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.

A global consensus on the definitions, diagnosis and management of fibrostenosing small bowel Crohn's disease in clinical practice.

Fibrostenosis of the small bowel is common in patients with Crohn's disease. No consensus recommendations on definition, diagnosis and management in clinical practice are currently available. In this Consensus Statement, we present a clinical practice RAND/UCLA appropriateness study on the definition, diagnosis and clinical management of fibrostenosing Crohn's disease. It was conducted by a panel of 28 global experts and one patient representative. Following a systematic literature review, 526 candidate items grouped into 136 questions were generated and subsequently evaluated for appropriateness. Strictures are best defined as wall thickening, luminal narrowing and prestenotic dilation. Cross-sectional imaging is required for accurate diagnosis of fibrostenosing Crohn's disease, and it is recommended before making treatment decisions. It should also assess the degree of inflammation in the bowel wall. Multiple options for medical anti-inflammatory, endoscopic and surgical therapies were suggested, including follow-up strategies following therapy. This Consensus Statement supports clinical practice through providing guidance on definitions, diagnosis and therapeutic management of patients with fibrostenosing small bowel Crohn's disease.

Comparative Effectiveness of Virtual Versus In-person Visits for Abdominal Pain During the COVID-19 Pandemic.

BACKGROUND AND AIMS: The COVID-19 pandemic has highlighted the importance of telemedicine in improving healthcare access and reducing costs. This study aimed to assess order compliance in the virtual versus in-person setting for the initial evaluation of abdominal pain (AP) prior to and during the pandemic. METHODS: A retrospective evaluation of virtual and in-person outpatient gastroenterology visits for AP were identified through natural language processing from January 2019 through September 2021 at the Cleveland Clinic main campus and regional hospitals in Ohio. We assessed the number and type of orders placed for patients and measured compliance through order completion. This study received Institutional Review Board approval (IRB 21-514). RESULTS: Among 20,356 patients at their initial visit, 79% had orders placed, of which 40% had pandemic in-person visits, 13% had pandemic virtual visits, and 47% had pre-pandemic in-person visits. Patients seen virtually were 65.1% less likely to complete orders compared to patients seen in-person (p < 0.001) during the pandemic. Patients seen in a pandemic virtual setting were 71.0% less likely to complete imaging orders (p < 0.001), 82.6% less likely to complete procedure orders (p < 0.001), and 60.5% less likely to complete lab orders (p < 0.001). CONCLUSION: Compared with in-person visits, patients seen virtually for their first presentation of AP were less likely to complete labs, imaging, and endoscopic evaluations. In-person visits were more successful with patient order completion during the pandemic. These findings highlight that virtual visits for AP, despite convenience, may compromise care delivery and warrant additional care coordination to achieve compliance with medical recommendations.

Preoperative Use of Multiple Advanced Therapies Is Not Associated With Endoscopic Inflammatory Pouch Diseases.

BACKGROUND: Patients with an ileal pouch-anal anastomosis (IPAA) can experience pouch inflammation postoperatively. The use of antitumor necrosis factor (anti-TNF) biologics may be associated with pouch inflammation, but limited data exist on the impact of multiple advanced therapies on development of subsequent pouch inflammation. The aim of this study was to assess for an association between preoperative use of multiple advanced therapies and risk of endoscopically detected inflammatory pouch diseases (EIPDs). METHODS: We performed a retrospective analysis of ulcerative colitis (UC) and indeterminate colitis (IBDU) patients who underwent an IPAA at a quaternary care center from January 2015 to December 2019. Patients were grouped based on number and type of preoperative drug exposures. The primary outcome was EIPD within 5 years of IPAA. RESULTS: Two hundred ninety-eight patients were included in this analysis. Most of these patients had UC (95.0%) and demonstrated pancolonic disease distribution (86.1%). The majority of patients were male (57.4%) and underwent surgery for medically refractory disease (79.2%). The overall median age at surgery was 38.6 years. Preoperatively, 68 patients were biologic/small molecule-naïve, 125 received anti-TNF agents only, and 105 received non-anti-TNF agents only or multiple classes. Ninety-one patients developed EIPD. There was no significant association between type (P = .38) or number (P = .58) of exposures and EIPD, but older individuals had a lower risk of EIPD (P = .001; hazard ratio, 0.972; 95% confidence interval, 0.956-0.989). CONCLUSION: Development of EIPD was not associated with number or type of preoperative advanced therapies.

