Showing papers by "University of Colorado Denver published in 2020"
TL;DR: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates, and there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries.
5,802 citations
Christopher J L Murray1, Christopher J L Murray2, Christopher J L Murray3, Aleksandr Y. Aravkin3 +2269 more•Institutions (286)
TL;DR: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure.
3,059 citations
Centers for Disease Control and Prevention1, University of Arizona2, University of Arkansas for Medical Sciences3, Colorado Department of Public Health and Environment4, University of Colorado Denver5, Johns Hopkins University6, University of Minnesota7, Washington University in St. Louis8, Rutgers University9, University of North Carolina at Chapel Hill10, Vanderbilt University11, University of Wisconsin-Madison12
TL;DR: The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014, highlighting the variability in the evaluation and detection of ASD across communities and between sociodemographic groups.
Abstract: Problem/condition Autism spectrum disorder (ASD). Period covered 2016. Description of system The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Results For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] ≤70); this percentage was higher among girls than boys (39% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively) [corrected]. Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ ≤70 had a later median age at ASD diagnosis than white children with IQ ≤70 (48 months versus 42 months). Interpretation The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children. Public health action These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services.
2,613 citations
United States Public Health Service1, Emory University2, Rutgers University3, Harvard University4, Central Michigan University5, Westchester Medical Center6, Icahn School of Medicine at Mount Sinai7, New York University8, Saint Barnabas Medical Center9, University of Pennsylvania10, SUNY Downstate Medical Center11, Yale University12, University of Colorado Denver13, Boston Children's Hospital14, Case Western Reserve University15, Louisiana State University16, University of Washington17, Johns Hopkins University18, University of Texas Health Science Center at Houston19, University of Mississippi20, Tufts University21, Vanderbilt University22
TL;DR: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents.
Abstract: Background Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19)...
1,887 citations
Harvard University1, Memorial Sloan Kettering Cancer Center2, Northwestern University3, University of Nebraska Medical Center4, University of Texas MD Anderson Cancer Center5, Beth Israel Deaconess Medical Center6, University of Alabama at Birmingham7, University of Colorado Denver8, Fred Hutchinson Cancer Research Center9, University of California, San Francisco10, University of Pittsburgh11, Northside Hospital12, Bristol-Myers Squibb13, City of Hope National Medical Center14
TL;DR: Overall safety and activity of liso-cel did not differ by dose level, with a high objective response rate, and a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory large B-cell lymphomas.
950 citations
United States Department of Energy1, Vanderbilt University2, Harvard University3, Wake Forest University4, Hennepin County Medical Center5, Tufts University6, Yeshiva University7, Ohio State University8, University of Washington9, Stanford University10, Oregon Health & Science University11, University of California, Los Angeles12, Primary Children's Hospital13, Johns Hopkins University14, University of Colorado Denver15
TL;DR: It is indicated that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults, and effective public health messaging targeting these groups is warranted.
Abstract: Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.
945 citations
Tulane University1, Cedars-Sinai Medical Center2, National Institutes of Health3, University of Arizona4, Karolinska Institutet5, Brigham and Women's Hospital6, Georgia State University7, University of Colorado Denver8, Washington University in St. Louis9, Johns Hopkins University10, University of Modena and Reggio Emilia11, University of Illinois at Chicago12, University of Texas Health Science Center at Houston13, University of Zurich14, Charité15, Georgetown University16, Veterans Health Administration17, Duke University18
TL;DR: Clinicians and researchers are guided to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine, which will benefit men's and women's health.
781 citations
Queen's University1, University of Texas Southwestern Medical Center2, Osaka University3, Ben-Gurion University of the Negev4, VU University Amsterdam5, University of Milan6, University of São Paulo7, Laval University8, Harvard University9, University of Surrey10, University of Padua11, University of New South Wales12, University of Colorado Denver13
TL;DR: The evidence is summarized that waist circumference and BMI together can provide improved assessments of cardiometabolic risk compared with either measurement alone, and it is recommended that health professionals are trained to properly perform this simple measurement in clinical practice.
