Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
1.
J Immunol Methods ; 499: 113165, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34634317

RESUMO

Monitoring the burden and spread of infection with the new coronavirus SARS-CoV-2, whether within small communities or in large geographical settings, is of paramount importance for public health purposes. Serology, which detects the host antibody response to the infection, is the most appropriate tool for this task, since virus-derived markers are most reliably detected during the acute phase of infection. Here we show that our ELISA protocol, which is based on antibody binding to the Receptor Binding Domain (RBD) of the S1 subunit of the viral Spike protein expressed as a novel fusion protein, detects antibody responses to SARS-CoV-2 infection and vaccination. We also show that our ELISA is accurate and versatile. It compares favorably with commercial assays widely used in clinical practice to determine exposure to SARS-CoV-2. Moreover, our protocol accommodates use of various blood- and non-blood-derived biospecimens, such as breast milk, as well as dried blood obtained with microsampling cartridges that are appropriate for remote collection. As a result, our RBD-based ELISA protocols are well suited for seroepidemiology and other large-scale studies requiring parsimonious sample collection outside of healthcare settings.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/diagnóstico , Teste em Amostras de Sangue Seco , Anticorpos Antivirais/imunologia , Sítios de Ligação , COVID-19/sangue , COVID-19/imunologia , Humanos , Vacinação
2.
Ann Am Thorac Soc ; 18(9): 1435-1443, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34468284

RESUMO

Poor air quality affects the health and wellbeing of large populations around the globe. Although source controls are the most effective approaches for improving air quality and reducing health risks, individuals can also take actions to reduce their personal exposure by staying indoors, reducing physical activity, altering modes of transportation, filtering indoor air, and using respirators and other types of face masks. A synthesis of available evidence on the efficacy, effectiveness, and potential adverse effects or unintended consequences of personal interventions for air pollution is needed by clinicians to assist patients and the public in making informed decisions about use of these interventions. To address this need, the American Thoracic Society convened a workshop in May of 2018 to bring together a multidisciplinary group of international experts to review the current state of knowledge about personal interventions for air pollution and important considerations when helping patients and the general public to make decisions about how best to protect themselves. From these discussions, recommendations were made regarding when, where, how, and for whom to consider personal interventions. In addition to the efficacy and safety of the various interventions, the committee considered evidence regarding the identification of patients at greatest risk, the reliability of air quality indices, the communication challenges, and the ethical and equity considerations that arise when discussing personal interventions to reduce exposure and risk from outdoor air pollution.


Assuntos
Poluição do Ar , Poluição do Ar/efeitos adversos , Poluição do Ar/prevenção & controle , Humanos , Reprodutibilidade dos Testes , Transportes , Estados Unidos
3.
Crit Care Explor ; 3(8): e0515, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34476402

RESUMO

OBJECTIVES: Critically ill patients with coronavirus disease 2019 have variable mortality. Risk scores could improve care and be used for prognostic enrichment in trials. We aimed to compare machine learning algorithms and develop a simple tool for predicting 28-day mortality in ICU patients with coronavirus disease 2019. DESIGN: This was an observational study of adult patients with coronavirus disease 2019. The primary outcome was 28-day inhospital mortality. Machine learning models and a simple tool were derived using variables from the first 48 hours of ICU admission and validated externally in independent sites and temporally with more recent admissions. Models were compared with a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 using the area under the receiver operating characteristic curve and calibration. SETTING: Sixty-eight U.S. ICUs. PATIENTS: Adults with coronavirus disease 2019 admitted to 68 ICUs in the United States between March 4, 2020, and June 29, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study included 5,075 patients, 1,846 (36.4%) of whom died by day 28. eXtreme Gradient Boosting had the highest area under the receiver operating characteristic curve in external validation (0.81) and was well-calibrated, while k-nearest neighbors were the lowest performing machine learning algorithm (area under the receiver operating characteristic curve 0.69). Findings were similar with temporal validation. The simple tool, which was created using the most important features from the eXtreme Gradient Boosting model, had a significantly higher area under the receiver operating characteristic curve in external validation (0.78) than the Sequential Organ Failure Assessment score (0.69), National Early Warning Score (0.60), and CURB-65 (0.65; p < 0.05 for all comparisons). Age, number of ICU beds, creatinine, lactate, arterial pH, and Pao2/Fio2 ratio were the most important predictors in the eXtreme Gradient Boosting model. CONCLUSIONS: eXtreme Gradient Boosting had the highest discrimination overall, and our simple tool had higher discrimination than a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 on external validation. These models could be used to improve triage decisions and clinical trial enrichment.

