63 results on '"Sanjay Bansal"'
Search Results
2. P-6 SOFOSBUVIR CONTAINING REGIMENS ARE SAFE AND EFFECTIVE IN ADOLESCENTS WITH CHRONIC HEPATITIS C INFECTION
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Stefan Wirth, Regino Gonzalez-Peralta, Philip Rosenthal, Winita Hardikar, Jessica Wen, Maureen M. Jonas, Naveen Mittal, Mary Whitworth, Ronen Arnon, Chuan-Hao Lin, Yury Lobzin, Rene Romero, Vladimir Chulanov, Girish Subbarao, Jeffrey Teckman, Vyacheslav Morozov, Eric Bassetti, Kathryn Kersey, Benedetta Massetto, Yanni Zhu, Polina German, Diana M. Brainard, Sanjay Bansal, Karen F. Murray, Kathleen Schwarz, and William Balistreri
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Specialties of internal medicine ,RC581-951 - Abstract
Background: HCV-specific DAAs have transformed treatment of chronic HCV, but few studies have evaluated these therapies in children. Methods: Patients aged 12–17 years old with chronic GT1 HCV were enrolled into an open-label study to receive 12 weeks of LDV/SOF 90 mg/400 mg once daily, and those with HCV GT2 or GT3 to receive SOF (400 mg once daily) + RBV (15 mg/kg/day) for 12 (GT2) or 24 weeks (GT3), respectively. Primary efficacy endpoint was SVR12. Safety was assessed by adverse events and clinical/laboratory data. Pharmacokinetic (PK) sampling was conducted to confirm the appropriateness of the doses. Results: 150 adolescents (100 GT1, 13 GT2 and 37 GT3) were enrolled and treated. The majority were female (56%), white (90%), treatment naive (81%), and vertically infected (80%). The mean age was 15 years (range 12–17). LDV, SOF and GS-331007 (primary metabolite) exposures were within the range of adult exposures observed in the SOF and LDV/SOF phase 2/3 studies. The SVR12 rate was 98% in GT1, 100% in GT2 and 97% in GT3; all 3 patients who were considered not to have achieved SVR12 were lost to follow-up. No adverse event (AE) leading to study drug discontinuation or serious AEs have been reported. Conclusion: In adolescents, LDV/SOF for 12 weeks and SOF + RBV for 12 or 24 weeks, resulted in a SVR12 rate of 97–100% with no virologic failures. These regimens were well tolerated, demonstrating their potential as an important treatment option for children with HCV infection.
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- 2021
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3. Assessment of Diet and Physical Activity in Paediatric Non-Alcoholic Fatty Liver Disease Patients: A United Kingdom Case Control Study
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Philippa S. Gibson, Sarah Lang, Marianne Gilbert, Deepa Kamat, Sanjay Bansal, Martha E. Ford-Adams, Ashish P. Desai, Anil Dhawan, Emer Fitzpatrick, J. Bernadette Moore, and Kathryn H. Hart
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non-alcoholic fatty liver disease ,nutrition ,obesity ,physical activity ,eating behaviour ,adolescence ,children ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children, with prevalence rising alongside childhood obesity rates. This study aimed to characterise the habitual diet and activity behaviours of children with NAFLD compared to obese children without liver disease in the United Kingdom (UK). Twenty-four biopsy-proven paediatric NAFLD cases and eight obese controls without biochemical or radiological evidence of NAFLD completed a 24-h dietary recall, a Physical Activity Questionnaire (PAQ), a Dutch Eating Behavior Questionnaire (DEBQ) and a 7-day food and activity diary (FAD), in conjunction with wearing a pedometer. Groups were well matched for age and gender. Obese children had higher BMI z-scores (p = 0.006) and BMI centiles (p = 0.002) than participants with NAFLD. After adjusting for multiple hypotheses testing and controlling for differences in BMI, no differences in macro- or micronutrient intake were observed as assessed using either 24-h recall or 7-day FAD (p > 0.001). Under-reporting was prevalent (NAFLD 75%, Obese Control 87%: p = 0.15). Restrained eating behaviours were significantly higher in the NAFLD group (p = 0.005), who also recorded more steps per day than the obese controls (p = 0.01). In conclusion, this is the first study to assess dietary and activity patterns in a UK paediatric NAFLD population. Only a minority of cases and controls were meeting current dietary and physical activity recommendations. Our findings do not support development of specific dietary/ physical activity guidelines for children with NAFLD; promoting adherence with current general paediatric recommendations for health should remain the focus of clinical management.
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- 2015
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4. Estimation & comparison of salivary glucose with blood glucose in diabetic individuals
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Mimansha Patel, Abhishek Gouraha, Pankaj Gupta, Sanjay Bansal, Prasoon Goyal, and Salona Kalra
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General Nursing ,Education - Abstract
Aim: Saliva play a diagnostic tool for oral and systematic diseases has multiple advantages over other body fluids especially . The aim of this study was to explore the potential of salivary glucose as a marker in diagnosis and monitoring of diabetes mellitus using glucoseoxidase method, and as a non-invasive method replacing an invasive blood glucose estimation method. Materials and methods: Fasting blood and unstimulated whole saliva were collected from 50 controls, 50 newly diagnosed diabetics, and 50 diabetics under treatment. Blood and salivary glucose were analyzed in the samples by glucose-oxidase method. Results: The mean level of salivary glucose was reported to be 0.53 ± 0.4mg/dl in controls, 1.14 ± 1.55mg/dl in newly diagnosed diabetics, and 1.22 mg/dl ± 1.99 in diabetics under treatment. Conclusion: The mean level of salivary glucose in diabetics was significantly higher than that in non-diabetics. A positive, linear and significant, yet weak correlation between salivary and blood glucose suggests some potential for saliva as a marker in diagnosis and monitoring of diabetes mellitus.
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- 2022
5. Supplementary Methods, Figure Legend from Estrogen Receptor α Inhibits p53-Mediated Transcriptional Repression: Implications for the Regulation of Apoptosis
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Gokul M. Das, Fengzhi Li, Sanjay Bansal, Wensheng Liu, Santhi D. Konduri, and Aejaz Sayeed
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Supplementary Methods, Figure Legend from Estrogen Receptor α Inhibits p53-Mediated Transcriptional Repression: Implications for the Regulation of Apoptosis
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- 2023
6. Supplementary Figure 1 from Estrogen Receptor α Inhibits p53-Mediated Transcriptional Repression: Implications for the Regulation of Apoptosis
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Gokul M. Das, Fengzhi Li, Sanjay Bansal, Wensheng Liu, Santhi D. Konduri, and Aejaz Sayeed
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Supplementary Figure 1 from Estrogen Receptor α Inhibits p53-Mediated Transcriptional Repression: Implications for the Regulation of Apoptosis
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- 2023
7. Data from Estrogen Receptor α Inhibits p53-Mediated Transcriptional Repression: Implications for the Regulation of Apoptosis
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Gokul M. Das, Fengzhi Li, Sanjay Bansal, Wensheng Liu, Santhi D. Konduri, and Aejaz Sayeed
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Estrogen receptor α (ERα) and tumor suppressor protein p53 exert opposing effects on cellular proliferation. As a transcriptional regulator, p53 is capable of activating or repressing various target genes. We have previously reported that ERα binds directly to p53, leading to down-regulation of transcriptional activation by p53. In addition to transcriptional activation, transcriptional repression of a subset of target genes by p53 plays important roles in diverse biological processes, such as apoptosis. Here, we report that ERα inhibits p53-mediated transcriptional repression. Chromatin immunoprecipitation assays reveal that ERα interacts in vivo with p53 bound to promoters of Survivin and multidrug resistance gene 1, both targets for transcriptional repression by p53. ERα binding to p53 leads to inhibition of p53-mediated transcriptional regulation of these genes in human cancer cells. Transcriptional derepression of Survivin by ERα is dependent on the p53-binding site on the Survivin promoter, consistent with our observation that p53 is necessary for ERα to access the promoters. Importantly, mutagenic conversion of this site to an activation element enabled ERα to repress p53-mediated transcriptional activation. Further, RNA interference–mediated knockdown of ERα resulted in reduced Survivin expression and enhanced the propensity of MCF-7 cells to undergo apoptosis in response to staurosporine treatment, an effect that was blocked by exogenous expression of Survivin. These results unravel a novel mechanism by which ERα opposes p53-mediated apoptosis in breast cancer cells. The findings could have translational implications in developing new therapeutic and prevention strategies against breast cancer. [Cancer Res 2007;67(16):7746–55]
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- 2023
8. Outbreak of indeterminate acute liver failure in children with adenoviraemia – Not a new disease
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Barath Jagadisan, Anita Verma, Maesha Deheragoda, Akash Deep, Tassos Grammatikopoulos, Malur Sudhanva, Sanjay Bansal, Nedim Hadzic, Sunitha Vimalesvaran, Nigel Heaton, and Anil Dhawan
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Hepatology - Published
- 2023
9. A new proposal for secondary surveillance following potentially curative therapy of HCC: alternating MRI and CEUS
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Levi Frehlich, Stephanie R. Wilson, Jason K. Wong, Sanjay Bansal, Fangshi Lu, and Kelly W. Burak
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medicine.medical_specialty ,Radiological and Ultrasound Technology ,business.industry ,Urology ,Significant difference ,Gastroenterology ,Diagnostic accuracy ,medicine.disease ,Tumor recurrence ,Recurrent Tumor ,Hepatocellular carcinoma ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,business ,Area under the roc curve ,After treatment ,Arterial phase - Abstract
Purpose A high recurrence rate following ablative therapy of hepatocellular carcinoma (HCC) necessitates routine follow-up imaging (secondary surveillance) to facilitate early re-treatment. We evaluate our unique secondary surveillance algorithm (with use of alternating MRI and CEUS) by assessment of the relative diagnostic accuracy of MRI and CEUS in detection of residual/recurrent tumor. Potential benefits of alternating surveillance are compared to the use of MRI alone. Materials and methods This prospective observational IRB approved study included 231 patients with 354 treated tumors between January 2017 and June 2020. Treated lesions underwent secondary surveillance for a minimum of 7 months and up to 3 years, median follow-up 14 months. Secondary surveillance involved MRI performed at 1 month after treatment, followed by CEUS and MRI at alternate 3-month intervals (i.e., CEUS at month 4, MRI at month 7, etc.), for a total of 2 years. An equivocal finding on one imaging modality triggered expeditious evaluation with the alternate modality. Arterial phase hyperenhancement and washout comprise the classic features of recurrent tumor on both modalities. Results A total of 746 MRI and 712 CEUS examinations were performed, and a total of 184 tumor recurrences detected, MRI (n = 82) and CEUS (n = 102) (p = 0.19). There was no difference in the sensitivity (71.0–85.0% and 80.9–92.0%), specificity (97.4–99.2% and 98.5–99.9%), and area under the ROC curve (0.85–0.92 and 0.91–0.96) between MRI and CEUS, respectively. 23 of 82 recurrent tumors identified on MRI were equivocal and confirmed with expedited CEUS. 9 equivocal cases on MRI were disproved by expedited CEUS. On CEUS, 1 of the 102 recurrent tumors was equivocal and confirmed on MRI, and 2 equivocal CEUS cases were disproved by MRI. Conclusion MRI and CEUS performed similarly in our secondary surveillance algorithm for HCC in their ability to detect tumor recurrence, and showed no significant difference in their relative diagnostic test accuracy measures. Of greater interest, equivocal results on MRI (typically due to difficulty in distinguishing tumor recurrence from post-treatment change/shunting) were either confirmed or disproven by CEUS in all cases. Secondary surveillance of treated HCC with alternating MRI and CEUS shows equivalent performance of each modality. CEUS resolves equivocal MRI and optimally demonstrates APHE and washout in tumor recurrence. Graphic abstract
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- 2021
10. Study of Acute Liver Failure in Children Using Next Generation Sequencing Technology
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Melissa Sambrotta, Sandra Strautnieks, S. Lillis, Sanjay Bansal, Tassos Grammatikopoulos, Robert Hegarty, Sian Ellard, Richard J. Thompson, Anil Dhawan, Roshni Vara, P. S. Gibson, Julia Baptista, and Pierre Foskett
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Male ,Pediatrics ,medicine.medical_specialty ,Candidate gene ,Compound heterozygosity ,DNA sequencing ,Cohort Studies ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,030225 pediatrics ,Humans ,Medicine ,030212 general & internal medicine ,Child ,MPV17 ,Survival rate ,Exome sequencing ,business.industry ,Infant, Newborn ,High-Throughput Nucleotide Sequencing ,Infant ,Liver Failure, Acute ,medicine.disease ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Etiology ,Female ,business - Abstract
Objective To use next generation sequencing (NGS) technology to identify undiagnosed, monogenic diseases in a cohort of children who suffered from acute liver failure (ALF) without an identifiable etiology. Study design We identified 148 under 10 years of age admitted to King's College Hospital, London, with ALF of indeterminate etiology between 2000 and 2018. A custom NGS panel of 64 candidate genes known to cause ALF and/or metabolic liver disease was constructed. Targeted sequencing was carried out on 41 children in whom DNA samples were available. Trio exome sequencing was performed on 4 children admitted during 2019. A comparison of the clinical characteristics of those identified with biallelic variants against those without biallelic variants was then made. Results Homozygous and compound heterozygous variants were identified in 8 out of 41 children (20%) and 4 out of 4 children (100%) in whom targeted and exome sequencing were carried out, respectively. The genes involved were NBAS (3 children); DLD (2 children); and CPT1A, FAH, LARS1, MPV17, NPC1, POLG, SUCLG1, and TWINK (1 each). The 12 children who were identified with biallelic variants were younger at presentation and more likely to die in comparison with those who did not: median age at presentation of 3 months and 30 months and survival rate 75% and 97%, respectively. Conclusions NGS was successful in identifying several specific etiologies of ALF. Variants in NBAS and mitochondrial DNA maintenance genes were the most common findings. In the future, a rapid sequencing NGS workflow could help in reaching a timely diagnosis and facilitate clinical decision making in children with ALF.
