402 results match your criteria: "London G.T.; and University of Texas M.D. Anderson Cancer Center[Affiliation]"
Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy.
N Engl J Med
May 2023
From the Section of Allergy and Immunology, Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora (M.G., D.M.F.); the Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford (S.B.S.), the University of California, San Francisco, San Francisco (M.J.D.), the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (M.G.-L.), the University of California, San Diego, La Jolla (S.L.), and Rady Children's Hospital San Diego, San Diego (S.L.) - all in California; the Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York (J.W., H.A.S.); the Department of Immunology, Perth Children's Hospital, and Telethon Kids Institute, Nedlands, WA (M.O.), Westmead Children's Hospital, Westmead, NSW (L.S.F., D.E.C.), Queensland Children's Hospital, University of Queensland, South Brisbane (J.P.), Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC (K.P.P.), Women's and Children's Hospital, North Adelaide, SA (P.Q.), and Sydney Children's Hospital, Randwick, NSW (B.W.) - all in Australia; Guy's and St. Thomas' NHS Foundation Trust (G.T.), and the National Heart and Lung Institute, Imperial College London (P.J.T.), London, the Lydia Becker Institute of Immunology and Inflammation, University of Manchester and Royal Manchester Children's Hospital, Manchester (P.D.A.), University Hospital Southampton NHS Foundation Trust, Southampton (M.E.-L.), and Sheffield Children's NHS Foundation Trust, Sheffield (N.J.) - all in the United Kingdom; the Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill (E.H.K., A.W.B.); UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh (D.A., T.D.G.); Baylor College of Medicine, Houston (S.A.), UT Southwestern Medical Center and Children's Medical Center, Dallas (C.P.), and Dell Medical School at the University of Texas, Dell Children's Medical Center of Central Texas, Austin (P.V.) - all in Texas; Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands (N.A.); Centre Hospitalier Universitaire (CHU) Sainte-Justine, Montreal (P.B.), British Columbia Children's Hospital, University of British Columbia, Vancouver (E.S.C.), the Translational Medicine Program, Research Institute, and the Department of Immunology (T.E.), and the Division of Immunology and Allergy, Department of Paediatrics (J.E.M.U.), Hospital for Sick Children, University of Toronto, Toronto - all in Canada; the Department of Children and Adolescent Medicine, Division of Pneumology, Allergology and Cystic Fibrosis, University Hospital Frankfurt, Goethe University, Frankfurt (K.B.), Philipps-Universität Marburg, Marburg (W.P.), and Universitätsklinikum Carl Gustav Carus, Dresden (C.V.) - all in Germany; Hôpitaux Pédiatriques de Nice CHU Lenval, Nice (T. Bourrier, L.G.-C.), Université de Lille, CHU Lille, Pediatric Pulmonology and Allergy Unit, Hôpital Jeanne de Flandre, Lille (A.D.), the Pediatric Allergy Unit, Children's Hospital, University Hospital of Nancy, and EA3450 Development, Adaptation and Handicap, Faculty of Medicine, University of Lorraine, Nancy (A.D.-C.), the Department of Pediatric Pulmonology and Allergy, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, and University of Paris Cité, Paris (G.L.), and DBV Technologies, Montrouge (K.J.B., D.E.C., T.D.G., R.R., A.P., H.T.B., T. Bois, H.A.S.) - all in France; Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.B.-W.); University of Arizona Medical Center, Tucson (H.C.); University of Chicago (C.E.C.), Northwestern University Feinberg School of Medicine (M.M.), and Ann and Robert H. Lurie Children's Hospital of Chicago (M.M., J.A.P., R.G.R.) - all in Chicago; the University of Tennessee Health Science Center, Memphis (J.A.L.); Vanderbilt University Medical Center, Nashville (S.L.D., R.G.R.); Karl Landsteiner University of Health Sciences, Krems, and the Department of Pediatric and Adolescent Medicine, University Hospital St. Pölten, St. Pölten - both in Austria (T.E.); Paediatrics and Child Health and the INFANT Center (J.O.H.) and the HRB Clinical Research Facility and the INFANT Research Center (J.T.), University College Cork, Cork University Hospital, Cork, and Paediatrics and Child Health, Royal College of Surgeons in Ireland, Dublin (J.O.H.) - both in Ireland; University of Arkansas for Medical Sciences and Arkansas Children's Hospital - both in Little Rock (S.M.J.); Cleveland Clinic, Cleveland (L.A.K.); the Division of Pulmonary, Allergy, and Sleep Medicine, Department of Pediatrics, Indiana University School of Medicine, Indianapolis (K.M.K.); University of Rochester, Rochester, NY (J.L., K.T.); Seattle Allergy and Asthma Research Institute, Seattle (D.P.); University of Michigan, Ann Arbor (G.S.); Boston Children's Hospital, Boston (L.S.); Children's National Health System, Washington, DC (H.P.S.); Emory University, Atlanta (B.P.V.); and Johns Hopkins Hospital, Baltimore (R.A.W.).
