ORCID Profile
0000-0003-3924-4830
Current Organisations
Nottingham University Hospitals NHS Trust
,
NIHR Nottingham Biomedical Research Centre
,
University of Nottingham
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Publisher: Elsevier BV
Date: 10-2023
Publisher: Springer Science and Business Media LLC
Date: 14-11-2010
DOI: 10.1007/S00464-009-0737-3
Abstract: Endoscopic ultrasound (EUS) is useful for detecting depth of invasion and nodal involvement in patients with early Barrett's neoplasia (EBN), precluding endoscopic management. This study aimed to determine whether the lesion morphology of the EBN shown on high-resolution endoscopy predicts EUS and histologic tumor stage. Retrospective series from two tertiary referral centers were studied. Patients with EBN referred for EUS evaluation before treatment were identified, and data were collected from endoscopies, a database, and case notes. All patients had high-resolution endoscopy followed by radial EUS. This study included 50 patients (22 men) with a median age of 69 years (interquartile range, 60-79 years). Visible lesions in the Barrett's segment were described as Paris types 0-1 (n = 9), 0-IIb (n = 12), 0-IIa (n = 12), 0-IIa + IIc (n = 6), and 0-IIc (n = 5). Of the 50 patients, 46 (92%) had either EMR (n = 17), esophagectomy (n = 23), or both (n = 6). All 12 patients (100%) with Paris 0-IIb lesions had T0/T1 m staging on EUS confirmed with resection histology. The sensitivity for EUS T-staging for Paris classification was 71.4% for type 0-I, 100% for type 0-IIb, 83% for type 0-IIa, 66.7% for type 0-IIa + IIc, and 66.7% for type IIc. Overall, 8 (17%) of the 46 patients were understaged and 2 (4%) were overstaged. For detecting submucosal invasion, EUS had a sensitivity of 66%, a specificity of 93%, a negative predictive value of 85%, and a diagnostic accuracy of 84.4%. Submucosal invasion is detected by EUS for 26% of patients with EBN. The value of EUS staging before resection for type 0-IIb early Barrett's cancer (flat lesions) is limited because 100% of these lesions are limited to the mucosa. For the management algorithm in this selected cohort, the use of EUS should be reconsidered.
Publisher: Wiley
Date: 19-03-2019
DOI: 10.1002/CPT.1375
Abstract: Some patients prescribed flucloxacillin (~ 0.01%) develop drug-induced liver injury (DILI). HLA-B*57:01 is an established genetic risk factor for flucloxacillin DILI. To consolidate this finding, identify additional genetic factors, and assess relevance of risk factors for flucloxacillin DILI in relation to DILI due to other penicillins, we performed a genomewide association study involving 197 flucloxacillin DILI cases and 6,835 controls. We imputed single-nucleotide polymorphism and human leukocyte antigen (HLA) genotypes. HLA-B*57:01 was the major risk factor (allelic odds ratio (OR) = 36.62 P = 2.67 × 10
Publisher: Elsevier BV
Date: 12-2012
Publisher: Georg Thieme Verlag KG
Date: 04-2009
Abstract: Esophageal and/or gastric wall thickening raises the possibility of malignancy. Endoscopic-ultrasound-(EUS-)guided targeted biopsy of the thickened wall is possible. We aimed to evaluate the efficacy and safety of EUS-guided mural trucut biopsies (TCB) in detecting underlying malignancy in patients with thickened esophagogastric wall and negative mucosal biopsies. Patients with alarm symptoms referred for EUS-guided s ling after negative endoscopy and mucosal biopsy were included in the study. All patients had radial EUS reporting abnormal thickening of the esophageal/gastric wall. A linear-array echoendoscope and a 19-gauge trucut needle were used for s ling. Clinical and investigatory data were collected prospectively between 2004 and 2008. Thirty-one patients (20 men) aged 60 - 74 years (median 67 years) were included. All patients had thickened esophageal wall (n = 10), gastric wall (n = 21), or both on radial EUS. Prior to EUS, patients had undergone 1 - 5 endoscopies (median 1.2) and 2 - 8 mucosal biopsies (median 4). The median esophageal and gastric wall thicknesses were 12 and 18 mm respectively. During s ling 1 - 5 needle punctures (median 3) were made. On EUS-TCB, an adequate specimen for histology was obtained in 28/31 patients (90 %). The size of the tissue cores was 4 - 10 mm (median 6mm). Malignancy was confirmed in 16/31 patients (54 %) on histology, and in 11/31 patients (35.4 %) an underlying malignancy was excluded. There was no significant correlation between wall thickness and biopsy size (rho = 0.11, 95 %CI- 0.25 to - 0.45, two-sided P = 0.53). EUS-TCB had sensitivity, specificity, and positive and negative predictive values of 85 %, 100 %, 100 %, and 74 % respectively. There were no immediate or late complications. EUS-guided mural TCB is a safe and effective technique in the investigation of esophagogastric wall thickening in patients with alarm symptoms and has high sensitivity and specificity for the diagnosis of a cancer.
