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Khanna, dinesh

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https://www.readbyqxmd.com/read/29760157/methyl-cpg-binding-protein-2-mediates-antifibrotic-effects-in-scleroderma-fibroblasts
#1
Ye He, Pei-Suen Tsou, Dinesh Khanna, Amr H Sawalha
OBJECTIVE: Emerging evidence supports a role for epigenetic regulation in the pathogenesis of scleroderma (SSc). We aimed to assess the role of methyl-CpG-binding protein 2 (MeCP2), a key epigenetic regulator, in fibroblast activation and fibrosis in SSc. METHODS: Dermal fibroblasts were isolated from patients with diffuse cutaneous SSc (dcSSc) and from healthy controls. MeCP2 expression was measured by qPCR and western blot. Myofibroblast differentiation was evaluated by gel contraction assay in vitro...
May 14, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29744756/regression-of-fibrosis-in-pediatric-liver-diseases
#2
Vikrant Sood, Bikrant Bihari Lal, Archana Rastogi, Rajeev Khanna, Dinesh Rawat, Seema Alam
The concept of irreversibility of cirrhosis has been challenged in the recent past with literature in this regard, albeit still scarce, now being accumulated across all age groups, etiologies, and geographical regions. This small series of nine pediatric cases elegantly recapitulates the concept of regression of hepatic fibrosis/cirrhosis and paves way for further detailed studies to enable development of therapeutic anti-fibrotic modalities in future.
May 9, 2018: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
https://www.readbyqxmd.com/read/29741230/a-randomized-controlled-trial-to-evaluate-an-internet-based-self-management-program-in-systemic-sclerosis
#3
Dinesh Khanna, Jennifer Serrano, Veronica J Berrocal, Richard M Silver, Pedro Cuencas, Sharon L Newbill, Josephine Battyany, Cynthia Maxwell, Mary Alore, Laura Dyas, Robert Riggs, Kerri Connolly, Saville Kellner, Jody J Fisher, Erica Bush, Anjali Sachdeva, Luke Evnin, Dennis W Raisch, Janet L Poole
OBJECTIVES: A pilot study showed that an internet-based self-management program improves self-efficacy in systemic sclerosis (SSc). The objective of the present study was to compare the internet-based self-management program to an educational book developed for people with SSc in measures of self-efficacy and other patient-reported outcomes. METHODS: A 16-week randomized, controlled trial. RESULTS: Of the 267 participants who completed baseline questionnaires and were randomized to the intervention (internet) or control (book) condition, 123 (93%) in the internet and 124 (94%) in the control completed the 16-week RCT...
May 9, 2018: Arthritis Care & Research
https://www.readbyqxmd.com/read/29732731/double-blind-randomized-8-week-placebo-controlled-followed-by-a-16-week-open-label-extension-study-with-the-lpa1-receptor-antagonist-sar100842-for-patients-with-diffuse-cutaneous-systemic-sclerosis
#4
Yannick Allanore, Oliver Distler, Alexandre Jagerschmidt, Stephane Illiano, Laetitia Ledein, Eric Boitier, Inoncent Agueusop, Christopher P Denton, Dinesh Khanna
BACKGROUND: Preclinical studies suggest a role for lysophosphatidic acid (LPA) in the pathogenesis of systemic sclerosis (SSc). OBJECTIVES: SAR100842, a potent selective oral antagonist of LPA1 receptor, was assessed for safety, biomarkers and clinical efficacy in patients with diffuse cutaneous SSc (dcSSc). METHODS: An 8-week double-blind, randomized, placebo-controlled study followed by a 16-week open label extension with SAR100842 was performed in patients with early dcSSc and a baseline Rodnan skin score (mRSS) of at least 15...
May 6, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29732714/whole-exome-sequencing-to-identify-rare-variants-and-gene-networks-that-increase-susceptibility-to-scleroderma-in-african-americans
#5
Pravitt Gourh, Elaine F Remmers, Steven E Boyden, Theresa Alexander, Nadia D Morgan, Ami A Shah, Maureen D Mayes, Ayo Doumatey, Amy R Bentley, Daniel Shriner, Robyn T Domsic, Thomas A Medsger, Virginia D Steen, Paula S Ramos, Richard M Silver, Benjamin Korman, John Varga, Elena Schiopu, Dinesh Khanna, Vivien Hsu, Jessica K Gordon, Lesley Ann Saketkoo, Heather Gladue, Brynn Kron, Lindsey A Criswell, Chris T Derk, S Louis Bridges, Victoria K Shanmugam, Kathleen D Kolstad, Lorinda Chung, Reem Jan, Elana J Bernstein, Avram Goldberg, Marcin Trojanowski, Suzanne Kafaja, Kathleen M Maksimowicz-McKinnon, James C Mullikin, Adebowale Adeyemo, Charles Rotimi, Francesco Boin, Daniel L Kastner, Fredrick M Wigley
OBJECTIVE: Whole-exome sequencing (WES) studies in systemic sclerosis (SSc) patients of European American (EA) ancestry have identified variants in the ATP8B4 gene and enrichment of variants in genes in the extracellular matrix (ECM)-related pathway increasing SSc susceptibility. Our goal was to evaluate the association of the ATP8B4 gene and the ECM-related pathway with SSc in a cohort of African Americans (AA). METHODS: SSc patients of AA ancestry were enrolled from 23 academic centers across the United States under the Genome Research in African American Scleroderma Patients (GRASP) consortium...
