Showing papers by "St Thomas' Hospital published in 2021"
TL;DR: The B.617.1.2 variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Coronavirus disease 2019 (Covid-19), has contributed to the development of the disease.
Abstract: Background The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to ...
2,032 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, Hadassah Medical Center44, 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 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: In this article, the authors examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine.
Abstract: Summary Background The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting. Methods In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI Findings Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49–68) for ChAdOx1 nCoV-19 and 69% (66–72) for BNT162b2 at 21–44 days and 72% (63–79) for BNT162b2 after 45–59 days. Interpretation Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days. Funding ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.
670 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
National Institute for Health Research1, University of London2, University of Auckland3, University of Cambridge4, Anglia Ruskin University5, Queen's University Belfast6, Sun Yat-sen University7, The Fred Hollows Foundation8, Mbarara University of Science and Technology9, Ministry of Health and Family Welfare10, University of Geneva11, St Thomas' Hospital12, Leeds Teaching Hospitals NHS Trust13, Southwest University of Visual Arts14, Orbis International15, International Agency for the Prevention of Blindness16, University of Cape Town17, University Hospitals Birmingham NHS Foundation Trust18, University of Michigan19, Emory University20, Johns Hopkins University21, Massachusetts Eye and Ear Infirmary22, University of São Paulo23, University of Nairobi24, Seva Foundation25, Tilganga Institute of Ophthalmology26, Heidelberg University27, University of New South Wales28, The George Institute for Global Health29, L V Prasad Eye Institute30, College of Health Sciences, Bahrain31, Muhimbili University of Health and Allied Sciences32, International Institute of Minnesota33, University of the West Indies34, University of Melbourne35, Kenya Medical Training College36, Federal University of São Paulo37, Capital Medical University38, Singapore National Eye Center39, National University of Singapore40, Pan American Health Organization41, Brien Holden Vision Institute42, University of Calabar43
TL;DR: In this paper, the authors defined eye health as maximised vision, ocular health, and functional ability, thereby contributing to overall health and wellbeing, social inclusion, and quality of life.
435 citations
TL;DR: In this article, the authors aimed to determine illness duration and characteristics in symptomatic UK school-aged children tested for SARS-CoV-2 using data from the COVID Symptom Study, one of the largest UK citizen participatory epidemiological studies to date.
268 citations
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, Brown University10, Rhode Island Hospital11, 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, The George Institute for Global Health28, Royal North Shore Hospital29, 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.
257 citations
TL;DR: In this article, the oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleucin-13 signaling, was investigated for the treatment of atopic dermatitis.
Abstract: Background The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Dat...
171 citations
TL;DR: Arterial stiffness, a leading marker of risk in hypertension, can be measured at material or structural levels, with the latter combining effects of the geometry and composition of the wall, including intramural organization as mentioned in this paper.
Abstract: Arterial stiffness, a leading marker of risk in hypertension, can be measured at material or structural levels, with the latter combining effects of the geometry and composition of the wall, including intramural organization. Numerous studies have shown that structural stiffness predicts outcomes in models that adjust for conventional risk factors. Elastic arteries, nearer to the heart, are most sensitive to effects of blood pressure and age, major determinants of stiffness. Stiffness is usually considered as an index of vascular aging, wherein individuals excessively affected by risk factor exposure represent early vascular aging, whereas those resistant to risk factors represent supernormal vascular aging. Stiffness affects the function of the brain and kidneys by increasing pulsatile loads within their microvascular beds, and the heart by increasing left ventricular systolic load; excessive pressure pulsatility also decreases diastolic pressure, necessary for coronary perfusion. Stiffness promotes inward remodeling of small arteries, which increases resistance, blood pressure, and in turn, central artery stiffness, thus creating an insidious feedback loop. Chronic antihypertensive treatments can reduce stiffness beyond passive reductions due to decreased blood pressure. Preventive drugs, such as lipid-lowering drugs and antidiabetic drugs, have additional effects on stiffness, independent of pressure. Newer anti-inflammatory drugs also have blood pressure independent effects. Reduction of stiffness is expected to confer benefit beyond the lowering of pressure, although this hypothesis is not yet proven. We summarize different steps for making arterial stiffness measurement a keystone in hypertension management and cardiovascular prevention as a whole.