4.
medRxiv ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34282427

RESUMO

Monitoring the burden and spread of infection with the new coronavirus SARS-CoV-2, whether within small communities or in large geographical settings, is of paramount importance for public health purposes. Serology, which detects the host antibody response to the infection, is the most appropriate tool for this task, since virus-derived markers are most reliably detected during the acute phase of infection. Here we show that our ELISA protocol, which is based on antibody binding to the Receptor Binding Domain (RBD) of the S1 subunit of the viral Spike protein expressed as a novel fusion protein, detects antibody responses to SARS-CoV-2 infection and COVID-19 vaccination. We also show that our ELISA is accurate and versatile. It compares favorably with commercial assays widely used in clinical practice to determine exposure to SARS-CoV-2. Moreover, our protocol accommodates use of various blood- and non-blood-derived biospecimens, such as breast milk, as well as dried blood obtained with microsampling cartridges that are appropriate for remote collection. As a result, our RBD-based ELISA protocols are well suited for seroepidemiology and other large-scale studies requiring parsimonious sample collection outside of healthcare settings.

6.
Crit Care Explor ; 3(3): e0372, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33786448

RESUMO

Objectives: About 15% of hospitalized coronavirus disease 2019 patients require ICU admission, and most (80%) of these require invasive mechanical ventilation. Lung-protective ventilation in coronavirus disease 2019 acute respiratory failure may result in severe respiratory acidosis without significant hypoxemia. Low-flow extracorporeal Co2 removal can facilitate lung-protective ventilation and avoid the adverse effects of severe respiratory acidosis. The objective was to evaluate the efficacy of extracorporeal Co2 removal using the Hemolung Respiratory Assist System in correcting severe respiratory acidosis in mechanically ventilated coronavirus disease 2019 patients with severe acute respiratory failure. Design: Retrospective cohort analysis of patients with coronavirus disease 2019 mechanically ventilated with severe hypercapnia and respiratory acidosis and treated with low-flow extracorporeal Co2 removal. Setting: Eight tertiary ICUs in the United States. Patients: Adult patients supported with the Hemolung Respiratory Assist System from March 1, to September 30, 2020. Interventions: Extracorporeal Co2 removal with Hemolung Respiratory Assist System under a Food and Drug Administration emergency use authorization for coronavirus disease 2019. Measurements and Main Results: The primary outcome was improvement in pH and Paco2 from baseline. Secondary outcomes included survival to decannulation, mortality, time on ventilator, and adverse events. Thirty-one patients were treated with Hemolung Respiratory Assist System with significant improvement in pH and Pco2 in this cohort. Two patients experienced complications that prevented treatment. Of the 29 treated patients, 58% survived to 48 hours post treatment and 38% to hospital discharge. No difference in age or comorbidities were noted between survivors and nonsurvivors. There was significant improvement in pH (7.24 ± 0.12 to 7.35 ± 0.07; p < 0.0001) and Paco2 (79 ± 23 to 58 ± 14; p < 0.0001) from baseline to 24 hours. Conclusions: In this retrospective case series of 29 patients, we have demonstrated efficacy of extracorporeal Co2 removal using the Hemolung Respiratory Assist System to improve respiratory acidosis in patients with severe hypercapnic respiratory failure due to coronavirus disease 2019.

