Ajay P. Belgaumkar

Bio: Ajay P. Belgaumkar is an academic researcher from University of Cambridge. The author has contributed to research in topics: Medicine & Insulin resistance. The author has an hindex of 9, co-authored 17 publications receiving 618 citations.

Surgery in Castleman's disease: a systematic review of 404 published cases.

Abstract: Objectives:We undertook a systematic review of 404 published cases of Castleman's disease to identify the role of the surgeon beyond assistance in tissue-based diagnosis.Background:Castleman's disease is a rare primary disease of the lymph node caused by infection with herpesviridae. Little is known

The Effect of Bariatric Surgery on Intestinal Absorption and Transit Time

Abstract: Bariatric surgical procedures are classified by their presumed mechanisms of action: restrictive, malabsorptive or a combination of both. However, this dogma is questionable and remains unproven. We investigated post-operative changes in nutrient absorption and transit time following bariatric surgery. Participants were recruited into four groups: obese controls (body mass index (BMI) >30 kg/m2, n = 7), adjustable gastric banding (n = 6), Roux-en-Y gastric bypass (RYGB, n = 7) and biliopancreatic diversion with duodenal switch (DS, n = 5). Participants underwent sulphasalazine/sulphapyridine tests (oro-caecal transit time); fasting plasma citrulline (functional enterocyte mass); 3 days faecal collection for faecal elastase 1 (FE-1); calprotectin (FCp); faecal fatty acids (pancreatic exocrine function, gut inflammation and fat excretion, respectively); and 5 h d-xylose, l-rhamnose and lactulose test (intestinal absorption and permeability). Age and gender were not different but BMI differed between groups (p = 0.001). No difference in oro-caecal transit time (p = 0.935) or functional enterocyte mass (p = 0.819) was detected. FCp was elevated post-RYGB vs obese (p = 0.016) and FE-1 was reduced post-RYGB vs obese (p = 0.002). Faecal fat concentrations were increased post-DS vs obese (p = 0.038) and RYGB (p = 0.024) and were also higher post-RYGB vs obese (p = 0.033). Urinary excretion of d-xylose and l-rhamnose was not different between the groups; however, lactulose/rhamnose ratio was elevated post-DS vs other groups (all p < 0.02), suggesting increased intestinal permeability. Following RYGB, there are surprisingly few abnormalities or indications of severe malabsorption of fats or sugars. Small bowel adaptation after bariatric surgery may be key to understanding the mechanisms responsible for the beneficial metabolic effects of these operations.

The impact of inflammatory bowel disease post-liver transplantation for primary sclerosing cholangitis.

Abstract: Background An association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) is well recognized. However, the disease course of IBD following liver transplantation (LT) for PSC remains ill-defined. Aims and methods We aimed to assess the impact of IBD in patients that had undergone LT for PSC to help identify risk factors for flare and to assess the impact of IBD on graft survival. Results 110 patients underwent LT for PSC (Oct 1990-Aug 2009) at King's College Hospital. 74 (67%) patients had concurrent IBD and 36 had PSC alone prior to transplant. 39 patients developed IBD (flare of IBD and de-novo) post transplant. Cumulative risk for IBD at 1-, 2-, 5- and 10-years was 16%, 24%, 38% and 72% respectively. Flare of IBD occurred in 33 patients with a mean time to flare of 30 ± 28 months. De-novo IBD occurred in 6 patients (all UC). Mean time to diagnosis was 29 ± 25 months. Multivariate cox-regression analysis identified active IBD at time of LT as a significant predictor of graft failure post LT (HR 10, CI 3-39, P = 0.001) and smoking at time of transplantation and subsequent cessation predictive of recurrent IBD post transplantation (HR 17, 2-180, P = 0.02). Conclusion In conclusion, smoking at time of LT was predictive of flare of IBD and active IBD at time of transplantation had a significant effect on graft survival. Medical therapy needs to be maximised in the pre-LT period. Patients with poorly controlled IBD refractory to medical therapy should be considered for colectomy at time of transplantation.

Changes in Bile Acid Profile After Laparoscopic Sleeve Gastrectomy are Associated with Improvements in Metabolic Profile and Fatty Liver Disease.

