Clinical Outcomes and Safety of Upper Endoscopy While on Glucagon-Like Peptide-1 Receptor Agonists.

Glucose-like peptide-1-receptor agonists (GLP-1RAs) have become integral to the management of type 2 diabetes and obesity. GLP-1RAs work in part through delaying gastric emptying, raising concerns about retained gastric contents (RGC) during esophagogastroduodenoscopy (EGD).1 The American Society of Anesthesiologists currently recommends holding GLP-1RAs for 1 dosing cycle before elective procedures, however, the American Gastroenterological Association (AGA) advocates proceeding with endoscopy in asymptomatic patients adhering to standard perioperative protocols without medication withholding and suggests implementing a liquid diet the day before endoscopy in lieu of stopping the medication.2,3 This variability in recommendations stems largely from a lack of GLP-1RA outcomes data from which to draw evidence-based conclusions.

Phylogenetic analysis and haplotype networking of Hepatozoon felis infecting wild animals in Gir National Park, Gujarat, India.

The present study was aimed to determine the phylogenetic relationship, haplotype network, and demographic dynamics of H. felis infecting the endangered Asiatic lions in Gir National Park, Gujarat, India, on the basis of partial 18S rRNA gene. The phylogenetic analysis based on the partial 18S rRNA gene sequences of H. felis exhibited the presence of two distinct genotypes of H. felis (HfG1 and HfG2) infecting the Indian wild felids, viz., the Asiatic lion, Royal Bengal tiger, and Indian leopard. The HfG1 and HfG2 genotypes exhibited 97.6-100% and 99.7-100%, and 96.9-98.7% nucleotide identity within and between themselves, respectively. The HfG1 genotype exhibited a higher genetic diversity as compared to HfG2. A total of 22 molecular signatures were identified in the 18S rRNA gene between these genotypes. Further, analysis of a total 67 sequences of H. felis (13 different host species from 13 countries of Africa, South America, Asia, and Europe) that were downloaded from GenBankTM, generated 30 haplotypes. Among all the haplotypes, Hap_17 (h=12) was the most frequent followed by Hap_12 (h=09) and Hap_4 (h=05). Out of 13 location-wise populations, India (h=12) shared the highest number of haplotypes followed by Japan (h=08), and the least number of haplotypes were found in Hungary (h=02). Population dynamics study involving neutrality tests and mismatch distribution, and genetic differentiation indices, revealed the presence of phylogeographic population structure and a constant population size indicating a uniform gene flow among the populations worldwide. In conclusion, a high genetic diversity along with the presence of two distinct genotypes of H. felis were observed on the basis of 18S rRNA gene sequence analysis.

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Alzheimer Disease Occurs More Frequently In Patients With Inflammatory Bowel Disease: Insight From a Nationwide Study.

Alzheimer disease (AD) affects 5 million Americans and early recognition improves cognitive function. Chronic inflammation and gut microbiome alteration are linked to cognitive decline which are common in inflammatory bowel disease (IBD). We investigated the association of IBD with development of AD. A commercial database (Explorys Inc., Cleveland, OH), an aggregate of electronic health records from 26 major US health care systems, was surveyed. Cohorts of patients with Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) diagnoses of Crohn's disease (CD), ulcerative colitis (UC), and AD were identified. IBD patients with new diagnosis of AD were characterized based on demographic and traditional AD risk factors and IBD-related features. Among 342,740 IBD patients in the database, AD developed in 5750 IBD patients (1.55%). After adjusting for traditional AD risk factors, IBD was identified as an independent risk factor for development of AD [odds ratio (OR)=2.30, 95% confidence interval (CI)=2.10-2.51]. IBD patients with AD were younger in comparison to AD patients without IBD. On sub-group analysis, patients with CD had higher odds of developing AD (adjusted OR=3.34, 95% CI=3.25-3.42) than UC (adjusted OR=1.09, 95% CI=1.06-1.14). Use of tumor necrosis factor (TNF-α) inhibitors in IBD was associated with significantly lower odds of developing AD in both CD and UC. In this population based study, IBD was independently associated with development of AD. Among IBD; the association was stronger in patients with CD in comparison with UC. Use of TNF-α inhibitors was associated with lower odds of developing AD.

