American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the management of chronic pancreatitis: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for the role of endoscopy in the management of chronic pancreatitis (CP). This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline addresses effectiveness of endoscopic therapies for the management of pain in CP, including celiac plexus block, endoscopic management of pancreatic duct (PD) stones and strictures, and adverse events such as benign biliary strictures (BBSs) and pseudocysts. In patients with painful CP and an obstructed PD, the ASGE suggests surgical evaluation in patients without contraindication to surgery before initiation of endoscopic management. In patients who have contraindications to surgery or who prefer a less-invasive approach, the ASGE suggests an endoscopic approach as the initial treatment over surgery, if complete ductal clearance is likely. When a decision is made to proceed with a celiac plexus block, the ASGE suggests an EUS-guided approach over a percutaneous approach. The ASGE suggests indications for when to consider ERCP alone or with pancreatoscopy and extracorporeal shock wave lithotripsy alone or followed by ERCP for treating obstructing PD stones based on size, location, and radiopacity. For the initial management of PD strictures, the ASGE suggests using a single plastic stent of the largest caliber that is feasible. For symptomatic BBSs caused by CP, the ASGE suggests the use of covered metal stents over multiple plastic stents. For symptomatic pseudocysts, the ASGE suggests endoscopic therapy over surgery. This document clearly outlines the process, analyses, and decision processes used to reach the final recommendations and represents the official ASGE recommendations on the above topics.

American Society for Gastrointestinal Endoscopy guideline on the role of therapeutic EUS in the management of biliary tract disorders: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach for the role of therapeutic EUS in the management of biliary tract disorders. This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation framework and addresses the following: 1: The role of EUS-guided biliary drainage (EUS-BD) versus percutaneous transhepatic biliary drainage (PTBD) in resolving biliary obstruction in patients after failed ERCP. 2: The role of EUS-guided hepaticogastrostomy versus EUS-guided choledochoduodenostomy in resolving distal malignant biliary obstruction after failed ERCP. 3: The role of EUS-directed transgastric ERCP (EDGE) versus laparoscopic-assisted ERCP and enteroscopy-assisted ERCP (E-ERCP) in resolving biliary obstruction in patients with Roux-en-Y gastric bypass (RYGB) anatomy. 4: The role of EUS-BD versus E-ERCP and PTBD in resolving biliary obstruction in patients with surgically altered anatomy other than RYGB. 5: The role of EUS-guided gallbladder drainage (EUS-GBD) versus percutaneous gallbladder drainage and endoscopic transpapillary transcystic gallbladder drainage in resolving acute cholecystitis in patients who are not candidates for cholecystectomy.

The assessment of sarcopenia using psoas muscle thickness per height is not predictive of post-operative complications in IBD.

BACKGROUND: Sarcopenia is associated with postoperative complications in inflammatory bowel disease. It has most commonly been defined using the skeletal muscle index, computed after analysis of cross-sectional muscle area at L3. Psoas muscle thickness normalized to height (PMTH), which is easier to derive, is a potential surrogate of SMI and sarcopenia in patients with cirrhosis and chronic pancreatitis. We investigate whether sarcopenia defined by PMTH has utility in predicting post-operative outcomes in patients with inflammatory bowel disease. METHODS: We performed a retrospective study of adults undergoing IBD-related surgery from 2009 to 2019 at two hospitals. Sarcopenia was defined by sex-specific PMTH at the umbilicus on cross-sectional imaging using a 50th percentile median cutoff. Predictive models were created using variables (BMI, age, sex, smoking status, albumin, INR, platelets, hemoglobin, hypertension, diabetes, CAD, medications) that may be associated with complications (mortality, reoperation, readmission, transfusions, ICU admission, infection, DVT/PE), and sarcopenia for comparison. RESULTS: 85 patients with IBD were included. Lower albumin level (OR = 0.52, p = 0.039) and biologic use (OR = 5.92, p = 0.006) were associated with postoperative complications. There was no significant difference using PMTH compared to a model incorporating hypoalbuminemia and biologic use in predicting complications. Sarcopenia on univariate analysis was associated with a lower 30 day rate of reoperation (p = 0.04). CONCLUSIONS: A low status of PMTH was not associated with increased postoperative complications, however hypoalbuminemia and biologic use were. PMTH as a surrogate for sarcopenia requires further study, ideally with prospective studies comparing PMTH with accepted radiographic surrogates for sarcopenia, to determine its role in clinical decision making.

Systematic review and meta-analysis: real-world data rates of deep remission with anti-TNFα in inflammatory bowel disease.