Abstract: Despite decades of unequivocal evidence that waist circumference provides both independent and additive information to BMI for predicting morbidity and risk of death, this measurement is not routinely obtained in clinical practice. This Consensus Statement proposes that measurements of waist circumference afford practitioners with an important opportunity to improve the management and health of patients. We argue that BMI alone is not sufficient to properly assess or manage the cardiometabolic risk associated with increased adiposity in adults and provide a thorough review of the evidence that will empower health practitioners and professional societies to routinely include waist circumference in the evaluation and management of patients with overweight or obesity. We recommend that decreases in waist circumference are a critically important treatment target for reducing adverse health risks for both men and women. Moreover, we describe evidence that clinically relevant reductions in waist circumference can be achieved by routine, moderate-intensity exercise and/or dietary interventions. We identify gaps in the knowledge, including the refinement of waist circumference threshold values for a given BMI category, to optimize obesity risk stratification across age, sex and ethnicity. We recommend that health professionals are trained to properly perform this simple measurement and consider it as an important 'vital sign' in clinical practice.
619 citations
Australian National University1, Argonne National Laboratory2, Scripps Health3, Iowa State University4, Western New England University5, Michigan State University6, National Institute of Advanced Industrial Science and Technology7, Microsoft8, University of Colorado Denver9, Oak Ridge National Laboratory10, Pacific Northwest National Laboratory11, University of Nebraska–Lincoln12, Nanjing University13, Sandia National Laboratories14, Moscow State University15, Kyocera16, Cray17, Purdue University18, Old Dominion University19, University of Rochester20
TL;DR: A discussion of many of the recently implemented features of GAMESS (General Atomic and Molecular Electronic Structure System) and LibCChem (the C++ CPU/GPU library associated with GAMESS) is presented, which include fragmentation methods, hybrid MPI/OpenMP approaches to Hartree-Fock, and resolution of the identity second order perturbation theory.
Abstract: A discussion of many of the recently implemented features of GAMESS (General Atomic and Molecular Electronic Structure System) and LibCChem (the C++ CPU/GPU library associated with GAMESS) is presented. These features include fragmentation methods such as the fragment molecular orbital, effective fragment potential and effective fragment molecular orbital methods, hybrid MPI/OpenMP approaches to Hartree-Fock, and resolution of the identity second order perturbation theory. Many new coupled cluster theory methods have been implemented in GAMESS, as have multiple levels of density functional/tight binding theory. The role of accelerators, especially graphical processing units, is discussed in the context of the new features of LibCChem, as it is the associated problem of power consumption as the power of computers increases dramatically. The process by which a complex program suite such as GAMESS is maintained and developed is considered. Future developments are briefly summarized.
575 citations
TL;DR: A series of three patients with severe COVID‐19 respiratory failure who were treated with tissue plasminogen activator had a temporally related improvement in their respiratory status, with one of them being a durable response.
469 citations
TL;DR: In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone.
Abstract: Background Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and ...
Boston University1, University of Virginia2, Icahn School of Medicine at Mount Sinai3, University of Pennsylvania4, Brighton and Sussex Medical School5, Harvard University6, Johns Hopkins University7, Cleveland Clinic8, Vanderbilt University9, Maastricht University10, University of Iowa11, Medical University of South Carolina12, Albany Medical College13, University of Colorado Denver14, University of California, San Francisco15, Aarhus University16, Ohio State University17, Kaiser Permanente18, Morehouse School of Medicine19, University of Cincinnati20
TL;DR: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis.
Abstract: Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or mo...
TL;DR: This practice guideline/guidance constitutes an update of the guidelines on AIH published in 2010 by the American Association for the Study of Liver Diseases (AASLD) and updates the epidemiology, diagnosis, management, and outcomes of AIH in adults and children.
University of Colorado Denver1, Scott & White Hospital2, Duke University3, University of Pennsylvania4, Brigham and Women's Hospital5, Beaumont Hospital6, University of Michigan7, Piedmont Hospital8, University of Missouri–Kansas City9, Columbia University10, American College of Cardiology11, Society of Thoracic Surgeons12, University of California, San Francisco13
TL;DR: The STS-ACC TVT Registry from 2011 to 2019 has collected data on 276,316 patients undergoing transcatheter aortic valve replacement (TAVR) at sites in all U.S. states, and TAVR now extends from extreme- to low-risk patients.
TL;DR: This commentary draws on the lessons of the policy sciences literature to understand the dynamics related to COVID-19, exploring the ways in which scientific and technical expertise, emotions, and narratives influence policy decisions and shape relationships among citizens, organizations, and governments.
Abstract: The world is in the grip of a crisis that stands unprecedented in living memory. The COVID-19 pandemic is urgent, global in scale, and massive in impacts. Following Harold D. Lasswell's goal for the policy sciences to offer insights into unfolding phenomena, this commentary draws on the lessons of the policy sciences literature to understand the dynamics related to COVID-19. We explore the ways in which scientific and technical expertise, emotions, and narratives influence policy decisions and shape relationships among citizens, organizations, and governments. We discuss varied processes of adaptation and change, including learning, surges in policy responses, alterations in networks (locally and globally), implementing policies across transboundary issues, and assessing policy success and failure. We conclude by identifying understudied aspects of the policy sciences that deserve attention in the pandemic's aftermath.