Background: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown.
Methods: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months.
The Role of Electrophysiological Study in the Risk Stratification of Brugada Syndrome.
Cardiol Rev
May 2023
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.
Article Synopsis
- Brugada syndrome (BrS) is a serious heart condition linked to sudden cardiac death, but the effectiveness of electrophysiological studies (EPS) for assessing risk in asymptomatic patients is debated.
- This study analyzed data from 19 research studies involving over 6200 BrS patients to evaluate the correlation between positive EPS results and subsequent arrhythmic events.
- The findings suggest that a positive EPS significantly predicts future arrhythmic events in BrS patients, reinforcing the utility of EPS as a method for identifying individuals who may benefit from preventative measures like implantable cardioverter-defibrillators (ICDs).
Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases.
NPJ Parkinsons Dis
April 2023
Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
Genetic correlation ([Formula: see text]) between traits can offer valuable insight into underlying shared biological mechanisms. Neurodegenerative diseases overlap neuropathologically and often manifest comorbid neuropsychiatric symptoms. However, global [Formula: see text] analyses show minimal [Formula: see text] among neurodegenerative and neuropsychiatric diseases.
View Article and Find Full Text PDFEffects of the Oral Angiotensin II Type 2 Receptor Agonist C21 in Sugen-Hypoxia Induced Pulmonary Hypertension in Rats.
Int J Mol Sci
April 2023
Centre for Rheumatology, Royal Free Hospital, University College Medical School, London NW3 2PS, UK.
Substantial evidence supports the involvement of the renin-angiotensin system in pulmonary hypertension (PH), and the angiotensin II type 2 receptor (ATR) is known to exert tissue protective actions. The effect of the selective ATR agonist C21 (also known as Compound or buloxibutid) was evaluated in the rat Sugen-hypoxia PH model. After a single injection of Sugen 5416 and hypoxia for 21 days, C21 (2 or 20 mg/kg) or vehicle was administered perorally twice daily from Day 21 to Day 55.
View Article and Find Full Text PDFDecompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma.
N Engl J Med
June 2023
From the Division of Neurosurgery, Addenbrooke's Hospital (P.J.H., H.A., M.M., E.V., A.E.H., I.S.T., C.T., A.G.K.), the Department of Clinical Neurosciences (P.J.H., H.A., M.M., H.M., M.G.S., E.V., A.E.H., I.S.T., C.T., A.G.K.), and the Division of Anaesthesia (D.K.M.), University of Cambridge, and the Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust (C.T.), Cambridge, the Neurosurgery Department, Royal London Hospital (C.U., S.H.), and the Department of Neurosurgery, Imperial Neurotrauma Centre, Imperial College Academic Health Sciences Centre, St. Mary's Hospital (M.H.W.), London, Wessex Neurological Centre, University Hospitals Southampton NHS Foundation Trust, Southampton (D.B., A.Z.), the Department of Neurosurgery, Walton Centre NHS Foundation Trust, Liverpool (C.J.M., M.G.S.), the Department of Neurosurgery and the Academic Directorate of Neurosciences, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield (Y.Z.A.-T.), the Department of Neurosurgery, Leeds General Infirmary, Leeds (S.T.), the Department of Neurosurgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham (A.B.), the Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Manchester (A.T.K.), Norwich Medical School, University of East Anglia, Norwich (S.P., G.B.), and the Neurosurgical Trials Group, Wolfson Research Centre, Newcastle University, Newcastle upon Tyne (B.G.) - all in the United Kingdom; the Department of Neurosurgery, National Institute of Mental Health and Neurosciences (B.I.D., D.P.S.), and the Department of Neurosurgery, Aster RV Hospital (D.I.B.), Bangalore, the Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi (D.K.G.), and the Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh (M.K.T., M.T.) - all in India; the Department of Neurosurgery, University Hospital Antwerp, Edegem, Belgium (A.R.M.); Humanitas Research Hospital-IRCCS and Humanitas University, Rozzano, Milan (F.S.); and the University of California, San Francisco, San Francisco (G.T.M.).
