Showing papers by "University of Miami published in 2021"
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
Memorial Sloan Kettering Cancer Center1, Yonsei University2, Royal Free London NHS Foundation Trust3, University of Duisburg-Essen4, Texas Oncology5, Catholic University of Korea6, McMaster University7, University of Miami8, University of Western Ontario9, Autonomous University of Barcelona10, University of Queensland11, Seoul National University12, Macquarie University13, Rambam Health Care Campus14, Kyushu University15, University of Tübingen16, Medical University of Vienna17, Eisai18, Merck & Co.19, Harvard University20
TL;DR: In this article, Lenvatinib in combination with pembrolizumab or everolimus has been shown to have activity against advanced renal cell carcinoma (RCC).
Abstract: Background Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib ...
722 citations
Hebrew University of Jerusalem1, Hospital for Sick Children2, University of Miami3, Humanitas University4, Cincinnati Children's Hospital Medical Center5, University of California, San Diego6, Icahn School of Medicine at Mount Sinai7, Medical University of Vienna8, University of Amsterdam9, University of Paris10, University of Chicago11, University of Lorraine12, Rabin Medical Center13, Goethe University Frankfurt14
TL;DR: In a recent survey of 89 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD), a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in 2 surveys and 2 voting rounds as mentioned in this paper.
674 citations
Baylor College of Medicine1, Veterans Health Administration2, Icahn School of Medicine at Mount Sinai3, Primary Children's Hospital4, Royal Free Hospital5, University of Massachusetts Boston6, Rush University Medical Center7, Imperial College London8, University of Colorado Denver9, Leeds Teaching Hospitals NHS Trust10, University Health Network11, University of Miami12, Genentech13, Hoffmann-La Roche14, University of California, San Diego15
TL;DR: In this paper, a randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days.
Abstract: Background Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials. Methods In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo. Results Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, -1.0; 95% CI, -2.5 to 0; P = 0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, -7.6 to 8.2; nominal P = 0.94). Conclusions In this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann-La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov number, NCT04320615.).
666 citations
TL;DR: The benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood as discussed by the authors.
Abstract: Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight US locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (628%) received both recommended mRNA doses and 477 (121%) received only one dose of mRNA vaccine† Among unvaccinated participants, 138 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days§ In contrast, among fully immunized (≥14 days after second dose) persons, 004 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 019 infections per 1,000 person-days were reported Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions COVID-19 vaccination is recommended for all eligible persons
576 citations
TL;DR: In this article, a provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination and found that delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions.
Abstract: Background Cutaneous reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but are not well characterized. Objective To evaluate the morphology and timing of cutaneous reactions after mRNA COVID-19 vaccines. Methods A provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination. Results From December 2020 to February 2021, we recorded 414 cutaneous reactions to mRNA COVID-19 vaccines from Moderna (83%) and Pfizer (17%). Delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions. Forty-three percent of patients with first-dose reactions experienced second-dose recurrence. Additional less common reactions included pernio/chilblains, cosmetic filler reactions, zoster, herpes simplex flares, and pityriasis rosea-like reactions. Limitations Registry analysis does not measure incidence. Morphologic misclassification is possible. Conclusions We report a spectrum of cutaneous reactions after mRNA COVID-19 vaccines. We observed some dermatologic reactions to Moderna and Pfizer vaccines that mimicked SARS-CoV-2 infection itself, such as pernio/chilblains. Most patients with first-dose reactions did not have a second-dose reaction and serious adverse events did not develop in any of the patients in the registry after the first or second dose. Our data support that cutaneous reactions to COVID-19 vaccination are generally minor and self-limited, and should not discourage vaccination.
546 citations
Charité1, Baylor College of Medicine2, United States Department of Veterans Affairs3, University of Padua4, Mayo Clinic5, University of Greifswald6, University of Miami7, Katholieke Universiteit Leuven8, Maastricht University9, Max Delbrück Center for Molecular Medicine10, University of Tübingen11, Cleveland Clinic12, Kyushu University13, University of Belgrade14
TL;DR: Improved standardization of available invasive and noninvasive diagnostic tools and a consensus on their specific use are needed to allow specific diagnosis and stratification of patient cohorts for the implementation of aetiology-based therapies.