Publisher: Georg Thieme Verlag KG
Date: 10-07-2007
Abstract: Both endoscopic ultrasound- (EUS-) guided tissue s ling techniques, fine-needle aspiration (FNA) and Trucut biopsy, have advantages and limitations. The aim of this study was to develop a strategy of combining these two EUS-guided s ling techniques in order to maximize the diagnostic accuracy and minimize duplication. In this multicenter study we performed "dual s ling" (i. e. with both FNA and Trucut biopsy) in 95 patients during phase 1 of the study and "sequential s ling" (i. e. performing FNA only when Trucut biopsy tissue cores were macroscopically inadequate) in 72 patients during phase 2. During the study period, 167/401 patients referred for EUS-guided s ling were eligible for the study only solid lesions were included. In 143/167 patients (86 %), s ling was performed via the transesophageal or transgastric routes. When the dual s ling strategy was used, an accurate diagnosis was achieved in 78/95 patients by FNA, compared with 85/95 by Trucut biopsy ( P = 0.21). The combined accuracy of the dual s ling strategy was higher than FNA alone (88/95 vs. 78/95, P = 0.048), but was not significantly higher than Trucut biopsy alone (88/95 vs. 85/95, P = 0.61). Using the sequential s ling strategy, an accurate diagnosis was achieved in 66/72 patients (92 %) compared with 88/95 (93 %) for dual s ling ( P = 1.0), and 8/72 patients (11 %) had to undergo FNA after Trucut biopsy failed to obtain an adequate s le. One patient with mediastinal tuberculosis developed a cold abscess following Trucut biopsy. A sequential s ling strategy, in which EUS-guided Trucut biopsy is attempted first, and FNA performed only when Trucut biopsy fails to obtain a macroscopically adequate s le, achieves a diagnostic accuracy of 92 %, with 11 % of patients requiring both s ling procedures.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2013
DOI: 10.1002/HEP.26030
Abstract: Liver biopsy is the reference standard for the detection of nonalcoholic steatohepatitis (NASH) within nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify a biomarker of NASH in patients without significant fibrosis. In all, 172 patients from two centers with biopsy-proven NAFLD were included in this study. Eighty-four patients from a single center were included as a derivation cohort and 88 patients from a second center were included as a validation cohort. Serum s les were tested for candidate markers of fibrosis and inflammation alongside hematological and biochemical markers. Among patients without advanced fibrosis, terminal peptide of procollagen III (PIIINP) was the only marker found to be associated with a histological diagnosis of NASH in both cohorts. PIIINP also correlated with the total NAFLD activity score (NAS) and its constituent components (P < 0.001). Area under receiver operating characteristic curve (AUROC) for PIIINP in discriminating between NASH and simple steatosis (SS) was 0.77-0.82 in patients with F0-2 fibrosis and 0.82-0.84 in patients with F0-3 fibrosis. PIIINP was elevated in patients with advanced fibrosis, the overwhelming majority of whom had NASH. When incorporating patients with all degrees of fibrosis from both cohorts, PIIINP was able to discriminate between patients with SS and those with NASH or advanced fibrosis with AUROC 0.85-0.87. PIIINP discriminates between SS and NASH or advanced fibrosis. The use of a single biomarker in this context will be of clinical utility in detecting the minority of patients with NAFLD who have NASH or advanced fibrosis related to NASH.
