Showing papers by "Vanderbilt University published in 2021"
Brigham and Women's Hospital1, Baylor College of Medicine2, Emory University3, University of Maryland, Baltimore4, Saint Louis University5, University of Illinois at Chicago6, George Washington University7, University of California, San Diego8, Vanderbilt University9, Fred Hutchinson Cancer Research Center10
TL;DR: The mRNA-1273 vaccine as discussed by the authors is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.
Abstract: Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).
2,721 citations
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
Harvard University1, State University of New York System2, French Institute of Health and Medical Research3, University of Toronto4, University of Texas Southwestern Medical Center5, Vanderbilt University6, Oregon Health & Science University7, University of Brescia8, Karolinska Institutet9, University of Paris10, Yale University11, Georgetown University12, Wrocław Medical University13, Duke University14, Lexicon Pharmaceuticals15, University of Michigan16
TL;DR: In patients with diabetes and recent worsening heart failure, sotagliflozin therapy, initiated before or shortly after discharge, resulted in a significantly lower total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure than placebo.
Abstract: Background Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure or death from cardiovascular causes among patients with stable heart failu...
913 citations
University of Washington1, St George’s University Hospitals NHS Foundation Trust2, McMaster University3, Agostino Gemelli University Polyclinic4, Emory University5, Federal University of São Paulo6, Ottawa Hospital7, St Thomas' Hospital8, University of Michigan9, Cooper University Hospital10, University of Kansas11, University of Amsterdam12, United Arab Emirates University13, University of Pittsburgh14, King Saud bin Abdulaziz University for Health Sciences15, University of São Paulo16, University of Minnesota17, Population Health Research Institute18, University of Toronto19, Humanitas University20, University of Kentucky21, Ghent University Hospital22, University of Tokyo23, Peking Union Medical College Hospital24, Hebron University25, Monash University26, Copenhagen University Hospital27, Liverpool School of Tropical Medicine28, Vanderbilt University29, Brigham and Women's Hospital30, Harvard University31, University of Ulsan32, University of Manitoba33, Makerere University34, Faculdade de Medicina de São José do Rio Preto35, Mount Sinai Hospital, Toronto36, Medanta37, University of the Witwatersrand38, New York University39, Washington University in St. Louis40, University of Alberta41, Hennepin County Medical Center42, University of Pennsylvania43, Hebrew University of Jerusalem44, Hadassah Medical Center45, Hochschule Hannover46, Brown University47
TL;DR: The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications as discussed by the authors, which are either strong or weak, or in the form of best practice statements.
Abstract: Background
Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.
Methods
We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.
Results
The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.
Conclusion
The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.
893 citations
TL;DR: It is shown that a family of causal effect parameters are identified in staggered DiD setups, even if differences in observed characteristics create non-parallel outcome dynamics between groups, and the asymptotic properties of the proposed estimators are established.
862 citations
TL;DR: In this article, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, the authors report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.
716 citations
University of Washington1, St George’s University Hospitals NHS Foundation Trust2, McMaster University3, Agostino Gemelli University Polyclinic4, Emory University5, Federal University of São Paulo6, Ottawa Hospital7, St Thomas' Hospital8, University of Michigan9, Cooper University Hospital10, University of Kansas11, University of Amsterdam12, United Arab Emirates University13, University of Pittsburgh14, King Saud bin Abdulaziz University for Health Sciences15, University of São Paulo16, University of Minnesota17, Population Health Research Institute18, University of Toronto19, Humanitas University20, University of Kentucky21, Ghent University Hospital22, University of Tokyo23, Peking Union Medical College Hospital24, Hebron University25, Monash University26, Copenhagen University Hospital27, Liverpool School of Tropical Medicine28, Vanderbilt University29, Brigham and Women's Hospital30, University of Ulsan31, University of Manitoba32, Makerere University33, Faculdade de Medicina de São José do Rio Preto34, National Institutes of Health35, Mount Sinai Hospital, Toronto36, Medanta37, University of the Witwatersrand38, New York University39, Washington University in St. Louis40, University of Alberta41, Hennepin County Medical Center42, Royal Brisbane and Women's Hospital43, University of Pennsylvania44, Hebrew University of Jerusalem45, Hochschule Hannover46, Brown University47
TL;DR: The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications as mentioned in this paper, which are either strong or weak, or in the form of best practice statements.
