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BACKGROUND AND AIM: Achalasia cardia, a primary motility disorder of the esophagus, poses significant malnutrition risks. This study aims at comprehensively assessing the nutritional status in untreated achalasia patients, contrasting it with functional gastrointestinal disorders (FGIDs) cases and impact of per-oral endoscopic myotomy (POEM) on nutrition at one-year. METHODS: We conducted a prospective study, including consecutive achalasia cases, from December 2021 to April 2022 at a tertiary care centre. Biochemical parameters, anthropometry, subjective global assessment (SGA) and malnutrition universal screening tool were used for nutritional assessment. Cases diagnosed with FGIDs served as controls. RESULTS: As many as 118 cases (41.2 ± 13.9 years, 61% males) with achalasia and 200 controls (43.4 ± 11.9 years, 69% males) were included in the study. Sub-types of achalasia included type I (16.9%), II (76.3%) and III (6.8%). Overall, 38.1% and 6.8% cases were moderately and severely malnourished, respectively. As compared to controls, cases with achalasia had lower pre-albumin (19.4 vs. 25.2; p = 0.001), serum calcium (p = 0.012), vitamin D (p = 0.001), serum iron (p = 0.001), triceps fold thickness (p = 0.002) and hand-grip strength (p = 0.001). On univariate analysis, type-I achalasia, body mass index, % weight loss, lower esophageal sphincter pressures and Eckardt scores were predictors of malnourishment (SGA). On multivariate analysis, type of achalasia, mid arm circumference and low body mass index were significant predictors of malnourishment in cases with achalasia. There was significant improvement in the nutritional status after POEM at one-year follow-up. CONCLUSION: Achalasia patients demonstrate a notably higher risk of malnutrition compared to individuals with FGIDs. Nutritional status significantly improves after POEM. (NCT05161923).
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AIMS: There is limited data on the prevalence and risk factors of colonic adenoma from the Indian sub-continent. We aimed at developing a machine-learning model to optimize colonic adenoma detection in a prospective cohort. METHODS: All consecutive adult patients undergoing diagnostic colonoscopy were enrolled between October 2020 and November 2022. Patients with a high risk of colonic adenoma were excluded. The predictive model was developed using the gradient-boosting machine (GBM)-learning method. The GBM model was optimized further by adjusting the learning rate and the number of trees and 10-fold cross-validation. RESULTS: Total 10,320 patients (mean age 45.18 ± 14.82 years; 69% men) were included in the study. In the overall population, 1152 (11.2%) patients had at least one adenoma. In patients with age > 50 years, hospital-based adenoma prevalence was 19.5% (808/4144). The area under the receiver operating curve (AUC) (SD) of the logistic regression model was 72.55% (4.91), while the AUCs for deep learning, decision tree, random forest and gradient-boosted tree model were 76.25% (4.22%), 65.95% (4.01%), 79.38% (4.91%) and 84.76% (2.86%), respectively. After model optimization and cross-validation, the AUC of the gradient-boosted tree model has increased to 92.2% (1.1%). CONCLUSIONS: Machine-learning models may predict colorectal adenoma more accurately than logistic regression. A machine-learning model may help optimize the use of colonoscopy to prevent colorectal cancers. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT04512729).
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Achalasia cardia, the most prevalent primary esophageal motility disorder, is predominantly characterized by symptoms of dysphagia and regurgitation. The principal therapeutic approaches for achalasia encompass pneumatic dilatation (PD), Heller's myotomy, and the more recent per-oral endoscopic myotomy (POEM). POEM has been substantiated as a safe and efficacious modality for the management of achalasia. Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy, the incidence of gastroesophageal reflux disease (GERD) following POEM is notably higher than with the aforementioned techniques. While symptomatic reflux post-POEM is relatively infrequent, the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications. Contemporary advancements in the field have enhanced our comprehension of the risk factors, diagnostic methodologies, preventative strategies, and therapeutic management of GERD subsequent to POEM. This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux, potential modifications in the POEM technique to mitigate GERD risk, and the strategies for managing reflux following POEM.