Publisher: Elsevier BV
Date: 2011
Publisher: Springer Science and Business Media LLC
Date: 03-06-2014
DOI: 10.1007/S00228-014-1703-0
Abstract: This study aims to assess whether NAT2 genotype affects susceptibility to moderate to severe liver injury in patients undergoing drug treatment for tuberculosis with isoniazid-containing regimens. Twenty-six patients of European or South Asian ethnicity, who had suffered liver injury during treatment with isoniazid-containing drug regimens and 101 ethnically matched controls were genotyped for the NAT2*5, NAT2*6, and NAT2*7 alleles. Genotyping for additional polymorphisms in the NAT gene region was also performed on 20 of the 26 cases. NAT2 genotype frequency between cases and controls was compared. NAT2 genotypes predicting a slow acetylator phenotype were found to be associated with an increased risk of isoniazid-related liver injury (odds ratio (OR) = 4.25 (95% confidence interval (CI), 1.36-13.22) p = 0.012) with 85% of the cases being slow acetylators compared with 56% of the controls. There was no evidence for an increased risk for the slow acetylator genotype in patients with the most severe cases of liver injury, who underwent liver transplantation. The NAT2 slow acetylator genotype appears to be a significant risk factor for moderate and severe drug- induced liver injury. However, the overall effect size is modest and generally in line with effects described previously for this genotype in milder drug-induced liver injury. Additional genetic risk factors may also contribute.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-11-2007
DOI: 10.1002/HEP.21984
Abstract: The detection of fibrosis within nonalcoholic fatty liver disease (NAFLD) is important for ascertaining prognosis and the stratification of patients for emerging therapeutic intervention. We validated the Original European Liver Fibrosis panel (OELF) and a simplified algorithm not containing age, the Enhanced Liver fibrosis panel (ELF), in an independent cohort of patients with NAFLD. Furthermore, we explored whether the addition of simple markers to the existing panel test could improve diagnostic performance. One hundred ninety-six consecutively recruited patients from 2 centers were included in the validation study. The diagnostic accuracy of the discriminant scores of the ELF panel, simple markers, and a combined panel were compared using receiver operator curves, predictive values, and a clinical utility model. The ELF panel had an area under the curve (AUC) of 0.90 for distinguishing severe fibrosis, 0.82 for moderate fibrosis, and 0.76 for no fibrosis. Simplification of the algorithm by removing age did not alter diagnostic performance. Addition of simple markers to the panel improved diagnostic performance with AUCs of 0.98, 0.93, and 0.84 for the detection of severe fibrosis, moderate fibrosis, and no fibrosis, respectively. The clinical utility model showed that 82% and 88% of liver biopsies could be potentially avoided for the diagnosis of severe fibrosis using ELF and the combined panel, respectively. The ELF panel has good diagnostic accuracy in an independent validation cohort of patients with NAFLD. The addition of established simple markers augments the diagnostic performance across different stages of fibrosis, which will potentially allow superior stratification of patients with NAFLD for emerging therapeutic strategies.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-02-2009
DOI: 10.1038/AJG.2008.97
