Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
World J Clin Cases ; 9(28): 8388-8403, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34754848

RESUMO

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic is a global threat caused by the severe acute respiratory syndrome coronavirus-2. AIM: To develop and validate a risk stratification tool for the early prediction of intensive care unit (ICU) admission among COVID-19 patients at hospital admission. METHODS: The training cohort included COVID-19 patients admitted to the Wuhan Third Hospital. We selected 13 of 65 baseline laboratory results to assess ICU admission risk, which were used to develop a risk prediction model with the random forest (RF) algorithm. A nomogram for the logistic regression model was built based on six selected variables. The predicted models were carefully calibrated, and the predictive performance was evaluated and compared with two previously published models. RESULTS: There were 681 and 296 patients in the training and validation cohorts, respectively. The patients in the training cohort were older than those in the validation cohort (median age: 63.0 vs 49.0 years, P < 0.001), and the percentages of male gender were similar (49.6% vs 49.3%, P = 0.958). The top predictors selected in the RF model were neutrophil-to-lymphocyte ratio, age, lactate dehydrogenase, C-reactive protein, creatinine, D-dimer, albumin, procalcitonin, glucose, platelet, total bilirubin, lactate and creatine kinase. The accuracy, sensitivity and specificity for the RF model were 91%, 88% and 93%, respectively, higher than those for the logistic regression model. The area under the receiver operating characteristic curve of our model was much better than those of two other published methods (0.90 vs 0.82 and 0.75). Model A underestimated risk of ICU admission in patients with a predicted risk less than 30%, whereas the RF risk score demonstrated excellent ability to categorize patients into different risk strata. Our predictive model provided a larger standardized net benefit across the major high-risk range compared with model A. CONCLUSION: Our model can identify ICU admission risk in COVID-19 patients at admission, who can then receive prompt care, thus improving medical resource allocation.

2.
World J Clin Cases ; 9(13): 2994-3007, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33969085

RESUMO

BACKGROUND: The widespread coronavirus disease 2019 (COVID-19) has led to high morbidity and mortality. Therefore, early risk identification of critically ill patients remains crucial. AIM: To develop predictive rules at the time of admission to identify COVID-19 patients who might require intensive care unit (ICU) care. METHODS: This retrospective study included a total of 361 patients with confirmed COVID-19 by reverse transcription-polymerase chain reaction between January 19, 2020, and March 14, 2020 in Shenzhen Third People's Hospital. Multivariate logistic regression was applied to develop the predictive model. The performance of the predictive model was externally validated and evaluated based on a dataset involving 126 patients from the Wuhan Asia General Hospital between December 2019 and March 2020, by area under the receiver operating curve (AUROC), goodness-of-fit and the performance matrix including the sensitivity, specificity, and precision. A nomogram was also used to visualize the model. RESULTS: Among the patients in the derivation and validation datasets, 38 and 9 participants (10.5% and 2.54%, respectively) developed severe COVID-19, respectively. In univariate analysis, 21 parameters such as age, sex (male), smoker, body mass index (BMI), time from onset to admission (> 5 d), asthenia, dry cough, expectoration, shortness of breath, asthenia, and Rox index < 18 (pulse oxygen saturation, SpO2)/(FiO2 × respiratory rate, RR) showed positive correlations with severe COVID-19. In multivariate logistic regression analysis, only six parameters including BMI [odds ratio (OR) 3.939; 95% confidence interval (CI): 1.409-11.015; P = 0.009], time from onset to admission (≥ 5 d) (OR 7.107; 95%CI: 1.449-34.849; P = 0.016), fever (OR 6.794; 95%CI: 1.401-32.951; P = 0.017), Charlson index (OR 2.917; 95%CI: 1.279-6.654; P = 0.011), PaO2/FiO2 ratio (OR 17.570; 95%CI: 1.117-276.383; P = 0.041), and neutrophil/lymphocyte ratio (OR 3.574; 95%CI: 1.048-12.191; P = 0.042) were found to be independent predictors of COVID-19. These factors were found to be significant risk factors for severe patients confirmed with COVID-19. The AUROC was 0.941 (95%CI: 0.901-0.981) and 0.936 (95%CI: 0.886-0.987) in both datasets. The calibration properties were good. CONCLUSION: The proposed predictive model had great potential in severity prediction of COVID-19 in the ICU. It assisted the ICU clinicians in making timely decisions for the target population.

