Development and Validation of a Machine Learning-based, Point-of-Care Risk Calculator for Post-ERCP Pancreatitis and Prophylaxis Selection.

BACKGROUND AND AIMS: A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning-based tool for PEP risk prediction to aid in clinical decision-making related to periprocedural prophylaxis selection and post-procedural monitoring. METHODS: Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a one-month period. RESULTS: A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on twenty PEP risk factors and 5 prophylactic interventions (rectal non-steroidal anti-inflammatory drugs [NSAID], aggressive hydration, combined rectal NSAID and aggressive hydration, pancreatic duct [PD] stenting, and combined rectal NSAID and PD stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74. CONCLUSIONS: This study demonstrates the feasibility and utility of a novel machine learning-based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended post-procedure monitoring.

Alcoholic Liver Disease/Non-Alcoholic Fatty Liver Disease Index for Classification of Patients with Steatotic Liver Disease.

Background: Steatotic liver disease (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (AALD) at extremes as well as an overlap group termed MASLD with increased alcohol intake (Met-ALD). The Alcoholic Liver Disease/Non-Alcoholic Fatty Liver Disease Index (ANI) was proposed to differentiate ALD from non-alcoholic fatty liver disease (NAFLD). We analysed the performance of the ANI in differentiating within the SLD spectrum. Methods: In a cross-sectional study at a tertiary care center, 202 adults (>18 years) who were prospectively diagnosed with SLD defined by magnetic resonance imaging-proton density fat fraction >6.4% were enrolled. Alcohol consumption (AC) was recorded according to thresholds for significant AC: 140-350 g/week (or 20-50 g/day) for females and 210-420 g/week (or 30-60 g/day) for males. The ANI was calculated, and area under the receiver operating characteristic curve (AUROC) was generated. Results: Of 202 patients (47 years [interquartile range, IQR, 38 to 55], 23.75% females, 77% obese, 42.1% diabetic, 38.1% hypertensive, 28.7% statin use), 40.5% were ever-alcohol consumers; 120 (59%), 50 (24.7%), and 32 (15.8%) were MASLD (ANI, -3.7 [IQR, -7 to -1.6]; Met-ALD, - 1.45 [IQR, -2.4 to 0.28]; and AALD, 0.71 [IQR, -1.3 to 4.8], respectively; P<0.05 for all). The AUROC of the ANI for MASLD and AALD was 0.79 (0.72 to 0.84; cut-off <-3.5) and 0.80 (0.74 to 0.86; cut-off >-1.49), respectively. The ANI outperformed aspartate transaminase/alanine transaminase (AST/ALT) ratio (AUROC=0.75 [0.69 to 0.81]) and gamma glutamyl transpeptidase (GGT) (AUROC=0.74 [0.67 to 0.80]). Addition of GGT did not improve model performance (AUCdiff=0.004; P=0.33). Conclusion: AC is common in MASLD. The ANI distinguishes MASLD and AALD, with individual cut-offs within the intermediate zone indicating Met-ALD. ANI also outperforms AST/ALT ratio or GGT.

Capsule endoscopy for small bowel bleed: Current update.

Small intestine, hitherto an obscure area for endoscopists before 2000, is now easily evaluated non-invasively using capsule endoscopy and invasively by device-assisted enteroscopies. Major advances in understanding the causes and management of small bowel diseases have been in obscure gastrointestinal (GI) bleed, currently re-named as small bowel bleed, after the discovery of capsule endoscopy. The current article is a narrative review of the technology of capsule endoscopy, its advantages and limitations, future perspective and Indian studies on its utility in patients with small bowel bleed. Till date, eight large series reporting 2319 patients with obscure GI bleed (1554 overt and 765 occult) undergoing capsule endoscopy have been reported from India. Overall yield of capsule endoscopy to detect lesions in these studies varied from 43.5% to 90%. The major causes detected in various studies for small bowel bleed include vascular malformation, portal hypertensive enteropathy, ulcer, stricture, tumor, polyps, etc. Hookworm can cause both occult as well as overt small bowel bleed as shown mainly from India. Capsule endoscopy has also been quite safe in patients with small bowel bleed as despite 0.6% to 15% retention of imaging capsule in Indian studies, development of clinically evident small bowel obstruction has rarely been reported. The major limitations of capsule endoscopy include lack of maneuvrability and therapeutic capability. Research is in progress to overcome some of the limitations of the current capsule endoscopy system. It is concluded that discovery of capsule endoscopy has brought a new paradigm in GI endoscopy and explored a hitherto unexplored area of GI tract, i.e. small bowel that continued to be a black box for the endoscopists.