Abstract: Background
Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.
Methods
We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.
Results
The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.
Conclusion
The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.
664 citations
TL;DR: A small number of adults received two 100-μg injections of Moderna’s mRNA SARS-CoV-2 vaccine, and serum anti–spike protein and neutralizing antibody titers revealed immunogenicity and safety concerns.
Abstract: Immunogenicity and the mRNA-1273 SARS-CoV-2 Vaccine Thirty-four adults received two 100-μg injections of the mRNA-1273 SARS-CoV-2 vaccine, and serum anti–spike protein and neutralizing antibody tit...
637 citations
Northwestern University1, University of California, San Francisco2, University of Michigan3, City of Hope National Medical Center4, Vanderbilt University5, Seattle Cancer Care Alliance6, Fox Chase Cancer Center7, University of Wisconsin-Madison8, University of Texas Southwestern Medical Center9, University of Utah10, University of Nebraska Medical Center11, University of Alabama at Birmingham12, University of California, Los Angeles13, University of South Florida14, Mayo Clinic15, Washington University in St. Louis16, Yale Cancer Center17, Stanford University18, Case Western Reserve University19, University of Colorado Boulder20, Brigham and Women's Hospital21, Ohio State University22, Roswell Park Cancer Institute23, University of Texas MD Anderson Cancer Center24, Harvard University25, University of California, San Diego26, Memorial Sloan Kettering Cancer Center27, University of Pennsylvania28, University of Tennessee29, Johns Hopkins University30, Duke University31, National Comprehensive Cancer Network32
TL;DR: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section as discussed by the authors.
Abstract: This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.
589 citations
Harvard University1, State University of New York System2, University of Michigan3, University of Toronto4, University of Texas at Dallas5, Vanderbilt University6, Oregon Health & Science University7, Yale University8, University of Missouri–Kansas City9, Imperial College London10, Duke University11, University of Paris12
TL;DR: In patients with diabetes and chronic kidney disease, with or without albuminuria, sotagliflozin resulted in a lower risk of the composite of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart Failure than placebo but was associated with adverse events.
Abstract: Background The efficacy and safety of sodium–glucose cotransporter 2 inhibitors such as sotagliflozin in preventing cardiovascular events in patients with diabetes with chronic kidney dise...
541 citations
Mayo Clinic1, Johns Hopkins University2, Seattle Cancer Care Alliance3, University of Colorado Boulder4, University of Utah5, Fox Chase Cancer Center6, Northwestern University7, Case Western Reserve University8, University of Texas MD Anderson Cancer Center9, Brigham and Women's Hospital10, Duke University11, University of South Florida12, University of Texas Southwestern Medical Center13, Yale Cancer Center14, University of California, San Francisco15, Roswell Park Cancer Institute16, Harvard University17, University of Wisconsin-Madison18, University of Michigan19, Stanford University20, Vanderbilt University21, City of Hope National Medical Center22, Washington University in St. Louis23, University of Tennessee Health Science Center24, Ohio State University25, University of California, San Diego26, Memorial Sloan Kettering Cancer Center27, University of Pennsylvania28, University of California, Los Angeles29, National Comprehensive Cancer Network30
TL;DR: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC as mentioned in this paper.
Abstract: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.
United States Public Health Service1, Centers for Disease Control and Prevention2, Harvard University3, New York University4, University of Colorado Denver5, University of Texas at Dallas6, Nationwide Children's Hospital7, Johns Hopkins University8, Yale University9, Westchester Medical Center10, Rutgers University11, University of Alabama at Birmingham12, Children's Mercy Hospital13, University of Miami14, University of North Carolina at Chapel Hill15, Baylor College of Medicine16, University of Mississippi17, Vanderbilt University18, SUNY Downstate Medical Center19, California State University, Long Beach20, University of Minnesota21, Saint Barnabas Medical Center22, University of Arkansas for Medical Sciences23, Children's Hospital Oakland Research Institute24, Boston Children's Hospital25, University of Washington26, Central Michigan University27, Icahn School of Medicine at Mount Sinai28, University of Iowa29, Indiana University30, Emory University31, Medical University of South Carolina32, University of Pennsylvania33, Northwestern University34
TL;DR: In this article, the authors compared clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19) at 66 US hospitals in 31 states.
