152 results match your criteria: "Toronto K.P.; and Clinical Development[Affiliation]"
Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.
N Engl J Med
August 2021
From the University of Toronto (E.C.G., P.R.L., L.C.G., M.E.F., V.D., R.A.F., J.P.G., M.H., A.S.S.), University Health Network (E.C.G., M.H.), Peter Munk Cardiac Centre at University Health Network (P.R.L., L.C.G., M.E.F., V.D.), Ozmosis Research (L.B., V.W.), Sunnybrook Health Sciences Centre (J.P.G.), Toronto, Ottawa Hospital Research Institute (M. Carrier, L.A.C., D.A.F., G.L.G., D.M.S.), Institut du Savoir Montfort (M. Carrier, G.L.G.), and the University of Ottawa (L.A.C., D.A.F., D.M.S.), Ottawa, the University of Manitoba (A. Kumar, B.L.H., R.Z., S.A.L., D.S., G.V.-G.) and CancerCare Manitoba (B.L.H., R.Z.), Winnipeg, Université Laval and Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Quebec, QC (A.F.T.), McGill University, Montreal (S.R.K., E.G.M.), St. Michael's Hospital Unity Health, Toronto (J.C.M., Z.B., M.S., A.S.S.), McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, ON (P.L.G.) Université de Sherbrooke, Sherbrooke, QC (F.L.), St. Boniface Hospital, Winnipeg, MB (N.M.), the University of British Columbia, Vancouver (S. Murthy), and the University of Alberta, Edmonton (S.D.) - all in Canada; University of Bristol and University Hospitals Bristol and Weston NHS Foundation Trust, Bristol (C.A.B.), the London School of Hygiene and Tropical Medicine (B.-A.K.), Imperial College London (A.C.G., F.A.-B., M.A.L.), Imperial College Healthcare NHS Trust, St. Mary's Hospital (A.C.G.), University College London Hospital (R.H.), Kings Healthcare Partners (B.J.H.), and Intensive Care National Audit and Research Centre (ICNARC) (P.R.M., K.R.), London, Queen's University Belfast and Royal Victoria Hospital, Belfast (D.F.M.), and Oxford University (A. Beane, L.J.E., S.J.S.) and NHS Blood and Transplant (L.J.E., S. Mavromichalis, S.J.S.), Oxford - all in the United Kingdom; the University of Pittsburgh (B.J.M., D.C.A., M.M.B., M.D.N., H.F.E., J.D.F., Z.F., D.T.H., A.J.K., C.M.L., K.L., M.M., S.K.M., C.W.S., Y.Z.), University of Pittsburgh Medical Center (B.J.M., D.C.A., M.D.N., K.L.), the Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, University of Pittsburgh (T.D.G.), and University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (C.M. Horvat) - all in Pittsburgh; New York University (NYU) Grossman School of Medicine (J.S.B., H.R.R., J.S.H., T.C., A.C., N.M.K., S. Mavromichalis, S.P.), NYU Langone Health, NYU Langone Hospital (T.A., T.C., A.C., J.M.H., E.Y.), and Bellevue Hospital (N.M.K.), Icahn School of Medicine at Mount Sinai (R.S.R.), and Mount Sinai Heart (R.S.R.), New York, Montefiore Medical Center (M.N.G., H.H.B., S.C., J.-T.C., A.A. Hope, R.N.) and Albert Einstein College of Medicine (M.N.G., H.H.B., B.T.G., A.A. Hope), Bronx, and NYU Langone Long Island, Mineola (A.A. Hindenburg) - all in New York; Zuckerberg San Francisco General Hospital-University of California, San Francisco (L.Z.K., C.M. Hendrickson, M.M.K., A.E.K., B.N.-G., J.J.P.), Harbor-UCLA Medical Center, Torrance (R.J.L.), Global Coalition for Adaptive Research (M. Buxton) and the University of California, Los Angeles (G.L.), Los Angeles, the University of California San Diego School of Medicine, San Diego (T.W.C.), and Stanford University School of Medicine, Palo Alto (J.G.W.) - all in California; the University of Illinois (K.S.K., J.R.J., J.G.Q.), the University of Chicago (J.D.P.), and the Chartis Group (J.S.) - all in Chicago; University Medical Center Utrecht, Utrecht University (L.P.G.D., M. Bonten, R.E.G.S., W.B.-P.), and Utrecht University (R.E.G.S.), Utrecht, and Radboud University Medical Center, Nijmegen (S. Middeldorp, F.L.V.) - all in the Netherlands; Larner College of Medicine at the University of Vermont, Burlington (M. Cushman); Inselspital, Bern University Hospital, University of Bern, Bern (T.T.), and SOCAR Research, Nyon (B.-A.K., S. Brouwer) - both in Switzerland; Instituto do Coracao, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (L.C.G., F.G.L., J.C.N.), Avanti Pesquisa Clínica (A.S.M.), and Hospital 9 de Julho (F.O.S.), Sao Paulo, Hospital do Coração de Mato Grosso do Sul (M.P.), the Federal University of Mato Grosso do Sul (M.P.), Hospital Universitário Maria Aparecida Pedrossia (D.G.S.), and Hospital Unimed Campo Grande (D.G.S.), Campo Grande, and Instituto Goiano de Oncologia e Hematologia, Clinical Research Center, Goiânia (M.O.S.) - all in Brazil; the Australian and New Zealand Intensive Care Research Centre, Monash University (Z.M., C.J.M., S.A.W., A. Buzgau, C.G., A.M.H., S.P.M., A.D.N., J.C.P.), Monash University (A.C.C.), and Alfred Health (A.C.C., A.D.N.), Melbourne, VIC, St. John of God Subiaco Hospital, Subiaco, WA (S.A.W., E. Litton), Flinders University, Bedford Park, SA (S. Bihari), and Fiona Stanley Hospital, Perth, WA (E. Litton) - all in Australia; Berry Consultants, Austin (R.J.L., L.R.B., E. Lorenzi, S.M.B., M.A.D., M.F., A.M., C.T.S.), and Baylor Scott and White Health, Temple (R.J.W.) - both in Texas; Auckland City Hospital (C.J.M., S.P.M., R.L.P.) and the University of Auckland (R.L.P.), Auckland, and the Medical Research Institute of New Zealand, Wellington (C.J.M., A.M.T.) - all in New Zealand; Fédération Hospitalo-Universitaire Saclay and Paris Seine Nord Endeavour to Personalize Interventions for Sepsis (FHU-SEPSIS), Raymond Poincaré Hospital, Université de Versailles Saint-Quentin-en-Yvelines, Garches (D. Annane), and Aix-Marseille University, Marseille (B.C.) - both in France; King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia (Y.M.A.); Nepal Mediciti Hospital, Lalitpur (D. Aryal), and the Nepal Intensive Care Research Foundation, Kathmandu (D. Aryal); Versiti Blood Research Institute, Milwaukee (L.B.K.); National Intensive Care Surveillance (NICS)-Mahidol Oxford Tropical Medicine Research Unit (MORU), Colombo, Sri Lanka (A. Beane); Jena University Hospital, Jena, Germany (F.B.); Cleveland Clinic, Cleveland (A.D.), and the University of Cincinnati, Cincinnati (K.H.) - both in Ohio; Ochsner Medical Center, University of Queensland-Ochsner Clinical School, New Orleans (M.B.E.); Instituto Mexicano del Seguro Social, Mexico City (J.E., E.M.G.); Brigham and Women's Hospital (B.M.E., Y.K., S.M.H.), Massachusetts General Hospital (N.S.R., A.B.S.), and Harvard Medical School (B.M.E., Y.K., N.S.R., A.B.S.) - all in Boston; University of Alabama, Birmingham (S.G.); TriStar Centennial Medical Center, Nashville (A.L.G.); University of Antwerp, Wilrijk, Belgium (H.G.); Rutgers New Jersey Medical School, Newark, New Jersey (Y.Y.G.); University of Oxford, Bangkok, Thailand (R.H.); the University of Michigan, Ann Arbor (R.C.H., P.K.P.), Beaumont Health, Royal Oak (G.B.N.), and Oakland University William Beaumont School of Medicine, Auburn Hills (G.B.N.) - all in Michigan; Apollo Speciality Hospital OMR, Chennai, India (D.J.); Oregon Health and Science University, Portland (A. Khan); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (A. Kindzelski, E.S.L.); University of Mississippi Medical Center, Jackson (M.E.K.); IdiPaz Research Institute, Universidad Autonoma, Madrid (J.L.-S.); University College Dublin, Dublin (A.D.N.); the University of Kansas School of Medicine, Kansas City (L.S.); and Duke University Hospital, Durham, North Carolina (L.W.).
