Budesonide Versus Mesalamine in Microscopic Colitis: A Comparative Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Microscopic colitis (MC) is an inflammatory bowel disease of autoimmune origin that causes chronic watery diarrhea. Medications, including budesonide, mesalamine, loperamide, cholestyramine, and bismuth subsalicylate, are first-line therapies. Meanwhile, azathioprine, 6-mercaptopurine, and methotrexate are indicated for refractory MC. OBJECTIVE: We aim to assess the efficacy and safety of budesonide compared with mesalamine for induction of remission in MC patients. METHODS: We searched the Cochrane Library, Scopus, Web of Science, and PubMed for relevant clinical trials comparing either mesalamine or budesonide with a control group. We included the following outcomes: clinical remission (3 or fewer stools/day), daily stool weight, daily stool frequency, number of patients with clinical response <50% in the disease activity, and daily stool consistency. Safety end points included: any adverse event, serious adverse events, any adverse event-related discontinuation, abdominal discomfort, constipation, flatulence, nausea, dizziness, headache, bronchitis, nasopharyngitis, and depression. We conducted a meta-analysis model using the generic inverse variance method and performed a subgroup analysis based on the intervention administered. RESULTS: Nineteen randomized clinical trials were included. We found that after 6 weeks of follow-up, budesonide is associated with increased clinical remission rates compared with mesalamine [RR=2.46 (2.27, 2.67), and RR=2.24 (1.95, 2.57), respectively]. However, the test of subgroup difference revealed that the difference is not significant (P=0.25). After 8 weeks of follow-up, budesonide showed significantly higher clinical remission rates than mesalamine RR=2.29 (2.14, 2.45), and RR=1.7 (1.41, 2.05), respectively (P=0.003). Regarding the daily stool weight, patients in the budesonide group showed nonsignificant less stool weight [MD=-351.62 (-534.25, -168.99)] compared with mesalamine [MD=-104.3 (-372.34, 163.74)], P=0.14. However, daily stool frequency was significantly less in the budesonide group compared with mesalamine (P<0.001). Budesonide is associated with a significantly lower incidence of adverse events compared with mesalamine (P=0.002). Analysis of other safety endpoints was not significant between both groups. CONCLUSIONS: Budesonide was found to be better than mesalamine in MC patients in terms of clinical remission rate, especially after 8 weeks of follow-up. Budesonide also showed less incidence of adverse events. There is an urgent need for randomized, double-blinded clinical trials to provide direct and reliable evidence.

Trainee Involvement and ERCP Complications: A Systematic Review and Meta-Analysis.

BACKGROUND: Therapeutic endoscopy and gastroenterology fellows often participate in endoscopic retrograde cholangiopancreatography (ERCP) during their training period. However, it is generally feared that trainee involvement may increase ERCP-related complications, mainly because of the side-viewing nature of the endoscope and the higher risk of pancreatic duct cannulation. There is no concrete evidence to support this notion. This systematic review and meta-analysis aims to investigate the resultsof trainee participation on adverse events related to ERCP. METHODS: PubMed, EMBASE, Google Scholar, SCOPUS, and Web of Science databases were searched from inception to 31 May 2023 for studies evaluating the ERCP outcomes defined as success rates, procedure time, failed attempts, and adverse events with and without trainee participation. A random effect model was used to perform the meta-analysis, and heterogeneity was assessed using the I2 statistics. RESULTS: Seven studies were included in the final analysis, including 17,088 ERCPs. The pooled odds ratio (pOR) of success rate, incomplete/failed attempts in the trainee and no trainee groups were 0.466 (95% CI 0.13 to 1.66, I2 = 97.8%, p = 0.239) and 3.2 (95% CI 0.70 to 14.55), I2 = 98.5%, p = 0.134), respectively. The pOR of post-ERCP pancreatitis and bleeding in the trainee vs. no trainee groups was 0.97 (95% CI 0.76 to 1.23, I2 = 0%, p = 0.78) and 1.3 (95% CI 0.59 to 2.83, I2 = 49%, p = 0.54). The pOR of all adverse events in both groups was 1.028 (95% CI 0.917 to 1.152, I2 = 0%, p = 0.636). Surprisingly, the pooled std mean difference for the procedure time was 0.217 (95% - 0.093 to 0.05, I2 = 98.5%, p = 0.17). CONCLUSION: This meta-analysis comprising of 17,088 ERCPs in seven studies demonstrated comparable ERCP outcomes related to trainee participation regarding success rates, procedure time, and adverse events. Trainees' involvement in ERCP within a proper teaching setting appears safe and does not compromise the overall procedure's success.