May 6, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29720568/pdcs-in-lung-and-skin-fibrosis-in-a-bleomycin-induced-model-and-patients-with-systemic-sclerosis
#6
Suzanne Kafaja, Isela Valera, Anagha A Divekar, Rajan Saggar, Fereidoun Abtin, Daniel E Furst, Dinesh Khanna, Ram Raj Singh
Fibrosis is the end result of most inflammatory conditions, but its pathogenesis remains unclear. We demonstrate that, in animals and humans with systemic fibrosis, plasmacytoid DCs (pDCs) are unaffected or are reduced systemically (spleen/peripheral blood), but they increase in the affected organs (lungs/skin/bronchoalveolar lavage). A pivotal role of pDCs was shown by depleting them in vivo, which ameliorated skin and/or lung fibrosis, reduced immune cell infiltration in the affected organs but not in spleen, and reduced the expression of genes and proteins implicated in chemotaxis, inflammation, and fibrosis in the affected organs of animals with bleomycin-induced fibrosis...
May 3, 2018: JCI Insight
https://www.readbyqxmd.com/read/29706243/practical-suggestions-on-intravenous-iloprost-in-raynaud-s-phenomenon-and-digital-ulcer-secondary-to-systemic-sclerosis-systematic-literature-review-and-expert-consensus
#7
REVIEW
Francesca Ingegnoli, Tommaso Schioppo, Yannick Allanore, Roberto Caporali, Michele Colaci, Oliver Distler, Daniel E Furst, Nicolas Hunzelmann, Florenzo Iannone, Dinesh Khanna, Marco Matucci-Cerinic
BACKGROUND: Systemic sclerosis (SSc) is an autoimmune chronic disease characterized by vascular impairment, immune dysfunction and collagen deposition. Raynaud's phenomenon (RP) and digital ulcers (DU) are prominent features of SSc. Intravenous (IV) iloprost (ILO), according to the recently updated EULAR recommendations, is indicated for RP after failure of oral therapy. Moreover, IV ILO could be useful in DU healing. IV ILO is currently available mainly on the European market approved for RP secondary to SSc with 3-5 days infusion cycle...
April 4, 2018: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29676525/leonine-facies-presenting-as-scleromyxedema
#8
Annie Y Park, Lori Lowe, Dinesh Khanna
A 61-year-old man previously in good health was referred to Scleroderma Clinic for a 2-year history of slowly progressive cutaneous eruption involving his dorsal hands, extremities, and central face. On physical examination, the patient had nodular, erythematous indurated lesions of his forehead and erythematous papular lesions on his nose with coalescence of firm erythematous papulonodules, resulting in a leonine facies. On the dorsal hands, arms, and legs were numerous, shiny, firm, closely set, 1-2 mm slightly translucent papules with background erythema (face and hand, shown in Panel A)...
April 20, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29538754/the-patient-experience-of-raynaud-s-phenomenon-in-systemic-sclerosis
#9
John D Pauling, Lesley Ann Saketkoo, Marco Matucci-Cerinic, Francesca Ingegnoli, Dinesh Khanna
RP is the most common manifestation of SSc and a major cause of disease-related morbidity. This review provides a detailed appraisal of the patient experience of SSc-RP and potential implications for disease classification, patient-reported outcome instrument development and SSc-RP clinical trial design. The review explores the clinical features of SSc-RP, the severity and burden of SSc-RP symptoms and the impact of SSc-RP on function, work and social participation, body image dissatisfaction and health-related quality of life in SSc...