Long-term recurrence after endoscopic versus surgical ampullectomy of sporadic ampullary adenomas: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Ampullary adenomas are treated both surgically and endoscopically, however, data comparing both techniques are lacking. We aimed to compare long-term recurrence of benign sporadic adenomas after endoscopic (EA) and surgical ampullectomy (SA). METHODS: A comprehensive literature search of multiple databases (until December 29, 2020) was performed to identify studies reporting outcomes of EA or SA of benign sporadic ampullary adenomas. The outcome was recurrence rate at 1 year, 2-year, 3 year and 5 years after EA and SA. RESULTS: A total of 39 studies with 1753 patients (1468 EA [age 61.1 ± 4.0 years, size 16.1 ± 4.0 mm], 285 SA [mean age 61.6 ± 4.48 years, size 22.7 ± 5.4 mm]) were included in the analysis. At year 1, pooled recurrence rate of EA was 13.0% (95% confidence interval [CI] 10.5-15.9], I2 = 31%) as compared to SA 14.1% (95% CI 9.5-20.3 I2 = 15.8%) (p = 0.82). Two (12.5%, [95% CI, 8.9-17.2] vs. 14.3 [95% CI, 9.1-21.6], p = 0.63), three (13.3%, [95% CI, 7.3-21.6] vs. 12.9 [95% CI, 7.3-21.6], p = 0.94) and 5 years (15.7%, [95% CI, 7.8-29.1] vs. 17.6% [95% CI, 6.2-40.8], p = 0.85) recurrence rate were comparable after EA and SA. On meta-regression, age, size of lesion or enbloc and complete resection were not significant predictors of recurrence. CONCLUSION: EA and SA of sporadic adenomas have similar recurrence rates at 1, 2, 3 and 5 years of follow up.

Crohn's Disease Is Associated with Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Chronic inflammation in IBD is postulated to drive NAFLD progression from steatosis to fibrosis. AIMS: To study the histopathological spectrum of NAFLD in Crohn disease (CD) and Ulcerative colitis (UC). METHODS: Patients with biopsy proven NAFLD at a quaternary center from 2008 to 2018 were included in this retrospective analysis. Inflammatory bowel disease (IBD) diagnosed either clinically and/or endoscopically at the time of liver biopsy. Multivariable regression and propensity score (PS) weighted analysis were conducted. Statistical analysis were performed using SAS statistical software. RESULTS: Among 1009 patients with NAFLD a diagnosis of IBD was identified in 50 cases (34 CD and 16 UC). On multivariable analysis; CD was independently associated with significantly higher odds of advanced fibrosis (AF) on liver biopsy (adjusted OR = 4.09, 95% CI = 1.40-11.94) compared to NAFLD patients without IBD. Similar results were obtained with both the overlap PS weighted model (OR = 3.17, 95% CI = 1.55-6.49) and the PS matched model (OR = 3.49, 95% CI = 1.50-8.13). CONCLUSION: In a large cohort of patients with histologically well characterized NAFLD, AF was more common in CD patients than NAFLD patients without IBD. These findings must be confirmed in a larger cohort, but suggest CD patients with NAFLD could be at greater risk for liver fibrosis.

Bi-directional Relationship Between Celiac Disease and Liver Chemistries: A Systematic Review and Meta-Analysis.

AIMS: Previous studies have reported conflicting results regarding prevalence of elevated LC (2-70%) in celiac disease (CD). This systematic review and meta-analysis assessed the prevalence of elevated LC at time of CD diagnosis and associated response to GFD. We also report the prevalence of CD in patients with unexplained elevation of LC. METHODS: Studies assessing LC (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in CD patients were eligible. Studies with < 50 cases or in pediatric populations were excluded. RESULTS: In total, 20 studies assessing prevalence of elevated LC in 4,265 participants with newly diagnosed CD (mean age = 35.6 ± 6.5 years, 69.8% female) were included. Pooled prevalence of elevated LC was 18.7% (95% CI 13.8-24.8; I2 = 95%). Normalization of elevated LC was seen in 83.1% (95% CI 73.4-89.7; I2 = 79%, 11 studies) of patients after GFD. On meta-regression, age at CD diagnosis, gender, and Marsh grading were not associated with elevated LC. Among 979 participants (7 studies) with unexplained elevation of LC, pooled seroprevalence and biopsy-proven CD was 6.4% (95% CI 2.9-10.3, I2 = 71%) and 4.5% (95% CI 2.6-7.7, I2 = 67%), respectively. CONCLUSION: Elevated LC are seen in approximately one-fifth of patients at CD diagnosis with majority normalizing after GFD. Age, gender, and degree of intestinal damage are not predictive of elevated LC. In the appropriate clinical scenario, liver tests should be serially monitored in CD reserving workup for additional causes after a trial of GFD. Patients with unexplained elevation of liver tests should be screened for celiac disease.