Endoscopic Advances in the Diagnosis and Management of Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is one of the most common diseases that occurs secondary to failure of the antireflux barrier system, resulting in the frequent and abnormal reflux of gastric contents to the esophagus. GERD is diagnosed in routine clinical practice based on the classic symptoms of heartburn and regurgitation. However, a subset of patients with atypical symptoms can pose challenges in diagnosing GERD. An esophagogastroduodenoscopy (EGD) is the most common initial diagnostic test used in the assessment for GERD, although half of these patients will not have any positive endoscopic findings suggestive of GERD. The advanced endoscopic techniques have improved the diagnostic yield of GERD diagnosis and its complications, such as Barrett's esophagus and early esophageal adenocarcinoma. These newer endoscopic tools can better detect subtle irregularities in the mucosa and vascular structures. The management options for GERD include lifestyle modifications, pharmacological therapy, and endoscopic and surgical interventions. The latest addition to the armamentarium is the minimally invasive endoscopic interventions in carefully selected patients, including the electrical stimulation of the LES, Antireflux mucosectomy, Radiofrequency therapy, Transoral Incisionless Fundoplication, Endoscopic Full-Thickness plication (GERDx™), and suturing devices. With the emergence of these advanced endoscopic techniques, it is crucial to understand their selection criteria, advantages, and disadvantages.

National Trends in the Incidence of Sporadic Malignant Colorectal Polyps in Young Patients (20-49 Years): An 18-Year SEER Database Analysis.

Background and Objectives: Conflicting guidelines exist for initiating average-risk colorectal cancer screening at the age of 45 years. The United States Preventive Services Task Force (USPSTF) changed its guidelines in 2021 to recommend initiating screening at 45 years due to an increasing incidence of young-onset colorectal cancer. However, the American College of Physicians (ACP) recently recommended not screening average-risk individuals between 45 and 49 years old. We aim to study the national trends in the incidence of sporadic malignant polyps (SMP) in patients from 20 to 49 years old. Materials and Methods: We analyzed the Surveillance, Epidemiology, and End Results database (2000-2017) on patients aged 20-49 years who underwent diagnostic colonoscopy with at least a single malignant sporadic colorectal polyp. Results: Of the 10,742 patients diagnosed with SMP, 42.9% were female. The mean age of incidence was 43.07 years (42.91-43.23, 95% CI). Approximately 50% of malignant polyps were diagnosed between 45 and 49 years of age, followed by 25-30% between 40 and 45. There was an upward trend in malignant polyps, with a decreased incidence of malignant villous adenomas and a rise in malignant adenomas and tubulovillous adenomas. Conclusions: Our findings suggest that almost half of the SMPs under 50 years occurred in individuals under age 45, younger than the current screening threshold recommended by the ACP. There has been an upward trend in malignant polyps in the last two decades. This reflects changes in tumor biology, and necessitates further research and support in the USPSTF guidelines to start screening at the age of 45 years.

Racial disparities in endoscopic retrograde cholangiopancreatography (ERCP) utilization in the United States: are we getting better?

BACKGROUND: We identified trends of inpatient therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in the United States (US), focusing on outcomes related to specific patient demographics. METHODS: The National Inpatient Sample was utilized to identify all adult inpatient ERCP in the US between 2007-2018. Trends of utilization and adverse outcomes were highlighted. P-values ≤ 0.05 were considered statistically significant. RESULTS: We noted a rising trend for total inpatient ERCP in the US from 126,921 in 2007 to 165,555 in 2018 (p = 0.0004), with a significant increase in utilization for Blacks, Hispanics, and Asians. Despite an increasing comorbidity burden [Charlson Comorbidity Index (CCI) score ≥ 2], the overall inpatient mortality declined from 1.56% [2007] to 1.46% [2018] without a statistically significant trend (p = 0.14). Moreover, there was a rising trend of inpatient mortality for Black and Hispanic populations, while a decline was noted for Asians. After a comparative analysis, we noted higher rates of inpatient mortality for Blacks (2.4% vs 1.82%, p = 0.0112) and Hispanics (1.17% vs 0.83%, p = 0.0052) at urban teaching hospitals between July toand September compared to the October to June study period; however, we did not find a statistically significant difference for the Asian cohort (1.9% vs 2.10%, p = 0.56). The mean length of stay (LOS) decreased from 7 days in 2007 to 6 days in 2018 (p < 0.0001), while the mean total hospital charge (THC) increased from $48,883 in 2007 to $85,909 in 2018 (p < 0.0001) for inpatient ERCPs. Compared to the 2015-2018 study period, we noted higher rates of post-ERCP pancreatitis (27.76% vs 17.25%, p < 0.0001) from 2007-2014. CONCLUSION: Therapeutic ERCP utilization and inpatient mortality were on the rise for a subset of the American minority population, including Black and Hispanics.