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.

A comparison between patients with various etiologies of cirrhosis and examination of cardiac risk factors limiting survival to liver transplantation.

BACKGROUND & AIMS: Objectives of this retrospective cohort study were to assess differences in patient survival between etiologies of cirrhosis while on the waitlist for liver transplantation (LT), and to identify cardiac risk factors that predict survival failure while on the waitlist for LT. METHODS: This single-center retrospective cohort design included adult patients who were listed for LT at a tertiary academic hospital with a high-volume liver transplant center. RESULTS: Of the 653 patients listed for LT during the study period, 507 (77.6%) survived to transplant and 146 (22.4%) died or clinically deteriorated prior to transplant. Cumulative incidence of death or clinical deterioration did not differ statistically between patient groups (log rank p = .11). In multivariate analysis, compared to patients with NAFLD, there were no significant differences between patients with alcoholic cirrhosis (HR .95, 95%, CI, .62-1.45), cryptogenic cirrhosis (HR 1.31, 95%, CI, .77-2.23), or hepatitis C cirrhosis (HR 1.12, 95%, CI, .66-1.90). However, higher MELD scores (HR = 1.52, 95% CI, 1.12-1.19), severe coronary artery disease (HR = 2.09 95% CI, 1.23-3.55), and tricuspid regurgitation (HR = 2.62, 95% CI, 1.31-5.26) were independently associated with increased risk for survival failure to LT. CONCLUSIONS: The presence of severe coronary artery disease and tricuspid regurgitation at the time of listing for transplant are associated with survival failure while on the LT waitlist across etiologies of liver disease. Diagnostic assessment of coronary and valvular disease should be considered in all patients undergoing evaluation for LT, such as cardiac catheterization and/or stress echocardiogram.

Thromboelastography characteristics in critically ill patients with liver disease.

OBJECTIVE: The purpose of this study was to determine how thromboelastography (TEG) parameters differ by various clinical conditions that commonly occur in patients with cirrhosis, including sepsis, acute on chronic liver failure (ACLF), alcohol-associated hepatitis (AAH) and portal vein thrombosis (PVT). BACKGROUND: TEG, a whole blood assay, is used to assess several parameters of coagulation and is becoming increasingly used in clinical practice. STUDY: This study was a retrospective chart review of 155 patients admitted to the ICU with decompensated cirrhosis from 2017 to 2019. RESULTS: The R time was significantly shorter in patients when they were septic compared to when they were not and longer in patients with vs. without ACLF grade 3. Alpha angle and maximum amplitude was decreased in patients with severe AAH compared to those without severe AAH; and maximum amplitude was increased in patients with acute PVT compared to those with chronic PVT. R time was positively correlated with Chronic Liver Failure Consortium Organ Failure and Chronic Liver Failure Consortium ACLF scores (rho = 0.22, P = 0.020), while alpha angle and maximum amplitude were negatively correlated with MELD-NA. CONCLUSION: Findings suggest TEG parameters vary in several clinical conditions in patients with decompensated cirrhosis who are admitted to the ICU. Prospective research is needed to confirm our findings and to determine how this knowledge can be used to guide clinical practice, as well as blood product transfusions in the setting of bleeding or prior to invasive procedures.

Referral, Uptake, and Outcome of Genetic Counseling and Testing in Patients With Early-Onset Colorectal Cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. Pathogenic germline variants (PGVs) are detected in 16% to 20% of patients who have EOCRC, highlighting a need for genetic counseling (GC) and multigene panel testing in these patients. We aimed to determine the rate of referral to GC and uptake and outcomes of germline testing in patients with EOCRC. METHODS: We conducted a retrospective cohort study of patients aged <50 years diagnosed with colorectal cancer (CRC) from 2010 to 2019 at Cleveland Clinic. Demographic data were extracted, including age, sex, self-reported race, and family history of CRC. The proportions of patients with GC referral and completion of GC and genetic testing were investigated, and genetic testing results were analyzed. Multivariable logistic regression analysis was conducted to identify factors independently associated with GC referral and uptake. RESULTS: A total of 791 patients with EOCRC (57% male and 43% female) were included; 62% were referred for GC, and of those who were referred, 79% completed a GC appointment and 77% underwent genetic testing. Of those who underwent testing, 21% had a PGV detected; 82% were in known CRC-associated genes, with those associated with Lynch syndrome and familial adenomatous polyposis the most common, and 11% were in other actionable genes. Referral to GC was positively associated with family history of CRC (odds ratio [OR], 2.11; 95% CI, 1.51-2.96) and more recent year of diagnosis (2010-2013 vs 2017-2019; OR, 5.36; 95% CI, 3.59-8.01) but negatively associated with older age at diagnosis (OR, 0.89; 95% CI, 0.86-0.92). CONCLUSIONS: Referral to GC for patients with EOCRC is increasing over time; however, even in recent years, almost 25% of patients were not referred for GC. We found that 1 in 5 patients with EOCRC carry actionable PGVs, highlighting the need for health systems to implement care pathways to optimize GC referral and testing in all patients with EOCRC.