National Institute for Health Research1, National Institutes of Health2, University of Sydney3, Royal Prince Alfred Hospital4, University of Colorado Denver5, Bristol-Myers Squibb6, Heidelberg University7, Regeneron8, Columbia University Medical Center9, Hoffmann-La Roche10, Claude Bernard University Lyon 111
TL;DR: A multicentre, double-blind, randomised, placebo-controlled phase 2 trial to assess the efficacy and safety of pirfenidone in patients with progressive fibrosing unclassifiable ILD, which is characterised by progressive fibrosis of the lung.
TL;DR: This cross-sectional study examines trends in emergency department visits and visits that led to hospitalizations during a 4-month period leading up to and during the COVID-19 outbreak in the US.
Abstract: Importance As coronavirus disease 2019 (COVID-19) spread throughout the US in the early months of 2020, acute care delivery changed to accommodate an influx of patients with a highly contagious infection about which little was known. Objective To examine trends in emergency department (ED) visits and visits that led to hospitalizations covering a 4-month period leading up to and during the COVID-19 outbreak in the US. Design, Setting, and Participants This retrospective, observational, cross-sectional study of 24 EDs in 5 large health care systems in Colorado (n = 4), Connecticut (n = 5), Massachusetts (n = 5), New York (n = 5), and North Carolina (n = 5) examined daily ED visit and hospital admission rates from January 1 to April 30, 2020, in relation to national and the 5 states’ COVID-19 case counts. Exposures Time (day) as a continuous variable. Main Outcomes and Measures Daily counts of ED visits, hospital admissions, and COVID-19 cases. Results A total of 24 EDs were studied. The annual ED volume before the COVID-19 pandemic ranged from 13 000 to 115 000 visits per year; the decrease in ED visits ranged from 41.5% in Colorado to 63.5% in New York. The weeks with the most rapid rates of decrease in visits were in March 2020, which corresponded with national public health messaging about COVID-19. Hospital admission rates from the ED were stable until new COVID-19 case rates began to increase locally; the largest relative increase in admission rates was 149.0% in New York, followed by 51.7% in Massachusetts, 36.2% in Connecticut, 29.4% in Colorado, and 22.0% in North Carolina. Conclusions and Relevance From January through April 2020, as the COVID-19 pandemic intensified in the US, temporal associations were observed with a decrease in ED visits and an increase in hospital admission rates in 5 health care systems in 5 states. These findings suggest that practitioners and public health officials should emphasize the importance of visiting the ED during the COVID-19 pandemic for serious symptoms, illnesses, and injuries that cannot be managed in other settings.
Baylor College of Medicine1, Oakland University2, Scripps Health3, Beth Israel Deaconess Medical Center4, Emory University5, Ochsner Medical Center6, Cedars-Sinai Medical Center7, University of Texas Health Science Center at San Antonio8, University of Alabama at Birmingham9, University of Washington10, University of Miami11, Washington University in St. Louis12, Icahn School of Medicine at Mount Sinai13, University of Colorado Denver14, University of California, Irvine15, Grady Memorial Hospital16
TL;DR: The objective of this study was to establish a baseline for the development of a strategy to manage the inflammatory bowel disease-related complications of type 2 diabetes using a proprotein convertase-like mechanism.
TL;DR: Weight gain is ubiquitous in clinical trials of ART initiation and is multifactorial in nature, with demographic factors, HIV-related factors, and the composition of ART regimens as contributors.
Abstract: Background Initiation of antiretroviral therapy (ART) often leads to weight gain. While some of this weight gain may be an appropriate return-to-health effect, excessive increases in weight may lead to obesity. We sought to explore factors associated with weight gain in several randomized comparative clinical trials of ART initiation. Methods We performed a pooled analysis of weight gain in 8 randomized controlled clinical trials of treatment-naive people living with human immunodeficiency virus (HIV) initiating ART between 2003 and 2015, comprising >5000 participants and 10 000 person-years of follow-up. We used multivariate modeling to explore relationships between demographic factors, HIV disease characteristics, and ART components and weight change following ART initiation. Results Weight gain was greater in more recent trials and with the use of newer ART regimens. Pooled analysis revealed baseline demographic factors associated with weight gain including lower CD4 cell count, higher HIV type 1 RNA, no injection drug use, female sex, and black race. Integrase strand transfer inhibitor use was associated with more weight gain than were protease inhibitors or nonnucleoside reverse transcriptase inhibitors (NNRTIs), with dolutegravir and bictegravir associated with more weight gain than elvitegravir/cobicistat. Among the NNRTIs, rilpivirine was associated with more weight gain than efavirenz. Among nucleoside/nucleotide reverse transcriptase inhibitors, tenofovir alafenamide was associated with more weight gain than tenofovir disoproxil fumarate, abacavir, or zidovudine. Conclusions Weight gain is ubiquitous in clinical trials of ART initiation and is multifactorial in nature, with demographic factors, HIV-related factors, and the composition of ART regimens as contributors. The mechanisms by which certain ART agents differentially contribute to weight gain are unknown.