Article Synopsis
- A clinical trial investigated whether therapeutic-dose anticoagulation could improve outcomes for critically ill patients with severe Covid-19 compared to standard thromboprophylaxis.
- The study found no significant difference in organ support-free days between the two groups, with the anticoagulation group showing a median of 1 day compared to 4 days for the usual-care group.
- The trial was halted due to a high probability of futility, with similar hospital discharge survival rates and a slightly higher occurrence of major bleeding in the anticoagulation group.
Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.
N Engl J Med
August 2021
From the Peter Munk Cardiac Centre at University Health Network (P.R.L., M.E.F., V.D., J.P.G., L.C.G., G.H.), the University of Toronto (P.R.L., E.C.G., A.S.S., M.E.F., V.D., R.A.F., L.C.G., G.H., M.H.), University Health Network (E.C.G., M.H.), St. Michael's Hospital Unity Health (A.S.S., Z.B., J.C.M., M.S.), Ozmosis Research (L.B., L.P.G.D., V.W.), and Sunnybrook Health Sciences Centre (J.P.G.), Toronto, Ottawa Hospital Research Institute (M. Carrier, L.A.C., D.A.F., G.L.G., D.M.S.), Institut du Savoir Montfort (Marc Carrier, G.L.G.), and the University of Ottawa (L.A.C., D.A.F., D.M.S.), Ottawa, Université Laval (A.F.T.) and CHU de Québec-Université Laval Research Center (A.F.T.), Quebec, QC, the University of Manitoba (B.L.H., A. Kumar, R.Z., S.A.L., D.S., G.V.-G.), CancerCare Manitoba (B.L.H., R.Z.), and St. Boniface Hospital (N.M.), Winnipeg, MB, McGill University, Montreal (S.R.K., E.G.M.), McMaster University (P.L.G.) and the Thrombosis and Atherosclerosis Research Institute (P.L.G.), Hamilton, ON, Université de Sherbrooke, Sherbrooke, QC (F.L.), the University of British Columbia, Vancouver (S. Murthy, K.R.), and the University of Alberta, Edmonton (S.D.) - all in Canada; NYU Grossman School of Medicine (J.S.B., H.R.R., J.S.H., T.C., N.M.K., S.P.), the Icahn School of Medicine at Mount Sinai and Mount Sinai Heart (R.S.R.), NYU Langone Health, NYU Langone Hospital (T.C., J.M.H., E.Y.), and Bellevue Hospital (N.M.K.), New York, Montefiore Medical Center (M.N.G., H.H.B., S.C., J.T.C., R.N.) and Albert Einstein College of Medicine (M.N.G., H.H.B., B.T.G., A. Hope), Bronx, and NYU Langone Long Island, Mineola (R.D.H., A. Hindenburg) - all in New York; the University of Pittsburgh (M.D.N., B.J.M., D.T.H., M.M.B., D.C.A., A.J.K., C.M.L., K.L., S.K.M., C.W.S.), UPMC (M.D.N., B.J.M., D.C.A., K.L., S.K.M.), the Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, University of Pittsburgh (T.D.G.), and UPMC Children's Hospital of Pittsburgh (C. Horvat), Pittsburgh, and Emergency Medicine, Penn State Hershey Medical Center, Hershey (S.C.M.) - all in Pennsylvania; Instituto do Coracao, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo (J.C.N., L.C.G., F.G.L.), Avanti Pesquisa Clínica (A.S.M.), Hospital de Julho (F.O.S.), and Hospital do Coracao (F.G.Z.), Sao Paulo, Hospital do Coração de Mato Grosso do Sul and the Federal University of Mato Grosso do Sul (M.P.), Hospital Universitário Maria Aparecida Pedrossia (D.G.S.J.), and Hospital Unimed Campo Grande (D.G.S.J.), Campo Grande, and INGOH, Clinical Research Center, Goiânia (M.O.S.) - all in Brazil; Instituto Mexicano del Seguro Social, Mexico City (J.E., Y.S.P.G.); the University of Bristol and University Hospitals Bristol and Weston NHS Foundation Trust (C.A.B.), Bristol, Imperial College London (A.C.G., F.A.-B., M.A.L.), Imperial College Healthcare NHS Trust, St. Mary's Hospital (A.C.G.), the London School of Hygiene and Tropical Medicine (B.-A.K.), University College London Hospital (R.H.), Kings Healthcare Partners (B.J.H.), the Intensive Care National Audit and Research Centre (P.R.M.), Guy's and St. Thomas' NHS Foundation Trust (M.S.-H.), and King's College London (M.S.-H.), London, Oxford University (A. Beane, S.J.S.) and NHS Blood and Transplant (L.J.E., S.J.S.), Oxford, and Queen's University Belfast and Royal Victoria Hospital, Belfast (D.F.M.) - all in the United Kingdom; Zuckerberg San Francisco General Hospital, University of California, San Francisco (L.Z.K., C. Hendrickson, M.M.K., A.E.K., M.A.M., B.N.-G.), Harbor-UCLA Medical Center, Torrance (R.J.L., S. Brouwer), Global Coalition for Adaptive Research (M. Buxton) and the University of California Los Angeles (G.L.), Los Angeles, the University of California San Diego School of Medicine, San Diego (T.W.C.), and Stanford University School of Medicine, Palo Alto (J.G.W.) - all in California; Larner College of Medicine at the University of Vermont, Burlington (M. Cushman); Australian and New Zealand Intensive Care Research Centre, Monash University (Z.M., A.M.H., C.J.M., S.A.W., A. Buzgau, C.G., S.P.M., A.D.N., J.C.P., A.C.C.), and Alfred Health (A.C.C., A.D.N.), Melbourne, VIC, St. John of God Subiaco Hospital (S.A.W., E. Litton) and Fiona Stanley Hospital (E. Litton), Perth, WA, and Flinders University, Bedford Park, SA (S. Bihari) - all in Australia; the University of Illinois (K.S.K., J.R.J., J.G.Q.), Cook County Health and Rush Medical College (S. Malhotra), and the University of Chicago (J.D.P.) - all in Chicago; SOCAR Research SA, Nyon (B.