March 12, 2018: Rheumatology
https://www.readbyqxmd.com/read/29504044/weekly-regimen-of-vitamin-d-supplementation-is-more-efficacious-than-stoss-regimen-for-treatment-of-vitamin-d-deficiency-in-children-with-chronic-liver-diseases
#10
Bikrant Bihari Lal, Seema Alam, Rajeev Khanna, Dinesh Rawat
There are no evidence-based recommendations on the ideal dose and regimen for supplementation of vitamin D in children with chronic liver disease (CLD). This study aimed to compare the safety and efficacy of weekly and stoss regimens for treatment of vitamin D deficiency in these children. Children between the ages of 1 to 18 years with CLD and hypovitaminosis D defined by 25-OH vitamin D (25(OH)D) < 30µg/l were included. They were randomized to receive either stoss regimen (600,000 IU on day 1) or weekly (60,000 IU weekly) regimen of vitamin D...
March 4, 2018: European Journal of Pediatrics
https://www.readbyqxmd.com/read/29473715/a-multi-national-qualitative-research-study-exploring-the-patient-experience-of-raynaud-s-phenomenon-in-systemic-sclerosis
#11
John D Pauling, Robyn T Domsic, Lesley A Saketkoo, Celia Almeida, Jane Withey, Hilary Jay, Tracy M Frech, Francesca Ingegnoli, Emma Dures, Joanna Robson, Neil J McHugh, Ariane L Herrick, Marco Matucci-Cerinic, Dinesh Khanna, Sarah Hewlett
OBJECTIVES: Raynaud's phenomenon (RP) is the commonest manifestation of systemic sclerosis (SSc). RP is an episodic phenomenon, not easily assessed in the clinic, leading to reliance on self-report. A thorough understanding of the patient experience of SSc-RP is essential to ensuring patient-reported outcome (PRO) instruments capture domains important to the target patient population. We report the findings of an international qualitative research study investigating the patient experience of SSc-RP...
November 21, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/29426066/screening-high-resolution-computed-tomography-of-the-chest-to-detect-interstitial-lung-disease-in-systemic-sclerosis-a-global-survey-of-rheumatologists
#12
Elana J Bernstein, Dinesh Khanna, David J Lederer
No abstract text is available yet for this article.
February 9, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29415230/factors-influencing-early-referral-early-diagnosis-and-management-in-patients-with-diffuse-cutaneous-systemic-sclerosis
#13
Oliver Distler, Yannick Allanore, Christopher P Denton, Marco Matucci-Cerinic, Janet E Pope, Barbara Hinzmann, Siobhan Davies, Janethe de Oliveira Pena, Dinesh Khanna
Objective: To gain insight into clinical practice regarding referral, early diagnosis and other aspects of the management of patients with dcSSc in Europe and the USA. Methods: Semi-structured interviews were conducted with 84 rheumatologists (or internal medicine physicians) and 40 dermatologists in different countries (the UK, France, Germany, Italy, Spain and the USA). Physicians were asked to identify key steps in the patient pathway relating to patient presentation, diagnosis and referral, in addition to other treatment and follow-up processes...
May 1, 2018: Rheumatology
https://www.readbyqxmd.com/read/29390428/clinical-and-serological-features-of-systemic-sclerosis-in-a-multicenter-african-american-cohort-analysis-of-the-genome-research-in-african-american-scleroderma-patients-clinical-database
#14
MULTICENTER STUDY
Nadia D Morgan, Ami A Shah, Maureen D Mayes, Robyn T Domsic, Thomas A Medsger, Virginia D Steen, John Varga, Mary Carns, Paula S Ramos, Richard M Silver, Elena Schiopu, Dinesh Khanna, Vivien Hsu, Jessica K Gordon, Heather Gladue, Lesley A Saketkoo, Lindsey A Criswell, Chris T Derk, Marcin A Trojanowski, Victoria K Shanmugam, Lorinda Chung, Antonia Valenzuela, Reem Jan, Avram Goldberg, Elaine F Remmers, Daniel L Kastner, Fredrick M Wigley, Pravitt Gourh, Francesco Boin
Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987-2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29381834/occupational-therapy-treatment-to-improve-upper-extremity-function-in-individuals-with-early-systemic-sclerosis-a-pilot-study
#15
Susan L Murphy, Mary Barber, Kristen Homer, Carole Dodge, Gary Cutter, Dinesh Khanna
OBJECTIVE: To determine feasibility and preliminary effects of an occupational therapy treatment to improve upper extremity (UE) function in patients with early systemic sclerosis (SSc) who have UE contractures. METHODS: A one-arm pilot clinical rehabilitation trial was conducted at a university health system. Participants with SSc and ≥ 1 UE contracture (n = 21) participated in a total of 8 weekly in-person occupational therapy sessions. The therapy consisted of thermal modalities, tissue mobilization, and UE mobility...
