17-Beta-Hydroxysteroid Dehydrogenase 13 Loss of Function Does Not Confer Protection to Nonalcoholic Fatty Liver Disease in Indian Population.

Background: A splice variant in HSD17B13 gene is demonstrated to protect against nonalcoholic fatty liver disease (NAFLD), and mitigate the effect of Patatin-like phospholipase domain-containing 3 (PNPLA3-I148M). It is being explored as a putative drug target and in polygenic risk scores. Based on whole exome sequencing (WES) in our cohort of biopsy proven NAFLD and limited data on the variant in our ethnicity, we sought to explore its role. Methods: This is a cross-sectional study that recruited 1,020 individuals with ultrasound/biopsy-confirmed NAFLD and matched controls. Liver enzymes and lipid profiles were estimated (Beckman coulter LX750/DXH800); WES was performed in NAFLD patients and controls (Illumina; HiSeqX); HSD17B13-A-INS/I148M-PNPLA3 variants were genotyped (sequencing/qR T-PCR); HSD17B13 protein expression was estimated (immunohistochemistry); the Student's t-test/Mann-Whitney U/Chi-square test and odds ratio (95% confidence interval) were used. Results: There was no significant difference (Odds ratio = 0.76; 95% CI -0.57 to 1.03; P = 0.76) in the frequency of the rs72613567-A-INS between controls and patients (17.8% vs. 14.4%). No difference in the ALT (Alanine transaminase; 72.24 ± 65.13 vs. 73.70 ± 60.06; P = 0.51) and AST levels (Aspartate aminotransferase; 60.72 ± 55.59 vs. 61.63 ± 60.33; P = 0.91) between HSD17B13-wild and variant carriers were noted. Significantly elevated liver enzymes were seen in PNPLA3-148-variant/HSD17B13-wild compared with PNPLA3-148-variant/HSD17B13-variant (90.44 ± 59.0 vs. 112.32 ± 61.78; P = 0.02). No difference in steatosis (P = 0.51) between HSD17B13-wild and variant carriers was noted. No other variants in the intron-exon boundaries were identified. Although, protein expression differences were noted between wild and variant carriers, no difference in the extent of steatosis was seen. Conclusion: Our study reports lack of association of the splice variant with reduced risk of NAFLD, and mitigating the effect of PNPLA3 variant. Ethnicity-based validation must be carried out before including it in assessing protection against NAFLD.

Impact of modified techniques on outcomes of peroral endoscopic myotomy: A narrative review.

Peroral endoscopic myotomy (POEM) is an established frontline treatment modality for achalasia cardia. Since its initial description, several modifications have been proposed to the technique of POEM. Broadly speaking, these modifications follow the basic principles of submucosal endoscopy, but incorporate variations in the POEM technique, including the difference in the orientation of myotomy (anterior or posterior), length of myotomy (short or long), and thickness of myotomy (selective circular or full thickness). Some of these modifications have been shown to reduce procedural duration without compromising the efficacy of the POEM procedure. More recently, several alterations have been reported that intend to reduce gastroesophageal reflux after POEM. These include preservation of sling fibers during posterior POEM and addition of NOTES fundoplication to the POEM procedure. Although some of the modified techniques have been compared with the conventional techniques in quality trials, randomized studies are awaited for others. The incorporation of some of these modifications will likely make POEM a technically easy and safer modality in near future. This review aims to discuss the current evidence with regard to the impact of modified techniques on the outcome of POEM.

Clinical outcomes in individuals hospitalized with SARS-CoV-2 Delta variant (B.1.617.2) who had been vaccinated with Covishield (ChAdOx1) and Covaxin (BBV-152).

