Pramod Garg

Acute variceal bleeding (AVB) is a medical emergency and associated with a mortality of 20% at 6 weeks. Significant advances have occurred in the recent past and hence there is a need to update the existing consensus guidelines. There is also a need to include the literature from the Eastern and Asian countries where majority of patients with portal hypertension (PHT) live.The expert working party, predominantly from the Asia-Pacific region, reviewed the existing literature and deliberated to develop consensus guidelines. The working party adopted the Oxford system for developing an evidence-based approach. Only those statements that were unanimously approved by the experts were accepted.AVB is defined as a bleed in a known or suspected case of PHT, with the presence of hematemesis within 24 h of presentation, and/or ongoing melena, with last melanic stool within last 24 h. The time frame for the AVB episode is 48 h. AVB is further classified as active or inactive at the time of endoscopy. Combination therapy with vasoactive drugs (<30 min of hospitalization) and endoscopic variceal ligation (door to scope time <6 h) is accepted as first-line therapy. Rebleeding (48 h of T (0)) is further sub-classified as very early rebleeding (48 to 120 h from T (0)), early rebleeding (6 to 42 days from T (0)) and late rebleeding (after 42 days from T (0)) to maintain uniformity in clinical trials. Emphasis should be to evaluate the role of adjusted blood requirement index (ABRI), assessment of associated comorbid conditions and poor predictors of non-response to combination therapy, and proposed APASL (Asian Pacific Association for Study of the Liver) Severity Score in assessing these patients. Role of hepatic venous pressure gradient in AVB is considered useful. Antibiotic (cephalosporins) prophylaxis is recommended and search for acute ischemic hepatic injury should be done. New guidelines have been developed for management of variceal bleed in patients with non-cirrhotic PHT and variceal bleed in pediatric patients.Management of acute variceal bleeding in Asia-Pacific region needs special attention for uniformity of treatment and future clinical trials.

<h3>Background & Aims</h3> Experimental studies in acute pancreatitis (AP) suggest a strong association of acinar cell injury with cathepsin B–dependent intracellular activation of trypsin. However, the molecular events subsequent to trypsin activation and their role, if any, in cell death is not clear. In this study, we have explored intra-acinar events downstream of trypsin activation that lead to acinar cell death. <h3>Methods</h3> Acinar cells prepared from the pancreas of rats or mice (wild-type, trypsinogen 7, or cathepsin B–deleted) were stimulated with supramaximal cerulein, and the cytosolic activity of cathepsin B and trypsin was evaluated. Permeabilized acini were used to understand the differential role of cytosolic trypsin vs cytosolic cathepsin B in activation of apoptosis. Cell death was evaluated by measuring specific markers for apoptosis and necrosis. <h3>Results</h3> Both in vitro and in vivo studies have suggested that during AP cathepsin B leaks into the cytosol from co-localized organelles, through a mechanism dependent on active trypsin. Cytosolic cathepsin B but not trypsin activates the intrinsic pathway of apoptosis through cleavage of bid and activation of bax. Finally, excessive release of cathepsin B into the cytosol can lead to cell death through necrosis. <h3>Conclusions</h3> This report defines the role of trypsin in AP and shows that cytosolic cathepsin B but not trypsin activates cell death pathways. This report also suggests that trypsin is a requisite for AP only because it causes release of cathepsin B into the cytosol.

Health-care-associated infections (HAIs) cause significant morbidity and mortality globally, including in low-income and middle-income countries (LMICs). Networks of hospitals implementing standardised HAI surveillance can provide valuable data on HAI burden, and identify and monitor HAI prevention gaps. Hospitals in many LMICs use HAI case definitions developed for higher-resourced settings, which require human resources and laboratory and imaging tests that are often not available.A network of 26 tertiary-level hospitals in India was created to implement HAI surveillance and prevention activities. Existing HAI case definitions were modified to facilitate standardised, resource-appropriate surveillance across hospitals. Hospitals identified health-care-associated bloodstream infections and urinary tract infections (UTIs) and reported clinical and microbiological data to the network for analysis.26 network hospitals reported 2622 health-care-associated bloodstream infections and 737 health-care-associated UTIs from 89 intensive care units (ICUs) between May 1, 2017, and Oct 31, 2018. Central line-associated bloodstream infection rates were highest in neonatal ICUs (>20 per 1000 central line days). Catheter-associated UTI rates were highest in paediatric medical ICUs (4·5 per 1000 urinary catheter days). Klebsiella spp (24·8%) were the most frequent organism in bloodstream infections and Candida spp (29·4%) in UTIs. Carbapenem resistance was common in Gram-negative infections, occurring in 72% of bloodstream infections and 76% of UTIs caused by Klebsiella spp, 77% of bloodstream infections and 76% of UTIs caused by Acinetobacter spp, and 64% of bloodstream infections and 72% of UTIs caused by Pseudomonas spp.The first standardised HAI surveillance network in India has succeeded in implementing locally adapted and context-appropriate protocols consistently across hospitals and has been able to identify a large number of HAIs. Network data show high HAI and antimicrobial resistance rates in tertiary hospitals, showing the importance of implementing multimodal HAI prevention and antimicrobial resistance containment strategies.US Centers for Disease Control and Prevention cooperative agreement with All India Institute of Medical Sciences, New Delhi.For the Hindi translation of the abstract see Supplementary Materials section.

Current knowledge about chronic pancreatitis (CP) is limited and there is a particular dearth of information about the entity known as tropical pancreatitis. A consensus working party was convened by the Trustees of the Journal of Gastroenterology and Hepatology Foundation to conduct a systematic investigation into available evidence about the epidemiology, etiopathogenesis, diagnosis and management of CP. A literature search and formal survey of international experts in the field were used to assemble reliable evidence about these issues. The present review summarizes the results of the working party's findings and presents a series of practice guidelines to improve diagnosis, investigation and treatment of patients with CP, particularly those in the Asia-Pacific region. Areas for further research have also been identified.

Subclinical hepatic encephalopathy (SHE) features in 30-84% of patients with cirrhosis of the liver. Its clinical significance with regards to progression to overt encephalopathy has however, not been established.The present study was conducted (i) to compare the diagnostic usefulness of neuropsychological tests with that of electrophysiological (EP) tests in detection of SHE, and (ii) to examine the natural course of SHE.Seventy-five-nonencephalopathic cirrhotics (11 females, 64 males; mean (+/- SD) age 43.6 (+/- 11.7) years; mean (+/- SD) education 11(+/- 3) years) were studied using a battery of tests for intelligence and memory, the number connection test (NCT), and EP tests viz. electroencephalogram (EEG) and auditory P300 event related potentials (P3ERP). All the patients were followed up for a period of 6 months to 2 years for development of overt encephalopathy.Thirty-five out of 75(47%) patients were diagnosed to have SHE based on at least one abnormal test result. The P3ERP latencies detected SHE in maximum number of patients (23%) followed by EEG (21%). Nearly 59% of patients with SHE progressed to overt encephalopathy within a mean duration of 4 months. Multivariate analysis showed that prior episode of encephalopathy (RR = 6.3; 95% CI = 2.0-19.7), abnormality on EEG (RR = 7.5; 95% CI = 2.2-25.3), abnormal performance on psychometric battery of tests (RR = 35.2; 95% CI = 4.3-287.3), occurrence of gastrointestinal bleed (RR = 19.3; 95% CI = 4.1-88.9), occurrence of dehydration (RR = 10.7; 95% CI = 2.5-45.4) and infection (RR = 11.4; 95% CI = 2.0-64.4) had significantly higher risk for development of overt encephalopathy.EP methods were more sensitive in detection of SHE. Amongst all the tests used, presence of only an abnormal EEG was significantly associated with development of overt encephalopathy along with the precipitating factors.

<h3>Objective</h3> To study the genetic predisposition, phenotype and prognosis of idiopathic chronic pancreatitis (CP). <h3>Design</h3> Prospective observational and case–control study. <h3>Setting</h3> Tertiary care academic centre. <h3>Patients</h3> Consecutive patients with CP. <h3>Interventions</h3> Detailed mutational analysis was done for the cationic trypsinogen, <i>SPINK1</i> and <i>CFTR</i> genes with single-strand conformational polymorphism or restricted fragment length polymorphism, and sequencing. Clinical and disease characteristics of idiopathic versus alcoholic CP, and early onset versus late onset idiopathic CP were compared. Response to multimodality treatment (medical, endoscopic and/or surgical) and prognosis were analysed. <h3>Main outcome measures</h3> Genetic mutations, phenotypic characterisation and prognosis of idiopathic CP. <h3>Results</h3> Of the 411 patients with CP, 242 had idiopathic aetiology (age 27.50±11.85 years; 154 men). Malnutrition and cassava were not risk factors. <i>SPINK1</i> N34S mutation was present in 42% of patients with idiopathic CP (vs 4% controls, p&lt;0.001) and 17% of patients with alcoholic CP (p=0.016 compared with controls). In the <i>CFTR</i> gene, nine patients with idiopathic CP had mutations and 41 patients had polymorphisms (50% vs 10% controls, p&lt;0.001). Diabetes developed in 35.53% of patients with idiopathic CP. About 85% of patients had significant pain relief with therapy. The probability of surviving for 35 years after onset of idiopathic CP was 83%. The typical features of tropical calcific pancreatitis were seen only in 5.8% of patients. <h3>Conclusion</h3> Strong genetic susceptibility due to <i>SPINK1</i> and <i>CFTR</i> gene mutations, and comparative phenotype of idiopathic CP in India suggest that the term ‘tropical calcific pancreatitis’ is a misnomer.

Chronic pancreatitis is common in India. However, its risk factors are not clear. There is sparse data on the current prevalence of tropical pancreatitis in India.To undertake a prospective nationwide study of the risk factors and clinical profile of chronic pancreatitis.Thirty-two major centers from different regions of India contributed data on 1,086 patients to a common online website (www.ipans.org).Risk factors, clinical features complications and treatment of chronic pancreatitis.Of the 1,086 subjects, complete data on risk factors were available for 1,033 subjects. Idiopathic pancreatitis was the most common form of pancreatitis (n=622; 60.2%) and alcoholic chronic pancreatitis accounted for about a third of the cases (n=400; 38.7%); the rest (n=11; 1.1%) had rare risk factors. Smoking and cassava intake were documented in 292 (28.3%) and 189 (18.3%) subjects, respectively. Using well-defined criteria, only 39 (3.8%)cases could be labeled as 'tropical pancreatitis'. Pain occurred in 971 patients (94.0%). Four hundred and eighteen (40.5%) subjects had diabetes mellitus. Of alcohol consumers, alcoholism and female gender were independent risk factors for diabetes in subjects with chronic pancreatitis (OR=1.48, P=0.003; and OR=1.75, P<0.001, respectively). The most common complications were pseudocysts (15.8%) and biliary obstruction (8.2%). Pancreatic cancer occurred in 42 subjects (4.1%). Ultrasound detected calculi in 69.7%, ductal dilatation in 63.4% and atrophy in 27.3%. The majority of patients were on medical therapy (n=849; 82.2%); endotherapy and surgery accounted for the rest. About 50% percent of the patients with diabetes required insulin (198/418).In this first nationwide prospective survey of chronic pancreatitis in India, idiopathic pancreatitis was the most common form, followed by alcoholic pancreatitis. The classical form of tropical chronic pancreatitis is becoming less common.