Abstract: Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.
502 citations
Centers for Disease Control and Prevention1, United States Public Health Service2, 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.
493 citations
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, University of Queensland16, Ochsner Health System17, 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.
359 citations
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).
359 citations
University of Oxford1, University of North Carolina at Chapel Hill2, Tanta University3, Rush University Medical Center4, Queen Elizabeth Hospital Birmingham5, University of Barcelona6, Beth Israel Deaconess Medical Center7, Stanford University8, Queen Mary University of London9, University of Miami10, Royal Free Hospital11, University of Liverpool12, University of Cambridge13, Icahn School of Medicine at Mount Sinai14, Lanzhou University15, University of Washington16, Harvard University17, National University of Singapore18, First Affiliated Hospital of Wenzhou Medical University19
TL;DR: It is demonstrated that baseline liver disease stage and ALD are independent risk factor for death from COVID-19, which is the largest reported cohort of CLD and cirrhosis patients with SARS-CoV-2 infection to date.
Vanderbilt University Medical Center1, Texas A&M University2, University of Colorado Denver3, University of Iowa4, Beth Israel Deaconess Medical Center5, Wake Forest University6, Johns Hopkins University School of Medicine7, Hennepin County Medical Center8, Ohio State University9, Albert Einstein College of Medicine10, University of Washington11, Baystate Medical Center12, Intermountain Medical Center13, University of Michigan14, Oregon Health & Science University15, Emory University16, Emory Healthcare17, Cleveland Clinic18, Stanford University19, University of California, Los Angeles20, University of Miami21, Washington University in St. Louis22
TL;DR: In this article, the authors evaluated the association between vaccination with mRNA COVID-19 vaccines and hospitalization, and the association with progression to critical disease, using multivariable logistic regression.
Abstract: Importance A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people. Objective To evaluate the association between vaccination with mRNA COVID-19 vaccines—mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)—and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease. Design, Setting, and Participants A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021. Exposures COVID-19 vaccination. Main Outcomes and Measures Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression. Results Among 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P Conclusions and Relevance Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination.
TL;DR: In this paper, the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) was evaluated.
Abstract: Background Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna) in preventing infection with ...
Baylor College of Medicine1, Brigham and Women's Hospital2, University of Miami3, University of Pittsburgh4, Emory University5, University of Colorado Denver6, University of California, Los Angeles7, Fred Hutchinson Cancer Research Center8, University of Cincinnati9, Henry Ford Health System10, University of Maryland, College Park11
TL;DR: The mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-... as discussed by the authors ) in a phase 3, observer-blinded, placebo-controlled clinical trial.
Abstract: Background At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-...
TL;DR: In this paper, the effect of COVID-19-related restrictions (i.e., stay at home orders, lockdown orders) on reported incidents of domestic violence was investigated.
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.
American Society of Clinical Oncology1, University of North Carolina at Chapel Hill2, Seattle Cancer Care Alliance3, Duke University4, Northwestern University5, Memorial Sloan Kettering Cancer Center6, University of Miami7, Harvard University8, Cooper University Hospital9, University of Texas MD Anderson Cancer Center10, Columbia University11
TL;DR: An Expert Panel to conduct a systematic review of the literature on neoadjuvant therapy for breast cancer and provide recommended care options found insufficient evidence to support adding immune checkpoint inhibitors to standard chemotherapy.
Abstract: PURPOSETo develop guideline recommendations concerning optimal neoadjuvant therapy for breast cancer.METHODSASCO convened an Expert Panel to conduct a systematic review of the literature on neoadju...
