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The International Rome Committee defines Disorders of Gut-Brain Interactions (DGBI) based upon distinct combinations of chronic and/or recurrent unexplained gastrointestinal symptoms. Yet patients often experience overlapping DGBI. Patients with DGBI frequently also suffer from extraintestinal symptoms, including fatigue, sleep disturbances, anxiety, and depression. Patients with overlapping DGBI typically experience more severe GI symptoms and increased psychosocial burden. Concerning the pathophysiology, DGBI are associated with disruptions in gut motility, function of the brain and enteric neurons, immune function, and genetic markers, with recent findings revealing gut microbiome alterations linked to these mechanisms of DGBI. Emerging evidence summarized in this review suggests that the microbiome influences various established disease mechanisms of different DGBI groups. Overall, changes in the gastrointestinal microbiome do not seem to be linked to a specific DGBI subgroup but may play a key role in the manifestation of different DGBI and, subsequently, overlap of DGBI. Understanding these shared mechanisms and the role of the gastrointestinal microbiome, particularly for overlapping DGBI, might aid in developing more precise diagnostic criteria and treatment strategies while developing personalized interventions that target specific mechanisms to improve patient outcomes.

Following acute gastroenteritis (AGE) due to bacteria, viruses, or protozoa, a subset of patients develop new onset Rome criteria positive irritable bowel syndrome (IBS), called postinfection IBS (PI-IBS). The pooled prevalence of PI-IBS following AGE was 11.5%. PI-IBS is the best natural model that suggests that a subset of patients with IBS may have an organic basis. Several factors are associated with a greater risk of development of PI-IBS following AGE including female sex, younger age, smoking, severity of AGE, abdominal pain, bleeding per rectum, treatment with antibiotics, anxiety, depression, somatization, neuroticism, recent adverse life events, hypochondriasis, extroversion, negative illness beliefs, history of stress, sleep disturbance, and family history of functional gastrointestinal disorders (FGIDs), currently called disorder of gut-brain interaction. Most patients with PI-IBS present with either diarrhea-predominant IBS or the mixed subtype of IBS, and overlap with other FGIDs, such as functional dyspepsia is common. The drugs used to treat non-constipation IBS may also be useful in PI-IBS treatment. Since randomized controlled trials on the efficacy of drugs to treat PI-IBS are rare, more studies are needed on this issue.

Abstract Functional gastrointestinal disorders (FGIDs), currently known as disorders of gut–brain interaction, are emerging microbiota–gut–brain abnormalities that are prevalent worldwide. The pathogenesis of FGIDs is heterogeneous and is intertwined with gut microbiota and its derived molecule‐modulated mechanisms, including gut dysmotility, visceral hypersensitivity, gut immune abnormalities, abnormal secretion, and impaired barrier function. There has been phenomenal progress in understanding the role of gut microbiota in FGIDs by underpinning the species alternations between healthy and pathological conditions such as FGIDs. However, the precise gut microbiota‐directed cellular and molecular pathogeneses of FGIDs are yet enigmatic. Determining the mechanistic link between the gut microbiota and gastrointestinal (GI) diseases has been difficult due to (i) the lack of robust animal models imitating the various aspects of human FGID pathophysiology; (ii) the absence of longitudinal human and/or animal studies to unveil the interaction of the gut microbiota with FGID‐relevant pathogenesis; (iii) uncertainty about connections between human and animal studies; and (iv) insufficient data supporting a holistic view of disease‐specific pathophysiological changes in FGID patients. These unidentified gaps open possibilities to explore pathological mechanisms directed through gut microbiota dysbiosis in FGIDs. The current treatment options for dysbiotic gut microbiota are limited; dietary interventions, antibiotics, probiotics, and fecal microbiota transplantation are the front‐line clinical options. Here, we review the contribution of gut microbiota and its derived molecules in gut homeostasis and explore the possible pathophysiological mechanisms involved in FGIDs leading to potential therapeutics options.