Abstract Background and Aims: The P300 event‐related potentials (P3ERP) have been recently advocated for detection of cognitive disturbances in early encephalopathy. However, no systematic follow‐up study has been conducted to understand the clinical significance of subclinical hepatic encephalopathy (SHE) detected by this or other methods. The present study was therefore undertaken to examine the diagnostic usefulness of auditory P3ERP in the detection of SHE, to compare it with that of the number connection test (NCT), and to investigate the clinical outcome of patients with SHE in terms of progression to overt encephalopathy. Methods: P300 event‐related potential latencies were measured and the NCT time was recorded in 81 non‐encephalopathic cirrhotic patients (Aged 43.8 ± 11 years, 23 alcoholic and 58 non‐alcoholics) attending the outpatient department at our tertiary care hospital (All India Institute of Medical Sciences Hospital). Cut‐off values for abnormality in the tests were developed from age‐, sex‐ and education‐matched controls. Patients were followed up at regular intervals for the development of overt encephalopathy, and the identifiable precipitating factors were noted. The P3ERP latencies (363 ± 34 msec vs 349 ± 23 msec), as well as NCT time (54.6 ± 30.6 s vs 39.5 ± 15.8 s) were significantly prolonged ( P &lt; 0.01) in patients with liver cirrhosis when compared with the non‐cirrhotic controls. Results: The P3ERP defects were seen in 24.6% of cirrhotic patients, while NCT time was prolonged in 19.7% of the patients. Nearly 43% of the patients with SHE progressed to overt encephalopathy within a mean duration of 5 months, while only 3.9% of the non‐SHE patients did so. Of the patients who developed overt encephalopathy, 64.2% had P3ERP latency prolongations while 35.7% had abnormal NCT. Conclusions: The results of the present study suggest that P3ERP and NCT are valid tools for the screening of SHE in cirrhotic patients as there is a greater likelihood of overt encephalopathy development in patients with an abnormality detected by these tests than in patients with no such abnormality.

Abstract Antituberculosis drug-induced hepatotoxicity is quite common. However, factors predicting its development are still controversial. The objective of the present study was to evaluate the role of certain factors (age and sex of the patient, alcoholism, chronic liver disease, hepatitis B virus carrier status, acetylator status, nutritional status and antituberculosis treatment (ATT) regimen) in predicting the development of ATT-induced hepatitis. In a case-control study, 60 consecutive patients with evidence of ATT-induced hepatitis were studied to assess the possible association of the above-mentioned factors with ATT-induced hepatitis. Body mass index was found to be significantly lower in ATT-induced hepatitis patients (17.2 +/- 2.7) than in controls (19.5 +/- 3.3) (p &amp;lt; 0.05). Pyrazinamide was used in addition to isoniazid and rifampicin in a significantly higher percentage of patients in the ATT-induced hepatitis group (70%) as compared with those in the control group (42%). No significant differences were observed between the two groups with regard to the rest of the parameters.

A recently emerged sub-lineage of Omicron, BA.5, together with BA.4, caused a fifth wave of coronavirus disease (COVID-19) in South Africa and subsequently emerged as a predominant strain globally due to its high transmissibility. The lethality of BA.5 infection has not been studied in an acute hACE2 transgenic (hACE2.Tg) mouse model. Here, we investigated tissue-tropism and immuno-pathology induced by BA.5 infection in hACE2.Tg mice. Our data show that intranasal infection of BA.5 in hACE2.Tg mice resulted in attenuated pulmonary infection and pathology with diminished COVID-19-induced clinical and pathological manifestations. BA.5, similar to Omicron (B.1.1.529), infection led to attenuated production of inflammatory cytokines, anti-viral response and effector T cell response as compared to the ancestral strain of SARS-CoV-2, Wuhan-Hu-1. We show that mice recovered from B.1.1.529 infection showed robust protection against BA.5 infection associated with reduced lung viral load and pathology. Together, our data provide insights as to why BA.5 infection escapes previous SARS-CoV-2 exposure induced-T cell immunity but may result in milder immuno-pathology and alleviated chances of re-infectivity in Omicron-recovered individuals.

The clinical profile of antituberculosis treatment (ATT)-induced hepatotoxicity is variable, and the reintroduction of ATT in patients who have developed such injury is controversial. We conducted a prospective study to determine the clinical profile in patients with ATT-induced hepatotoxicity and to test a predefined strategy of reintroduction of ATT. Seventy-two consecutive patients with clinical evidence of ATT-induced hepatotoxicity were included. Jaundice was the presenting symptom in 44 (61%) patients; prodromal symptoms were present in 28 (39%). Serious complications developed in 12 (16.6%) patients (fulminant hepatic failure in seven, subacute hepatic failure in four, hepatic encephalopathy in one). Nine patients (three males, six females) died from these complications. The mean duration of treatment before the onset of hepatitis was significantly longer in the group that died (53.22 +/- 36.22 days) than in the rest of the patients (31.07 +/- 30.30 days; p < 0.01). Malnutrition was present in 37 of the 72 patients. After resolution of drug induced hepatitis, reintroduction of isoniazid and rifampicin was possible in 41 of 44 patients. Thus, our results showed that ATT-induced hepatitis carried significant morbidity and mortality, that malnutrition was common in patients with ATT-related hepatitis, and that potentially hepatotoxic antituberculosis agents could be safely reintroduced after recovery from hepatitis.

Abstract Background and Aim: Secondary infection of pancreatic necrotic tissue and peripancreatic fluid is a serious complication of acute pancreatitis resulting in significant morbidity and mortality. The aim of this study was to find out the spectrum of bacterial infections, and their antibiotic sensitivity pattern in patients with acute pancreatitis. Methods: All consecutive patients with acute pancreatitis were studied prospectively. Detailed investigations were carried out to identify bacterial infections and their antibiotic sensitivities in patients with suspected infection. These investigations included cultures of various body fluids, throat swabs, indwelling cannula and catheter tips. Pancreatic tissue was obtained by using needle aspiration or at surgery for Gram's stain, culture and sensitivity. All cultures were repeated until the presence of infection was confirmed or excluded. Results: A total of 169 patients with acute pancreatitis were studied during the period between January 1997 and June 2000 (mean age 41.3 years; 116 males and 53 females). Of the 169 patients, 63 had infections at various sites. A total of 80 cultures were positive, and 12 different bacterial isolates were cultured from samples taken from these 63 patients. Polymicrobial infection was seen in 32% of patients. Twenty‐four patients had a confirmed pancreatic infection. Blood cultures had a growth of organisms in 19 patients, with evidence of ongoing or worsening pancreatitis, thus raising a strong suspicion of infected necrosis in them. The commonest organisms were Escherichia coli from 20 cultures and Pseudomonas aeruginosa from 18 cultures. The antibiotic sensitivity pattern showed that most bacteria were sensitive to third generation cephalosporins and quinolones; notably among them were cefotaxime, ceftazidime, and ciprofloxacin. Conclusion: Bacterial infections were seen in 37% of patients with acute pancreatitis. The commonest organisms were Pseudomonas aeruginosa and Escherichia coli . Most bacterial isolates were sensitive to third generation cephalosporins and quinolones.

Several factors have been suggested to mediate pain in patients with chronic pancreatitis. However, it is unknown whether these factors are overlapping and if they have cumulative effects on patient-reported outcomes (PROs).We performed a multicentre cross-sectional study of 201 prospectively enrolled subjects with definitive chronic pancreatitis. All subjects underwent evaluation for pancreatic duct obstruction, abnormalities in pain processing using quantitative sensory testing, and screening for psychological distress (anxiety, depression and pain catastrophising) based on validated questionnaires. Abnormality was defined by normal reference values. PROs included pain symptom severity (Brief Pain Inventory short form) and quality of life (EORTC-QLQ-C30 questionnaire). Associations between pain-related factors and PROs were investigated by linear trend analyses, multiple regression models and mediation analyses.Clinical evaluation suggestive of pancreatic duct obstruction was observed in 29%, abnormal pain processing in 23%, anxiety in 47%, depression in 39% and pain catastrophising in 28%; each of these factors was associated with severity of at least one PRO. Two or more factors were present in 51% of subjects. With an increasing number of factors, there was an increase in pain severity scores (p<0.001) and pain interference scores (p<0.001), and a reduction in quality of life (p<0.001). All factors had independent and direct effects on PROs, with the strongest effect size observed for psychological distress.Pain-related factors in chronic pancreatitis are often present in an overlapping manner and have a cumulative detrimental effect on PROs. These findings support a multidisciplinary strategy for pain management.The study was registered with ClinicalTrials.gov (NCT03434392).

Abstract Background Rapid expansion of the omicron SARS-CoV-2 variant of concern despite extensive vaccine coverage might be related to decreased neutralising ability of vaccine induced antibodies. The neutralising ability of different vaccines with or without natural SARS-CoV-2 infection against omicron is however not well known. Methods We tested the ability of vaccine and natural infection induced antibodies to neutralise omicron variant in a live virus neutralisation assay. Four groups of individuals were included: (i) complete vaccination with ChAdOx1 nCoV-19 (n=20), (ii) complete vaccination with ChAdOx1 nCoV-19 plus prior SARS-CoV-2 infection during the delta variant driven surge (n=20), (iii) complete vaccination with inactivated whole virus vaccine (BBV152) (n=20), (iv) complete vaccination with BBV152 plus prior SARS-CoV-2 infection (n=20). Primary outcome was fold-change in the virus neutralisation ability of plasma against the omicron variant compared with ancestral and delta variant. Findings The neutralisation geometric mean titre (GMT) was 384 (95% CI: 662, 223) against the ancestral virus with BBV152 vaccination alone and 383 (95% CI: 709, 207) with ChAdOx1 nCov-19 vaccination alone. The corresponding values for hybrid immunity groups were 795 (95% CI: 1302, 486) and 1424 (95% CI: 2581,786) respectively. Against the omicron variant, only 5 out of 20 in both BBV152 and ChAdOx1 nCoV-19 vaccine only groups, 5 out of 19 in BBV152 plus SARS-CoV-2 infection group, and 9 out of 20 in ChAdOx1 nCoV-19 plus SARS-CoV-2 infection group exhibited neutralisation titres above the lower limit of quantification (1:20) suggesting better neutralization in those with prior infection. The 50% neutralisation against ancestral strain and omicron demonstrated strong correlation with anti-RBD IgG levels [Pearson r: 0.94 (0.91, 0.96) p: &lt;0.001 and 0.92 (0.88, 0.95) p:&lt;0.001 respectively]. Interpretation Omicron variant shows significant reduction in neutralising ability of both vaccine induced and hybrid immunity induced antibodies which might explain immune escape and high transmission even in the presence of widespread vaccine coverage. Funding DBT, India; GIISER-BMGF, USA Research in context Evidence before this study The Omicron variant of SARS-CoV-2 is fast becoming the dominant circulating strain world-wide. We did a literature search on PubMed between 01 November 2020 to 04 January 2022 using the terms “Omicron” and “neutralisation” and found 11 results for virus neutralisation against omicron by vaccine/natural infection induced antibodies. We identified two published and one preprint articles relevant to omicron virus neutralisation using live virus neutralization. Preliminary reports suggest that omicron variant is significantly less susceptible to in-vitro neutralisation by antibodies among recipients of mRNA vaccines (BNT162b2 and mRNA-1273), adenovirus vectored vaccine (ChAdOx1 nCoV-19 vaccines) and no virus neutralization was observed in subjects who received Coronavac (inactivated virus vaccine). Data regarding immune escape among those with natural SARS-CoV2 infection and vaccination are not available. Added value of this study We report here that the proportion of neutralisers (those who demonstrated a FRNT50 titre &gt;1:20) was significantly reduced against the omicron variant as compared to the ancestral and delta variant. The geometric mean titre of neutralisation among the vaccinated individuals without a history of previous natural infection was significantly reduced against the omicron variant as compared with ancestral and delta variants. The titres among the those with a history of previous infection also followed the same pattern, but the neutralising ability was better in them than those who did not have previous infection. Implications of all the available evidence Omicron variant of SARS-CoV-2 is capable of escaping immunity provided by currently available vaccines and even natural infection due to significant mutations in its spike protein. The drop in neutralisation might be alarming, but the real-world impact of these reduced neutralisation titres on major public health indices like hospitalisation rates and mortality rates have to be interpreted along with the other factors such as inherent pathogenicity of the variant, immunization uptakes and seroprevalence from natural infection in different geographical regions and the expected role of cellular immune responses to the variant. Our data may guide policy on booster vaccination to deal with an impending public health emergency as a result of surge in omicron cases.