The Role of Red Cell Distribution Width as a Prognostic Marker in Chronic Liver Disease: A Literature Review.

Liver disease is one of the leading public health problems faced by healthcare practitioners regularly. As such, there has been a search for an inexpensive, readily available, non-invasive marker to aid in monitoring and prognosticating hepatic disorders. Recently, red blood cell distribution width (RDW) has been found to be associated with various inflammatory conditions with implications for its use as a potential marker for assessing disease progression and prognosis in multiple conditions. Multiple factors effect red blood cell production whereby a dysfunction in any process can lead to anisocytosis. Furthermore, a chronic inflammatory state leads to increased oxidative stress and produces inflammatory cytokines causing dysregulation and increased intracellular uptake and use of both iron and vitamin B12, which leads to a reduction in erythropoiesis causing an increase in RDW. This literature review reviews in-depth pathophysiology that may lead to an increase in RDW and its potential correlation with chronic liver diseases, including hepatitis B, hepatitis C, hepatitis E, non-alcoholic fatty liver disease, autoimmune hepatitis, primary biliary cirrhosis, and hepatocellular carcinoma. In our review, we examine the use of RDW as a prognostic and predictive marker for hepatic injury and chronic liver disease.

Global prevalence of occult hepatitis B: A systematic review and meta-analysis.

The study aimed to investigate the prevalence and risk factors associated with occult hepatitis B virus (HBV) infection (OBI) in the global population. We searched PubMed, Embase, CINAHL, Cochrane and Web of Science from database inception through 27 Dec, 2018. Studies reporting HBV-DNA serological data in previously undiagnosed hepatitis B patients were included. The data were further categorized according to the presence of risk factors. After an initial screening of 2,325 records, we finally included 98 articles about the prevalence of OBI from 34 countries and regions. The OBI prevalence was 0.82% (95% CI:0.69-0.96) in the general population, 16.26% (95% CI:10.97-22.34) in HIV patients, 13.99% (95% CI:8.33-20.79) in patients with other liver diseases, 4.25% (95% CI:1.64-7.87) in haemodialysis patients and 5.14% (95% CI:2.26-9.01) patients with other risk factors. In conclusion, OBI prevalence varies significantly across different populations and nations, which deserve attention from the public health authorities. Our results generate further epidemiological data to identify the population with OBI, which has important clinical implications in finding these high-risk populations to design preventive and management strategies.

Proton Pump Inhibitors Versus Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients: A Meta-analysis and Trial Sequential Analysis.

GOALS AND BACKGROUND: Stress ulcer prophylaxis has been shown to lower gastrointestinal bleeding (GIB) rates. Various agents have been studied, and the optimal strategy continues to be contested. This study evaluates the efficacy between proton pump inhibitors (PPIs) and histamine-2-receptor antagonists. Small sample sizes and methodology flaws limited prior studies. STUDY: A systematic search of MEDLINE, EMBASE, CENTRAL, Web of Science, and ClinicalTrials.gov for randomized controlled trials reporting the use of PPI and histamine-2-receptor antagonist reporting rates of GIB and standardized intensive care outcomes. Risk ratios (RR) and standardized mean difference (SMD) with 95% confidence intervals (CIs). A trial sequential analysis was performed to guard against errors. RESULTS: A total of 14 randomized controlled trials of 28,526 patients with a mean age of 57.83±17.35 years and 30.82% females. In our pooled analysis, PPI outperformed its comparator (RR: 0.68; 95% CI: 0.57-0.82) in clinically significant GIB. PPI re-demonstrated significant reduction in overt GIB (RR: 0.61; 95% CI: 0.39-0.97). No differences between groups was noted toward all-cause mortality (RR: 1.05; 95% CI: 1.00-1.10) or incidence of pneumonia (RR: 1.11; 95% CI: 0.82-1.51). Duration of stay (SMD: 0.07; 95% CI: -0.04-0.17) and ventilator days (SMD: 0.01; 95% CI: -0.01-0.04) were indifferent between the groups. CONCLUSIONS: Among critically ill patients, PPI was associated with reduced clinically significant or overt GIB. No differences in pneumonia were seen with the use of either agent. Trial sequential analysis for clinically significant GIB ruled out the risk for false-positive results, and thereby it is unlikely that future trials will affect our conclusions.