Abstract: Endoscopic ultrasound-guided trucut biopsy (EUS-TCB) technique has the advantage of obtaining tissue for histological examination rather than for cytology alone. However, the diagnostic yield may depend on factors related to both technical aspects and the lesions s led. Safety of EUS-TCB is yet to be established in a large number of procedures. The aim of the study was to determine factors predicting a positive diagnostic yield, and safety for EUS-TCB in a large tertiary referral center-based service. All patients were referred for EUS-guided tissue s ling as a part of their diagnostic workup. Linear-array echoendoscope (GF-2000-OL5, KeyMed) with a 19-gauge trucut needle (Quick-Core, Wilson-Cook) was used by two operators to obtain tissue s les. Clinical data, details of the EUS-TCB, post-procedure complications, and histology were prospectively collected between May 2002 and February 2008. In total, 247 patients (143 men) aged 57-73 (median 66) had EUS-TCB performed. Lesions s led were in the pancreas (113), esophagogastric wall (34), and extra-pancreatic areas (100) (lymph nodes: 52). The maximum diameter of the lesion/wall thickness ranged from 0.6 to 5.4 cm (median 3). One to five passes were made (median 3) to obtain tissue cores 2-18 mm (median 10) in length. The procedure failed in 6% of cases. The overall diagnostic accuracy was 75%. The overall complication rate was 2% (bronchopneumonia, minor hemoptysis, minor hematemesis, mucosal tear, retropharyngeal abscess) with no procedure-related deaths. Site of lesion (pancreatic vs. extra-pancreatic, P<0.032), site of biopsy (stomach vs. duodenum vs. esophagus, P<0.001), and number of passes ( 2, P<0.013) were predictors of a positive diagnostic yield in univariate analysis. However, only the site of biopsy (P<0.001, 95% CI: 0.58-2.32) and number of passes (P=0.05) were independent predictors in multinominal logistic regression. Diagnostic yield of EUS-TCB is higher when lesion is approached through the stomach and better when more than two passes were made. In this large series, the complication rate of 2% associated with EUS-TCB was similar to that reported with EUS-fine needle aspiration technique.
Publisher: Springer Science and Business Media LLC
Date: 30-06-2014
DOI: 10.1038/NCOMMS5309
Abstract: Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure. Subtle inter-patient genetic variation and environmental factors combine to determine variation in disease progression. A common non-synonymous polymorphism in TM6SF2 (rs58542926 c.449 C T, p.Glu167Lys) was recently associated with increased hepatic triglyceride content, but whether this variant promotes clinically relevant hepatic fibrosis is unknown. Here we confirm that TM6SF2 minor allele carriage is associated with NAFLD and is causally related to a previously reported chromosome 19 GWAS signal that was ascribed to the gene NCAN . Furthermore, using two histologically characterized cohorts encompassing steatosis, steatohepatitis, fibrosis and cirrhosis (combined n =1,074), we demonstrate a new association, independent of potential confounding factors (age, BMI, type 2 diabetes mellitus and PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis. These findings establish new and important clinical relevance to TM6SF2 in NAFLD.
Publisher: American College of Physicians
Date: 07-02-2017
DOI: 10.7326/L16-0628
Publisher: Informa UK Limited
Date: 30-03-2017
Publisher: Baishideng Publishing Group Inc.