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- 2021
11. Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry
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Maria Serena Longhi, Marianne Samyn, Guan-Wee Wong, Nedim Hadzic, Yoh Zen, Li Yang, Mark J. W. McPhail, Diego Vergani, Giorgina Mieli-Vergani, Muhammed Yuksel, Jonathon Graham, Derek G. Doherty, Sanjay Bansal, Michael A. Heneghan, Richard J. Thompson, Haibin Su, Pengyun Wang, Alberto Quaglia, Yun Ma, Yüksel, Muhammed, Ma, Yun, Su, Haibin, Longhi, Maria Serena, McPhail, Mark J., Wang, Pengyun, Bansal, Sanjay, Wong, Guan-Wee, Graham, Jonathon, Yang, Li, Thompson, Richard J., Doherty, Derek G., Hadzic, Nedim, Zen, Yoh, Quaglia, Alberto, Heneghan, Michael A., Samyn, Marianne, Vergani, Diego, Mieli-Vergani, Giorgina, and Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)
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Male ,musculoskeletal diseases ,0301 basic medicine ,Adolescent ,Gastroenterology and hepatology ,Class II region ,HLA-DRB1 alleles ,Overlap syndrome ,Hepatitis ,HLA ,Susceptibility ,Protection ,Diagnosis ,Immunogenetics ,Cholangitis, Sclerosing ,Human leukocyte antigen ,Autoimmune hepatitis ,medicine.disease_cause ,Severity of Illness Index ,White People ,Article ,HLA-B8 Antigen ,Autoimmunity ,03 medical and health sciences ,HLA-DR3 Antigen ,0302 clinical medicine ,HLA Antigens ,immune system diseases ,Genetic predisposition ,Humans ,Medicine ,Genetic Predisposition to Disease ,Allele ,Risk factor ,Child ,HLA-A1 Antigen ,Hepatology ,business.industry ,Infant ,medicine.disease ,Hepatitis, Autoimmune ,030104 developmental biology ,Child, Preschool ,Immunology ,Female ,030211 gastroenterology & hepatology ,business ,HLA-DRB1 Chains - Abstract
Background and aims: genetic predisposition to autoimmune hepatitis (AIH) in adults is associated with possession of human leukocyte antigen (HLA) class I (A*01, B*08) and class II (DRB1*03, -04, -07, or -13) alleles, depending on geographic region. Juvenile autoimmune liver disease (AILD) comprises AIH-1, AIH-2, and autoimmune sclerosing cholangitis (ASC), which are phenotypically different from their adult counterparts. We aimed to define the relationship between HLA profile and disease course, severity, and outcome in juvenile AILD. Approach and results: we studied 236 children of European ancestry (152 female [64%], median age 11.15 years, range 0.8-17), including 100 with AIH-1, 59 with AIH-2, and 77 with ASC. The follow-up period was from 1977 to June 2019 (median 14.5 years). Class I and II HLA genotyping was performed using PCR/sequence-specific primers. HLA B*08, -DRB1*03, and the A1-B8-DR3 haplotype impart predisposition to all three forms of AILD. Homozygosity for DRB1*03 represented the strongest risk factor (8.8). HLA DRB1*04, which independently confers susceptibility to AIH in adults, was infrequent in AIH-1 and ASC, suggesting protection; and DRB1*15 (DR15) was protective against all forms of AILD. Distinct HLA class II alleles predispose to the different subgroups of juvenile AILD: DRB1*03 to AIH-1, DRB1*13 to ASC, and DRB1*07 to AIH-2. Possession of homozygous DRB1*03 or of DRB1*13 is associated with fibrosis at disease onset, and possession of these two genes in addition to DRB1*07 is associated with a more severe disease in all three subgroups. Conclusions: unique HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be useful in predicting responsiveness to immunosuppressive treatment and course., Fifth Medical Center of PLA General Hospital; Roger Dobson Funds; King's College Hospital Charity; Medical Research Council Clinician Scientist Fellowship; Medical Research Council PhD Studentship; Alex Mowat PhD Studentship; King's College Hospital Charity; National Institute for Health Research University College London Hospital/University College London Biomedical Research Centre
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- 2021
12. Thermo-hydrodynamic simulation study of twin-groove elliptical (two-lobe) journal bearing of steam turbine with experimental investigations
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Navin Kumar, Gannath D Thakre, Akash Shukla, Saurabh Yadav, Sanjay Bansal, Satish C. Sharma, Chandra B. Khatri, and S. P. Harsha
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Materials science ,Bearing (mechanical) ,Mechanical Engineering ,02 engineering and technology ,Surfaces and Interfaces ,021001 nanoscience & nanotechnology ,Lobe ,Surfaces, Coatings and Films ,law.invention ,020303 mechanical engineering & transports ,medicine.anatomical_structure ,0203 mechanical engineering ,law ,Steam turbine ,medicine ,White metal ,Composite material ,0210 nano-technology ,Groove (engineering) - Abstract
The present paper reports an experimental and theoretical investigation on performance behaviour of twin-groove elliptical (two-lobe) white metal hydrodynamic journal bearing used in steam turbines. The experiments are performed on a fully automatic journal bearing test rig with provisions to various operating conditions (i.e. load, speed, and lubricant temperature). The performance behaviour in terms of coefficient of friction, lubricant inlet temperature, load carrying capacity, journal displacement, weight loss etc. has been presented. In addition to this, numerical investigations have also been performed with the numerical solution of governing Reynolds equation using FEM (finite element method) technique and Jakobsson-Floberg-Olsson (JFO) boundary condition. The experimentally obtained and theoretical results have been correlated.
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- 2020
13. O9 Treating children with HCV close to home through a virtual national multidisciplinary network
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Deirdre Kelly, Carla Lloyd, Maxine Brown, Kinza Ahmed, Ivana Carey, Sarah Ann Tizzard, Joanne Crook, Penny North-Lewis, Palaniswamy Karthikeyan, Sanjay Bansal, Will Irving, and Graham Foster
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- 2022
14. Management of Hepatitis B Virus Infection and Prevention of Hepatitis B Virus Reactivation in Children With Acquired Immunodeficiencies or Undergoing Immune Suppressive, Cytotoxic, or Biological Modifier Therapies
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Henkjan J. Verkade, Dominique Debray, Giuseppe Indolfi, Yael Mozer-Glassberg, Joerg Jahnel, Mona Abdel-Hady, Aglaia Zellos, Etienne Sokal, Piotr Czubkowski, Björn Fischler, Françoise Smets, Sanjay Bansal, Wendy L. van der Woerd, Girish Gupte, M. Samyn, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, Lifestyle Medicine (LM), and Center for Liver, Digestive and Metabolic Diseases (CLDM)
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Hepatitis B virus ,medicine.medical_specialty ,MEDLINE ,secretory IgAs ,Antineoplastic Agents ,medicine.disease_cause ,GUIDELINES ,Inflammatory bowel disease ,Pediatrics ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,030225 pediatrics ,Internal medicine ,protein profile ,HIGH-PRESSURE ,medicine ,donor human milk ,Humans ,QUALITY ,Child ,Pediatric gastroenterology ,Immunosuppression Therapy ,business.industry ,Gastroenterology ,Hepatology ,Hepatitis B ,medicine.disease ,Perinatology ,DONOR HUMAN-MILK ,human milk pasteurization ,lactoferrin ,Biological Therapy ,and Child Health ,BANK ,SAFETY ,Pediatrics, Perinatology and Child Health ,Position paper ,OPERATION ,030211 gastroenterology & hepatology ,business ,Viral hepatitis - Abstract
Reactivation of hepatitis B virus (HBV) is a known complication of immune-suppressive, cytotoxic, and biological modifier therapies in patients currently infected with HBV or who have had past exposure to HBV. Nowadays, newer and emerging forms of targeted biologic therapies are available for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions and solid-organ, bone marrow, or haematologic stem cell transplant but there is currently a lack of a systematic approach to the care of patients with or at risk of HBV reactivation. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) together with a working group of ESPGHAN members with clinical and research expertise in viral hepatitis developed an evidence-based position paper on reactivation of HBV infection in children identifying pertinent issues addressing the diagnosis, prevention, and treatment of this condition. Relevant clinical questions were formulated and agreed upon by all the members of the working group. Questions were answered and positions were based on evidence resulting from a systematic literature search on PubMed and Embase from their inception to July 1, 2019. A document was produced and the working group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique. A recommendation was accepted provided upon agreement by at least 75% of the working group members. This position paper provides a comprehensive update on the diagnosis, prevention and treatment of HBV reactivation in children.