-A.K.), and Inselspital, Bern University Hospital, University of Bern (T.T.), Bern - all in Switzerland; Berry Consultants, Austin (R.J.L., E. Lorenzi, S.M.B., L.R.B., M.A.D., M.F., A.M., C.T.S.), University of Texas Southwestern Medical Center, Dallas (A.P.), and Baylor Scott and White Health, Temple (R.J.W.) - all in Texas; Auckland City Hospital (C.J.M., S.P.M., R.L.P.) and the University of Auckland (R.L.P.), Auckland, and the Medical Research Institute of New Zealand, Wellington (C.J.M., A.M.T.) - all in New Zealand; Vanderbilt University Medical Center (A.W.A.) and TriStar Centennial Medical Center (A.L.G.) - both in Nashville; Fédération Hospitalo Universitaire, Raymond Poincaré Hospital, Université de Versailles Saint-Quentin-en-Yvelines, Garches (D. Annane), and Aix-Marseille University, Marseille (B.C.) - both in France; King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia (Y.M.A.); Nepal Mediciti Hospital, Lalitpur, and Nepal Intensive Care Research Foundation, Kathmandu (D. Aryal) - both in Nepal; Versiti Blood Research Institute, Milwaukee (L.B.K., L.J.E.), and the University of Wisconsin School of Medicine and Public Health, Madison (J.P.S.); National Intensive Care Surveillance-Mahidol Oxford Tropical Medicine Research Unit, Colombo, Sri Lanka (A. Beane); the University Medical Center Utrecht, Utrecht University, Utrecht (M. Bonten, R.E.G.S., W.B.-P.), and Radboud University Medical Center, Nijmegen (S. Middeldorp, F.L.V.) - both in the Netherlands; Jena University Hospital, Jena, Germany (F.B.); Cleveland Clinic (A.D.) and Case Western Reserve University, the Metro Health Medical Centre (V.K.) - both in Cleveland; Ochsner Medical Center, University of Queensland-Ochsner Clinical School, New Orleans (M.B.E.); Harvard Medical School (B.M.E., Y.K., N.S.R., A.B.S), Brigham and Women's Hospital (B.M.E., Y.K., S.M.H.), Boston University School of Medicine and Boston Medical Center (N.M.H.), and Massachusetts General Hospital (A.B.S., N.S.R.) - all in Boston; University of Alabama, Birmingham (S.G.); Hospital Ramón y Cajal (S.G.-M., J.L.L.-S.M., R.M.G.) and IdiPaz Research Institute, Universidad Autonoma (J.L.-S.), Madrid, and University Hospital of Salamanca-University of Salamanca-IBSAL, Salamanca (M.M.) - all in Spain; University of Antwerp, Wilrijk, Belgium (H.G.); Rutgers New Jersey Medical School, Newark (Y.Y.G.); University of Oxford, Bangkok, Thailand (R.H.); Ascension St. John Heart and Vascular Center, Tulsa (N.H.), and the University of Oklahoma College of Medicine, Oklahoma City (N.H.); the University of Cincinnati, Cincinnati (K.H.); University of Michigan, Ann Arbor (R.C.H., P.K.P.), Beaumont Health, Royal Oak, and the OUWB School of Medicine, Auburn Hills (G.B.N.) - all in Michigan; Mayo Clinic, Rochester (V.N.I.), and the Hennepin County Medical Center, Minneapolis (M.E.P.) - both in Minnesota; Apollo Speciality Hospital-OMR, Chennai, India (D.J.); Oregon Health and Science University, Portland (A. Khan, E.S.L.); the National Heart, Lung, and Blood Institute, Bethesda, MD (A.L.K.); University of Mississippi Medical Center, Jackson (M.E.K.); University College Dublin, Dublin (A.D.N.); University of Kansas School of Medicine, Kansas City (L.S.); Duke University Hospital, Durham, NC (L.W.); and Emory University, Atlanta (B.J.W.).
Background: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.
Methods: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis.
Making the Correct Diagnosis in Thrombotic Microangiopathy: A Narrative Review.
Can J Kidney Health Dis
April 2021
Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.
Purpose Of Review: Thrombotic microangiopathy (TMA) is suspected in patients presenting with thrombocytopenia and evidence of a microangiopathic hemolytic anemia. Patients with TMA can be critically ill, so rapid and accurate identification of the underlying etiology is essential. Due to better insights into pathophysiology and causes of TMA, we can now categorize TMAs as thrombotic thrombocytopenic purpura, postinfectious (mainly Shiga toxin-producing -induced) hemolytic uremic syndrome (HUS), TMA associated with a coexisting condition, or atypical HUS (aHUS).
View Article and Find Full Text PDFMDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study.
Nat Med
June 2021
Multidisciplinary Association for Psychedelic Studies (MAPS), San Jose, CA, USA.
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions.
View Article and Find Full Text PDFThe North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Management of Metastatic and/or Unresectable Pheochromocytoma and Paraganglioma.
Pancreas
April 2021
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX.
Article Synopsis
- The manuscript outlines the findings from a conference held by the North American Neuroendocrine Tumor Society focused on treating metastatic and unresectable pheochromocytoma and paraganglioma.
- A diverse group of specialists reviewed existing literature and discussed medical management strategies and surveillance protocols post-surgery.
- Panelists voted on key issues and finalized recommendations, which were then distributed for approval among all participants.
Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis.
Blood Adv
April 2021
Medical Affairs, Sanofi, Diegem, Belgium.
The efficacy and safety of caplacizumab in individuals with acquired thrombotic thrombocytopenic purpura (aTTP) have been established in the phase 2 TITAN and phase 3 HERCULES trials. Integrated analysis of data from both trials was conducted to increase statistical power for assessing treatment differences in efficacy and safety outcomes. Caplacizumab was associated with a significant reduction in the number of deaths (0 vs 4; P < .
View Article and Find Full Text PDFRecognition memory and divergent cognitive profiles in prodromal genetic frontotemporal dementia.