142 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, University of Kentucky20, Ghent University Hospital21, University of Tokyo22, Peking Union Medical College Hospital23, Hebron University24, Monash University25, Copenhagen University Hospital26, Liverpool School of Tropical Medicine27, Vanderbilt University28, Brigham and Women's Hospital29, University of Ulsan30, University of Manitoba31, Makerere University32, Faculdade de Medicina de São José do Rio Preto33, National Institutes of Health34, Mount Sinai Hospital, Toronto35, Medanta36, University of the Witwatersrand37, New York University38, Washington University in St. Louis39, University of Alberta40, Hennepin County Medical Center41, Royal Brisbane and Women's Hospital42, University of Pennsylvania43, Hebrew University of Jerusalem44, Hochschule Hannover45, Brown University46
141 citations
Tehran University of Medical Sciences1, Iran University of Medical Sciences2, Virginia Commonwealth University3, University of Toronto4, Universidad Católica San Antonio de Murcia5, University of Alcalá6, Brigham and Women's Hospital7, NewYork–Presbyterian Hospital8, Population Health Research Institute9, St Thomas' Hospital10, University of Mainz11, University of Vermont Medical Center12, McMaster University13, Icahn School of Medicine at Mount Sinai14, Yale University15, University of Liverpool16
TL;DR: In this paper, a variety of antithrombotic agents, doses, and durations of therapy are assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and patients critically ill with COVID-19.
TL;DR: The population of patients with COVID-19 admitted to ICU, and the processes of care in ICUs, changed over the first wave of the epidemic, and after adjustment for important risk factors, there was a substantial improvement in patient outcomes.
Abstract: Rationale: By describing trends in intensive care for patients with coronavirus disease (COVID-19) we aim to support clinical learning, service planning, and hypothesis generation.Objectives: To describe variation in ICU admission rates over time and by geography during the first wave of the epidemic in England, Wales, and Northern Ireland; to describe trends in patient characteristics on admission to ICU, first-24-hours physiology in ICU, processes of care in ICU and patient outcomes; and to explore deviations in trends during the peak period.Methods: A cohort of 10,741 patients with COVID-19 in the Case Mix Program national clinical audit from February 1 to July 31, 2020, was used. Analyses were stratified by time period (prepeak, peak, and postpeak periods) and geographical region. Logistic regression was used to estimate adjusted differences in 28-day in-hospital mortality between periods.Measurements and Main Results: Admissions to ICUs peaked almost simultaneously across regions but varied 4.6-fold in magnitude. Compared with patients admitted in the prepeak period, patients admitted in the postpeak period were slightly younger but with higher degrees of dependency and comorbidity on admission to ICUs and more deranged first-24-hours physiology. Despite this, receipt of invasive ventilation and renal replacement therapy decreased, and adjusted 28-day in-hospital mortality was reduced by 11.8% (95% confidence interval, 8.7%-15.0%). Many variables exhibited u-shaped or n-shaped curves during the peak.Conclusions: The population of patients with COVID-19 admitted to ICUs, and the processes of care in ICUs, changed over the first wave of the epidemic. After adjustment for important risk factors, there was a substantial improvement in patient outcomes.
TL;DR: Prendergast et al. as discussed by the authors discuss the global burden of VHD, geographical variation in the presentation and clinical management, and temporal trends in disease burden, with a predominance of functional and degenerative disease in high-income countries, and a majority of rheumatic heart disease in low-income and middle income countries.