Abstract: Importance Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. Objective To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). Setting, Design, and Participants Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase–polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. Exposure SARS-CoV-2. Main Outcomes and Measures Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. Results Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7,P Conclusions and Relevance This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.
Fox Chase Cancer Center1, Vanderbilt University2, University of Tennessee Health Science Center3, University of Utah4, Washington University in St. Louis5, University of Pennsylvania6, University of Alabama at Birmingham7, Johns Hopkins University8, Roswell Park Cancer Institute9, University of California, Los Angeles10, Northwestern University11, University of Colorado Boulder12, Stanford University13, University of South Florida14, University of Texas MD Anderson Cancer Center15, University of California, San Francisco16, Duke University17, University of Michigan18, Seattle Cancer Care Alliance19, Memorial Sloan Kettering Cancer Center20, Case Western Reserve University21, University of Nebraska Medical Center22, Ohio State University23, Harvard University24, University of California, San Diego25, City of Hope National Medical Center26, Mayo Clinic27, University of Wisconsin-Madison28, Brigham and Women's Hospital29, National Comprehensive Cancer Network30
TL;DR: The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies as mentioned in this paper.
Abstract: The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.
Centers for Disease Control and Prevention1, United States Public Health Service2, Scientific Atlanta3, Emory University4, Veterans Health Administration5, Anschutz Medical Campus6, University of Rochester7, Ohio Department of Health8, Lake County9, New York State Department of Health10, University of California, Berkeley11, Vanderbilt University12, Oregon Health Authority13, New Mexico Department of Health14, Yale University15, Oak Ridge Institute for Science and Education16
TL;DR: Aggressive implementation of prevention strategies, including social distancing and rigorous hand hygiene, may benefit the population as a whole, as well as those at highest risk for COVID-19-related complications.
Abstract: Author(s): Kim, Lindsay; Garg, Shikha; O'Halloran, Alissa; Whitaker, Michael; Pham, Huong; Anderson, Evan J; Armistead, Isaac; Bennett, Nancy M; Billing, Laurie; Como-Sabetti, Kathryn; Hill, Mary; Kim, Sue; Monroe, Maya L; Muse, Alison; Reingold, Arthur L; Schaffner, William; Sutton, Melissa; Talbot, H Keipp; Torres, Salina M; Yousey-Hindes, Kimberly; Holstein, Rachel; Cummings, Charisse; Brammer, Lynnette; Hall, Aron J; Fry, Alicia M; Langley, Gayle E | Abstract: BackgroundCurrently, the United States has the largest number of reported coronavirus disease 2019 (COVID-19) cases and deaths globally. Using a geographically diverse surveillance network, we describe risk factors for severe outcomes among adults hospitalized with COVID-19.MethodsWe analyzed data from 2491 adults hospitalized with laboratory-confirmed COVID-19 between 1 March-2 May 2020, as identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network, which comprises 154 acute-care hospitals in 74 counties in 13 states. We used multivariable analyses to assess associations between age, sex, race and ethnicity, and underlying conditions with intensive care unit (ICU) admission and in-hospital mortality.ResultsThe data show that 92% of patients had ≥1 underlying condition; 32% required ICU admission; 19% required invasive mechanical ventilation; and 17% died. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84, and ≥85 years versus 18-39 years (adjusted risk ratios [aRRs], 1.53, 1.65, 1.84, and 1.43, respectively); male sex (aRR, 1.34); obesity (aRR, 1.31); immunosuppression (aRR, 1.29); and diabetes (aRR, 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84, and ≥ 85 years versus 18-39 years (aRRs, 3.11, 5.77, 7.67, and 10.98, respectively); male sex (aRR, 1.30); immunosuppression (aRR, 1.39); renal disease (aRR, 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR, 1.28); neurologic disorders (aRR, 1.25); and diabetes (aRR, 1.19).ConclusionsIn-hospital mortality increased markedly with increasing age. Aggressive implementation of prevention strategies, including social distancing and rigorous hand hygiene, may benefit the population as a whole, as well as those at highest risk for COVID-19-related complications.