Background: Covishield (ChAdOx) and Covaxin (BBV-152) are the mainstream vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) used in India and a few other countries. Objective: To assess the clinical outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) who had been vaccinated with either Covishield or Covaxin. Methods: This prospective, single-centre, observational cohort study of 1160 patients hospitalized with COVID-19 was conducted between April and June 2021. Severity of disease at admission and during hospitalization, requirement for intensive care unit (ICU) admission and ventilatory support, inflammatory markers (C-reactive protein, ferritin, lactate dehydrogenase, D-dimer), neutralizing antibody levels and mortality were assessed in vaccinated and unvaccinated patients. Results: More than 90% of patients in this study harboured the Delta variant (Pango lineage B.1.617.2) of SARS-CoV-2. Severity of disease at admission and during hospitalization (3.44% vs 7.51%; P=0.0032) and requirement for ICU admission and ventilatory support (2.83% vs 5.86%; P=0.0154) were significantly lower in vaccinated patients compared with unvaccinated patients. Vaccinated patients also had significantly (P<0.0001) higher antibody levels and lower inflammatory marker levels compared with unvaccinated patients. A subset of vaccinated, deceased patients mounted minimal antibody response ['non-responders': 4.53 (standard deviation 1.40) AU/mL]. Conclusion: These results demonstrate the effectiveness of Covishield and Covaxin against severe disease in patients hospitalized with COVID-19 with breakthrough infections caused by the Delta variant. Strategies targeting non-responders are desirable to minimize morbidity and mortality.

Clinical outcomes in vaccinated individuals hospitalized with Delta variant of SARS-CoV-2

Emerging variants of SARS-CoV-2 with increased transmissibility or immune escape have been causing large outbreaks of COVID-19 infections across the world. As most of the vaccines currently in use have been derived from viral strains circulating in the early part of the pandemic, it becomes imperative to constantly assess the efficacy of these vaccines against emerging variants. In this hospital-based cohort study, we analysed clinical profiles and outcomes of 1161 COVID-19 hospitalized patients (vaccinated with COVISHIELD (ChAdOx1) or COVAXIN (BBV-152), n = 495 and unvaccinated n = 666) in Hyderabad, India between April 24th and May 31st 2021. Viral genome sequencing revealed that >90% of patients in both groups were harbouring the Delta variant (Pango lineage B.1.617.2) of SARS-CoV-2. Vaccinated individuals showed higher neutralizing antibodies (545{+/-}1256 AU/ml Vs 51.1{+/-}296 AU/ml; p<0.001) and significantly decreased Ferritin (392.26 {+/-} 448.4 ng/mL Vs 544.82 {+/-} 641.41 ng/mL; p<0.001) and LDH (559.45 {+/-} 324.05 U/L Vs 644.99 {+/-} 294.03 U/L; p<0.001), when compared to the unvaccinated group. Severity of the disease (3.2% Vs 7.2%; p=0.0039) and requirement of ventilatory support (2.8% Vs 5.9%; p=0.0154) were significantly low in the vaccinated group despite the fact that these individuals had significantly higher age and risk factors. The rate of mortality was about 50% lower (2/132=1.51%) in the completely vaccinated breakthrough infections although mortality in individuals who had received a single dose was similar to the unvaccinated group (9/269=3.35% vs 23/666= 3.45%). Our results demonstrate that both COVISHIELD and COVAXIN are effective in preventing disease severity and mortality against the Delta variant in completely vaccinated hospitalized patients.

Fatty acid ethyl ester (FAEE) associated acute pancreatitis: An ex-vivo study using human pancreatic acini.

BACKGROUND & AIM: Fatty acid ethyl esters (FAEEs), are produced by non-oxidative alcohol metabolism and can cause acinar cell damage and subsequent acute pancreatitis in rodent models. Even though experimental studies have elucidated the FAEE mediated early intra-acinar events, these mechanisms have not been well studied in humans. In the present study, we evaluate the early intra-acinar events and inflammatory response in human pancreatic acinar tissues and cells in an ex-vivo model. METHODS: Experiments were conducted using normal human pancreatic tissues exposed to FAEE. Subcellular fractionation was performed on tissue homogenates and trypsin and cathepsin B activities were estimated in these fractions. Acinar cell injury was evaluated by histology and immunohistochemistry. Cytokine release from exposed acinar cells was evaluated by performing Immuno-fluorescence. Serum was collected from patients with AP within the first 72 h of symptom onset for cytokine estimation using FACS. RESULTS: We observed significant trypsin activation and acinar cell injury in FAEE treated tissue. Cathepsin B was redistributed from lysosomal to zymogen compartment at 30 min of FAEE exposure. IHC results indicated the presence of apoptosis in pancreatic tissue at 1 & 2hrs of FAEE exposure. We also observed a time dependent increase in secretion of cytokines IL-6, IL-8, TNF-α from FAEE treated acinar tissue. There was also a significant elevation in plasma cytokines in patents with alcohol associated AP within 72 h of symptom onset. CONCLUSION: Our data suggest that alcohol metabolites can cause acute acinar cell damage and subsequent cytokine release which could eventually culminant in SIRS.