Abstract: Valvular heart disease (VHD) is a major contributor to loss of physical function, quality of life and longevity. The epidemiology of VHD varies substantially around the world, with a predominance of functional and degenerative disease in high-income countries, and a predominance of rheumatic heart disease in low-income and middle-income countries. Reflecting this distribution, rheumatic heart disease remains by far the most common manifestation of VHD worldwide and affects approximately 41 million people. By contrast, the prevalence of calcific aortic stenosis and degenerative mitral valve disease is 9 and 24 million people, respectively. Despite a reduction in global mortality related to rheumatic heart disease since 1900, the death rate has remained fairly static since 2000. Meanwhile, deaths from calcific aortic stenosis have continued to rise in the past 20 years. Epidemiological data on other important acquired and congenital forms of VHD are limited. An ageing population and advances in therapies make an examination of the changing global epidemiology of VHD crucial for advances in clinical practice and formulation of health policy. In this Review, we discuss the global burden of VHD, geographical variation in the presentation and clinical management, and temporal trends in disease burden. Valvular heart disease (VHD) is a major contributor to loss of physical function, quality of life and longevity. In this Review, Prendergast and colleagues discuss the global burden of VHD, geographical variation in the presentation and clinical management, and temporal trends in disease burden.
Radboud University Nijmegen1, University of Paris2, Research Foundation - Flanders3, Ghent University Hospital4, Innsbruck Medical University5, University of California, San Francisco6, St Thomas' Hospital7, Barts Health NHS Trust8, Queen Mary University of London9, University Hospital of Lausanne10, Katholieke Universiteit Leuven11
TL;DR: In this article, an update on various aspects of acute kidney injury (AKI) in critically ill patients is provided, focusing on prediction and early detection of AKI (e.g., the role of biomarkers to identify high-risk patients and the use of machine learning to predict AKI).
Abstract: Acute kidney injury (AKI) is now recognized as a heterogeneous syndrome that not only affects acute morbidity and mortality, but also a patient's long-term prognosis. In this narrative review, an update on various aspects of AKI in critically ill patients will be provided. Focus will be on prediction and early detection of AKI (e.g., the role of biomarkers to identify high-risk patients and the use of machine learning to predict AKI), aspects of pathophysiology and progress in the recognition of different phenotypes of AKI, as well as an update on nephrotoxicity and organ cross-talk. In addition, prevention of AKI (focusing on fluid management, kidney perfusion pressure, and the choice of vasopressor) and supportive treatment of AKI is discussed. Finally, post-AKI risk of long-term sequelae including incident or progression of chronic kidney disease, cardiovascular events and mortality, will be addressed.
TL;DR: In this paper, the authors present a review of the most relevant and up-to-date knowledge available in this field, and support the efficient clinical translation of future nanomedicinal products for in vivo imaging and/or therapy.
Abstract: Nanomaterials offer unique physical, chemical and biological properties of interest for medical imaging and therapy. Over the last two decades, there has been an increasing effort to translate nanomaterial-based medicinal products (so-called nanomedicines) into clinical practice and, although multiple nanoparticle-based formulations are clinically available, there is still a disparity between the number of pre-clinical products and those that reach clinical approval. To facilitate the efficient clinical translation of nanomedicinal-drugs, it is important to study their whole-body biodistribution and pharmacokinetics from the early stages of their development. Integrating this knowledge with that of their therapeutic profile and/or toxicity should provide a powerful combination to efficiently inform nanomedicine trials and allow early selection of the most promising candidates. In this context, radiolabelling nanomaterials allows whole-body and non-invasive in vivo tracking by the sensitive clinical imaging techniques positron emission tomography (PET), and single photon emission computed tomography (SPECT). Furthermore, certain radionuclides with specific nuclear emissions can elicit therapeutic effects by themselves, leading to radionuclide-based therapy. To ensure robust information during the development of nanomaterials for PET/SPECT imaging and/or radionuclide therapy, selection of the most appropriate radiolabelling method and knowledge of its limitations are critical. Different radiolabelling strategies are available depending on the type of material, the radionuclide and/or the final application. In this review we describe the different radiolabelling strategies currently available, with a critical vision over their advantages and disadvantages. The final aim is to review the most relevant and up-to-date knowledge available in this field, and support the efficient clinical translation of future nanomedicinal products for in vivo imaging and/or therapy.