Date: 16-09-2020
Publisher: Elsevier BV
Date: 12-2019
Publisher: BMJ
Date: 23-03-2017
Publisher: Wiley
Date: 24-05-2016
DOI: 10.1111/LIV.13152
Abstract: Screening for oesophageal varices (OV) using conventional oesophagogastroduodenoscopy (C-OGD) is invasive and requires costly monitoring, recovery, and decontamination facilities. We aimed to evaluate the technical feasibility, acceptability and accuracy of a novel, portable and disposable office-based transnasal endoscope (EG Scan This was a prospective cohort study. Consecutive adult patients with cirrhosis were invited to participate. All subjects underwent the two procedures on the same day performed by two endoscopists in a blinded design. Patients completed preference and validated tolerability (10-point visual analogue scale (VAS)) questionnaires on day 0 and day 14 post procedures. Forty-five of 50 patients (90%) completed both interventions. Mean age was 59 years and OV prevalence was 49%. Patients reported higher preference (percentage) and better experience (mean VAS) with EG Scan compared to C-OGD on day 0 (76.5% vs. 23.5%, P < 0.001 7.8 vs. 6.8, P = 0.058, respectively) and day 14 (77.8% vs. 22.2%, P < 0.001 7.0 vs. 5.5, P = 0.0013 respectively). Sensitivity and specificity of the EG Scan for the diagnosis of any size OV were 0.82 (95% confidence interval (CI) 0.60-0.95), and 0.78 (95% CI 0.56-0.93) respectively. Corresponding values for the diagnosis of clinically significant (medium/large) OV were 0.92 (95% CI 0.62-1.0), 0.97 (95% CI 0.84-1.0) respectively. No serious adverse events occurred. EG Scan accuracy was higher for the diagnosis of medium/large OV compared to any size OV. Patients' preference and overall experience of the EG Scan was favourable compared to C-OGD 14 days after procedures.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Elsevier BV
Date: 11-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-04-2021
DOI: 10.1002/HEP.31535
Abstract: Only a minority of heavy drinkers progress to alcohol‐associated cirrhosis (ALC). The aim of this study was to identify common genetic variants that underlie risk for ALC. We analyzed data from 1,128 subjects of European ancestry with ALC and 614 heavy‐drinking subjects without known liver disease from Australia, the United States, the United Kingdom, and three countries in Europe. A genome‐wide association study (GWAS) was performed, adjusting for principal components and clinical covariates (alcohol use, age, sex, body mass index, and diabetes). We validated our GWAS findings using UK Biobank. We then performed a meta‐analysis combining data from our study, the UK Biobank, and a previously published GWAS. Our GWAS found genome‐wide significant risk association of rs738409 in patatin‐like phospholipase domain containing 3 ( PNPLA3 ) (odds ratio [OR] = 2.19 [G allele], P = 4.93 × 10 −17 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10 −10 ) with ALC. Conditional analysis accounting for the PNPLA3 and HSD17B13 loci identified a protective association at rs374702773 in Fas‐associated factor family member 2 ( FAF2 ) (OR = 0.61 [del(T) allele], P = 2.56 × 10 −8 ) for ALC. This association was replicated in the UK Biobank using conditional analysis (OR = 0.79, P = 0.001). Meta‐analysis (without conditioning) confirmed genome‐wide significance for the identified FAF2 locus as well as PNPLA3 and HSD17B13 . Two other previously known loci ( SERPINA1 and SUGP1/TM6SF2 ) were also genome‐wide significant in the meta‐analysis. GeneOntology pathway analysis identified lipid droplets as the target for several identified genes. In conclusion, our GWAS identified a locus at FAF2 associated with reduced risk of ALC among heavy drinkers. Like the PNPLA3 and HSD17B13 gene products, the FAF2 product has been localized to fat droplets in hepatocytes. Our genetic findings implicate lipid droplets in the biological pathway(s) underlying ALC.
Publisher: Elsevier BV
Date: 04-2017
Publisher: Wiley
Date: 26-04-2007
Publisher: BMJ
Date: 17-05-2021
DOI: 10.1136/GUTJNL-2021-324243
Abstract: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the in idual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. In idual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed in idually and in sequential combinations. Data were included from 37 primary studies (n=5735 45% women median age: 54 years median body mass index: 30 kg/m 2 33% had type 2 diabetes 30% had advanced fibrosis). AUROCs of in idual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs ( .3 ≥2.67) followed by LSM-VCTE cut-offs ( .0 ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63–68) and 86% (84–87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs ( .3 ≥3.48) followed by LSM cut-offs ( .0 ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37–39) and specificity of 90% (89–91) with 19% needing biopsy. Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.
Publisher: Elsevier BV
Date: 05-2021
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Guruprasad Aithal.