Background: Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear.
Methods: We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy.
Pharmacokinetics of N,N-dimethyltryptamine in Humans.
Eur J Drug Metab Pharmacokinet
May 2023
Small Pharma, 6-8 Bonhill Street, London, EC2A 4BX, UK.
Background And Objective: N,N-dimethyltryptamine (DMT) is a psychedelic compound under development for the treatment of major depressive disorder (MDD). This study evaluated the preclinical and clinical pharmacokinetics and metabolism of DMT in healthy subjects.
Methods: The physiochemical properties of DMT were determined using a series of in vitro experiments and its metabolic profile was assessed using monoamine oxidase (MAO) and cytochrome P450 (CYP) inhibitors in hepatocyte and mitochondrial fractions.
Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.
medRxiv
March 2023
Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.
View Article and Find Full Text PDFAssociation of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.
Neurology
May 2023
From the Laboratory of Neuro Imaging (G.B.), Imaging Genetics Center (N.J., P.M.T.), and Department of Neurology (N. Sanossian, C.J.W.), Mark and Mary Stevens Neuroimaging and Informatics Institute (S.-L.L., J.H.K., H.K., G.P.), Keck School of Medicine, University of Southern California, Los Angeles; Chan Division of Occupational Science and Occupational Therapy (S.-L.L., B.P.L., M.R.D., J.N.J., Z.W., A.A., A.H., J.A.H., J.L.M.), Division of Biokinesiology and Physical Therapy (N. Schweighofer, C.J.W., S.-L.L.), and Herman Ostrow School of Dentistry, University of Southern California, Los Angeles; Centre for Medical Image Computing (J.H.C.), Department of Computer Science, Dementia Research Centre (J.H.C.), Queen Square Institute of Neurology, University College London, United Kingdom; Brain Mapping Center (A.Z.-P.), Department of Neurology, Geffen School of Medicine, University of California, Los Angeles; Centre for Youth Mental Health (L.K.M.H., L.S.) and Melbourne School of Psychological Sciences (N.E.-B.), University of Melbourne, Parkville, Victoria, Australia; Institute for Translational Psychiatry (T.H.), University of Münster, Germany; Department of Physical Therapy and Djavad Mowafaghian Centre for Brain Health (L.A.B.), University of British Columbia, Vancouver, Canada; The Florey Institute of Neuroscience and Mental Health (A.B., K.H., M.S.K.); Eastern Cognitive Disorders Clinic (A.B.); Royal Melbourne Hospital (A.B.), Victoria, Australia; Department of Neurology (C.M.B.) and Facility for Education and Research in Neuroscience (K.P.R.), Emory University, Atlanta, GA; Centre for Brain Research and Department of Exercise Sciences (W.D.B.), University of Auckland, New Zealand; Department of Health Sciences (J.M.C.), University of North Carolina at Chapel Hill; Department of Basic and Clinical Sciences (C.C.C.), Center for Neuroscience and Integrative Brain Research (CENIBRE) (C.C.C.), University of Nicosia Medical School, Cyprus; Laboratory of Neuropsychiatry (V.C., F.P.), IRCCS Santa Lucia Foundation, Rome, Italy; Hospital das Clínicas (A.B.C.), São Paulo University; Hospital Israelita Albert Einstein (A.B.C.), São Paulo, Brazil; Department of Psychiatry and Clinical Psychobiology (R.D.-A.), Universitat de Barcelona, Spain; Center for Neurotechnology and Neurorecovery (J.A.D., D.J.