Mortality Trends, Outcomes, and Predictors of Portal Vein Thrombosis in Acute Pancreatitis Patients: A Propensity-Matched National Study.

BACKGROUND: Portal vein thrombosis (PVT) is a rare complication of acute pancreatitis (AP) and might be associated with worse outcomes. We aimed to study trends, outcomes, and predictors of PVT in AP patients. METHODS: The National Inpatient Sample database was utilized to identify the adult patients (≥ 18 years) with primary diagnosis of AP from 2004 to 2013 using International Classification of Disease, Ninth Revision. Patients with and without PVT were entered into propensity matching model based on baseline variables. Outcomes were compared between both groups and predictors of PVT in AP were identified. RESULTS: Among the total of 2,389,337 AP cases, 7046 (0.3%) had associated PVT. The overall mortality of AP decreased throughout the study period (p trend ≤ 0.0001), whereas mortality of AP with PVT remained stable (1-5.7%, p trend = 0.3). After propensity matching, AP patients with PVT patients had significantly higher in-hospital mortality (3.3% vs. 1.2%), AKI (13.4% vs. 7.7%), shock (6.9% vs. 2.5%), and need for mechanical ventilation (9.2% vs. 2.5%) along with mean higher cost of hospitalization and length of stay (p < 0.001 for all). Lower age (Odd ratio [OR] 0.99), female (OR 0.75), and gallstone pancreatitis (OR 0.79) were negative predictors, whereas alcoholic pancreatitis (OR 1.51), cirrhosis (OR 2.19), CCI > 2 (OR 1.81), and chronic pancreatitis (OR 2.28) were positive predictors of PVT (p < 0.001 for all) in AP patients. CONCLUSION: PVT in AP is associated with significantly higher risk of death, AKI, shock, and need for mechanical ventilation. Chronic and alcoholic pancreatitis is associated with higher risk of PVT in AP.

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.

Tacrolimus loaded nanostructured lipid carriers using Moringa oleifera seed oil: design, optimization and in-vitro evaluations.

The proposed research aims to develop Tacrolimus-loaded nanostructured lipid carriers (TAC-loaded NLCs) to overcome poor aqueous solubility and dissolution rate to enhance its oral absorption. A central composite design was used to optimise the amount of Poloxamer 188 and D-α-Tocopherol-polyethylene-glycol-succinate (TPGS). The optimised TAC-loaded NLCs contain stearic acid (250 mg), Moringa oleifera (MO) seed oil (50 mg), TAC (Tacrolimus: 10 mg), TPGS (60 mg), and Poloxamer 188 (1% w/v) with a mean diameter of 393.3 ± 29.68 nm, a zeta potential of -18.3 ± 6.19 mV, high entrapment efficiency (92.12 ± 1.14% w/w), and desirability (0.989). TAC-loaded NLCs showed ∼12 times higher drug dissolution efficiency, while in-vitro anti-inflammatory studies showed ∼1.8 times lower IC50 (half-maximal inhibitory concentration) than TAC suspension. The lyophilised TAC-loaded NLCs were found to be stable after 3 months. Thus, the present study concludes the successful encapsulation of TAC in NLCs made of stearic acid and MO seed oil.

Diabetes Liver Fibrosis Score to Detect Advanced Fibrosis in Diabetics with Nonalcoholic Fatty Liver Disease.