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- 2020
15. Abstract P3-10-03: Exploiting p53-dependent functional duality of estrogen receptor-beta to repurpose tamoxifen for triple negative breast cancer therapy
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Christina Adams, Creighton J Creighton, Chetan C. Oturkar, Benny Abraham Kaipparettu, Jun Hyoung Park, Nadi Wickramasekera, Sanjay Bansal, Wendy M. Swetzig, Laxmi Silwal-Pandit, Alka Mukhopadhyay, Santhi D. Konduri, Utpal K. Mukhopadhyay, Anne Lise Børresen-Dale, Alexander Caradori, Austin Miller, Gokul M. Das, and Rajesh Medisetty
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Cancer Research ,Proximity ligation assay ,Cell cycle ,Biology ,medicine.disease ,Breast cancer ,Oncology ,Cancer cell ,medicine ,Cancer research ,Doxorubicin ,Tamoxifen ,Triple-negative breast cancer ,Estrogen receptor beta ,medicine.drug - Abstract
Whether estrogen receptor beta (ERβ/ESR2) is a pro- or anti-oncogenic protein in breast cancer has been controversial. ERβ levels are generally high in triple-negative breast cancer (TNBC). Reports including the Cancer Genome Atlas (TCGA) show that about 80% of TNBC express mutant p53 and it is a major driver of these cancers. We tested the hypothesis that WT versus mutant status of p53 will have an important role in determining the duality of ERβ functions. We showed that ERβ directly binds to TP53 in human breast cancer cells. Using glutathione-S-transferase (GST)-pull down and co-imunoprecipitation assays, we have delineated the DNA binding domain (DBD) along with the hinge domain of ERβ and the C-terminal regulatory domain of p53 to be essential for the interaction. The highly sensitive in situ proximity ligation assay (PLA) showed that ERβ is capable of interacting with both wild type (WT) and mutant p53 in breast cancer cells and tumor tissues. ERβ and p53 antibodies validated for specificity were used for all experiments. Combination of proliferation, cell cycle, and apoptosis assays, RNAi technology, quantitative ChIP (qChIP), and real-time PCR (qRT-PCR) showed that ERβ is pro-proliferative in the context of WTp53, whereas it is anti-proliferative in the context of mutant p53 in multiple breast cancer cell lines. The p53-dependent diametrically opposite functions of ERβ were recapitulated in isogenic MDA-MB-231 TNBC cells (generated by CRISPR) that differ only in the presence of WT versus mutant p53. A major gain-of-function of mutant p53 is its ability to bind and inactivate tumor suppressor p73. We show that ERβ binds and sequesters mutant p53 from mutant p53−p73 complex leading to reactivation of p73. Consistent with these observations, immunohistochemistry (IHC) in TNBC patient tumor tissue microarray (TMA) showed that patients with tumors expressing mutant p53 along with high levels of ERβ were of smaller size and lower stage. Complementing these findings, our analysis of the subgroup of the basal-like/TNBC tumors expressing mutant p53 (but not WTp53) in the METABRIC dataset showed that patients with tumors expressing higher levels of ERβ RNA (ESR2) had significantly better breast cancer-specific survival. The finding that ERβ–mutant p53 combination prognosticates survival in TNBC is important as to date there are no effective prognostic markers for TNBC and suggest the potential for using ERβ−mutant p53 combination in stratification of TNBC into therapeutically actionable subgroups.Furthermore, our findings provide a mechanistic explanation for the functional duality of ERβ and the controversy over its pro-versus anti-tumorigenic role.Surprisingly, Tamoxifen (Tam) increased ERβ-mut-p53 interaction in TNBC cells leading to increased transcription of anti-proliferation genes and knockdown experiments showed that the effect on transcription was dependent on both p73 and ERβ. Importantly, when combined with doxorubicin (Adriamycin) Tam decreased several fold the IC50 of doxorubicin resulting in increased apoptosis. The combination was more effective in inhibiting TNBC xenograft tumor growth in vivo compared to either treatment alone. Significant clinical implications of these findings include the potential for treating patients with doxorubicin at much lower dose than what is currently used in the management of TNBC, thereby reducing its major cumulative dose side effects. Importantly, although at present Tam is not indicated for TNBC, our data suggest the possibility for repurposing Tam therapy alone or in combination with chemotherapy to treat TNBC stratified based on ERβ and p53 status. If validated in a clinical trial, our findings could lead to a therapy that is fundamentally better in terms of effectiveness, cost and time needed to reach the TNBC patients. Citation Format: Gokul M Das, Utpal K Mukhopadhyay, Chetan C Oturkar, Christina Adams, Nadi Wickramasekera, Sanjay Bansal, Rajesh Medisetty, Austin Miller, Wendy M Swetzig, Laxmi Silwal-Pandit, Anne-Lise Borresen-Dale, Creighton J Creighton, Jun Hyoung Park, Santhi D Konduri, Alka Mukhopadhyay, Alexander Caradori, Benny Abraham Kaipparettu. Exploiting p53-dependent functional duality of estrogen receptor-beta to repurpose tamoxifen for triple negative breast cancer therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-10-03.
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- 2020
16. Foreword by Sanjay Bansal
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Sanjay Bansal
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- 2022
17. Sofosbuvir-velpatasvir-voxilaprevir in adolescents 12 to 17 years old with HCV infection
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Guiseppe Indolfi, Deirdre Kelly, Gabriella Nebbia, Raffaele Iorio, Anna Mania, Vania Giacomet, Leszek Szenborn, Jiang Shao, Mun Sang Yue, Chia‐Hsiang Hsueh, Bandita Parhy, Kathryn Kersey, Alessandra Mangia, Malgorzata Pawlowska, Sanjay Bansal, Indolfi, Guiseppe, Kelly, Deirdre, Nebbia, Gabriella, Iorio, Raffaele, Mania, Anna, Giacomet, Vania, Szenborn, Leszek, Shao, Jiang, Sang Yue, Mun, Hsueh, Chia-Hsiang, Parhy, Bandita, Kersey, Kathryn, Mangia, Alessandra, Pawlowska, Malgorzata, and Bansal, Sanjay
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Adult ,Cyclopropanes ,Liver Cirrhosis ,Sulfonamides ,Aminoisobutyric Acids ,Hepatology ,Adolescent ,Genotype ,Proline ,Sustained Virologic Response ,Lactams, Macrocyclic ,Hepacivirus ,Hepatitis C, Chronic ,Antiviral Agents ,Hepatitis C ,Heterocyclic Compounds, 4 or More Rings ,Treatment Outcome ,Leucine ,Quinoxalines ,Humans ,Carbamates ,Sofosbuvir ,Child - Abstract
Sofosbuvir-velpatasvir-voxilaprevir is a pangenotypic regimen for chronic HCV infection. In the USA and Europe, sofosbuvir-velpatasvir-voxilaprevir once daily for 12 weeks is indicated for adults who previously received an HCV NS5A inhibitor. In Europe, sofosbuvir-velpatasvir-voxilaprevir is also indicated in the absence of prior HCV direct-acting antiviral (DAA) therapy as an 8-week or 12-week regimen. In an open-label study, we evaluated the safety, efficacy, and pharmacokinetics of sofosbuvir-velpatasvir-voxilaprevir in adolescents 12 to 17 years with chronic HCV of any genotype.In this Phase 2, multicenter study, sofosbuvir-velpatasvir-voxilaprevir 400/100/100 mg daily was administered to adolescents for 8 weeks if DAA-naïve or for 12 weeks for cirrhosis or prior DAA failure. The key efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Intensive pharmacokinetic sampling was done in 14 patients at week 2 or 4, and samples for population pharmacokinetics were collected in all patients.All patients (n = 21) were naïve to HCV DAAs, and none had cirrhosis. HCV genotype 3a infection was most common, occurring in 43% of patients. Overall, 100% of patients (21 of 21) reached SVR12. The most common adverse events were abdominal pain and headache (24% each) and nausea (19%); no adverse events led to discontinuation. The only serious adverse event, hypotension, was considered related to study drug and resolved the same day without interruption of treatment. Sofosbuvir-velpatasvir-voxilaprevir exposures were similar to those observed in adults.The pangenotypic regimen of sofosbuvir-velpatasvir-voxilaprevir is highly efficacious and well-tolerated in treating chronic HCV infection in adolescents.
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- 2021
18. P-6 SOFOSBUVIR CONTAINING REGIMENS ARE SAFE AND EFFECTIVE IN ADOLESCENTS WITH CHRONIC HEPATITIS C INFECTION
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Yanni Zhu, Karen F. Murray, Regino P. Gonzalez-Peralta, Vladimir Chulanov, Kathryn Kersey, Chuan-Hao Lin, Philip J. Rosenthal, Naveen Mittal, William F. Balistreri, Kathleen B. Schwarz, Winita Hardikar, Diana M. Brainard, Polina German, Jeffrey Teckman, Benedetta Massetto, Stefan Wirth, Vyacheslav Morozov, Yury Lobzin, Jessica Wen, Mary Whitworth, Maureen M. Jonas, Girish Subbarao, Ronen Arnon, Eric Bassetti, Sanjay Bansal, and Rene Romero
- Subjects
medicine.medical_specialty ,Study drug ,Hepatology ,Sofosbuvir ,business.industry ,Treatment options ,Specialties of internal medicine ,General Medicine ,Discontinuation ,Therapy naive ,Pharmacokinetics ,Chronic hepatitis ,RC581-951 ,Internal medicine ,medicine ,Adverse effect ,business ,medicine.drug - Abstract
Background HCV-specific DAAs have transformed treatment of chronic HCV, but few studies have evaluated these therapies in children. Methods Patients aged 12–17 years old with chronic GT1 HCV were enrolled into an open-label study to receive 12 weeks of LDV/SOF 90 mg/400 mg once daily, and those with HCV GT2 or GT3 to receive SOF (400 mg once daily) + RBV (15 mg/kg/day) for 12 (GT2) or 24 weeks (GT3), respectively. Primary efficacy endpoint was SVR12. Safety was assessed by adverse events and clinical/laboratory data. Pharmacokinetic (PK) sampling was conducted to confirm the appropriateness of the doses. Results 150 adolescents (100 GT1, 13 GT2 and 37 GT3) were enrolled and treated. The majority were female (56%), white (90%), treatment naive (81%), and vertically infected (80%). The mean age was 15 years (range 12–17). LDV, SOF and GS-331007 (primary metabolite) exposures were within the range of adult exposures observed in the SOF and LDV/SOF phase 2/3 studies. The SVR12 rate was 98% in GT1, 100% in GT2 and 97% in GT3; all 3 patients who were considered not to have achieved SVR12 were lost to follow-up. No adverse event (AE) leading to study drug discontinuation or serious AEs have been reported. Conclusion In adolescents, LDV/SOF for 12 weeks and SOF + RBV for 12 or 24 weeks, resulted in a SVR12 rate of 97–100% with no virologic failures. These regimens were well tolerated, demonstrating their potential as an important treatment option for children with HCV infection.