Subject(s)
Esophageal Achalasia , Esophagitis , Gastroesophageal Reflux , Myotomy , Natural Orifice Endoscopic Surgery , Humans , Esophageal Achalasia/surgery , Esophageal Achalasia/etiology , Gastroesophageal Reflux/etiology , Gastroesophageal Reflux/prevention & control , Esophagitis/etiology , Myotomy/adverse effects , Myotomy/methods , Natural Orifice Endoscopic Surgery/methods , Treatment Outcome , Esophageal Sphincter, Lower/surgeryABSTRACT
Introduction Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has cast a gloom spell on healthcare worldwide, infecting millions of people. Objective The aim of the present study is to determine the prevalence and review the contributing comorbidities and the precipitating factors leading to the emergence of the fungal infections in COVID-19-affected patients. To assess the utility of different laboratory techniques for confirmation of fungal infections. To assess the strengths and limitations of the diagnostic methods. Methods We have studied 252 clinical samples obtained from 121 COVID-positive patients. Results Among the 121 patients clinically diagnosed with fungal infections, 88 had diabetes and were given steroids for treatment ( p -value = 0.001). Ninety-five patients (78.5%) had a positive laboratory diagnosis (either culture positive, potassium hydroxide [KOH]-positive or positive histopathology report). Fungal culture was positive in 75 (61.9%) patients and histopathology report was positive in 62 (51.2%). Histopathology was positive in 7 (5.8%) patients in whom culture and KOH were negative. Conclusion Aggressive treatment methods, administration of immune suppressants, and antibiotics, with an intention to salvage, have made patients susceptible to the benign fungus, causing it to evade the host immunity, thus leading to invasive infections. Applying different laboratory modalities would not only aid in providing fast and valuable information but also help in understanding the pathology which would assist the clinician in selecting the correct treatment for the patient.
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Background: A splice variant in HSD17B13 gene is demonstrated to protect against nonalcoholic fatty liver disease (NAFLD), and mitigate the effect of Patatin-like phospholipase domain-containing 3 (PNPLA3-I148M). It is being explored as a putative drug target and in polygenic risk scores. Based on whole exome sequencing (WES) in our cohort of biopsy proven NAFLD and limited data on the variant in our ethnicity, we sought to explore its role. Methods: This is a cross-sectional study that recruited 1,020 individuals with ultrasound/biopsy-confirmed NAFLD and matched controls. Liver enzymes and lipid profiles were estimated (Beckman coulter LX750/DXH800); WES was performed in NAFLD patients and controls (Illumina; HiSeqX); HSD17B13-A-INS/I148M-PNPLA3 variants were genotyped (sequencing/qR T-PCR); HSD17B13 protein expression was estimated (immunohistochemistry); the Student's t-test/Mann-Whitney U/Chi-square test and odds ratio (95% confidence interval) were used. Results: There was no significant difference (Odds ratio = 0.76; 95% CI -0.57 to 1.03; P = 0.76) in the frequency of the rs72613567-A-INS between controls and patients (17.8% vs. 14.4%). No difference in the ALT (Alanine transaminase; 72.24 ± 65.13 vs. 73.70 ± 60.06; P = 0.51) and AST levels (Aspartate aminotransferase; 60.72 ± 55.59 vs. 61.63 ± 60.33; P = 0.91) between HSD17B13-wild and variant carriers were noted. Significantly elevated liver enzymes were seen in PNPLA3-148-variant/HSD17B13-wild compared with PNPLA3-148-variant/HSD17B13-variant (90.44 ± 59.0 vs. 112.32 ± 61.78; P = 0.02). No difference in steatosis (P = 0.51) between HSD17B13-wild and variant carriers was noted. No other variants in the intron-exon boundaries were identified. Although, protein expression differences were noted between wild and variant carriers, no difference in the extent of steatosis was seen. Conclusion: Our study reports lack of association of the splice variant with reduced risk of NAFLD, and mitigating the effect of PNPLA3 variant. Ethnicity-based validation must be carried out before including it in assessing protection against NAFLD.