27 Oct 2021
TL;DR: In this paper, the authors present the first evidence that naturally-occurring microbiomes display network properties characteristic of unstable communities when under persistent stress, showing that prokaryotic and fungal diversity decline in high stress, and negative:positive cohesion have a clear negative relationship with environmental stress.
Abstract: Environmental stress is increasing worldwide, yet we lack a clear picture of how stress disrupts the stability of microbial communities and the ecosystem services they provide. Here, we present the first evidence that naturally-occurring microbiomes display network properties characteristic of unstable communities when under persistent stress. By assessing changes in diversity and structure of soil microbiomes along 40 replicate stress gradients (elevation/water availability gradients) in the Florida scrub ecosystem, we show that: (1) prokaryotic and fungal diversity decline in high stress, and (2) two network properties of stable microbial communities-modularity and negative:positive cohesion-have a clear negative relationship with environmental stress, explaining 51-78% of their variation. Interestingly, pathogenic taxa/functional guilds decreased in relative abundance along the stress gradient, while oligotrophs and mutualists increased, suggesting that the shift in negative:positive cohesion could result from decreasing negative:positive biotic interactions consistent with the predictions of the Stress Gradient Hypothesis. Given the crucial role microbiomes play in ecosystem functions, our results suggest that, by limiting the compartmentalization of microbial associations and creating communities dominated by positive associations, increasing stress in the Anthropocene could destabilize microbiomes and undermine their ecosystem services.
University of California, Los Angeles1, Fred Hutchinson Cancer Research Center2, LSU Health Sciences Center New Orleans3, University of São Paulo4, Asociación Civil Impacta Salud y Educación5, Chiang Mai University6, Centers for Disease Control and Prevention7, University of Pennsylvania8, St. Jude Children's Research Hospital9, University of North Carolina at Chapel Hill10, University of Cape Town11, University of Alabama at Birmingham12, Rutgers University13, Cornell University14, Johns Hopkins University15, Anschutz Medical Campus16, Harvard University17, University of Miami18, National Institutes of Health19
TL;DR: In this paper, safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preve...
Abstract: Background Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preve...
TL;DR: In this article, a double-blind, phase 1/2a, randomized, controlled trial was performed to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC-MSC) infusions in subjects with COVID-19 ARDS.
Abstract: Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC-MSC) infusions in subjects with COVID-19 ARDS. A double-blind, phase 1/2a, randomized, controlled trial was performed. Randomization and stratification by ARDS severity was used to foster balance among groups. All subjects were analyzed under intention to treat design. Twenty-four subjects were randomized 1:1 to either UC-MSC treatment (n = 12) or the control group (n = 12). Subjects in the UC-MSC treatment group received two intravenous infusions (at day 0 and 3) of 100 ± 20 × 106 UC-MSCs; controls received two infusions of vehicle solution. Both groups received best standard of care. Primary endpoint was safety (adverse events [AEs]) within 6 hours; cardiac arrest or death within 24 hours postinfusion). Secondary endpoints included patient survival at 31 days after the first infusion and time to recovery. No difference was observed between groups in infusion-associated AEs. No serious adverse events (SAEs) were observed related to UC-MSC infusions. UC-MSC infusions in COVID-19 ARDS were found to be safe. Inflammatory cytokines were significantly decreased in UC-MSC-treated subjects at day 6. Treatment was associated with significantly improved patient survival (91% vs 42%, P = .015), SAE-free survival (P = .008), and time to recovery (P = .03). UC-MSC infusions are safe and could be beneficial in treating subjects with COVID-19 ARDS.