7.
Crit Care Med ; 49(7): 1026-1037, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33595960

RESUMO

OBJECTIVES: Therapies for patients with respiratory failure from coronavirus disease 2019 are urgently needed. Early implementation of prone positioning ventilation improves survival in patients with acute respiratory distress syndrome, but studies examining the effect of proning on survival in patients with coronavirus disease 2019 are lacking. Our objective was to estimate the effect of early proning initiation on survival in patients with coronavirus disease 2019-associated respiratory failure. DESIGN: Data were derived from the Study of the Treatment and Outcomes in Critically Ill Patients with coronavirus disease 2019, a multicenter cohort study of critically ill adults with coronavirus disease 2019 admitted to 68 U.S. hospitals. Using these data, we emulated a target trial of prone positioning ventilation by categorizing mechanically ventilated hypoxemic (ratio of Pao2 over the corresponding Fio2 ≤ 200 mm Hg) patients as having been initiated on proning or not within 2 days of ICU admission. We fit an inverse probability-weighted Cox model to estimate the mortality hazard ratio for early proning versus no early proning. Patients were followed until death, hospital discharge, or end of follow-up. SETTING: ICUs at 68 U.S. sites. PATIENTS: Critically ill adults with laboratory-confirmed coronavirus disease 2019 receiving invasive mechanical ventilation with ratio of Pao2 over the corresponding Fio2 less than or equal to 200 mm Hg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 2,338 eligible patients, 702 (30.0%) were proned within the first 2 days of ICU admission. After inverse probability weighting, baseline and severity of illness characteristics were well-balanced between groups. A total of 1,017 (43.5%) of the 2,338 patients were discharged alive, 1,101 (47.1%) died, and 220 (9.4%) were still hospitalized at last follow-up. Patients proned within the first 2 days of ICU admission had a lower adjusted risk of death compared with nonproned patients (hazard ratio, 0.84; 95% CI, 0.73-0.97). CONCLUSIONS: In-hospital mortality was lower in mechanically ventilated hypoxemic patients with coronavirus disease 2019 treated with early proning compared with patients whose treatment did not include early proning.


Assuntos
COVID-19/complicações , Hipóxia/terapia , Posicionamento do Paciente , Decúbito Ventral , Respiração Artificial , Insuficiência Respiratória/etiologia , Idoso , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Análise de Sobrevida , Tempo para o Tratamento , Estados Unidos/epidemiologia
8.
J Asthma ; : 1-7, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33577360

RESUMO

OBJECTIVE: Several therapeutic agents have been assessed for the treatment of COVID-19, but few approaches have been proven efficacious. Because leukotriene receptor antagonists, such as montelukast have been shown to reduce both cytokine release and lung inflammation in preclinical models of viral influenza and acute respiratory distress syndrome, we hypothesized that therapy with montelukast could be used to treat COVID-19. The objective of this study was to determine if montelukast treatment would reduce the rate of clinical deterioration as measured by the COVID-19 Ordinal Scale. METHODS: We performed a retrospective analysis of COVID-19 confirmed hospitalized patients treated with or without montelukast. We used "clinical deterioration" as the primary endpoint, a binary outcome defined as any increase in the Ordinal Scale value from Day 1 to Day 3 of the hospital stay, as these data were uniformly available for all admitted patients before hospital discharge. Rates of clinical deterioration between the montelukast and non-montelukast groups were compared using the Fisher's exact test. Univariate logistic regression was also used to assess the association between montelukast use and clinical deterioration. A total of 92 patients were analyzed, 30 who received montelukast at the discretion of the treating physician and 62 patients who did not receive montelukast. RESULTS: Patients receiving montelukast experienced significantly fewer events of clinical deterioration compared with patients not receiving montelukast (10% vs 32%, p = 0.022). Our findings suggest that montelukast associates with a reduction in clinical deterioration for COVID-19 confirmed patients as measured on the COVID-19 Ordinal Scale. CONCLUSIONS: Hospitalized COVID-19 patients treated with montelukast had fewer events of clinical deterioration, indicating that this treatment may have clinical activity. While this retrospective study highlights a potential pathway for COVID-19 treatment, this hypothesis requires further study by prospective studies.

9.
Ann Intern Med ; 174(5): 622-632, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33493012

RESUMO

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. DESIGN: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). LIMITATION: Observational design. CONCLUSION: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. PRIMARY FUNDING SOURCE: None.


Assuntos
Anticoagulantes/administração & dosagem , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/virologia , COVID-19/complicações , Idoso , Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/mortalidade , COVID-19/mortalidade , Estado Terminal , Feminino , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Hemorragia/virologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Taxa de Sobrevida , Estados Unidos/epidemiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/virologia
10.
JAMA Intern Med ; 181(1): 41-51, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33080002

RESUMO

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 <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). 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.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/tratamento farmacológico , Mortalidade Hospitalar , Insuficiência Respiratória/terapia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Anticoagulantes/uso terapêutico , COVID-19/fisiopatologia , Estudos de Coortes , Estado Terminal , Intervenção Médica Precoce , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Mortalidade , Escores de Disfunção Orgânica , Posicionamento do Paciente , Decúbito Ventral , Modelos de Riscos Proporcionais , Receptores de Interleucina-6/antagonistas & inibidores , Respiração Artificial , Insuficiência Respiratória/fisiopatologia , SARS-CoV-2 , Adulto Jovem
11.
ERJ Open Res ; 6(4)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33043052

RESUMO

#COVID19-induced ARDS is partly explained by the presence of microthrombi, motivating the use of thrombolytics. This study shows that thrombolytics decrease dead space ventilation in COVID-19 ARDS patients. https://bit.ly/2GdM44a.