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BACKGROUND/PURPOSE: Genome-wide association studies have reported the association of common variants with nonalcoholic fatty liver disease in genes, namely, PNPLA3/TM6SF2/MBOAT7/HSD17B13, across ethnicities. However, the approach does not identify rarer variants with a higher effect size. We therefore sequenced the complete exonic regions of patients with nonalcoholic steatohepatitis and controls to compare rare and common variants with a role in the pathogenesis. METHODS: This is a prospective study that recruited 54 individuals with/without fatty infiltration. Patients with biopsy-proven nonalcoholic steatohepatitis and persistently elevated liver enzymes were included. Controls were with normal CT/MR fat fraction. DNA was isolated from whole blood, amplified (SureSelectXT Human All Exon V5 + UTR kit) and sequenced (Illumina). Data were filtered for quality, aligned (hg19), and annotated (OpenCRAVAT). Pathogenic (Polyphen-2/SIFT/ClinVar) variants and variants reported to be associated with NAFLD based on published literature were extracted from our data and compared between patients and controls. RESULTS: The mean age of controls (N = 17) and patients (N = 37) was 46.88 ± 6.94 and 37.46 ± 13.34 years, respectively. A total of 251 missense variants out of 89 286 were classified as pathogenic. Of these, 106 (42.23%) were unique to the patients and remaining (n = 145; 57.77%) were found in both patients and controls. Majority (25/37; 67.57%) patients had a minimum of one or more rare pathogenic variant(s) related to liver pathology that was not seen in the controls. CONCLUSION: Elucidating the contribution of rare pathogenic variants would enhance our understanding of the pathogenesis. Including the rarer genes in the polygenic risk scores would enhance prediction power.
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Non-alcoholic Fatty Liver Disease , Humans , Adult , Middle Aged , Non-alcoholic Fatty Liver Disease/pathology , Genome-Wide Association Study , Prospective Studies , Exome Sequencing , Liver/pathology , Genetic Predisposition to Disease , Polymorphism, Single NucleotideABSTRACT
Colorectal cancer (CRC) is known to follow adenoma carcinoma sequence (ACS) in majority of the tumors and the driver variants and associated pathways are well delineated. However, most of the published data are from the west and information in other ethnicities is sparse. We therefore comprehensively evaluated the CRC tumors from Indian ethnicity for the prevalence of ACS. In this cohort study, clinical data of 100,497 patients who attended hospital between 2013 and 2018 were accessed. Tumors from patients (n = 130) with CRC who were treated primarily by surgery were included. DNA and RNA were isolated to assess variants (direct sequencing) and WNT-pathway dysregulation in genes related to ACS. Global gene expression was generated and analyzed on microarrays (Affymetrix; N = 10) and next generation sequencing platforms (Illumina; N = 25). Gene expression at mRNA (qRT-PCR) and protein level (IHC) of JUP/CTNNB1/MYC were assessed. Correlation between expression of JUP and MYC was evaluated by Karl Pearson's correlation coefficient. The prevalence of polyps was 16.75%, while 18.26% variants in APC/CTNNB1, 20.00% in KRAS, and 18.33% WNT dysregulation were noted. Interestingly, 29/60 (48.33%) tumors showed only MYC upregulation with normal APC/CTNNB1 expression. Global gene expression and validation in an independent tumor cohort confirmed concomitant upregulation of JUP (gamma-catenin) & MYC (r = 0.71; p = 0.001) at mRNA and protein in sizeable number of tumors (45/96; 46.88%). Our study provides evidence for limited prevalence of ACS in the Indian ethnicity. Preventive colonoscopies for early identification and management of CRC may not be an effective strategy in this ethnicity.
