Strategies to Improve Colonoscopy Preparation in Inflammatory Bowel Disease. A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND AND AIMS: Colonoscopy has a vital role in the diagnosis of inflammatory bowel disease (IBD), as well as in the estimation of disease severity, monitoring response to therapy, and surveillance for neoplasia. We performed a systematic review of randomised trials of various bowel preparations for colonoscopy in IBD. METHODS: We searched various electronic databases (PubMed, Embase, and CENTRAL) for studies reporting about the use of various strategies to improve colonoscopy preparation in IBD. We included only randomized clinical trials (RCTs). A network meta-analysis was done using a frequentist approach to compare the effectiveness of various bowel preparations. The risk of bias was assessed using Cochrane risk of bias tool 2.0. Other outcome parameters like compliance, tolerance, acceptance, and adverse effects were assessed qualitatively. RESULTS: Seven RCTs reporting about 960 patients were included. On comparison with 4 liter (L) of poliethylen glycol (PEG), oral sulfate solution (OR=1.1, 95%CI: 0.65-1.86); PEG2L/Ascorbate (OR=0.98, 95%CI: 0.65-1.48); PEG1L (OR=1, 95%CI: 0.55-1.81); PEG2L plus bisacodyl (OR=1.08, 95%CI: 0.71-1.65); PEG4L plus simethicone (OR=1, 95%CI: 0.67-1.50); PEG/ sodium picosulfate and magnesium citrate (SPMC) 1.5L (OR=0.99, 95%CI: 0.55-1.78); SPMC 2L (OR=1.09, 95%CI: 0.61-1.97) had similar effectiveness. Three RCTs reported compliance, five RCTs reported tolerance, two studies reported patient acceptance and five RCTs reported data on the willingness of patients to repeat the procedure in the future. Low-volume preparations had better compliance, tolerance, acceptance, and willingness to repeat. No difference in additional outcomes like change in disease activity after colonoscopy, procedure-related outcomes after colonoscopy like cecal intubation rate, and change in electrolyte levels were found. CONCLUSION: Various bowel preparations had similar effectiveness in respect to colonoscopy preparation in IBD patients. Low-volume preparations have better compliance, tolerance, and acceptance. The systematic review was limited by a small number of included RCTs.

Adequacy of sigmoidoscopy as compared to colonoscopy for assessment of disease activity in patients of ulcerative colitis: a prospective study.

Background/Aims: Patients of ulcerative colitis (UC) on follow-up are routinely evaluated by sigmoidoscopy. There is no prospective literature to support this practice. We assessed agreement between sigmoidoscopy and colonoscopy prospectively in patients with disease extent beyond the sigmoid colon. Methods: We conducted a prospective observational study at a tertiary care institute for agreement between sigmoidoscopy and colonoscopy. We assessed endoscopic activity using the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and histological activity using the Nancy Index (NI), Robarts Histopathology Index (RHI), and Simplified Geboes Score (SGS). Results: Sigmoidoscopy showed a strong agreement with colonoscopy for MES and UCEIS with a kappa (K) of 0.96 and 0.94 respectively. The misclassification rate for MES and UCEIS was 3% and 5% respectively. Sigmoidoscopy showed perfect agreement (K = 1.00) with colonoscopy for assessment of the presence of endoscopic activity in the colon using MES ??1 as activity criteria and strong agreement (K = 0.93) using MES > 1 as activity criteria. Sigmoidoscopy showed strong agreement with colonoscopy for assessment of the presence of endoscopic activity using UCEIS (K = 0.92). Strong agreement was observed between sigmoidoscopy and colonoscopy using NI (K = 0.86), RHI (K = 1.00), and SGS (K = 0.92) for the detection of histological activity. The misclassification rate for the detection of histological activity was 2%, 0%, and 1% for NI, RHI, and SGS respectively. Conclusions: Sigmoidoscopy showed strong agreement with colonoscopy for endoscopic and histologic disease activity. Sigmoidoscopy is adequate for assessment of disease activity in patients with UC during follow-up evaluation.

Perceptions regarding the impact of gender on training and career advancement among gastroenterologists in India and other South Asian countries.