Abstract Background and Aim Although telemedicine is an option for the care of inflammatory bowel disease (IBD) patients during the Coronavirus Disease (COVID)‐19 pandemic, its feasibility and acceptability data are scant. Data on the frequency of COVID‐19 among patients with IBD, quality of life (QOL), access to health care, psychological stress, and anxiety during the COVID‐19 pandemic are scant. Methods Video/audio consultation for IBD patients was undertaken after a web‐based appointment, and data on acceptability, IBD control, Hospital Anxiety Depression Scale (HADS), and World Health Organization Quality of Life questionnaire (WHOQOL‐Bref) were obtained electronically. IBD patients were assessed for COVID‐19 symptoms or contact history and tested using reverse transcriptase polymerase chain reaction (RT‐PCR) on naso‐ oro‐pharyngeal swabs, and data were compared with 16,317 non‐IBD controls. Results Teleconsultation was feasible and acceptable. IBD patients had COVID‐19 as frequently as non‐IBD controls despite immunosuppressive therapy, possibly due to their awareness and preventive practices. Although the physical, psychological, and social QOL scores during the COVID‐19 pandemic were comparable to the prepandemic period, the environmental scores were worse. Psychological tension and interference with work due to pain were lower during the pandemic, which might be influenced by the control of the disease. Conclusions Teleconsultation is a feasible and acceptable alternative for IBD patients. They had COVID‐19 as frequently as non‐IBD controls despite a high frequency of immunosuppressive treatment, possibly due to their awareness of the disease and preventive practices. The QOL scores (except the environmental domains) and psychological issues were quite comparable or even better during the COVID‐19 pandemic than earlier.

Abstract Background and Aim About 15% patients with acute severe ulcerative colitis (UC) fail to respond to medical treatment and may require colectomy. An early prediction of response may help the treating team and the patients and their family to prepare for alternative treatment options. Methods Data of 263 patients (mean age 37.0 ± 14.0‐years, 176, 77% male) with acute severe UC admitted during a 12‐year period were used to study predictors of response using univariate analysis, multivariate linear principal component analysis (PCA), and nonlinear artificial neural network (ANN). Results Of 263 patients, 231 (87.8%) responded to the initial medical treatment that included oral prednisolone (n = 14, 5.3%), intravenous (IV) hydrocortisone (n = 238, 90.5%), IV cyclosporine (n = 9, 3.4%), and inflixmab (n = 2, 0.7%), and 28 (10.6%) did not respond and the remaining 4 (1.5%) died, all of whom did were also nonresponders. Nonresponding patients had to stay longer in the hospital and died more often. On univariate analysis, the presence of complications, the need for use of cyclosporin, lower Hb, platelets, albumin, serum potassium, and higher C‐reactive protein were predictors of nonresponse. Hb and albumin were strong predictive factors on both PCA and ANN. Though the nonlinear modeling using ANN had a good predictive accuracy for the response, its accuracy for predicting nonresponse was lower. Conclusion It is possible to predict the response to medical treatment in patients with UC using linear and nonlinear modeling technique. Serum albumin and Hb are strong predictive factors.

Functional gastrointestinal disorders (FGIDs) have been re-named as disorders of gut-brain interactions. These conditions are not only common in clinical practice, but also in the community. In reference to the Rome IV criteria, the most common FGIDs, include functional dyspepsia (FD) and irritable bowel syndrome (IBS). Additionally, there is substantial overlap of these disorders and other specific gastrointestinal motility disorders, such as gastroparesis. These disorders are heterogeneous and are intertwined with several proposed pathophysiological mechanisms, such as altered gut motility, intestinal barrier dysfunction, gut immune dysfunction, visceral hypersensitivity, altered GI secretion, presence and degree of bile acid malabsorption, microbial dysbiosis, and alterations to the gut-brain axis. The treatment options currently available include lifestyle modifications, dietary and gut microbiota manipulation interventions including fecal microbiota transplantation, prokinetics, antispasmodics, laxatives, and centrally and peripherally acting neuromodulators. However, treatment that targets the pathophysiological mechanisms underlying the symptoms are scanty. Pharmacological agents that are developed based on the cellular and molecular mechanisms underlying pathologies of these disorders might provide the best avenue for future pharmaceutical development. The currently available therapies lack long-term effectiveness and safety for their use to treat motility disorders and FGIDs. Furthermore, the fundamental challenges in treating these disorders should be defined; for instance, 1. Cause and effect cannot be disentangled between symptoms and pathophysiological mechanisms due to current therapies that entail the off-label use of medications to treat symptoms. 2. Despite the knowledge that the microbiota in our gut plays an essential part in maintaining gut health, their exact functions in gut homeostasis are still unclear. What constitutes a healthy microbiome and further, the precise definition of gut microbial dysbiosis is lacking. More comprehensive, large-scale, and longitudinal studies utilizing multi-omics data are needed to dissect the exact contribution of gut microbial alterations in disease pathogenesis. Accordingly, we review the current treatment options, clinical insight on pathophysiology, therapeutic modalities, current challenges, and therapeutic clues for the clinical care and management of functional dyspepsia, gastroparesis, irritable bowel syndrome, functional constipation, and functional diarrhea.

