Non-invasive assessment of esophageal varices:Status of today

With increasing burden of compensated cirrhosis,we desperately need noninvasive methods for assessment of clinically significant portal hypertension.The use of liver and spleen stiffness measurement helps in deferring unnecessary endoscopies for low risk esophageal varices.This would reduce cost and patient discomfort.However,these special techniques may not be feasible at remote areas where still we need only biochemical parameters.More prospective studies validating the non-invasive risk prediction models are definitely needed.

Emerging molecules,tools,technology,and future of surgical knife in gastroenterology

The 21^(st) century has started with several innovations in the medical sciences,with wide applications in health care management.This development has taken in the field of medicines(newer drugs/molecules),various tools and technology which has completely changed the patient management including abdominal surgery.Surgery for abdominal diseases has moved from maximally invasive to minimally invasive(laparoscopic and robotic)surgery.Some of the newer medicines have its impact on need for surgical intervention.This article focuses on the development of these emerging molecules,tools,and technology and their impact on present surgical form and its future effects on the surgical intervention in gastroenterological diseases.

Knowledge and practice skills on home-based urinary catheter care among parents of under-five children with urinary catheter

Objectives:The objectives of this study were to assess the knowledge and practice skills on home-based urinary catheter care among parents of under-five children with urinary catheter.Materials and Methods:This cross-sectional study was conducted from June 1,2021,to September 11,2021,in a tertiary hospital in north India.Purposive sampling was used to select 50 participants.Three instruments were employed for data collection after fulfilling sample criteria;for baseline information demographic tool,knowledge questionnaires,and a practice checklist.Data were analyzed using descriptive and inferential statistics.Results:On assessment of 50 participants,the majority of parents aged above 30 years(74%).Most of the participants were male(82%),graduated(38%),and working in the private sector(58%).Similarly,two-thirds of participants were residing in a nuclear family(64%)with a single child 32(64%)and family income<5000 rupees per month(60%).The mean score of knowledge was 1.94±0.81 and that of practice skills was 1.98±0.85 on home-based care.Regression analysis showed that knowledge of parents was significantly associated with qualification(β:1.821,P=0.002).Similarly,association of practice skills of parents with gender(β:1.235,P=0.050)and qualification(β:1.889,P=0.00)was significant.Conclusion:The general findings of our study showed that parents’education and occupation played a significant role in a child’s care.Parental education and catheter care skills positively affect the child and reduce readmission rates.

Endoscopic full-thickness plication along with argon plasma coagulation for treatment of proton pump inhibitor dependent gastroesophageal reflux disease

BACKGROUND Most endoscopic anti-reflux interventions for gastroesophageal reflux disease(GERD)management are technically challenging to practice with inadequate data to support it utility.Therefore,this study was carried to evaluate the effectiveness and safety newer endoscopic full-thickness fundoplication(EFTP)device along with Argon Plasma Coagulation to treat individuals with GERD.AIM To evaluate the effectiveness and safety newer EFTP device along with Argon Plasma Coagulation to treat individuals with GERD.METHODS This study was a single-center comparative analysis conducted on patients treated at a Noble Institute of Gastroenterology,Ahmedabad,hospital between 2020 and 2022.The research aimed to retrospectively analyze patient data on GERD symptoms and proton pump inhibitor(PPI)dependence who underwent EFTP using the GERD-X system along with argon plasma coagulation(APC).The primary endpoint was the mean change in the total gastroesophageal reflux disease health-related quality of life(GERD-HRQL)score compared to the baseline measurement at the 3-month follow-up.Secondary endpoints encompassed enhancements in the overall GERD-HRQL score,improvements in GERD symptom scores at the 3 and changes in PPI usage at the 3 and 12-month time points.RESULTS In this study,patients most were in Hill Class II,and over half had ineffective esophageal motility.Following the EFTP procedure,there were significant improvements in heartburn and regurgitation scores,as well as GERDHRQL scores(P<0.001).PPI use significantly decreased,with 82.6%not needing PPIs or prokinetics at end of 1 year.No significant adverse events related to the procedures were observed in either group.CONCLUSION The EFTP along with APC procedure shows promise in addressing GERD symptoms and improving patients'quality of life,particularly for suitable candidates.Moreover,the application of a lone clip with APC yielded superior outcomes and exhibited greater cost-effectiveness.