BACKGROUND: There are limited studies on the impact of gender on training and career advancement in gastroenterology. AIM: The aim was to study this impact and understand the perceptions of work-life balance and beliefs regarding gender dynamics among gastroenterologists in India and other South Asian countries. METHODS: A web-based survey was conducted among trainees and attending physicians in South Asia from November 15, 2021, to March 30, 2022. The survey instrument had four components: demographic features, training, career advancement and work-life balance. RESULTS: As many as 622 gastroenterologists completed the survey, of which 467 responses were from India (mean age: 41.1 years; females: 11.5%). A higher proportion of female respondents from India believed that gender bias in recruiting and training had negatively impacted their careers (40.7% females vs. 1.5% males). Radiation hazard for fertility (11.1% females vs. 1.9% males, p < 0.001) and as a health concern (14.8% females vs. 5.1% males, p = 0.005) were significant career deterrents for females. A higher proportion of female participants from India faced a career interruption (59.3% females vs. 30.3% males, p ≤ 0.001). Common reasons were pregnancy (37%) and childcare provision (25.9%). More females believed that women were more productive than men (40.8% females vs. 16.9% males, p < 0.001) and that a salary gap existed (44.7% females vs. 29.1% males, p < 0.001). The incidence of self-perceived burnout was 63% among females and 51.6% among males (p = 0.115). CONCLUSION: Gender-related factors impact the training and career of female gastroenterologists.

Comprehensive assessment of nutritional and functional status of patients with ulcerative colitis and their impact on quality of life.

INTRODUCTION: Patients with ulcerative colitis (UC) are likely to have poor nutritional intake and increased gut losses. This study was designed to study the prevalence and predictors of nutritional deficiencies in patients with UC and their impact on the quality of life (QOL). METHODS: A prospective study was conducted among consenting patients with UC (cases) and healthy relatives of the cases (controls) visiting a university teaching hospital. They were assessed for clinical, demographic, endoscopic (Mayo score) and histological profile (Robart's score). They were assessed for the presence of macronutrient and micronutrient deficiency, anthropometry, functional status (muscle strength by dynamometer and sit-to-stand test) and the quality of life (short inflammatory bowel disease questionnaire [SIBDQ]). A SIBDQ score of ≤ 50 was considered poor QOL. RESULTS: We studied 126 cases and 57 healthy controls (age [mean ± SD] 37.7 ± 13.2 years vs. 34.40 ± 11.05 years; [p = 0.10] females [38.1% vs. 38.7%]; p = 0.94). Cases more often were underweight (28% vs. 3.5%; p < 0.001), had low mid arm circumference (45% vs. 12%; p < 0.0001), lower functional status in the form of weaker hand grip strength (67% vs. 45.6%; p = 0.007) and weaker lower limb strength (80% vs. 42%; p < 0.0001). Cases more often had the evidence of macronutrient deficiencies: total serum protein deficiency (31% vs. 3.5%; p < 0.0001), serum albumin deficiency (25.4% vs. 0.00%; p < 0.0001) and cholesterol deficiency (63% vs. 28%; p < 0.0001). Micronutrient deficiencies were highly prevalent among cases: calcium (44%), phosphate (21%), magnesium (11%), zinc (76%), iron (87%), folate (16%), vitamin B12 (10%) and vitamin D (81%). Most cases had a poor quality of life (85/126; 67.5%). Factors associated with poor QOL were low hemoglobin, serum albumin, zinc and vitamin D levels and histologically active disease. On multi-variate analysis, low vitamin D levels (odds ratio [OR] = 6.1; 95% confidence interval [CI]: 1.9-19.7) and histologically active disease (OR = 4.0; 95% CI: 1.6-9.9) were identified as independent predictors of poor QOL. CONCLUSIONS: Macronutrient deficiency, micronutrient deficiency, lower functional status and poorer QOL are highly prevalent among patients with UC. The independent predictors of poor QOL were histologically active disease and low serum vitamin D levels. Identifying and correcting the deficiencies may help in improving the QOL of patients with UC.

Tofacitinib use in ulcerative colitis: An expert consensus for day-to-day clinical practice.