Harvard University1, Johns Hopkins University2, University of Texas at Dallas3, University of North Carolina at Chapel Hill4, Westchester Medical Center5, New York University6, University of Mississippi7, University of Miami8, University of Colorado Denver9, Boston Children's Hospital10, Indiana University – Purdue University Indianapolis11, University of Washington12, University of Pennsylvania13, Saint Barnabas Medical Center14, University of Texas Health Science Center at Houston15, University of Arkansas for Medical Sciences16, Mayo Clinic17, University of Cincinnati18, Centers for Disease Control and Prevention19, Vanderbilt University20, Yale University21, Nationwide Children's Hospital22, University of Alabama at Birmingham23, Children's Mercy Hospital24, SUNY Downstate Medical Center25, Baylor College of Medicine26, Emory University27, California State University, Long Beach28, Rutgers University29, University of California, San Francisco30, Washington University in St. Louis31, University of Minnesota32, University of Iowa33, Medical University of South Carolina34, Northwestern University35, University of Michigan36
TL;DR: In this article, the authors investigated the range and severity of neurologic involvement among children and adolescents associated with COVID-19 and found that patients with involvement were more likely to have underlying neurologic disorders (81 of 365 [22] compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]).
Abstract: Importance Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants Case series of patients (age Exposures Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barre syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19–related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.
Carlos III Health Institute1, Universidad Pública de Navarra2, University of Navarra3, National University of Singapore4, Saint Louis University5, Charité6, Université du Québec à Montréal7, Agostino Gemelli University Polyclinic8, Universidade Federal do Rio Grande do Sul9, University of Milan10, University of Toulouse11, University of Melbourne12, Tufts University13, King's College London14, Wake Forest University15, University of Florida16, University of Miami17, Dalhousie University18, Baylor College of Medicine19, University of Otago20, Kyung Hee University21, The Chinese University of Hong Kong22, RMIT University23
TL;DR: In this paper, the authors provide evidence-based rationale for using exercise and physical activity (PA) for health promotion and disease prevention and treatment in older adults, and discuss the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability.
Abstract: The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.
TL;DR: This article identified key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors.
TL;DR: This paper conducted a meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants.
Abstract: Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
TL;DR: In this paper, the authors examined outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS and concomitant SARS-CoV-2 infections.
Abstract: Importance Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections. Objective To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS. Design, Setting, and Participants This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry. Health care professionals were asked to report patients after a minimum of 7 days from initial symptom onset and after sufficient time had passed to observe the COVID-19 disease course through resolution of acute illness or death. Data collection began April 1, 2020, and is ongoing. Exposures Laboratory-positive SARS-CoV-2 infection or highly suspected COVID-19. Main Outcomes and Measures Clinical outcome with 4 levels of increasing severity: not hospitalized, hospitalization only, admission to the intensive care unit and/or required ventilator support, and death. Results Of 1626 patients, most had laboratory-positive SARS-CoV-2 infection (1345 [82.7%]), were female (1202 [74.0%]), and had relapsing-remitting MS (1255 [80.4%]). A total of 996 patients (61.5%) were non-Hispanic White, 337 (20.8%) were Black, and 190 (11.7%) were Hispanic/Latinx. The mean (SD) age was 47.7 (13.2) years, and 797 (49.5%) had 1 or more comorbidity. The overall mortality rate was 3.3% (95% CI, 2.5%-4.3%). Ambulatory disability and older age were each independently associated with increased odds of all clinical severity levels compared with those not hospitalized after adjusting for other risk factors (nonambulatory: hospitalization only, odds ratio [OR], 2.8 [95% CI, 1.6-4.8]; intensive care unit/required ventilator support, OR, 3.5 [95% CI, 1.6-7.8]; death, OR, 25.4 [95% CI, 9.3-69.1]; age [every 10 years]: hospitalization only, OR, 1.3 [95% CI, 1.1-1.6]; intensive care unit/required ventilator support, OR, 1.3 [95% CI, 0.99-1.7]; death, OR, 1.8 [95% CI, 1.2-2.6]). Conclusions and Relevance In this registry-based cross-sectional study, increased disability was independently associated with worse clinical severity including death from COVID-19. Other risk factors for worse outcomes included older age, Black race, cardiovascular comorbidities, and recent treatment with corticosteroids. Knowledge of these risk factors may improve the treatment of patients with MS and COVID-19 by helping clinicians identify patients requiring more intense monitoring or COVID-19 treatment.