Abstract: Bile acids (BA) modulate lipid and glucose metabolism in a feedback loop through production of fibroblast growth factor (FGF) 19 in the terminal ileum Changes in BA after bariatric surgery may lead to improvements in the metabolic syndrome, including fatty liver disease This study investigated the relationship between BA and metabolic and inflammatory profiles after laparoscopic sleeve gastrectomy (LSG) Patients undergoing LSG had fasting blood samples taken pre-operatively and 6 months post-surgery Liver injury was measured using cytokeratin (CK) 18 fragments BA were measured using liquid chromatography tandem-mass spectrometry FGF-19 was measured using enzyme-linked immunosorbent assay The study included 18 patients (12 females), with mean age 463 years (SEM ± 29) and BMI 601 kg/m2 (±26) After 6 months, patients lost 398 kg (±31; p < 0001) Fourteen patients (78 %) had steatosis FGF-19 increased from median 1281 (IQR 894–2101) to 1771 (1218–2889, p = 0045) at 6 months Although total BA did not change, primary glycine- and taurine-conjugated BA, cholic acid decreased, and secondary BA, glycine-conjugated urodeoxycholic acid increased over the study period These changes are associated with reduction in insulin resistance, pro-inflammatory cytokines and CK-18 levels The profile of individual BA is altered after LSG These changes occur in the presence of reductions in inflammatory cytokines and markers of liver injury This study supports evidence from recent animal models that LSG may have an effect on fatty liver through changes in BA metabolism

A living WHO guideline on drugs for covid-19

Abstract: Clinical question What is the role of drug interventions in the treatment of patients with covid-19? New recommendation Increased attention on ivermectin as a potential treatment for covid-19 triggered this recommendation. The panel made a recommendation against ivermectin in patients with covid-19 regardless of disease severity, except in the context of a clinical trial. Prior recommendations (a) a strong recommendation against the use of hydroxychloroquine in patients with covid-19, regardless of disease severity; (b) a strong recommendation against the use of lopinavir-ritonavir in patients with covid-19, regardless of disease severity; (c) a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19; (d) a conditional recommendation against systemic corticosteroids in patients with non-severe covid-19, and (e) a conditional recommendation against remdesivir in hospitalised patients with covid-19. How this guideline was created This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development group (GDG) of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Understanding the new recommendation There is insufficient evidence to be clear to what extent, if any, ivermectin is helpful or harmful in treating covid-19. There was a large degree of uncertainty in the evidence about ivermectin on mortality, need for mechanical ventilation, need for hospital admission, time to clinical improvement, and other patient-important outcomes. There is potential for harm with an increased risk of adverse events leading to study drug discontinuation. Applying pre-determined values and preferences, the panel inferred that almost all well informed patients would want to receive ivermectin only in the context of a randomised trial, given that the evidence left a very high degree of uncertainty on important effects. Updates This is a living guideline. It replaces earlier versions (4 September, 20 November, and 17 December 2020) and supersedes the BMJ Rapid Recommendations on remdesivir published on 2 July 2020. The previous versions can be found as data supplements. New recommendations will be published as updates to this guideline. Readers note This is the fourth version (update 3) of the living guideline (BMJ 2020;370:m3379). When citing this article, please consider adding the update number and date of access for clarity.

Drug treatments for covid-19: living systematic review and network meta-analysis.

Abstract: Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 12 February 2021 were included in the analysis. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 196 trials enrolling 76 767 patients were included; 111 (56.6%) trials and 35 098 (45.72%) patients are new from the previous iteration; 113 (57.7%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 20 fewer per 1000 patients, 95% credible interval 36 fewer to 3 fewer, moderate certainty), mechanical ventilation (25 fewer per 1000, 44 fewer to 1 fewer, moderate certainty), and increase the number of days free from mechanical ventilation (2.6 more, 0.3 more to 5.0 more, moderate certainty). Interleukin-6 inhibitors probably reduce mechanical ventilation (30 fewer per 1000, 46 fewer to 10 fewer, moderate certainty) and may reduce length of hospital stay (4.3 days fewer, 8.1 fewer to 0.5 fewer, low certainty), but whether or not they reduce mortality is uncertain (15 fewer per 1000, 30 fewer to 6 more, low certainty). Janus kinase inhibitors may reduce mortality (50 fewer per 1000, 84 fewer to no difference, low certainty), mechanical ventilation (46 fewer per 1000, 74 fewer to 5 fewer, low certainty), and duration of mechanical ventilation (3.8 days fewer, 7.5 fewer to 0.1 fewer, moderate certainty). The impact of remdesivir on mortality and most other outcomes is uncertain. The effects of ivermectin were rated as very low certainty for all critical outcomes, including mortality. In patients with non-severe disease, colchicine may reduce mortality (78 fewer per 1000, 110 fewer to 9 fewer, low certainty) and mechanical ventilation (57 fewer per 1000, 90 fewer to 3 more, low certainty). Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. Conclusion Corticosteroids and interleukin-6 inhibitors probably confer important benefits in patients with severe covid-19. Janus kinase inhibitors appear to have promising benefits, but certainty is low. Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to have any important benefits. Whether or not remdesivir, ivermectin, and other drugs confer any patient-important benefit remains uncertain. Systematic review registration This review was not registered. The protocol is publicly available in the supplementary material. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fourth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.