TL;DR: Based on pathophysiological derangements observed in COVID-19 patients, a rationale emerges for sequential extracorporeal therapies designed to remove inflammatory mediators and support different organ systems.
Abstract: Critically ill COVID-19 patients are generally admitted to the ICU for respiratory insufficiency which can evolve into a multiple-organ dysfunction syndrome requiring extracorporeal organ support. Ongoing advances in technology and science and progress in information technology support the development of integrated multi-organ support platforms for personalized treatment according to the changing needs of the patient. Based on pathophysiological derangements observed in COVID-19 patients, a rationale emerges for sequential extracorporeal therapies designed to remove inflammatory mediators and support different organ systems. In the absence of vaccines or direct therapy for COVID-19, extracorporeal therapies could represent an option to prevent organ failure and improve survival. The enormous demand in care for COVID-19 patients requires an immediate response from the scientific community. Thus, a detailed review of the available technology is provided by experts followed by a series of recommendation based on current experience and opinions, while waiting for generation of robust evidence from trials.
TL;DR: This is the first study demonstrating higher prevalence of probable delirium as a COVID-19 symptom in older adults with frailty compared to other older adults, emphasising need for systematic frailty assessment and screening for delIRium in acutely ill older patients in hospital and community settings.
Abstract: Background Frailty, increased vulnerability to physiological stressors, is associated with adverse outcomes. COVID-19 exhibits a more severe disease course in older, comorbid adults. Awareness of atypical presentations is critical to facilitate early identification. Objective To assess how frailty affects presenting COVID-19 symptoms in older adults. Design Observational cohort study of hospitalised older patients and self-report data for community-based older adults. Setting Admissions to St Thomas' Hospital, London with laboratory-confirmed COVID-19. Community-based data for older adults using the COVID Symptom Study mobile application. Subjects Hospital cohort: patients aged 65 and over (n = 322); unscheduled hospital admission between 1 March 2020 and 5 May 2020; COVID-19 confirmed by RT-PCR of nasopharyngeal swab. Community-based cohort: participants aged 65 and over enrolled in the COVID Symptom Study (n = 535); reported test-positive for COVID-19 from 24 March (application launch) to 8 May 2020. Methods Multivariable logistic regression analysis performed on age-matched samples from hospital and community-based cohorts to ascertain association of frailty with symptoms of confirmed COVID-19. Results Hospital cohort: significantly higher prevalence of probable delirium in the frail sample, with no difference in fever or cough. Community-based cohort: significantly higher prevalence of possible delirium in frailer, older adults and fatigue and shortness of breath. Conclusions This is the first study demonstrating higher prevalence of probable delirium as a COVID-19 symptom in older adults with frailty compared to other older adults. This emphasises need for systematic frailty assessment and screening for delirium in acutely ill older patients in hospital and community settings. Clinicians should suspect COVID-19 in frail adults with delirium.
Brigham and Women's Hospital1, University of Vermont2, Harvard University3, Ohio State University4, Hebron University5, St Thomas' Hospital6, Mayo Clinic7, University of Texas MD Anderson Cancer Center8, Stanford University9, Memorial Sloan Kettering Cancer Center10, Hofstra University11, Duke University12, University Hospitals of Cleveland13, Rega Institute for Medical Research14, Katholieke Universiteit Leuven15, Northwestern University16, University of Washington17, Charité18, University of California, San Francisco19, Southern Taiwan University of Science and Technology20, National Cheng Kung University21, Sheba Medical Center22, University of Miami23, University of Florida24, University of Virginia Health System25, University Health Network26, University of California, Los Angeles27, University of Alabama28, Mount Sinai Hospital29, University of Pennsylvania30, University Medical Center Groningen31, King Chulalongkorn Memorial Hospital32, I.M. Sechenov First Moscow State Medical University33, Max Delbrück Center for Molecular Medicine34
TL;DR: In this paper, a multivariable logistic regression model was used to identify predictors of ICPi-AKI and its recovery, and the effect of rechallenge versus no re-challenge on survival was estimated.
