Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort Study.

BACKGROUND & AIMS: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.

Vedolizumab Therapy in Refractory Microscopic Colitis: A Single Center Case Series.

Microscopic colitis (MC) is a disease characterized by chronic watery diarrhea secondary to colonic inflammation. Endoscopically, the mucosa is usually normal but biopsies show characteristic histologic findings.1.

Alcohol Use after Liver Transplantation is Independent of Liver Disease Etiology.

AIM: To assess alcohol use after liver transplantation (LT) and compare liver transplant recipients for alcoholic liver disease (ALD) with recipients for non-ALD causes. METHODS: National Institute of Diabetes and Digestive and Kidney Diseases liver transplant database stratified to ALD and non-ALD causes. RESULTS: Among 488 LT recipients reporting pre-transplant alcohol use (147 ALD), proportion of LT recipients reporting alcohol use was similar comparing ALD and non-ALD transplants (25.4% vs. 27.2%; P = 0.56). Among ALD transplants, of 31 with alcohol use, 23 (74%) relapsed at ≥2 year, 25 (80%) reported intermittent drinking and 4 (13%) reported heavy drinking. Among Non-ALD recipients, alcohol use was equally distributed to within 2, 2-5 and after 5 years of LT with 82% reporting intermittent drinking and 9% heavy drinking. Patients with pre-transplant drinking of >20 years and abstinence duration of <2 years were over 2.5-fold likely to report post-transplant alcohol use compared to drinking of >20 years and abstinence of >2 years, 2.56 [95% CI: 1.41-4.67]. Etiology (ALD vs. non-ALD) did not predict post-transplant alcohol use. Of 139 ALD patients with follow-up biopsy data, 13 (7 with post-transplant alcohol use) had steatohepatitis. Histology on 319 non-ALD recipients showed recurrent disease in 91, none due to alcohol. Overall survival was similar between drinkers and abstainers (71% vs. 66%; P = 0.35). Recurrent ALD was cause of death in one ALD and none of non-ALD patients. CONCLUSION: Alcohol use after LT is independent of LT indication. Patients with non-ALD etiology should be carefully screened for alcohol use prior to LT to identify those at risk for post-LT alcohol use.

Successful de-implementation of an ineffective practice: The fall of docusate.

BACKGROUND: Reducing wasteful practices optimizes value in medicine. Docusate lacks treatment efficacy yet is widely prescribed. This quality improvement project aimed to de-implement docusate in place of a new evidence-based order set. METHODS: This is an ambidirectional study of inpatient laxative orders from 2018 to 2022 â€‹at one institution. We stratified docusate data by service/unit to target prospective deimplementation initiatives. A new evidence-based constipation order set was embedded in Cerner. RESULTS: There were 701,732 docusate orders across 75 services on 68 units. Top docusate ordering services were Trauma, Obstetrics and Hospitalist. Docusate administration rates were higher than for other laxatives. Our efforts reduced docusate orders by 44% over 4 months. PEG and senna orders increased by 58% and 35%. CONCLUSION: Docusate has no efficacy yet is widely prescribed. A structured de-implementation strategy can drive systematic change by leveraging technology and applying multidisciplinary improvement efforts. Our work removed docusate from the inpatient formulary.

Human intestinal stromal cells promote homeostasis in normal mucosa but inflammation in Crohn's disease in a retinoic acid-deficient manner.

Intestinal stromal cells (SCs), which synthesize the extracellular matrix that gives the mucosa its structure, are newly appreciated to play a role in mucosal inflammation. Here we show that human intestinal vimentin+CD90+SMA- SCs synthesize retinoic acid (RA) at levels equivalent to intestinal epithelial cells, a function in the human intestine previously attributed exclusively to epithelial cells. Crohn's disease SCs (Crohn's SCs), however, synthesized markedly less RA than SCs from healthy intestine (Normal SCs). We also show that microbe-stimulated Crohn's SCs, which are more inflammatory than stimulated Normal SCs, induced less RA-regulated differentiation of mucosal DCS (circulating pre-DCs and monocyte-derived DCs), leading to the generation of more potent inflammatory IFN-γhi/IL-17hi T cells than Normal SCs. Explaining these results, Crohn's SCs expressed more DHRS3, a retinaldehyde reductase that inhibits retinol conversion to retinal, and thus synthesized less RA than Normal SCs. These findings uncover a microbe-SC-DC crosstalk in which luminal microbes induce Crohn's disease SCs to initiate and perpetuate inflammation through impaired synthesis of RA.

Cholecystectomy does not worsen progression or outcomes in non-alcoholic fatty liver disease.