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston; Functional Imaging Unit (M.D.), Diagnostic and Neuroradiology and Functional Imaging Unit (M.L.), Diagnostic Radiology and Neuroradiology, Universitymedicine Greifswald, Germany; Departments of Neurology (A.N.D.) and Physical Medicine & Rehabilitation (K.A.W.), Dell Medical School at The University of Texas Austin; Department of Neurology (W.F.), Duke University School of Medicine, Durham, NC; Clinical Language and Cognition (CLC) Lab (F.G.), Department of Brain Sciences, Imperial College London, United Kingdom; Department of Health Sciences & Research (C.M.G., S.A.K.), Medical University of South Carolina, Charleston; Cancer Biology (C.A.H.), Wake Forest School of Medicine, Winston Salem, NC; Innovation, Implementation and Clinical Translation (IIMPACT) in Health (B.H.), Allied Health and Human Performance, University of South Australia, Adelaide; Ralph H. Johnson VA Medical Center (S.A.K., N.J.S.), Charleston, SC; Department of Radiology (A.K., E.R.O.), Weill Cornell Medicine, New York, NY; Department of Radiology (J.L., C.Y.), Tianjin Medical University General Hospital, China; Hurvitz Brain Sciences Program (B.J.M.), Centre for Brain Resilience & Recovery and Canadian Partnership for Stroke Recovery (A.D.R.), Sunnybrook Research Institute, Toronto, Ontario, Canada; Computational Radiology Artificial Intelligence Unit (B.J.M.) and Norwegian Centre for Mental Disorders Research (NORMENT) (L.T.W.), Department of Mental Health and Addiction, Oslo University Hospital, Norway; Department of Clinical Psychology and Psychobiology (M.M.), and Institut de Neurociències (M.M.), University of Barcelona; Institut de Recerca Pediàtrica (M.M.), Hospital Sant Joan de Déu, Esplugues de Llobregat, Spain; Jefferson Integrated MRI Center (F.B.M.), Department of Radiology, Thomas Jefferson University, Philadelphia, PA; Cedars-Sinai (P.R.), Los Angeles, CA; California Rehabilitation Institute (P.R., S.C.C.), Los Angeles; Department of Kinesiology and Health Sciences (A.D.R.), University of Waterloo, Ontario, Canada; Department of Neurology (H.M.S., M.T.), NYU Langone, New York; Department of Rehabilitation Sciences (N.J.S.), and Department of Health Sciences and Research (N.J.S.), Medical University of South Carolina, Charleston; Department of Psychiatry and Neurosciences (S.R.S.), Clinical Neurotechnology Laboratory, Charité-Universitätsmedizin Berlin, Germany; Laboratory of Neuropsychiatry (G.S.), IRCCS Santa Lucia Foundation, Rome, Italy; Division of Neuropsychiatry (G.S.), Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX; Department of Medicine (C.M.S.), University of Auckland, New Zealand; Department of Psychiatry (W.K.T.), Faculty of Medicine, The Chinese University of Hong Kong; Department of Physical Therapy and Neuroscience (G.T.T.), University of the Sciences, Philadelphia, PA; Department of Clinical and Behavioral Neurology (D.V.), IRCCS Santa Lucia Foundation, Rome, Italy; UCL Queen Square Institute of Neurology (N.S.W.), London, United Kingdom; Department of Psychology (L.T.W.), University of Oslo, Norway; Department of Neurology & RNEL (G.F.W.), University of Pittsburgh; GRECC/HERL (G.F.W.), VA Pittsburgh Healthcare System, PA; Department of Rehabilitation Medicine Division of Physical Therapy (M.R.B., S.L.W.), Department of Rehabilitation Medicine, Division of Geriatric Medicine (S.L.W.), Department of Medicine, and Department of Cell Biology (S.L.W.), Emory University School of Medicine; Center for Visual and Neurocognitive Rehabilitation (S.L.W.), Atlanta VA Health Care System, GA; and Department of Neurology (S.C.C.), University of California, Los Angeles. Giuseppe Barisano is currently at the department of Neurosurgery, Stanford Medicine, Stanford University, CA; Kathryn Hayward is currently at the departments of Physiotherapy and Medicine (RMH), University of Melbourne, Parkville, Victoria, Australia; and Gregory T. Thielman is currently at Physical Therapy and Neuroscience, School of Health Professions, Saint Joseph's University, Philadelphia, PA.