Cortex
June 2021
Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA.
Although executive dysfunction is the characteristic cognitive marker of behavioral variant frontotemporal dementia (bvFTD), episodic memory deficits are relatively common, and may be present even during the prodromal disease phase. In a cohort of mutation carriers with mild behavioral and/or cognitive symptoms consistent with prodromal bvFTD, we aimed to investigate patterns of performance on an abbreviated list learning task, with a particular focus on recognition memory. We further aimed to characterize the cognitive prodromes associated with the three major genetic causes of frontotemporal dementia, as emerging evidence suggests there may be subtle differences in cognitive profiles among carriers of different genetic mutations.
View Article and Find Full Text PDFTerlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome.
N Engl J Med
March 2021
From the Department of Medicine, University of Toronto, Toronto (F.W.); Orphan Therapeutics, Annandale (S.C.P.), and Mallinckrodt Pharmaceuticals, Bedminster (S.E., K.J.) - both in New Jersey; the Department of Medicine, Beth Israel Deaconess Medical Center, Boston (M.P.C.); the University of Pennsylvania, Philadelphia (K.R.R.); Piedmont Transplant Institute, Piedmont Healthcare, Atlanta (R.A.R.); the Department of Medicine, Vanderbilt University Medical Center, Nashville (M.K.P.); the Department of Medicine, Baylor Scott and White All Saints Medical Center, Fort Worth (S.A.G.), and the Department of Medicine, University of Texas Southwestern Medical Center, Dallas (M.J.M.) - both in Texas; Ohio State University, Columbus (K.M.); the Department of Medicine, University of Minnesota, Minneapolis (N.L.), and the Department of Medicine, Mayo Clinic, Rochester (D.A.S.) - both in Minnesota; the Department of Medicine, University of Michigan Medical Center, Ann Arbor (P.S.); Virginia Commonwealth University, Richmond (A.J.S.); and Hepatology and Liver Transplantation, California Pacific Medical Center, San Francisco (R.T.F.).
Background: The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe.
Methods: We conducted a phase 3 trial to confirm the efficacy and safety of terlipressin plus albumin in adults with HRS-1. The patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days; in both groups, concomitant use of albumin was strongly recommended.
Utilization of Whole Exome Sequencing Data to Identify Clinically Relevant Pharmacogenomic Variants in Pediatric Inflammatory Bowel Disease.
Clin Transl Gastroenterol
December 2020
Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
Introduction: We hypothesized that variants within clinically relevant pharmacogenes could be identified using a whole exome sequencing data set derived from a cohort of more than 1,000 patients with inflammatory bowel disease (IBD).
Methods: Pediatric patients diagnosed with IBD underwent whole exome sequencing. We selected 18 genes with supporting literature where specific exonic variants would influence clinical care.
Pharmacokinetic equivalence of CT-P17 to high-concentration (100 mg/ml) reference adalimumab: A randomized phase I study in healthy subjects.
Clin Transl Sci
July 2021
University of Massachusetts Medical School and UMass Memorial Medical Center, Worcester, Massachusetts, USA.
Article Synopsis
- The study tested the pharmacokinetic (PK) equivalence of the adalimumab biosimilar CT-P17 compared to both US-licensed and EU-approved adalimumab through a clinical trial with healthy participants.
- Participants were randomly assigned to receive either CT-P17, US-adalimumab, or EU-adalimumab, and the study measured key PK indicators like concentration-time curves and maximum serum concentration.
- Results showed that CT-P17 was pharmacokinetically equivalent to the other adalimumab versions, with similar safety and immunogenicity profiles, supporting its potential as a viable biosimilar option.
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.
N Engl J Med
February 2021
The authors' affiliations are as follows: the Centre for Cancer Genetic Epidemiology, Departments of Public Health and Primary Care (L.D., S. Carvalho, J.A., K.A.P., Q.W., M.K.B., J.D., B.D., N. Mavaddat, K. Michailidou, A.C.A., P.D.P.P., D.F.E.) and Oncology (C.L., P.A.H., C. Baynes, D.M.C., L.F., V.R., M. Shah, P.D.P.P., A.M.D., D.F.E.), University of Cambridge, Cambridge, the Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine (A. Campbell, D.J.P.), and the Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology (D.J.P.), University of Edinburgh, the Cancer Research UK Edinburgh Centre (D.A.C., J.F.), and the Usher Institute of Population Health Sciences and Informatics, University of Edinburgh Medical School (A. Campbell, J.F.), Edinburgh, the Divisions of Informatics, Imaging, and Data Sciences (E.F.H.), Cancer Sciences (A. Howell), Population Health, Health Services Research, and Primary Care (A. Lophatananon, K. Muir), and Evolution and Genomic Sciences, School of Biological Sciences (W.G.N., E.M.V., D.G.E.), University of Manchester, the NIHR Manchester Biomedical Research Unit (E.F.H.) and the Nightingale Breast Screening Centre, Wythenshawe Hospital (E.F.H., H.I.), Academic Health Science Centre and North West Genomics Laboratory Hub, and the Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester University NHS Foundation Trust (W.G.N., E.M.V., D.G.E.), Manchester, the School of Cancer and Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, King's College London, London (E.J.S.), the Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham (I.T.), and the Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford (I.T.) - all in the United Kingdom; the Human Genotyping-CEGEN Unit, Human Cancer Genetic Program (A.G.-N., M.R.A., N.Á., B.H., R.N.-T.), and the Human Genetics Group (V.F., A.O., J.B.), Spanish National Cancer Research Center, Centro de Investigación en Red de Enfermedades Raras (A.O., J.B.), Servicio de Oncología Médica, Hospital Universitario La Paz (M.P.Z.), and Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (M. de la Hoya), Madrid, the Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela, Complejo Hospitalario Universitario de Santiago (A. Carracedo, M.G.-D.), and Centro de Investigación en Red de Enfermedades Raras y Centro Nacional de Genotipado, Universidad de Santiago de Compostela (A. Carracedo), Santiago de Compostela, the Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur, Xerencia de Xestion Integrada de Vigo-Servizo Galeo de Saúde, Vigo (J.E.C.), and Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo (J.I.A.P.) - all in Spain; the Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund (C. Wahlström, J.V., M.L., T. Törngren, Å.B., A.K.), the Department of Oncology, Örebro University Hospital, Örebro (C. Blomqvist), and the Departments of Medical Epidemiology and Biostatistics (K.C., M.E., M.G., P. Hall, W.H., K.H.), Oncology, Södersjukhuset (P. Hall, S. Margolin), Molecular Medicine and Surgery (A. Lindblom), and Clinical Science and Education, Södersjukhuset (S. Margolin, C. Wendt), Karolinska Institutet, and the Department of Clinical Genetics, Karolinska University Hospital (A. Lindblom), Stockholm - all in Sweden; the Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD (M.T.P., C.F., G.C.