Memorial Sloan Kettering Cancer Center1, Medical College of Wisconsin2, University of Western Australia3, Ohio State University4, University of California, San Francisco5, University of Oxford6, Columbia University7, Sarah Cannon Research Institute8, University of Miami9, University of Texas MD Anderson Cancer Center10, University of North Carolina at Chapel Hill11, University of Pennsylvania12, Vita-Salute San Raffaele University13, University of Nantes14, Roswell Park Cancer Institute15, Emory University16, Royal Melbourne Hospital17, Flinders University18, Harvard University19
TL;DR: Pirtobrutinib was shown to be safe and effective in multiple B-cell malignancies, including patients previously treated with covalent BTK inhibitors as mentioned in this paper.
TL;DR: Estimates indicate elevated psychosocial symptomatology and suggest that symptoms could have worsened since the pandemic, underscore the importance of prevention and intervention to address these public health problems.
Abstract: As COVID-19 converges with loneliness and addiction epidemics in the US, both public health and mental health experts forecast dramatic increases in substance use and mental health conditions. This cross-sectional study evaluated relationships of loneliness with depression, anxiety, alcohol use, and drug use during COVID-19, and assessed perceived increases in these symptoms in young adults. Between April 22 and May 11, 2020, 1,008 participants ages 18-35 were recruited through social media to a one-time, online anonymous survey. Symptomatology was assessed using six scales. Perceived changes since COVID-19 were evaluated using 5-point Likert scales. Forty-nine percent of respondents reported loneliness scores above 50; 80% reported significant depressive symptoms; 61% reported moderate to severe anxiety; 30% disclosed harmful levels of drinking. While only 22% of the population reported using drugs, 38% reported severe drug use. Loneliness was associated with higher levels of mental health symptomatology. Participants reported significant increases across mental health and substance use symptoms since COVID-19. While direct impacts of COVID-19 could only be calculated with pre-pandemic assessments of these symptoms, estimates indicate elevated psychosocial symptomatology and suggest that symptoms could have worsened since the pandemic. Findings underscore the importance of prevention and intervention to address these public health problems.
Fred Hutchinson Cancer Research Center1, Stanford University2, University of Cincinnati3, Vanderbilt University Medical Center4, Vanderbilt University5, Harvard University6, Broad Institute7, University of Lausanne8, University of Hawaii9, University of Colorado Denver10, Thomas Jefferson University11, Mayo Clinic12, Loyola University Medical Center13, Houston Methodist Hospital14, Emory University15, Beth Israel Deaconess Medical Center16, University of Florida17, McGill University Health Centre18, University of California, San Diego19, Case Western Reserve University20, St. Elizabeth Healthcare21, Icahn School of Medicine at Mount Sinai22, University of Kentucky23, Brown University24, Tufts Medical Center25, University of Michigan26, Henry Ford Health System27, Intermountain Healthcare28, George Washington University29, Cleveland Clinic30, Duke University31, Montefiore Medical Center32, Columbia University33, University of Connecticut34, Mount Auburn Hospital35, University of Kansas36, University of California, San Francisco37, Baylor College of Medicine38, Cancer Treatment Centers of America39, Ohio State University40, Penn State Cancer Institute41, University of Texas Health Science Center at San Antonio42, Loma Linda University43, University of California, Davis44, Medical University of South Carolina45, University of North Carolina at Chapel Hill46, Rutgers University47, Washington University in St. Louis48, LSU Health Sciences Center New Orleans49, University of Miami50
TL;DR: In this article, the authors analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.
University of Pennsylvania1, Hospital of the University of Pennsylvania2, University of Arizona3, National University of Cuyo4, Stanford University5, Ottawa Hospital Research Institute6, University of Guadalajara7, Duke University8, Karolinska Institutet9, University of Miami10, University of Michigan11
TL;DR: The REPLACE COVID trial as mentioned in this paper evaluated whether continuing versus discontinuing renin-angiotensin system inhibitors (ANGI-converting enzyme inhibitors or angiotENSin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.