Challenges in predictive modelling of chronic kidney disease:A narrative review

The exponential rise in the burden of chronic kidney disease(CKD)worldwide has put enormous pressure on the economy.Predictive modeling of CKD can ease this burden by predicting the future disease occurrence ahead of its onset.There are various regression methods for predictive modeling based on the distribution of the outcome variable.However,the accuracy of the predictive model depends on how well the model is developed by taking into account the goodness of fit,choice of covariates,handling of covariates measured on a continuous scale,handling of categorical covariates,and number of outcome events per predictor parameter or sample size.Optimal performance of a predictive model on an independent cohort is desired.However,there are several challenges in the predictive modeling of CKD.Disease-specific methodological challenges hinder the development of a predictive model that is cost-effective and universally applicable to predict CKD onset.In this review,we discuss the advantages and challenges of various regression models available for predictive modeling and highlight those best for future CKD prediction.

Role of artificial intelligence in the characterization of indeterminate pancreatic head mass and its usefulness in preoperative diagnosis

Artificial intelligence(AI)has been used in various fields of day-to-day life and its role in medicine is immense.Understanding of oncology has been improved with the introduction of AI which helps in diagnosis,treatment planning,management,prognosis,and follow-up.It also helps to identify high-risk groups who can be subjected to timely screening for early detection of malignant conditions.It is more important in pancreatic cancer as it is one of the major causes of cancer-related deaths worldwide and there are no specific early features(clinical and radiological)for diagnosis.With improvement in imaging modalities(computed tomography,magnetic resonance imaging,endoscopic ultrasound),most often clinicians were being challenged with lesions that were difficult to diagnose with human competence.AI has been used in various other branches of medicine to differentiate such indeterminate lesions including the thyroid gland,breast,lungs,liver,adrenal gland,kidney,etc.In the case of pancreatic cancer,the role of AI has been explored and is still ongoing.This review article will focus on how AI can be used to diagnose pancreatic cancer early or differentiate it from benign pancreatic lesions,therefore,management can be planned at an earlier stage.

Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status

Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage.The recent description of the tumor microenvironment(TME)in HCC has provided a new concept of immunogenicity within the HCC.Virusrelated HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells.This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors(ICIs).In addition,the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity.Therefore,data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.

Gallbladder cancer:Progress in the Indian subcontinent

Gallbladder cancer(GBC)is one of the commonest biliary malignancies seen in India,Argentina,and Japan.The disease has dismal outcome as it is detected quite late due to nonspecific symptoms and signs.Early detection is the only way to improve the outcome.There have been several advances in basic as well as clinical research in the hepatobiliary and pancreatic diseases in the West and other developed countries but not enough has been done in GBC.Therefore,it is imp-ortant and the responsibility of the countries with high burden of GBC to find solutions to the many unanswered questions like etiopathogenesis,early diagn-osis,treatment,and prognostication.As India being one of the largest hubs for GBC in the world,it is important to know how the country has progressed on GBC.In this review,we will discuss the outcome of the publications from India highlighting the work and the developments taken place in past several decades both in basic and clinical research.

Circular RNA: The evolving potential in the disease world

Circular RNAs(circRNAs),a new star of noncoding RNAs,are a group of endogenous RNAs that form a covalently closed circle and occur widely in the mammalian genome.Most circRNAs are conserved throughout species and fre-quently show stage-specific expression during various stages of tissue develop-ment.CircRNAs were a mystery discovery,as they were initially believed to be a product of splicing errors;however,subsequent research has shown that ci-rcRNAs can perform various functions and help in the regulation of splicing and transcription,including playing a role as microRNA(miRNA)sponges.With the application of high throughput next-generation technologies,circRNA hotspots were discovered.There are emerging indications that explain the association of circRNAs with human diseases,like cancers,developmental disorders,and in-flammation,and circRNAs may be a new potential biomarker for the diagnosis and treatment outcome of various diseases,including cancer.After the discoveries of miRNAs and long noncoding RNAs,circRNAs are now acting as a novel re-search entity of interest in the field of RNA disease biology.In this review,we aim to focus on major updates on the biogeny and metabolism of circRNAs,along with their possible/established roles in major human diseases.