-T., A.B.S.), the Cancer Epidemiology Division, Cancer Council Victoria (G.G.G., R.J.M., R.L.M.), the Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health (G.G.G., R.J.M., R.L.M.), and the Department of Clinical Pathology (M.C.S.), University of Melbourne, Anatomical Pathology, Alfred Hospital (C.M.), and the Cancer Epidemiology Division, Cancer Council Victoria (M.C.S.), Melbourne, VIC, and Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC (G.G.G., M.C.S., R.L.M.) - all in Australia; the Division of Molecular Pathology (R.K., S. Cornelissen, M.K.S.), Family Cancer Clinic (F.B.L.H., L.E.K.), Department of Epidemiology (M.A.R.), and Division of Psychosocial Research and Epidemiology (M.K.S.), the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Division Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Center, Utrecht (M.G.E.M.A.), the Department of Clinical Genetics, Erasmus University Medical Center (J.M.C., A.M.W.O.), and the Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute (B.A.M.H.-G., A. Hollestelle, M.J.H.), Rotterdam, the Department of Clinical Genetics, Maastricht University Medical Center, Maastricht (E.B.G.G.), the Departments of Human Genetics (I.M.M.L., M.P.G.V., P.D.), Clinical Genetics (C.J.A.), and Pathology (P.D.), Leiden University Medical Center, Leiden, the Department of Human Genetics, Radboud University Medical Center, Nijmegen (A.R.M.), and the Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen (J.C.O.) - all in the Netherlands; the Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute (B.D.), and the Division of Cancer Epidemiology and Genetics, National Cancer Institute (T.A., S.J.C., X.R.Y., M.G.-C.), National Institutes of Health, Bethesda, MD; the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School (B.D.), and the Department of Nutrition, Harvard T.H. Chan School of Public Health (R.M.V.D.), Boston; the Departments of Clinical Genetics (K.A.), Oncology (C. Blomqvist), and Obstetrics and Gynecology (H.N., M. Suvanto), Helsinki University Hospital, University of Helsinki, Helsinki, and the Unit of Clinical Oncology, Kuopio University Hospital (P. Auvinen), the Institute of Clinical Medicine, Oncology (P. Auvinen), the Translational Cancer Research Area (J.M.H., V.-M.K., A. Mannermaa), and the Institute of Clinical Medicine, Pathology, and Forensic Medicine (J.M.H., V.-M.K., A. Mannermaa), University of Eastern Finland, and the Biobank of Eastern Finland, Kuopio University Hospital (V.-M.K., A. Mannermaa), Kuopio - both in Finland; the N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus (N.N.A., N.V.B.); the Department of Gynecology and Obstetrics and Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel (N.A.), the Institute of Medical Biometry and Epidemiology (H. Becher) and Cancer Epidemiology Group (T.M., J.C.-C.), University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, the Department of Gynecology and Obstetrics (M.W.B., P.A.F., L.H.) and Institute of Human Genetics (A.B.E.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Erlangen, the Division of Cancer Epidemiology (S.B., A. Jung, P.M.K., J.C.-C.), Molecular Epidemiology Group, C080 (B. Burwinkel, H.S.), Division of Pediatric Neurooncology (A.F.), and Molecular Genetics of Breast Cancer (U.H., M.M., M.U.R., D.T.), German Cancer Research Center, Molecular Biology of Breast Cancer, University Women's Clinic Heidelberg, University of Heidelberg (B. Burwinkel, A.S., H.S.), Hopp Children's Cancer Center (A.F.), Faculty of Medicine, University of Heidelberg (P.M.K.), and National Center for Tumor Diseases, University Hospital and German Cancer Research Center (A.S., C.S.), Heidelberg, the Department of Radiation Oncology (N.V.B., M. Bremer, H.C.) and the Gynecology Research Unit (N.V.B., T.D., P. Hillemanns, T.-W.P.-S., P.S.), Hannover Medical School, Hannover, the Institute of Human Genetics, University of Münster, Münster (N.B.-M.), Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart (H. Brauch, W.-Y.L.), iFIT-Cluster of Excellence, University of Tübingen, and the German Cancer Consortium, German Cancer Research Center, Partner Site Tübingen (H. Brauch), and the University of Tübingen (W.-Y.L.), Tübingen, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum (T.B.), Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig (C.E.), Center for Hereditary Breast and Ovarian Cancer (E.H., R.K.S.) and Center for Integrated Oncology (E.H., R.K.S.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, the Department of Internal Medicine, Evangelische Kliniken Bonn, Johanniter Krankenhaus, Bonn (Y.-D.K.), the Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich (A. Meindl), and the Institute of Pathology, Städtisches Klinikum Karlsruhe, Karlsruhe (T.R.) - all in Germany; the Gynecological Cancer Registry, Centre Georges-François Leclerc, Dijon (P. Arveux), and the Center for Research in Epidemiology and Population Health, Team Exposome and Heredity, INSERM, University Paris-Saclay, Villejuif (E.C.-D., P.G., T. Truong) - both in France; the Institute of Biochemistry and Genetics, Ufa Federal Research Center of the Russian Academy of Sciences (M. Bermisheva, E.K.), the Department of Genetics and Fundamental Medicine, Bashkir State University (E.K., D.P., Y.V.), and the Ufa Research Institute of Occupational Health and Human Ecology (Y.V.), Ufa, Russia; the Department of Genetics and Pathology (K.B., A. Jakubowska, J. Lubiński, K.P.) and the Independent Laboratory of Molecular Biology and Genetic Diagnostics (A. Jakubowska), Pomeranian Medical University, Szczecin, Poland; the Copenhagen General Population Study, the Department of Clinical Biochemistry (S.E.B., B.G.N.), and the Department of Breast Surgery (H.F.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, and the Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (S.E.B., B.G.N.) - both in Denmark; the Division of Cancer Prevention and Genetics, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) (B. Bonanni), the Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (S. Manoukian), the Genome Diagnostics Program, FIRC Institute of Molecular Oncology (P.P.), and the Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (P.R.), Milan; the Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet (A.-L.B.-D., G.I.G.A., V.N.K.), and the Institute of Clinical Medicine, Faculty of Medicine, University of Oslo (A.-L.B.-D., V.N.K.), Oslo; Medical Faculty, Universidad de La Sabana (I.B.), and the Clinical Epidemiology and Biostatistics Department (F.G.) and Institute of Human Genetics (D.T.), Pontificia Universidad Javeriana, Bogota, Colombia; the Department of Internal Medicine and Huntsman Cancer Institute, University of Utah (N.J.C., M.J.M., J.A.W.), and the Intermountain Healthcare Biorepository and Department of Pathology, Intermountain Healthcare (M.H.C.), Salt Lake City; the David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California, Los Angeles (P.A.F.), and Moores Cancer Center (M.G.