Introduction Regardless of having effective vaccines against COVID-19, containment measures such as enhanced physical distancing and good practice of personal hygiene remain the mainstay of controlling the COVID-19 pandemic. Countries across Asia have imposed these containment measures to varying extents. However, residents in different countries would have a differing degree of compliance to these containment measures potentially due to differences in the level of awareness and motivation in the early phase of pandemic.Objectives In our study, we aimed to describe and correlate the level of knowledge and attitude with the level of compliance with personal hygiene and physical distancing practices among Asian countries in the early phase of pandemic.Methods A multinational cross-sectional study was carried out using electronic surveys between May and June 2020 across 14 geographical areas. Subjects aged 21 years and above were invited to participate through social media, word of mouth and electronic mail.Results Among the 2574 responses obtained, 762 (29.6%) participants were from East Asia and 1812 (70.4%) were from Southeast Asia (SEA). A greater proportion of participants from SEA will practise physical distancing as long as it takes (72.8% vs 60.6%). Having safe distancing practices such as standing more than 1 or 2 m apart (AdjOR 5.09 95% CI (1.08 to 24.01)) or more than 3 or 4 m apart (AdjOR 7.05 95% CI (1.32 to 37.67)), wearing a mask when they had influenza-like symptoms before the COVID-19 pandemic, preferring online news channels such as online news websites/applications (AdjOR 1.73 95% CI (1.21 to 2.49)) and social media (AdjOR 1.68 95% CI (1.13 to 2.50) as sources of obtaining information about COVID-19 and high psychological well-being (AdjOR 1.39 95% CI (1.04 to 1.87)) were independent factors associated with high compliance.Conclusions We found factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic and it will be useful to consider them in risk assessment, communication and pandemic preparedness.

ImportanceKnowledge and attitude influence compliance and individuals' practices. The risk and protective factors associated with high compliance to these preventive measures are critical to enhancing pandemic preparedness.ObjectiveThis survey aims to assess differences in mental health, knowledge, attitudes, and practices (KAP) of preventive measures for COVID-19 amongst healthcare professionals (HCP) and non-healthcare professionals.DesignMulti-national cross-sectional study was carried out using electronic surveys between May-June 2020.SettingMulti-national survey was distributed across 36 countries through social media, word-of-mouth, and electronic mail.ParticipantsParticipants ≥21 years working in healthcare and non-healthcare related professions.Main outcomeRisk factors determining the difference in KAP towards personal hygiene and social distancing measures during COVID-19 amongst HCP and non-HCP.ResultsHCP were significantly more knowledgeable on personal hygiene (AdjOR 1.45, 95% CI -1.14 to 1.83) and social distancing (AdjOR 1.31, 95% CI -1.06 to 1.61) compared to non-HCP. They were more likely to have a positive attitude towards personal hygiene and 1.5 times more willing to participate in the contact tracing app. There was high compliance towards personal hygiene and social distancing measures amongst HCP. HCP with high compliance were 1.8 times more likely to flourish and more likely to have a high sense of emotional (AdjOR 1.94, 95% CI (1.44 to 2.61), social (AdjOR 2.07, 95% CI -1.55 to 2.78), and psychological (AdjOR 2.13, 95% CI (1.59-2.85) well-being.Conclusion and relevanceWhile healthcare professionals were more knowledgeable, had more positive attitudes, their higher sense of total well-being was seen to be more critical to enhance compliance. Therefore, focusing on the well-being of the general population would help to enhance their compliance towards the preventive measures for COVID-19.