Determinants, profile and outcomes of hepatitis A virus-associated severe acute liver injury in adults.

BACKGROUND AND OBJECTIVES: Hepatitis A virus (HAV)-related hepatitis is witnessing an epidemiological transition with increasing trends in adults. While uncomplicated hepatitis remains common, evidence suggests it to be a growing cause for acute liver failure (ALF). In between the two extremes exists severe acute liver injury (s-ALI) which has a propensity to transition to ALF. We aimed at describing the clinical profile of patients with HAV-related s-ALI and identifying potential predictors of progression to ALF. METHODS: This was a single-center retrospective analysis of adult patients admitted with HAV-related s-ALI between April 2022 and December 2023. Demographic and laboratory parameters were compared between patients with only s-ALI and those with ALF. Predictors of progression from s-ALI to ALF were identified using logistic regression. RESULTS: Forty-three patients satisfied criteria of s-ALI, of which 33 (76.7%) had only s-ALI, while 10 (23.3%) had ALF. Patients with s-ALI had lesser leukocytosis (6.3 ± 3 vs. 13.2 ± 4.8), less incidence of acute kidney injury (9.1% vs. 40%) and lower model for end-stage liver disease (MELD) (20 [18-24.5] vs. 31.5 [26-42]), arterial lactate (2.1 [1.3-3.1] vs. 6.3 [5.2-8.0]), arterial ammonia (94 [72-118] vs. 299 [188-573]), procalcitonin (0.5 [0.28-1.25] vs. 3.2 [1.2-6.1]) and ferritin (482 [213-1633] vs. 5186 [1341-11,053]) compared to HAV-ALF (p < 0.05 for all). Three patients (9.09%) with s-ALI progressed to ALF of whom one (3%) died. Baseline ammonia levels (unadjusted odds ratio [OR] 1.03 [1.01-1.06]) and leukocyte count (OR 1.00 [1.00-1.01]) tended to be associated with ALF progression, although none was significant after multi-variable adjustment. Ammonia levels had an area under receiver operating curve of 0.816 (0.64-0.93) (p = 0.009) (cut-off of 144 µmol/L). Additional comorbidities did not impact overall outcomes. CONCLUSION: HAV presents as s-ALI in young adults, with almost one in 10 progressing to ALF. Baseline ammonia may be an important predictor of progression even in s-ALI, but mandates larger well-designed studies.

Definitive Role of Contrast-enhanced Endoscopic Ultrasound (EUS) in the Diagnosis of Hepatocellular Carcinoma With Non-diagnostic Cross-sectional Imaging: A Case Report.

The diagnosis of hepatocellular carcinoma is usually centered around cross-sectional imaging (CSI) modalities. However, in some instances focal hepatic lesions may be missed on CSI. Endoscopic ultrasound (EUS) has an evolving role in hepatology and have been shown to be useful in diagnosing focal lesions with advantages of tissue acquisition. We report a case hepatitis B-related cirrhosis presenting with acute decompensation, wherein EUS was used to identify HCC and perform tissue acquisition as CSI was non-diagnostic.

Post-infection irritable bowel syndrome following Coronavirus disease-19: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Persistent gastrointestinal (GI) symptoms and functional gastrointestinal disorders (FGIDs) are increasingly being recognized after Coronavirus disease-19 (COVID-19). Though quite a few studies addressed irritable bowel syndrome (IBS) following COVID-19, the disorders' prevalence varies greatly. We evaluated, (i) overall frequency of post-COVID-19 IBS, (ii) relative risk of development of IBS among COVID-19 patients compared to healthy controls using systematic review and meta-analysis techniques. METHODS: Literature search was performed for studies on GI symptoms and FGIDs after COVID-19 using electronic databases (Medline, Scopus, Cochrane Central Register of Controlled Trials, Google Scholar and Web of Science) till April 28, 2023. We included studies reporting IBS after COVID-19 with any duration of follow-up and any number of subjects. Studies on pediatric population and those not providing relevant information were excluded. Relative risk of development of IBS using Rome criteria among COVID-19 patients compared to healthy controls was calculated. Analysis was done using MedCalc (Applied Math, Mariakerke, Belgium, version 7.2) and Comprehensive Meta-Analysis version 3.3.070 (Biostat Inc. Englewood, NJ 07631, USA). RESULTS: Of the available studies, 13 (four case-control) reporting on IBS after COVID-19 met inclusion criteria. Among 3950 COVID-19 patients and 991 controls, 7.2% of COVID-19 patients and 4.9% of healthy controls developed IBS. Of the four case-control studies reporting post-COVID-19 IBS, patients with COVID-19 were 2.65 (95% confidence interval [CI] 0.538 to 13.039) times more likely to have post-COVID-19 IBS as compared to healthy controls. CONCLUSIONS: Patients with COVID-19 are more likely to develop post-COVID-19 IBS than healthy controls. The heterogeneity of studies, different criteria used by various studies to diagnose post-COVID-19 IBS and some studies not meeting the six-month follow-up duration of the Rome criteria for diagnosing IBS are limitations of this systematic review.