-D., M.E.M.) and the Department of Family Medicine and Public Health (M.E.M.), University of California San Diego, La Jolla; the Departments of Medical Oncology (V.G., D.M.) and Pathology (M.T.), University Hospital of Heraklion, Heraklion, and the Department of Oncology, University Hospital of Larissa, Larissa (E.S.) - both in Greece; the Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital (G.G., I.L.A.), the Departments of Laboratory Medicine and Pathobiology (A.M.M.) and Molecular Genetics (I.L.A.), University of Toronto, and the Laboratory Medicine Program, University Health Network (A.M.M.), Toronto, and the Genomics Center, Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Québec City, QC (J.S.) - both in Canada; the Department of Electron Microscopy and Molecular Pathology (A. Hadjisavvas, K.K., M.A.L.), the Cyprus School of Molecular Medicine (A. Hadjisavvas, K.K., M.A.L., K. Michailidou), and the Biostatistics Unit (K. Michailidou), Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; the Saw Swee Hock School of Public Health (M. Hartman, R.M.V.D.) and the Department of Medicine, Yong Loo Lin School of Medicine (R.M.V.D.), National University of Singapore, the Department of Surgery, National University Health System (M. Hartman, J. Li), and the Human Genetics Division, Genome Institute of Singapore (J. Li), Singapore; the Department of Mathematical Sciences, Faculty of Science and Engineering, University of Nottingham Malaysia (W.K.H.), and the Breast Cancer Research Programme, Cancer Research Malaysia (W.K.H., P.S.N., S.-Y.Y., S.H.T.), Selangor, and the Breast Cancer Research Unit, Cancer Research Institute (N.A.M.T.), and the Department of Surgery, Faculty of Medicine (N.A.M.T., P.S.N., S.H.T.), University Malaya, Kuala Lumpur - both in Malaysia; Surgery, School of Medicine, National University of Ireland, Galway (M.J.K., N. Miller); the Department of Surgery, Daerim Saint Mary's Hospital (S.-W.K.), the Department of Surgery, Ulsan University College of Medicine and Asan Medical Center (J.W.L.), the Department of Surgery, Soonchunhyang University College of Medicine and Soonchunhyang University Hospital (M.H.L.), Integrated Major in Innovative Medical Science, Seoul National University College of Medicine (S.K.P.), and the Cancer Research Institute, Seoul National University (S.K.P.), Seoul, South Korea; the Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan (M.U.R.); and the National Cancer Institute, Ministry of Public Health, Nonthaburi, Thailand (S.T.).
Background: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.
Methods: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes.
Using a simulation centre to evaluate preliminary acceptability and impact of an artificial intelligence-powered clinical decision support system for depression treatment on the physician-patient interaction.
BJPsych Open
January 2021
Department of Psychiatry, McGill University, Canada.
Background: Recently, artificial intelligence-powered devices have been put forward as potentially powerful tools for the improvement of mental healthcare. An important question is how these devices impact the physician-patient interaction.
Aims: Aifred is an artificial intelligence-powered clinical decision support system (CDSS) for the treatment of major depression.
Radiation Impacts Early Atherosclerosis by Suppressing Intimal LDL Accumulation.
Circ Res
February 2021
Toronto General Hospital Research Institute (J.I., C.A.S., S.J.H., M.G.A., J.A., S.A.D., T.E., J.M., N.I., H.M.I., C.K.P., X.G., K.T., J.J.-B., S.E., C.S.R., S.A.M., M.I.C.), University Health Network, Toronto, Canada.
Rationale: Bone marrow transplantation (BMT) is used frequently to study the role of hematopoietic cells in atherosclerosis, but aortic arch lesions are smaller in mice after BMT.
Objective: To identify the earliest stage of atherosclerosis inhibited by BMT and elucidate potential mechanisms.
Methods And Results: mice underwent total body γ-irradiation, bone marrow reconstitution, and 6-week recovery.
Myocardial Infarction in the ISCHEMIA Trial: Impact of Different Definitions on Incidence, Prognosis, and Treatment Comparisons.
Circulation
February 2021
New York University Grossman School of Medicine, New York (J.S.B., H.R.R., S.B., J.S.H.).
Article Synopsis
- The ISCHEMIA trial found that an initial invasive treatment strategy did not significantly lower cardiovascular events or overall mortality compared to a conservative approach in patients with stable ischemic heart disease and moderate to severe ischemia.
- The study evaluated two definitions of myocardial infarction (MI) to analyze procedural events, using different biomarker thresholds and criteria for determining MI occurrences.
- Results showed that procedural MIs were more common in invasive strategies than conservative ones, with higher percentages for both MI definitions; yet, type 1 MIs were less frequent in patients undergoing invasive treatment.
Slopes and intercepts from log-log correlations of gas/particle quotient and octanol-air partition coefficient (vapor-pressure) for semi-volatile organic compounds: I. Theoretical analysis.
Chemosphere
June 2021
Institute of Ocean Sciences, Department of Fisheries and Oceans, P.O. Box 6000, Sidney, BC, V8L 4B2, Canada.
Gas/particle partitioning governs the transport and fate of semi-volatile organic compounds (SVOCs) released to the atmosphere. The partition quotient of SVOCs, K, is related to their subcooled liquid vapor pressure (logK = m logP + b) and to their octanol-air partition coefficient (logK = m logK + b). Previous theory predicts that -m and m should be close to, or equal to 1 based on the assumption that gas- and particle-phases are at equilibrium in the atmosphere.
View Article and Find Full Text PDFNatural History of Hemodynamics in Vertebrobasilar Disease: Temporal Changes in the VERiTAS Study Cohort.
Stroke
November 2020
Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City (C.P.D.).
Background And Purpose: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort.
Methods: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries.
KRAS Inhibition with Sotorasib in Advanced Solid Tumors.
N Engl J Med
September 2020
From the Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, University of Texas M.D. Anderson Cancer Center, Houston (D.S.H., F.M.-B.); the Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte (M.G.F.), the University of California, San Francisco, San Francisco (P.N.M.), and Amgen, Thousand Oaks (H.H., J.N., G.N., J.K., B.E.H., J.C., J.R.L., G.F.) - all in California; Duke University Medical Center, Durham, NC (J.H.S.); Royal Melbourne Hospital/Peter MacCallum Cancer Centre, Melbourne, VIC (J.D.), Queen Elizabeth Hospital and University of Adelaide, Woodville South, SA (T.J.P.), and Scientia Clinical Research, Randwick, NSW (J.C. Kuo) - all in Australia; the Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis (G.A.D.); Dana-Farber Cancer Institute, Harvard Medical School, Boston (G.I.S.); the Sarah Cannon Research Institute at HealthONE, Denver (G.S.F.); Princess Margaret Cancer Centre, University Health Network, Toronto (A.S.); Fox Chase Cancer Center, Philadelphia (C.S.D.); the University of Pittsburgh Medical Center Hillman Cancer Center, University of Pittsburgh, Pittsburgh (T.F.B.); Seoul National University College of Medicine (Y.-J.B.), Samsung Medical Center, Sungkyunkwan University School of Medicine (K.P.), and the Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine (T.W.K.) - all in Seoul, South Korea; Roswell Park Cancer Institute, Buffalo (G.K.D.), and Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York (P.L., B.T.L.) - all in New York; the University of Michigan, Ann Arbor (J.C. Krauss); the Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan (Y.K.); the Department of Medicine, Division of Oncology, University of Washington, Seattle (A.L.C.); Aix Marseille University, Centre National de la Recherche Scientifique, INSERM, Centre de Recherche en Cancérologie de Marseille, Assistance Publique-Hôpitaux de Marseille, Marseille, France (F.B.); Winship Cancer Institute of Emory University, Atlanta (S.S.R.); and the Alvin J. Siteman Cancer Center at Washington University School of Medicine, St. Louis (R.G.).