University of California, San Francisco1, University of South Florida2, University of Michigan3, University of Tennessee Health Science Center4, Northwestern University5, Vanderbilt University6, Seattle Cancer Care Alliance7, City of Hope National Medical Center8, Duke University9, University of Colorado Boulder10, Ohio State University11, University of California, Los Angeles12, Fox Chase Cancer Center13, Harvard University14, Roswell Park Cancer Institute15, Case Western Reserve University16, Washington University in St. Louis17, University of Nebraska Medical Center18, Yale Cancer Center19, University of Wisconsin-Madison20, University of California, San Diego21, Pancreatic Cancer Action Network22, Johns Hopkins University23, University of Texas Southwestern Medical Center24, University of Alabama at Birmingham25, Memorial Sloan Kettering Cancer Center26, University of Utah27, Stanford University28, University of Pennsylvania29, University of Texas MD Anderson Cancer Center30, Brigham and Women's Hospital31, National Comprehensive Cancer Network32
Abstract: Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients' advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.
Harvard University1, University of Michigan2, Icahn School of Medicine at Mount Sinai3, Yeshiva University4, Rutgers University5, Seton Hall University6, University of Pennsylvania7, Cornell University8, Rush University Medical Center9, Anschutz Medical Campus10, Northwestern University11, Medical College of Wisconsin12, Rowan University13, Tufts University14, Thomas Jefferson University15, Ochsner Health System16, University of Queensland17, Johns Hopkins University18, New York University19, Indiana University – Purdue University Indianapolis20, ProMedica21, University of Vermont22, University of Miami23, Vanderbilt University24
TL;DR: Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilzumab, and the findings may be susceptible to unmeasured confounding.
Abstract: Importance Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. Objective To test whether tocilizumab decreases mortality in this population. Design, setting, and participants The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. Exposures Treatment with tocilizumab in the first 2 days of ICU admission. Main outcomes and measures Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. Results Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of Conclusions and relevance Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.
University of Colorado Boulder1, University of North Carolina at Chapel Hill2, University of Notre Dame3, University of South Florida4, Columbia University5, University of California, Irvine6, Rutgers University7, Stony Brook University8, University of Pittsburgh9, Yale University10, University of Oregon11, University of California, Berkeley12, Boston University13, Vanderbilt University14, University of Miami15, University of Minnesota16, Fordham University17, Harvard University18, Cornell University19, University of Michigan20, University of Central Florida21, University of California, Los Angeles22, University of Virginia23, Brown University24
TL;DR: COVID-19 is conceptualized as a unique, compounding, multidimensional stressor that will create a vast need for intervention and necessitate new paradigms for mental health service delivery and training.
Abstract: COVID-19 presents significant social, economic, and medical challenges. Because COVID-19 has already begun to precipitate huge increases in mental health problems, clinical psychological science must assert a leadership role in guiding a national response to this secondary crisis. In this article, COVID-19 is conceptualized as a unique, compounding, multidimensional stressor that will create a vast need for intervention and necessitate new paradigms for mental health service delivery and training. Urgent challenge areas across developmental periods are discussed, followed by a review of psychological symptoms that likely will increase in prevalence and require innovative solutions in both science and practice. Implications for new research directions, clinical approaches, and policy issues are discussed to highlight the opportunities for clinical psychological science to emerge as an updated, contemporary field capable of addressing the burden of mental illness and distress in the wake of COVID-19 and beyond. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Northwestern University1, Memorial Sloan Kettering Cancer Center2, University of Wisconsin-Madison3, University of South Florida4, Johns Hopkins University5, University of Nebraska Medical Center6, Mayo Clinic7, Vanderbilt University8, University of California, San Diego9, Case Western Reserve University10, Stanford University11, Ohio State University12, University of Tennessee Health Science Center13, Harvard University14, Washington University in St. Louis15, Roswell Park Cancer Institute16, University of Alabama at Birmingham17, University of California, San Francisco18, University of Utah19, University of Pennsylvania20, Duke University21, Seattle Cancer Care Alliance22, University of California, Los Angeles23, Fox Chase Cancer Center24, University of Michigan25, University of Colorado Boulder26, City of Hope National Medical Center27, Yale University28, University of Texas MD Anderson Cancer Center29, University of Texas Southwestern Medical Center30, National Comprehensive Cancer Network31
TL;DR: The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts as discussed by the authors.