Abstract: Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results ICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.
TL;DR: In this paper, Hawkey et al. evaluated the landscape of targetable genomic alterations detected in ctDNA and assessed concordance with tissue-based CGP results, with a high level of agreement in detection of BRCA1/2 mutations.
Abstract: Purpose: Comprehensive genomic profiling (CGP) is of increasing value for patients with metastatic castration-resistant prostate cancer (mCRPC) mCRPC tends to metastasize to bone, making tissue biopsies challenging to obtain We hypothesized CGP of cell-free circulating tumor DNA (ctDNA) could offer a minimally invasive alternative to detect targetable genomic alterations (GA) that inform clinical care Experimental Design: Using plasma from 3,334 patients with mCRPC (including 1,674 screening samples from TRITON2/3), we evaluated the landscape of GAs detected in ctDNA and assessed concordance with tissue-based CGP Results: A total of 3,129 patients (94%) had detectable ctDNA with a median ctDNA fraction of 75%; BRCA1/2 was mutated in 295 (88%) In concordance analysis, 72 of 837 patients had BRCA1/2 mutations detected in tissue, 67 (93%) of which were also identified using ctDNA, including 100% of predicted germline variants ctDNA harbored some BRCA1/2 alterations not identified by tissue testing, and ctDNA was enriched in therapy resistance alterations, as well as possible clonal hematopoiesis mutations (eg, in ATM and CHEK2) Potential androgen receptor resistance alterations were detected in 940 of 2,213 patients (42%), including amplifications, polyclonal and compound mutations, rearrangements, and novel deletions in exon 8 Conclusions: Genomic analysis of ctDNA from patients with mCRPC recapitulates the genomic landscape detected in tissue biopsies, with a high level of agreement in detection of BRCA1/2 mutations, but more acquired resistance alterations detected in ctDNA CGP of ctDNA is a compelling clinical complement to tissue CGP, with reflex to tissue CGP if negative for actionable variants See related commentary by Hawkey and Armstrong, p 2961
Norfolk and Norwich University Hospital1, University of Lausanne2, University of Toronto3, Cleveland Clinic4, Case Western Reserve University5, Mayo Clinic6, Westchester Medical Center7, New York Medical College8, Pennsylvania State University9, Muğla University10, St. Vincent's Health System11, University of Cambridge12, Harvard University13, University of Antwerp14, Royal Gwent Hospital15, Stanford University16, University of New South Wales17, Katholieke Universiteit Leuven18, University of Ottawa19, Abertawe Bro Morgannwg University Health Board20, Duke University21, University of North Carolina at Chapel Hill22, University of Melbourne23, University of Texas at Austin24, Belfast Health and Social Care Trust25, The Chinese University of Hong Kong26, Dalhousie University27, Columbia University Medical Center28, Glasgow Royal Infirmary29, University Hospital Galway30, Cork University Hospital31, St Thomas' Hospital32, Toronto Western Hospital33, University of Barcelona34, Saint Francis University35, Hospital for Special Surgery36, Canterbury Hospital37, Maltepe University38, Radboud University Nijmegen39, Saarland University40, University of Pennsylvania41
TL;DR: In this paper, the authors conducted an international consensus study involving experts using a three-round Delphi method to produce a list of names and corresponding descriptions of anatomical targets for abdominal wall, chest wall, and paraspinal blocks.
TL;DR: In this paper, a Delphi study was conducted with a panel of primary and secondary care doctors to provide a rapid expert guide for GPs and long COVID clinical services, which eliciting a response of ‘strongly agree, ‘agree, or ‘neither agree nor disagree’ from 90% or more of responders.