Sympatico-vagal balance is essential for regulating cardiac electrophysiology and plays an important role in arrhythmogenic conditions. Various noninvasive methods, including electrocardiography (ECG), have been used for clinical assessment of the sympatico-vagal balance. This study aimed to use a custom-designed wearable device to record ECG and ECG-based cardiac function biomarkers to assess sympatico-vagal balance during tonic pain in healthy controls. Nineteen healthy volunteers were included for the ECG measurements using the custom-designed amplifier based on the Texas Instruments ADS1299. The ECG-based biomarkers of the sympatico-vagal balance, (including heart rate variability, deceleration capacity of the heart rate, and periodic repolarization dynamic), were calculated and compared between resting and pain conditions (tonic pain). The custom-designed device provided technically satisfactory ECG recordings. During exposure to tonic pain, the periodic repolarization dynamics increased significantly (p = 0.02), indicating enhancement of sympathetic nervous activity. This study showed that custom-designed wearable devices can potentially be useful in healthcare as a new telemetry technology. The ECG-based novel biomarkers, including periodic repolarization dynamic and deceleration capacity of heart rate, can be used to identify the cold pressor-induced activation of sympathetic and parasympathetic systems, making it useful for future studies on pain-evoked biomarkers.

Abstract Background The initial management of patients with acute pancreatitis impacts both morbidity and mortality. Point‐of‐care decisions have been reported to differ from clinical guideline recommendations. Methods An online anonymous questionnaire was distributed through scientific associations and social media using REDCap. Multivariable logistic regression was used to identify the characteristics of participants associated with compliance with the recommendations. Results A total of 1054 participants from 94 countries completed the questionnaire; median age (IQR) was 39 (32–47) years; 30.7% were women. Among the participants, 37% opted for nonmoderate flow of i.v. fluid, 31% for fluid type other than Ringer’s lactate; 73.4% were in favor of nil per os to patients who could eat, 75.5% for other than enteral feeding to patients with oral intolerance; 15.5% used prophylactic antibiotic in patients with severe acute pancreatitis, 34.1% in necrotizing acute pancreatitis, and 27.4% in patients with systemic inflammatory response syndrome; 27.8% delayed cholecystectomy after biliary acute pancreatitis. Participants with publications in PubMed on acute pancreatitis showed better compliance (OR, 1.62; 95% CI: 1.15–2.32; P = .007) with recommendations of the clinical guidelines. Conclusions Feeding and nutrition require the greatest improvement efforts, but also the use of prophylactic antibiotics and timing of cholecystectomy should be improved.

The emergence of new variants of SARS-CoV-2 necessitates unremitting efforts to discover novel therapeutic monoclonal antibodies (mAbs). Here, we report an extremely potent mAb named P4A2 that can neutralize all the circulating variants of concern (VOCs) with high efficiency, including the highly transmissible Omicron. The crystal structure of the P4A2 Fab:RBD complex revealed that the residues of the RBD that interact with P4A2 are a part of the ACE2-receptor-binding motif and are not mutated in any of the VOCs. The pan coronavirus pseudotyped neutralization assay confirmed that the P4A2 mAb is specific for SARS-CoV-2 and its VOCs. Passive administration of P4A2 to K18-hACE2 transgenic mice conferred protection, both prophylactically and therapeutically, against challenge with VOCs. Overall, our data shows that, the P4A2 mAb has immense therapeutic potential to neutralize the current circulating VOCs. Due to the overlap between the P4A2 epitope and ACE2 binding site on spike-RBD, P4A2 may also be highly effective against a number of future variants.

Abstract Background Coronavirus Disease 2019 (COVID-19) pandemic continues unabated in many parts of the world. In the absence of any definite antiviral therapy except some benefit of remdesivir, there is an ongoing search for effective therapy. Famotidine has been shown to reduce mortality in hospitalized patients in a few studies. We conducted a systematic review on the use of famotidine in COVID-19. Methods We searched the databases Medline, Embase, Cochrane CENTRAL and Medrxiv. Title/abstract screening, full text screening and data abstraction were carried out in by two reviewers. Case series, cohort studies and randomized trials were included. Results Five studies were eligible for inclusion: all were retrospective cohort or case series. Low quality evidence suggests a likely clinical benefit for the use of famotidine in decreasing mortality in hospitalized patients with moderate to severe COVID-19. A meta-analysis of two cohort studies showed a statistically significant decrease in the composite outcome for death and intubation with famotidine (HR 0.44, 95% CI 0.27 to 0.73). Conclusion Further evidence from RCTs is required for famotidine to treat COVID 19.

Background Cell-mediated immunity (CMI), or specifically T-cell-mediated immunity, is proven to remain largely preserved against the variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including Omicron. The persistence of cell-mediated immune response in individuals longitudinally followed up for an extended period remains largely unelucidated. To address this, the current study was planned to study whether the effect of cell-mediated immunity persists after an extended period of convalescence or vaccination. Methods Whole blood specimens of 150 selected participants were collected and tested for Anti-SARS-CoV-2 Interferon-gamma (IFN-γ) response. Ex vivo SARS-CoV-2-specific interferon-gamma Enzyme-linked Immunospot (IFN-γ ELISpot) assay was carried out to determine the levels of virus-specific IFN-γ producing cells in individual samples. Findings Out of all the samples tested for anti-SARS-CoV-2 T-cell-mediated IFN-γ response, 78.4% of samples were positive. The median (interquartile range) spots forming units (SFU) per million levels of SARS-CoV-2-specific IFN-γ producing cells of the vaccinated and diagnosed participants was 336 (138-474) while those who were vaccinated but did not have the disease diagnosis was 18 (0-102); the difference between the groups was statistically significant. Since almost all the participants were vaccinated, a similar pattern of significance was observed when the diagnosed and the never-diagnosed participants were compared, irrespective of their vaccination status. Interpretations Cell-mediated immunity against SARS-CoV-2 persisted, irrespective of age and sex of the participant, for more than six months of previous exposure. Participants who had a history of diagnosed COVID-19 infection had better T-cell response compared to those who had never been diagnosed, in spite of being vaccinated.

Acute necrotising pancreatitis—a severe form of acute pancreatitis—can lead to acute necrotic fluid collections. The necrotic fluid collections can remain sterile or get infected, which is referred to as infected necrotising pancreatitis. Patients with acute pancreatitis who develop persistent organ failure (lasting >48 h) are classified as having severe acute pancreatitis.1 Organ failure and infected necrotising pancreatitis are the two major determinants of survival in acute pancreatitis.1 The initial management of acute pancreatitis is largely supportive, and no invasive intervention is recommended.

Strong light-matter interaction is emerging as an exciting tool for controlling chemical reactions. Here, we demonstrate an L-proline-catalyzed direct asymmetric Aldol reaction under vibrational strong coupling. Both the reactants (4-nitrobenzaldehyde and acetone) carbonyl bands are coupled to an infrared photon and react in the presence of L-proline. The reaction mixture is eluted from the cavity, and the conversion yields and enantiomeric excess are quantified using NMR and chiral HPLC. The conversion yields increase by up to 90 % in ON-resonance conditions. Interestingly, a large increase in the conversion yield does not affect the enantiomeric excess. Further control experiments were carried out by varying the temperature, and we propose that the rate-limiting step may not be the deciding factor in enantioselectivity. Whereas the formation of the enamine intermediate is modified by cavity coupling experiments. For this class of enantioselective reactions, strong coupling does not change the enantiomeric excess, possibly due to the large energy difference in chiral transition states. Strong coupling can boost the formation of enamine intermediate, thereby favouring the product yield. This gives more hope to test polaritonic chemistry based on enantioselective reactions in which the branching ratios can be controlled.

Background: Pneumomediastinum refers to the presence of extraluminal gas within the mediastinum. If signs of pneumomediastinum are not present on chest X-ray and it is detected on contrast-enhanced computed tomography (CECT) thorax then it is known as occult pneumomediastinum. There is a dearth of literature regarding occult pneumomediastinum in patients with blunt chest trauma. Aims and Objectives: This study was done to see the incidence as well as outcome of occult pneumomediastinum in patients of blunt chest trauma. Materials and Methods: A prospective study was done in the department of general surgery at a tertiary care institute in which a total of 32 patients with blunt chest trauma were taken. The patients with occult pneumomediastinum were identified using CECT and appropriate management was done in all patients. Correlation of occult pneumomediastinum with subcutaneous emphysema, rib fracture, jugular venous pressure (JVP), pleural effusion, and outcome was seen. Results: It was evident from this study that 18.8% of patients of with chest trauma had occult pneumomediastinum. Incidence of blunt chest trauma is most common in the age group of 31–60 years as this age group is more vulnerable to roadside accidents and other accidents. There is a strong correlation between the presence of central subcutaneous emphysema, raised JVP, and worse outcomes with occult pneumomediastinum (P&lt;0.05). Conclusion: This study showed a high incidence of occult pneumomediastinum in patients with chest trauma which is ultimately associated with high mortality. Hence, we should keep high index of suspicion regarding the presence of occult pneumomediastinum so that timely management of these patients can be done to prevent morbidity and mortality.

Background: Endoscopic variceal sclerotherapy and band ligation both have certain limitations such as, respectively, esophageal complications and early recurrence of varices. Methods: From February 1994 to March 1996, all consecutive patients with portal hypertension due to either cirrhosis or noncirrhotic portal fibrosis and a history of variceal bleeding were included in a prospective study and randomly assigned to receive either endoscopic variceal sclerotherapy alone or endoscopic variceal band ligation plus low-dose endoscopic variceal sclerotherapy. Results: Of 69 patients, 34 were randomly assigned to receive endoscopic variceal sclerotherapy alone; 35 received endoscopic variceal band ligation plus endoscopic variceal sclerotherapy. Complete variceal eradication rates (85% vs. 80%) and the number of endoscopic sessions required for eradication (6.61 ± 2.94 vs. 7.85 ± 3.31) were similar in the endoscopic variceal sclerotherapy and endoscopic variceal band ligation plus endoscopic variceal sclerotherapy groups, respectively. The mean volume of sclerosant required in the combined group (54.94 ± 33.74 mL) was significantly less than that in the endoscopic variceal sclerotherapy group (81.91 ± 34.80 mL). The complication and recurrent bleeding rates were significantly higher in the endoscopic variceal sclerotherapy group than those in the combined group (20% and 16% vs. 3% and 3%, respectively). Conclusions: Both endoscopic variceal sclerotherapy and endoscopic variceal band ligation plus endoscopic variceal sclerotherapy were comparable in eradicating varices but the combined technique was associated with significantly lower complication and recurrent bleeding rates. (Gastrointest Endosc 1999;50:369-73.)

3α-Hydroxysteroid dehydrogenase (3α-HSD) from Pseudomonas testosteroni and diaphorase (lipoyl dehyrogenase) from Clostridium spp. have been immobilized individually onto arylamine glass beads through diazotization. A cost-effective enzymic colorimetric method for determination of bile acid in serum and bile employing a mixture of these immobilized enzymes was developed. The method is based on measurement of reduced nicotinamide adenine dinucleotide generated from bile acid in serum/bile by immobilized 3α-HSD with a color reagent consisting of nitro blue tetrazolium chloride salt, oxidized nicotinamide adenine dinucleotide, and immobilized lipoyl dehyrogenase in 0.065 M sodium phosphate buffer, pH 7.0. Analytical recovery of added bile acid (50 and 200 μmol/L) was 95.57 and 85.46% in serum and 97.6 and 91.6% in bile, respectively. Within- and between-batch coefficients of variation (CV) for bile acid determination were <1.2 and <0.2% in serum and >0.1 and <0.1% in bile, respectively. Good correlations for bile acid in serum (r1=0.92) and in bile (r2=0.97) were obtained by use of a standard chemical method and the present method. The mixture of immobilized 3α-HSD dehydrogenase and lipoyl dehyrogenase lost 50% of its initial activity after 6 months of regular use. The cost of bile acid determination in 100 serum and bile samples by the present method has been compared with that of the Sigma kit method.