Background/AimsBecause Methanobrevibacter smithii produces methane, delaying gut transit, we evaluated M. smithii loads in irritable bowel syndrome (IBS) patients and healthy controls (HC).Methods : Quantitative real-time polymerase chain reaction for M. smithii was performed on the feces of 47 IBS patients (Rome III) and 30 HC. On the lactulose hydrogen breath test (LHBT, done for 25 IBS patients), a fasting methane result ≥10 ppm using 10 g of lactulose defined methane-producers.Results : Of 47, 20 had constipation (IBS-C), 20 had diarrhea (IBS-D) and seven were not sub-typed. The M. smithii copy number was higher among IBS patients than HC (Log105.4, interquartile range [IQR; 3.2 to 6.3] vs 1.9 [0.0 to 3.4], p

Gastric outlet obstruction (GOO) is usually a late presentation of gastric cancer, pancreaticobiliary malignancy, and extrinsic lymph nodal compression. Presenting symptoms are abdominal pain, postprandial epigastric fullness, and recurrent vomiting, which lead to severe malnutrition and dehydration and poor quality of life (QoL). Endoscopic enteral stent placement has become the acceptable alternative modality for palliation of malignant GOO because it is safe, minimally invasive, and a cost-effective procedure. In addition, endoscopic stent placement leads to shorter time to resume oral diet and shorter hospital stay in comparison to surgical bypass. Endoscopic stent placement is associated with high technical as well as clinical success rates and improvement in QoL, but no survival improvement. Recurrence of symptoms occurs due to stent occlusion, or stent migration, which can be successfully managed with repeat endoscopic stent placement. Perforation and bleeding are serious but rare complications.

Background and study aims Gastrointestinal endoscopy, being an aerosol-generating procedure, has the potential to transmit Severe Acute Respiratory Distress Syndrome Corona Virus-2 (SARS-CoV-2) during the current pandemic. Adequate knowledge is the key to prevention. A survey, perhaps the first, was conducted among Indian endoscopists to assess the impact of Coronavirus Disease (COVID)-19 on gastroinestinal endoscopy practice in the country. Methods From April 24 to 28, 2020, an electronic survey (using Google Form) was conducted with 23 questions (single or multiple answers) on: (1) endoscopy practice before the pandemic; (2) knowledge about COVID-19; and (3) its impact on endoscopy practice. Results Responses were received from 375 of 1205 (31.1 %) endoscopists. Most (35.7 %) were young (31–40 years), practicing in corporate multi-speciality hospitals (44.6 %) or independent practice set-up (17.7 %) in metropolitan cities (55.6 %) and urban areas (42.3 %). In most units (75.4 %), fewer than 10 % of procedures performed are endoscopies, as compared to before the pandemic. A reduction in volume of endoscopy related to restriction of the routine procedures by the latest guideline was reported by 86.9 % of respondents. Most are using N95 masks (74.7 %) and/or complete personal protective equipment (PPE, 49.2 %) during endoscopic procedures. Only 18.3 % of respondents had access to negative pressure rooms either within (5.4 %) or outside (12.9 %) the usual endoscopy suite. Conclusion Endoscopy units in India are performing fewer than 10 % of their usual volumes due to current restrictions. Resources to follow current international guidelines, including use of negative pressure rooms and PPE, are limited. Alternate measures are needed to keep up the services.

Chronic inflammation and long-term tissue injury are related to many malignancies, including gastric cancer (GC). Helicobacter pylori (H. pylori), classified as a class I carcinogen, induces chronic superficial gastritis followed by gastric carcinogenesis. Despite a high prevalence of H. pylori infection, only about 1–3% of people infected with this bacterium develop GC worldwide. Furthermore, the development of chronic gastritis in some, but not all, H. pylori-infected subjects remains unexplained. These conflicting findings indicate that clinical outcomes of aggressive inflammation (atrophic gastritis) to gastric carcinogenesis are influenced by several other factors (in addition to H. pylori infection), such as gut microbiota, co-existence of intestinal helminths, dietary habits, and host genetic factors. This review has five goals: (1) to assess our current understanding of the process of H. pylori-triggered inflammation and gastric precursor lesions; (2) to present a hypothesis on risk modulation by the gut microbiota and infestation with intestinal helminths; (3) to identify the dietary behavior of the people at risk of GC; (4) to check the inflammation-related genetic polymorphisms and role of exosomes together with other factors as initiators of precancerous lesions and gastric carcinoma; and (5) finally, to conclude and suggest a new direction for future research.