Epidemiology and outcomes of gastrointestinal mucosal melanomas: a national database analysis.

AIM: Gastrointestinal malignant melanoma is a rare mucosal melanoma (MM). Other MM include the respiratory and the genitourinary tract. All mucosal melanomas have a poor prognosis when compared to cutaneous melanomas. Ano-rectal melanomas are by far the most common and most studied gastrointestinal MM. Large-scale clinical data is lacking due to the rarity of the disease. We aim to analyze epidemiology and survival of the Gastrointestinal (G.I.) MM over 45 years using a national database. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients with biopsy-proven G.I. Melanomas. We selected tumor site, intervention, and survival information for oncology codes as per the international classification of diseases. Survival analysis was performed using the SPSS v 27 ® IBM software. RESULTS: Of the 1105 biopsy-proven confirmed cases of primary G.I. melanoma's, 191 (17.3%) received chemotherapy (C.T.), 202 (18.3%) received radiotherapy (R.T.), 63 (5.7%) received both C.T and R.T., while 684 (61.9%) of the population received surgery alone or combined with C.T. and/or R.T. Statistically significant improvement in survival was noted in all treatment strategies that utilized surgery and also when site-specific MM cohorts underwent a surgical approach with or without C.T and/or R.T. CONCLUSION: This is the most extensive study reporting epidemiological and survival data of treatment strategy outcomes of primary G.I. mucosal melanoma elucidating best overall survival with a management strategy involving surgical intervention.

Early readmissions of spontaneous bacterial peritonitis in the USA: Insights into an emerging challenge.

BACKGROUND AND AIM: Early readmissions of spontaneous bacterial peritonitis (SBP) are often associated with poor outcomes. We compared characteristics and outcomes for index and 30-day readmissions of SBP in the USA. METHODS: We analyzed the Nationwide Readmissions Database for 2018 to identify all adult (≥ 18 years) 30-day readmissions of SBP in the USA. Hospitalization characteristics and outcomes for index and 30-day readmissions of SBP were compared. Independent predictors of 30-day readmissions were also identified. RESULTS: In 2018, of the 5,797 index admissions for SBP, 30% (1726) were readmitted within 30 day. At the time of readmission, the most common admitting diagnosis was alcoholic cirrhosis of the liver with ascites (11.8%) followed by sepsis due to an unspecified organism (9.2%). SBP as an admitting diagnosis was identified for only 8.3% of these 30-day readmissions. Compared with index admissions, 30-day readmissions of SBP had a lower mean age (56.1 vs 58.6 years, P < 0.001) without a statistically significant difference for gender. Furthermore, 30-day readmissions of SBP were associated with significantly higher odds of inpatient mortality (10% vs 4.9%, OR: 2.15, 95% CI: 1.66-2.79, P < 0.001), and mean total hospital charge ($85,031 vs $56,000, mean difference: 29,032, 95% CI: 12,867-45,197, P < 0.001) compared with index admissions. The presence of chronic pulmonary disease, liver failure, inpatient dialysis, and discharge against medical advice were identified as independent predictors for increased 30-day readmissions of SBP. CONCLUSION: The 30-day readmission rate of SBP was 30% and these readmissions were associated with higher odds of inpatient mortality compared with index admissions.

Gastrointestinal Endoscopy-Associated Infections: Update on an Emerging Issue.