3.
Br J Pharmacol ; 178(4): 964-982, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33300167

RESUMO

BACKGROUND AND PURPOSE: Chronic alcohol consumption contributes to contractile dysfunction and unfavourable geometric changes in myocardium, accompanied by altered autophagy and disturbed mitochondrial homeostasis. The E3 ubiquitin ligase Parkin encoded by PARK2 gene maintains a fundamental role in regulating mitophagy and mitochondrial homeostasis, although little is known of its role in the aetiology of alcoholic cardiomyopathy. Here we assessed the effects of Parkin deletion in chronic alcohol-evoked cardiotoxicity. EXPERIMENTAL APPROACH: Following alcohol (4%) or control diet intake for 8 weeks, adult male wild-type (WT) and PARK2 knockout (Parkin-/- ) mice were examined using echocardiography. Cardiomyocyte mechanical properties, morphology of myocardium, and mitochondrial damage were also evaluated. Autophagy and mitophagy levels were assessed by LC3B and GFP-LC3 puncta, and lysosome-dependent autophagic flux was scrutinized using GFP-mRFP-LC3 puncta and Bafilomycin A1 treatment. KEY RESULTS: Chronic alcohol exposure provoked unfavourable geometric changes in myocardium and led to mitochondrial dysfunction and cardiac contractile defects, effects further exacerbated by Parkin knockout. Chronic alcohol exposure provoked autophagy and PINK1/Parkin-mediated mitophagy without affecting lysosome-dependent autophagic flux, the effects of which were diminished by Parkin deletion. Parkin adenovirus infection in neonatal rat cardiomyocytes further increased autophagy and protected against alcohol-induced myocardial injury, effects blocked by siRNA for Ambra1 (Autophagy and Beclin1 regulator 1). Immunofluorescence staining and co-immunoprecipitation assays showed interactions between Parkin and Ambra1. CONCLUSIONS AND IMPLICATIONS: Parkin was essential for cardiac homeostasis in alcohol challenge, accompanied by increased autophagy/mitophagy and maintenance of mitochondrial integrity through its interaction with Ambra1.


Assuntos
Cardiomiopatia Alcoólica , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Consumo de Bebidas Alcoólicas , Animais , Autofagia , Masculino , Camundongos , Mitocôndrias/metabolismo , Mitofagia , Ratos , Ubiquitina-Proteína Ligases/metabolismo
4.
Trials ; 21(1): 738, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831151

RESUMO

OBJECTIVES: This study aims to determine the protection provided by Shenfu injection (a traditional Chinese medicine) against development of organ dysfunction in critically ill patients with coronavirus disease 2019 (COVID-19). TRIAL DESIGN: This study is a multicenter, randomized, controlled, open-label, two-arm ratio 1:1, parallel group clinical trial. PARTICIPANTS: The patients, who are aged from 18 to 75 years old, with a confirmed or suspected diagnosis of severe or critical COVID-19, will be consecutively recruited in the study, according to the guideline on diagnosis and treatment of COVID-19 (the 7th version) issued by National Health Commission of the People's Republic of China. Exclusion criteria include pregnant and breastfeeding women, atopy or allergies to Shenfu Injection (SFI), severe underlying disease (malignant tumor with multiple metastases, uncontrolled hemopathy, cachexia, severe malnutrition, HIV), active bleeding, obstructive pneumonia caused by lung tumor, severe pulmonary interstitial fibrosis, alveolar proteinosis and allergic alveolitis, continuous use of immunosuppressive drugs in last 6 months, organ transplantation, expected death within 48 hours, the patients considered unsuitable for this study by researchers. The study is conducted in 11 ICUs of designated hospitals for COVID-19, located in 5 cities of China. INTERVENTION AND COMPARATOR: The enrolled patients will randomly receive 100 ml SFI (study group) or identical volume of saline (control group) twice a day for seven consecutive days. Patients in the both groups will be given usual care and the necessary supportive therapies as recommended by the latest edition of the management guidelines for COVID-19 (the 7th version so far). MAIN OUTCOMES: The primary endpoint is a composite of newly developed or exacerbated organ dysfunction. This is defined as an increase in the sequential organ failure assessment (SOFA) score of two or more, indicating sepsis and involvement of at least one organ. The SOFA score will be measured for the 14 days after enrolment from the baseline (the score at randomization). The secondary endpoints are shown below: • SOFA score in total • Pneumonia severity index score • Dosage of vasoactive drugs • Ventilation free days within 28 days • Length of stay in intensive care unit • Total hospital costs to treat the patient • 28-day mortality • The incidence of adverse drug events related to SFI RANDOMISATION: The block randomization codes were generated by SAS V.9.1 for allocation of participants in this study. The ratio of random distribution is 1:1. The sealed envelope method is used for allocation concealment. BLINDING (MASKING): The patients and statistical personnel analyzing study data are both blinded. The blinding of group assignment is not adopted for the medical staff. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study is expected to recruit 300 patients with COVID-19, (150 in each group). TRIAL STATUS: Protocol version 2.0, February 15, 2020. Patient recruitment started on February 25, and will end on August 31, 2020. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000030043. Registered February 21, 2020, http://www.chictr.org.cn/showprojen.aspx?proj=49866 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Escores de Disfunção Orgânica , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , COVID-19 , China , Infecções por Coronavirus/fisiopatologia , Estado Terminal , Humanos , Pandemias , Pneumonia Viral/fisiopatologia , SARS-CoV-2
5.
Crit Care ; 24(1): 394, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631393