Anticoagulant use before COVID-19 diagnosis prevent COVID-19 associated acute venous thromboembolism or not:A systematic review and meta-analysis

BACKGROUND Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019(COVID-19)patients.There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease.AIM To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients.METHODS A Literature search was performed on LitCovid PubMed,WHO,and Scopus databases from inception(December 2019)till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19.The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants.Secondary outcomes included COVID-19 disease severity,in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection,and mortality.The random effects models were used to calculate crude and adjusted odds ratios(aORs)with 95%confidence intervals(95%CIs).RESULTS Forty-six observational studies met our inclusion criteria.The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk[n=43851,9 studies,odds ratio(OR)=0.67(0.22,2.07);P=0.49;I2=95%].The association between prior anticoagulation and disease severity was non-significant[n=186782;22 studies,OR=1.08(0.78,1.49);P=0.64;I2=89%].However,pre-hospital anticoagulation significantly increased all-cause mortality risk[n=207292;35 studies,OR=1.72(1.37,2.17);P<0.00001;I2=93%].Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk[aOR=0.87(0.42,1.80);P=0.71],mortality[aOR=0.94(0.84,1.05);P=0.31],and disease severity[aOR=0.96(0.72,1.26);P=0.76].CONCLUSION Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events,improved survival,and lower disease severity in COVID-19 patients.

Ultra-minimally invasive endoscopic techniques and colorectal diseases:Current status and its future

Colorectal diseases are increasing due to altered lifestyle,genetic,and environmental factors.Colonoscopy plays an important role in diagnosis.Advances in colonoscope(ultrathin scope,magnetic scope,capsule)and technological gadgets(Balloon assisted scope,third eye retroscope,NaviAid G-EYE,dye-based chromoendoscopy,virtual chromoendoscopy,narrow band imaging,i-SCAN,etc.)have made colonoscopy more comfortable and efficient.Now in-vivo microscopy can be performed using confocal laser endomicroscopy,optical coherence tomography,spectroscopy,etc.Besides developments in diagnostic colonoscopy,therapeutic colonoscopy has improved to manage lower gastrointestinal tract bleeding,obstruction,perforations,resection polyps,and early colorectal cancers.The introduction of combined endo-laparoscopic surgery and robotic endoscopic surgery has made these interventions feasible.The role of artificial intelligence in the diagnosis and management of colorectal diseases is also increasing day by day.Hence,this article is to review cutting-edge developments in endoscopic principles for the management of colorectal diseases.

Pathogenesis of achalasia cardia

Achalasia cardia is one of the common causes of motor dysphagia.Though the disease was first described more than 300 years ago,exact pathogenesis of this condition still remains enigmatic.Pathophysiologically,achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus.In the initial stage,degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine,resulting in high amplitude non-peristaltic contractions(vigorous achalasia);progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body(classic achalasia).Since the initial description,several studies have attempted to explore initiating agents that may cause the disease,such as viral infection,other environmental factors,autoimmunity,and genetic factors.Though Chagas disease,which mimics achalasia,is caused by an infective agent,available evidence suggests that infection may not be an independent cause of primary achalasia.A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins,siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down's syndrome and Parkinson's disease.Polymorphisms in genes encoding for nitric oxide synthase,receptors for vasoactive intestinal peptide,interleukin 23 and the ALADIN gene have been reported.However,studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained.Currently,the disease is believed to be multi-factorial,with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus.

Evaluation of mannitol effect in patients with acute hepatic failure and acute-on-chronic liver failure using conventional MRI,diffusion tensor imaging and in-vivo proton MR spectroscopy

AIM： To evaluate the effect of an intravenous bolus of mannitol in altering brain metabolites, brain water content, brain parenchyma volume, cerebrospinal fluid （CSF） volume and clinical signs in controls and in patients with acute liver failure （ALF） and acute- on-chronic liver failure （ACLF）, by comparing changes in conventional magnetic resonance imaging （MRI）, in vivo proton magnetic resonance spectroscopy （PMRS） and diffusion tensor imaging （DTI） before and after its infusion.METHODS： Five patients each with ALF and ACLF in grade 3 or 4 hepatic encephalopathy and with clinical signs of raised intracranial pressure were studied along with five healthy volunteers. After baseline MRI, an intravenous bolus of 20% mannitol solution was given over 10 min in controls as well as in patients with ALF and ACLE Repeat MRI for the same position was acquired 30 rnin after completing the rnannitol injection. RESULTS： No statistically significant difference was observed between controls and patients with ALF and ACLF in metabolite ratios, DTI metrics and brain volume or CSF volume following 45 rain of mannitol infusion. There was no change in clinical status at the end of post-mannitol imaging. CONCLUSION： The osmotic effect of mannitol did not result in significant reduction of brain water content, alteration in metabolite ratios or any change in the clinical status of these patients during or within 45 min of mannitol infusion.