Global prospective case series of ERCPs using a single-use duodenoscope.

BACKGROUND: The first commercialized single-use duodenoscope was cleared by the US Food and Drug Administration in December 2019. Data regarding endoscopic retrograde cholangiopancreatography (ERCP) using a single-use duodenoscope are needed on a broader range of cases conducted by endoscopists with varying levels of experience in a wide range of geographic areas. METHODS: 61 endoscopists at 22 academic centers in 11 countries performed ERCP procedures in adult patients aged ≥ 18. Outcomes included ERCP completion for the intended indication, rate of crossover to a reusable endoscope, device performance ratings, and serious adverse events (SAEs). RESULTS: Among 551 patients, 236 (42.8 %) were aged > 65, 281 (51.0 %) were men, and 256 (46.5 %) had their procedure as an inpatient. ERCPs included 196 (35.6 %) with American Society for Gastrointestinal Endoscopy complexity of grades 3-4. A total of 529 ERCPs (96.0 %) were completed: 503 (91.3 %) using only the single-use duodenoscope, and 26 (4.7 %) with crossover to a reusable endoscope. There were 22 ERCPs (4.0 %) that were not completed, of which 11 (2.0 %) included a crossover and 11 (2.0 %) were aborted cases (no crossover). Median ERCP completion time was 24.0 minutes. Median overall satisfaction with the single-use duodenoscope was 8.0 (scale of 1 to 10 [best]). SAEs were reported in 43 patients (7.8 %), including 17 (3.1 %) who developed post-ERCP pancreatitis. CONCLUSIONS: In academic medical centers over a wide geographic distribution, endoscopists with varying levels of experience using the first marketed single-use duodenoscope had good ERCP procedural success and reported high performance ratings for this device.

Frequent guidewire passage into the pancreatic duct is an independent risk factor for postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among high-risk individuals: A post-hoc analysis of a randomized controlled trial data.

OBJECTIVES: To systematically evaluate the patient and procedural risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among patients receiving rectal indomethacin. METHODS: Data from a randomized controlled trial (RCT) of high-risk patients undergoing ERCP who received rectal indomethacin with or without topical epinephrine was evaluated. PEP was defined based on the consensus criteria. Pancreatic stenting was excluded to avoid confounding results with the role of epinephrine spray. Multivariable logistic regression analysis was used to identify patient and procedural risk factors for PEP. RESULTS: Among 960 patients enrolled in the RCT, the PEP incidence was 6.4%. An increased risk of PEP was seen with age <50 years and female gender (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.35-4.26), malignant biliary stricture(s) (OR 3.51, 95% CI 1.52-8.10), >2 guidewire passes into the pancreatic duct (PD) (OR 2.84, 95% CI 1.43-5.64), and pancreatic brush cytology (OR 6.37, 95% CI 1.10-36.90), whereas a decreased risk of PEP was seen with contrast- over guidewire-assisted cannulation (OR 0.14, 95% CI 0.02-0.99) and the use of lactated Ringer's (LR) over other fluid types (OR 0.52, 95% CI 0.27-0.98). There was a significant trend between the number of guidewire passes into the PD and PEP risk (P = 0.002). CONCLUSIONS: More than two guidewire passes into the PD and pancreatic brush cytology increased while the use of LR decreased the risk of PEP among high-risk patients receiving rectal indomethacin. Pancreatic stent placement and/or LR should be considered in patients with >2 guidewire passes into the PD.

Spur Cell Anaemia in Cirrhosis: A Narrative Review.

The presence of anaemia has been linked to increased complications and a worse prognosis in cirrhosis. Spur cell anaemia (SCA) is a specific form of haemolytic anaemia reported in patients with advanced cirrhosis. The literature on the entity has not been systematically reviewed, despite the classical association and frequent association with worse outcomes. We undertook a narrative review of available literature on SCA which yielded only 4 were original studies, one case series and the rest of the literature as case reports and clinical images. SCA is usually defined by the presence of spur cell rate of ≥5%, although there remains a lack of consensus in the definition. SCA has been classically associated with alcohol-related cirrhosis but can be seen across the spectrum of cirrhosis and acute to chronic liver failure. Patients with SCA tend to have evidence of higher grades of liver dysfunction, abnormal lipid profiles, worse prognostic scores and a high mortality. Experimental therapies including corticosteroids, pentoxifylline, flunarizine and plasmapheresis has been tried with variable effect, but liver transplantation remains the management of choice. We propose a stepwise approach to diagnosis and re-enforce the need for further prospective research, especially in subgroups of advanced cirrhosis like acute to chronic liver failure.