Incidence and risk factors for recurrence of ampullary adenomas after endoscopic papillectomy: Comparative analysis of familial adenomatous polyposis and sporadic ampullary adenomas in an international multicenter cohort.

OBJECTIVES: Endoscopic papillectomy (EP) is a minimally invasive therapy for the management of ampullary adenomas (AA). We conducted this multicenter study to assess the incidence of and factors related to the recurrence of AA after EP in patients with familial adenomatous polyposis (FAP) compared to sporadic AA. METHODS: We included patients who underwent EP for AA at 10 tertiary hospitals. Adenomatous tissue at the resection site at the time of surveillance endoscopies was considered recurrent disease. RESULTS: In all, 257 patients, 100 (38.9%) with FAP and 157 (61%) patients with sporadic AA, were included. Over a median of 31 (range, 11-61) months, recurrence occurred in 48/100 (48%) of patients with FAP and 58/157 (36.9%) with sporadic AA (P = 0.07). Two (2%) FAP patients and 10 (6.3%) patients with sporadic AA underwent surgery for recurrence. On multivariable regression analysis, the recurrence in FAP was higher than in sporadic patients after the first year of follow-up. AA size (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.001, 1.056), periampullary extension (HR 2.5, 95% CI 1.5, 4.01), and biliary duct dilation (HR 2.04, 95% CI 1.2, 3.4) increased the risk, while en bloc resection (HR 0.6, 95% CI 0.41, 0.9) decreased the risk of recurrence. CONCLUSION: Recurrence rates are high after EP. Most recurrences in sporadic patients occur within the first year of follow-up, but after the first year of follow-up in patients with FAP. Recurrences are higher with larger adenomas, biliary duct dilation, and periampullary extensions, and may be mitigated by en bloc resection. These factors should be considered in decision-making with the patients.

Defining the Roles of Inflammatory Bowel Disease Clinical Pharmacists in the United States: A Systematic Review and National RAND/UCLA Consensus.

BACKGROUND: Given the complexity of inflammatory bowel disease (IBD) care, utilization of multidisciplinary teams is recommended to optimize outcomes. There is a growing recognition that clinical pharmacists should be an integral part of this care model. We sought to define the roles of IBD clinical pharmacists in the United States. METHODS: A national multidisciplinary expert panel of 12 gastroenterologists and clinical pharmacists practicing in IBD clinics was assembled. We used the RAND/University of California, Los Angeles appropriateness method, with a total of 281 statements generated based on a systematic literature review and expert opinion. Each statement was anonymously rated as appropriate, uncertain, or inappropriate in 2 rounds of voting. RESULTS: The number of publications evaluating the clinical pharmacists' roles in IBD is limited, primarily focusing on thiopurine initiation and monitoring, medication adherence, and switching to biosimilars. Medication education; medication initiation and monitoring; therapeutic drug monitoring; biosimilar management; health maintenance review; and transitions of care were deemed by the panel to be appropriate roles for IBD clinical pharmacists. In considering real-world settings, IBD clinical pharmacists should practice clinically under a predefined scope and primarily focus on complex treatments (eg, immunomodulators, biologics, and small molecules). Clinical pharmacists should also be included in practice settings with IBD specialized physicians. Additionally, clinical pharmacists caring for patients with IBD should be residency trained and board certified. CONCLUSIONS: This consensus defines IBD clinical pharmacists' roles and provides a framework for embedded clinical pharmacists in IBD care.

Relationship between gluten availability and celiac disease prevalence: A geo-epidemiologic systematic review.