BACKGROUND: Cholecystectomy is a frequently performed surgical procedure for symptomatic cholelithiasis, which is reported to be more common in patients with non-alcoholic steatohepatitis (NASH), given the common risk factors. However, the data remains unclear on the association of cholecystectomy with NASH. We performed a retrospective study to examine the association of cholecystectomy and NASH. METHODS: Medical charts of patients with steatohepatitis related liver disease at a tertiary care center from 2004 to 2011 were stratified by cholecystectomy and defined by its history and/or absence of gallbladder on ultrasonography. Logistic regression model was built for predictors of cholecystectomy. Patients with NASH were stratified based on timing of cholecystectomy. The diagnosis of NASH and timing of cholecystectomy were compared based on baseline characteristics and outcomes (liver disease complications and survival) on follow up. Kaplan-Meier curves were generated for the two group comparisons. Chi-square and unpaired t-tests were used for comparing outcomes on follow up. P value <0.05 was considered significant. RESULTS: Analysis of 584 patients [379 non-alcoholic fatty liver disease (NAFLD)] showed that patients with cholecystectomy (N=191) were more likely to be female (57% vs. 44%), diabetic (53% vs. 37%), have liver biopsy (43% vs. 25%) and diagnosis of NAFLD (80% vs. 58%) P<0.001 for all. NAFLD diagnosis was associated with 2.79 folds odds of cholecystectomy. Among 379 (192 cholecystectomy) NAFLD patients, cirrhosis and female gender were associated with over 2 and 1.5 folds of cholecystectomy. Of 141 patients with data on timing of cholecystectomy, 55 (39%) with cholecystectomy at or after NAFLD diagnosis vs. 86 with cholecystectomy within median of 6 years prior to NAFLD diagnosis were similar on all characteristics except on model for end-stage liver disease (MELD) score (9.2±8.4 vs. 6.4±7.1, P=0.045). Of 28 with available histology data, there were no differences on histology based on timing of cholecystectomy. On a median follow up of 5 years, timing of cholecystectomy did not impact on development of cirrhosis (74% vs. 67%, P=0.45), ascites (31% vs. 38%, P=0.76), variceal bleeding (11% vs. 16%, P=0.44), hepatic encephalopathy (22% vs. 29%, P=0.74), hepatocellular carcinoma (HCC) (15% vs. 9%, P=0.59), and patient survival (95% vs. 98%, P=0.3). CONCLUSIONS: Cholecystectomy is associated with NAFLD diagnosis. We did not find cause and effect of cholecystectomy in the development of severity of NAFLD. Prospective studies are suggested to examine the role of cholecystectomy and bile acids in the pathogenesis of NAFLD.

Gastrointestinal Stromal Tumor: GIST Another Duodenal Ulcer.

Background: Gastrointestinal stromal tumors (GISTs), although exceedingly rare, are the most common mesenchymal tumors in the gastrointestinal (GI) tract. GISTs are often asymptomatic; approximately 10% are found incidentally on imaging or endoscopy for other indications, although GI bleeding, intestinal obstruction, and perforation can occur. We present a case of upper GI bleeding from a duodenal GIST. Proton-pump inhibitor (PPI) therapy resulted in complete endoscopic ulcer healing, yet a discrete mass lesion was identified on endoscopic ultrasound (EUS). Case Report: A 70-year-old female presented with upper GI bleeding, and a duodenal ulcer was identified with esophagogastroduodenoscopy (EGD). Computed tomography (CT) scan of the abdomen and pelvis showed duodenal bulb thickening without clear mass. The ulcer was treated with 1:10,000 concentration epinephrine, injected in 4 quadrants around the ulcer base. The patient's GI bleeding resolved, and she was discharged with a referral for outpatient EUS follow-up. One month later, EUS showed resolution of the ulcer after PPI therapy but also showed a lesion consistent with GIST that was confirmed by cytologic analysis. The patient was started on imatinib therapy and had no further bleeding. Conclusion: Initial EGD and CT findings could have easily been attributed to duodenal peptic ulcer disease for which follow-up endoscopy is not routinely recommended given the low risk of malignancy. However, because of the high index of suspicion on the part of the referring physicians, duodenal GIST was diagnosed. This case extends the spectrum of the presentation, evaluation, and diagnosis of GISTs and stresses the importance of keeping this rare disease on the provider's differential, even after routine workup shows no findings of tumor.

Model for End-Stage Liver Disease Score Predicts Development of First Episode of Spontaneous Bacterial Peritonitis in Patients With Cirrhosis.