Subject(s)
Adenoma , Colorectal Neoplasms , Humans , Adenoma/genetics , beta Catenin/metabolism , Cohort Studies , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , gamma Catenin/genetics , gamma Catenin/metabolism , Prevalence , RNA, Messenger , Up-Regulation , Wnt Signaling Pathway/geneticsABSTRACT
The management of a patient in the peri-transplantation period is highly challenging, and it is even more difficult while the patient is on the transplantation waitlist. Keeping the patient alive during this period involves managing the complications of liver disease and preventing the disease's progression. Based on the pre-transplantation etiology and type of liver failure, there is a difference in the management protocol. The current review is divided into different sections, which include: the management of underlying cirrhosis and complications of portal hypertension, treatment and identification of infections, portal vein thrombosis management, and particular emphasis on the management of patients of hepatocellular carcinoma and acute liver failure in the transplantation waitlist. The review highlights special concerns in the management of patients in the Asian subcontinent also. The review also addresses the issue of delisting from the transplant waitlist to see that futility does not overtake the utility of organs. The treatment modalities are primarily expressed in tabular format for quick reference. The following review integrates the vast issues in this period concisely so that the management during this crucial period is taken care of in the best possible way.
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Abstract Introduction Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has cast a gloom spell on healthcare worldwide, infecting millions of people. Objective The aim of the present study is to determine the prevalence and review the contributing comorbidities and the precipitating factors leading to the emergence of the fungal infections in COVID-19-affected patients. To assess the utility of different laboratory techniques for confirmation of fungal infections. To assess the strengths and limitations of the diagnostic methods. Methods We have studied 252 clinical samples obtained from 121 COVID-positive patients. Results Among the 121 patients clinically diagnosed with fungal infections, 88 had diabetes and were given steroids for treatment (p-value = 0.001). Ninety-five patients (78.5%) had a positive laboratory diagnosis (either culture positive, potassium hydroxide [KOH]-positive or positive histopathology report). Fungal culture was positive in 75 (61.9%) patients and histopathology report was positive in 62 (51.2%). Histopathology was positive in 7 (5.8%) patients in whom culture and KOH were negative. Conclusion Aggressive treatment methods, administration of immune suppressants, and antibiotics, with an intention to salvage, have made patients susceptible to the benign fungus, causing it to evade the host immunity, thus leading to invasive infections. Applying different laboratory modalities would not only aid in providing fast and valuable information but also help in understanding the pathology which would assist the clinician in selecting the correct treatment for the patient.
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BACKGROUND: Patients with cirrhosis are susceptible to infections, especially by multidrug-resistant organisms (MDROs). There are limited data on the incidence of culture-positive infections and the validity of Sepsis 3-criteria in patients with cirrhosis admitted to the intensive care unit (ICU) in India, which we aimed to assess. METHODS: In this prospective study, we included consecutive patients with cirrhosis admitted to the ICU between November 1, 2021, and April 30, 2022. The primary objective was to compare the outcomes of patients with microbiologically proven infections with those without proven infections. The secondary objective was to assess the predictors of infections and mortality and the impact of drug-resistant organisms. RESULTS: A total of 298 patients (9.4% women) were included. The incidence of microbiologically proven infection was 34% (101/298; 95%CI=27.6-41.2). Most patients (61%) had healthcare-associated infections, Gram-negative organisms accounted for 75.3%, and bacteremia was the commonest site. Drug-resistant organisms accounted for 52.5% (53/101; 95%CI=39.3-68.7), of which 39.6% were multidrug-resistant (MDR) and 12.8% were extensively drug-resistant (XDR). Mortality was significantly higher in patients with proven infections than those without (61.4% vs. 44.2%; P=0.007). The sequential organ failure assessment (SOFA) score (OR=1.91; 95%CI=1.04-3.52; P<0.001) and presence of fever and/or positive quick SOFA (qSOFA; OR=1.91;1.04-3.52; P=0.03) were associated with an increased risk of infections. The SOFA score (OR=1.06;95%CI=1.002-1.12; P=0.04), MELD NA score (OR=1.08;95%CI=1.05-1.12; P<0.001), and presence of fever and/or positive qSOFA (OR=2.19; 95%CI=1.27-3.76; P=0.005) predicted mortality. CONCLUSIONS: One-third of the patients with cirrhosis admitted to the ICU had microbiologically proven infection, and the mortality rate in such patients was high. SOFA, qSOFA, and fever can predict microbiologically proven infections and mortality in patients with cirrhosis.
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Video 1Contrast-enhanced harmonic EUS-guided radiofrequency ablation of hepatocellular carcinoma.