- Published
- 2021
19. A new proposal for secondary surveillance following potentially curative therapy of HCC: alternating MRI and CEUS
- Author
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Sanjay, Bansal, Fangshi, Lu, Levi, Frehlich, Jason K, Wong, Kelly W, Burak, and Stephanie R, Wilson
- Subjects
Carcinoma, Hepatocellular ,Liver Neoplasms ,Contrast Media ,Humans ,Magnetic Resonance Imaging ,Ultrasonography - Abstract
A high recurrence rate following ablative therapy of hepatocellular carcinoma (HCC) necessitates routine follow-up imaging (secondary surveillance) to facilitate early re-treatment. We evaluate our unique secondary surveillance algorithm (with use of alternating MRI and CEUS) by assessment of the relative diagnostic accuracy of MRI and CEUS in detection of residual/recurrent tumor. Potential benefits of alternating surveillance are compared to the use of MRI alone.This prospective observational IRB approved study included 231 patients with 354 treated tumors between January 2017 and June 2020. Treated lesions underwent secondary surveillance for a minimum of 7 months and up to 3 years, median follow-up 14 months. Secondary surveillance involved MRI performed at 1 month after treatment, followed by CEUS and MRI at alternate 3-month intervals (i.e., CEUS at month 4, MRI at month 7, etc.), for a total of 2 years. An equivocal finding on one imaging modality triggered expeditious evaluation with the alternate modality. Arterial phase hyperenhancement and washout comprise the classic features of recurrent tumor on both modalities.A total of 746 MRI and 712 CEUS examinations were performed, and a total of 184 tumor recurrences detected, MRI (n = 82) and CEUS (n = 102) (p = 0.19). There was no difference in the sensitivity (71.0-85.0% and 80.9-92.0%), specificity (97.4-99.2% and 98.5-99.9%), and area under the ROC curve (0.85-0.92 and 0.91-0.96) between MRI and CEUS, respectively. 23 of 82 recurrent tumors identified on MRI were equivocal and confirmed with expedited CEUS. 9 equivocal cases on MRI were disproved by expedited CEUS. On CEUS, 1 of the 102 recurrent tumors was equivocal and confirmed on MRI, and 2 equivocal CEUS cases were disproved by MRI.MRI and CEUS performed similarly in our secondary surveillance algorithm for HCC in their ability to detect tumor recurrence, and showed no significant difference in their relative diagnostic test accuracy measures. Of greater interest, equivocal results on MRI (typically due to difficulty in distinguishing tumor recurrence from post-treatment change/shunting) were either confirmed or disproven by CEUS in all cases. Secondary surveillance of treated HCC with alternating MRI and CEUS shows equivalent performance of each modality. CEUS resolves equivocal MRI and optimally demonstrates APHE and washout in tumor recurrence.
- Published
- 2021
20. Contrast-enhanced US in Local Ablative Therapy and Secondary Surveillance for Hepatocellular Carcinoma
- Author
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Jonathan Gui, Jason Wong, Christina Merrill, Stephanie R. Wilson, Sanjay Bansal, and Kelly W. Burak
- Subjects
Ablation Techniques ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Neoplasm, Residual ,Contrast Media ,Disease ,030218 nuclear medicine & medical imaging ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Ablative case ,medicine ,Carcinoma ,Humans ,Radiology, Nuclear Medicine and imaging ,Local Ablative Therapy ,In patient ,Vein ,Ultrasonography ,business.industry ,Liver Neoplasms ,medicine.disease ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Radiology ,Neoplasm Recurrence, Local ,business ,After treatment - Abstract
Hepatocellular carcinoma (HCC) has a high incidence of recurrence following therapy. Therefore, secondary surveillance (scheduled follow-up imaging after treatment) is an important part of disease management. The recent approval in the United States for use of a microbubble-based contrast agent for US liver imaging promotes the increased use of contrast-enhanced US (CEUS) in patients with HCC. Although the criteria for the diagnosis of HCC at CEUS are well described, there is a paucity of published literature describing the role of CEUS in ablative therapy and secondary surveillance. In the setting of ablative therapy, CEUS can have vital roles, including patient selection, intraprocedural guidance, and immediate postprocedural assessment. Although CEUS is not widely used, the authors found that it can be used to accurately detect residual or recurrent tumor, characterize the geographic pattern of recurrence (intrazonal, extrazonal, segmental, or remote), and assess for tumor in vein. In addition, similar to primary surveillance, secondary surveillance includes assessment of the entire liver for evaluation of new nodules. Arterial phase hyperenhancement is the reference standard characteristic of disease recurrence at secondary surveillance with CEUS. ©RSNA, 2019 See discussion on this article by Rodgers.
- Published
- 2019
21. Ledipasvir‐Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C
- Author
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Kathleen B. Schwarz, Bandita Parhy, William F. Balistreri, Benedetta Massetto, Suzanne Whitworth, Karen F. Murray, Chia Hsiang Hsueh, Philip J. Rosenthal, Jiang Shao, Diana M. Brainard, Rosie Hague, Girish S. Rao, Naveen Mittal, Michael R. Narkewicz, Winita Hardikar, Jonathan Honegger, and Sanjay Bansal
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Time Factors ,Cirrhosis ,Sustained Virologic Response ,Sofosbuvir ,Viral Hepatitis ,Antiviral Agents ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Child ,Adverse effect ,Fluorenes ,Hepatology ,business.industry ,Original Articles ,Hepatitis C ,Hepatitis C, Chronic ,medicine.disease ,Treatment Outcome ,030104 developmental biology ,Child, Preschool ,Hepatocellular carcinoma ,Vomiting ,Original Article ,Benzimidazoles ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,Uridine Monophosphate ,business ,medicine.drug - Abstract
For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct‐acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir‐sofosbuvir in HCV‐infected children aged 3 to
- Published
- 2019
22. Sofosbuvir and Ribavirin Therapy for Children Aged 3 to <12 Years With Hepatitis C Virus Genotype 2 or 3 Infection
- Author
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William F. Balistreri, Kathleen B. Schwarz, Etienne Sokal, Chia Hsiang Hsueh, Suzanne Davison, Diana M. Brainard, Cornelia Feiterna-Sperling, Sanjay Bansal, Jiang Shao, Karen F. Murray, Giuseppe Indolfi, Lynette A. Gillis, Maureen M. Jonas, Scott Nightingale, Bandita Parhy, DA Kelly, Benedetta Massetto, Regino P. Gonzalez-Peralta, Stefan Wirth, Chuan Hao Lin, and Philip J. Rosenthal
- Subjects
Male ,0301 basic medicine ,Sustained Virologic Response ,Sofosbuvir ,Viral Hepatitis ,Hepacivirus ,Medical Biochemistry and Metabolomics ,medicine.disease_cause ,Hepatitis ,chemistry.chemical_compound ,0302 clinical medicine ,7.1 Individual care needs ,Pegylated interferon ,Chronic ,Child ,Pediatric ,Liver Disease ,Hepatitis C ,Drug Combinations ,Treatment Outcome ,Infectious Diseases ,Child, Preschool ,6.1 Pharmaceuticals ,Vomiting ,Original Article ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,Infection ,medicine.drug ,medicine.medical_specialty ,Genotype ,Hepatitis C virus ,Chronic Liver Disease and Cirrhosis ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Immunology ,Antiviral Agents ,03 medical and health sciences ,Hepatitis - C ,Clinical Research ,Internal medicine ,Ribavirin ,medicine ,Humans ,Dosing ,Preschool ,Adverse effect ,Gastroenterology & Hepatology ,Hepatology ,business.industry ,Evaluation of treatments and therapeutic interventions ,Original Articles ,Hepatitis C, Chronic ,medicine.disease ,Emerging Infectious Diseases ,Good Health and Well Being ,030104 developmental biology ,chemistry ,Management of diseases and conditions ,Digestive Diseases ,business - Abstract
Currently, the only approved hepatitis C virus (HCV) treatment for children aged
- Published
- 2019
23. TP53 Status as a Determinant of Pro- vs Anti-Tumorigenic Effects of Estrogen Receptor-Beta in Breast Cancer
- Author
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Alka Mukhopadhyay, Wiam Bshara, Alexander Caradori, Sanjay Bansal, Jun Hyoung Park, Benny Abraham Kaipparettu, Christina Adams, Anne Lise Børresen-Dale, Austin Miller, Wendy M. Swetzig, Chad J. Creighton, Laxmi Silwal-Pandit, Gokul M. Das, Rajesh Medisetty, Santhi D. Konduri, Utpal K. Mukhopadhyay, Nadi Wickramasekera, Angela Omilian, and Chetan C. Oturkar
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Carcinogenesis ,Receptor, ErbB-2 ,medicine.drug_class ,Breast Neoplasms ,Triple Negative Breast Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Estrogen Receptor beta ,Humans ,Medicine ,Survival rate ,Estrogen receptor beta ,Triple-negative breast cancer ,030304 developmental biology ,0303 health sciences ,business.industry ,Hazard ratio ,Cancer ,Estrogens ,Articles ,medicine.disease ,3. Good health ,Estrogen ,030220 oncology & carcinogenesis ,Tumor Suppressor Protein p53 ,business ,Tamoxifen ,medicine.drug - Abstract
BackgroundAnti-tumorigenic vs pro-tumorigenic roles of estrogen receptor-beta (ESR2) in breast cancer remain unsettled. We investigated the potential of TP53 status to be a determinant of the bi-faceted role of ESR2 and associated therapeutic implications for triple negative breast cancer (TNBC).MethodsESR2-TP53 interaction was analyzed with multiple assays including the in situ proximity ligation assay. Transcriptional effects on TP53-target genes and cell proliferation in response to knocking down or overexpressing ESR2 were determined. Patient survival according to ESR2 expression levels and TP53 mutation status was analyzed in the basal-like TNBC subgroup in the Molecular Taxonomy of Breast Cancer International Consortium (n = 308) and Roswell Park Comprehensive Cancer Center (n = 46) patient cohorts by univariate Cox regression and log-rank test. All statistical tests are two-sided.ResultsESR2 interaction with wild-type and mutant TP53 caused pro-proliferative and anti-proliferative effects, respectively. Depleting ESR2 in cells expressing wild-type TP53 resulted in increased expression of TP53-target genes CDKN1A (control group mean [SD] = 1 [0.13] vs ESR2 depletion group mean [SD] = 2.08 [0.24], P = .003) and BBC3 (control group mean [SD] = 1 [0.06] vs ESR2 depleted group mean [SD] = 1.92 [0.25], P = .003); however, expression of CDKN1A (control group mean [SD] = 1 [0.21] vs ESR2 depleted group mean [SD] = 0.56 [0.12], P = .02) and BBC3 (control group mean [SD] = 1 [0.03] vs ESR2 depleted group mean [SD] = 0.55 [0.09], P = .008) was decreased in cells expressing mutant TP53. Overexpressing ESR2 had opposite effects. Tamoxifen increased ESR2-mutant TP53 interaction, leading to reactivation of TP73 and apoptosis. High levels of ESR2 expression in mutant TP53-expressing basal-like tumors is associated with better prognosis (Molecular Taxonomy of Breast Cancer International Consortium cohort: log-rank P = .001; hazard ratio = 0.26, 95% confidence interval = 0.08 to 0.84, univariate Cox P = .02).ConclusionsTP53 status is a determinant of the functional duality of ESR2. Our study suggests that ESR2-mutant TP53 combination prognosticates survival in TNBC revealing a novel strategy to stratify TNBC for therapeutic intervention potentially by repurposing tamoxifen.