Reduced pancreatic polypeptide response is associated with early alteration of glycemic control in chronic pancreatitis.

AIM: To study the incidence of glucose intolerance in CP patients without diabetes by performing oral glucose tolerance test (OGTT). METHODS: We screened consecutive Indian CP patients without diabetes over 6 months by performing OGTT and correlated with physical characteristics and glycated hemoglobin (HbA1c). We also compared c-peptide and pancreatic polypeptide response in different groups based on OGTT. Relevant statistical tests were performed. P < 0.05 was considered significant. RESULTS: Total of 171 patients were screened. Mean duration of CP was 5.03 ± 4.32 years. 55 were detected to have prediabetes and 40 DM on OGTT. CP patients with diabetes and prediabetes had significantly dilated pancreatic duct compared to non-diabetic CP (4.2 ± 2.7 mm, 3.6 ± 2.7 mm, 2.84 ± 2.25 mm; p = 0.018). Fasting blood glucose (FBS) and 2-hour OGTT were 109.35 ± 19.06, 97.47 ± 11.94, 85.24 ± 9.95 and 236.13 ± 31.42, 154.65 ± 19.53, 112.89 ± 16.32 in patients with DM, prediabetes and CP patients without diabetes (p < 0.0001). There was a good c-peptide response (p = 0.001) and reduced pancreatic polypeptide response (p = 0.003) in CP patients compared to controls. CONCLUSION: Early in the course of disease reduced pancreatic polypeptide response in the presence of good c-peptide response may result in development of DM.

ESWL for large pancreatic calculi: Report of over 5000 patients.

INTRODUCTION: The primary aim of this study was to evaluate efficacy, safety and short-term pain relief after ESWL for large pancreatic calculi in over 5000 patients at a single center. METHODS: This is a retrospective analysis of prospectively collected data. Patients with painful calculi >5 mm, located in the head, neck and body region in the MPD, who were not amenable for extraction by the standard procedure of endoscopic pancreatic sphincterotomy were subjected to ESWL using a third generation dual focus lithotripter. Patients were followed up at 6 months for outcome evaluation. RESULTS: A total of 5124 patients (66% males) were subjected to ESWL. Majority of stones (79.2%) were radiopaque. Single calculi were seen in 3851 (75.1%).The majority of stones were located in head region of MPD in 2824 (55.1%) patients. 4386 (85.5%) patients required 3 or less sessions for fragmentation and complete stone clearance was achieved in 3722 (72.6%). EPS was performed in 5022 (98%) while PD stenting was required in 3536 (69%) patients. Of the 4280 patients followed up for 6 months, 3529 (82.6%) patients were pain free. Another 512 (11.9%) patients had significant reduction in VAS score. In 229 (5.3%) there was no decrease in pain intensity. Minor and self-limiting complications were reported in 1153 (22.5%). DISCUSSION: Our study confirms the safety and efficacy and short-term pain relief of ESWL for large calculi in the MPD. In properly selected patients, this should be offered as the first line of therapy for all large MPD calculi not amenable to the standard techniques of stone extraction.

Distal pancreatectomy with autologous islet transplantation in chronic pancreatitis patients: First case series from India.

Pancreatectomy and autologous islet transplantation (AIT) are performed in highly specialized centers to alleviate abdominal pain and preserve endocrine function in patients with chronic pancreatitis. We aimed at initiating AIT studies in India for the first time in patients undergoing distal pancreatectomy (DP) to prevent development of diabetes. Four out of 14 chronic pancreatitis patients screened underwent DP with AIT. Pancreatectomy specimen preserved in Wisconsin solution was subjected to islet isolation employing standard protocol using collagenase V. Isolated islets were infused into the liver through portal vein after quality assessment and the four patients were followed for 1 year. During the study period, blood glucose, fasting insulin, and C-peptide were analyzed and glucose tolerance was assessed. Three patients could be infused with islets (4363 Islet equivalents, IEQ/kg, 3860 IEQ/kg, 3600 IEQ/kg) into liver without any infusion-related complications. Two of these patients maintained glucose tolerance and glycemic control (HbA1c: 6.0%) and one became diabetic at the end of 1 year (HbA1c: 7.5%). Circulating fasting insulin increased (2.7-24.4 µU/mL and 4.0-21.2 µU/mL) and C-peptide levels increased (2.2 to 3.6, 3.4-5.6 ng/mL) in these two patients. Circulating insulin was 2.7 µU/mL and C-peptide was 2.4 ng/mL in the patient who became diabetic at the end of 1 year, while insulin was 2.3 µU/mL and C-peptide was 1.2 ng/mL in the patient who could not be infused with islets after DP. Safety and feasibility of autologous islet transplantation is established in India for the first time.