Rising number of inflammatory bowel disease (IBD) cases in developing countries necessitate clear guidance for clinicians for the appropriate use of advanced therapies. An expert consensus document was generated to guide the usage of tofacitinib, a Janus kinase inhibitor, in ulcerative colitis. Tofacitinib is a useful agent for the induction and maintenance of remission in ulcerative colitis. It can be used in the setting of biological failure or even steroid-dependent and thiopurine refractory disease. Typically, the induction dose is 10 mg BD orally. Usually, clinical response is evident within eight weeks of therapy. In those with clinical response, the dose can be reduced from 10 mg BD to 5 mg BD. Tofacitinib should be avoided or used cautiously in the elderly, patients with cardiovascular co-morbidity, uncontrolled cardiac risk factors, previous thrombotic episodes and those at high risk for venous thrombosis or previous malignancy. Baseline evaluation should include testing for and management of hepatitis B infection and latent tuberculosis. Where feasible, it is prudent to ensure complete adult vaccination, including Herpes zoster, before starting tofacitinib. The use of tofacitinib may be associated with an increased risk of infections such as herpes zoster and tuberculosis reactivation. Maternal exposure to tofacitinib should be avoided during pre-conception, pregnancy, and lactation. There is emerging evidence of tofacitinib in acute severe colitis, although the exact positioning (first-line with steroids or second-line) is uncertain.

Corrosive induced esophageal and gastric injury: Histopathological evaluation of surgically resected specimens over a decade in a tertiary care center.

BACKGROUND: Caustic ingestion is associated with long-term sequelae like esophageal stricture, gastric cicatrization, and long-term risk of dysplasia or even carcinoma. However, only a few small studies have explored histopathological aspects of caustic-induced esophageal/gastric injury. MATERIALS AND METHODS: We retrospectively evaluated specimens of patients undergoing surgery due to caustic ingestion-related complications from 2008 to 2020. Pathological examination was conducted by two independent gastro-pathologists to evaluate the extent and depth of the caustic injury, presence or absence of tissue necrosis, type and degree of inflammation, or presence of any dysplastic cells. RESULTS: A total of 54 patients underwent surgical exploration during the inclusion period and complete details of 39 specimens could be retrieved. The mean age of the included patients was 28.66 ± 9.31 years and 25 (64.1%) were male. The majority of patients (30; 76.9%) had a history of caustic ingestion more than three months before the surgery and the presence of long or refractory stricture was the most common indication for the surgery (20; 51.28%). In the resected specimen, a majority of patients had superficial esophageal or gastric ulcer (90.6%; 60.0%), transmural inflammation (68.8%; 65.6%), transmural fibrosis (62.5%; 34.4%), and hypertrophied muscularis mucosa (78.13%; 53.3%). However, none of the patients had dysplasia in the resected esophageal or gastric specimens. CONCLUSION: Caustic ingestion leads to mucosal ulceration, transmural inflammation, and transmural fibrosis which might be the reason for refractory stricture in such patients.

Osteonecrosis in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: The relationship of inflammatory bowel disease (IBD) with osteonecrosis or avascular necrosis (AVN) is uncertain. METHODS: Systematic review to estimate the frequency of osteonecrosis in IBD was performed. Electronic databases were searched on 12 December 2022 to identify relevant studies. We planned to estimate the pooled prevalence of AVN in IBD, the risk in IBD when compared to the healthy population (without any chronic disease), and the impact of steroid use on osteonecrosis (IBD with and without steroid use). The risk of Bias was assessed with the Joanna Briggs Institute appraisal tool. RESULTS: Fifteen studies including 105 154 individuals were included. The pooled rate AVN was 10.39 per 1000 patients (95% confidence interval, 4.44-24.11, I 2  = 97%). Subgroup analysis suggested that the prevalence was lower in larger studies (>1000 participants) at 3.10, 1.07; 8.98, I 2  = 98% versus 21.03, 8.69; 50.01, I 2  = 83%. The use of steroids did not seem to increase the risk of osteonecrosis in the included studies (pooled odds ratio: 1.88, 0.55-6.41, I 2  = 39%). The systematic review was limited by the absence of comparison with the control population free of chronic disease. CONCLUSION: IBD may be associated with a risk of osteonecrosis. Future studies should assess the risk in comparison to the healthy population and the impact of disease activity and IBD therapies on the risk.

