80% were placed on an anti-TNF agent (n = 223) followed by ustekinumab (n = 28, 10%) and vedolizumab (n = 27, 10%). Prophylaxis was initiated in 35% within 4 weeks following an ICR and in 65% within 4 to 12 weeks. After adjusting for factors associated with POR, compared with no biologic prophylaxis, the initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR (adjusted hazard ratio, 0.61; 95% CI, 0.40-0.93). Prophylaxis after 4 weeks following an ICR or with vedolizumab or ustekinumab was not associated with a reduction in POR compared with those who did not receive prophylaxis. CONCLUSION: Early initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR. Vedolizumab or ustekinumab, at any time following surgery, was not associated with a reduction in POR, although sample size was limited.

Postoperative recurrence of Crohn's disease is common after ileocecal resection. In this dual-center study, early initiation of an anti-TNF agent within 4 weeks following an ileocecal resection was associated with a reduction in postoperative recurrence of Crohn's disease.

Intra-abdominal septic complications after ileocolic resection increases risk for endoscopic and surgical postoperative Crohn's disease recurrence.

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.

Mild neoterminal ileal post-operative recurrence of Crohn's disease conveys higher risk for severe endoscopic disease progression than isolated anastomotic lesions.

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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Test Characteristics of Cross-sectional Imaging and Concordance With Endoscopy in Postoperative Crohn's Disease.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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 P < .01). Radiographic disease severity was associated with increasing Rutgeerts' score (P < .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). CONCLUSIONS: 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.

The Epidemiology of Annular Pancreas in the United States: A Population-based Study.

BACKGROUND AND AIMS: Annular pancreas is a rare congenital condition where the second part of the duodenum is encircled by pancreatic tissue. There is a scarcity of data on its natural history therefore, we aimed to evaluate the epidemiology of annular pancreas and identify underlying associations using a large database. METHODS: A multi-institutional database (Explorys) was surveyed. A cohort of patients with a Systematized Nomenclature of Medicine-Clinical Terms diagnosis of "MRI, CT, EUS and/or ERCP" between April 2015 and April 2020 was identified. Subsequently a cohort of patients with history of "annular pancreas" was identified. RESULTS: There were a total of 40,075,980 individuals in the database with 6,162,600 (15.38%) who had an magnetic resonance imaging, computed tomography, endoscopic retrograde cholangiopancreatography, and/or endoscopic ultrasound. There were 210 (3.4/100,000) had a diagnosis of annular pancreas. When compared with the control group, patients with annular pancreas were more likely to have a history of alcohol use, smoking, acute pancreatitis, chronic pancreatitis, gastritis, duodenitis, jaundice, and gastrointestinal outlet obstruction. CONCLUSIONS: This is the largest study evaluating the epidemiology of annular pancreas. We found the estimated prevalence rate of annular pancreas to be 3.4/100,000 in those who had abdominal imaging. Annular pancreas was more likely to be diagnosed in patients with symptoms pertaining to acute or chronic pancreatitis, biliary, and gastric outlet obstruction.

Machine Learning Models to Predict Major Adverse Cardiovascular Events After Orthotopic Liver Transplantation: A Cohort Study.

OBJECTIVE: To develop machine learning models that can predict post-transplantation major adverse cardiovascular events (MACE), all-cause mortality, and cardiovascular mortality in patients undergoing liver transplantation (LT). DESIGN: Retrospective cohort study. SETTING: High-volume tertiary care center. PARTICIPANTS: The study comprised 1,459 consecutive patients undergoing LT between January 2008 and December 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: MACE, all-cause mortality, and cardiovascular mortality were modeled using logistic regression, least absolute shrinkage and selection surgery regression, random forests, support vector machine, and gradient-boosted modeling (GBM). All models were built by splitting data into training and testing cohorts, and performance was assessed using five-fold cross-validation based on the area under the receiver operating characteristic curve and Harrell's C statistic. A total of 1,459 patients were included in the final cohort; 1,425 (97.7%) underwent index transplantation, 963 (66.0%) were female, the median age at transplantation was 57 (11-70) years, and the median Model for End-Stage Liver Disease score was 20 (6-40). Across all outcomes, the GBM model XGBoost achieved the highest performance, with an area under the receiver operating curve of 0.71 (95% confidence interval [CI] 0.63-0.79) for MACE, a Harrell's C statistic of 0.64 (95% CI 0.57-0.73) for overall survival, and 0.72 (95% CI 0.59-0.85) for cardiovascular mortality over a mean follow-up of 4.4 years. Examination of Shapley values for the GBM model revealed that on the cohort-wide level, the top influential factors for postoperative MACE were age at transplantation, diabetes, serum creatinine, cirrhosis caused by nonalcoholic steatohepatitis, right ventricular systolic pressure, and left ventricular ejection fraction. CONCLUSION: Machine learning models developed using data from a tertiary care transplantation center achieved good discriminant function in predicting post-LT MACE, all-cause mortality, and cardiovascular mortality. These models can support clinicians in recipient selection and help screen individuals who may be at elevated risk for post-transplantation MACE.

Hypoalbuminaemia, Not Biologic Exposure, Is Associated with Postoperative Complications in Crohn's Disease Patients Undergoing Ileocolic Resection.

BACKGROUND: There are limited data on the postoperative outcomes in Crohn's disease patients exposed to preoperative ustekinumab or vedolizumab. We hypothesised that preoperative biologic use in Crohn's disease is not associated with postoperative complications after ileocolic resection. METHODS: Crohn's disease patients who underwent ileocolic resection over 2009-2019 were identified at a large regional health system. Preoperative biologic use within 12 weeks of surgery was categorised as no biologic, anti-tumour necrosis factor, vedolizumab, or ustekinumab. The primary endpoint was 90-day intra-abdominal septic complication. Risk factors included preoperative medical therapies, demographics, disease characteristics, laboratory values, and surgical approach. Regression models assessed the association of biologic use with intra-abdominal septic complication. RESULTS: A total of 815 Crohn's disease patients who underwent an ileocolic resection were included [62% no biologic, 31.4% anti-tumour necrosis factor, 3.9% vedolizumab, 2.6% ustekinumab]. Primary anastomosis was performed in 85.9% of patients [side-to-side 48.8%, end-to-side 26%, end-to-end 25%] in primarily a stapled [77.2%] manner. Minimally invasive approach was used in 41.4%. The 90-day postoperative intra-abdominal sepsis rate of 810 patients was 12%, abscess rate was 9.6%, and anastomotic leak rate was 3.2%. Multivariable regression modelling controlling for confounding variables demonstrated that preoperative biologic use with anti-tumour necrosis factor [p = 0.21], vedolizumab [p = 0.17], or ustekinumab [p = 0.52] was not significantly associated with intra-abdominal septic complication. Preoperative albumin < 3.5 g/dl was independently associated with intra-abdominal septic complication (odds ratio [OR] 1.76 [1.03, 3.01]). CONCLUSIONS: In Crohn's disease patients undergoing ileocolic resection, preoperative biologics are not associated with 90-day postoperative intra-abdominal septic complication. Preoperative biologic exposure should not delay necessary surgery.