Background And Objectives: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance.
View Article and Find Full Text PDFGenetic effects on the timing of parturition and links to fetal birth weight.
Nat Genet
April 2023
Department of Obstetrics and Gynaecology, Sahlgrenska Academy, Institute of Clinical Science, University of Gothenburg, Gothenburg, Sweden.
Article Synopsis
- - The study investigates the genetic factors influencing the timing of parturition, finding 22 genetic loci associated with gestational duration from a large sample of almost 200,000 participants.
- - A meta-analysis of preterm delivery cases identified six genetic loci and highlighted similarities between genetic influences on gestational duration and preterm birth.
- - The research reveals that maternal genetics play a significant role in gestational timing, with some variants negatively impacting fetal birth weight, indicating a complex interaction between maternal and fetal genetics.
Acetone-Gasoline Blend as an Alternative Fuel in SI Engines: A Novel Comparison of Performance, Emission, and Lube Oil Degradation.
ACS Omega
March 2023
Faculty of Energy and Fuels, AGH University of Science and Technology, Mickiewicza 30, 30-059 Krakow, Poland.
The disproportionate use of petroleum products and stringent exhaust emissions has emphasized the need for alternative green fuels. Although several studies have been conducted to ascertain the performance of acetone-gasoline blends in spark-ignition (SI) engines, limited work has been done to determine the influence of fuel on lubricant oil deterioration. The current study fills the gap through lubricant oil testing by running the engine for 120 h on pure gasoline (G) and gasoline with 10% by volume acetone (A10).
View Article and Find Full Text PDFLate-Onset Psoriatic Arthritis: Are There Any Distinct Characteristics? A Retrospective Cohort Data Analysis.
Life (Basel)
March 2023
Centre for Rheumatic Diseases, School of Immunology and Microbial Sciences, King's College Hospital, London SE1 9RT, UK.
Article Synopsis
- The study investigates the differences between late-onset (diagnosed at age 60 or older) and earlier-onset psoriatic arthritis (PsA) patients in terms of clinical features, treatment, and comorbidities.
- The analysis included 281 PsA patients from two rheumatology centers, finding that 14.2% had late-onset PsA, with no significant differences in demographics or initial clinical features at diagnosis.
- While late-onset PsA patients had fewer cases of enthesitis, they had higher risks for dyslipidemia and major cardiovascular events compared to those diagnosed earlier, highlighting that age at diagnosis can impact disease progression and health risks.
Response by Tabák et al to Letters Regarding Article, "Risk of Macrovascular and Microvascular Disease in Diabetes Diagnosed Using Oral Glucose Tolerance Test With and Without Confirmation by Hemoglobin A1c: The Whitehall II Cohort Study".
Circulation
March 2023
Brain Sciences, University College London, United Kingdom (A.G.T., M.K.).
The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.
Nat Genet
March 2023
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis.
View Article and Find Full Text PDFThe management of atrial fibrillation (AF), the most common sustained arrhythmia, impacts healthcare resource utilization (HCRU). This study aims to estimate global resource use in AF patients, using the GARFIELD-AF registry. A prospective cohort study was conducted to characterize HCRU in AF patients enrolled in sequential cohorts from 2012 to 2016 in 35 countries.
View Article and Find Full Text PDFNirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors.