Artificial intelligence for discrimination of Crohn's disease and gastrointestinal tuberculosis: A systematic review.

BACKGROUND AND AIM: Discrimination of gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) is difficult. Use of artificial intelligence (AI)-based technologies may help in discriminating these two entities. METHODS: We conducted a systematic review on the use of AI for discrimination of GITB and CD. Electronic databases (PubMed and Embase) were searched on June 6, 2022, to identify relevant studies. We included any study reporting the use of clinical, endoscopic, and radiological information (textual or images) to discriminate GITB and CD using any AI technique. Quality of studies was assessed with MI-CLAIM checklist. RESULTS: Out of 27 identified results, a total of 9 studies were included. All studies used retrospective databases. There were five studies of only endoscopy-based AI, one of radiology-based AI, and three of multiparameter-based AI. The AI models performed fairly well with high accuracy ranging from 69.6-100%. Text-based convolutional neural network was used in three studies and Classification and regression tree analysis used in two studies. Interestingly, irrespective of the AI method used, the performance of discriminating GITB and CD did not match in discriminating from other diseases (in studies where a third disease was also considered). CONCLUSION: The use of AI in differentiating GITB and CD seem to have acceptable accuracy but there were no direct comparisons with traditional multiparameter models. The use of multiple parameter-based AI models have the potential for further exploration in search of an ideal tool and improve on the accuracy of traditional models.

Conventional vs Short Duration of Antibiotics in Patients With Moderate or Severe Cholangitis: Noninferiority Randomized Trial.

INTRODUCTION: Successful biliary drainage and antibiotics are the mainstays of therapy in management of patients with acute cholangitis. However, the duration of antibiotic therapy after successful biliary drainage has not been prospectively evaluated. We conducted a single-center, randomized, noninferiority trial to compare short duration of antibiotic therapy with conventional duration of antibiotic therapy in patients with moderate or severe cholangitis. METHODS: Consecutive patients were screened for the inclusion criteria and randomized into either conventional duration (CD) group (8 days) or short duration (SD) group (4 days) of antibiotic therapy. The primary outcome was clinical cure (absence of recurrence of cholangitis at day 30 and >50% reduction of bilirubin at day 15). Secondary outcomes were total days of antibiotic therapy and hospitalization within 30 days, antibiotic-related adverse events, and all-cause mortality at day 30. RESULTS: The study included 120 patients (the mean age was 55.85 ± 13.52 years, and 50% were male patients). Of them, 51.7% patients had malignant etiology and 76.7% patients had moderate cholangitis. Clinical cure was seen in 79.66% (95% confidence interval, 67.58%-88.12%) patients in the CD group and 77.97% (95% confidence interval, 65.74%-86.78%) patients in the SD group ( P = 0.822). On multivariate analysis, malignant etiology and hypotension at presentation were associated with lower clinical cure. Total duration of antibiotics required postintervention was lower in the SD group (8.58 ± 1.92 and 4.75 ± 2.32 days; P < 0.001). Duration of hospitalization and mortality were similar in both the groups. DISCUSSION: Short duration of antibiotics is noninferior to conventional duration in patients with moderate-to-severe cholangitis in terms of clinical cure, recurrence of cholangitis, and overall mortality.

Indigo naturalis (Qing dai) for inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND: Indigo naturalis (Qing dai) is a traditional therapy reported to be useful in inflammatory bowel disease (IBD), especially for ulcerative colitis. We performed a systematic review of its efficacy and safety in IBD. METHODS: Electronic databases (Pubmed, Embase, and Scopus) were searched on 4th March 2023 to identify reports about the use of indigo naturalis in IBD. We extracted data with respect to clinical response, remission, endoscopic and histological responses, and adverse events with the use of indigo naturalis in IBD. Pooled clinical response rates and remission rates were calculated. The quality of studies was assessed using Joanna-Briggs tools. RESULTS: Nine studies reporting on 299 patients were included. The pooled clinical response rate was 0.796 (95 %CI, 0.7465-0.8379, I2=0), and the clinical remission rate in ulcerative colitis was 0.668 (0.488- 0.809, I2=85.2 %). The pooled relative risk of clinical response was higher in the indigo naturalis group as compared to placebo in the two randomized trials [3.82 (2.04; 7.14, I2=0)]. Except for one reversible pulmonary arterial hypertension case, most reported adverse effects were mild. The endoscopic and histological responses, when reported, suggested that indigo naturalis is effective for ulcerative colitis. The limitations of the systematic review included a small number of randomized studies, reports only from East Asia and a relatively small number of patients, especially for Crohn's disease. CONCLUSION: Indigo naturalis is effective in the treatment of ulcerative colitis. Future studies should evaluate the comparative efficacy with other drugs.