Fever, as a significant event, has not been studied systematically in patients with acute pancreatitis. We studied prospectively incidence, etiology, and impact of fever on the management and outcome in patients with acute pancreatitis.All consecutive patients with acute pancreatitis were studied for the development of fever, its etiology, and its influence on the management and outcome of acute pancreatitis. Fever was considered to be significant, if the temperature was >38 degrees C and persisted for >2 days.A total of 75 patients (51 males; mean age 41 years) with acute pancreatitis were included between January 1997 and June 1998. The causes of pancreatitis were gallstones in 48%, alcohol in 28%, and others in 24% of the patients. 20 patients had pancreatic necrosis, and 45 (60%) developed fever during the course of pancreatitis. The etiology of fever was infected pancreatic necrosis in 8 (18%), pancreatitis per se in 10 (22%), cholangitis in 4 (9%), nonpancreatic infections in 17 (38%), and an undetermined one in 6 (13%) patients. Of the 45 patients with fever, 17 had pancreatic necrosis as compared with only 3 of 30 patients who did not develop fever (p < 0.05). Patients with fever had a higher pancreatitis-related mortality than those without fever (p = 0.03).60% of the patients with acute pancreatitis developed fever. Infected pancreatic necrosis was the cause of fever in 18% of the patients and not in the majority, i.e., 82% of the patients. The mortality rate was higher in patients who developed fever than in those who did not.

Background: The emergence of SARS-CoV-2 variants of concern (VoC) has threatened the effectiveness of vaccination due to decreased neutralisation ability of the vaccine generated antibodies. Our objective was to assess ChAdOx1 nCoV-19 vaccine effectiveness during the massive surge from 1st April to 31stMay 2021 predominantly due to the more infectious B·1·617·2 (Delta) in India.Methods: We conducted a test-negative case-control study to assess the effectiveness of ChAdOx1 nCoV-19 vaccine. Cases were RT-PCR positive for SARS-CoV-2 infection. In addition, we tested live virus neutralisation and cellular immune responses against VoC among healthy recipients of ChAdOx1 nCoV-19 vaccine. The outcomes were effectiveness of ChAdOx1 nCoV-19 against infection and severe coronavirus disease-19, virus neutralisation effectivity and T-cell responses against the VoC among healthy vaccine recipients.Findings: Of the 2766 cases of confirmed SARS-CoV-2 infection, 3·1% were fully vaccinated compared with 7·1% of the 2377 controls giving an adjusted OR of 0·37 (95%CI 0·28, 0·48); this translated to 63·1% (95%CI 51·5, 72·1) vaccine effectiveness against SARS-CoV-2 B·1·617·2 variant, seen in 90% of the infected population as confirmed by whole-genome virus sequencing. Full vaccination prevented moderate-severe COVID-19 in 81·5% (95%CI: 9·9, 99·0). The effectiveness of single-dose vaccine was 46·2% (95%CI: 31·6, 57·7) against infection but 79·2% (95%CI: 46·1, 94·0) in preventing moderate-severe Covid-19. Among healthy vaccinated persons, plasma live virus neutralisation was 2·5-6·8 fold lower against B·1·1·7, B·1·351, B·1·617·1 and B·1·617·2 being lowest against B·1·617·2. However, T-cell responses were preserved against the recombinant mutant receptor binding domain antigens suggesting cell-mediated immune protection.Interpretation: Despite significantly reduced virus neutralisation, the effectiveness of ChAdOx1 nCoV-19 vaccine was 63% against B·1·617·2 infection and 81·5% in preventing severe disease. Spike specific T cells responses against virus variants were maintained and might contribute to immune protection following vaccination.Funding Information: Department of Biotechnology, Government of India; Council for Scientific and Industrial Research, India; Fondation Botnar.Declaration of Interests: None to declare.Ethics Approval Statement: The studies were approved by the Institute Ethics Committees of the partnering institutions.

Abstract Background : The efficacy of anti‐ Helicobacter pylori treatment and cytoprotective drugs in H. pylori ‐positive and ‐negative non‐ulcer dyspepsia (NUD), respectively, is debatable. Methods : In a randomized study, the efficacy of anti‐ H. pylori treatment versus sucralphate was tested in patients with NUD. One hundred and twelve patients with NUD, 62 positive and 50 negative for H. pylori were studied. Of 62 patients positive for H. pylori , 32 were treated with triple therapy (colloidal bismuth subcitrate, tetracycline and metronidazole) for 2 weeks and the remaining 30 were treated with sucralphate (1 g, q.i.d.) for 4 weeks. Of 50 patients negative for H. pylori , 25 each were treated with either sucralphate (1 g, q.i.d.) or ranitidine (150 mg, b.d.) for 4 weeks. Results : In patients with NUD and H. pylori infection, triple therapy eradicated H. pylori in 88% and was superior to sucralphate in producing symptom relief (81 vs 33%, P = 0.0003) and histological improvement in gastritis (73 vs 30%, P = 0.003). In the H. pylori ‐negative group, sucralphate was superior to ranitidine with regard to symptom relief (68 vs 36%, P = 0.04) and improvement in gastritis (44 vs 12%, P = 0.09). The symptomatic improvement persisted until 12 weeks after the start of treatment in triple therapy group only. Conclusions : In patients with NUD associated with H. pylori , triple therapy was better than sucralphate in terms of symptomatic and histological improvement. However, sucralphate was superior to ranitidine in providing symptom relief in patients with H. pylori ‐negative NUD. © 1999 Blackwell Science Asia Pty Ltd

Abstract Background There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. Objective We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19. Methods Two reviewers searched for published and pre-published relevant articles between December 2019 to 8th June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa scale. The quality of evidence was graded as per the GRADE approach. Results We reviewed 12 observational and 3 randomized trials which included 10659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46], time to fever resolution [mean difference −0.54 days (-1.19-011)] or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes. Author’s Conclusion The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19..

Patients with spinal cord injury (SCI) have an increased prevalence of gallstones.To study prospectively the incidence of gallstones and gall bladder contractility in patients with SCI.Thirty six consecutive patients with SCI were studied: 18 patients with SCI above thoracic 10 neuronal segment (> T10) and 18 patients with SCI below T10 (< T10). An equal number each of disease controls (multiple fractures) and healthy controls were also studied. All patients and controls underwent serial ultrasonography to detect development of gallstones and ultrasonographic measurement of gall bladder contractility.A significantly higher number (9/18) of patients with SCI > T10 developed biliary sludge compared with patients with SCI < T10 (2/18), disease controls (2/18), and healthy controls (1/18) (p < 0.05). No patient developed gallstones. The gall bladder fasting volume was significantly decreased in patients with SCI > T10 (20.56 ml; 95% confidence intervals (CI) 19.74 to 21.38) compared with that in patients with SCI < T10 (27.33 ml, 95% CI 26.17 to 28.49; p < 0.05), disease controls (27.92 ml, 95% CI 26.69 to 29.15; p < 0.05), and healthy controls (28.35 ml, 95% CI 27.25 to 29.45; p < 0.05). Gall bladder contractility was normal in patients with SCI as shown by normal gall bladder residual volume and emptying time.Patients with SCI above T10 have an increased incidence of biliary sludge and a decreased gall bladder fasting volume. Gall bladder contractility is, however, normal.

The chemical composition and clinical significance of white bile in patients with malignant biliary obstruction were evaluated in a prospective study.Consecutive patients (January 1996 through December 1997) with inoperable malignant biliary obstruction underwent endoscopic placement of 10F straight, plastic biliary stents. Bile was aspirated during the endoscopic procedure. Patients were divided into 2 groups: those with white and those with yellow bile. The chemical composition of bile was analyzed. Levels of bile acids in the serum and bile (11 samples) were estimated by high-performance thin-layer chromatography. The groups were compared for decremental fall in bilirubin (b value), cholangitis after stent insertion, and survival.Thirty-five patients (15 men, 20 women; mean age 54 years) underwent endoscopic drainage for malignant obstruction (29 hilar, 6 distal bile duct). Eighteen patients had white bile. Refractory jaundice (b > -0.025) was seen in 9 (50%) patients with white bile compared with 3 (17.6%) with yellow bile; mean difference -42.2 (95% CI [-62.4, -22.0]) and -45.7 (95% CI [-72.0, -19.4]), respectively. The bilirubin (0.48 mg/L) and bile acid (15.6 mmol/L) concentrations in white bile were significantly less than bilirubin (42.7 mg/L) and bile acid (61.3 mmol/L) concentrations in yellow bile; mean difference -42.2 (95% CI [-62.4, -22.0]) and mean difference -45.7 (95% CI [-72.0, -19.4]), respectively. Cholangitis developed in 66.6% of patients with white bile compared with 35% of those with yellow bile (OR 3.67: 95% CI [0.74, 19.25]). Kaplan-Meier curves showed that median survival (interquartile range) was shorter in patients with white bile (35 [23-60] versus 77 [35-220] days) (p = 0.004, log rank test), which was significant even after adjusting for potential confounders with Cox proportional hazards regression.White bile is largely devoid of bilirubin and bile acids. The presence of white bile was associated with significantly worse survival in patients with malignant biliary obstruction.

Abstract The characteristics of immune memory established in response to inactivated SARS-CoV-2 vaccines remains unclear. We determined the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months after vaccination with BBV152/Covaxin. Here, we show that the quantity of vaccine-induced spike- and nucleoprotein-antibodies is comparable to that following natural infection and the antibodies are detectable up to 6 months. The RBD-specific antibodies decline in the range of 3 to 10-fold against the SARS-CoV-2 variants in the order of alpha (B.1.1.7) &gt; delta (B.1.617.2) &gt; beta (B.1.351), with no observed impact of gamma (P.1) and kappa (B.1.617.1) variant. We found that the vaccine induces memory B cells, similar to natural infection, which are impacted by virus variants in the same order as antibodies. The vaccine further induced antigen-specific functionally potent multi-cytokine expressing CD4 + T cells in ∼85% of the subjects, targeting spike and nucleoprotein of SARS-CoV-2. Marginal ∼1.3 fold-reduction was observed in vaccine-induced CD4 + T cells against the beta variant, with no significant impact of the alpha and the delta variants. The antigen-specific CD4 + T cells were populated in the central memory compartment and persisted up to 6 months of vaccination. Importantly the vaccine generated Tfh cells that are endowed with B cell help potential, similar to the Tfh cells induced after natural infection. Altogether, these findings establish that the inactivated virus vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern, which persist for at least 6 months after vaccination. This study provides insight into the attributes of BBV152-elicited immune memory, and has implication for future vaccine development, guidance for use of inactivated virus vaccine, and booster immunization.

Leprosy is a medical - social disease, it is associated with stigma in the society due to the resulting deformities in some persons. Although stigma has decreased after the widespread use of MDT, some disabilities do occur which are mostly due to late initiation of treatment and inappropriate care. Besides the nerve and skin involvement bone changes have been reported to be common in leprosy. These bony changes need to be understood in the present MDT era specially in the context of clinical spectrum and duration of disease/ deformities. Fifty clinically diagnosed and histologically classified leprosy patients with deformities/ disabilities of either hands/feet/face who attended the OPD of Department of Dermatology, Venereology and Leprosy, Government Medical College, Amritsar were examined and evaluated in the study. Radiological examination of hands, feet and skull was done in each case and the bone changes in hands and feet; and skull and paranasal sinus changes were correlated with clinical parameters. Bone changes were observed in 90% of cases radiologically. Specific bone changes in hands and feet, non-specific bone changes in hands, feet, skull and paranasal sinuses were seen in 66%, 82% and 32% of cases respectively. Common specific bone changes in hands and feet observed were primary periostitis (14%), honey combing (46%), bone cyst (36%), thinning and irregularity of cortex (28%) and area of bone destruction (20%); Among the non-specific bone changes observed were contracted fingers/claw hands/claw toes (64%) and absorption of terminal phalanges (40%). The maxillary sinus, and paranasal sinus changes were the most common radiological findings observed in skull. The study of the radiological changes may help the clinicians to understand the gravity of the situation and undertake steps for timely prevention of permanent loss of function and the occurrence of deformities and disabilities.