- Published
- 2019
24. Treating children with HCV close to home through a virtual national multidisciplinary network
- Author
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Deirdre Kelly, Carla Lloyd, Maxine Brown, Kinza Ahmed, Ivana Carey, Sarah Tizzard, Joanne Crook, Penny North-Lewis, Palaniswamy Karthikeyan, Sanjay Bansal, and Graham Foster
- Subjects
Hepatology - Published
- 2022
25. Peginterferon Alfa-2a (40KD) Plus Lamivudine or Entecavir in Children With Immune-Tolerant Chronic Hepatitis B
- Author
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Giorgina, Mieli-Vergani, Sanjay, Bansal, James F, Daniel, Aydan, Kansu, Deirdre, Kelly, Carmen, Martin, Sarah, Tizzard, Stefan, Wirth, Julian, Zhou, and Diego, Vergani
- Subjects
Adult ,Guanine ,Adolescent ,Interferon-alpha ,Pilot Projects ,Antiviral Agents ,Recombinant Proteins ,Polyethylene Glycols ,Hepatitis B, Chronic ,Treatment Outcome ,Lamivudine ,DNA, Viral ,Humans ,Drug Therapy, Combination ,Hepatitis B e Antigens ,Child - Abstract
Treatment guidelines for chronic hepatitis B (CHB) do not recommend antiviral therapy for patients in the immune-tolerant phase of the disease, which generally occurs in children who acquire hepatitis B virus (HBV) vertically and may last for decades. On the basis of promising results of a pilot study, we conducted a randomized, controlled, multicenter study to evaluate the efficacy and safety of antiviral therapy in children and adolescents with immune-tolerant CHB.Fifty-nine children aged 3 to18 years hepatitis B e antigen-positive with an HBV DNA titer20,000 IU/mL and persistently normal alanine aminotransferase levels were randomized to 56 weeks of antiviral therapy with an oral nucleoside analogue [entecavir or lamivudine], combined with subcutaneous peginterferon alfa-2a from week 8, or 80 weeks of untreated observation. The primary efficacy outcome was hepatitis B surface antigen loss 24 weeks post-treatment in the antiviral therapy group or at the end of observation in the control group.Enrollment was terminated after the results of two similar studies showed that similar antiviral regimens were ineffective in children and adults with immune-tolerant CHB. At 24 weeks post-treatment, 1 of 26 patients in the antiviral treatment group experienced HBsAg loss (vs none of 33 patients in the control group). No serious treatment-related adverse events were reported, and no patients discontinued treatment because of adverse events.The antiviral regimen evaluated in this trial had an acceptable tolerability profile, but was ineffective in children and adolescents with immune-tolerant CHB.
- Published
- 2021
26. IDDF2020-ABS-0059 Safety and efficacy of sofosbuvir/velpatasvir (SOF/VEL) in pediatric patients 6 to < 18 years old with chronic hepatitis C (CHC) infection
- Author
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Anuj Gaggar, Kathryn Kersey, Kathleen B. Schwarz, Philip J. Rosenthal, Sean Hsueh, Jessica Wen, Karen F. Murray, Gabriella Verucchi, William F. Balistreri, Daniel Leung, Carol Yee Kwan Chan, Michael R. Narkewicz, Maureen M. Jonas, Etienne Sokal, Sanjay Bansal, Jiang Shao, Regino P. Gonzalez-Peralta, Chuan-Hao Lin, and Rene Romero
- Subjects
0301 basic medicine ,medicine.medical_specialty ,business.industry ,Nausea ,Sofosbuvir/velpatasvir ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Chronic hepatitis ,Internal medicine ,medicine ,Vomiting ,030211 gastroenterology & hepatology ,In patient ,medicine.symptom ,business - Abstract
Background DAA regimens have been approved for CHC treatment in 12 to Methods Patients 6 to Results 102 patients 12 to 15%) were headache, fatigue, and nausea in adolescents and vomiting, cough and headache in 6 to Conclusions In patients 6 to
- Published
- 2020
27. Persistent Hepatitis E virus infection across England and Wales 2009-2017: Demography, virology and outcomes
- Author
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Belinda Claire Smith, Bengü Said, Emanuela Pelosi, Kushala Abeysekera, Stuart McPherson, Michael Ankcorn, Claire Bethune, Dilys Morgan, Louisa Vine, Ahmed M. Elsharkawy, Deepak Suri, Sanjay Bansal, Fiona H. Gordon, Jack Galliford, Stephen D. Ryder, David Sheridan, James Maggs, Talal Valliani, Richard S. Tedder, and Samreen Ijaz
- Subjects
viruses ,medicine.medical_treatment ,Human immunodeficiency virus (HIV) ,HIV Infections ,Reference laboratory ,medicine.disease_cause ,Serology ,03 medical and health sciences ,chemistry.chemical_compound ,Immunocompromised Host ,0302 clinical medicine ,Virology ,Hepatitis E virus ,Medicine ,Humans ,030212 general & internal medicine ,Demography ,Retrospective Studies ,Wales ,Hepatology ,business.industry ,Ribavirin ,virus diseases ,Immunosuppression ,digestive system diseases ,Hepatitis E ,Transplantation ,Infectious Diseases ,chemistry ,RNA, Viral ,030211 gastroenterology & hepatology ,Neoplasm Recurrence, Local ,business ,Haematological malignancy ,Hepatitis E virus infection - Abstract
The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified through routine reference laboratory testing. Virology, serology and clinical data were recorded through an approved PHE Enhanced Surveillance System. Sixty-six cases (70.2%) were transplant recipients, 16 (17.0%) had an underlying haematological malignancy without stem cell transplantation, six (6.4%) had advanced HIV infection, five (5.3%) were otherwise immunosuppressed, and one patient (1.1%) had no identified immunosuppression. Retrospective analysis of 46 patients demonstrated a median 38 weeks of viraemia before diagnostic HEV testing. At initial diagnosis, 16 patients (17.0%) had no detectable anti-HEV serological response. Of 65 patients treated with ribavirin monotherapy, 11 (16.9%) suffered virological relapse despite undetectable RNA in plasma or stool at treatment cessation. Persistent HEV infection remains a rare diagnosis, but we demonstrate that a broad range of immunocompromised patients are susceptible. Both lack of awareness and the pauci-symptomatic nature of persistent HEV infection likely contribute to significant delays in diagnosis. Diagnosis should rely on molecular testing since anti-HEV serology is insufficient to exclude persistent HEV infection. Finally, despite treatment with ribavirin, relapses occur even after cessation of detectable faecal shedding of HEV RNA, further emphasising the requirement to demonstrate sustained virological responses to treatment.
- Published
- 2020
28. Correction to: A new proposal for secondary surveillance following potentially curative therapy of HCC: alternating MRI and CEUS
- Author
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Sanjay Bansal, Fangshi Lu, Levi Frehlich, Jason K. Wong, Kelly W. Burak, and Stephanie R. Wilson
- Subjects
Radiological and Ultrasound Technology ,Urology ,Gastroenterology ,Radiology, Nuclear Medicine and imaging - Published
- 2022
29. NAFLD to MAFLD in adults but the saga continues in children: an opportunity to advocate change
- Author
-
Anil Dhawan, Sobha Singh, Robert Hegarty, Sanjay Bansal, and Emer Fitzpatrick
- Subjects
Adult ,Gerontology ,Hepatology ,Non-alcoholic Fatty Liver Disease ,business.industry ,Prevalence ,MEDLINE ,Humans ,Medicine ,Child ,business - Published
- 2021
30. Novel post-transcriptional and post-translational regulation of pro-apoptotic protein BOK and anti-apoptotic protein Mcl-1 determine the fate of breast cancer cells to survive or die
- Author
-
Tabrez A. Mohammad, Subapriya Rajamanickam, Manjeet K. Rao, Benjamin C. Onyeagucha, Sanjay Bansal, Panneerdoss Subbarayalu, Carla Zeballos, Yi Chen, Nourhan Abdelfattah, Vijay Kumar Eedunuri, Ratna K. Vadlamudi, Rosa M. Guzman, and Santosh Timilsina
- Subjects
0301 basic medicine ,Cell ,03 medical and health sciences ,BOK ,0302 clinical medicine ,breast cancer ,GSK-3 ,medicine ,Gene silencing ,Post-translational regulation ,GSK3α/β ,Cell growth ,business.industry ,apoptosis ,Cancer ,Mcl-1 ,medicine.disease ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Immunology ,Cancer cell ,Cancer research ,business ,Research Paper - Abstract
Deregulation of apoptosis is central to cancer progression and a major obstacle to effective treatment. The Bcl-2 gene family members play important roles in the regulation of apoptosis and are frequently altered in cancers. One such member is pro-apoptotic protein Bcl-2-related Ovarian Killer (BOK). Despite its critical role in apoptosis, the regulation of BOK expression is poorly understood in cancers. Here, we discovered that miR-296-5p regulates BOK expression by binding to its 3'-UTR in breast cancers. Interestingly, miR-296-5p also regulates the expression of anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1), which is highly expressed in breast cancers. Our results reveal that Mcl-1 and BOK constitute a regulatory feedback loop as ectopic BOK expression induces Mcl-1, whereas silencing of Mcl-1 results in reduced BOK levels in breast cancer cells. In addition, we show that silencing of Mcl-1 but not BOK reduced the long-term growth of breast cancer cells. Silencing of both Mcl-1 and BOK rescued the effect of Mcl-1 silencing on breast cancer cell growth, suggesting that BOK is important for attenuating cell growth in the absence of Mcl-1. Depletion of BOK suppressed caspase-3 activation in the presence of paclitaxel and in turn protected cells from paclitaxel-induced apoptosis. Furthermore, we demonstrate that glycogen synthase kinase (GSK3) α/β interacts with BOK and regulates its level post-translationally in breast cancer cells. Taken together, our results suggest that fine tuning of the levels of pro-apoptotic protein BOK and anti-apoptotic protein Mcl-1 may decide the fate of cancer cells to either undergo apoptosis or proliferation.