A Rare Cause of Acute on Chronic Liver Failure (ACLF): Bakuchi-Induced Liver Injury.

Psoralea corylifolia Linn (Bakuchi or Babchi), commonly known as purple fleabane, is a popular herb used in Ayurvedic traditional medicine. Its seeds, called Fructus Psoraleae, are traditionally used for treating leprosy, vitiligo, and psoriasis in the absence of empirical evidence. We report the first case of acute on chronic liver failure (ACLF) caused by Bakuchi, a well-documented hepatotoxic agent, in a middle-aged female. Her liver function deteriorated progressively which prompted us to go for a liver biopsy which was consistent with diagnosis of herb-induced liver injury after excluding all competing causes. Fortunately, the patient improved gradually after herb withdrawal and supportive care. Patients with underlying chronic liver disease (CLD) should be aware of risks in using untested herbal formulations. This case emphasizes the need for increased surveillance to formulate guidelines regarding the regulation and informed use of herbal supplements in patients with chronic liver disease.

Endoscopic ultrasound-guided drainage of early pancreatic necrotic collection: Single-center retrospective study.

BACKGROUND: Endoscopic ultrasound (EUS)-guided drainage is the standard of care for drainage of pancreatic necrosis. Though initially it was mainly used for drainage of only walled-off necrosis, recently, a few studies have also shown its safety in the management of acute necrotic collections. We did a retrospective study to evaluate the safety and efficacy of EUS-guided drainage in the early phase of pancreatitis as compared to interventions in the late phase. METHODS: We retrieved baseline disease-related, procedure-related and outcome-related details of patients who underwent EUS-guided drainage of pancreatic necrosis. Patients were divided into early (≤ 28 days from onset of pancreatitis) or delayed (> 28 days) drainage groups. Both groups were compared for disease-related characteristics and outcomes. RESULTS: Total 101 patients were included in the study. The mean age of included patients was 35.54 ± 13.58 years and 75 were male. Thirty-five patients (34.7%) underwent early drainage. In the early group, a majority of patients underwent intervention due to infected collection (88.6% vs. 18.2%; p < 0.001). More patients in the early group had < 30% wall formation (28.6% vs. 0%; p < 0.001) and > 30% solid debris within the collection (42.9% vs. 15.2%; p = 0.005). Patients in the early group were also more likely to require endoscopic necrosectomy (57.1% vs. 27.3%; p = 0.003) and additional percutaneous drainage (31.4% vs. 12.1%; p = 0.018). Overall, three patients in the early group and one patient in the delayed group had procedure-related complications. Four patients in the early group and one patient in the delayed group succumbed to illness (p = 0.029). CONCLUSION: Though delayed interventions remain standard of care in the management of acute pancreatitis, some patients may require early intervention due to infected collection with deteriorating clinical status. Early EUS-guided interventions in such carefully selected patients have in similar clinical outcomes and complication rates compared to delayed intervention. However, such patients are more likely to require additional endoscopic or percutaneous interventions.

Representation and reporting of diverse groups in randomised controlled trials of pharmacological agents in inflammatory bowel disease: a systematic review.