Over 17.7 million gastrointestinal (GI) endoscopic procedures are performed annually, contributing to 68% of all endoscopic procedures in the United States. Usually, endoscopic procedures are low risk, but adverse events may occur, including cardiopulmonary complications, bleeding, perforation, pancreatitis, cholangitis, and infection. Infections after the GI endoscopies most commonly result from the patient's endogenous gut flora. Although many studies have reported infection after GI endoscopic procedures, a true estimate of the incidence rate of post-endoscopy infection is lacking. In addition, the infection profile and causative organisms have evolved over time. In recent times, multi-drug-resistant microorganisms have emerged as a cause of outbreaks of endoscope-associated infections (EAI). In addition, lapses in endoscope reprocessing have been reported, with some but not all outbreaks in recent times. This systematic review summarizes the demographical, clinical, and management data of EAI events reported in the literature. A total of 117 articles were included in the systematic review, with the majority reported from North America and Western Europe. The composite infection rate was calculated to be 0.2% following GI endoscopic procedures, 0.8% following ERCP, 0.123% following non-ERCP upper GI endoscopic procedures, and 0.073% following lower GI endoscopic procedures. Pseudomonas aeruginosa was the most common culprit organism, followed by other Enterobacteriaceae groups of organisms and Gram-positive cocci. We have also elaborated different prevention methods such as antimicrobial prophylaxis, adequate sterilization methods for reprocessing endoscopes, periodic surveillance, and current evidence supporting their utilization. Finally, we discuss disposable endoscopes, which could be an alternative to reprocessing to minimize the chances of EAIs with their effects on the environmental and financial situation.

Global Impact of COVID-19 on Colorectal Cancer Screening: Current Insights and Future Directions.

The coronavirus disease 2019 (COVID-19) pandemic has brought significant challenges to many aspects of healthcare delivery since the first reported case in early December 2019. Once in the body, SARS-CoV-2 can spread to other digestive organs, such as the liver, because of the presence of ACE2 receptors. Colorectal cancer (CRC) remains the second-leading cause of death in the United States (US). Therefore, individuals are routinely screened using either endoscopic methods (i.e., flexible sigmoidoscopy and colonoscopy) or stool-based tests, as per the published guidelines. At the beginning of the COVID-19 pandemic, the Centers for Medicare and Medicaid Services (CMS) recommended that all non-urgent surgical and medical procedures, including screening colonoscopies, be delayed until the pandemic stabilization. This article aims to review the impact of COVID-19 on CRC screening.

Epidemiology estimates of hepatitis D in individuals co-infected with human immunodeficiency virus and hepatitis B virus, 2002-2018: A systematic review and meta-analysis.

Hepatitis delta virus (HDV) is an obligate satellite of hepatitis B virus (HBV). HIV/HDV co-infection is associated with a high rate of hepatic decompensation events and death. We aimed to characterize the epidemiology of HDV infection in HIV/HBV co-infected individuals. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, CINAHL and Scopus for studies published from 1 Jan 2002 to 7 May 2018 measuring prevalence of HDV among the HIV population. Pooled seroprevalence was calculated with the DerSimonian-Laird random-effects model. Our search returned 4624 records, 38 of which met the inclusion and exclusion criteria. These studies included data for 63 cohorts from 18 countries and regions. The overall HDV seroprevalence of HIV-infected individuals was 1.03% (95% CI 0.43-1.85) in 2002-2018 globally. Moreover, the estimated pooled HDV seroprevalence among the general population was 1.07% (95% CI 0.65-1.59) in 2002-2018, which was not significantly different from the HDV seroprevalence of individuals living with HIV (p = 0.951). The overall HDV seroprevalence of the HBsAg positive population was 12.15% (95% CI 10.22-14.20), p = 0.434 when compared with the corresponding data of HIV/HBV co-infected individuals. This meta-analysis suggested that there was no difference between the HDV seroprevalence in HIV-infected individuals and the general population.

Successful Distancing: Telemedicine in Gastroenterology and Hepatology During the COVID-19 Pandemic.

Telemedicine involves delivering healthcare and preventative care services to patients without the need for in-person encounters. Traditionally, telemedicine has been used for acute events (e.g., stroke, used to relay essential information to the emergency department) and chronic disease management (e.g., diabetes and chronic kidney disease management). Though the utilization of telemedicine in gastroenterology and hepatology has been modest at best, especially for inflammatory bowel diseases and chronic liver disease management, since the onset of coronavirus disease 2019 (COVID-19) pandemic, utilization of telemedicine in gastroenterology increased by 4000% in the first two weeks, equivalent to the last six years of growth before the pandemic. The Center for Medicare and Medicaid (CMS) relaxed rules for the use of telemedicine with easing restrictions on reimbursements, location, licensing requirements (across state lines), and the need for a prior provider-patient relationship. These changes increased the use of telemedicine in inpatient and outpatient settings for gastroenterology-related referrals. The use of inpatient telephonic or video consults helps provide timely care during the pandemic while conserving personal protective equipment and decreasing provider and patient exposure. Nevertheless, telehealth use comes at the cost of no direct patient contact and lesser reimbursements. The appropriate use of technology and equipment, training of healthcare providers, use of platforms that can be integrated into the electronic health record while protecting the privacy and the flow of information are essential components of telemedicine. Furthermore, encouraging patients to seek medical care remotely with the proper equipment and improving digital literacy without the need for physical examinations is a challenge, further compounded in elderly or hard-of-hearing patients and in patients who are more comfortable with in-person visits. The authors will systematically review and discuss how telemedicine can be integrated into the practice of gastroenterology and hepatology, with emphasis placed on discussing barriers to success and the ways they can be mitigated.