Celiac disease is a global disease requiring genetic susceptibility and gluten exposure to trigger immune-mediated enteropathy. The effect of the degree of gluten-containing grain availability on celiac disease prevalence is unknown. Our objective was to compare country-based gluten availability to celiac prevalence using a systematic literature review. We searched MEDLINE, Embase, Cochrane, and Scopus until May 2021. We included population-based serum screening with confirmatory testing (second serological study or small intestine biopsy) and excluded specific, high-risk, or referral populations. We determined country-specific gluten availability using the United Nations food balance for wheat, barley, and rye. Human leukocyte antigen (HLA) frequencies were obtained from allelefrequencies.net. The primary outcome was association between gluten-containing grain availability and celiac disease prevalence. Generalized linear mixed models method with Poisson's link was used for analysis. We identified 5641 articles and included 120 studies on 427 146 subjects from 41 countries. Celiac disease prevalence was 0-3.1%, median 0.75% (interquartile range 0.35, 1.22). Median wheat supply was 246 g/capita/day (interquartile range 214.8, 360.7). The risk ratio (RR) for wheat availability on celiac disease was 1.002 (95% confidence interval [CI]: 1.0001, 1.004, P = 0.036). A protective association was seen with barley, RR 0.973 (95% CI: 0.956, 0.99, P = 0.003), and rye, RR 0.989 (95% CI: 0.982, 0.997, P = 0.006). The RR for gross domestic product on celiac disease prevalence was 1.009 (95% CI: 1.005, 1.014, P < 0.001). The RR for HLA-DQ2 was 0.982 (95% CI: 0.979, 0.986, P < 0.001), and that for HLA-DQ8 was 0.957 (95% CI: 0.950, 0.964, P < 0.001). In this geo-epidemiologic study, gluten-containing grain availability showed mixed associations with celiac disease prevalence.

Frequency of endoscopic photodocumentation of large colorectal polyps.

BACKGROUND AND AIMS: Colonoscopy quality affects colorectal cancer (CRC) incidence and mortality. The U.S. Multi-Society Task Force on Colorectal Cancer strongly recommends photodocumentation (PD) of lesions ≥10 mm in size (ie, large polyps [LPs]) pre-resection and suggests PD postresection to enhance the quality of colonoscopy. No studies have assessed the frequency of LP PD. We evaluated the frequency of and factors associated with PD of LPs. METHODS: Reports from endoscopists performing ≥50 colonoscopies with LP resection between 2016 and 2021 were reviewed. The frequency of LP PD pre-resection and post-resection and factors associated with PD were collected. A composite score of 2 quality metrics (PD of completeness of examination and bowel preparation quality) was created. Endoscopists were divided into 2 tiers based on the frequency of the score on all included examinations: Tier 1, ≥95% of examinations; and Tier 2, <95% of examinations. Univariate and multivariate analyses were used to assess factors associated with PD. RESULTS: A total of 1322 colonoscopies, 1693 LPs, and 25 endoscopists were included in this study. PD of LPs occurred in 1392 (82%) pre-resection and in 878 (52%) post-resection. Factors associated with pre-resection PD include endoscopist subspecialty (colorectal surgery vs gastroenterology: odds ratio [OR], .12; 95% confidence interval [CI], .04-.42); >1 LP on examination (2 vs 1 LP: OR, .41 [95% CI, .27-.61]; and ≥3 vs 1 LP: OR, .41 [95% CI, .24-.70]), and longer withdrawal time (OR, 1.02; 95% CI, 1.01-1.04). CONCLUSIONS: We provide the first data on PD of LP pre-resection and post-resection, which can inform future benchmarking in this area. The implications of PD on metachronous advanced neoplasia need to be studied.

Increased Risk of Hospitalization in Celiac Disease With COVID-19 Infection Is Mitigated by Vaccination.