Background: We evaluated short‑ and long‑term results of endoscopic drainage (a minimally invasive nonsurgical treatment) of pancreatic pseudocysts (PPCs) and factors associated with its success at a multilevel teaching hospital in Northern India, as such data are scanty from India. Patients and Methods: Retrospective review of records of consecutive patients undergoing endoscopic drainage of PPC from January 2002 to June 2013 was undertaken. Results: Seventy‑seven patients (56 males), median age 36 years (range, 15–73), underwent endoscopic drainage of PPC with 98% technical success. Pseudocysts drained were symptomatic (duration 11 weeks, range, 8–68), large (volume 582 mL [range, 80–2706]), located in head (n = 32, 46%), body and tail (n = 37, 54%), and infected (n = 39, 49%). Drainage procedures included cystogastrostomy (n = 54, 78%), cystoduodenostomy (n = 9, 13%), transpapillary drainage (n = 2, 3%), and multiple route (n = 4, 6%), with additional endoscopic nasocystic drainage (ENCD) in 41 (59%). Sixty‑nine patients were followed up (median 28 months, range 2–156; other eight lost to follow‑up). Complications (n = 21, 30%) included stent occlusion and migration (13), bleeding (5), perforation (2), and death (1). Endoscopic procedure had to be repeated in 19 patients (28%; 16 for sepsis, 3 for recurrence). The reasons for additional nonendoscopic treatment (n = 8, 12%) included incomplete cyst resolution (3), recurrence (2), bleeding (1), and perforation (2). Overall success rate of endoscopic drainage was 88%. Whereas infected pseudocysts were associated with poorer outcome (odds ratio [OR] 0.016; 95% confidence interval [CI] 0.001–0.037), placement of ENCD led to better results (OR 11.85; 95% CI 1.03–135.95). Conclusion: Endoscopic drainage is safe and effective for PPC.

Summary: Microsporidia cause diarrhea among human immunodeficiency virus (HIV) infected patients worldwide. Enterocytozoon bieneusi and Encephalitozoon intestinalis are the most common species infecting HIV patients. Various genotypes of E. bieneusi are transmitted from human to human (anthroponotic route) or from animal to human (zoonotic route). However, there is no study from India on genotypes of E. bieneusi among infected hosts. Therefore, we aimed to (a) study the prevalence, clinical symptoms, and species identification of microsporidia among HIV infected patients and (b) perform a genotypic analysis of E. bieneusi and a phylogenetic interpretation of the transmission of different genotypes among infected hosts. Two hundred and twenty-two HIV-infected patients and 220 healthy controls (HC) were tested for the presence of microsporidia using modified trichrome (MT) staining and PCR. Demographic, clinical and laboratory parameters were studied. Species identification was performed using PCR-RFLP. All E. bieneusi isolates were subjected to genotypic and phylogenetic analysis. Patients with HIV [n = 222, age 37.4 ± 10.4 y, 169 (76%) male] were more commonly infected with microsporidia than the HC [n = 220, age 34.5 ± 6.5 y, 156 (71%) male], using MT stain and PCR [4/222, 1.8% vs. 0/220, p = 0.04]. Patients infected with microsporidia more commonly presented with diarrhea than those not infected with microsporidia [4, 100% vs. 98/218, 45%; p = 0.04]. E. bieneusi was detected in all patients with microsporidia. Four novel genotypes (Ind1 to Ind4) were identified. Ind1 showed 95% similarity with genotype L (AF267142.1) reported in cats (Germany). Genotypes Ind2 to Ind4 showed 94–96% similarity to host-specific genotype A (AF101197.1) reported in humans. Phylogenetic analysis mainly showed an anthroponotic route of transmission (3/4), while the zoonotic route (1/4) was also observed. The prevalence of microsporidia among HIV-infected patients was 1.8%. Patients with microsporidia commonly present with diarrhea. E. bieneusi is the most common species infecting the study population. Four novel genotypes of E. bieneusi were identified, suggesting presumptive transmission mainly through the anthropological route. Keywords: Microsporidia, Diarrhea, Internal transcribed spacer, Phylogenetic analysis

Here, we report a patient with bile duct injury (BDI) following open cholecystectomy, who developed a very large biloma, causing duodenal and biliary obstruction, and also had a biliary stricture at the site of BDI. We successfully managed the patient by endoscopic biloma-gastrostomy with biliary stenting that resulted in resolution of the biloma and aggressive endoscopic management of the biliary stricture with stent bundles till resolution. Pertaining this case to be the one with largest biloma in the literature (approximately 6.5 L), which developed following open cholecystectomy that resulted in biliary stricture following injury to BD. We successfully managed the patient by endoscopic biloma-gastric stenting and an aggressive endoscopic management of biliary stricture.