Acute on chronic pancreatitis (ACP) is a relatively common condition, but there are significant gaps in our knowledge on the definition, incidence, diagnosis, treatment and prognosis.A systematic review that followed PICO (Population; Intervention; Comparator; Outcome) recommendation for quantitative questions and PICo (Population, Phenomenon of Interest, Context) for qualitative research was done to answer 10 of the most relevant questions about ACP. Quality of evidence was judged by the GRADE criteria (Grades of Recommendation, Assessment, Development and Evaluation). The manuscript was sent for review to 12 international experts from various disciplines and continents using a Delphi process.The quality of evidence, for most statements, was low to very low, which means that the recommendations in general are only conditional. Despite that, it was possible to reach strong levels of agreement by the expert panel for all 10 questions. A new consensus definition of ACP was reached. Although common, the real incidence of ACP is not known, with alcohol as a major risk factor. Although pain dominates, other non-specific symptoms and signs can be present. Serum levels of pancreatic enzymes may be less than 3 times the upper limit of normal and cross-sectional imaging is considered more accurate for the diagnosis in many cases. It appears that it is less severe and with a lower mortality risk than acute pancreatitis.Although the evidence base is poor, this position statement provides a foundation from which to advance management of ACP.

Abstract One of the fundamental mechanisms developed by the host to contain the highly infectious and rapidly proliferating SARS coronavirus is elevation of body temperature, a natural fallout of which is Heat Shock Protein (HSP) over-expression. Here, for the first time, we demonstrate that the SARS-CoV-2 virus exploits the host Hsp70 chaperone for its entry and propagation and blocking it can combat the infection. SARS-CoV-2 infection as well as febrile temperature enhanced Hsp70 overexpression in host Vero E6 cells. In turn, Hsp70 overexpression elevated the host cell autophagic response that is a prerequisite for viral propagation. Suppressive and prophylactic treatment of Vero E6 cells with HSP70 inhibitor PES-Cl, a small molecule derivative of Pifithrin μ, abrogated viral infection more potently than the currently used drug Remdesivir by suppressing host HSP70 and autophagic response. In conclusion, our study not only provides a fundamental insight into the role of host Hsp70 in SARS-CoV-2 pathogenesis, it paves the way for the development of potent and irresistible anti-viral therapeutics.

A 45-year-old male presented with severe abdominal pain, hyperamylasaemia and a bulky pancreas. In addition, he had deep jaundice and markedly raised serum transaminases, and his serum was positive for IgM anti-hepatitis E virus (HEV) antibodies. The common aetiologies of acute pancreatitis were excluded. The patient ran a benign course for both acute viral hepatitis and acute pancreatitis, and recovered completely. Acute pancreatitis caused by HEV infection has been reported only occasionally.

The endoscopic management of pancreatic fluid collections (PFC) is in flux due to changes in how we classify them, as well as rapid advances in technology. The revised Atlanta classification of PFC[1] clearly distinguished pseudocysts from walled-off necrosis (WON) and acute peri PFC from acute necrotic collections, based upon presence of necrosis, time since the onset of attack of pancreatitis and formation of a mature wall around the fluid collection. The literature prior to this had both, a mix of WON and pseudocyst, usually labeled as pseudocysts.[1] [2] The subsequent publications have clearly demonstrated that the management issues are different for pseudocyst and WON, although clarity still eludes several areas. Another major development has been the application of biflanged metal (BFMS) and lumen apposing metal stents (LAMS) for PFC. Despite a lot of literature available for BFMS and LAMS, controversies still exist about their appropriate role. The Society of Gastrointestinal Endoscopy of India and Indian endoscopic ultrasound (EUS) club developed these guidelines to conduct an updated literature review, and provide recommendations based upon strength of available evidence.[3]

<h3>Background and Aims</h3> Although abdominal pain is one of the major criteria to diagnose acute pancreatitis (AP), there are no standardized guidelines to treat this troublesome symptom in the hospital setting. The aims of the study are to conduct a meta-analysis and to assess the efficacy of nonopioids vs opioids for pain management in AP. <h3>Methods</h3> We searched the medical literature through May 2021 to identify randomized controlled trials that examined the efficacy of opioids with nonopioids in AP pain management. Efficacy was reported as odds ratio (OR) with 95% confidence intervals (CIs) of each comparison tested. <h3>Results</h3> We identified 7 eligible randomized controlled trials, containing 389 patients. No significant difference in terms of pain intensity at day 1 (OR 0.82, 95% CI −2.55 to 4.19) was found between opioids and nonopioids. Nonopioids have a significantly high risk of supplementary analgesic use compared with opioids (OR 3.87, 95% CI 1.25–12.04). However, this significance is not seen when comparing nonsteroidal anti-inflammatory drugs and paracetamol with opioids (OR 1.67, 95% CI 0.73–3.82) after excluding trials with procaine. Opioids did not show a significant increase in the complications of pancreatitis, nausea and vomiting, sedation, and deaths when compared with nonopioids. <h3>Conclusion</h3> We found nonopioids, especially nonsteroidal anti-inflammatory drugs and paracetamol, can provide adequate pain relief in patients with AP with no change in supplementary analgesic use and adverse events when compared with opioids. Further research is needed to optimize the use of nonopioids along or in combination with opioids for better pain control in patients with AP.

Chronic diarrhea is a common clinical problem. To determine the possible causes in North India, we studied prospectively 71 patients with chronic diarrhea of the large bowel type. A definite diagnosis could be established in 70 patients. Ulcerative colitis was found in 18 patients, colorectal malignancies in three, colonic polyps in three, and irritable bowel syndrome in 32. In addition, seven patients with seronegative polyarthritis and chronic diarrhea were found to have chronic inflammation of the colon on histology. Two patients had pseudodiarrhea, and no diagnosis could be established in one patient. The remaining five patients with chronic diarrhea showed histologic evidence of chronic colonic inflammation with predominantly mononuclear cell infiltration of the lamina propria and increased intraepithelial lymphocytes, but results of their radiologic and endoscopic studies were normal. These five patients were classified as having microscopic (lymphocytic) colitis. We conclude that the causes of chronic diarrhea in North Indian patients are similar to a large extent to those seen in Western populations. Microscopic (lymphocytic) colitis is a definite clinicopathologic entity that should be considered in the differential diagnosis of chronic diarrhea.

Anti tubercular drug related hepatotoxicity is common. The mechanism of injury and factors predisposing to its development are not fully understood. Forty patients with anti tubercular drugs related hepatotoxicity were studied to see the clinical and biochemical profile of these patients and to find out the significance of acetylator phenotype in the development of hepatotoxicity. Mean age of patients with liver damage (37.82 +/- 10.0 years) was similar to those without liver damage (36.48 +/- 12.5 years). Pyrazinamide appeared to increase the hepatotoxicity of isoniazid and rifampicin. The percentage of rapid acetylators and slow acetylators among patients with hepatotoxicity (70% and 30% respectively) was similar to controls (66.6% rapid and 33.3% slow acetylators). Acetylator phenotype probably has no role in anti tubercular drugs induced hepatotoxicity.

Natural viral infections provide immunity from subsequent infection through a repertoire of memory T cells and B cells, except when the virus mutates to an extent that it evades recognition by memory cells.1 Vaccines are designed to represent the virus either in the form of an inactivated or attenuated whole virus or an immunogenic subunit such as the spike protein in the case of SARS-CoV-2.2 After a natural infection, the immune system assesses the virus in multiple ways and provides both antibody-mediated and cellular protection.

Abstract The emergence of new variants of SARS-CoV-2 necessitates unremitting efforts to discover novel therapeutic mAbs. Here, we report an extremely potent mAb named P4A2 that can neutralize all the circulating variants of concerns (VOCs) with high efficiency, including the highly transmissible Omicron. The crystal structure of the P4A2 Fab:RBD complex revealed that the residues of the RBD that interact with P4A2 are part of the ACE2-receptor-binding motif and are not mutated in any of the VOCs. The pan coronavirus pseudotyped neutralization assay confirmed that the P4A2 mAb is specific for SARS-CoV-2 and its VOCs. Passive administration of P4A2 to K18-hACE2 transgenic mice conferred protection, both prophylactically and therapeutically, against challenge with VOCs. Overall, our data shows that, the P4A2 mAb has immense therapeutic potential to neutralize the current circulating VOCs and will be highly effective against future variants as well due to its unique mode of binding.

This chapter focuses on the pathophysiology of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) in acute pancreatitis (AP). Severe systemic inflammation is associated with dysfunction of vital end organs, including the cardiovascular, respiratory, and renal systems. While the inflammatory and immune responses to acute disease can be protective, in the setting of severe AP, there is an out of proportion and dysregulated immune response and hyperinflammation, which can result in end-organ dysfunction and failure. The innate immune system is activated by foreign antigens particularly microbe-related peptides. Cells involved in innate immunity possess pattern recognition receptors (PRRs), which recognize what are termed as ‘pathogen-associated molecular patterns’ (PAMPs) present on the microbes. After activation, immune cells secrete many proinflammatory cytokines, including TNF-a and IL-1. The initial inflammatory response by itself does not have significant clinical consequences, but it leads to the adherence, migration, and activation of leukocytes.

Acute pancreatitis (AP) is usually associated with acute fluid collections which may evolve into pseudocyst or Walled-off Necrosis (WON). If symptomatic, pseudocyst/WON require drainage. Endoscopic internal drainage being minimally invasive is preferred over surgery. An unresolved issue is whether transpapillary drainage through ERCP is required before endoscopic transenteral drainage for any suspected pancreatic ductal communication.

Background. Coronavirus disease 2019 (Covid-19) has emerged as a pandemic by end-January 2020. Of the infected patients, 10%–15% may develop severe or critical illness. So far, no definite treatment is available for Covid-19. Cytokine release syndrome may underlie the pathogenesis of severe and critical disease. Anti-interleukin (IL)-6 therapies are being tried to improve clinical outcomes. Methods. We did a systematic review to identify the available literature on anti-IL-6 therapies in the treatment of Covid-19 and used the GRADE method to assess the quality of evidence. Results. Four case series and 10 case reports were identified. On critical assessment, we found that these studies reported some beneficial effect of anti-IL-6 therapy, but all the studies had a high risk of bias. The pooled estimate showed that 42% of patients improved but with a very wide confidence interval (CI) (95% CI 1%–91%) and substantial heterogeneity (I2 = 95%). The overall quality of evidence was graded as ‘very low’. Conclusions. Although promising, anti-IL-6 therapy for Covid-19 needs to be tested in randomized controlled trials to provide robust evidence.

Development of robust neutralizing antibodies in SARS-CoV-2 convalescent individuals is known; however, it varies at the population level. We isolated monoclonal antibodies from an individual infected with ancestral SARS-CoV-2 in early 2020 that not only varied in their B cell lineage origin but also varied in their capability and potency to neutralize all the known variants of concern (VOCs) and currently circulating Omicron variants.

Patients with acute pancreatitis might develop infected necrotic fluid collections which are associated with significant morbidity and mortality. Patients with infected necrotizing pancreatitis not responding to antibiotics require drainage and subsequent necrosectomy (Step-up approach). Percutaneous endoscopic necrosectomy (PEN) has evolved as a minimally invasive approach for necrosectomy through the percutaneous catheter route using a flexible endoscope and can be done under conscious sedation. It is best suited for predominantly laterally placed infected necrotic fluid collections and also can be performed at the bedside for sick patients admitted to an ICU. PEN has a clinical success rate of 80% with minimal adverse events.