Recent Advances in Third-Space Endoscopy.

The capabilities of interventional gastrointestinal endoscopy have significantly increased over the past several decades. Improvements in devices and techniques have eased the transfer of novel concepts from bench to bedside. The concept of submucosal endoscopy with mucosal flap safety valve has enabled endoscopists to securely use submucosal space, or third space. Peroral endoscopic myotomy was the initial procedure performed utilizing submucosal space in patients with achalasia. Subsequently, this technique has been used successfully for removal of subepithelial tumors from the esophagus and the stomach. All third-space endoscopy procedures use a similar technique-a submucosal tunnel is created, and then a myotomy is performed or a subepithelial tumor is dissected away from the initial site of the mucosal incision. The other potential indications for third-space endoscopy include refractory gastroparesis, Zenker diverticulum, and restoration of completely obstructed esophageal lumen. Although the emerging data look promising for peroral endoscopic myotomy and pyloromyotomy, randomized studies with long-term follow-up are lacking. Submucosal endoscopy is largely safe, and the occurrence of major adverse events is uncommon. Therefore, the majority of third-space endoscopy procedures can be performed in an endoscopy suite. The most frequently encountered adverse events during submucosal endoscopy include those related to insufflation, bleeding, and perforations.

Management of achalasia cardia: Expert consensus statements.

Achalasia cardia (AC) is a frequently encountered motility disorder of the esophagus resulting from an irreversible degeneration of neurons. Treatment modalities are palliative in nature, and there is no curative treatment available for AC as of now. Significant advancements have been made in the management of AC over last decade. The introduction of high resolution manometry and per-oral endoscopic myotomy (POEM) has strengthened the diagnostic and therapeutic armamentarium of AC. High resolution manometry allows for the characterization of the type of achalasia, which in turn has important therapeutic implications. The endoscopic management of AC has been reinforced with the introduction of POEM that has been found to be highly effective and safe in palliating the symptoms in short-term to mid-term follow-up studies. POEM is less invasive than Heller's myotomy and provides the endoscopist with the opportunity of adjusting the length and orientation of esophageal myotomy according to the type of AC. The management of achalasia needs to be tailored for each patient, and the role of pneumatic balloon dilatation, POEM, or Heller's myotomy needs to be revisited. In this review, we discuss the important aspects of diagnosis as well as management of AC. The statements presented in the manuscript reflect the cumulative efforts of an expert consensus group.

Treatment of gastroesophageal reflux disease using radiofrequency ablation (Stretta procedure): An interim analysis of a randomized trial.

BACKGROUND: Gastroesophageal reflux disease (GERD) is the most common chronic gastrointestinal disorder, affecting one third of the population worldwide. Recently, there has been a renewed interest in Stretta therapy in view of potential long-term side effects of PPIs and the durability of relief with fundoplication. METHOD: Prospective randomized study comparing the Stretta treatment with controls receiving PPIs. Patient (> 18 years, n = 20) with symptoms of heartburn, regurgitation, abnormal esophageal acid exposure (≥ 4%), and endoscopically confirmed esophagitis were included into the study. The primary measure was improvement in quality of life (QOL) and decrease in the frequency and severity of GERD symptoms. RESULTS: The mean age of the patients was 39 (± 15) years and controls were 34 (± 11) years. Three months after Stretta, 80% reported improvement in QOL compared to 40% in the control group. At the end of 3 months, significant (p < 0.05) improvement in GERD symptom score for heartburn, regurgitation, chest pain, and cough compared with the control group was observed. After Stretta treatment, 60% of the patients were free of PPIs whereas there was no change in the control group. Almost 80% of the patients on Stretta treatment were satisfied with the treatment compared to 30% of the patients in the control group. CONCLUSION: Stretta was effective in the short-term for the management of GERD.

Anesthesia in per-oral endoscopic myotomy: A large tertiary care centre experience.