Liver Biopsy in Pregnancy: Two Case Reports and Review of the Literature.

The etiology of most cases of liver diseases in pregnancy can be diagnosed with a thorough history, physical examination, laboratory values, serology, and noninvasive imaging. However, atypical clinical and laboratory presentations of liver diseases/chemistries require a liver biopsy to render an accurate diagnosis in cases where the biopsy results affect the timing of delivery or impact choice of medical therapy. According to the American College of Gastroenterology, liver biopsy can be effectively and safely conducted in pregnant women. Conventional routes of performing a liver biopsy include the percutaneous, transjugular route, and surgical methods. Endoscopic ultrasound-guided liver biopsy is a recent technique that has not yet gained widespread adoption but can potentially serve as an alternative route for obtaining the liver sample. Adverse events associated with liver biopsy include abdominal pain and hemorrhage. Maternal and fetal outcomes are limited to increased risk of preterm birth and small for gestational age neonate. However, very few studies have formally evaluated the safety of liver biopsy in pregnant women. In this review, we present two successful cases of liver biopsy performed during pregnancy and summarize the most recent evidence regarding the safety and outcomes of the procedure in pregnancy to assist clinicians in their decision to perform a liver biopsy during pregnancy or postpone it until after delivery.

Ferritin index is a strong prognostic marker in adult hemophagocytic lymphohistiocytosis.

AIMS: The relationship between ferritin levels and survival in adult hemophagocytic lymphohistiocytosis (HLH) has been evaluated in previous studies. However, Admission-to-discharge percentage ferritin reduction (named as ferritin index) level in adult patients with HLH has never been evaluated to predict 6-month survival. METHODS: The demographic, laboratory and clinical information of 102 newly diagnosed adult HLH patients were collected. Regression analysis, receiver operating curve and Kaplan-Meier curves were analysed to explore the performance of ferritin levels. RESULTS: Ferritin index and discharge ferritin level were significantly different between survivour and non-survivour group (all P < .001). Ferritin index had the highest area under the curve (AUC) for predicting the survival (AUC = 0.802, P < .001) followed by discharge ferritin (AUC = 0.746, P < .001). Kaplan-Meier analysis showed a significant difference in survival according to optimum cutoff values of ferritin index ≥ 10.19% (P < .001) or discharge ferritin ≤ 1056.1 µg/L (P < .001). Multivariate analysis confirmed that ferritin index and discharge ferritin are independent predictors of 6-month survival (ferritin index: odds ratio (HR) 6.237, 95% confidence interval (CI) 2.075-18.774, P = .001; discharge ferritin: HR 6.024, 95% CI 1.894-19.231, P = .002). In addition, the combination of a ferritin index ≥ 10.19% and discharge ferritin ≤ 1056.1 µg/L had a significantly higher 6-month survival (P < .001). CONCLUSION: Ferritin index is a better predictor of 6-month survival than admission and discharges ferritin levels in adult patients with HLH.

COVID-19 presenting as acute pancreatitis.

The ongoing pandemic of Coronavirus disease-2019 (COVID-19) has spread over 200 countries worldwide, affecting >2 million people and >120,000 deaths. COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The most common symptoms include cough, shortness of breath, and fever. However, gastrointestinal manifestations of COVID-19 are increasingly being recognized. Herein, we report a case of COVID-19 who presented with acute pancreatitis (AP) without any other risk factors.

Nationwide Analysis of Resource Utilization and In-Hospital Outcomes in the Obese Patients With Lower Gastrointestinal Hemorrhage.