N Engl J Med
March 2023
From Sarcoma Medical Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York (M.G.), and Northwell Health Cancer Institute, New Hyde Park (T.P.) - all in New York; the Department of Sarcoma Medical Oncology, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston (R.R.); the Department of Oncology, McGill University, Montreal (T.A.); the Department of General Medical Oncology, University Hospitals Leuven, KU Leuven, Leuven (P.S.), the Department of Medical Oncology, Ghent University Hospital, Ghent University, Ghent (L.L.), and King Albert II Cancer Institute, Cliniques Universitaires Saint-Luc, Catholic University of Louvain, Brussels (F.M.) - all in Belgium; the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (W.T.G.), and the Department of Medical Oncology, Leiden University Medical Center, Leiden (H.G.) - both in the Netherlands; the Department of Medicine, University of Colorado Cancer Center, Aurora (B.A.W.); Duke Cancer Institute, Duke University Medical Center (R.F.R.), and PharPoint Research (S.M.) - both in Durham, NC; SpringWorks Therapeutics, Stamford (A.L., L.M.S.), and Smilow Cancer Hospital, Yale Cancer Center, Yale School of Medicine, Yale University, New Haven (H.D.) - both in Connecticut; the Department of Hematology and Oncology, Mayo Clinic, Jacksonville (S.A.), and Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami (G.D.) - both in Florida; the Sarcoma Oncology Center, Santa Monica (S.C.), the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (N.F.), and the Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford (N.Q.B.) - all in California; the Sarcoma and Bone Cancer Treatment Center, Dana-Farber Cancer Institute and Harvard Medical School (P.M.), and the Henri and Belinda Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center (G.M.C.) - both in Boston; Washington University in St. Louis, St. Louis (B.A.V.T.); the Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, and Fondazione Policlinico Universitario Campus Bio-Medico - both in Rome (B.V.), the Osteoncology, Bone and Soft Tissue Sarcoma, and Innovative Therapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna (E.P.), the Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (S.S.), and Medical Oncology, Candiolo Cancer Institute FPO-IRCCS, Candiolo (G.G.) - all in Italy; the Royal Marsden NHS Foundation Trust (C.B.) and the Department of Medical Oncology, University College London Hospital Foundation Trust (P.D.) - both in London; the University of Michigan Rogel Cancer Center, Ann Arbor (R.C.); the Ohio State University Comprehensive Cancer Center, Columbus (G.T.), and the Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati (J.G.P.); the Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee (J.C.), and the University of Wisconsin Carbone Cancer Center, Madison (H.H.B.); the Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia (L.H.), and the University of Pittsburgh Medical Center, Pittsburgh (M.A.B.); the Sarcoma Center Berlin-Brandenburg, Helios Klinikum Berlin-Buch, Berlin (P.R.), and the University of Heidelberg, Mannheim University Medical Center, Mannheim Cancer Center, Sarcoma Unit, Mannheim (B.K.) - both in Germany; the Knight Cancer Institute, Oregon Health and Science University, Portland (L.E.D., S.K.); and the Division of Medical Oncology, University of Washington, the Clinical Research Division, Fred Hutchinson Cancer Research Center, and Seattle Cancer Care Alliance, Seattle (E.L.).
Article Synopsis
- * ! The trial showed that nirogacestat significantly improved progression-free survival (76% event-free at 2 years) compared to placebo (44%), with a higher rate of objective responses (41% vs. 8%).
- * ! While nirogacestat had notable benefits, it also caused common side effects like diarrhea (84%) and nausea (54%), and 75% of women of childbearing potential experienced issues related to ovarian function.
Codon-specific KRAS mutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer.
Nat Med
March 2023
Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK.
Article Synopsis
- Genomics is transforming cancer treatment, but solid, clinical-grade genomic biomarkers for chemotherapy are still needed.
- A study with 37 patients found KRAS mutations linked to resistance against the chemotherapy trifluridine/tipiracil (FTD/TPI), and a larger real-world analysis with 960 patients confirmed that these mutations correspond to lower survival rates.
- Data from a phase 3 trial with 800 patients showed that those with KRAS mutations did not benefit from FTD/TPI, indicating that identifying these mutations could guide treatment decisions for around 28% of metastatic colorectal cancer patients.
Perceptions and reasons for quitting and transitioning between smoking and smokeless tobacco products: Findings from four waves of the ITC Bangladesh survey.
Tob Induc Dis
February 2023
Public Health Policy Evaluation Unit, School of Public Health, Imperial College London, London, United Kingdom.
Introduction: Transitions between different tobacco products are frequent among tobacco users in Bangladesh; however, the reasons leading to such transitions and why they quit are not well researched. The aim of the study is to examine perceptions and reasons reported by tobacco users in Bangladesh to transition to other products or quit.
Methods: Data from four waves (2009-2015) of the International Tobacco Control (ITC) Bangladesh Survey were used.
Hypothesis-free phenotype prediction within a genetics-first framework.