BACKGROUND AND OBJECTIVES: Per-oral endoscopic myotomy (POEM) is safe and efficacious for the management of achalasia cardia (AC). POEM is usually performed under general anesthesia in an endoscopy suite or operating theatre. The current study was conducted with the aim to analyse anesthetic management of patients with AC who underwent POEM at our institution. METHODS: We retrospectively analysed the data of patients with AC who underwent POEM at our institution from January 2013 to September 2016. All cases were performed in an endoscopy suite under supervision of an anesthesia management team. Pre-procedure endoscopic evacuation of esophagogastric contents was done in all cases. Management strategies used for gas-related adverse events and outcomes were assessed. RESULTS: Four hundred and eighty patients (median age 40 years, range 4-77 years) underwent POEM during the study period. The sub-types of AC were type I (163), type II (297), and type III (20). POEM was successfully completed in 97.5% patients. Gas-related events were noted in 30.6% cases including-capno-thorax in 1%, capno-peritoneum in 12.3%, retroperitoneal air in 16.5%, capno-mediastinum in 0.2%, and capno-pericardium in 0.4% patients. Significant rise in end tidal CO2 (> 45) and peak airway pressure were observed in 8.1% and 5.4% cases, respectively. Drainage was required in 12.3% patients. There was no occurrence of aspiration during or after POEM. CONCLUSIONS: POEM could be safely performed in an endoscopy suite under supervision of an expert anesthesia management team. Gas-related adverse events were common during POEM and could be managed with a standardized approach.

Endoscopic drainage of pancreatic fluid collections: Long-term outcomes in children.

BACKGROUND AND AIM: Endoscopic drainage of pancreatic fluid collections (PFC) is the standard of care in adult patients. The literature is limited in children. In the present study, we aim to evaluate the safety and long-term efficacy of endoscopic ultrasound (EUS)-guided drainage of PFC in children. METHODS: Data of all children (<18 years) with PFC who underwent EUS-guided drainage with plastic stents were analyzed retrospectively for technical feasibility, clinical efficacy and adverse events (AE). RESULTS: Thirty children (boys 22, girls 8) with PFC underwent EUS drainage (January 2013 to June 2016). Mean age of children was 13.07 ± 3.41 years (5-17 years). Majority of children had idiopathic pancreatitis (23), followed by trauma-related (6) and gallstone-related pancreatitis (1). Of 30 PFC, 13 (43.3%) and 17 (56.7%) were classified as pseudocyst and walled-off necrosis, respectively. Median size of PFC was 95 mm (61-175). EUS drainage was successfully completed in 29 children (technical success 96.7%). Clinical success was achieved in 28/30 (93.3%) children. AE included perforation (2), major bleed (1), minor bleed (2), stent migration (4) and readmission as a result of hematemesis (1). Imaging revealed disconnected pancreatic duct in nine, ductal leak in two and stricture in one child. Cystogastric stents were left in situ in children with disconnected duct. At median follow up of 829 days (150-1230), two recurrences of PFC were noticed. CONCLUSIONS: EUS-guided drainage using plastic stents is safe and effective in children with PFC. Cystogastric plastic stents can be left safely long term. However, more studies with larger sample sizes are required.

Giant Intrahepatic Portal Vein Aneurysm: Leave it or Treat it?

Portal vein aneurysm (PVA) is a rare vascular dilatation of the portal vein. It is a rare vascular anomaly representing less than 3% of all visceral aneurysms and is not well understood. Usually, PVA are incidental findings, are asymptomatic, and clinical symptoms are proportionally related to size. Patients present with nonspecific epigastric pain or gastrointestinal bleeding with underlying portal hypertension. PVA may be associated with various complications such as biliary tract compression, portal vein thrombosis/rupture, duodenal compression, gastrointestinal bleeding, and inferior vena cava obstruction. Differential diagnoses of portal vein aneurysms are solid, cystic, and hypervascular abdominal masses, and it is important that the radiologists be aware of their multi-modality appearance; hence, the aim of this article was to provide an overview of the available literature to better simplify various aspects of this rare entity and diagnostic appearance on different modality with available treatment options. In our case, a 55-year-old male patient came to the gastroenterology OPD for further management of pancreatitis with portal hypertension and biliary obstruction with plastic stents in CBD and PD for the same. In this article, we have reported a case of largest intrahepatic portal vein aneurysm and its management by endovascular technique. As per our knowledge, this is the largest intrahepatic portal vein aneurysm and first case where the endovascular technique was used for the treatment of the same.