- Published
- 2017
31. Resolution by deep sequencing of a dual hepatitis E virus infection transmitted via blood components
- Author
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Richard S. Tedder, Felicia Adelina Stanford, Juan Ledesma, Jean L. Mbisa, David J. Williams, Mark Zuckerman, Patricia E. Hewitt, Sanjay Bansal, Anil Dhawan, and Samreen Ijaz
- Subjects
0301 basic medicine ,Genotype ,030106 microbiology ,Biology ,medicine.disease_cause ,Deep sequencing ,03 medical and health sciences ,symbols.namesake ,Hepatitis E virus ,Virology ,medicine ,Disease Transmission, Infectious ,Humans ,Blood Transfusion ,Phylogeny ,Hepatitis ,Whole genome sequencing ,Sanger sequencing ,Phylogenetic tree ,Transmission (medicine) ,High-Throughput Nucleotide Sequencing ,medicine.disease ,Hepatitis E ,Transplantation ,030104 developmental biology ,Blood ,England ,symbols - Abstract
Hepatitis E virus (HEV) is a zoonotic infection, with consumption of processed pork products thought to be the major route of transmission in England. The clinical features of HEV infection range from asymptomatic infection to mild hepatitis to fulminant liver failure. Persistent, chronic hepatitis is increasingly recognized in immunocompromised patients. Infection via HEV-containing blood components and organs has been reported and measures to reduce this transmission risk were introduced into the blood service in England in 2016. We report here the sequence and phylogenetic findings from investigations into a transmission event from an HEV-infected donor to two recipients. Phylogenetic analysis of HEV genome sequence fragments obtained by Sanger sequencing showed that, whilst most of the sequences from both recipients' samples grouped with the sequence from the blood donor sample, the relationship of five sequences from recipient 2 were unresolved. Analysis of Illumina short-read deep sequence data demonstrated the presence of two divergent viral populations in the donor's sample that were also present in samples from both recipients. A clear phylogenetic relationship was established, indicating a probable transmission of both populations from the donor to each of the immunocompromised recipients. This study demonstrates the value of the application of new sequencing technologies combined with bioinformatic data analysis when Sanger sequencing is not able to clarify a proper phylogenetic relationship in the investigation of transmission events.
- Published
- 2019
32. Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children
- Author
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Sanjay Bansal, Anil Dhawan, Nigel Heaton, Nataruks Chaijitraruch, Celine Filippi, Ragai R. Mitry, Anita Verma, Robin D. Hughes, Sharon C. Lehec, Emer Fitzpatrick, and Pauline Kane
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Tissue and Organ Procurement ,Alginates ,medicine.medical_treatment ,Transplantation, Heterologous ,Liver transplantation ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,Neonatal hemochromatosis ,Animals ,Humans ,Transplantation, Homologous ,Child ,Cells, Cultured ,Hepatology ,business.industry ,Liver cell ,Infant, Newborn ,Infant ,Immunosuppression ,Cell Encapsulation ,Liver Failure, Acute ,medicine.disease ,Liver regeneration ,Microspheres ,Liver Regeneration ,Liver Transplantation ,Rats ,Transplantation ,030104 developmental biology ,medicine.anatomical_structure ,Treatment Outcome ,Hepatocyte ,Child, Preschool ,Models, Animal ,Hepatocytes ,Feasibility Studies ,030211 gastroenterology & hepatology ,Female ,business - Abstract
Background & Aims Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF), but is limited by surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbead transplantation have been shown in animal models. We report our experience of this therapy in children with ALF treated on a named-patient basis. Methods Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads were tested in immunocompetent healthy rats. Subsequently, 8 children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessing the host immune response and residual function of the retrieved HMBs, either after spontaneous native liver regeneration or at the time of LT. Results Intraperitoneal transplantation of HMBs in healthy rats was safe and preserved synthetic and detoxification functions, without the need for immunosuppression. Subsequently, 8 children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion) at a median age of 14.5 days, range 1 day to 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions. Conclusion The results demonstrate the feasibility and safety of an HMB infusion in children with ALF. Lay summary Acute liver failure in children is a rare but devastating condition. Liver transplantation is the most effective treatment, but it has several important limitations. Liver cell (hepatocyte) transplantation is an attractive option, as many patients only require short-term liver support while their own liver recovers. Human hepatocytes encapsulated in alginate beads can perform the functions of the liver while alginate coating protects the cells from immune attack. Herein, we demonstrated that transplantation of these beads was safe and feasible in children with acute liver failure.
- Published
- 2019
33. QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil
- Author
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Bhupinder Singh, Sarwar Beg, Gyati Shilakari Asthana, Babita Garg, Sanjay Bansal, and Abhay Asthana
- Subjects
Male ,Materials science ,Polymers ,Chemistry, Pharmaceutical ,Bioadhesive ,Pharmaceutical Science ,Nanotechnology ,02 engineering and technology ,Aquatic Science ,030226 pharmacology & pharmacy ,Excipients ,03 medical and health sciences ,Granulation ,Drug Delivery Systems ,0302 clinical medicine ,IVIVC ,Polymer ratio ,In vivo ,Adhesives ,Drug Discovery ,medicine ,Mucoadhesion ,Animals ,Dissolution testing ,Ecology, Evolution, Behavior and Systematics ,Cefuroxime ,Ecology ,General Medicine ,021001 nanoscience & nanotechnology ,Drug Liberation ,Solubility ,Gastric Mucosa ,Delayed-Action Preparations ,Rabbits ,0210 nano-technology ,Hydrophobic and Hydrophilic Interactions ,Agronomy and Crop Science ,Tablets ,medicine.drug ,Biomedical engineering - Abstract
The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.
- Published
- 2015
34. Acute liver failure
- Author
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Naresh P Shanmugam and Sanjay Bansal
- Subjects
3. Good health - Abstract
The chapter on acute liver failure includes the definition, aetiology, and management of this condition. It discusses the frequently associated complications (neurological, haemodynamic, coagulopathy, infectious, and metabolic) and its prognosis, as well as the role of liver transplantation and liver support systems in its management.
- Published
- 2018
35. Hepatitis C
- Author
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Sanjay Bansal
- Abstract
The chapter on hepatitis C discusses the epidemiology, risk of transmission, and the clinical features of this infection. It explains the serology and then gives an update of treatment recommendations for children with interferon as well as directly acting antiviral agents.
- Published
- 2018
36. Gastroretentive Drug Delivery Systems
- Author
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Meena Bansal, Praveen K. Srivastava, Hetal Thakkar, Sumant Saini, Sanjay Bansal, and Bhupinder Singh
- Subjects
business.industry ,Drug delivery ,Medicine ,Pharmacology ,business - Published
- 2018
37. The Kasai procedure in a baby with complex congenital heart disease
- Author
-
Chulananda Goonasekera, Mark Davenport, Cathie Hill, Mariese Cooper, and Sanjay Bansal
- Subjects
medicine.medical_specialty ,Kasai procedure ,business.industry ,Medicine ,Geology ,Ocean Engineering ,Complex congenital heart disease ,business ,Water Science and Technology ,Surgery - Published
- 2015
38. Study of the Clinical Profile and Site Proclivity of Extrapulmonary Tuberculosis at Tertiary Care Center of Rohilkhand Region, Bareilly
- Author
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Rajat Agarwal, Rishi Kumar Saini, Javed Ahmad Khan, VK Tiwari, Sanjay Bansal, and Abhishek Kumar
- Subjects
03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,business.industry ,Extrapulmonary tuberculosis ,030231 tropical medicine ,Emergency medicine ,medicine ,Center (algebra and category theory) ,030212 general & internal medicine ,Intensive care medicine ,business ,Tertiary care - Abstract
Aim To study the clinical profile and site proclivity of extrapulmonary tuberculosis (EPTB) at tertiary care center of Rohilkhand region, Bareilly. Materials and methods Among 329 patients, the study was conducted on 108 patients with EPTB. The analysis included patients who were diagnosed for EPTB between May 1, 2015 and October 31, 2015 in a tertiary care hospital, Rohilkhand region, Bareilly, Uttar Pradesh. Results Among the EPTB cases studied, 62 (57.4%) were males. About 96 (88.8%) patients received Category (CAT)1 treatment and 12 (11.1%) patients received CAT2 treatment. Overall, the total number of different types of EPTB cases included lymph node (n = 44, 40.7%), human gastrointestinal tract (n = 18, 16.6%), pleura (n = 34, 31.4%), skeletal (n = 5, 4.6%), central nervous system (n = 3, 2.7%); other sites included mainly breast (n = 2, 3.2%), genitourinary (n = 1, 2.6%), and skin (n = 1, 2.6%). Conclusion Extrapulmonary tuberculosis still constitutes an important clinical problem. In this study, we assessed the site of predilection of EPTB patients, which constituted 32.8% of all tuberculosis cases presented to our center during the study period. Lymph node tuberculosis is the most common type. How to cite this article Tiwari VK, Agarwal R, Bansal S, Saini RK, Kumar A, Khan J. Study of the Clinical Profile and Site Proclivity of Extrapulmonary Tuberculosis at Tertiary Care Center of Rohilkhand Region, Bareilly. Int J Adv Integ Med Sci 2016;1(3):95-97.
- Published
- 2016
39. Hepatitis B virus in children: More therapeutic options—but unknown and known unknowns still present
- Author
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Sanjay Bansal and Nedim Hadžić
- Subjects
0301 basic medicine ,Hepatitis B virus ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Hepatology ,business.industry ,Immunology ,Medicine ,030211 gastroenterology & hepatology ,business ,medicine.disease_cause ,Virology - Published
- 2015
40. Health-related Quality of Life in Adolescent Patients With Hepatitis C Genotype 1 Treated With Sofosbuvir and Ledipasvir
- Author
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Kathleen B. Schwarz, William F. Balistreri, Maria Stepanova, Karen F. Murray, Philip J. Rosenthal, Sharon A. Hunt, Zobair M. Younossi, and Sanjay Bansal
- Subjects
Ledipasvir ,Male ,medicine.medical_specialty ,Sofosbuvir ,Adolescent ,Antiviral Agents ,Virus ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Quality of life ,Internal medicine ,Medicine ,Health Status Indicators ,Humans ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,Child ,Fluorenes ,business.industry ,Ribavirin ,Gastroenterology ,Hepatitis C ,Hepatitis C, Chronic ,medicine.disease ,Clinical trial ,Treatment Outcome ,chemistry ,Caregivers ,Pediatrics, Perinatology and Child Health ,Quality of Life ,030211 gastroenterology & hepatology ,Benzimidazoles ,Female ,Self Report ,business ,Uridine Monophosphate ,medicine.drug ,Follow-Up Studies - Abstract
The aim of the study was to assess the effect of treatment with ledipasvir/sofosbuvir (LDV/SOF) on the health-related quality of life (HRQL) of pediatric patients with chronic hepatitis C virus (HCV) infection.Adolescents (12-17 years) with HCV were treated with LDV/SOF (90/400 mg daily) for 12 weeks. HRQL was assessed using the PedsQLv4.0-SF15 completed by the children and caregivers before, during, and after treatment.We included 100 adolescents with HCV genotype 1 infection (14.7 ± 2.0 years, 1% known cirrhosis, 80% treatment-naïve, 97% sustained virologic response-12). At baseline, HRQL the caregiver- perceived HRQL scores were lower than adolescents' self-reported scores (by 6.7-7.9 points, all P 0.01). At the end of 12 weeks of treatment, however, the caregiver-reported HRQL scores showed a significant improvement (+all P 0.04), whereas the adolescents' self-reported scores did not change from the baseline. HRQL scores reported by caregivers remained higher than baseline (by +4.7-+7.5, P 0.01) through 12 weeks after treatment, as did the adolescents' self-reported Emotional Functioning scores (+4.3 from baseline, P = 0.0009); observed improvements were sustained after 24 weeks of follow-up (all P 0.04). Multivariate analysis showed that, after adjustment for location, age, and sex, having a history of anxiety and panic disorders were consistent predictors of impaired HRQL in adolescents with HCV infection (P 0.05).Treatment of HCV in adolescents with LDV/SOF is associated with some improvement in HRQL. Caregivers' reports of HRQL in adolescents with HCV significantly increased with treatment and were similar to the adolescent self-reported HRQL after sustained virologic response-12.