BACKGROUND: We sought to describe clinical characteristics of celiac disease (CD) patients infected with coronavirus disease 2019 (COVID-19) and estimate hospitalization risk, intensive care unit (ICU) requirement, mortality, and thrombosis, and the impact of vaccination on these outcomes. METHODS: We performed a single-center, retrospective cohort study comparing biopsy-proven CD patients with a matched sample of non-CD (referent) patients diagnosed with COVID-19 between March 2020 and January 2022. Matching ensured 2 referent patients for every 1 CD patient by age, sex, ethnicity, and COVID-19 diagnosis date. We also adjusted for general and celiac-specific comorbidity. The primary outcome was hospitalization. Secondary outcomes included ICU requirement, mortality, and thrombosis. We also compared these outcomes between vaccinated and unvaccinated individuals. RESULTS: We included 330 patients: 110 with CD (mean age 47 years, 83% female) and 220 matched referents. Hospitalization occurred in 27 CD patients (24%) and 25 referent patients (11%) (hazard ratio, 2.10; 95% confidence interval, 1.21-3.65; P = .009). Vaccination was associated with significantly decreased risk of hospitalization (hazard ratio, 0.53; 95% confidence interval, 0.31-0.93; P = .026). Four unvaccinated CD patients and 2 unvaccinated referent patients required ICU. No mortality occurred among CD patients, and 2 referent patients died. No thrombosis occurred in either group. CONCLUSIONS: CD patients with COVID-19 have a higher risk of hospitalization compared with non-CD referents. This risk is mitigated by vaccination in CD patients as it is in non-CD referents. ICU requirement occurred only in unvaccinated CD patients, and no CD patient died. Vaccination against COVID-19 should be strongly recommended in patients with CD as it is for non-CD patients in the general population.

Prevalence and risk factors of barrett's esophagus in lynch syndrome.

Lynch syndrome (LS), the most common hereditary cause of colorectal cancer, predisposes to upper gastrointestinal neoplasia. The prevalence of Barrett's esophagus (BE) is elevated in some hereditary gastrointestinal cancer syndromes but has not been systematically evaluated in LS. We assessed the prevalence of BE, BE-related dysplasia, esophageal adenocarcinoma (EAC), and factors associated with BE in LS. Asymptomatic patients with a germline pathogenic variant (PV) in the DNA mismatch repair (MMR) genes undergoing EGD for LS surveillance were identified from a hereditary colorectal cancer registry. We assessed the prevalence of BE and compared demographic, clinical, and endoscopic factors in LS patients with and without BE by logistic regression analysis. 323 patients were included. 21 patients (6.5%) were diagnosed with BE including 38% of females and 33% without gastroesophageal reflux disease (GERD). Dysplasia was diagnosed in two patients (9.5%) and EAC in one (4.8%) patient. Factors associated with BE included male gender (OR 3.00, 1.21-7.46), age at last LS EGD (OR 1.04, 1.01-1.08), presence of hiatal hernia (OR 20.09, 4.57-88.23), hiatal hernia > 3 cm (OR 11.25, 2.41-51.94), and GERD (OR 3.39, 1.32-8.67). No MMR PV was associated with BE. BE was diagnosed in 1 of 15 patients undergoing EGD surveillance for LS and nearly 10% had dysplasia including one EAC. Risk factors associated with BE in LS are similar to those established for BE in the general population. More studies are needed to evaluate if an association between BE and LS exists.

Validation of stricture length, duration and obstructive symptoms as predictors for intervention in ileal stricturing Crohn's disease.

BACKGROUND: Risk factors for intervention in terminal ileal (TI) stricturing Crohn's disease (CD) are poorly defined. Novel and rigorous definitions for TI strictures recently became available. OBJECTIVE: We aimed to describe the rates of symptoms or need for endoscopic balloon dilation (EBD) or surgery as well as risk factors of progression in a well-defined stricturing CD cohort. METHODS: Consecutive adult patients with non-penetrating stricturing TI CD, as defined by centrally-read magnetic resonance enterography CONSTRICT criteria, were separated into a derivation and validation cohort. Clinical and imaging characteristics were collected following prespecified scoring conventions. Primary outcome was a composite endpoint of EBD or surgery ("intervention"). Multivariable analysis was performed. RESULTS: Eighty-six patients (48.8% female, median age 36 years) met selection criteria, 17.4% had prior EBD, 59.3% previously received biologics and 58.1% of strictures were anastomotic. Median follow-up was 63.4 [95% CI: 57, 68.9] months. In the derivation cohort, at 12 and 48 months, 26% and 45% of patients had intervention, respectively. Multivariable analysis showed obstructive symptoms (Hazard ratio [HR] 1.444; 95% CI 1.126-1.852), stricture duration (HR 0.974; 95% CI, 0.954-0.995) and length (HR 1.039; 95% CI, 1.011-1.069) predicted intervention. The concordance index for split-sample validation was 0.74 and 0.67, respectively. Biologics were not associated with intervention. An online risk calculator was constructed. CONCLUSION: In patients with TI stricturing CD, 26% and 45% required intervention at 1 and 4 years. Obstructive symptoms, stricture duration and length were independent and validated predictors of the need for intervention. These findings are important for clinical practice and aid in the design of future trials for CD strictures.