Background: No therapies for targeting mutations in cancer have been approved. The p.G12C mutation occurs in 13% of non-small-cell lung cancers (NSCLCs) and in 1 to 3% of colorectal cancers and other cancers.
View Article and Find Full Text PDFExpanding the phenotypic and molecular spectrum of RNA polymerase III-related leukodystrophy.
Neurol Genet
June 2020
Department of Neurology and Neurosurgery (S.P., L.G., M.A.M.-R., L.T.T., K.G., L.D., M. Srour, K.P., G.B.), McGill University; Child Health and Human Development Program (S.P., M.A.M.-R., L.T.T., K.G., L.D., M. Srour, G.B.), Research Institute of the McGill University Health Centre; Department of Pediatrics (L.G., L.T.T., K.G., L.D., M. Srour, G.B.), McGill University, Montreal, Quebec, Canada; Division of Clinical and Metabolic Genetics (L.G.), Division of Neurology, the Hospital for Sick Children, University of Toronto, Ontario, Canada; Department of Pathology (C.F.-B.), CHU Sainte-Justine, Université de Montreal, Quebec, Canada; Division of Pathology and Laboratory Medicine (M.K.D.), Phoenix Children's Hospital, AZ; Department of Human Genetics (L.T.T., K.G., L.D., G.B.), McGill University, Montreal, Quebec, Canada; McGill University (K.P.), Brain Tumour Research Center Montreal Neurological Institute and Hospital, Quebec, Canada; Department of Neurology (D.L.R.), Department of Clinical Genomics, Department of Pediatrics, Mayo Clinic, Rochester, MN; Department of Pediatrics (M. Saito), University of California Riverside School of Medicine, Riverside Medical Clinic, CA; Department of Pediatrics (S.C.), Beaver Medical Group, Redlands, CA; Division of Pediatric Neurology (S.L.), Department of Pediatrics, Klinikum Dritter Orden, Munich, Germany; Institute of Human Genetics (B.A., T.B.H.), Technische Universität München, Munich, Germany; Institute of Medical Genetics and Applied Genomics (T.B.H.), University of Tübingen, Germany; Department of Neurology (I.T.-M., F.I.M., N.R.-E.), Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Canary Islands, Spain; Department of Neurology (D.P.), Children's Hospital of Eastern Ontario, University of Ottawa, Ontario, Canada; Department of Pediatrics (S.N.) and Department of Neurology (A.G.), Wake Forest School of Medicine, Winston-Salem, NC; Adult and Paediatric National Metabolic Service (E.G.), Starship Children's Hospital, Auckland, New Zealand; and Division of Medical Genetics (G.B.), Department of Specialized Medicine, Montreal Children's Hospital and McGill University Health Centre, Quebec, Canada.
Objective: To expand the phenotypic spectrum of severity of POLR3-related leukodystrophy and identify genotype-phenotype correlations through study of patients with extremely severe phenotypes.
Methods: We performed an international cross-sectional study on patients with genetically proven POLR3-related leukodystrophy and atypical phenotypes to identify 6 children, 3 males and 3 females, with an extremely severe phenotype compared with that typically reported. Clinical, radiologic, and molecular features were evaluated for all patients, and functional and neuropathologic studies were performed on 1 patient.
Saving Lives and Improving the Quality of Pediatric Resuscitation Across the World: A 1-Day Research Accelerator Hosted by the International Network for Simulation-based Pediatric Innovation, Research, and Education and the International Pediatric Simulation Society.
Simul Healthc
August 2020
From the Seattle Children's Hospital (K.P.S.), Seattle, WA; Keck School of Medicine (T.P.C.), Children's Hospital of Los Angeles, Los Angeles, CA; AiSolve Ltd (T.D.), Luton, United Kingdom; Department of Anaesthesia & Peri-operative Medicine (R.G.), University of Cape Town, Red Cross War Memorial Children's Hospital, Cape Town, South Africa; Johns Hopkins University School of Medicine (N.A.S., J.D-A); Children's Hospital of Philadelphia (E.D., V.M.M.), Philadelphia, PA; University of Calgary (A.C.); NYU Langone Health (M.P.), New York City, NY; and Health Informatics and Health Policy and Management (E.A.H.), Johns Hopkins University School of Medicine and Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
The International Network for Simulation-based Pediatric Innovation, Research, and Education co-hosted a novel research accelerator meeting with the International Pediatric Simulation Society in May of 2019 in Toronto. The purpose of the meeting was to bring together healthcare simulation scientists with resuscitation stakeholders to brainstorm strategies for accelerating progress in the science of saving pediatric lives from cardiac arrest. This was achieved by working in teams to draft targeted requests for proposals calling the research community to action investigating this topic.
View Article and Find Full Text PDFVitamin D, smoking, EBV, and long-term cognitive performance in MS: 11-year follow-up of BENEFIT.
Neurology
May 2020
From the Department of Nutrition (M.C., K.L.M, A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Global Public Health and Primary Care (M.C.), University of Bergen, Bergen, Norway; Department of Neurology (E.H.M.-L.), Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Departments of Medicine, Biomedicine and Clinical Research (C.B., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel, Basel, Switzerland; CHU Hôpital Pontchaillou (G.E.), Rennes, France; University of Ottawa and Ottawa Hospital Research Institute (M.S.F.), Ottawa, Canada; Department of Neurology (H.-P.H.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf, Germany; St. Michael's Hospital (X.M.), University of Toronto, Canada and Multiple Sclerosis Center of Catalonia (Cemcat) (X.M.), Vall d'Hebron University Hospital, Barcelona, Spain; Ferkauf Graduate School of Psychology (F.W.F.), Yeshiva University, New York, NY; Department of Neurology (I.K.P.), Medical Faculty, Heinrich-Heine Universität, Düsseldorf and COGITO Center for Applied Neurocognition and Neuropsychological Research (I.K.P.), Düsseldorf, Germany; Technical University of Munich (B.H.), School of Medicine and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany; Central Texas Neurology Consultants (E.J.F.), Round Rock, TX; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zurich, University of Zurich and Center for Neuroscience Zurich (S.S.), Federal Institute of Technology (ETH), Zurich, Switzerland; Bayer AG (E.-M.W.), Berlin, Germany; Department of Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA and Channing Division of Network Medicine (A.A.); and Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Article Synopsis
- The study examined the impact of vitamin D levels, smoking, and anti-EBV antibodies on cognitive health and neuroaxonal injury in multiple sclerosis (MS) patients over 11 years.