Genetics of coronary heart disease with reference to ApoAICⅡI-AIV gene region

Cardiovascular diseases are affected by multiple factors like genetic as well as environmental hence they reveal factorial nature. The evidences that genetic factors are susceptible for developing cardiovascular diseases come from twin studies and familial aggregation. Different ethnic populations reveal differences in the prevalence coronary artery disease(CAD) pointing towards the genetic susceptibility. With progression in molecular techniques different developments have been made to comprehend the disease physiology. Molecular markers have also assisted to recognize genes that may provide evidences to evaluate the role of genetic factors in causation of susceptibility towards CAD. Numerous studies suggest the contribution of specific "candidate genes", which correlate with various roles/pathways that are involved in the coronary heart disease. Different studies have revealed that there are large numbers of genes which are involved towards the predisposition of CAD. However, these reports are not consistent. One of the reasons could be weak contribution of genetic susceptibility of these genes. Genome wide associations show different chromosomal locations which dock, earlier unknown, genes which may attribute to CAD. In the present review different ApoAI-CⅡI-AIV gene clusters have been discussed.

Primary tuberculosis of the thyroid gland:a case report

Tuberculosis of the thyroid gland is an uncommon disease and primary involvement of Uiyroid is even more rare.It is a rare disease even in countries in which tuberculosis is endemic.The diagnosis is often difficult as the clinical presentation has no distinct characteristics.Clinical course of the disease may resemble toxic goiter or acute thyroiditis or may follow a subacute or chronic growth pattern without specific symptomatology.Histologically presence of necrotizing epithelioid cell granulomas along with langhans type giant cells are the hallmark of thyroid tuberculosis.Demonstration of acid fast bacilli by ZN staining confirms the diagnosis,but this stain is frequently negative in tissue sections.

The role of tunica vaginalis flap in staged repair of hypospadias

Objective:The surgical repair of hypospadias is done in two stages in a select group of patients with severe anomaly.The first stage(Ⅰ)procedure consists of correction of penile shaft curvature and second stage(Ⅱ)repair involves the creation of a neourethra.This neourethra needs a cover of an intermediate layer in order to have good functional and cosmetic results.Among the various local flaps,tunica vaginalis flap is a good option for the use as an intermediate layer.Methods:We have managed 22 patients of chordee with hypospadias by staged repair.In Stage I,chordee correction was done by dividing the urethral plate and covering the penile shaft with dorsal prepucial flaps.In Stage Ⅱ,a neourethra was created and covered with tunica vaginalis flap either through the same incision(14/22)or via a subcutaneous tunnel(8/22).An indwelling catheter was kept for 10 to 12 days.Results:Eighteen(81.8%)patients had successful functional and cosmetic repair.Two patients(9.1%)had urethrocutaneous fistula of which one healed on subsequent dilatation while the other one(4.5%)needed repair.Overall fistula formation rate was 4.5%.In two patients,the external urinary meatus could be made upto subglanular or coronal level.Conclusion:Staged repair of chordee with hypospadias is valuable in selected group of patients and tunica vaginalis flap is an excellent intermediate layer to cover the neourethra.However preoperative counseling is particularly essential in patients where the external urinary meatus can be created at coronal or subglanular level.

Prevalence of internet addiction among college students in the Indian setting:a systematic review and meta-analysis

Background The internet is an integral part of everyone’s life.College going adolescents are highly vulnerable to the misuse of the internet.Aims To estimate the pooled prevalence of internet addiction(IA)among college students in India.Methods Literature databases(PubMed,Web of Science,Scopus,EMBASE,PsycINFO and Google Scholar)were searched for studies assessing IA using the Young Internet Addiction Test(Y-IAT)among adolescents from India,published in the English language up to December 2020.We included studies from 2010 to 2020 as this is the marked era of momentum in wireless internet connectivity in India.The methodological quality of each study was scored,and data were extracted from the published reports.Pooled prevalence was estimated using the fixed-effects model.Publication bias was evaluated using Egger’s test and visual inspection of the symmetry in funnel plots.Results Fifty studies conducted in 19 states of India estimated the prevalence of IA and the overall prevalence of IA as 19.9%(95%CI:19.3%to 20.5%)and 40.7%(95%CI:38.7%to 42.8%)based on the Y-IAT cut-off scores of 50 and 40,respectively.The estimated prevalence of severe IA was significantly higher in the Y-IAT cut-off points of 70 than 80(12.7%(95%CI:11.2%to 14.3%)vs 4.6%(95%CI:4.1%to 5.2%)).The sampling method and quality of included studies had a significant effect on the estimation of prevalence in which studies using non-probability sampling and low risk of bias(total quality score≥7)reported lower prevalence.The overall quality of evidence was rated as‘moderate’based on the Grading of Recommendations Assessment,Development and Evaluation criteria.Conclusions Our nationally representative data suggest that about 20%to 40%of college students in India are at risk for IA.There is a need for further research in the reconsideration of Y-IAT cut-off points among Indian college students.