GOALS: The goal of this study was to evaluate the impact of obesity on the outcomes of patients with lower gastrointestinal hemorrhage (LGIH). BACKGROUND: Obesity is considered as an independent risk factor for LGIH. We sought to analyze in-hospital outcomes and characteristics of nonobese and obese patients who presented with LGIH, and further, identify resource utilization during their hospital stay. MATERIALS AND METHODS: With the use of National Inpatient Sample from January 2005 through December 2014, LGIH-related hospitalizations (age≥18 y) were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic codes. Patients were stratified into the nonobese and obese groups depending on their body mass index (>30 kg/m). The statistical analyses were performed using SAS 9.4. RESULTS: Of the total 482,711 patients with LGIH-related hospitalizations, 38,592 patients were found to be obese. In a propensity-matched analysis, the in-hospital mortality was higher in the nonobese patients (4.2% vs. 3.8%, P=0.004), however, the mean length of hospital stay and mean cost was higher in the obese group which could be due to a higher number of comorbidities in the obese group. Secondary outcomes such as the need for mechanical ventilation vasopressor use and colonoscopy was significantly higher in the obese group. CONCLUSIONS: The study results demonstrate that 'obesity paradox' do exist for LGIH-related hospitalizations for mortality. LGIH hospitalizations in the obese patients are associated with higher resource utilization as evidenced by the longer length of stay and higher cost of hospitalizations as compared with the nonobese patients.

Gastrointestinal Symptoms and Outcomes in Hospitalized Coronavirus Disease 2019 Patients.

INTRODUCTION: Gastrointestinal (GI) symptoms are increasingly being recognized in coronavirus disease 2019 (COVID-19). It is unclear if the presence of GI symptoms is associated with poor outcomes in COVID-19. We aim to assess if GI symptoms could be used for prognostication in hospitalized patients with COVID-19. METHODS: We retrospectively analyzed patients admitted to a tertiary medical center in Brooklyn, NY, from March 18, 2020, to March 31, 2020, with COVID-19. The patients' medical charts were reviewed for the presence of GI symptoms at admission, including nausea, vomiting, diarrhea, and abdominal pain. COVID-19 patients with GI symptoms (cases) were compared with COVID-19 patients without GI symptoms (control). RESULTS: A total of 150 hospitalized COVID-19 patients were included, of which 31 (20.6%) patients had at least 1 or more of the GI symptoms (cases). They were compared with the 119 COVID-19 patients without GI symptoms (controls). The average age among cases was 57.6 years (SD 17.2) and control was 63.3 years (SD 14.6). No statistically significant difference was noted in comorbidities and laboratory findings. The primary outcome was mortality, which did not differ between cases and controls (41.9 vs. 37.8%, p = 0.68). No statistically significant differences were noted in secondary outcomes, including the length of stay (LOS, 7.8 vs. 7.9 days, p = 0.87) and need for mechanical ventilation (29 vs. 26.9%, p = 0.82). DISCUSSION: In our study, the presence of GI manifestations in COVID-19 at the time of admission was not associated with increased mortality, LOS, or mechanical ventilation.

Discovery of isoquinolinone and naphthyridinone-based inhibitors of poly(ADP-ribose) polymerase-1 (PARP1) as anticancer agents: Structure activity relationship and preclinical characterization.

The exploitation of GLU988 and LYS903 residues in PARP1 as targets to design isoquinolinone (I & II) and naphthyridinone (III) analogues is described. Compounds of structure I have good biochemical and cellular potency but suffered from inferior PK. Constraining the linear propylene linker of structure I into a cyclopentene ring (II) offered improved PK parameters, while maintaining potency for PARP1. Finally, to avoid potential issues that may arise from the presence of an anilinic moiety, the nitrogen substituent on the isoquinolinone ring was incorporated as part of the bicyclic ring. This afforded a naphthyridinone scaffold, as shown in structure III. Further optimization of naphthyridinone series led to identification of a novel and highly potent PARP1 inhibitor 34, which was further characterized as preclinical candidate molecule. Compound 34 is orally bioavailable and displayed favorable pharmacokinetic (PK) properties. Compound 34 demonstrated remarkable antitumor efficacy both as a single-agent as well as in combination with chemotherapeutic agents in the BRCA1 mutant MDA-MB-436 breast cancer xenograft model. Additionally, compound 34 also potentiated the effect of agents such as temozolomide in breast cancer, pancreatic cancer and Ewing's sarcoma models.