BACKGROUND: Deep remission (DR) is a treatment target in IBD associated with reduced hospitalization and improved outcome. Randomized control trial (RCT) data demonstrates efficacy of anti-TNFα agents in achieving DR; however, real-world data (RWD) can provide information complementary to RCTs, specifically regarding treatment duration. In this systematic review with meta-analysis, we use real-world data (RWD) to determine rates of DR in IBD treated with anti-TNFα. METHODS: We completed a systematic search of MEDLINE and EMBASE on July 8, 2019 with review of major gastrointestinal conference abstracts from 2012 to 2019. Studies utilizing RWD (data not from phase I-III RCTs) of adult IBD patients treated with anti-TNFα agents were included. DR was defined by clinical and endoscopic remission at minimum. DR was assessed at 8 weeks, 6 months, 1 year, and 2 years. Risk of bias was assessed with the Newcastle Ottawa Scale. RESULTS: 29,033 publications were identified. Fifteen publications, nine manuscripts and six conference abstracts, were included encompassing 1212 patients (769 Crohn's disease-CD, 443 ulcerative colitis-UC), and analyzed using Comprehensive Meta-Analysis. Rate of DR was 36.4% (95% CI 12.6-69.4%) at 8 weeks, 39.1% (95% CI 10.4-78%) at 6 months, 44.4% (95% CI 34.6-54.6%) at 1 year, and 36% (95% CI 18.7-58%) at 2 years. DR in CD at 1 year was 48.6% (95% CI 32.8-64.7%) and in UC was 43.6% (95% CI 32.8-55.1%). CONCLUSIONS: The rate of DR was highest after 1 year of therapy, in nearly 45% of IBD patients treated with anti-TNFα. Similar rates were achieved between patients with UC and CD. The findings highlight the efficacy of anti-TNFα in real-world setting. Future studies using RWD can determine efficacy of newer IBD therapeutics in routine clinical practice.

Relapse From Deep Remission After Therapeutic De-escalation in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: We conducted a systematic review and meta-analysis evaluating the relapse rate after therapeutic de-escalation in inflammatory bowel disease [IBD] patients who achieved deep remission [DR]. METHODS: We searched MEDLINE, EMBASE, and major gastroenterology conferences up to July 2019 for studies reporting relapse in adult patients with DR who subsequently underwent therapeutic de-escalation. Eligible studies defined DR as at least a combination of clinical remission and mucosal healing/endoscopic remission. The primary outcome was cumulative 1-year and 2-year relapse rates after therapeutic de-escalation. Secondary outcomes were relapse rates in ulcerative colitis [UC] and Crohn's disease [CD], relapse after anti-tumour necrosis factor-α [anti-TNFα] de-escalation, and the rate of disease response recapture following re-escalation. RESULTS: Thirteen studies encompassing 837 patients were identified. The cumulative relapse rate after therapeutic de-escalation was 28.7% within 1 year [12 studies], and 38.4% within 2 years [eight studies]. Relapse rates within 1 year and 2 years were comparable between UC [five studies; 25.4% and 37.4%] and CD [seven studies; 34.1% and 39.9%]. Ten studies reported de-escalation of anti-TNFα, of which 29.8% patients relapsed within 1 year and 41.4% within 2 years. Response recapture following re-escalation [eight studies] was 75.4%. CONCLUSIONS: Despite achieving deep remission, therapeutic de-escalation in this patient population is associated with significant relapse risk within 1 year and 2 years. This risk is more pronounced in patients requiring anti-TNFα for management, likely because of more severe disease. Similar rates of relapse were reported among UC and CD within these time periods. These findings suggest that combined clinical and endoscopic remission should not be an impetus to consider therapeutic de-escalation.

The IBD-associated long noncoding RNA IFNG-AS1 regulates the balance between inflammatory and anti-inflammatory cytokine production after T-cell stimulation.

The inflammatory bowel diseases (IBD) are a complex set of chronic gastrointestinal inflammatory conditions arising from the interplay of genetic and environmental factors. This study focuses on noncoding RNA transcripts as potential mediators of IBD pathophysiology. One particular gene, interferon γ-antisense 1 (IFNG-AS1), has been consistently observed to be elevated in the intestinal mucosa of patients with actively inflamed IBD versus healthy controls. This study builds on these observations, demonstrating that the second splice variant is specifically altered, and this alteration even stratifies within inflamed patients. With the use of a CRISPR-based overexpression system, IFNG-AS1 was selectively overexpressed directly from its genomic loci in T cells. An unbiased mRNA array on these cells identified a large increase in many inflammatory cytokines and a decrease in anti-inflammatory cytokines after IFNG-AS1 overexpression. Media from T cells overexpressing IFNG-AS1 elicited an inflammatory signaling cascade in primary human peripheral blood mononuclear cells, suggesting the potential functional importance of IFNG-AS1 in IBD pathophysiology. The significance of these results is amplified by studies suggesting that a single-nucleotide polymorphism in IFNG-AS1, rs7134599, was associated with both subtypes of patients with IBD independently of race.NEW & NOTEWORTHY Long noncoding RNAs are an emerging field of inflammatory bowel disease (IBD) research. This study mechanistically analyzes the role of a commonly upregulated gene in IBD and shows IFNG-AS1 as a mediator of an inflammatory signaling cascade.