Progress in the understanding of the pathophysiology of irritable bowel syndrome (IBS), once thought to be a purely psychosomatic disease, has advanced considerably and low-grade inflammation and changes in the gut microbiota now feature as potentially important. The human gut harbours a huge microbial ecosystem, which is equipped to perform a variety of functions such as digestion of food, metabolism of drugs, detoxification of toxic compounds, production of essential vitamins, prevention of attachment of pathogenic bacteria to the gut wall, and maintenance of homeostasis in the gastrointestinal tract. A subset of patients with IBS may have a quantitative increase in bacteria in the small bowel (small intestinal bacterial overgrowth). Qualitative changes in gut microbiota have also been associated with IBS. Targeting the gut microbiota using probiotics and antibiotics has emerged as a potentially effective approach to the treatment of this, hitherto enigmatic, functional bowel disorder. The gut microbiota in health, quantitative and qualitative microbiota changes, and therapeutic manipulations targeting the microbiota in patients with IBS are reviewed in this paper.

Gastrointestinal mucormycosis, a rare fatal fungal infection in an immunocompromised host, affects mainly the stomach. Colonic mucormycosis is infrequent and is associated with high mortality. Perianal involvement is seen in almost one-third of patients with Crohn’s disease. Perianal Crohn’s disease is a particularly debilitating form of the disease, which requires multidisciplinary care. It may also require profound immunosuppression with biological agents to control disease activity. Opportunistic infections can complicate the disease course in these patients. We present a case of a middle-aged female with perianal Crohn’s disease on adalimumab who developed colonic mucormycosis causing a flare in her disease activity. This patient highlights the need to increase awareness about fungal infections as a cause of disease flare in inflammatory bowel disease.

Artificial intelligence (AI) is a computer technology for mathematical modeling that uses nonlinear statistical analysis. While multilayer perceptron network is used for prediction of clinical outcome, convolutional neural network is used for detection of lesion in an image and its classification. In this issue of the journal, an article reviewed the impact of AI in colorectal polyp detection and characterization. This is an upcoming area of gastroenterology, which has already reached the doorstep of practicing clinicians and in the near future, it may bring a paradigm shift in clinical practice. It is expected that this thought-provoking review will stimulate endoscopists to take up research in this important field of application of an AI-based computer technology for endoscopic detection of gastrointestinal lesions.

Background: Giardiasis is an important cause of diarrheal disease and is associated with morbidity in children and adults worldwide. We aimed to study the prevalence of Giardiasis, its clinical presentations, seasonal trends in detection, and coinfection with other intestinal parasites along with comparison of fecal antigen and microscopy for the detection of Giardiasis. Materials and Methods: It is a retrospective study conducted from Jan. 2017 to Dec. 2021 at our university hospital. Iodine and normal saline mounts and enzyme-linked immunosorbent assay (ELISA) were used for the detection of Giardiasis in stool samples. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of tests were computed. Results: Of 8364 patients, 432 (5.2%) had Giardiasis by microscopy and/or ELISA. Giardiasis was more common in males compared to females (318/5613 [5.6%] vs. 114/2751 [4.1%]; P = 0.003) and among those ≤10 y compared to older individuals (102/560 [18.2%] vs. 330/7804 [4.2%]; P