12.
Ann N Y Acad Sci ; 1480(1): 14-29, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32726497

RESUMO

Acute respiratory distress syndrome (ARDS) is a highly morbid lung pathology induced by exposure to chemical warfare agents, including vesicants, phosgene, chlorine, and ricin. In this review, we describe the pathology associated with the development of ARDS in humans and experimental models of acute lung injury following animal exposure to these high-priority threat agents. Potential future approaches to disease-modifying treatment used in preclinical animal studies, including antioxidants, anti-inflammatories, biologics, and mesenchymal stem cells, are also described. As respiratory pathologies, including ARDS, are the major cause of morbidity and mortality following exposure to chemical threat agents, understanding mechanisms of disease pathogenesis is key to the development of efficacious therapeutics beyond the primary intervention principle, which remains mechanical ventilation.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Substâncias para a Guerra Química/envenenamento , Respiração Artificial , Síndrome do Desconforto Respiratório/terapia , Animais , Humanos , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia
13.
JAMA Intern Med ; 180(11): 1436-1447, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32667668

RESUMO

Importance: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. Objectives: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. Design, Setting, and Participants: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. Exposures: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. Results: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2-4 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. Conclusions and Relevance: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.


Assuntos
COVID-19/mortalidade , Estado Terminal/mortalidade , Unidades de Terapia Intensiva , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estado Terminal/terapia , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , Estados Unidos
15.
J Mol Diagn ; 22(7): 871-875, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32405270

RESUMO

As the coronavirus disease 2019 (COVID-19) pandemic sweeps across the world, the availability of viral transport medium (VTM) has become severely limited, contributing to delays in diagnosis and rationing of diagnostic testing. Given that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA has demonstrated stability, we posited that phosphate-buffered saline (PBS) may be a viable transport medium, as an alternative to VTM, for clinical real-time quantitative PCR (qPCR) testing. The intra-individual reliability and interindividual reliability of SARS-CoV-2 qPCR were assessed in clinical endotracheal secretion samples transported in VTM or PBS to evaluate the stability of the qPCR signal for three viral targets (N gene, ORF1ab, and S gene) when samples were stored in these media at room temperature for up to 18 hours. We report that the use of PBS as a transport medium allows high intra-individual and interindividual reliability, maintains viral stability, and compares with VTM in the detection of the three SARS-CoV-2 genes through 18 hours of storage. This study establishes PBS as a clinically useful medium that can be readily deployed for transporting and short-term preservation of specimens containing SARS-CoV-2. Use of PBS as a transport medium has the potential to increase testing capacity for SARS-CoV-2, aiding more widespread screening and early diagnosis of COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , RNA Viral/análise , Solução Salina/química , Manejo de Espécimes/métodos , Cultura de Vírus/métodos , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Valor Preditivo dos Testes , Preservação Biológica , RNA Viral/genética , SARS-CoV-2
16.
Chest ; 158(1): e15-e19, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32343968

RESUMO

Novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in Wuhan, China. Since then, COVID-19 has become a pandemic affecting more than 4.1 million people worldwide. Patients with COVID-19 have a wide spectrum of manifestations, one being cytokine release syndrome (CRS) and its fatal correlate, secondary hemophagocytic lymphohistiocytosis (sHLH). Anti-cytokine therapy such as tocilizumab, an IL-6 receptor antagonist, is a potential treatment for COVID-19; however, data regarding the efficacy of this anti-IL-6 therapy are currently lacking. We report two cases of patients who received a diagnosis of COVID-19 complicated by CRS and were treated with tocilizumab. Both patients progressed to sHLH despite treatment with tocilizumab, and one developed viral myocarditis, challenging the safety and clinical usefulness of tocilizumab in the treatment of COVID-19-induced CRS. These cases highlight the need for clinical trials to determine optimal patient selection and timing for the use of tocilizumab during this disease process.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Infecções por Coronavirus , Síndrome da Liberação de Citocina , Linfo-Histiocitose Hemofagocítica , Pandemias , Pneumonia Viral , Adulto , Idoso , Anti-Infecciosos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Azitromicina/administração & dosagem , Betacoronavirus/isolamento & purificação , Proteína C-Reativa/análise , COVID-19 , Deterioração Clínica , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/terapia , Síndrome da Liberação de Citocina/virologia , Evolução Fatal , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hipóxia/etiologia , Hipóxia/terapia , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/terapia , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Miocardite/terapia , Miocardite/virologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Respiração Artificial/métodos , SARS-CoV-2 , Choque Séptico/etiologia , Choque Séptico/terapia
17.
Artigo em Inglês | MEDLINE | ID: mdl-30845693