Chronic pancreatitis (CP) is characterized by repeated episodes of pancreatic injury and inflammation. It presents clinically with episodic or chronic pain, diabetes, and exocrine insufficiency. The pathophysiological mechanisms causing CP are not well understood. Free radical production is an integral part of cellular physiology. The free radicals are neutralized by specific cellular enzymes and other small molecules called scavengers and antioxidants. In health, an intricate balance exists between pro-oxidants and antioxidants called “redox homeostasis.” Experimental and human studies have implicated oxidative stress in the pathogenesis of CP. In patients with CP, exogenous substances such as smoking, alcohol, and environmental toxins induce production of free radicals by induction of CYP 450 in acinar cells resulting in oxidative stress. The antioxidant capacity is low in patients with CP either due to increased consumption of antioxidants to mitigate oxidative stress, dietary deficiency, or impaired absorption. Oxidative stress may lead to lipid peroxidation, DNA damage, and protein denaturation resulting in cellular injury. Serum thiobarbituric acid reactive substances (TBARS), malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE), which are products of lipid peroxidation, are commonly used to measure oxidative stress. Ferric acid-reducing ability of plasma (FRAP) is a good measure of the total antioxidant capacity of the body. Micronutrient-based combination antioxidants have been shown to be effective in reducing oxidative stress and relieving pain in randomized controlled trials particularly in patients with idiopathic CP. It is recommended that antioxidant supplementation should be included in the optimized medical management for pain in patients with CP prior to consideration of invasive endoscopic or surgical intervention.

Dengue is currently the most rapidly spreading mosquito-borne viral infection in the world, with half of the world's population at risk of becoming infected.1WHOGeographical expansion of cases of dengue and chikungunya beyond the historical areas of transmission in the Region of the Americas.https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON448Date: March 23, 2023Date accessed: June 12, 2023Google Scholar As a result of climate change, rapid urbanisation, and widespread international travel, the incidence of dengue is rapidly increasing, overwhelming health-care systems in many lower-income countries. Climate change has increased the burden of dengue in endemic countries and has also led to expansion of this infection to new territories in Europe and North America.2Colón-González FJ Sewe MO Tompkins AM et al.Projecting the risk of mosquito-borne diseases in a warmer and more populated world: a multi-model, multi-scenario intercomparison modelling study.Lancet Planet Health. 2021; 5: e404-e414Summary Full Text Full Text PDF PubMed Scopus (79) Google Scholar Dengue is estimated to infect approximately 390 million individuals annually, with 96 million infections being symptomatic.1WHOGeographical expansion of cases of dengue and chikungunya beyond the historical areas of transmission in the Region of the Americas.https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON448Date: March 23, 2023Date accessed: June 12, 2023Google Scholar So far, the only strategy adopted to reduce the burden of dengue is vector control. Although techniques such as using Wolbachia bacteria to reduce dengue transmission by Aedes mosquitoes look promising,3Utarini A Indriani C Ahmad RA et al.Efficacy of Wolbachia-infected mosquito deployments for the control of dengue.N Engl J Med. 2021; 384: 2177-2186Crossref PubMed Scopus (155) Google Scholar it is evident that vector control alone is unlikely to be adequate to reduce the burden of dengue. The currently available dengue vaccines (CYD-TDV and TAK-003) have been shown to reduce hospitalisations, especially in dengue-seropositive individuals, but lack efficacy against some dengue virus serotypes.4Biswal S Borja-Tabora C Martinez Vargas L et al.Efficacy of a tetravalent dengue vaccine in healthy children aged 4–16 years: a randomised, placebo-controlled, phase 3 trial.Lancet. 2020; 395: 1423-1433Summary Full Text Full Text PDF PubMed Scopus (99) Google Scholar Furthermore, CYD-TDV showed a higher incidence of severe dengue in dengue-naive vaccine recipients, and both vaccines show some degree of waning immunity with time, especially in seronegative individuals.5Thomas SJ Is new dengue vaccine efficacy data a relief or cause for concern?.NPJ Vaccines. 2023; 8: 55Crossref Scopus (2) Google Scholar, 6Hadinegoro SR Arredondo-García JL Capeding MR et al.Efficacy and long-term safety of a dengue vaccine in regions of endemic disease.N Engl J Med. 2015; 373: 1195-1206Crossref PubMed Scopus (772) Google Scholar Therefore, an integrated approach that comprises vector control, use of safe and effective vaccines, and an effective treatment is needed to face the growing challenges of dengue infection. Efforts focused on finding a treatment have been scarce, with some investigator-led clinical trials conducted, and a few performed by pharmaceutical companies.7Troost B Smit JM Recent advances in antiviral drug development towards dengue virus.Curr Opin Virol. 2020; 43: 9-21Crossref Scopus (48) Google Scholar, 8Biering SB Harris E A step towards therapeutics for dengue.Nature. 2021; 598: 420-421Crossref Scopus (3) Google Scholar The importance of developing a treatment for dengue has largely been ignored.9Palanichamy Kala M St John AL Rathore APS Dengue: update on clinically relevant therapeutic strategies and vaccines.Curr Treat Options Infect Dis. 2023; 15: 27-52Crossref Google Scholar The Drugs for Neglected Diseases initiative, which is focused on finding novel affordable treatment solutions for neglected tropical diseases since its inception in 2003, has recently formed a Global Dengue Alliance with several institutions in dengue-endemic countries, including the Faculty of Medicine at Siriraj Hospital, Mahidol University in Thailand; the Ministry of Health in Malaysia; the Translational Health Science and Technology Institute in India; the Oswaldo Cruz Foundation in Brazil; and the Federal University of Minas Gerais in Brazil. The mission of this alliance is to accelerate research and development and deliver dengue therapeutics through an inclusive partnership. It aims to deliver a new treatment for dengue, within 5 years, from repurposed drugs and combinations (including novel antivirals from pharmaceutical companies). This alliance is co-created, co-owned, and co-funded by dengue-endemic countries, with a tiered governance mechanism allowing collaborative decision making at different levels. The organisations have formed a preclinical working group, a clinical working group, and a translational working group for effective communication and scientific planning. All three working groups feed into the Joint Steering Committee, which is responsible for delivering on the vision and mission of the alliance. The partners of this alliance share knowledge, experience, technologies, and capabilities to jointly validate preclinical assays with the ambition in the initial phase to identify currently available drugs that can be repurposed for use as dengue therapeutics. In parallel, clinical trials for these drug candidates are being designed using the expertise of clinicians in these countries who have been treating patients with dengue for many years, with initiation planned by the end of 2023. Formation of this alliance is a major step towards developing a treatment for dengue, by aggregating resources from endemic countries, and ensuring engagement, scientific leadership, clinical guidance, and political interest in these countries. The different working groups and the steering committee coordinate efforts to address gaps in knowledge, such as epidemiology (specifically in Africa), biomarkers and diagnostics, clinical trials, and regulatory framework, while promoting open science. Although currently the alliance has a small number of partners, it is open to collaborations with new partners and key stakeholders in therapeutics and diagnostics. Working with and aligning many partners and stakeholders to deliver objectives in a new model of collaboration is challenging, as is filling the existing knowledge gaps and need for integration, and leveraging information from different geographies and epidemiological settings. Furthermore, doing clinical trials aimed at treating dengue disease is challenging due to the seasonal nature of the disease, and with climate change, disease patterns could become more unpredictable. Although this approach is likely to accelerate development of a treatment, funding remains a challenge. With climate change becoming more of a concern in high-income countries, there is an increasing possibility that many global funding organisations will acknowledge the true burden of dengue, the devastation it causes to health systems and patients in endemic countries, and, therefore, the importance of funding initiatives to accelerate the development of new treatments for dengue. We declare no competing interests.

Abstract The global pandemic due to COVID-19 presents an unprecedented challenge to mankind including healthcare providers. Many COVID-19 infected patients may present with gastrointestinal symptoms. Endoscopic services may be required in complicated COVID-19 infected or suspected patients. In addition, resource allocation would demand judicious use of endoscopy services. There is a definite risk of transmission of COVID-19 during endoscopy to healthcare professionals. We recommend that only emergency and life-saving endoscopic procedures should be performed during COVID-19 pandemic, and semi-elective procedures should be performed after careful consideration. All routine endoscopy procedures should be deferred till normal hospital services resume. For emergency endoscopy procedures, prescreening of patients is critical to avoid nosocomial transmission. To prevent cross-infection among healthcare professionals, strict infection control measures should be practiced in endoscopy suite while providing essential endoscopic services to the patients.

Background: Healthcare-associated infections (HAIs) are a major global threat to patient safety. Systematic surveillance is crucial for understanding HAI rates and antimicrobial resistance trends and to guide infection prevention and control (IPC) activities based on local epidemiology. In India, no standardized national HAI surveillance system was in place before 2017. Methods: Public and private hospitals from across 21 states in India were recruited to participate in an HAI surveillance network. Baseline assessments followed by trainings ensured that basic microbiology and IPC implementation capacity existed at all sites. Standardized surveillance protocols for central-line–associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) were modified from the NHSN for the Indian context. IPC nurses were trained to implement surveillance protocols. Data were reported through a locally developed web portal. Standardized external data quality checks were performed to assure data quality. Results: Between May 2017 and April 2019, 109 ICUs from 37 hospitals (29 public and 8 private) enrolled in the network, of which 33 were teaching hospitals with &gt;500 beds. The network recorded 679,109 patient days, 212,081 central-line days, and 387,092 urinary catheter days. Overall, 4,301 bloodstream infection (BSI) events and 1,402 urinary tract infection (UTI) events were reported. The network CLABSI rate was 9.4 per 1,000 central-line days and the CAUTI rate was 3.4 per 1,000 catheter days. The central-line utilization ratio was 0.31 and the urinary catheter utilization ratio was 0.57. Moreover, 3,542 (73%) of 4,742 pathogens reported from BSIs and 868 (53%) of 1,644 pathogens reported from UTIs were gram negative. Also, 1,680 (26.3%) of all 6,386 pathogens reported were Enterobacteriaceae. Of 1,486 Enterobacteriaceae with complete antibiotic susceptibility testing data reported, 832 (57%) were carbapenem resistant. Of 951 Enterobacteriaceae subjected to colistin broth microdilution testing, 62 (7%) were colistin resistant. The surveillance platform identified 2 separate hospital-level HAI outbreaks; one caused by colistin-resistant K. pneumoniae and another due to Burkholderia cepacia . Phased expansion of surveillance to additional hospitals continues. Conclusions: HAI surveillance was successfully implemented across a national network of diverse hospitals using modified NHSN protocols. Surveillance data are being used to understand HAI burden and trends at the facility and national levels, to inform public policy, and to direct efforts to implement effective hospital IPC activities. This network approach to HAI surveillance may provide lessons to other countries or contexts with limited surveillance capacity. Funding: None Disclosures: None

Background: Aggressive hydration with lactated Ringer's solution (LRS) has been shown in a preliminary research to reduce the incidence of post-ERCP pancreatitis (PEP) but conflicting results have been demonstrated in follow-up studies.Aim: This randomized, controlled trial was designed to assess the effect of peri-procedural aggressive intravenous (IV) hydration with LRS on the incidence of PEP.Methods: Patients underwent first-time ERCP were randomly assigned (1:1) to receive either LRS at a rate of 150 ml/hr starting 2 hours prior to procedure, and continued during and after procedure to complete 24 hours (aggressive hydration) or LRS at a rate calculated by the Holliday-Segar method given peri-procedurally as described earlier (standard hydration).Visual analog scale, serum amylase, lipase, Creactive protein (CRP), and urine analysis were assessed prior to procedure and 24 hours after.The primary endpoint was PEP defined as new or increased epigastric pain persisting for ‡24 hours, elevation of amylase or lipase >3 times the upper limit of normal.Results: A total of 171 patients were enrolled, 86 were in standard hydration, and 85 in aggressive hydration group.In the standard hydration arm, 65/86 underwent ERCP and 3/65 excluded due to subsequent pancreatic duct (PD) stent placement.In aggressive hydration group, 59/ 85 underwent ERCP and 1/59 excluded due to PD stent placement.A total of 120 patients were analyzed.56% of patients were considered to be at increased risk for PEP based on age, sex, and procedure-related risk factors; however patient demographics and risk factors for PEP were similar in both groups.The majority of patients had common bile duct stone (50%) and malignant stricture (38%).PEP developed in 13 of 58 patients (22.4%) in aggressive hydration group vs. 11 of 62 patients (17.7%) in standard hydration group (OR= 1.34, 95%CI,.Serum amylase, lipase and CRP level were similar between two groups at 24 hours post ERCP.One patient in the standard hydration group developed leg edema but no other complications reported.In univariate analysis, TB >1.5 mg/dl, malignant obstruction, distal cholangiocarcinoma (CCA), difficult cannulation, PD cannulation, PD injection, double wire technique, metal stent placement were found to be risk factors for PEP.However, only distal CCA (OR=7.52,95%CI, 1.14-49.5),PD cannulation (OR=5.81,95%CI, 1.92-17.6),metal stent (OR=3.49,95%CI, 1.11-11.0),and difficult cannulation (OR=3.33,95%CI, 1.45-9.7)were independent risk factors for PEP in multivariate analysis.Subgroup analysis failed to show the effect of aggressive hydration on prevention of PEP in high risk patients.Conclusion: The results of this study suggested that aggressive hydration with LRS neither reduced the incidence of PEP nor improved markers of inflammatory process regardless of patient's risks for PEP.