RESUMO

BACKGROUND: The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. METHODS: Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. RESULTS: Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6-81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3-36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. CONCLUSIONS: Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Idoso , COVID-19 , China/epidemiologia , Infecções por Coronavirus/terapia , Estado Terminal , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Estudos Retrospectivos , Fatores de Risco
7.
Hepatology ; 72(2): 389-398, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32359177

RESUMO

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID-19 pneumonia in Hubei Province. APPROACH AND RESULTS: We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non-severe and the severe groups. AST abnormality was associated with the highest mortality risk compared with the other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. CONCLUSION: The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID-19-associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.


Assuntos
Betacoronavirus , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Fígado/fisiopatologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Adulto , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores , COVID-19 , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2
8.
Clin J Am Soc Nephrol ; 15(8): 1139-1145, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32444393

RESUMO

BACKGROUND AND OBJECTIVES: Previous reports on the outbreak of coronavirus disease 2019 were on the basis of data from the general population. Our study aimed to investigate the clinical features of patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective, single-center study, we included 49 hospitalized patients on maintenance hemodialysis and 52 hospitalized patients without kidney failure (controls) with confirmed coronavirus disease 2019 at Tongren Hospital of Wuhan University from January 30, 2020 to March 10, 2020. Demographic, clinical, laboratory, and radiologic characteristics and treatment and outcomes data were analyzed. The final date of follow-up was March 19, 2020. RESULTS: The median age of 101 patients was 62 years (interquartile range, 49-72). All patients were local residents of Wuhan. In terms of common symptoms, there were differences between patients on hemodialysis and controls (fatigue [59% versus 83%], dry cough [49% versus 71%], and fever [47% versus 90%]). Lymphocyte counts were decreased (0.8×109/L [patients on hemodialysis] versus 0.9×109/L [controls], P=0.02). Comparing patients on hemodialysis with controls, creatine kinase-muscle and brain type, myoglobin, hypersensitive troponin I, B-type natriuretic peptide, and procalcitonin were increased, and the percentage of abnormalities in bilateral lung was higher in computed tomographic scan (82% versus 69%, P=0.15) and unilateral lung was lower (10% versus 27%, P=0.03). Common complications including shock, acute respiratory distress syndrome, arrhythmia, and acute cardiac injury in patients on hemodialysis were significantly higher. Compared with controls, more patients on hemodialysis received noninvasive ventilation (25% versus 6%, P=0.008). As of March 19, 2020, three patients on hemodialysis (6%) were transferred to the intensive care unit and received invasive ventilation. Seven patients on hemodialysis (14%) had died. CONCLUSIONS: The main symptoms of coronavirus disease 2019 pneumonia, including fever and cough, were less common in patients on hemodialysis. Patients on hemodialysis with coronavirus disease 2019 were at higher risk of death.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Diálise Renal , Idoso , COVID-19 , China/epidemiologia , Infecções por Coronavirus/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Radiografia Torácica , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X
9.
Trials ; 21(1): 422, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448345