Clinicohistopathological implications of phosphoserine 9 glycogen synthase kinase-3β/β-catenin in urinary bladder cancer patients

BACKGROUND Aberrant activation of phosphorylated form of glycogen synthase kinase-3β[pS9 GSK-3β(Serine 9 phosphorylation)] is known to trigger Wnt/β-catenin signal cascade but its clinicohistopathological implications in bladder carcinogenesis remain unknown.AIM To investigate the diagnostic and prognostic relevance of expressions of pS9 GSK-3β, β-catenin and its target genes in the pathobiology of bladder cancer.METHODS Bladder tumor tissues from ninety patients were analyzed for quantitative expression and cellular localization of pS9 GSK-3β by immunohistochemical(IHC) staining. Real time-quantitative polymerase chain reaction and IHC were done to check the expression of β-catenin, Cyclin D1, Snail and Slug at transcriptome and protein level respectively. Clinicohistopathological variables were obtained from histology reports, follow up and OPD visits of patients.Expressions of the markers were statistically correlated with these variables to determine their significance in clinical setting. Results were analysed using SPSS20.0 software.RESULTS Aberrant(low or no membranous/high nuclear/high cytoplasmic) expression of pS9 GSK-3β was noted in 51% patients and found to be significantly associated with tumor stage and tumor grade(P = 0.01 and 0.04; Mann Whitney U test).Thirty one percent tumors exhibited aberrant co-expression of pS9 GSK-3β andβ–catenin proteins and showed strong statistical association with tumor stage,tumor type, smoking/tobacco chewing status(P = 0.01, 0.02 and 0.04, MannWhitney U test) and shorter overall survival probabilities of patients(P = 0.02;Kaplan Meier test). Nuclear immunostaining of Cyclin D1 in tumors with altered pS9 GSK-3β/β–catenin showed relevance with tumor stage, grade and type.CONCLUSIONβ–catenin and pS9 GSK-3β proteins are identified as markers of diagnostic/prognostic significance in disease pathogenesis. Observed histopathological association of Cyclin D1 identifies it as marker of potential relevance in tumors with altered pS9 GSK-3β/β-catenin.

Primary Combined Intra-articular and Extra-articular Synovial Osteochondromatosis of Shoulder: a Case Report

PRIMARY synovial chondromatosis is a rarecondition in which foci of cartilage develop in thesynovial membrane of joints, bursae and tendonsheaths. It typically involves a single large jointin a young adult male.1 The ectopic foci of cartilage canresult in painful joint effusion, and the generation of loosebodies can cause mechanical symptoms.2,3 The etiology ofprimary synovial chondromatosis remains unknown, butmetaplastic theory is the most popular hypothesis. Thecommonly involved joints are knee, elbow, and hip.^4 Theshoulder is a rare site of synovial chondromatosis2,3,5 andthe extra-articular involvement even rarer, with only fewcases presented in literature. This report presents a rarecase of primary combined intra-articular andextra-articular synovial chondromatosis of shoulder jointtreated with arthroscopy.

Nonalcoholic steatohepatitis and hepatocellular carcinoma: Beyond the boundaries of the liver

The burden of non-alcoholic steatohepatitis (NASH) related hepatocellularcarcinoma (HCC) is drawing attention due to the emerging epidemic of obesityand metabolic syndrome and is expected to increase in the near future.Antidiabetic medications, air pollutants, and newer genetic mutations are latestconcerns as risk factors for HCC development in patients with NASH. Althoughmolecular signatures are very accurate, they are not cost-effective and cannot beapplied in larger population due to logistic issues. We need multicentric longitudinalstudies including diverse geographical areas to evaluate the complexinterplay of different risk factors and genetics in these patients.