Altered mitochondrial function without a well-defined cause has been documented in patients with ulcerative colitis (UC). In our efforts to understand UC pathogenesis, we observed reduced expression of clustered mitochondrial homolog (CLUH) only in the active UC tissues compared with the unaffected areas from the same patient and healthy controls. Stimulation with bacterial Toll-like receptor (TLR) ligands similarly reduced CLUH expression in human primary macrophages. Further, CLUH negatively regulated secretion of proinflammatory cytokines IL-6 and TNF-α and rendered a proinflammatory niche in TLR ligand–stimulated macrophages. CLUH was further found to bind to mitochondrial fission protein dynamin related protein 1 (DRP1) and regulated DRP1 transcription in human macrophages. In the TLR ligand–stimulated macrophages, absence of CLUH led to enhanced DRP1 availability for mitochondrial fission, and a smaller dysfunctional mitochondrial pool was observed. Mechanistically, this fissioned mitochondrial pool in turn enhanced mitochondrial ROS production and reduced mitophagy and lysosomal function in CLUH-knockout macrophages. Remarkably, our studies in the mouse model of colitis with CLUH knockdown displayed exacerbated disease pathology. Taken together, this is the first report to our knowledge explaining the role of CLUH in UC pathogenesis, by means of regulating inflammation via maintaining mitochondrial-lysosomal functions in the human macrophages and intestinal mucosa.

The emergence and rapid evolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a global crisis that required a detailed characterization of the dynamics of mutational pattern of the viral genome for comprehending its epidemiology, pathogenesis and containment. We investigated the molecular evolution of the SASR-CoV-2 genome during the first, second and third waves of COVID-19 in Uttar Pradesh, India. Nanopore sequencing of the SARS-CoV-2 genome was undertaken in 544 confirmed cases of COVID-19, which included vaccinated and unvaccinated individuals. In the first wave (unvaccinated population), the 20A clade (56.32%) was superior that was replaced by 21A Delta in the second wave, which was more often seen in vaccinated individuals in comparison to unvaccinated (75.84% versus 16.17%, respectively). Subsequently, 21A delta got outcompeted by Omicron (71.8%), especially the 21L variant, in the third wave. We noticed that Q677H appeared in 20A Alpha and stayed up to Delta, D614G appeared in 20A Alpha and stayed in Delta and Omicron variants (got fixed), and several other mutations appeared in Delta and stayed in Omicron. A cross-sectional analysis of the vaccinated and unvaccinated individuals during the second wave revealed signature combinations of E156G, F157Del, L452R, T478K, D614G mutations in the Spike protein that might have facilitated vaccination breach in India. Interestingly, some of these mutation combinations were carried forward from Delta to Omicron. In silico protein docking showed that Omicron had a higher binding affinity with the host ACE2 receptor, resulting in enhanced infectivity of Omicron over the Delta variant. This work has identified the combinations of key mutations causing vaccination breach in India and provided insights into the change of [virus’s] binding affinity with evolution, resulting in more virulence in Delta and more infectivity in Omicron variants of SARS-CoV-2. Our findings will help in understanding the COVID-19 disease biology and guide further surveillance of the SARS-CoV-2 genome to facilitate the development of vaccines with better efficacies.

Esophageal motility disorders (EMDs) form a significant part of a busy endoscopist's practice. Endoscopy plays an all-encompassing role in the diagnosis and management of EMDs including achalasia cardia. The focus on in-vogue third-space endoscopic procedures such as per-oral endoscopic myotomy often digresses the important role of endoscopy. Endoscopic evaluation forms the part of standard first-line evaluation of any dysphagia and serves to rule out a secondary cause such as an esophagogastric junction malignancy and eosinophilic esophagitis. Moreover, endoscopic evaluation may itself provide corroborative evidence that may contribute to the diagnosis of the motility disorder. Achalasia cardia may present with a wide spectrum of endoscopic findings from being entirely normal and the well-known and pathognomonic dilated sigmoid-shaped esophagus with food residue, to lesser-known ornate signs. The evidence on the role of endosonography in EMDs is conflicting and largely restricted to evaluation of pseudoachalasia. High-resolution manometry (HRM) remains the gold standard in the diagnosis of EMDs. Endoscopists must also keep abreast of the latest iteration of the Chicago classification version 4.0, which differs significantly from its predecessor in being more stringent in making diagnosis of esophagogastric junction outflow obstruction and disorders of peristalsis since these manometric findings may be seen in normal individuals and may be mimicked by opioid use and gastroesophageal reflux. The latest rendition also includes the use of provocative maneuvers and testing in both supine and sitting posture. Despite being the gold standard, there are certain lacunae in the use and interpretation of the Chicago classification of which the users should be well aware. Emerging technologies such as functional lumen imaging probe and planimetry, and timed barium esophagogram fill the lacuna in diagnosis of these motility disorders, which at times is beyond the resolution of HRM.