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Alanina/administração & dosagem , Alanina/efeitos adversos , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , COVID-19 , China , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Método Duplo-Cego , Estudos de Equivalência como Asunto , Feminino , Humanos , Infusões Intravenosas , Masculino , Estudos Multicêntricos como Assunto , Pandemias , Segurança do Paciente , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Medição de Risco , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
10.
Crit Care ; 24(1): 219, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410714

RESUMO

BACKGROUND: A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. METHODS: A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. RESULTS: A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57-70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5-17) days, and the duration from onset of symptoms to the study date was 31 (24-36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2-8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. CONCLUSIONS: Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Cuidados Críticos , Surtos de Doenças , Unidades de Terapia Intensiva , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Idoso , COVID-19 , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Resultado do Tratamento
11.
Lancet ; 395(10236): 1569-1578, 2020 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-32423584

RESUMO

BACKGROUND: No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. FINDINGS: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. INTERPRETATION: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. FUNDING: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Idoso , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Betacoronavirus , COVID-19 , China , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Pandemias , SARS-CoV-2
12.
Circ Res ; 126(12): 1671-1681, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32302265

RESUMO

RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.


Assuntos
Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Infecções por Coronavirus/epidemiologia , Mortalidade Hospitalar , Hipertensão/epidemiologia , Pneumonia Viral/epidemiologia , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19 , Infecções por Coronavirus/complicações , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações
14.
Front Med (Lausanne) ; 7: 607821, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33425951

RESUMO

Background: High-flow nasal cannula (HFNC) has been recommended as a suitable choice for the management of coronavirus disease 2019 (COVID-19) patients with acute hypoxemic respiratory failure before mechanical ventilation (MV); however, delaying MV with HFNC therapy is still a dilemma between the technique and clinical management during the ongoing pandemic. Methods: Retrospective analysis of COVID-19 patients treated with HFNC therapy from four hospitals of Wuhan, China. Demographic information and clinical variables before, at, and shortly after HFNC initiation were collected and analyzed. A risk-stratification model of HFNC failure (the need for MV) was developed with the 324 patients of Jin Yin-tan Hospital and validated its accuracy with 69 patients of other hospitals. Results: Among the training cohort, the median duration of HFNC therapy was 6 (range, 3-11), and 147 experienced HFNC failure within 7 days of HFNC initiation. Early predictors of HFNC failure on the basis of a multivariate regression analysis included age older than 60 years [odds ratio (OR), 1.93; 95% confidence interval (CI), 1.08-3.44; p = 0.027; 2 points], respiratory rate-oxygenation index (ROX) <5.31 (OR, 5.22; 95% CI, 2.96-9.20; p < 0.001; 5 points) within the first 4 h of HFNC initiation, platelets < 125 × 109/L (OR, 3.04; 95% CI, 1.46-6.35; p = 0.003; 3 points), and interleukin 6 (IL-6) >7.0 pg/mL (OR, 3.34; 95% CI, 1.79-6.23; p < 0.001; 3 points) at HFNC initiation. A weighted risk-stratification model of these predictors showed sensitivity of 80.3%, specificity of 71.2% and a better predictive ability than ROX index alone [area under the curve (AUC) = 0.807 vs. 0.779, p < 0.001]. Six points were used as a cutoff value for the risk of HFNC failure stratification. The HFNC success probability of patients in low-risk group (84.2%) was 9.84 times that in the high-risk group (34.8%). In the subsequent validation cohort, the AUC of the model was 0.815 (0.71-0.92). Conclusions: Aged patients with lower ROX index, thrombocytopenia, and elevated IL-6 values are at increased risk of HFNC failure. The risk-stratification models accurately predicted the HFNC failure and early stratified COVID-19 patients with HFNC therapy into relevant risk categories.