Identification of functional missense single-nucleotide polymorphisms in TNFAIP3 in a predominantly Hispanic population.

Background: Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) is a multifunctional ubiquitin binding and editing enzyme that regulates inflammation. Genetic studies have implicated polymorphisms within the TNFAIP3 locus to the development of numerous immune-related diseases. This study evaluated the frequencies of single nucleotide polymorphism (SNPs) within the exonic regions of the TNFAIP3 gene and an associated point mutation from the Illumina array among a predominantly Hispanic cohort. Methods: Genomic DNA was obtained from 721 participants and sequencing of all TNFAIP3 exons and an intergenic point mutation (rs6920220) was performed. In vitro functional assessment was performed by transfecting mutated TNFAIP3 constructs into TNFAIP3 knockout cells containing the NF-kB luciferase reporter and stimulating with TNFα. Comparative statistics were performed with Student's t-test for continuous variables and Chi-squared test for categorical variables. Results: Sequencing revealed two missense SNPs, rs146534657:A>G and rs2230926:T>G, both within exon 3 of TNFAIP3, which encodes the protein's deubiquitinating enzymatic domain. Frequencies of all three point mutations differed significantly across racial groups (χ2-test, P=0.014 to P<0.001). Compared to Caucasians, rs146534657:A>G was overrepresented among Hispanics (odds ratio (OR) [95% CI] 4.05 [1.24-13.18]), and rs2230926:T>G was more prevalent among African Americans (OR [95% CI] 3.65 [1.58-8.43]). In vitro assays confirm rs146534657:A>G and rs2230926:T>G decrease the ability of TNFAIP3 to abrogate NF-κB activation by 2-fold (P<0.01) and 1.7-fold (P<0.01), respectively. Conclusions: This study reports the frequency of rs146534657:A>G among Hispanics and is the first to evaluate its potential physiologic impact, establishing a basis for future research as a potential biomarker among this population.

Effects of end-stage renal disease and dialysis modalities on blood ammonia level.

INTRODUCTION: Uremia results in a characteristic breath odor (uremic fetor) which is largely due to its high ammonia content. Earlier studies have shown a strong correlation between breath ammonia and blood urea levels and a 10-fold reduction in breath ammonia after hemodialysis in patients with chronic kidney disease. Potential sources of breath ammonia include: (i) local ammonia production from hydrolysis of urea in the oropharyngeal and respiratory tracts by bacterial flora, and (ii) release of circulating blood ammonia by the lungs. While the effects of uremia and hemodialysis on breath ammonia are well known their effects on blood ammonia are unknown and were explored here. METHODS: Blood samples were obtained from 23 hemodialysis patients (immediately before and after dialysis), 14 peritoneal dialysis patients, and 10 healthy controls. Blood levels of ammonia, creatinine, urea, and electrolytes were measured. FINDINGS: No significant difference was found in baseline blood ammonia between hemodialysis, peritoneal dialysis and control groups. Hemodialysis procedure led to a significant reduction in urea concentration (P < 0.001) which was paradoxically accompanied by a modest but significant (P < 0.05) rise in blood ammonia level in 10 of the 23 patients studied. Change in blood ammonia pre- and post-hemodialysis correlated with change in serum bicarbonate levels (r = 0.61, P < 0.01). On subgroup analysis of patients who had a rise in blood ammonia levels after dialysis, there was a strong correlation with drop in mean arterial pressure (r = 0.88, P < 0.01). The nadir intradialytic systolic blood pressure trended lower in the hemodialysis patients who had a rise in blood ammonia compared to the patients who manifested a fall in blood ammonia (124 ± 8 vs. 136 ± 6 mmHg respectively, P = 0.27). DISCUSSION: Fall in blood urea following hemodialysis in ESRD patients was paradoxically accompanied by a modest rise in blood ammonia levels in 43% of the patients studied, contrasting prior reported effects of hemodialysis on breath ammonia. In this subgroup of patients, changes in blood ammonia during hemodialysis correlated with rise in blood bicarbonate and fall in mean arterial blood pressure.