Abstract: Background In the absence of research into therapies and care pathways for long COVID, guidance based on ‘emerging experience’ is needed. Aim To provide a rapid expert guide for GPs and long COVID clinical services. Design and setting A Delphi study was conducted with a panel of primary and secondary care doctors. Method Recommendations were generated relating to the investigation and management of long COVID. These were distributed online to a panel of UK doctors (any specialty) with an interest in, lived experience of, and/or experience treating long COVID. Over two rounds of Delphi testing, panellists indicated their agreement with each recommendation (using a five-point Likert scale) and provided comments. Recommendations eliciting a response of ‘strongly agree’, ‘agree’, or ‘neither agree nor disagree’ from 90% or more of responders were taken as showing consensus. Results Thirty-three clinicians representing 14 specialties reached consensus on 35 recommendations. Chiefly, GPs should consider long COVID in the presence of a wide range of presenting features (not limited to fatigue and breathlessness) and exclude differential diagnoses where appropriate. Detailed history and examination with baseline investigations should be conducted in primary care. Indications for further investigation and specific therapies (for myocarditis, postural tachycardia syndrome, mast cell disorder) include hypoxia/desaturation, chest pain, palpitations, and histamine-related symptoms. Rehabilitation should be individualised, with careful activity pacing (to avoid relapse) and multidisciplinary support. Conclusion Long COVID clinics should operate as part of an integrated care system, with GPs playing a key role in the multidisciplinary team. Holistic care pathways, investigation of specific complications, management of potential symptom clusters, and tailored rehabilitation are needed.
University of Southampton1, Imperial College London2, Queen Alexandra Hospital3, University of Leicester4, British Heart Foundation5, University Hospital of North Tees6, Derriford Hospital7, Royal Stoke University Hospital8, St Thomas' Hospital9, Robertson Centre for Biostatistics10, Duke University11, Stanford University12
TL;DR: In this article, the authors tested whether fractional flow reserve (FFRCT) using computed tomography coronary angiography (CTCA) would improve economic and clinical outcomes compared with standard care.
Abstract: Aims:
Fractional flow reserve (FFRCT) using computed tomography coronary angiography (CTCA) determines both the presence of coronary artery disease and vessel-specific ischaemia. We tested whether an evaluation strategy based on FFRCT would improve economic and clinical outcomes compared with standard care.
Methods and Results:
Overall, 1400 patients with stable chest pain in 11 centres were randomized to initial testing with CTCA with selective FFRCT (experimental group) or standard clinical care pathways (standard group). The primary endpoint was total cardiac costs at 9 months; secondary endpoints were angina status, quality of life, major adverse cardiac and cerebrovascular events, and use of invasive coronary angiography. Randomized patients were similar at baseline. Most patients had an initial CTCA: 439 (63%) in the standard group vs. 674 (96%) in the experimental group, 254 of whom (38%) underwent FFRCT. Mean total cardiac costs were higher by £114 (+8%) in the experimental group, with a 95% confidence interval from -£112 (-8%) to +£337 (+23%), though the difference was not significant (P = 0.10). Major adverse cardiac and cerebrovascular events did not differ significantly (10.2% in the experimental group vs. 10.6% in the standard group) and angina and quality of life improved to a similar degree over follow-up in both randomized groups. Invasive angiography was reduced significantly in the experimental group (19% vs. 25%, P = 0.01).
Conclusion:
A strategy of CTCA with selective FFRCT in patients with stable angina did not differ significantly from standard clinical care pathways in cost or clinical outcomes, but did reduce the use of invasive coronary angiography.
University of Warwick1, Yale University2, Valve Corporation3, Hannover Medical School4, Leiden University5, Vilnius University6, Robertson Centre for Biostatistics7, Leipzig University8, University of Cyprus9, National and Kapodistrian University of Athens10, Ludwig Maximilian University of Munich11, Wrocław Medical University12, University of Ljubljana13, University of Rennes14, Karolinska University Hospital15, University of Cambridge16, Brigham and Women's Hospital17, University of Brescia18, University Hospital of Basel19, University of Hasselt20, University of Bern21, Ruhr University Bochum22, University of Zurich23, University of Paris24, Carlos III Health Institute25, Oslo University Hospital26, University of Oslo27, University of Belgrade28, St Thomas' Hospital29
TL;DR: In this paper, a collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA), presents an updated practical approach to the evaluation and management of patients with chronic heart failure and secondary mitral regurgitation based upon a Heart Team approach.