15.
Front Med (Lausanne) ; 7: 615845, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33425960

RESUMO

Background: The outbreak of coronavirus disease 2019 (COVID-19) has led to a large and increasing number of patients requiring prolonged mechanical ventilation and tracheostomy. The indication and optimal timing of tracheostomy in COVID-19 patients are still unclear, and the outcomes about tracheostomy have not been extensively reported. We aimed to describe the clinical characteristics and outcomes of patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who underwent elective tracheostomies. Methods: The multi-center, retrospective, observational study investigated all the COVID-19 patients who underwent elective tracheostomies in intensive care units (ICUs) of 23 hospitals in Hubei province, China, from January 8, 2020 to March 25, 2020. Demographic information, clinical characteristics, treatment, details of the tracheostomy procedure, successful weaning after tracheostomy, and living status were collected and analyzed. Data were compared between early tracheostomy patients (tracheostomy performed within 14 days of intubation) and late tracheostomy patients (tracheostomy performed after 14 days). Results: A total of 80 patients were included. The median duration from endotracheal intubation to tracheostomy was 17.5 [IQR 11.3-27.0] days. Most tracheotomies were performed by ICU physician [62 (77.5%)], and using percutaneous techniques [63 (78.8%)] at the ICU bedside [76 (95.0%)]. The most common complication was tracheostoma bleeding [14 (17.5%)], and major bleeding occurred in 4 (5.0%) patients. At 60 days after intubation, 31 (38.8%) patients experienced successful weaning from ventilator, 17 (21.2%) patients discharged from ICU, and 43 (53.8%) patients had died. Higher 60 day mortality [22 (73.3%) vs. 21 (42.0%)] were identified in patients who underwent early tracheostomy. Conclusions: In patients with SARS-CoV-2 pneumonia, tracheostomies were feasible to conduct by ICU physician at bedside with few major complications. Compared with tracheostomies conducted after 14 days of intubation, tracheostomies within 14 days were associated with an increased mortality rate.

16.
Medicine (Baltimore) ; 98(12): e14920, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30896649

RESUMO

Serum YKL-40, a potential inflammatory marker, is greatly increased at the early stage of ST-segment elevation myocardial infarction (STEMI). Here, we hypothesized that YKL-40 levels at admission could predict the long-term outcomes after STEMI.A total of 324 patients with acute STEMI undergoing primary percutaneous coronary intervention (PCI) were consecutively enrolled and followed for 24 months. The baseline clinical and procedural data were recorded, and serum YKL-40 levels at admission were measured using ELISA method. The endpoint of interest was major adverse cardiac event (MACE), including all-cause death, recurrent myocardial infarction, and hospitalization for heart failure.Patients with elevated serum YKL-40 levels (≥126.8 ng/mL) were more likely to be older and smoker and to present with type 2 diabetes, advanced Killip class, multivessel disease and intra-aortic balloon pump, with increased levels of admission glucose, triglyceride, and high-sensitivity C-reactive protein and decreased level of high-density lipoprotein cholesterol. During the follow-up period, the incidence of MACE was notably higher in the high than in the low YKL-40 groups (28.4% vs 11.1%, P < .001). Kaplan-Meier curve showed that elevated YKL-40 levels were associated with reduced MACE-free survivals (log-rank P < .001). In multivariate Cox regression analysis, we found that high serum YKL-40 level was an independent predictor of MACE after controlling for clinical and angiographic variables (hazard ratio: 1.65, 95% confidence interval: 1.14-2.39, P = .008).The results of our study indicate that serum YKL-40 may be used as a biomarker to predict the long-term outcome after PCI in patients with STEMI.


Assuntos
Proteína 1 Semelhante à Quitinase-3/sangue , Intervenção Coronária Percutânea/estatística & dados numéricos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Fatores Etários , Idoso , Biomarcadores , Glicemia , Proteína C-Reativa/análise , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Índice de Gravidade de Doença , Fumar/epidemiologia , Fatores Socioeconômicos
17.
Inflammation ; 42(2): 637-649, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30392071