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Background: Paracentesis-induced circulatory disturbance (PICD) occurs in 12-20% of patients receiving human albumin for large-volume paracentesis, and can occur at lower than five liter paracentesis in acute-on-chronic liver failure (ACLF). Albumin infusions are associated with higher costs and more prolonged daycare admissions. The aim of the study was to determine if oral midodrine-hydrochloride can prevent PICD in these patients by increasing the mean arterial pressure (MAP). Methods: This open-labeled randomized controlled trial included ACLF patients undergoing paracentesis between 3 and 5 L, who were randomized to receive either 20% human albumin or midodrine hydrochloride 7.5 mg thrice daily for three days, 2 h before paracentesis. MAP was recorded daily. The primary outcome was the plasma renin activity (PRA) on day six, and a 50% increase from baseline was considered PICD. Results: 183 consecutive patients of ACLF were screened, and 50 patients were randomized to either arms. Alcohol was the most common underlying cause of cirrhosis. On day 6, PRA was non-significantly (P = 0.056) higher in the midodrine group. The absolute change of PRA between the two groups was not significant (P = 0.093). Four (16%) patients in the albumin group and five (20%) in the midodrine group developed PICD. MAP increase was not different between the albumin and midodrine arms (P = 0.851). Midodrine was found to be more cost-effective. Conclusions: Three days of oral midodrine is as effective as a human-albumin infusion in preventing PICD in ACLF patients undergoing paracentesis lesser than that done in large volume paracentesis.
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After oncologic resection, histological grading and staging of the tumor give important prognostic information about the future risk of recurrence and hence influence the subsequent management plan. Several studies and their meta-analysis have shown that various histological features (e.g., microscopic positive resection margins, plexitis, granuloma, mesenteric inflammatory activity) can predict postoperative clinical/endoscopic/surgical recurrence after resection in Crohn’s disease (CD). Inclusion of mesentery in surgical resection specimens has been shown to reduce surgical recurrence after ileocolonic resection in CD. However, there is no uniform histopathological staging system for risk stratification in postoperative CD to systematically predict postoperative recurrence. This is because the prediction to date is based on clinical characteristics (smoking status, disease phenotype, surgical history). Histopathological predictors are still not adopted in routine clinical practice due to the lack of a uniform staging system, heterogeneity of published studies and lack of standardized definition of histological features. In this article, we attempted to incorporate all such histological features in a single histological staging system CNM (Crohn’s primary site [resection margin positivity, plexitis, granuloma, depth of infiltration], nodes [presence of granuloma], mesentery [involved or not]) in surgical resection specimen in CD. The proposed CNM classification would help to enable systematic reporting, design future clinical trials, stratify postoperative recurrence risk and choose appropriate postoperative prophylaxis.
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Submucosal endoscopy or third-space endoscopy utilizes the potential space between the mucosal and muscularis layers of the gastrointestinal tract to execute therapeutic interventions for various diseases. Over the last decade, endoscopic access to the submucosal space has revolutionized the field of therapeutic endoscopy. Submucosal endoscopy was originally used to perform endoscopic myotomy in patients with achalasia cardia, and its use has grown exponentially since. Currently, submucosal endoscopy is widely used to resect subepithelial tumors and to manage refractory gastroparesis and Zenker’s diverticulum. While the utility of submucosal endoscopy has stood the test of time in esophageal motility disorders and subepithelial tumors, its durability remains to be established in conditions such as Zenker’s diverticulum and refractory gastroparesis. Other emerging indications for submucosal endoscopy include esophageal epiphrenic diverticulum, Hirschsprung’s disease, and esophageal strictures not amenable to conventional endoscopic treatment. The potential of submucosal endoscopy to provide easy and safe access to the mediastinum and peritoneal spaces may open doors to novel indications and rejuvenate the interest of endoscopists in natural orifice transluminal endoscopic surgery in the future. This review focuses on the current spectrum, recent updates, and future direction of submucosal endoscopy in the gastrointestinal tract.