Abstract: Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach.
Beijing Jishuitan Hospital1, Wannan Medical College2, Guiyang Medical University3, Zhengzhou University4, Fudan University5, Sun Yat-sen University6, Shanghai Jiao Tong University7, The University of Nottingham Ningbo China8, Harbin Medical University9, China-Japan Friendship Hospital10, Third Military Medical University11, Chinese Center for Disease Control and Prevention12, St Thomas' Hospital13, University of Wisconsin-Madison14, Chinese PLA General Hospital15, Durham University16
TL;DR: It is shown that LDCT‐based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses.
Abstract: Opportunistic screening for osteoporosis can be performed using low-dose computed tomography (LDCT) imaging obtained for other clinical indications. In this study we explored the CT-derived bone mineral density (BMD) and prevalence of osteoporosis from thoracic LDCT in a large population cohort of Chinese men and women. A total of 69,095 adults (40,733 men and 28,362 women) received a thoracic LDCT scan for the purpose of lung cancer screening between 2018 and 2019, and data were obtained for analysis from the China Biobank Project, a prospective nationwide multicenter population study. Lumbar spine (L1 -L2 ) trabecular volumetric bone mineral density (vBMD) was derived from these scans using quantitative computed tomography (QCT) software and the American College of Radiology QCT diagnostic criteria for osteoporosis were applied. Geographic regional differences in the prevalence of osteoporosis were assessed and the age-standardized, population prevalence of osteoporosis in Chinese men and women was estimated from the 2010 China census. The prevalence of osteoporosis by QCT for the Chinese population aged >50 years was 29.0% for women and 13.5% for men, equating to 49.0 million and 22.8 million, respectively. In women, this rate is comparable to estimates from dual-energy X-ray absorptiometry (DXA), but in men, the prevalence is double. Prevalence varied geographically across China, with higher rates in the southwest and lower rates in the northeast. Trabecular vBMD decreased with age in both men and women. Women had higher peak trabecular vBMD (185.4 mg/cm3 ) than men (176.6 mg/cm3 ) at age 30 to 34 years, but older women had lower trabecular vBMD (62.4 mg/cm3 ) than men (92.1 mg/cm3 ) at age 80 years. We show that LDCT-based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..
TL;DR: In this article, the effects of cagrilintide on bodyweight, safety, and tolerability were evaluated in a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial at 57 sites including hospitals, specialist clinics, and primary care centres in ten countries (Canada, Denmark, Finland, Ireland, Japan, Poland, Serbia, South Africa, the UK, and the USA).
University of Pittsburgh1, University of California, San Francisco2, Boston Children's Hospital3, University of Michigan4, Imperial College London5, University of Oxford6, Vanderbilt University Medical Center7, Kaiser Permanente8, St. Michael's Hospital9, St Thomas' Hospital10, King's College London11, Beth Israel Deaconess Medical Center12, Nepean Hospital13, Harvard University14, Duke University15, University of Amsterdam16, Cincinnati Children's Hospital Medical Center17, Peking University18
TL;DR: In this paper, the authors present a framework for the broader study of sepsis subclasses and provide a mechanism for explaining subclasses generated by different methodologic approaches, and guide clinicians in how to consider subclasses in bedside care.