Journal of Gastroenterology and HepatologyVolume 14, Issue 7 p. 615-617 Preoperative assessment of cholangiocarcinoma: Meeting the challenge Pramod Kumar Garg, Pramod Kumar Garg Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this authorRakesh Tandon, Rakesh Tandon Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this author Pramod Kumar Garg, Pramod Kumar Garg Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this authorRakesh Tandon, Rakesh Tandon Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this author First published: 19 April 2002 https://doi.org/10.1046/j.1440-1746.1999.01927.xCitations: 5 Rakesh K Tandon Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India. Email: <rtandon@medinst.ernet.in> Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume14, Issue7July 1999Pages 615-617 RelatedInformation

Descriptions of ten new species of the typical tropical genus Melanagromyza Hendel, from the Gangetic basin are given.

Infected pancreatic necrosis (IPN) is a dreaded complication of acute pancreatitis (AP). Most patients with IPN require drainage and necrosectomy preferably by minimally invasive method.

Rupture into the portal vein is a rare complication of a pancreatic pseudocyst. Only 15 cases of such an incidence have been described in the literature. Only one of these was diagnosed with magnetic resonance imaging (MRI), the rest being diagnosed using other invasive diagnostic modalities or at surgery. We report a case of this rare complication diagnosed on MRI and also describe the demonstration of residual lysed thrombus within the portal vein as a new feature on MRI which supports this diagnosis. The presence of liver necrosis present in our case is a probable effect of this complication not described in the literature before. Early diagnosis of this potentially lethal complication can help in the proper management of these patients.

Background Impaired autophagy contributes to development of acute pancreatitis (AP). We studied the effect of inducing autophagy by calorie-restriction and rapamycin, separately, in the caerulein-induced model of severe AP. Methods Adult, male, Swiss albino mice were given eight, hourly, intraperitoneal injections of caerulein (Ce) (50µg/Kg/dose). The interventions were calorie restriction (CR) and rapamycin (2mg/Kg). Mice were sacrificed at the 9 th hour. Pancreas was harvested for histopathology and immunoblotting. Amylase activity and the levels of cytokines were measured in plasma. Results The histopathological score and amylase activity were significantly lower in calorie-restricted caerulein-induced AP (CRCeAP) in comparison to animals that had unrestricted access to chow. In the CRCeAP group, levels of IL-6 and GM-CSF in plasma were lower and the expression of LC3II and Beclin-1 were higher. On transmission electron-microscopy, the area occupied by autophagic vacuoles was higher in CRCeAP. The expression of caspase-8 and caspase-9 was also higher in CRCeAP. In rapamycin with caerulein-induced AP (Rapa+CeAP), the histopathological score and amylase activity were significantly lower than caerulein-induced AP (CeAP). In Rapa+CeAP, the expression of LC3II and Beclin-1 were higher, whereas; SQSTM1 was decreased. The number of autophagic vacuoles in Rapa+CeAP group was fewer. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were lower in Rapa+CeAP. Caspase-3 increased and high mobility group box 1 (HMGB1) decreased in Rapa+CeAP. Conclusion Calorie-restriction and rapamycin can individually decrease the severity of injury in the caerulein-induced model of severe AP.

3alpha-Hydroxysteroid dehydrogenase (3alpha-HSD) from Pseudomonas testosteronei and diaphorase (lipoyl dehydrogenase) from Clostridium spp were immobilized individually onto alkylamine glass beads through glutaraldehyde coupling. A cost-effective enzymic colorimetric method for determination of bile acid in the serum and bile was developed employing mixture of the immobilized enzymes. The method was based upon measurement of NADH generated from NAD+ during oxidation of bile acid by immobilized 3alpha-HSD with a color reagent consisting of nitrobluetetrazolium (NBT) chloride salt and immobilized diaphorase in 0.065 M sodium phosphate buffer (pH 7.0). The minimum detection limit of the method was 4.8 pmol/L in the serum and 19.5 micromol/L in bile. The per cent recovery of added bile acid in the serum and bile was 89.1 and 95.0, respectively. Within and between batch coefficients of variation (CV) for bile acid determination were <1.0% and <0.2% in the serum and <0.2% and <0.6% in bile, respectively. A good correlation for bile acid in the serum (r1= 0.95) and in bile (r2 = 0.93) was obtained by a standard chemical method (a commonly used method in India) and the present method. The mixture of immobilized 3alpha-HSD and diaphorase lost 30% of its initial activity after 4 months of regular use. The cost of bile acid determination for 100 the serum and bile samples by the present method was found to be lower than by a commercially available method (Sigma kit 450-A).

effects of genetic ablation of p50 and p65/RelA NF-kB proteins on the recovery after acute caerulein pancreatitis (CER-AP).We also examined links between NF-kB and autophagy, the principal cellular degradative process which we and others found to play an important role in pancreatitis pathogenesis.Methods: CER-AP was induced in wild type, p50-/-, and p50-/-;p65+/-mice (p65 total deletion is embryonically lethal); isolated acinar cells were treated with 100 nM CCK-8.We measured histological and biochemical parameters of pancreatitis, as well as autophagy, at different times during the acute and recovery phase of CER-AP.Results: Genetic ablation of p50 and p65 modestly facilitated the recovery after CER-AP, that is, the return of parameters measured to their basal values in pancreas.In particular, inflammatory cell infiltration was dampened in NF-kB deficient pancreas, both in the acute and recovery phase.The beneficial effects were more pronounced in p50-/-;p65+/-versus p50 null mice; for example, 24 h after start of CER-AP serum lipase level was elevated 7.3x in wild type, 4.0x in p50-/-, and 1.6x in p50-/-;p65+/-mice.Interestingly, CER-induced increase in pancreatic trypsin activity was significantly (by >50% at 7 h) inhibited in NF-kB deficient mice; but there was no difference in CCK-induced trypsinogen activation in acinar cells isolated from NF-kB deficient versus wild type mice.These results provide strong evidence that infiltrating inflammatory cells mediate trypsinogen activation in pancreatitis; and against direct linkage between NF-kB and trypsinogen activation in acinar cells.We found that NF-kB activation plays a role in regulating autophagy pathways in pancreatitis.For example, pancreatic level of p62/SQSTM1 protein dramatically increased in CER-AP, indicating impaired autophagic flux; the increase was much less in NF-kB deficient pancreas.Of note, the role of NF-kB in regulating autophagy, in general, is complex and poorly understood.Conclusion: The results indicate that preventing NF-kB activation does not impede but (modestly) facilitates the recovery after experimental acute pancreatitis.Thus, approaches to dampen NF-kB activation can be beneficial in treatment of acute pancreatitis.

Makharia, Govind K. M.D., D.M., D.N.B.; Nandi, Bhaskar M.D.; Garg, Pramod K. M.D., D.M.; Tandon, Rakesh K. M.D., Ph.D. Author Information

Introduction: Systemic inflammation in severe acute pancreatitis (SAP) is due to excessive release of pro-inflammatory cytokines, which may be decreased by glucocorticoids or specific monoclonal antibodies. Here, we explored the effect of dexamethasone and infliximab in L-arginine induced experimental SAP in mice. Methods: Ninety-four, male, Swiss albino mice were randomly divided into 9 groups. Severe AP was induced by intraperitoneal injections of L-arginine (4.5 g/Kg, two doses, one hour apart). The four treatment groups were given either dexamethasone (10 mg/Kg intravenous) or infliximab (16 mg/KG intravenous) either prophylactically (30 minutes prior to L-arginine injection) or therapeutically (24 hours after L-arginine injection). Animals were euthanized at 72 hours, histopathological evaluation and biochemical analyses performed on the harvested blood, lungs and pancreas. Results: The histopathological scores were not significantly different between the SAP and the SAP with treatment with dexamethasone. Pancreatic histopathology didn't significantly improve with infliximab. Therapeutic infliximab decreased lung histopathology score (p = 0.005) but lung myeloperoxidase remained unchanged in the drug treated groups (p = ns). Plasma amylase was not significantly different in the SAP, or treatment with dexamethasone (median 5809.9 vs 3697.6 vs 3327.5 U/L, p = ns) or infliximab (median 5809.9 vs 4830.7 vs 4566.8 U/L, p = ns). No significant difference in the serum levels of cytokines TNF-alpha, IL-6 and IL-10 was noted. Conclusions: Dexamethasone and infliximab did not decrease the severity of L-arginine-induced murine AP.

Abstract Descriptions of three new species of Agromyzidae from the Gangetic basin (India), viz., Cerodontha (Dizygomyza) graminiphila, sp. nov., Liriomyza tarala, sp. nov. and Phytomyza culmicola, sp. nov. are given.

Abstract Background/Objective There is a paucity of data on the management of gastrointestinal (GI) bleeding in patients with COVID-19 amid concerns about the risk of transmission during endoscopic procedures. We aimed to study the outcomes of conservative treatment for GI bleeding in patients with COVID-19. Methods In this retrospective analysis, 24 of 1342 (1.8%) patients with COVID-19, presenting with GI bleeding from 22 April to 22 July 2020, were included. Results The mean age of patients was 45.8±12.7 years; 17 (70.8%) were males; upper GI (UGI) bleeding: lower GI (LGI) 23:1. Twenty-two (91.6%) patients had evidence of cirrhosis-21 presented with UGI bleeding while one had bleeding from hemorrhoids. Two patients without cirrhosis were presumed to have non-variceal bleeding. The medical therapy for UGI bleeding included vasoconstrictors-somatostatin in 17 (73.9%) and terlipressin in 4 (17.4%) patients. All patients with UGI bleeding received proton pump inhibitors and antibiotics. Packed red blood cells (PRBCs), fresh frozen plasma and platelets were transfused in 14 (60.9%), 3 (13.0%) and 3 (13.0%), respectively. The median PRBCs transfused was 1 (0-3) unit(s). The initial control of UGI bleeding was achieved in all 23 patients and none required an emergency endoscopy. At 5-day follow-up, none rebled or died. Two patients later rebled, one had intermittent bleed due to gastric antral vascular ectasia, while another had rebleed 19 days after discharge. Three (12.5%) cirrhosis patients succumbed to acute hypoxemic respiratory failure during hospital stay. Conclusion Conservative management strategies including pharmacotherapy, restrictive transfusion strategy, and close hemodynamic monitoring can successfully manage GI bleeding in COVID-19 patients and reduce need for urgent endoscopy. The decision for proceeding with endoscopy should be taken by a multidisciplinary team after consideration of the patient’s condition, response to treatment, resources and the risks involved, on a case to case basis.