- Published
- 2017
41. Social media data sensitivity and privacy scanning an experimental analysis with hadoop
- Author
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Ashish Lokhande and Sanjay Bansal
- Subjects
Information privacy ,Information retrieval ,Parsing ,Social network ,Computer science ,business.industry ,computer.software_genre ,Data modeling ,Index (publishing) ,Reachability ,Social media ,business ,computer ,Linear search - Abstract
Now in these days the social network has becomes a daily habit for all. Most of the young and teenager are consuming their time on social media. Due to frequent reachability of users the different marketing companies are also usages this platform for publishing advertises. But not only legitimate users are available in this platform, sometimes this platform is also used for abusing someone or harshen someone. Therefore, it is need to identify the sensitive contents on the social media platforms before publishing the contents. A number of different kinds of approaches are available for scanning the contents, but all these techniques are much time-consuming. Therefore, these techniques are not directly used with the social networks. In order to find an efficient technique an effort is presented in this work. The proposed technique is an enhancement over the traditional finger print scan method for sensitive content evaluation. The proposed technique incorporates the NLP (natural language processing) parsers for identifying the sensitive features. The sensitive features are considered here as the noun words in any twit, because in most of the cases the identity of person or places are used for misguiding the social network users. Additionally, in place of linear search technique, a random index scan method is introduced for improving the time consumption of the traditional approaches. Because this technique produces the results equal as the linear search in worst case. The proposed technique is evaluated over the twitter data using the Hadoop, Strom and twitter API implementation. After the successfully implementation the technique is compared with the traditional available technique over the time and space complexity. The experimental results show the performance in terms of time requirement is three times efficient than the traditional approach of sensitivity scan.
- Published
- 2017
42. 500 – Health-Related Quality of Life in Young Children with Hepatitis C Treated with Sofosbuvir and Ribavirin and Sofosbuvir/Ledipasvir
- Author
-
Kathleen B. Schwarz, Regino P. Gonzalez-Peralta, Sanjay Bansal, William F. Balistreri, Zobair M. Younossi, Fatema Nader, Philip J. Rosenthal, Maria Stepanova, Stefan Wirth, and Karen F. Murray
- Subjects
Ledipasvir ,Health related quality of life ,Pediatrics ,medicine.medical_specialty ,Hepatology ,Sofosbuvir ,business.industry ,Ribavirin ,Gastroenterology ,Hepatitis C ,medicine.disease ,chemistry.chemical_compound ,chemistry ,Medicine ,business ,medicine.drug - Published
- 2019
43. The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12-17 years old with hepatitis C virus genotype 1 infection
- Author
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Yanni Zhu, Kathleen B. Schwarz, Sanjay Bansal, Regino P. Gonzalez-Peralta, Evguenia S. Svarovskaia, Kathryn Kersey, Maureen M. Jonas, William F. Balistreri, Diana M. Brainard, Bittoo Kanwar, Benedetta Massetto, Karen F. Murray, Chuan Hao Lin, Philip J. Rosenthal, Jessica Wen, and Polina German
- Subjects
Ledipasvir ,Male ,medicine.medical_specialty ,Sofosbuvir ,Adolescent ,Genotype ,Administration, Oral ,Hepacivirus ,Antiviral Agents ,Risk Assessment ,Severity of Illness Index ,Drug Administration Schedule ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,030225 pediatrics ,Internal medicine ,Severity of illness ,Medicine ,Humans ,Dosing ,Adverse effect ,Child ,Fluorenes ,Hepatology ,Dose-Response Relationship, Drug ,business.industry ,Hepatitis C ,Hepatitis C, Chronic ,Viral Load ,medicine.disease ,Surgery ,Drug Combinations ,Treatment Outcome ,chemistry ,030211 gastroenterology & hepatology ,Benzimidazoles ,Female ,Patient Safety ,business ,medicine.drug ,Follow-Up Studies - Abstract
No all-oral, direct-acting antiviral regimens have been approved for children with chronic hepatitis C virus (HCV) infection. We conducted a phase 2, multicenter, open-label study to evaluate the efficacy and safety of ledipasvir–sofosbuvir in adolescents with chronic HCV genotype 1 infection. One hundred patients aged 12-17 years received a combination tablet of 90 mg ledipasvir and 400 mg sofosbuvir once daily for 12 weeks. On the tenth day following initiation of dosing, 10 patients underwent an intensive pharmacokinetic evaluation of the concentrations of sofosbuvir, ledipasvir, and the sofosbuvir metabolite GS-331007. The primary efficacy endpoint was the percentage of patients with a sustained virologic response at 12 weeks posttreatment. Median age of patients was 15 years (range 12-17). A majority (80%) were HCV treatment-naive, and 84% were infected through perinatal transmission. One patient had cirrhosis, and 42 did not; in 57 patients the degree of fibrosis was unknown. Overall, 98% (98/100; 95% confidence interval 93%-100%) of patients reached sustained virologic response at 12 weeks. No patient had virologic failure. The 2 patients who did not achieve sustained virologic response at 12 weeks were lost to follow-up either during or after treatment. The three most commonly reported adverse events were headache (27% of patients), diarrhea (14%), and fatigue (13%). No serious adverse events were reported. Area under the concentration-time curve (tau) and maximum concentration values for sofosbuvir, ledipasvir, and GS-331007 were within the predefined pharmacokinetic equivalence boundaries of 50%-200% when compared with adults from phase 2 and 3 studies of ledipasvir and sofosbuvir. Conclusion: Ledipasvir−sofosbuvir was highly effective at treating adolescents with chronic HCV genotype 1 infection; the dose of ledipasvir−sofosbuvir currently used in adults was well tolerated in adolescents and had an appropriate pharmacokinetic profile. (Hepatology 2017;66:371–378).
- Published
- 2016
44. Acute infectious hepatitis in hospitalised children: a British Paediatric Surveillance Unit study
- Author
-
Deirdre Kelly, Mary Ramsay, Adam Irwin, Serena Braccio, Shamez N Ladhani, Delane Shingadia, Sanjay Bansal, and Andrew Riordan
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Pediatrics ,Household contact ,Adolescent ,medicine.medical_treatment ,030106 microbiology ,Liver transplantation ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Child ,Hepatitis B virus ,Hepatitis ,Travel ,business.industry ,Public health ,Incidence ,virus diseases ,Infant ,Hepatitis A ,medicine.disease ,Hepatitis B ,Prognosis ,digestive system diseases ,United Kingdom ,Vaccination ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Acute Disease ,Etiology ,Electronic database ,business ,Child, Hospitalized ,Ireland - Abstract
Background Hepatitis remains a key public health priority globally. Most childhood cases are caused by viruses, especially hepatitis A virus (HAV) and hepatitis B virus (HBV). This study aimed to estimate the burden of acute infectious hepatitis in hospitalised children and to describe their clinical characteristics and outcomes. Methods Paediatricians in the UK and Ireland reported cases in children aged 1 month to 14 years diagnosed between January 2014 and January 2015 (inclusive) through the British Paediatric Surveillance Unit (BPSU) and completed a detailed questionnaire. Additional HAV and HBV cases in England and Wales were identified through a national electronic database, LabBase2. All confirmed cases were followed up at 6 months with a second questionnaire. Results The BPSU survey identified 69 children (annual incidence, 0.52/100 000), including 27 HAV (39%), three HBV (4%), 16 other viruses (23%) and 23 with no aetiology identified (33%). LabBase2 identified an additional 10 HAV and 2 HBV cases in England. Of the 37 hospitalised HAV cases, 70% had travelled abroad, but only 8% had been vaccinated. Similarly, three of the five children with acute HBV had not been immunised, despite being a household contact of a known infectious individual. All patients with HAV recovered uneventfully. In contrast, three children with acute HBV developed liver failure and two required liver transplantation. Conclusions Acute infectious hepatitis is a rare cause of hospital admission. Most children recovered without complications, but those with acute HBV had severe presentations. At least three of the five HBV cases could have been prevented through appopriate vaccination of household contacts.
- Published
- 2016
45. Assessment of Diet and Physical Activity in Paediatric Non-Alcoholic Fatty Liver Disease Patients: A United Kingdom Case Control Study
- Author
-
Deepa Kamat, Emer Fitzpatrick, Martha Ford-Adams, Anil Dhawan, Ashish Desai, Marianne Gilbert, P.S. Gibson, J. Bernadette Moore, Kathryn Hart, Sarah Louise Lang, and Sanjay Bansal
- Subjects
Male ,obesity ,medicine.medical_specialty ,Adolescent ,Population ,Physical fitness ,physical activity ,lcsh:TX341-641 ,Motor Activity ,Chronic liver disease ,Article ,Childhood obesity ,Liver disease ,children ,Surveys and Questionnaires ,Internal medicine ,medicine ,Humans ,Child ,education ,eating behaviour ,education.field_of_study ,Nutrition and Dietetics ,business.industry ,Data Collection ,Fatty liver ,Case-control study ,non-alcoholic fatty liver disease ,nutritional and metabolic diseases ,Feeding Behavior ,medicine.disease ,Obesity ,Diet ,nutrition ,Case-Control Studies ,Mental Recall ,Physical therapy ,Female ,adolescence ,business ,lcsh:Nutrition. Foods and food supply ,Food Science - Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children, with prevalence rising alongside childhood obesity rates. This study aimed to characterise the habitual diet and activity behaviours of children with NAFLD compared to obese children without liver disease in the United Kingdom (UK). Twenty-four biopsy-proven paediatric NAFLD cases and eight obese controls without biochemical or radiological evidence of NAFLD completed a 24-h dietary recall, a Physical Activity Questionnaire (PAQ), a Dutch Eating Behavior Questionnaire (DEBQ) and a 7-day food and activity diary (FAD), in conjunction with wearing a pedometer. Groups were well matched for age and gender. Obese children had higher BMI z-scores (p = 0.006) and BMI centiles (p = 0.002) than participants with NAFLD. After adjusting for multiple hypotheses testing and controlling for differences in BMI, no differences in macro- or micronutrient intake were observed as assessed using either 24-h recall or 7-day FAD (p >, 0.001). Under-reporting was prevalent (NAFLD 75%, Obese Control 87%: p = 0.15). Restrained eating behaviours were significantly higher in the NAFLD group (p = 0.005), who also recorded more steps per day than the obese controls (p = 0.01). In conclusion, this is the first study to assess dietary and activity patterns in a UK paediatric NAFLD population. Only a minority of cases and controls were meeting current dietary and physical activity recommendations. Our findings do not support development of specific dietary/ physical activity guidelines for children with NAFLD, promoting adherence with current general paediatric recommendations for health should remain the focus of clinical management.