Liver Transplant Outcomes in Patients With Postcapillary Pulmonary Hypertension.

Postcapillary pulmonary hypertension (PH) can be seen in cirrhosis. Research and treatment goals exist for patients with portopulmonary hypertension but not for postcapillary PH. The aim of this study was to investigate outcomes after liver transplant (LT) for patients with postcapillary PH. Methods: This was a retrospective cohort study of 1173 patients who underwent LT at our center between 2010 and 2020. Using a propensity score matched analysis followed by multivariable Cox modeling on matched patients, we compared post-LT survival between patients with and without postcapillary PH. We also compared several post-LT outcomes between patient with different types of PH. Results: Sixty-eight patients had PH, and 50 had postcapillary PH. The median age was 59 y and the sample was 54% male. There was no significant difference in mortality between patients with postcapillary PH and patients without PH (hazard ratio, 1.72; 95% confidence interval, 0.90-3.31; P = 0.10). There was no significant difference in survival between patients with any type of PH and those without PH. There was no significance difference in post-LT survival, acute kidney injury, or pulmonary edema between patients with different types of PH. Patients with postcapillary PH who survived had a higher cardiac output than those who died (11 L/min in patients who lived, as compared with 8 L/min in patients who died; P = 0.03). Conclusions: Postcapillary PH does not appear to convey a negative impact on post-LT survival. A higher cardiac output may be protective against mortality in patients with postcapillary PH.

Human intestinal myofibroblasts deposited collagen VI enhances adhesiveness for T cells - A novel mechanism for maintenance of intestinal inflammation.

OBJECTIVE: Inflammatory bowel diseases (IBD) cause chronic intestinal damage and extracellular matrix (ECM) remodeling. The ECM may play an active role in inflammation by modulating immune cell functions, including cell adhesion, but this hypothesis has not been tested in IBD. DESIGN: Primary human intestinal myofibroblast (HIMF)-derived ECM from IBD and controls, 3D decellularized colon or ECM molecule-coated scaffolds were tested for their adhesiveness for T cells. Matrisome was analysed via proteomics. Functional integrin blockade was used to investigate the underlying mechanism. Analysis of the pediatric Crohn's disease (CD) RISK inception cohort was used to explore an altered ECM gene expression as a potential predictor for a future complicated disease course. RESULTS: HIMF-derived ECM and 3D decellularized colonic ECM from IBD bound more T cells compared to control. Control HIMFs exposed to the pro-inflammatory cytokines Iinterleukin-1ß (IL-1ß) and tumor necrosis factor (TNF) increased, and to transforming growth factor-ß1 (TGF-ß1) decreased ECM adhesiveness to T cells. Matrisome analysis of the HIMF-derived ECM revealed collagen VI as a major culprit for differences in T cell adhesion. Collagen VI knockdown in HIMF reduced adhesion T cell as did the blockage of integrin αvß1. Elevated gene expression of collagen VI in biopsies of pediatric CD patients was linked to risk for future stricturing disease. CONCLUSION: HIMF-derived ECM in IBD binds a remarkably enhanced number of T cells, which is dependent on Collagen VI and integrin αvß1. Collagen VI expression is a risk factor for a future complicated CD course. Blocking immune cells retention may represent a novel approach to treatment in IBD.