Abstract: The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.
TL;DR: In this article, the authors used positron emission tomography (PET) tracers to measure the access to and uptake of glucose and glutamine by specific cell subsets in the TME.
Abstract: Cancer cells characteristically consume glucose through Warburg metabolism1, a process that forms the basis of tumour imaging by positron emission tomography (PET) Tumour-infiltrating immune cells also rely on glucose, and impaired immune cell metabolism in the tumour microenvironment (TME) contributes to immune evasion by tumour cells2–4 However, whether the metabolism of immune cells is dysregulated in the TME by cell-intrinsic programs or by competition with cancer cells for limited nutrients remains unclear Here we used PET tracers to measure the access to and uptake of glucose and glutamine by specific cell subsets in the TME Notably, myeloid cells had the greatest capacity to take up intratumoral glucose, followed by T cells and cancer cells, across a range of cancer models By contrast, cancer cells showed the highest uptake of glutamine This distinct nutrient partitioning was programmed in a cell-intrinsic manner through mTORC1 signalling and the expression of genes related to the metabolism of glucose and glutamine Inhibiting glutamine uptake enhanced glucose uptake across tumour-resident cell types, showing that glutamine metabolism suppresses glucose uptake without glucose being a limiting factor in the TME Thus, cell-intrinsic programs drive the preferential acquisition of glucose and glutamine by immune and cancer cells, respectively Cell-selective partitioning of these nutrients could be exploited to develop therapies and imaging strategies to enhance or monitor the metabolic programs and activities of specific cell populations in the TME Positron emission tomography measurements of nutrient uptake in cells of the tumour microenvironment reveal cell-intrinsic partitioning in which glucose uptake is higher in myeloid cells, whereas glutamine is preferentially acquired by cancer cells
University of California, San Diego1, Northwestern University2, University of Zurich3, University of Amsterdam4, Washington University in St. Louis5, Claude Bernard University Lyon 16, University of Colorado Denver7, United States Department of Veterans Affairs8, Katholieke Universiteit Leuven9, University of Padua10, Queen Mary University of London11, Vanderbilt University12, University of Bordeaux13, Ege University14, University of Michigan15, Universidad del Desarrollo16, Flinders University17, University of Pisa18, University of Chile19, Case Western Reserve University20, Sanjay Gandhi Post Graduate Institute of Medical Sciences21, Chulalongkorn University22, University of Melbourne23, University of Ulsan24, Cornell University25, Mayo Clinic26, New York University27, Monash University28, University of Alberta29, University of Bern30, Kosin University31, University of Milan32, University of South Florida33, Autonomous University of Barcelona34, University College Hospital35, University of Washington36, National University of Singapore37, The Chinese University of Hong Kong38, Sun Yat-sen University39
TL;DR: The Chicago Classification v4.4.0 as discussed by the authors is the most recent version of the Chicago Classification, which uses high-resolution manometry (HRM) for motility disorders.
Abstract: Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.
Vanderbilt University1, Scott & White Hospital2, Texas A&M University3, University of Colorado Denver4, University of Iowa5, Wake Forest University6, Johns Hopkins University7, Hennepin County Medical Center8, Yeshiva University9, University of Washington10, Tufts University11, University of Utah12, University of Michigan13, Oregon Health & Science University14, Emory University15, Cleveland Clinic16, Stanford University17, University of California, Los Angeles18, University of Miami19, Washington University in St. Louis20, Ohio State University21
TL;DR: In this paper, a case-control analysis was conducted among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021.