Type 2 diabetes (T2D) is a risk for advanced fibrosis (AF) in patients with nonalcoholic fatty liver disease (NAFLD). Recent data suggest that commonly used fibrosis scores (NAFLD fibrosis score [NFS], aspartate to alanine aminotransferase ratio [AST/ALT], AST to platelet ratio index, and Fibrosis-4) may have low sensitivity and negative predictive value to detect AF in patients with diabetes.1,2 The aim of this study was to develop a simple noninvasive fibrosis score to detect AF in patients with diabetes and compare its performance with other fibrosis scores.

Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection : Meta-analysis of Randomized Controlled Trials.

GOALS: The aim was to assess the effectiveness of fecal microbiota transplantation (FMT) against medical therapy (MT). BACKGROUND: FMT has shown good outcomes in the treatment of Clostridium difficile infection (CDI). We aimed to conduct a systematic review and meta-analysis to compare the effectiveness of FMT versus MT for CDI. STUDY: We performed a comprehensive search to identify randomized controlled trials comparing FMT against MT in patients with CDI. Outcomes of interest were clinical cure as determined by the resolution of diarrhea and/or negative C. difficile testing. Primary CDI is defined as the first episode of CDI confirmed endoscopically or by laboratory analysis. Recurrent C. difficile infection (RCDI) is defined as laboratory or endoscopically confirmed episode of CDI after at least 1 course of approved antibiotic regimen. RESULTS: A total of 7 studies with 238 patients were included in meta-analysis. Compared with MT, FMT did not have a statistically significant difference for clinical cure of combined primary and RCDI after first session [risk ratio (RR): 1.52, 95% confidence interval (CI): 0.90, 2.58; P =0.12; I2 =77%] and multiple sessions of FMT (RR: 1.68; CI: 0.96, 2.94; P =0.07; I2 =82%). On subgroup analysis, FMT has statistically higher rate of response than MT (RR: 2.41; CI: 1.20, 4.83; I2 =78%) for RCDI. However, for primary CDI there is no statistically significant difference between FMT and MT (RR: 1.00; CI: 0.72, 1.39; I2 =0%). CONCLUSION: As per our analysis, FMT should not be utilized for every patient with CDI. It is more effective in RCDI, but the results were not significant in patients with primary CDI.

Pneumatic dilation for esophageal achalasia: patient selection and perspectives.

Achalasia is an esophageal motility disorder characterized by esophageal aperistalsis and impaired relaxation of the lower esophageal sphincter. Treatment is palliative, aimed at decreasing the lower esophageal sphincter pressure. Pneumatic dilation (PD) is a safe and effective treatment for achalasia. Several other invasive and minimally invasive treatment modalities, such as Laparoscopic Heller Myotomy (LHM) and Peroral Endoscopic Myotomy (POEM), also have a comparable safety and efficacy profile to PD. The current review focuses on the indications, contraindications, techniques, and outcomes of PD in various patient populations and its comparison to LHM and POEM. This review also provides relevant information to help endoscopists identify those patients who will benefit the most from PD.

Lower rates of endoscopy and higher mortality in end-stage renal disease patients with gastrointestinal bleeding: A propensity matched national study.

BACKGROUND AND AIM: Patients with end-stage renal disease (ESRD) on hemodialysis are considered to be at higher risk of gastrointestinal bleeding (GIB) as compared with those without renal disease (NRD). We conducted a population-based study using the National Inpatient Sample (NIS) database to study the outcomes of GIB in ESRD. METHODS: Patients admitted with GIB (upper and lower) from 2005 to 2013 were extracted from the NIS database using ICD-9 codes. Patients were divided into NRD and ESRD groups, and a 1:1 propensity matched analysis was performed. Various outcomes were compared in both groups, and subgroup analysis based on the timing of endoscopy was also performed. RESULTS: A total of 218 032 patients were included in the study. There was an increase in inpatient admissions among ESRD patients with GIB with significant reduction in mortality (P < 0.001). In-hospital mortality, length of stay, and total costs were significantly higher in ESRD patients as compared with NRD. ESRD patients were less likely to undergo endoscopic evaluation compared with NRD (P < 0.001). Late endoscopy (> 48 h) was associated with increased need for transfusion and health-care utilization but without a significant difference in mortality as compared with early endoscopy. On multivariate analysis, endoscopy was associated with significantly lower rate of mortality in ESRD patients with GIB (odds ratio 0.28, P < 0.0001). CONCLUSION: End-stage renal disease patients with GIB had a significantly higher rate of mortality and a higher health-care utilization with a lower rate of endoscopic evaluation. Endoscopy was associated with a lower mortality rate on multivariate analysis.