- Published
- 2015
46. Abstract 3748: p53 status as a determinant of functional duality of estrogen receptor beta in breast cancer: Therapeutic implications
- Author
-
Angela Omilian, Utpal K. Mukhopadhyay, Alka Mukhopadhyay, Sanjay Bansal, Gokul M. Das, Wiam Bshara, Rajesh Medisetty, Christina Adams, Austin Miller, Wendy M. Sweizig, Anne Lise Børresen-Dale, Laxmi Silwal-Pandit, and Nadi Wickramasekera
- Subjects
Cancer Research ,Proximity ligation assay ,Biology ,medicine.disease ,Breast cancer ,Oncology ,Cancer cell ,Cancer research ,medicine ,Immunohistochemistry ,Doxorubicin ,Chromatin immunoprecipitation ,Estrogen receptor beta ,Tamoxifen ,medicine.drug - Abstract
Whether estrogen receptor beta (ERβ) is a pro- or anti-oncogenic protein in breast cancer has been controversial. ERβ levels are high in ERα negative cancers including triple-negative breast cancer (TNBCs). Recent reports including the Cancer Genome Atlas (TCGA) show that about 80% of TNBC express mutant p53 (mut-p53) and it is the most predominant driver in these cancers. We tested the hypothesis that p53 status in breast cancer will have an important role in determining the duality of ERβ functions. We have shown that ERβ directly binds to p53 in human breast cancer cells. Using glutathione-S-transferase (GST)-pull down and co-imunoprecipitation assays, we have delineated the domains of both proteins that are required for the ERβ-p53 interaction. The DNA binding domain (DBD) along with the hinge domain of ERβ and the C-terminal regulatory domain of p53 are essential for the interaction. Using the highly sensitive proximity ligation assay (PLA), we show ERβ-p53 interaction in situ in breast cancer cells expressing either wild type (wt)- or mut-p53. ERβ and p53 antibodies validated for specificity were used. In multiple cell lines, a combination of proliferation and apoptosis assays, RNAi technology, quantitative chromatin immunoprecipitation (qChIP), and quantitative real-time PCR (qRT-PCR) showed that ERβ is pro-proliferative in the context of wt-p53, whereas it is anti-proliferative in the context of mut-p53. The results were recapitulated in isogenic MDA-MB-231 TNBC cells (generated by CRISPR technology) that differ only in the presence of wt-versus mut-p53. ERβ binds and sequesters mut-p53 from mut-p53−p73 complex leading to reactivation of tumor suppressor p73. Consistent with these data, combination of immunohistochemistry (IHC) and PLA in TNBC patient tumor tissue microarray (TMA) showed that patients with tumors expressing wt-p53/ high ERβ had worse prognosis, both in terms of overall survival (OS) and progression-free survival (PFS). On the contrary, tumors expressing mut-p53/ high ERβ were of smaller size and stage. These findings were complemented by data from our analysis of the mut-p53 subgroup of the basal-like tumors in the METABRIC dataset which showed that patients with tumors expressing higher levels of ERβ RNA (ESR2) had better prognosis. Surprisingly, 4-Hyroxy Tamoxifen (Tam) increased ERβ-mut-p53 interaction in TNBC cells and combination of doxorubicin (Adriamycin) and Tam decreased the IC50 of doxorubicin by 10 fold leading to increased apoptosis. These data have significant clinical implications in targeting ERβ and mutant p53 signaling pathways for therapeutic purposes especially in ERα negative cancers such as TNBC. Importantly, although at present Tam is not standard of care for TNBC, our data suggest a possibility for repurposing Tam therapy alone or in combination with chemotherapy to treat TNBC stratified based on p53 status. Citation Format: Gokul M. Das, Utpal K. Mukhopadhyay, Christina Adams, Nadi Wickramasekera, Rajesh Medisetty, Sanjay Bansal, Laxmi Silwal-Pandit, Anne-Lise Borresen-Dale, Austin Miller, Wendy M. Sweizig, Angela Omilian, Wiam Bshara, Alka Mukhopadhyay. p53 status as a determinant of functional duality of estrogen receptor beta in breast cancer: Therapeutic implications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3748.
- Published
- 2018
47. Effect of implementation of a new inpatient diabetes curriculum on resident education and clinical decision making
- Author
-
Johnna McKelvey Sizemore, Sanjay Bansal, and Tanvi Shah
- Subjects
Pediatrics, Perinatology and Child Health - Published
- 2018
48. CLINICAL AND ETIOLOGICAL PROFILE OF PATIENTS WITH LUNG ABSCESS AT A TERTIARY CARE CENTRE
- Author
-
Manoj Kumar Agrawal, Sanjay Bansal, Amit Kumar, and Ankit Khurana
- Subjects
Anaerobic ,medicine.medical_specialty ,business.industry ,lcsh:R5-130.5 ,Lung abscess ,medicine.disease ,Tertiary care ,E tiological type ,Internal medicine ,Etiology ,Medicine ,business ,lcsh:General works - Abstract
BACKGROUND: Lung abscess is a type of liquefactive necrosis of the lung tissue and formation of cavities (more than 2 cm) containing necrotic debris or fluid caused by microbial infection. This pus - filled cavity is often caused by aspiration, which may occur during altered consciousness. OBJECTIVE: To study the clinical and etiological profile of lung abscess in patients admitted at a tertiary care centre. MATERIAL AND METHODS : A prospective study was condu cted on 142 cases with age more than 15 years, who were the suspected cases of lung abscess and the cases with evidence of lung abscess on the X - ray, CT scan presented to the OPD/ IPD clinic, Department of Pulmonary Medicine, Rohilkhand Medical College and Hospital (RMCH), Bareilly from January 2013 to December 2014 were included in the study. RESULTS: out of 142 patients enrolled in the study, 47(33.09%) belonged to age group of ›60 years followed by 42(29.57%) belong to 41 - 60 years of age. 116(81.6%) wer e male and 26(18.3%) were female. The most frequent symptom was cough (92.95%), followed by expectoration (91.54%), fever (87.32%) and hemoptysis (41.5%). CONCLUSION: In our study conducted, data collection shows that lung abscess was more seen in the elderly and male patients 116( 81.6%) as compared to female patients 26(18.3%). Majority of the patients had a risk factor of smoking, dental diseases, altered sensorium, comatosed patients, alcohol, diabetes, on steroid therapy and immunocompromised immune status. The following were the major symptoms in our patients : - Cough (92.95%), expectoration (91.54%) , Fever(87.32%), Foul smell (66.90%) , Chest pain (58.45%) , Hemoptysis (41.5%), Impaired consciousness (29.57%). In our study locus of lesion was more pro minently on right side i.e. 101 patients ( 71.12%) as compared to 36 ( 25.35%),while lung abscess was seen bilateral in 5 patients ( 3.5%). Primary lung abscess is a common presentation amongst the patients with the periodontal diseases, seizure disorders, co ma patients, tuberculosis, and dysphagia. The patients are counseled for postural drainage to harbor the culture and respiratory specimens obtained from patients with cavitary lung lesions for bacteria, mycobacteria, and fungi is first wise step in assessi ng the etiology of a cavity. In those patients in which sputum can’t be obtained can be considered for broncoscopy for the collection of BAL for further evaluation process
- Published
- 2015
49. HBsAg plasma level kinetics:a new role for an old marker as a therapy response predictor in vertically infected children on combination therapy
- Author
-
Lorenzo D'Antiga, M. Horner, Giorgina Mieli-Vergani, Diego Vergani, Irene Carey, Matt Bruce, Yoh Zen, and Sanjay Bansal
- Subjects
Male ,HBsAg ,Gastroenterology ,Plasma ,Interferon ,DNA, Viral/analysis ,Child ,Antiviral Agents/therapeutic use ,Lamivudine ,virus diseases ,Interferon-alpha/therapeutic use ,cccDNA ,Prognosis ,Immunohistochemistry ,HBcAg ,Infectious Diseases ,Treatment Outcome ,Liver ,Child, Preschool ,Drug Therapy, Combination ,Female ,Drug Monitoring ,Drug Monitoring/methods ,medicine.drug ,medicine.medical_specialty ,Hepatitis B, Chronic/drug therapy ,Combination therapy ,Adolescent ,Drug Therapy, Combination/methods ,Antiviral Agents ,Hepatitis B, Chronic ,Virology ,Internal medicine ,medicine ,Humans ,Lamivudine/therapeutic use ,Seroconversion ,Hepatitis B Surface Antigens ,Hepatology ,business.industry ,Gene Expression Profiling ,Interferon-alpha ,Hepatitis B Surface Antigens/analysis ,Plasma/chemistry ,digestive system diseases ,Liver/virology ,DNA, Viral ,Immunology ,business ,Biomarkers ,Biomarkers/blood - Abstract
We aimed to investigate the ability of HBsAg plasma level kinetics to predict therapy response by studying 23 children with infancy-acquired chronic hepatitis B (CHB) during combination sequential therapy with lead-in lamivudine (LAM) and add-on interferon-α (IFN-α) [5 responders (R = anti-HBs seroconversion) and 18 nonresponders (NR)] and to assess their relationship with pretreatment intrahepatic HBV-DNA and cccDNA and HBsAg and HBcAg liver expression. Plasma HBsAg levels were measured in samples before (treatment week 0 = TW0), during (TW9, TW28, TW52) and after (follow-up week = FUW24) therapy by Abbott ARCHITECT(®) assay [log10 IU/mL]. Baseline liver HBV-DNA and cccDNA were quantified by real-time TaqMan PCR [log10 copies/ng genomic DNA]. HBsAg and HBcAg liver expression was evaluated by immunostaining of formalin-fixed, paraffin-embedded specimens [number of positive cells/1000 hepatocytes]. All results are presented as medians. Plasma: at baseline, on-treatment and during follow-up, HBsAg levels were lower in R than NR (TW0: 4.36 vs 4.75;TW28: 2.44 vs 4.35;TW52: 0 vs 4.08 and FUW24: 0.17 vs 4.35, all P < 0.05). Liver: baseline HBV-DNA (3.82 vs 4.71, P = 0.16) and cccDNA (1.98 vs 2.26, P = 0.18) tended to be lower in R than NR, HBsAg expression was lower in R than NR (0.5 vs 4.7, P = 0.03), and HBcAg expression was similar between R and NR. There were positive correlations between plasma HBsAg levels and liver HBV-DNA (r = 0.44, P = 0.04), cccDNA (r = 0.41, P = 0.04) and HBsAg liver expression (r = 0.38, P = 0.05). Lower baseline HBsAg plasma levels, lower HBsAg expression in liver and on-treatment decline of plasma HBsAg levels heralds HBsAg clearance and response to treatment in tolerant children with CHB.
- Published
- 2015
50. High Rates of Svr12 in Adolescents Treated with the Combination of Ledipasvir/Sofosbuvir
- Author
-
Kathleen B. Schwarz, Philip J. Rosenthal, C.-H. Lin, Sanjay Bansal, P. German, Karen F. Murray, B. Kanwar, L. Ni, Regino P. Gonzalez-Peralta, W. Balistreri, Jessica Wen, J. Fraser, Maureen M. Jonas, and Diana M. Brainard
- Subjects
High rate ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,Hepatology ,business.industry ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,LEDIPASVIR/SOFOSBUVIR ,030211 gastroenterology & hepatology ,business ,Gastroenterology - Published
- 2016
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