Abstract: Sepsis is defined as a dysregulated host response to infection that leads to life-threatening acute organ dysfunction. It afflicts approximately 50 million people worldwide annually and is often deadly, even when evidence-based guidelines are applied promptly. Many randomized trials tested therapies for sepsis over the past 2 decades, but most have not proven beneficial. This may be because sepsis is a heterogeneous syndrome, characterized by a vast set of clinical and biologic features. Combinations of these features, however, may identify previously unrecognized groups, or "subclasses" with different risks of outcome and response to a given treatment. As efforts to identify sepsis subclasses become more common, many unanswered questions and challenges arise. These include: 1) the semantic underpinning of sepsis subclasses, 2) the conceptual goal of subclasses, 3) considerations about study design, data sources, and statistical methods, 4) the role of emerging data types, and 5) how to determine whether subclasses represent "truth." We discuss these challenges and present a framework for the broader study of sepsis subclasses. This framework is intended to aid in the understanding and interpretation of sepsis subclasses, provide a mechanism for explaining subclasses generated by different methodologic approaches, and guide clinicians in how to consider subclasses in bedside care.
TL;DR: A review of the role of the Gut Microbiome (GM) in cancer can be found in this article, where the authors provide clinicians with an overview of the current understanding of the GM and its role in cancer.
Abstract: The gut microbiome (GM) has been implicated in a vast number of human pathologies and has become a focus of oncology research over the past 5 years. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation and protection against pathogens. Strong evidence is emerging to support the effects of the GM on the development of some malignancies but also on responses to cancer therapies, most notably, immune checkpoint inhibition. Tools for manipulating the GM including dietary modification, probiotics and faecal microbiota transfer (FMT) are in development. Current understandings of the many complex interrelationships between the GM, cancer, the immune system, nutrition and medication are ultimately based on a combination of short-term clinical trials and observational studies, paired with an ever-evolving understanding of cancer biology. The next generation of personalised cancer therapies focusses on molecular and phenotypic heterogeneity, tumour evolution and immune status; it is distinctly possible that the GM will become an increasingly central focus amongst them. The aim of this review is to provide clinicians with an overview of microbiome science and our current understanding of the role the GM plays in cancer.
TL;DR: Gut organoid cocultures with type-1 innate lymphoid cells (ILC1) with MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations are developed to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.
Abstract: Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.
TL;DR: In this article, the authors discuss the latest advances in the application of NIR QDs in preclinical settings, together with the synthetic approaches and material developments that make NIRQDs promising for future biomedical applications.
Freeman Hospital1, Altnagelvin Area Hospital2, East Surrey Hospital3, Manchester Royal Infirmary4, Frimley Park Hospital5, Princess Alexandra Hospital6, Whittington Hospital7, Liverpool Hospital8, Mater Dei Hospital9, Nottingham City Hospital10, Edinburgh Royal Infirmary11, Southampton General Hospital12, Northampton General Hospital13, St Thomas' Hospital14, St James's University Hospital15, Bristol Royal Infirmary16, Aberdeen Royal Infirmary17, Dumfries and Galloway Royal Infirmary18, Wexham Park Hospital19, Auckland City Hospital20, Wigan21, Glasgow Royal Infirmary22, Musgrove Park Hospital23, Royal Surrey County Hospital24, Southmead Hospital25, Forth Valley Royal Hospital26, Coventry Health Care27, University Hospital of Wales28, Northern General Hospital29, Sapienza University of Rome30, Policlinico Umberto I31, Arrowe Park Hospital32, Morriston Hospital33, Aintree University Hospitals NHS Foundation Trust34, University Hospitals Birmingham NHS Foundation Trust35, Doncaster Royal Infirmary36, University of Health Sciences Antigua37, Brighton and Sussex University Hospitals NHS Trust38, Gloucestershire Hospitals NHS Foundation Trust39, Royal Gwent Hospital40, James Cook University Hospital41, Ziauddin University42
TL;DR: In this article, the authors used CC-NC permission for CC BY-NC No commercial re-use See rights and permissions published by BMJ and their employer(s) (or their employer's partner(s).
Abstract: © Author(s) (or their employer(s)) 2021 Re-use permitted under CC BY-NC No commercial re-use See rights and permissions Published by BMJ