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.

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients.

INTRODUCTION: The efficacy and safety profile of ustekinumab (UST) in Crohn's disease (CD) is favorable; however, data in elderly patients are lacking. We aimed to assess the safety and efficacy of UST in elderly CD. METHODS: We performed a retrospective cohort study of CD patients classified as elderly (age ≥ 65 years at UST initiation) or nonelderly (<65 years) treated at a large, tertiary referral center. Outcomes assessed were clinical (measured by physician global assessment [PGA]) and steroid-free response, remission, adverse events, and postsurgical complications were compared by age category. Multivariable regression modeling and survival analysis was also performed. RESULTS: In total, 117 patients (elderly n = 39, nonelderly n = 78) were included in the study. Elderly patients had predominantly moderate disease (87.2%), while nonelderly had a higher proportion of severe disease activity (44.9%) (p = 0.001), though no differences in baseline endoscopic activity, prior biologic use, or steroid or immunomodulator use at baseline existed (p > 0.05 all). While nearly 90% patients in both groups experienced clinical response to UST, compared to nonelderly, elderly patients were less likely to achieve complete clinical remission (28.2% vs. 52.6%, p = 0.01). On regression modeling, age was not associated with clinical outcomes (p > 0.05 all). Mucosal healing was achieved in 26% elderly and 30% nonelderly patients (p = 0.74). There were no significant differences in infusion reactions (2.6% vs. 6.4%, p = 0.77), infection (5.2% vs. 7.7%, p = 0.7), or postsurgical complications (p = 0.99) by age category. CONCLUSION: UST is safe and effective in elderly CD. Although limited by sample size and retrospective design, such real-world data can inform biologic positioning in this IBD population.

Genetic and population diversity of Toxocara cati (Schrank, 1788) Brumpt, 1927, on the basis of the internal transcribed spacer (ITS) region.

The present investigation was aimed to study the sequence, phylogenetic and haplotype analyses of Toxocara cati based on the ITS region, along with the genetic diversity, demographic history and population-genetic structure. The maximum likelihood tree based on Kimura 2-parameter model was constructed using the complete ITS region of all the nucleotide sequences (n = 57) of Toxocara spp. and other related ascarid worms available in the GenBank™. It placed all the sequences of T. cati into four major clades designated as T. cati genotypes 1-4 (TcG1-G4). A total of 66 signature nucleotides were identified in the ITS region between genotypes. The median-joining haplotype network displayed a total of 24 haplotypes, with China exhibiting the highest number of haplotypes (h = 20) followed by India (h = 4), and Japan and Russia (h = 1). It indicated a clear distinction between all the four genotypes. The pairwise FST values between all the genotypes indicated huge genetic differentiation (> 0.25) between different T. cati genotypes. Moreover, the gene flow (Nm) between T. cati genotypes was very low. Results of AMOVA revealed higher genetic variation between genotypes (92.82%) as compared to the variation within genotypes (7.18%). The neutrality indices and mismatch distributions for the G1-G4 genotypes, Indian isolates and the overall dataset of T. cati indicated either a constant population size or a slight population increase. The geographical distribution of all the genotypes of T. cati is also reported. This is the first report of genotyping of T. cati on the basis of the ITS region.

Spontaneous Internal Pancreatic Fistulae Complicating Acute Pancreatitis.