RESUMO

Sarcoid-like granulomatous diseases (SGD) have been previously identified in cohorts of World Trade Center (WTC) dust-exposed individuals. In the present studies, we analyzed lung and/or lymph node biopsies from patients referred to our clinic with suspected WTC dust-induced lung disease to evaluate potential pathophysiologic mechanisms. Histologic sections of lung and/or lymph node samples were analyzed for markers of injury, oxidative stress, inflammation, fibrosis, and epigenetic modifications. Out of seven patients examined, we diagnosed four with SGD and two with pulmonary fibrosis; one was diagnosed later with SGD at another medical facility. Patients with SGD were predominantly white, obese men, who were less than 50 years old and never smoked. Cytochrome b5, cytokeratin 17, heme oxygenase-1, lipocalin-2, inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor α, ADP-ribosylation factor-like GTPase 11, mannose receptor-1, galectin-3, transforming growth factor ß, histone-3 and methylated histone-3 were identified in lung and lymph nodes at varying levels in all samples examined. Three of the biopsy samples with granulomas displayed peri-granulomatous fibrosis. These findings are important and suggest the potential of WTC dust-induced fibrotic sarcoid. It is likely that patient demographics and/or genetic factors influence the response to WTC dust injury and that these contribute to different pathological outcomes.


Assuntos
Exposição Ocupacional , Sarcoidose/etiologia , Ataques Terroristas de 11 de Setembro , Adulto , Poeira , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Emerg Med Clin North Am ; 35(1): 11-23, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27908328

RESUMO

Recent literature continues to refine which components of the early goal-directed therapy (EGDT) algorithm are necessary. Given it utilizes central venous pressure, continuous central venous oxygen saturation, routine blood transfusions, and inotropic medications, this algorithm can be timely, invasive, costly, and potentially harmful. New trials highlight early recognition, early fluid resuscitation, appropriate antibiotic treatment, source control, and the application of a multidisciplinary evidence-based approach as essential components of current sepsis management. This article discusses the landmark sepsis trials that have been published over the past several decades and offers recommendations on what should currently be considered 'usual care'.


Assuntos
Sepse/terapia , Antibacterianos/uso terapêutico , Cateterismo Venoso Central , Protocolos Clínicos/normas , Medicina Baseada em Evidências , Hidratação , Humanos , Sepse/diagnóstico
19.
Int J Nephrol Renovasc Dis ; 9: 257-262, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27822078

RESUMO

Critically ill patients receive a significant amount of fluids leading to a positive fluid balance; this dilutes serum creatinine resulting in an overestimated glomerular filtration rate. The goal of our study is to identify undiagnosed or underestimated acute kidney injury (AKI) in the intensive care unit (ICU). It will also identify the morbidity and mortality associated with an underestimated AKI. We reviewed records of patients admitted to our institution (Staten Island University Hospital) between 2012 and 2013 for more than 2 days. Patients with end stage renal disease were excluded. AKI was defined using the Acute Kidney Injury Network criteria. The following formula was used to identify and restage patients with AKI: adjusted creatinine = serum creatinine × [(hospital admission weight (kg) 0.6 + Σ (daily cumulative fluid balance (L))/hospital admission weight × 0.6]. The primary outcome identified newly diagnosed AKI and those who were restaged. The secondary outcome identified associated morbidities. Seven-hundred and thirty-three out of 1,982 ICU records reviewed, were used. Two-hundred and fifty-seven (mean age 69.8±14.9) had AKI, out of which 15.9% were restaged using the equation. Comparison of mean by Student's t-test showed no difference between patients who were restaged. Similarly, chi-square revealed no differences between both arms, except mean admission weight (lower in patients who were restaged), fluid balance on days 1, 2, and 3 (higher in the restaged arm), and the presence of congestive heart failure (more prevalent in the restaged arm). Of note, the mean cost of stay was US$150,562.82 vs $197,174.63 for same stage vs restaged, respectively, however, without statistical significance (P=0.74). Applying the adjustment equation showed a modest (15.9%) increase in the AKI staging slightly impacting outcomes (mortality, length, and cost of stay) without statistical significance.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...