“White bile” is a colorless bilirubin-free fluid found as an uncommon manifestation of biliary tract disease. Reports of “white bile” are limited to one or a few patients and date to the 1930s.1Edington GH McCallum G The occurrence of “white bile” in gall stone obstruction: note of a case.Glasg Med J. 1930; 114: 257-264Google Scholar, 2Lake NC White bile.Lancet. 1934; 2: 753-755Abstract Scopus (3) Google Scholar, 3Flint ER Obstruction of the common bile duct.Br Med J. 1937; 2: 253-256Crossref PubMed Scopus (6) Google Scholar, 4Griffiths DB Haber MH Rees KR Smith JF Analysis of white bile in a case of cholangiocarcinoma of the hepatic ducts.J Path Bact. 1963; 85: 389-393Crossref PubMed Scopus (6) Google Scholar, 5Bouchier AD Cooperbrand SR The characteristics of “white bile.”.Gastroenterology. 1965; 49: 354-359Abstract Full Text PDF PubMed Google Scholar, 6Aronsohn HG Pathogenesis of “white bile”.Proc Soc Exp Biol. 1935; 32: 695-697Crossref Scopus (1) Google Scholar, 7Hawthorne HR Sterling JA White bile in the common bile duct.Am J Surg. 1955; 90: 397-401Abstract Full Text PDF PubMed Scopus (5) Google Scholar, 8Elmslie RG Thorpe MEC Colman JVL Boughton CR Pritchard GR Hoy RJ Clinical significance of white bile in the biliary tree.Gut. 1969; 10: 530-533Crossref PubMed Scopus (6) Google Scholar In these reports, certain generalizations about the clinical significance of “white bile” are claimed, although the conclusions are conflicting. Bouchier et al.5Bouchier AD Cooperbrand SR The characteristics of “white bile.”.Gastroenterology. 1965; 49: 354-359Abstract Full Text PDF PubMed Google Scholar in 1985 studied 2 cases: in one, “white bile” was described as “thick, glary, translucent and viscous” and the other as “thin, transparent and sterile.” Lake2Lake NC White bile.Lancet. 1934; 2: 753-755Abstract Scopus (3) Google Scholar described “white bile” from the gallbladder as “putty colored, pultaceous” in contrast to the watery nature of “white bile” from the common bile duct. Bouchier et al.5Bouchier AD Cooperbrand SR The characteristics of “white bile.”.Gastroenterology. 1965; 49: 354-359Abstract Full Text PDF PubMed Google Scholar demonstrated that “white bile” accompanied different pathologic states of the biliary system and could have varying characteristics. “White bile” was used to describe secretions obtained from the bile duct after prolonged obstruction, despite the fact that it exhibited a spectrum of macroscopic appearances rather than a specific appearance. As the term denotes, white bile is certainly different from the purulent, thick fluid found in the infected biliary system. Even infected bile may range in color from dark green or black to white, thick pus-like fluid. Hence the term “white bile” cannot be confused with purulent bile. But because these terms have become part of the history of medicine, the names have not changed. The primary aim of our study was to reevaluate this loosely defined entity and, most importantly, to define its prognostic significance; that is, to evaluate the prognosis of patients with “white bile” and for this purpose we used the term “white bile” as has been used conventionally. Misnomers are abundant in medical publications: biliary colic, pulsus paradoxus, herpes gestationalis, pretibial myxoedema, superficial femoral vein, and retinitis pigmentosa. Other more vivid terms are tennis elbow, carpal tunnel syndrome, rodent ulcer, and pyoderma gangrenosum. Although misnomers, these terms have a special niche in medical parlance because they identify specific entities. As medical knowledge evolves, the basis for coining these names has in many cases been found to be incorrect and hence the term becomes a misnomer. Similarly, “white bile” was the name used by surgeons decades ago to describe a particular entity encountered during biliary surgery. With biliary endoscopic interventions, endoscopists also encounter this entity. In recent decades, our series is perhaps one of the largest in which the clinical importance of “white bile” was investigated. Yet, to call “white bile” a clear misnomer would require a study to define its macroscopic characters in relation to different pathologic states of the gallbladder and biliary tract. Based on available data, the term denotes a spectrum of macroscopic characteristics ranging from “putty-thick fluid” to “colorless, watery fluid.” Judd and Lyons9Judd LS Lyons JH White bile in the common duct.Ann Surg. 1923; 77: 281-292PubMed Google Scholar described a peculiar case of obstruction caused by biliary stone in which the gallbladder contained green, watery material although there was no trace of bile in the fluid from the common duct. We hesitated to change the term “white bile” to “colorless biliary secretions” in our report because we studied only common duct bile and not bile from the gallbladder in patients with biliary obstruction. A more appropriate term, based on present knowledge, may be “stasis fluid” rather than “colorless biliary secretions.” Although available reports are dated, these show that the macroscopic characters of “white bile” obtained from the gallbladder may differ from those of “white bile” obtained from the common bile duct. Although we have reservations with regard to labeling the term “white bile” as unequivocally a misnomer, it remains a matter of mere semantics and it is not necessary to be dogmatic about it. “Horned toad” and “horned frog” are the most commonly used misnomers for “horned lizard.”

Abstract Melanagromyza campanularia, sp. nov. and Cerodontha (Pöemyza) siwalikensis, sp. nov. are described as new from India. Descriptions of external genitalia of the male flies are also included.

Stroke ranges third in mortality in industrialized nations and is the leading cause of disability in older people. Ischemic stroke following thrombotic or embolic vessel occlusion accounts for more than 80% of cerebrovascular events. Immediate restoration of cerebral blood flow is crucial in order to salvage brain tissue. Experimental thrombolytic treatment was introduced into the clinical setting in the late 1950s and required more than 30 years of intense research till its breakthrough and subsequent routine clinical use by the presentation of the NINDS trial results in 1995. To date, intravenous thrombolysis with tissue plasminogen activator up to 4.5 h after symptom onset is the only proven reperfusion therapy for acute ischemic stroke. In this review, we summarize the evolution of intravenous and intra-arterial pharmacological recanalization therapies in acute ischemic stroke and present current clinical practice as well as its promising perspectives.

Introduction: Pancreatic resections are associated with POPF which occur less frequently with a firm pancreas. We used EUSE to assess pancreatic texture at the resection margin and its relation to pancreatic fibrosis and POPF. Methods: Between June 2012 and December 2013 all patients who underwent EUS for diagnosis/assessment of resectability had an EUSE done. An area (A) in the neck/body (intended resection site) and another area (B) in the peripancreatic soft tissue were analysed. The strain ratio (B/A) was used to assess pancreatic texture. The main pancreatic duct (MPD) size was measured and the degree of fibrosis at the resected pancreatic margin was assessed histologically. Results: Thirty-four patients were studied. A strain ratio of ≤2.75 defined normal/soft and >2.75 as firm/very firm pancreas. Nine had clinically relevant POPF (26.5%; ISGPF grades B: 6 and C: 3). A higher proportion of patients with strain ratio ≤2.75 developed POPF (34.7% vs. 9.1%; p = 0.21) and had a sensitivity and negative predictive value of 88.9% and 91%, respectively Patients with no/minimal fibrosis had a higher rate of POPF(32% vs. 11.1%; p = 0.39). Strain ratio correlated well with pancreatic texture, fibrosis grade and MPD size (p < 0.001). POPF occurred more frequently in those with a higher mean BMI (22.5 ± 3.6 vs. 20.1 ± 2.7; P = 0.04). Strain ratio had an accuracy, sensitivity, specificity, PPV and NPV of 88.2%, 89%, 88%, 72.7% and 95%, respectively for assessment of fibrosis. Conclusions: EUSE of the pancreas did not predict POPF but correlated well with pancreatic texture, degree of pancreatic fibrosis and MPD size.

MicroRNA expression patterns in many physiological and oncogenic processes have been established. However, the role of aberrant miRNA expression in periampullary carcinoma (PAC) has not been elucidated. We hypothesize that PAC may have differential expression of miRNAs which may differentiate the tumor histological subtypes.Fresh paired tumor and control samples were collected from the PAC patients undergoing Whipple's pancreaticoduodenectomy. Microarray miRNA profiling was performed utilizing tumor (n = 40) and control tissues; adjacent normal pancreas (n = 22), six each distal CBD, duodenum and ampulla. Data obtained was subjected to statistical and bioinformatic analysis. Differentially expressed miRNAs obtained were validated using qPCR in an independent set of samples.Comparison of PAC tissue samples with controls revealed 29 common and differentially expressed miRNAs (20 upregulated and 9 downregulated) with a higher statistical significance (p < 0.001) and fold change (log2 FC > 1.5). A subset of 16 miRNAs (15 overexpressed and 1 underexpressed) differed in expression levels between pancreatobiliary and intestinal subtypes. Among these, miR-375, miR-31 and miR-196a expressions varied significantly between histological subtypes. Differential expression profiles of miRNAs specific to TNM staging was also observed in PAC subtypes. Target gene prediction for the differentially expressed miRNAs in PAC revealed that target genes are enriched for certain pathways. Particularly, Wnt signaling pathway genes appear to be relevant targets for most of the differentially expressed miRNAs.Differentially expressed common miRNA signatures identified in PAC subgroups may have a role in pathogenesis of PAC and miR-375, miR-31 and miR-196a expression patterns may differentiate PAC subtypes.

We present 2 techniques for treatment of intractable pancreatic fistula: percutaneous transfistulous pancreatic duct drainage and interventional pancreatojejunostomy. Percutaneous transfistulous pancreatic duct drainage can be effective for intractable fistulas that communicate with the main pancreatic duct. Because drainage itself is not enough for a complete cure of this complication when it occurs in cases after pancreatoduodenectomy (PD), interventional pancreatojejunostomy is applicable.

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure used to treat severe complications of chronic pancreatitis or very high risk of pancreatic cancer while reducing the risk of severe diabetes mellitus. However, clear guidance on indications, contraindications, evaluation, timing, and follow-up are lacking.A working group reviewed the medical, psychological, and surgical options and supporting literature related to TPIAT for a consensus meeting during PancreasFest.Five major areas requiring clinical evaluation and management were addressed: These included: 1) indications for TPIAT; 2) contraindications for TPIAT; 3) optimal timing of the procedure; 4) need for a multi-disciplinary team and the roles of the members; 5) life-long management issues following TPIAP including diabetes monitoring and nutrition evaluation.TPIAT is an effective method of managing the disabling complications of chronic pancreatitis and risk of pancreatic cancer in very high risk patients. Careful evaluation and long-term management of candidate patients by qualified multidisciplinary teams is required. Multiple recommendations for further research were also identified.

Infected pancreatic necrosis (IPN) is a dreaded complication of acute pancreatitis (AP). Most patients with IPN require drainage and necrosectomy preferably by minimally invasive method. We have previously shown that single or multiport percutaneous endoscopic necrosectomy (PEN) is a safe and effective minimally invasive technique for IPN.

Benzophenone-3 (BP-3) is a widespread environmental contaminant and an estrogenic compound. Very little is known with regard to the occurrence in indoor air and the inhalation exposure of humans to BP-3. In this study, 81 indoor air samples were collected from various locations in Albany, New York, USA, in 2014 and analyzed for BP-3 by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). BP-3 was found in all indoor air samples and the overall concentrations in bulk air (vapor plus particulate phases) were in the range of 0.19–72.0 ng/m3 (geometric mean: 2.67 ng/m3). The highest concentrations (geometric mean: 10.7 ng/m3) were found in cars, followed by barber shops (6.57) ˃ public places (5.75) > homes (3.27) ˃ offices (1.96) ˃ garages (1.04) ˃ laboratories (0.47). The estimated geometric mean daily intake (EDI) of BP-3 for infants, toddlers, children, teenagers, and adults through indoor air inhalation from homes was 1.83, 1.74, 1.18, 0.69, and 0.51 ng/kg-bw/day, respectively. Although high concentrations of BP-3 were measured in some microenvironments, the estimated contribution of indoor air to total BP-3 intake was < 5% of the total BP-3 intake in humans. This is the first survey on the occurrence of BP-3 in indoor air.