Abstract: Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization.
University of Utah1, University of Colorado Denver2, Oregon Health & Science University3, Harvard University4, University of California, San Diego5, University of Texas Health Science Center at Houston6, Medical College of Wisconsin7, Medical University of South Carolina8, Northwestern University9, Emory University10, University of Pennsylvania11, University of São Paulo12, Ghent University13, Sun Yat-sen University14, Karolinska Institutet15, University of Chicago16, Rush University Medical Center17, University of Barcelona18, University of California, Los Angeles19, Vanderbilt University20, University of Arizona21, University of Kansas22, Université de Montréal23, University of Auckland24, Rutgers University25, University of Amsterdam26, Columbia University27, Eastern Virginia Medical School28, University of New South Wales29, Katholieke Universiteit Leuven30, Guy's Hospital31, Stanford University32, University of British Columbia33, Mayo Clinic34, Johns Hopkins University35, Korea University36, Uniformed Services University of the Health Sciences37, Jikei University School of Medicine38, University of Washington39, University of Siena40, University of East Anglia41, University of Adelaide42, Pusan National University43, University of Calgary44, University of Cincinnati45, University of North Carolina at Chapel Hill46, Cleveland Clinic47, University of Winnipeg48, Chulalongkorn University49, Cornell University50, National University of Singapore51, University of Alabama at Birmingham52, University of Alberta53, Capital Medical University54
TL;DR: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in the understanding and treatment of rhinologic disease.
Abstract: I. Executive summary BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. Methods ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. Conclusion This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.
Mayo Clinic1, Harvard University2, Roswell Park Cancer Institute3, University of California, Irvine4, University of Wisconsin–Milwaukee5, Rutgers University6, City of Hope National Medical Center7, Boston University8, University of Wisconsin-Madison9, American Cancer Society10, University of Southern California11, University of Oxford12, Stanford University13, Fred Hutchinson Cancer Research Center14, University of Washington15, National Institutes of Health16, Vanderbilt University17, Cornell University18, University of Utah19, University of Pennsylvania20
TL;DR: In this paper, population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and risk assessment.
Abstract: Background Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and...
TL;DR: The first vaccines for prevention of coronavirus disease 2019 (COVID-19) in the United States were authorized for emergency use by the Food and Drug Administration (FDA) and recommended by the Advisory Committee on Immunization Practices (ACIP) in December 2020 as mentioned in this paper.
Abstract: The first vaccines for prevention of coronavirus disease 2019 (COVID-19) in the United States were authorized for emergency use by the Food and Drug Administration (FDA) (1) and recommended by the Advisory Committee on Immunization Practices (ACIP) in December 2020.* However, demand for COVID-19 vaccines is expected to exceed supply during the first months of the national COVID-19 vaccination program. ACIP advises CDC on population groups and circumstances for vaccine use.† On December 1, ACIP recommended that 1) health care personnel§ and 2) residents of long-term care facilities¶ be offered COVID-19 vaccination first, in Phase 1a of the vaccination program (2). On December 20, 2020, ACIP recommended that in Phase 1b, vaccine should be offered to persons aged ≥75 years and frontline essential workers (non-health care workers), and that in Phase 1c, persons aged 65-74 years, persons aged 16-64 years with high-risk medical conditions, and essential workers not recommended for vaccination in Phase 1b should be offered vaccine.** These recommendations for phased allocation provide guidance for federal, state, and local jurisdictions while vaccine supply is limited. In its deliberations, ACIP considered scientific evidence regarding COVID-19 epidemiology, ethical principles, and vaccination program implementation considerations. ACIP's recommendations for COVID-19 vaccine allocation are interim and might be updated based on changes in conditions of FDA Emergency Use Authorization, FDA authorization for new COVID-19 vaccines, changes in vaccine supply, or changes in COVID-19 epidemiology.