Cardiac risk factors limiting survival to liver transplantation in patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) describes the hepatic manifestations of metabolic syndrome, which is estimated to affect 25% of adults, and currently represents the second most common indication for liver transplant in the United States. Studies have shown that patients with NAFLD are at an increased risk for heart failure, arrhythmia, and coronary artery disease (CAD), which may impact outcomes of liver transplantation. However, it remains unclear whether the presence of cardiac disease affects survival prior to liver transplant. If so, this would represent an important opportunity to optimize cardiac status and improve outcomes before liver transplant. AIM: To identify cardiac factors that impact survival to liver transplantation in patients with NAFLD and on the transplant waitlist. METHODS: The aim of this study was to identify cardiac risk factors that limit survival to transplant in patients with NAFLD. We performed a retrospective analysis of patients with NAFLD listed for liver transplant at a tertiary academic medical center in the United States from January 2015 to January 2021, identified through United Network of Organ Sharing registry. Exclusion criteria included a concurrent etiology of liver disease and removal from the transplant list due to chemical dependency, lack of social support, improvement in liver disease, or being lost to follow-up. We manually reviewed patient charts including electrocardiogram, echocardiogram, and cardiac catheterization reports as well as physician notes to identify cardiac disease states (i.e., heart failure, arrhythmia, valvular disease and CAD) and other related diagnoses. We performed a survival analysis by Cox proportional hazards regression model to analyze the association between cardiac factors at the time listed for transplant and death or clinical deterioration prior to transplant. RESULTS: Between January 2015 and January 2021, 265 patients with nonalcoholic fatty liver disease were listed for liver transplant at our institution. Our patient sample had a median age of 63 and an even distribution between sexes. The median Model for End-Stage Liver Disease (MELD) score was 17 and the median body mass index was 31.6. Of these 265 patients, 197 (74.3%) survived to transplant and 68 (25.7%) died or clinically deteriorated prior to transplant. The presence of mild or moderate CAD represented a hazard ratio of 2.013 (95%CI 1.078-3.759, P = 0.029) for death or clinical deterioration when compared to patients without CAD, after adjustment for age, sex, and MELD. MELD represented an adjusted hazard ratio of 1.188. CONCLUSION: Mild or moderate CAD represents a hazard for waitlist mortality prior to liver transplant in patients with NAFLD. Aggressive management of CAD may be needed to improve patient outcomes.

Disease progression in patients with PI*ZZ alpha-1 antitrypsin deficiency.

BACKGROUND AND OBJECTIVE: Alpha-1 antitrypsin deficiency (AATD) is an uncommon but underdiagnosed cause of cirrhosis and lacks medical treatment options. It is important to recognize risk factors that contribute to disease progression and liver transplantation. We aimed to assess if age, sex, or smoking status was associated with liver or lung disease progression. METHODS: Forty-three patients with ZZ-AATD cirrhosis were consecutively sampled from an Institutional Review Board-approved registry of 240 patients with AATD of any genotype seen as outpatients in the Cleveland Clinic between 1999 and 2019. To determine the association between risk factors and lung or liver disease progression, linear mixed-effects models with fixed effects for linear time, risk factor, and time-by-risk factor interaction, and the random intercepts for intra-patient correlation were used. RESULTS: Based on the mixed-effects model analysis, there was a significant association between liver disease progression and smoking history, and no association with age or sex. There was no association between lung disease progression and age, sex, or smoking history. However, smoking history was significantly associated with lower forced expiratory volume values. CONCLUSION: This study found that in a cohort of patients with PI*ZZ genotype AATD (ZZ-AATD) and cirrhosis, smoking history was associated with liver disease progression, whereas age and sex were not.

Comparison of pre-intestinal transplant and posttransplant sarcopenia and visceral adiposity measurements using computed tomography in the diagnosis of malnutrition during a nutrition-focused physical examination.

BACKGROUND: Registered dietitian nutritionists subjectively assess muscle loss as part of the nutrition-focused physical examination (NFPE), using guidelines to standardize malnutrition diagnosis. Computed tomography (CT) scans provide an objective measure of skeletal muscle mass and abdominal wall and visceral adipose tissue and can be used to determine skeletal muscle loss. METHODS: In this retrospective review, our team compared muscle measurements including the psoas, paraspinal muscles, and abdominal wall muscle area at the level of the third lumbar vertebral body (using CT)-as well as visceral and subcutaneous adipose tissue measurements-before and after gut transplant with the malnutrition diagnosis found on the NFPE. We also examined the association between CT measurements and postoperative infection, length of stay, and mortality. RESULTS: Forty-two patients were included in the study. Adipose tissue measurements on CT analysis were significantly lower in the malnutrition group compared with those without malnutrition (P ≤ 0.05) in both the pretransplant and posttransplant groups. Skeletal muscle size measurements were not significantly associated with malnutrition, but when adjusted for patients' height by calculating skeletal muscle index, an association between low skeletal muscle index scores and malnutrition diagnosis was found (P = 0.026). Pretransplant malnutrition diagnosis did not predict infection, length of stay, or mortality. CONCLUSION: Objective assessment of subcutaneous adipose tissue by CT analysis was significantly correlated with the subjective assessment of malnutrition by NFPE in both pretransplant and posttransplant patients. Skeletal muscle index scores were significantly lower in pretransplant patients who were diagnosed with malnutrition.