Nat Commun
February 2023
MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Cohort-wide sequencing studies have revealed that the largest category of variants is those deemed 'rare', even for the subset located in coding regions (99% of known coding variants are seen in less than 1% of the population. Associative methods give some understanding how rare genetic variants influence disease and organism-level phenotypes. But here we show that additional discoveries can be made through a knowledge-based approach using protein domains and ontologies (function and phenotype) that considers all coding variants regardless of allele frequency.
View Article and Find Full Text PDFEfficient clinical-grade γ-retroviral vector purification by high-speed centrifugation for CAR T cell manufacturing.
Mol Ther Methods Clin Dev
March 2023
Autolus Limited, The MediaWorks, 191 Wood Lane, London W12 7FP, UK.
γ-Retroviral vectors (γ-RV) are powerful tools for gene therapy applications. Current clinical vectors are produced from stable producer cell lines which require minimal further downstream processing, while purification schemes for γ-RV produced by transient transfection have not been thoroughly investigated. We aimed to develop a method to purify transiently produced γ-RV for early clinical studies.
View Article and Find Full Text PDFSpecific clinical vignettes in high-risk protected percutaneous coronary intervention.
Eur Heart J Suppl
November 2022
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua Medical School, Italy.
There are several cardiac- and patient-related factors that come into play when considering patients for protected percutaneous coronary intervention (PCI). Cardiac factors include complexity/location of coronary lesions, the degree of left or right ventricular impairment, the presence of valvular lesions, and ventricular arrhythmias. Patient related factors include comorbidities that would render the patient at a higher risk of death should cardiogenic shock ensue during the procedure.
View Article and Find Full Text PDFClinical, Neuroimaging, and Genetic Markers in Cerebral Amyloid Angiopathy-Related Inflammation: A Systematic Review and Meta-Analysis.
Stroke
January 2023
Second Department of Neurology (A.T., L.P., C.Z., G.P.P., G.T.), National & Kapodistrian University of Athens, "Attikon" University Hospital, Greece.
Background: There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri.
Methods: A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings.
On-treatment Comparative Effectiveness of Vitamin K Antagonists and Direct Oral Anticoagulants in GARFIELD-VTE, and Focus on Cancer and Renal Disease.
TH Open
October 2022
Thrombosis Research Institute, London, United Kingdom.
Direct oral anticoagulants (DOACs) provide a safe, effective alternative to vitamin K antagonists (VKAs) for venous thromboembolism (VTE) treatment, as shown via intention-to-treat comparative effectiveness analysis. However, on-treatment analysis is imperative in observational studies because anticoagulation choice and duration are at investigators' discretion. The aim of the study is to compare the effectiveness of DOACs and VKAs on 12-month outcomes in VTE patients using on-treatment analysis.
View Article and Find Full Text PDFPembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer.
Cancer Sci
March 2023
Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
The phase 3 KEYNOTE-177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite-instability-high (MSI-H)/mismatch-repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS).
View Article and Find Full Text PDFThe International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis.
Phytomedicine
January 2023
Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Xinchuan Road 2222, Chengdu, Sichuan, China. Electronic address:
Article Synopsis
- Digital technologies and open innovation have led to the creation of virtual organizations, exemplified by the International Natural Product Sciences Taskforce (INPST), established in 2018 for collaboration in natural product research.
- The INPST utilized Twitter for a week-long networking event in June 2021, using the hashtag #INPST to facilitate interactions among participants.
- Analysis of the event revealed 6,036 tweets from 686 users, resulting in over 65 million impressions, highlighting Twitter's effectiveness for hosting international biomedical research discussions.
A saturated map of common genetic variants associated with human height.
Nature
October 2022
Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.
Article Synopsis
- Common SNPs may account for 40-50% of human height variation, and this study identifies 12,111 SNPs linked to height from a large sample of 5.4 million individuals.
- These SNPs cluster in 7,209 genomic segments, encompassing about 21% of the genome and showing varying densities enriched in relevant genes.
- While these SNPs explain a substantial portion of height variance in European populations (40-45%), their predictive power is lower (10-24%) in other ancestries, suggesting a need for more research to enhance understanding in diverse populations.