Background and AimsThe over-prescription of antibiotics is thought to represent a major threat to public health worldwide and is more frequently observed in some low- and middle-income countries. In the Asia-Pacific region, economic development, health care organization and population demographics are very heterogenous. The objective of this survey was to investigate antibiotic use and probiotic co-prescription among adult patients in this area.MethodsAn online survey of physicians from seven countries of the Asia-Pacific region (Australia, Japan, Indonesia, India, China, Singapore and South Korea) was performed in 2018. The questionnaire explored current practices of physicians concerning antibiotics and probiotics and factors related to prescribing decisions.ResultsA total of 387 general practitioners and 350 gastroenterologists completed the questionnaire. Physicians in Australia, Japan and South-Korea were low prescribers of antibiotics (11% to 19% of visits resulted in an antibiotic prescription), while physicians in Indonesia, India, China and Singapore were high prescribers (41% to 61%). A large majority (85%) of physicians agreed that antibiotics disrupted intestinal microbiota. The rates of co-prescription of probiotics varied from 16% in Japan to 39% in Singapore (overall, 27%). Conditions considered by physicians to be prevented by probiotics were mostly antibiotic-associated diarrhea (62%) and Clostridium difficile colitis (43%).ConclusionsRates of probiotic co-prescription remain low in many countries although the negative effects of antibiotics on the gut microbiota and the benefits of co-prescribing probiotics are generally known.

La Clasificación de Chicago v4.0 (CCv4.0) es el esquema actualizado para clasificar las alteraciones de la motilidad esofágica utilizando la métrica de la manometría de alta resolución (HRM). Para desarrollar la CCv4.0, 52 expertos internacionales diversos separados en siete subgrupos de trabajo utilizaron una metodología formalmente validada, en un periodo de dos años. Las actualizaciones claves de la CCv4.0 consisten en un protocolo de HRM más riguroso y expansivo que incorpora las posiciones en decúbito supino y sedestación, así como pruebas provocadoras; una definición refinada de la obstrucción del flujo de salida de la unión esofagogástrica (EGJOO), criterios diagnósticos más estrictos para la motilidad esofágica inefectiva, y descripción de la métrica basal de la EGJ. Adicionalmente, la CCv4.0 se propuso definir el diagnóstico de alteración de la motilidad como conclusivo o no conclusivo con base en los síntomas asociados, los hallazgos en las pruebas provocadoras, y los resultados de los exámenes de apoyo como el esofagograma con tableta de bario y/o la prueba con sonda para imagen endoluminal funcional. Estos cambios buscan minimizar la ambigüedad presente en iteraciones previas de la Clasificación de Chicago; además proveen criterios más estandarizados y rigurosos para los patrones de alteración de la peristalsis y obstrucción de la EGJ.

The pathogenesis of irritable bowel syndrome (IBS), once thought to be largely psychogenic in origin, is now understood to be multifactorial. One of the reasons for this paradigm shift is the realization that gut dysbiosis, including small intestinal bacterial overgrowth (SIBO), causes IBS symptoms. Between 4% and 78% of patients with IBS and 1% and 40% of controls have SIBO; such wide variations in prevalence might result from population differences, IBS diagnostic criteria, and, most importantly, methods to diagnose SIBO. Although quantitative jejunal aspirate culture is considered the gold standard for the diagnosis of SIBO, noninvasive hydrogen breath tests have been popular. Although the glucose hydrogen breath test is highly specific, its sensitivity is low; in contrast, the early-peak criteria in the lactulose hydrogen breath test are highly nonspecific. Female gender, older age, diarrhea-predominant IBS, bloating and flatulence, proton pump inhibitor and narcotic intake, and low hemoglobin are associated with SIBO among IBS patients. Several therapeutic trials targeting gut microbes using antibiotics and probiotics have further demonstrated that not all symptoms in patients with IBS originate in the brain but rather in the gut, providing support for the micro-organic basis of IBS. A recent proof-of-concept study showing the high frequency of symptom improvement in patients with IBS with SIBO further supports this hypothesis.