January 30, 2018: Arthritis Care & Research
https://www.readbyqxmd.com/read/29325220/profile-risk-factors-and-outcome-of-acute-kidney-injury-in-paediatric-acute-on-chronic-liver-failure
#16
Bikrant B Lal, Seema Alam, Vikrant Sood, Dinesh Rawat, Rajeev Khanna
BACKGROUND & AIMS: There are no studies on acute kidney injury in paediatric acute-on-chronic liver failure. This study was planned with aim to describe the clinical presentation and outcome of acute kidney injury among paediatric acute-on-chronic liver failure patients. METHODS: Data of all children 1-18 years of age presenting with acute chronic liver failure (Asia pacific association for the study of the liver definition) was reviewed. Acute kidney injury was defined as per Kidney Diseases-Improving Global Outcomes guidelines...
January 11, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29298160/myeloablative-autologous-stem-cell-transplantation-for-severe-scleroderma
#17
RANDOMIZED CONTROLLED TRIAL
Keith M Sullivan, Ellen A Goldmuntz, Lynette Keyes-Elstein, Peter A McSweeney, Ashley Pinckney, Beverly Welch, Maureen D Mayes, Richard A Nash, Leslie J Crofford, Barry Eggleston, Sharon Castina, Linda M Griffith, Julia S Goldstein, Dennis Wallace, Oana Craciunescu, Dinesh Khanna, Rodney J Folz, Jonathan Goldin, E William St Clair, James R Seibold, Kristine Phillips, Shin Mineishi, Robert W Simms, Karen Ballen, Mark H Wener, George E Georges, Shelly Heimfeld, Chitra Hosing, Stephen Forman, Suzanne Kafaja, Richard M Silver, Leroy Griffing, Jan Storek, Sharon LeClercq, Richard Brasington, Mary E Csuka, Christopher Bredeson, Carolyn Keever-Taylor, Robyn T Domsic, M Bashar Kahaleh, Thomas Medsger, Daniel E Furst
BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants)...
January 4, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29247427/clinical-spectrum-and-outcome-of-pediatric-drug-induced-liver-injury
#18
Aditi Kumar, Vikrant Sood, Rajeev Khanna, Sanjeev Kumar Verma, Nikhil Mehra, Dinesh Rawat, Seema Alam
Limited literature is available in pediatric population regarding drug-induced liver injury (DILI) making it a diagnostic challenge. This study was thus planned to determine the clinical spectrum and the outcome of DILI in children. All patients with DILI under 18 y of age were retrospectively reviewed and details regarding clinical presentation, Roussel Uclaf Causality Assessment Method (RUCAM) scale, drugs implicated, biochemical abnormalities and outcome were noted. DILI constituted 3.7% of all children with liver disease...
December 16, 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/29099620/reliability-and-minimal-clinically-important-differences-of-forced-vital-capacity-results-from-the-scleroderma-lung-studies-sls-i-and-sls-ii
#19
Suzanne Kafaja, Philip J Clements, Holly Wilhalme, Chi-Hong Tseng, Daniel E Furst, Grace Hyun Kim, Jonathan Goldin, Elizabeth R Volkmann, Michael D Roth, Donald P Tashkin, Dinesh Khanna
OBJECTIVES: To assess the reliability and the minimal clinically important differences (MCID) for FVC% predicted in the Scleroderma Lung Study I and II. METHODS: Using data from SLS I and II (N=300), we evaluated the test-retest reliability for FVC% predicted (FVC%; screening vs. baseline) using intra-class correlation (ICC). MCID estimates at 12 months were calculated in the pooled cohort (SLS-I and II) using 2 anchors: Transition Dyspnea Index (≥change of 1...
November 3, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29077900/patient-acceptable-symptom-state-in-scleroderma-results-from-the-tocilizumab-compared-with-placebo-trial-in-active-diffuse-cutaneous-systemic-sclerosis
#20
RANDOMIZED CONTROLLED TRIAL
Michael B Arnold, Dinesh Khanna, Christopher P Denton, Jacob M van Laar, Tracy M Frech, Marina E Anderson, Murray Baron, Lorinda Chung, Gerhard Fierlbeck, Santhanam Lakshminarayanan, Yannick Allanore, Gabriela Riemekasten, Virginia Steen, Ulf Müller-Ladner, Helen Spotswood, Laura Burke, Jeffrey Siegel, Angelika Jahreis, Daniel E Furst, Janet E Pope
Objectives: Patient acceptable symptom state (PASS) as an absolute state of well-being has shown promise as an outcome measure in many rheumatologic conditions. We aimed to assess whether PASS may be effective in active diffuse cutaneous SSc differentiating active from placebo. Methods: Data from the phase 2 Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (faSScinate) trial were used, which compared tocilizumab (TCZ) vs placebo over 48 weeks followed by an open-label TCZ period to 96 weeks...
January 1, 2018: Rheumatology
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