OBJECTIVE: To examine whether baseline model for end-stage liver disease (MELD) score in patients with cirrhosis and ascites predicts the future development of first spontaneous bacterial peritonitis (SBP) episode. METHODS: A retrospective case-control study was performed at three academic centers to select patients admitted with first SBP episode (cases) and those with ascites admitted for decompensation without SBP (controls). Medical records from these centers were reviewed between January 1, 2008, and December 31, 2013. Cases and controls were matched (1:2) for age, sex, and race. Conditional logistic recession models were built to determine whether baseline MELD score (within a month before hospitalization) predicts first SBP episode. RESULTS: Of 697 patients (308, 230, and 159 from centers A, B, and C, respectively), cases and controls were matched in 94%, 89%, and 100% at three respective centers. In the pooled sample, probability of SBP was 11%, 31%, 71%, and 93% at baseline MELD scores less than or equal to 10, from 11 to 20, from 21 to 30, and greater than 30, respectively. Compared with MELD score less than or equal to 10, patients with MELD scores from 11 to 20, 21 to 30, and greater than 30 had six- (3- to 11-), 29- (12- to 69-), and 115- (22- to 598-) folds (95% CI) risk of SBP, respectively. Based on different MELD score cutoff points, MELD score greater than 17 was most accurate in predicting SBP occurrence. Analyzing 315 patients (152 cases) with available data on ascitic fluid protein level controlling for age, sex, and center, MELD score but not ascitic fluid protein associated with first SBP episode with respective odds ratios of 1.20 (1.14 to 1.26) and 0.88 (0.70 to 1.11). CONCLUSION: Baseline MELD score predicts first SBP episode in patients with cirrhosis and ascites.

Biomarkers of Renal Injury in Cirrhosis: Association with Acute Kidney Injury and Recovery after Liver Transplantation.

BACKGROUND: To define urine or serum biomarkers in predicting renal function recovery after liver transplantation (LT). METHODS: Adults listed for LT (February 2011-July 2014) and with modified diet for renal disease-6 (MDRD-6) <60 mL/min provided urine/blood samples at baseline and serially until LT for biomarkers in serum (pg/mL) and urine (pg/mg creatinine). RESULTS: Of 271 LT listed patients (mean age 57 years, 63% males, median listing MELD 17.5), 1 year acute kidney injury (AKI) probability was 49%, with odds of 1.3-, 3.0-, 4.6-, and 8.5-fold times for listing MELD 16-20, 21-25, 26-30, and >30, compared to MELD <16. Thirty-seven people died over 1 year from the time of listing, with twofold increased odds with AKI. Among 67 patients with MDRD <60, only urinary epidermal growth factor was different comparing AKI (increase in serum creatinine ≥0.3 mg/dL from baseline within past 3 months) vs. no AKI (2,254 vs. 4,253, p = 0.003). Differences between acute tubular necrosis (ATN) and hepatorenal syndrome could not be ascertained for a small sample of 3 patients with ATN. Analyzing 15 of 43 receiving LT and MDRD-6 <30 prior to LT, biomarkers were not different comparing 5 patients recovering renal function (MDRD-6 >50 mL/min) at 6 months vs. 10 without recovery. CONCLUSIONS: AKI is common among LT listed patients, with a negative impact on transplant-free survival. Serum and urine biomarkers are not associated with the recovery of renal function after LT. Multicenter studies are suggested to (a) develop strategies to reduce the development of AKI and (b) derive novel biomarkers for use in accurately predicting renal recovery after LT.

Severe Alcoholic Hepatitis: Atypical Presentation with Markedly Elevated Alkaline Phosphatase.

Alcoholic hepatitis (AH) is an acute inflammatory liver disease with poor prognosis. Infections in AH are difficult to detect and contribute to short-term mortality. Intrahepatic cholestasis and elevated alkaline phosphatase levels are also associated with worse outcomes. This report describes an uncommon presentation of severe AH.

Acute Kidney Injury in Patients with Cirrhosis.

Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK.

Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tube placement is recommended in amyotrophic lateral sclerosis (ALS) patients with dysphagia to provide reliable access for medications and nutrition. It is preferably done while forced vital capacity (FVC) is greater than 50% of predicted to reduce risk of postprocedural respiratory complications. Percutaneous radiologic gastrostomy has been shown to have higher success rates and lower complication rates compared with PEG. The authors sought to investigate the safety of PEG placement in ALS patients with varying respiratory compromise. METHODS: The records of 21 patients with ALS who underwent PEG tube placement from October 2010 to October 2013 were retrospectively reviewed to determine rates of successful placement, complication, mortality and survival. RESULTS: PEG was placed successfully in 95.2% of patients. There was 1 major complication, procedure-related death, and failed placement in a patient with FVC 15% predicted who developed procedure-related aspiration and hypoxic respiratory failure and death 8 days after failed PEG attempt. Minor complications included 3 patients with minor pain at insertion site, 1 patient with minor bleeding requiring cauterization and 2 patients requiring PEG tube replacement within 6 months of procedure for accidental dislodgement. After PEG placement, median survival was 327 days (95% confidence interval: 180-687). CONCLUSIONS: In conclusion, PEG tube placement in patients with ALS seems to be a safe procedure in patients without significant respiratory compromise. In patients with FVC <50%, based on literature review and the results of this study, the authors recommend percutaneous radiologic gastrostomy over PEG placement.