Inflammatory bowel disease (IBD) is now recognised as a global disease, with incidence rapidly increasing in newly industrialised countries in South America, Asia, and Africa. Trials in IBD, therefore, should adequately represent diverse groups with respect to gender, age, place of residence, race, and ethnicity to ensure the global applicability and generalisability of their findings. In this systematic review, we searched PubMed and Embase for randomised controlled trials (RCTs) published in English from Jan 1, 1995, to Jan 13, 2023, evaluating the efficacy of any pharmacological intervention in patients with IBD. Of 7543 records yielded in the search, we included 617 records reporting data from 627 RCTs and 108 986 participants. The results show a paucity of adequate representation of diverse groups in these RCTs. This finding was true for various groups, including racially and ethnically diverse populations, older (aged >65 years) and younger (aged <18 years) populations, those who identify outside of the gender binary, and people from South America and Africa. Also, some regions had an apparent scarcity of funding sources for trials. Pharmaceutical companies and clinical trial organisations should aim to ensure adequate representation of such under-represented groups in future IBD trials.

Endoscopic Ultrasound (EUS)-guided Drainage of Caudate Lobe Abscess: A Single Center Experience.

BACKGROUND: Liver abscess is usually treated with medical therapy. Few patients require drainage of the collection due to large size, certain high-risk location or rupture of the collection. Percutaneous drainage is most commonly used modality for the drainage of such collection. However, caudate lobe poses a unique difficulty in percutaneous drainage due to its deep location. METHODS: We did a retrospective analysis of all patients with caudate lobe abscess who underwent endoscopic ultrasound (EUS)-guided drainage at our center. We reviewed their indications, technical and clinical success rates of the procedure from 2020 to 2023. We also performed systemic review of published literature till June 12, 2023 showing use of EUS-guided drainage of caudate lobe abscess. RESULTS: Total of 8 patients (age: 37.33 ± 12.8 y; Males 62.5%) underwent EUS-guided drainage of caudate lobe collection at our center. Six patients underwent drainage using plastic stents, 1 patient underwent using metal stent, and 1 patient had aspiration of the abscess. Technical success was achieved in all patients. One patient succumbed to background illness and clinical success could be achieved in rest of the patients. In systemic review of literature on EUS-guided drainage of caudate lobe, a total of 10 studies (17 patients) were included. All patients achieved technical success. Majority studies reported use of plastic stents or naso-cystic drains whereas only 1 case reported use of metal stents. One procedure related complication (localized para-esophageal abscess) was reported requiring endoscopic intervention for management. CONCLUSION: EUS-guided drainage of caudate lobe abscess is safe and effective. It should be used as a first-line intervention after a failed medical management.

Endoscopic dilation with bougies versus balloons in caustic esophageal strictures: 17-year experience from a tertiary care center.

INTRODUCTION: Endoscopic dilation is the preferred management strategy for caustic esophageal strictures (CES). However, the differences in outcome for different dilators are not clear. We compared the outcome of CES using bougie and balloon dilators. METHODS: Between January 2000 and December 2016, the following data of all the patients with CES were collected: demographic parameters, substance ingestion, number of strictures, number of dilations required to achieve ≥ 14 mm dilation, post-dilation recurrence, and total dilations. Patients were divided into two groups for the type of dilator, i.e., bougie or balloon. The two groups were compared for baseline parameter, technical success, short- and long-term clinical success, refractory strictures, recurrence rates, and major complications. RESULTS: Of the 189 patients (mean age 32.17 ± 12.12 years) studied, 119 (62.9%) were males. 122 (64.5%) patients underwent bougie dilation and 67 (35.5%) received balloon dilation. Technical success (90.1% vs. 68.7%, p < 0.001), short-term clinical success (65.6% vs. 46.3%, p value 0.01), and long-term clinical success (86.9% vs. 64.2%, p < 0.01) were higher for bougie dilators compared to balloon dilators. Twenty-four (12.7%) patients developed adverse events which were similar for two groups. On multivariate analysis, use of bougie dilators (aOR 4.868, 95% CI 1.027-23.079), short-term clinical success (aOR 5.785, 95% CI 1.203-27.825), and refractory strictures (aOR 0.151, 95% CI 0.033-0.690) were independent predictors of long-term clinical success. CONCLUSION: Use of bougie dilators is associated with better clinical success in patients with CES compared to balloon dilators with similar rates of adverse events.

Safety and efficacy of personalized versus standard initial dosing of thiopurines: Systematic review and meta-analysis of randomized trials.