- Higher vitamin D levels were linked to better cognitive performance, while smoking was associated with poorer outcomes; specifically, a significant decrease in cognitive performance was observed in smokers.
- The anti-EBV antibody levels did not show a predictive relationship for cognitive function or neuroaxonal injury, reinforcing the significance of vitamin D and smoking status in MS patient management.
Initial Invasive or Conservative Strategy for Stable Coronary Disease.
N Engl J Med
April 2020
From the Department of Medicine, Stanford University School of Medicine, Stanford (D.J.M., R.A.H.), and Cedars-Sinai Medical Center, Los Angeles (D.S.B.) - both in California; New York University Grossman School of Medicine (J.S.H., H.R.R., S. Bangalore, J.S.B., J.D.N., S.M.), Weill Cornell Medicine/New York-Presbyterian Hospital (L.J.S.), Cleerly (J.K.M.), the Cardiovascular Research Foundation (Z.A.A., G.W.S.), Columbia University Irving Medical Center/New York-Presbyterian Hospital (Z.A.A.), and Icahn School of Medicine at Mount Sinai (G.W.S.), New York, Albany Medical College and Albany Medical Center, Albany (M.S.S.), and St. Francis Hospital, Roslyn (Z.A.A.) - all in New York; Duke Clinical Research Institute, Durham (S.M.O., K.P.A., R.D.L., D.B.M., F.W.R., S. Broderick), and Brody School of Medicine, East Carolina University, Greenville (T.B.F.) - both in North Carolina; Veterans Affairs (VA) New England Healthcare System and Boston University School of Medicine (W.E.B.), Massachusetts General Hospital and Harvard Medical School (M.H.P.), and Brigham and Women's Hospital (R.Y.K., D.O.W.) - all in Boston; Saint Louis University School of Medicine, St. Louis (B.R.C.), and the Saint Luke's Mid America Heart Institute and the University of Missouri-Kansas City School of Medicine, Kansas City (J.A.S.); Northwick Park Hospital (R.S., A.E.) and Imperial College London and Royal Brompton Hospital (R.S.) - all in London; Hospital Universitario La Paz, Instituto de Investigación de La Paz, Centro de Investigación Biomédica en Red Cardiovascular, Madrid (J.L.-S.), and Complejo Hospitalario Universitario A Coruna, Centro de Investigación Biomédica en Red Cardiovascular, A Coruna (J.P.) - all in Spain; Canadian Heart Research Centre and St. Michael's Hospital, University of Toronto, Toronto (S.G.G.), Montreal Heart Institute Research Center, Montreal (G.G.), and the University of British Columbia, Vancouver (G.B.J.M.) - all in Canada; the Department of Coronary and Structural Heart Diseases (M.D.), National Institute of Cardiology (W.R., M.D., H.S.), Warsaw, Poland; Associazione Nazionale Medici Cardiologi Ospedalieri, Florence, Italy (A.P.M.); Auckland Hospital Green Lane Cardiovascular Services, Auckland, New Zealand (H.D.W.); All India Institute of Medical Sciences, New Delhi (B.B.), Government Medical College Kozhikode, Kerala (M.N.K.), and Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bangalore (N.M.) - all in India; Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo (W.A.H.); Emory University School of Medicine-Atlanta VA Medical Center, Decatur, Georgia (K.M.); the National Research Center for Cardiovascular Surgery, Moscow (O.B.); Mayo Clinic, Rochester, MN (T.D.M.); Praxisklinik Herz und Gefaesse, Dresden, Germany (R.D.); Semmelweis University, Budapest, Hungary (M.K.); Flinders University, Flinders Medical Centre, Adelaide, SA, Australia (J.B.S.); Université de Paris, Assistance Publique-Hôpitaux de Paris, and INSERM Unité 1148, Paris (P.G.S.); the Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden (C.H.); Keio University School of Medicine, Shinjuku, Tokyo (S.K.); the National Institutes of Health, Bethesda, MD (R.K., N.O.J., Y.R.); and Vanderbilt University School of Medicine, Nashville (F.E.H.).
Background: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.
Methods: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.
Clinical Characteristics and Outcome of Canadian Patients Diagnosed With Atypical Hemolytic Uremic Syndrome.
Can J Kidney Health Dis
January 2020
Hôtel-Dieu de Québec, Quebec, QC, Canada.
Background: Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, heterogeneous disease of uncontrolled activation of the alternative complement pathway that is difficult to diagnose. We have evaluated the Canadian patients enrolled in the Global aHUS Registry to provide a Canadian perspective regarding the diagnosis and management of aHUS and the specific challenges faced.
Objective: To evaluate Canadian patients enrolled in the Global aHUS Registry to provide a Canadian perspective regarding the diagnosis and management of aHUS and the specific challenges faced.
mHealth and wearable technology should replace motor diaries to track motor fluctuations in Parkinson's disease.
NPJ Digit Med
January 2020
5Department of Physical Medicine and Rehabilitation, Harvard Medical School, Spaulding Rehabilitation Hospital, Charlestown, MA USA.
Accurately monitoring motor and non-motor symptoms as well as complications in people with Parkinson's disease (PD) is a major challenge, both during clinical management and when conducting clinical trials investigating new treatments. A variety of strategies have been relied upon including questionnaires, motor diaries, and the serial administration of structured clinical exams like part III of the MDS-UPDRS. To evaluate the potential use of mobile and wearable technologies in clinical trials of new pharmacotherapies targeting PD symptoms, we carried out a project (project BlueSky) encompassing four clinical studies, in which 60 healthy volunteers (aged 23-69; 33 females) and 95 people with PD (aged 42-80; 37 females; years since diagnosis 1-24 years; Hoehn and Yahr 1-3) participated and were monitored in either a laboratory environment, a simulated apartment, or at home and in the community.
View Article and Find Full Text PDFAtrial Cardiopathy and Nonstenosing Large Artery Plaque in Patients With Embolic Stroke of Undetermined Source.
Stroke
March 2020
Division of Cardiology, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (S.J.C., J.S.H.).
Background and Purpose- Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies.
View Article and Find Full Text PDFThe Brain Exposure Efficiency (BEE) Score.
ACS Chem Neurosci
January 2020
Krembil Research Institute , University Health Network, 60 Leonard Avenue , Toronto , Ontario M5T 2S8 , Canada.
The blood-brain barrier (BBB), composed of microvascular tight junctions and glial cell sheathing, selectively controls drug permeation into the central nervous system (CNS) by either passive diffusion or active transport. Computational techniques capable of predicting molecular brain penetration are important to neurological drug design. A novel prediction algorithm, termed the Brain Exposure Efficiency Score (BEE), is presented.
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