University of Colorado Denver1, University of South Florida2, National Institutes of Health3, University of Leicester4, Federal University of Paraná5, Monash University6, Emory University7, University of Rochester8, University of Newcastle9, McMaster University10, Wake Forest University11, Cochrane Collaboration12, University of Bern13, University of Arizona14, Laval University15, University of California, San Francisco16, Washington University in St. Louis17, University of Southampton18, Boston Children's Hospital19, University of Wisconsin-Madison20, Hokkaido University21, Zhejiang University22, University of Pittsburgh23
TL;DR: Clinical recommendations for the management of severe asthma are provided and the use of novel therapies for severe asthma, specifically biologicals for type 2 high asthma, and antimuscarinic agents and macrolides, as well as on biomarkers for predicting treatment response are made.
Abstract: This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force9s questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using a blood eosinophil cut-point ≥150 μL−1 to guide anti-IL-5 initiation in adult patients with severe asthma; 3) suggest considering specific eosinophil (≥260 μL−1) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy; 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4–5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies; 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.
TL;DR: COVID-19 has enabled the spread of racism and created national insecurity, fear of foreigners, and general xenophobia, which may be related to the increase in anti-Asian hate crimes during the pandemic.
Abstract: Coronavirus Disease 2019 (COVID-19) is believed to have emerged in Wuhan, China in late December 2019 and began rapidly spreading around the globe throughout the spring months of 2020. As COVID-19 proliferated across the United States, Asian Americans reported a surge in racially motivated hate crimes involving physical violence and harassment. Throughout history, pandemic-related health crises have been associated with the stigmatization and “othering” of people of Asian descent. Asian Americans have experienced verbal and physical violence motivated by individual-level racism and xenophobia from the time they arrived in America in the late 1700s up until the present day. At the institutional level, the state has often implicitly reinforced, encouraged, and perpetuated this violence through bigoted rhetoric and exclusionary policies. COVID-19 has enabled the spread of racism and created national insecurity, fear of foreigners, and general xenophobia, which may be related to the increase in anti-Asian hate crimes during the pandemic. We examine how these crimes – situated in historically entrenched and intersecting individual-level and institutional-level racism and xenophobia – have operated to “other” Asian Americans and reproduce inequality.
TL;DR: This initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.
Abstract: BACKGROUNDReprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocksMETHODSTo investigate metabolic effects of SARS-CoV-2 infection, we evaluated serum metabolites of patients with COVID-19 (n = 33; diagnosed by nucleic acid testing), as compared with COVID-19-negative controls (n = 16)RESULTSTargeted and untargeted metabolomics analyses identified altered tryptophan metabolism into the kynurenine pathway, which regulates inflammation and immunity Indeed, these changes in tryptophan metabolism correlated with interleukin-6 (IL-6) levels Widespread dysregulation of nitrogen metabolism was also seen in infected patients, with altered levels of most amino acids, along with increased markers of oxidant stress (eg, methionine sulfoxide, cystine), proteolysis, and renal dysfunction (eg, creatine, creatinine, polyamines) Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis Interestingly, metabolite levels in these pathways correlated with clinical laboratory markers of inflammation (ie, IL-6 and C-reactive protein) and renal function (ie, blood urea nitrogen)CONCLUSIONIn conclusion, this initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targetsFUNDINGBoettcher Foundation Webb-Waring Biomedical Research Award; National Institute of General and Medical Sciences, NIH; and National Heart, Lung, and Blood Institute, NIH
TL;DR: The understanding of SARS‐CoV‐2 neuropathogenesis is still incomplete and knowledge is evolving rapidly, it is hoped that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID‐19.