BACKGROUND: Pretherapy assessment of specific genetic polymorphism (TPMT, NUDT15, FTO, RUNX1, etc) or enzyme levels (for TPMT) may help personalize the dose of thiopurines and avoid adverse effects. RESEARCH DESIGN AND METHODS: A systematic review of randomized controlled trials (RCTs) comparing personalized versus standard strategy for initial thiopurine dosing was performed. The electronic databases were searched on 27 September 2022. The outcomes were overall adverse effects, myelotoxicity, drug interruptions, and therapeutic efficacy with either strategy. The certainty of evidence was assessed using GRADE methodology. RESULTS: We included six randomized trials, done dominantly in patients with inflammatory bowel disease (IBD). The personalized strategies were genotype testing in 4 trials (TPMT in three trials, NUDT15 in two) and enzyme levels for TPMT in two trials. The pooled risk of myelotoxicity in personalized dosing was lower [RR = 0.72 (95%CI, 0.55-0.94, I2 = 0%)]. The pooled risk of pancreatitis (RR = 1.10I, 0.78-1.56, I2 = 0%), hepatotoxicity (RR = 1.13, 0.69-1.88, I2 = 45), and GI intolerance (RR = 1.01, 0.92-1.10, I2 = 0) were similar in two groups. The pooled risk of drug interruption in individualized dosing was similar to the standard dosing group (RR = 0.97, I2 = 68%). CONCLUSION: Personalized testing-based initial thiopurine dosing is protective against myelotoxicity as compared to standard weight-based dosing.

Hyperglycemia is associated with duodenal dysbiosis and altered duodenal microenvironment.

The gut microbiome influences the pathogenesis and course of metabolic disorders such as diabetes. While it is likely that duodenal mucosa associated microbiota contributes to the genesis and progression of increased blood sugar, including the pre-diabetic stage, it is much less studied than stool. We investigated paired stool and duodenal microbiota in subjects with hyperglycemia (HbA1c ≥ 5.7% and fasting plasma glucose > 100 mg/dl) compared to normoglycemic. We found patients with hyperglycemia (n = 33) had higher duodenal bacterial count (p = 0.008), increased pathobionts and reduction in beneficial flora compared to normoglycemic (n = 21). The microenvironment of duodenum was assessed by measuring oxygen saturation using T-Stat, serum inflammatory markers and zonulin for gut permeability. We observed that bacterial overload was correlated with increased serum zonulin (p = 0.061) and higher TNF-α (p = 0.054). Moreover, reduced oxygen saturation (p = 0.021) and a systemic proinflammatory state [increased total leukocyte count (p = 0.031) and reduced IL-10 (p = 0.015)] characterized the duodenum of hyperglycemic. Unlike stool flora, the variability in duodenal bacterial profile was associated with glycemic status and was predicted by bioinformatic analysis to adversely affect nutrient metabolism. Our findings offer new understanding of the compositional changes in the small intestine bacteria by identifying duodenal dysbiosis and altered local metabolism as potentially early events in hyperglycemia.

Electrosurgical unit in GI endoscopy: the proper settings for practice.

INTRODUCTION: Electrosurgical unit (ESU) is integral to the endoscopy unit. The proper knowledge of the Mode with setting is essential for good therapeutic outcomes and the safety of the patients. AREAS COVERED: ESU generates high-frequency electric current, which could perform cutting and coagulation for various therapeutic interventions. We review the proper settings for common endoscopic interventions like hemostasis, polypectomy, sphincterotomy, and advanced procedures like endoscopic ultrasound-guided cysto-gastrostomy, bile duct drainage, and endoscopic Ampullectomy. We review the various waveforms of ESU in practice in endoscopy, including special conditions like patients with pacemakers. EXPERT OPINION: Knowledge of the waveforms' duty cycle and crest factor is necessary. A high-duty cycle and lower crest factor lead to a good cutting effect on the tissue. Endocut is the most commonly used Mode in ESU in endoscopic practices like sphincterotomy and polypectomy. Endocut I mode (effect 1-2, duration 3, interval 3) is used for endoscopic sphincterotomy, while Forced Coag mode (Effect 2, 60 W) controls post-sphincterotomy bleeding. Endocut Q mode (Effect 2-3, duration 1, interval 3) is used for cutting the polyp, while Forced Coag mode (Effect 2, 60 W) is used before cutting for pre-coagulation of the stalk.