Obesity and alcoholic etiology as risk factors for multisystem organ failure in acute pancreatitis: Multinational study.

BACKGROUND: Multisystem organ failure (MSOF) is the most important determinant of mortality in acute pancreatitis (AP). Obesity and alcoholic etiology have been examined as potential risk factors for MSOF, but prior studies have not adequately elucidated their independent effects on the risk of MSOF. OBJECTIVE: We aimed to determine the adjusted effects of body mass index (BMI) and alcoholic etiology on the risk of MSOF in subjects with AP. METHODS: A prospective observational study of 22 centers from 10 countries was conducted. Patients admitted to an APPRENTICE consortium center with AP between August 2015 and January 2018 were enrolled. Multivariable logistic regression was used to estimate the adjusted effects of BMI, etiology, and other relevant covariates on the risk of MSOF. Models were stratified by sex. RESULTS: Among 1544 AP subjects, there was a sex-dependent association between BMI and the risk of MSOF. Increasing BMI was associated with increased odds of MSOF in males (OR 1.10, 95% confidence interval [CI] 1.04-1.15) but not in females (OR 0.98, 95% CI 0.90-1.1). Male subjects with AP, whose BMIs were 30-34 and >35 kg/m2 , had odds ratios of 3.78 (95% CI 1.62-8.83) and 3.44 (95% CI 1.08-9.99), respectively. In females, neither higher grades of obesity nor increasing age increased the risk of MSOF. Alcoholic etiology was independently associated with increased odds of MSOF compared with non-alcohol etiologies (OR 4.17, 95% CI 2.16-8.05). CONCLUSION: Patients with alcoholic etiology and obese men (but not women) are at substantially increased risk of MSOF in AP.

Psoas Muscle Index: A Simple and Reliable Method of Sarcopenia Assessment on Computed Tomography Scan in Chronic Liver Disease and its Impact on Mortality.

Objectives: Psoas muscle parameters have been proposed as a simple and quick method for sarcopenia assessment. The aim of this study was to assess sarcopenia in cirrhotics by psoas muscle on computed tomography and its impact on mortality. Methods: One hundred and fifty patients (75 cirrhotics, 75 subjects) were assessed for psoas muscle on CT scan. Psoas muscle index (PMI) was calculated as 'total psoas muscle area/(height of subject)2'. Cut off values for sarcopenia diagnosis were derived from local subjects (n = 75) who did not have cirrhosis/other causes of sarcopenia. Results: Sarcopenia assessed by PMI was seen in 36% (n = 27) of the cirrhotics. Sarcopenia was significantly higher in patients having Child-Pugh C. Ascites, hepatic encephalopathy (HE) and gastro-intestinal bleed were seen in 48%, 18.7% and 24%, respectively. Sarcopenia was significantly associated with ascites and HE (P < 0.05). Out of the 75 cases, 53 cases completed the follow-up period of 1 year. Among the 20 cases who had sarcopenia, 35% (n = 7) succumbed to liver-related illness during 1 year follow-up, and out of the 33 cases without sarcopenia, only 6% (n = 2) died. The association of sarcopenia and 1 year mortality was statistically significant (P = 0.01). Conclusions: The PMI, a simple method for sarcopenia assessment detected sarcopenia in 36% of cirrhotics. Patients with sarcopenia had a significantly higher 1 year mortality rate and appropriate prognostication of such patients is needed.

Rectal INdomethacin, oral TacROlimus, or their combination for the prevention of post-ERCP pancreatitis (INTRO Trial): Protocol for a randomized, controlled, double-blinded trial.