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Despite effective vaccination programs, waning immunity in the vaccinated populations and the emergence of variants of concern posed a risk of breakthrough infections. A booster dose was demonstrated to provide substantially increased protection against symptomatic disease and hospitalization. We aimed to evaluate immune memory and the efficacy of reducing the rate of SARS-CoV-2 infection post heterologous booster with CORBEVAX after primary vaccination with two doses of COVISHIELD. SARS-CoV-2 S1/S2 spike IgG and RBD-specific antibody responses were elicited with both booster vaccines, with a greater response in individuals receiving heterologous booster. T and B memory responses were increased with booster dose, whereas B memory needed a longer duration to develop in individuals who received a homologous booster (90 days) in comparison to a heterologous booster (30 days). RBD-specific B memory and antibody-secreting (non-memory) B lymphocytes were enhanced with both boosters; however, the duration of response was longer with the heterologous booster compared to the homologous, indicating greater protection with the heterologous booster. The rate of infection 14 days after administration of the heterologous booster was comparatively lower than that of the homologous booster, with the symptoms being much less or asymptomatic.
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Background: Covishield (ChAdOx) and Covaxin (BBV-152) are the mainstream vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) used in India and a few other countries. Objective: To assess the clinical outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) who had been vaccinated with either Covishield or Covaxin. Methods: This prospective, single-centre, observational cohort study of 1160 patients hospitalized with COVID-19 was conducted between April and June 2021. Severity of disease at admission and during hospitalization, requirement for intensive care unit (ICU) admission and ventilatory support, inflammatory markers (C-reactive protein, ferritin, lactate dehydrogenase, D-dimer), neutralizing antibody levels and mortality were assessed in vaccinated and unvaccinated patients. Results: More than 90% of patients in this study harboured the Delta variant (Pango lineage B.1.617.2) of SARS-CoV-2. Severity of disease at admission and during hospitalization (3.44% vs 7.51%; P=0.0032) and requirement for ICU admission and ventilatory support (2.83% vs 5.86%; P=0.0154) were significantly lower in vaccinated patients compared with unvaccinated patients. Vaccinated patients also had significantly (P<0.0001) higher antibody levels and lower inflammatory marker levels compared with unvaccinated patients. A subset of vaccinated, deceased patients mounted minimal antibody response ['non-responders': 4.53 (standard deviation 1.40) AU/mL]. Conclusion: These results demonstrate the effectiveness of Covishield and Covaxin against severe disease in patients hospitalized with COVID-19 with breakthrough infections caused by the Delta variant. Strategies targeting non-responders are desirable to minimize morbidity and mortality.
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Peroral endoscopic myotomy (POEM) is an established frontline treatment modality for achalasia cardia. Since its initial description, several modifications have been proposed to the technique of POEM. Broadly speaking, these modifications follow the basic principles of submucosal endoscopy, but incorporate variations in the POEM technique, including the difference in the orientation of myotomy (anterior or posterior), length of myotomy (short or long), and thickness of myotomy (selective circular or full thickness). Some of these modifications have been shown to reduce procedural duration without compromising the efficacy of the POEM procedure. More recently, several alterations have been reported that intend to reduce gastroesophageal reflux after POEM. These include preservation of sling fibers during posterior POEM and addition of NOTES fundoplication to the POEM procedure. Although some of the modified techniques have been compared with the conventional techniques in quality trials, randomized studies are awaited for others. The incorporation of some of these modifications will likely make POEM a technically easy and safer modality in near future. This review aims to discuss the current evidence with regard to the impact of modified techniques on the outcome of POEM.
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The COVID-19 pandemic has impacted transplantation worldwide in a major way with infections and post-COVID-19 complications contributing to increased mortality and morbidity. We present a case of a 42-year-old lady who developed rhino-orbital mucormycosis in a postliver transplantation period. The initial presentation of the patient was very subtle. She never had overt COVID-19 infection before surgery and in the recovery period. Though cases of mucormycosis in the wound site have been reported, this would be one of the rare cases of rhino-orbital mucormycosis postliver transplantation. This infection leads to a rapid downhill course and the death of the patient. Atypical infections and presentations need to be monitored in postliver transplantation patients who are getting operated on during this pandemic, and a high level of clinical suspicion is required to pick up these cases at an early stage.