McMaster University1, University of Washington2, United Arab Emirates University3, Copenhagen University Hospital4, St Thomas' Hospital5, University of Michigan6, King Saud bin Abdulaziz University for Health Sciences7, Albert Einstein College of Medicine8, University of Toronto9, Rhode Island Hospital10, Brown University11, Utrecht University12, NewYork–Presbyterian Hospital13, Peking Union Medical College Hospital14, Federal University of São Paulo15, Humanitas University16, University of Ulsan17, National Institutes of Health18, Jagiellonian University Medical College19, Population Health Research Institute20, University of Manitoba21, University at Buffalo22, Homi Bhabha National Institute23, Baylor College of Medicine24, Vanderbilt University25, University of Milano-Bicocca26, King Saud Medical City27, Royal North Shore Hospital28, The George Institute for Global Health29, University of Virginia30, University of Dammam31, Emory University32, University of Pennsylvania33, Agostino Gemelli University Polyclinic34, St George’s University Hospitals NHS Foundation Trust35
TL;DR: The Surviving Sepsis Campaign Coronavirus Diease 2019 (SCCD) 2019 panel as mentioned in this paper provided guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU.
Abstract: Background The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. Methods The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Results The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. Conclusion The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.
Johns Hopkins University1, Vanderbilt University2, Mayo Clinic3, University of Wisconsin-Madison4, University of Colorado Boulder5, Duke University6, University of California, San Francisco7, City of Hope National Medical Center8, Harvard University9, University of Texas at Austin10, Fred Hutchinson Cancer Research Center11, Memorial Sloan Kettering Cancer Center12, University of South Florida13, Fox Chase Cancer Center14, Stanford University15, University of California, Los Angeles16, Brigham and Women's Hospital17, Case Western Reserve University18, University of Pennsylvania19, Northwestern University20, University of California, San Diego21, University of Michigan22, University of Texas Southwestern Medical Center23, Ohio State University24, Yale University25, University of Nebraska Medical Center26, University of Utah27, Roswell Park Cancer Institute28, National Comprehensive Cancer Network29
Washington University in St. Louis1, Vanderbilt University2, University of California, San Francisco3, University of Washington4, University of Chicago5, University of California, San Diego6, University of Rochester7, Emory University8, Mayo Clinic9, University of Maryland, College Park10, University of California, Los Angeles11, Memorial Sloan Kettering Cancer Center12, Ludwig Maximilian University of Munich13, University of California, Davis14, Utrecht University15, University of Texas MD Anderson Cancer Center16, Harvard University17, Loyola University Chicago18, University of California, Irvine19, University of Rennes20
TL;DR: The pivotal phase 2 results of ZUMA-3, an international, multicentre, single-arm, open-label study evaluating the efficacy and safety of the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy KTE-X19 in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia remain poor, underlining the need for more effective therapies.
Northwestern University1, Stanford University2, Johns Hopkins University3, Duke University4, University of Pennsylvania5, Fred Hutchinson Cancer Research Center6, Harvard University7, Mayo Clinic8, University of Texas Southwestern Medical Center9, City of Hope National Medical Center10, Memorial Sloan Kettering Cancer Center11, Fox Chase Cancer Center12, Washington University in St. Louis13, Roswell Park Cancer Institute14, University of Wisconsin-Madison15, University of California, San Diego16, Case Western Reserve University17, Vanderbilt University18, University of South Florida19, University of California, Los Angeles20, University of Tennessee Health Science Center21, University of California, San Francisco22, Ohio State University23, University of Michigan24, University of Nebraska Medical Center25, University of Utah26, National Comprehensive Cancer Network27
TL;DR: The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease Recommendations for disease monitoring and treatment of recurrent disease are also included as mentioned in this paper.
Abstract: The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease Recommendations for disease monitoring and treatment of recurrent disease are also included The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities This article summarizes the panel's discussions for the 2021 update of the guidelines with regard to systemic therapy for metastatic castration-resistant prostate cancer
Stephen P.H. Alexander1, Arthur Christopoulos2, Anthony P. Davenport3, Eamonn Kelly4 +151 more•Institutions (85)
TL;DR: The Concise Guide to PHARMACOLOGY 2021/22 as mentioned in this paper provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands.
Abstract: The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.