Spontaneous pancreatic fistula (PF) is a rare but challenging complication of acute pancreatitis (AP). The fistulae could be internal (draining into another viscera or cavity, e.g., pancreaticocolonic, gastric, duodenal, jejunal, ileal, pleural, or bronchial) or external (draining to skin, i.e., pancreaticocutaneous). Internal fistulae constitute the majority of PF and will be discussed in this review. Male sex, alcohol abuse, severe AP, and infected necrosis are the major risk factors for development of internal PF. A high index of suspicion is required to diagnose PF. Broad availability of computed tomography makes it the initial test of choice. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography have higher sensitivity compared with computed tomography scan and also allow for assessment of pancreatic duct for leak or disconnection, which affects treatment approaches. Certain complications of PF including hemorrhage and sepsis could be life-threatening and require urgent intervention. In nonurgent/chronic cases, management of internal PF involves control of sepsis, which requires effective drainage of any residual pancreatic collection/necrosis, sometimes by enlarging the fistula. Decreasing fistula output with somatostatin analogs (in pancreaticopleural fistula) and decreasing intraductal pressure with endoscopic retrograde cholangiopancreatography or endoscopic ultrasound/interventional radiology-guided interventions or surgery are commonly used strategies for management of PF. More than 60% of the internal PF close with medical and nonsurgical interventions. Colonic fistula, medical refractory-PF, or PF associated with disconnected pancreatic duct can require surgical intervention including bowel resection or distal pancreatectomy. In conclusion, AP-induced spontaneous internal PF is a complex complication requiring multidisciplinary care for successful management.

Hydrogen peroxide assisted endoscopic necrosectomy for walled-off pancreatic necrosis: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopic necrosectomy (EN) is the preferred approach for management of symptomatic or infected walled-off pancreatic necrosis (WOPN). Hydrogen peroxide (H2O2) has been reported to be a good adjunctive therapy for EN. We performed a systematic review and meta-analysis to evaluate effectiveness and safety of H2O2 assisted EN for WOPN. METHODS: A comprehensive search of multiple databases (through December 2020) was performed to identify studies that reported outcomes of H2O2 assisted EN for WOPN. Outcomes assessed included clinical success, technical success, and adverse events. RESULTS: A total of 454 patients with mean age (47.3 ± 7.9 years) and WOPN size (12.4 ± 3.1 cm) were included from 15 studies. The median H2O2 concentration was 3% (range 0.1-3%), with dilution and volume ranging from 1:1 to 10:1 and 20 ml to 1 L, respectively. The rates of technical success, clinical success and adverse events was 97.3% (95% confidence interval [CI]: 94.8-98.6, I2 = 0), 89.8% (95% CI: 86.3-92.5, I2 = 0) and 17.9% (95% CI: 12.6-24.7, I2 = 38), respectively. The most common adverse event was bleeding (7.1%) followed by stent migration (5.3%). On meta-regression, WOPN size, patient age, use of metal stent, number of necrosectomies and transgastric access were not significant predictor for technical success, clinical success or adverse events. CONCLUSION: H2O2 assisted EN is effective and safe for management of WOPN. Its use may be encouraged, and future randomized controlled studies are needed to study the optimal technique, concentration and best predictors of success.

Pancreatic cyst fluid glucose in differentiating mucinous from nonmucinous pancreatic cysts: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Recently, low levels of intracystic glucose acquired with EUS-guided pancreatic cyst fluid sampling have been shown to help to differentiate mucinous from nonmucinous cystic neoplasms. The aim of this study was to perform a systematic review and meta-analysis to evaluate the diagnostic characteristics of pancreatic cyst fluid glucose compared with carcinoembryonic antigen (CEA) for pancreatic cystic lesions. METHODS: Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines and meta-analysis analyzed according to Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristics curve for intracystic glucose or CEA alone or combination testing. RESULTS: Eight studies (609 lesions; mean patient age, 63.56 ± 2.75 years; 60.36% women) were included. The pooled sensitivity for pancreatic cyst fluid glucose was significantly higher compared with CEA alone (91% [95% confidence interval {CI}, 88-94; I2 = .00] vs 56% [95% CI, 46-66; I2 = 537.14]; P < .001) with no difference in specificity (86% [95% CI, 81-90; I2 = 24.16] vs 96% [95% CI, 90-99; I2 = 38.06]; P > .05). Diagnostic accuracy was significantly higher for pancreatic cyst fluid glucose versus CEA alone (94% [95% CI, 91-96] vs 85% [95% CI, 82-88]; P < .001). Combination testing with pancreatic cyst fluid glucose and CEA did not improve the diagnostic accuracy compared with glucose alone (97% [95% CI, 95-98] vs 94% [95% CI, 91-96]; P > .05). CONCLUSIONS: Low pancreatic cyst fluid glucose was associated with a high sensitivity and specificity with significantly improved diagnostic accuracy compared with CEA alone for the diagnosis of mucinous versus nonmucinous pancreatic cystic lesions.