BACKGROUND: Acute pancreatitis remains the most common and morbid complication of endoscopic retrograde cholangiopancreatography (ERCP). The use of rectal indomethacin and pancreatic duct stenting has been shown to reduce the incidence and severity of post-ERCP pancreatitis (PEP), but these interventions have limitations. Recent clinical and translational evidence suggests a role for calcineurin inhibitors in the prevention of pancreatitis, with multiple retrospective case series showing a reduction in PEP rates in tacrolimus users. METHODS: The INTRO trial is a multicenter, international, randomized, double-blinded, controlled trial. A total of 4,874 patients undergoing ERCP will be randomized to receive either oral tacrolimus (5 mg) or oral placebo 1-2 h before ERCP, and followed for 30 days post-procedure. Blood and pancreatic aspirate samples will also be collected in a subset of patients to quantify tacrolimus levels. The primary outcome of the study is the incidence of PEP. Secondary endpoints include the severity of PEP, ERCP-related complications, adverse drug events, length of hospital stay, cost-effectiveness, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of tacrolimus immune modulation in the pancreas. CONCLUSIONS: The INTRO trial will assess the role of calcineurin inhibitors in PEP prophylaxis and develop a foundation for the clinical optimization of this therapeutic strategy from a pharmacologic and economic standpoint. With this clinical trial, we hope to demonstrate a novel approach to PEP prophylaxis using a widely available and well-characterized class of drugs. TRIAL REGISTRATION: NCT05252754, registered on February 14, 2022.

Management of Refractory Variceal Bleed in Cirrhosis.

Acute variceal bleeding is the major cause of mortality in patients with cirrhosis. The standard medical and endoscopic treatment has reduced the mortality of variceal bleeding from 50% to 10-20%. The refractory variceal bleed is either because of failure to control the bleed or failure of secondary prophylaxis. The patients refractory to standard medical therapy need further interventions. The rescue therapies include balloon tamponade, self-expanding metal stents (SEMS) placement, shunt procedures, including transjugular intrahepatic portosystemic shunt (TIPS), balloon-occluded retrograde transvenous obliteration (BRTO), and endoscopic ultrasound (EUS) guided coiling. In cases where endoscopic variceal ligation (EVL) has failed and the variceal bleeding continues, temporary measures like balloon tamponade can be used to achieve hemostasis and as a bridge to definitive measures. SEMS being in use for refractory bleed is preferred over balloon tamponade due to the reduced complication rate. The shunting procedures are highly effective in reducing portal pressure and represent the gold standard for uncontrolled variceal bleeding. The surgical shunts, as well as nonshunt surgeries such as devascularization have become less popular with the increasing use of minimally invasive techniques like TIPS. TIPS have high success rates in controlling refractory variceal bleeding. The mortality rate is greater in high-risk patients undergoing salvage TIPS, and hence, pre-emptive TIPS should be considered in these patients. BRTO is an interventional radiologic procedure used in the management of bleeding gastric and ectopic varices. The availability of gastrorenal or splenorenal shunts is required for the BRTO procedure, which helps to reach and obliterate the cardiofundal varices through the femoral or jugular vein approach. The EUS guided coiling and glue injection have shown promising results, and further randomized controlled trials are required to establish their efficacy for refractory variceal bleeding.

The relationship between pre-existing diabetes mellitus and the severity of acute pancreatitis: Report from a large international registry.

BACKGROUND/OBJECTIVES: The relationship between pre-existing diabetes mellitus (DM) and acute pancreatitis (AP) severity has not been established. We assessed the impact of pre-existing DM on AP severity in an international, prospectively ascertained registry. METHODS: APPRENTICE registry prospectively enrolled 1543 AP patients from 22 centers across 4 continents (8 US, 6 Europe, 5 Latin America, 3 India) between 2015 and 2018, and collected detailed clinical information. Pre-existing DM was defined a diagnosis of DM prior to AP admission. The primary outcome was AP severity defined by the Revised Atlanta Classification (RAC). Secondary outcomes were development of systemic inflammatory response syndrome (SIRS) or intensive care unit (ICU) admission. RESULTS: Pre-existing DM was present in 270 (17.5%) AP patients, of whom 252 (93.3%) had type 2 DM. Patients with pre-existing DM were significantly (p < 0.05) older (55.8 ± 16 vs. 48.3 ± 18.7 years), more likely to be overweight (BMI 29.5 ± 7 vs. 27.2 ± 6.2), have hypertriglyceridemia as the etiology (15% vs. 2%) and prior AP (33 vs. 24%). Mild, moderate, and severe AP were noted in 66%, 23%, and 11% of patients, respectively. On multivariable analysis, pre-existing DM did not significantly impact AP severity assessed by the RAC (moderate-severe vs. mild AP, OR = 0.86, 95% CI 0.63-1.18; severe vs. mild-moderate AP, OR = 1.05, 95% CI, 0.67-1.63), development of SIRS, or the need for ICU admission. No interaction was noted between DM status and continent. CONCLUSION: About one in 5 patients with AP have pre-existing DM. Once confounding risk factors are considered, pre-existing DM per se is not a risk factor for severe AP.