Abstract: In less than 6 months, the severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID-19) also involves multiple other organs, including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS-CoV-2 infection is rapidly accumulating. These may result from a variety of mechanisms, including virus-induced hyperinflammatory and hypercoagulable states, direct virus infection of the central nervous system (CNS), and postinfectious immune mediated processes. Example of COVID-19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis, and endothelialitis. In the peripheral nervous system, COVID-19 is associated with dysfunction of smell and taste, muscle injury, the Guillain-Barre syndrome, and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID-19 poses a global threat to the entire nervous system. Although our understanding of SARS-CoV-2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID-19. ANN NEUROL 2020;88:1-11 ANN NEUROL 2020;88:1-11.
TL;DR: There is overwhelming evidence linking the NLRP3 inflammasome and the IL-1 cytokines with the pathogenetic role of atherosclerosis, in ischemic (acute myocardial infarction), and nonischemic injury to the myocardium (myocarditis) and the progression to heart failure.
Abstract: The intracellular sensing protein termed NLRP3 (for NACHT, LRR, and PYD domains-containing protein 3) forms a macromolecular structure called the NLRP3 inflammasome. The NLRP3 inflammasome plays a ...
University of Colorado Denver1, Boston University2, Paris Diderot University3, University of Texas System4, University of Zurich5, McMaster University6, University of Texas Health Science Center at San Antonio7, Pierre-and-Marie-Curie University8, University Health Network9, Bellvitge University Hospital10, Duke University11, Radboud University Nijmegen12, University of Freiburg13, Oregon Health & Science University14
TL;DR: This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, MycOBacterium kansasii, and Myc Cobacterium xenopi among the slowly growing NTM and MyCobacterius abscessus among the rapidly growing N TM.
Abstract: Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
Vanderbilt University1, Primary Children's Hospital2, University of Utah3, University of Pittsburgh4, Johns Hopkins University5, University of California, Los Angeles6, Duke University7, Harvard University8, Wake Forest University9, University of Colorado Denver10, Yeshiva University11, Oregon Health & Science University12, University of Washington13, University of California, San Francisco14, University of Michigan15, University of Massachusetts Medical School16
TL;DR: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14, and these findings do not support the use of hydroxy chloroquine for treatment of CO VID-19 among hospitalized adults.
Abstract: Importance Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, −0.2% [95% CI, −5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration ClinicalTrials.gov:NCT04332991
TL;DR: Recommendations for a systematic approach for the care of patients with an acute myocardial infarction (AMI) during the COVID-19 pandemic are provided.
Northwestern University1, Huntsman Cancer Institute2, Aix-Marseille University3, University of Texas MD Anderson Cancer Center4, Mayo Clinic5, University of Washington6, University of Colorado Denver7, Erasmus University Rotterdam8, Harvard University9, University of California, San Francisco10, University of Düsseldorf11, All India Institute of Medical Sciences12, Heidelberg University13, University of Zurich14
TL;DR: This exhibition celebrates the 50th anniversary of the publication of the first book of this kind to be published in the United States, edited by David N. Louis and written by Andreas von Deimling.
Abstract: Daniel J. Brat1 · Kenneth Aldape2 · Howard Colman3 · Dominique Figrarella‐Branger4 · Gregory N. Fuller5 · Caterina Giannini6 · Eric C. Holland7 · Robert B. Jenkins6 · Bette Kleinschmidt‐DeMasters8 · Takashi Komori9 · Johan M. Kros10 · David N. Louis11 · Catriona McLean12 · Arie Perry13 · Guido Reifenberger14,15 · Chitra Sarkar16 · Roger Stupp17 · Martin J. van den Bent18 · Andreas von Deimling19,20 · Michael Weller21
Indiana University1, University of Michigan2, American Society of Clinical Oncology3, Virginia Commonwealth University4, Johns Hopkins University5, Juravinski Cancer Centre6, University of Texas MD Anderson Cancer Center7, University of Colorado Denver8, Lahey Hospital & Medical Center9, Beaumont Hospital10, University of Texas Southwestern Medical Center11, Princess Margaret Cancer Centre12, City of Hope National Medical Center13, Memorial Sloan Kettering Cancer Center14, Queen's University15, Post Graduate Institute of Medical Education and Research16, Sarah Cannon Research Institute17
TL;DR: This guideline update reflects changes in evidence since the previous guideline update and is conditional on the basis of histology, PD-L1 status, and/or the presence of contraindications.
Abstract: PURPOSEThe aim of this work is to provide evidence-based recommendations updating the 2017 ASCO guideline on systemic therapy for patients with stage IV non–small-cell lung cancer (NSCLC) without d...