RESUMO

Previous studies have been indicated that tumor necrosis factor receptor-associated factor 6 (TRAF6)-induced inflammation leads to acute kidney injury (AKI). How microRNA (miR) contributes to this process is poorly defined. The aim of this study was to investigate whether miR-590-3p regulated lipopolysaccharide (LPS)-induced inflammatory response by inhibiting TRAF6. LPS-induced septic mice were treated with adenovirus expressing miR-590-3p (ad-miR-590-3p) via tail-vein injection. AKI was evaluated by examining serum cystatin C (CysC), serum ß2-microglobulin (ß2-MG), and blood urea nitrogen (BUN). The mRNA and protein levels were assayed by RT-qPCR and western blotting, respectively. The proliferation of podocytes was monitored using the MTT assay. Cell apoptosis was analyzed by flow cytometry. Survival outcomes in ad-miR-590-3p-transfected septic mice were markedly improved compared with mice with LPS-induced sepsis. Ad-miR-590-3p transfection significantly attenuated LPS-induced AKI, which was reflected by an improved glomerular filtration rate (GFR) as determined by measuring CysC, ß2-MG, and BUN. Moreover, we observed that miR-590-3p was a novel regulator of TRAF6, binding to its 3'-untranslated regions (3'-UTRs). In vitro, a miR-590-3p gain-of-function mutation blocked LPS-induced podocyte growth inhibition and apoptosis, as well as overactivation of the inflammatory response. miR-590-3p has the ability to suppress LPS-induced AKI and podocyte apoptosis by targeting TRAF6. This might provide a novel strategy for the treatment of LPS-induced renal injuries.


Assuntos
Injúria Renal Aguda/prevenção & controle , MicroRNAs/genética , Sepse/patologia , Fator 6 Associado a Receptor de TNF/antagonistas & inibidores , Injúria Renal Aguda/tratamento farmacológico , Animais , Apoptose , Inflamação/induzido quimicamente , Lipopolissacarídeos , Camundongos , Podócitos/patologia , Sepse/complicações , Taxa de Sobrevida
18.
Resuscitation ; 82(8): 1081-6, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21531066

RESUMO

AIM OF THE STUDY: Reperfusion following cerebral ischemia leads to excessive production of reactive oxygen species (ROS) and consumption of endogenous antioxidants. Antioxidant enzymes are considered to have beneficial effects against various diseases mediated by ROS. Copper, zinc-superoxide dismutase (SOD1) is one of the major defensive mechanisms by which cells counteract the deleterious effects of ROS after ischemia. However, exogenous SOD1 can not be delivered into living cells because of the poor permeability and selectivity of the cell membrane, thus its application for protecting cells/tissues from oxidative stress damage is greatly limited. METHODS: The purified SOD1 or PEP-1-SOD1 fusion proteins were injected into rats via their tail veins, the transduction ability of PEP-1-SOD1 was examined with immunofluorescent staining and SOD1 activity was measured. Moreover, we determined whether or not PEP-1-SOD1 can protect brain from ischemic injury in an experimental asphyxial cardiac arrest rat model through histopathologic analysis, evaluating the levels of malondialdehyde (MDA), S100ß and neuron specific enolase (NSE). RESULTS: SOD1 protein was observed in PEP-1-SOD1-treated animals and SOD1 activity was significantly increased. However, SOD1 protein was not detected in SOD1-treated animals. The transduced PEP-1-SOD1 significantly attenuated cerebral ischemia-reperfusion damage, inhibited ischemia-induced lipid peroxidation, and protected neurons in hippocampus from the damage induced by transient global ischemic insults. CONCLUSIONS: PEP-1-SOD1 fusion protein can be transduced into the neurons in vivo and protect the neurons from the transient global ischemia-induced damage, suggesting PEP-1-SOD1 may be used for the treatment of oxidative stress-associated disorders such as transient global cerebral ischemia.


Assuntos
Isquemia Encefálica/prevenção & controle , Cisteamina/análogos & derivados , Parada Cardíaca/complicações , Peptídeos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Superóxido Dismutase/farmacologia , Análise de Variância , Animais , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Distribuição de Qui-Quadrado , Cisteamina/administração & dosagem , Cisteamina/metabolismo , Cisteamina/farmacologia , Parada Cardíaca/fisiopatologia , Peroxidação de Lipídeos , Masculino , Fatores de Crescimento Neural/metabolismo , Estresse Oxidativo , Peptídeos/administração & dosagem , Peptídeos/metabolismo , Fosfopiruvato Hidratase/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/fisiopatologia , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/metabolismo , Superóxido Dismutase/administração & dosagem , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1
19.
J Hum Genet ; 56(4): 330-4, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21307863

RESUMO

Parkinson's disease is a degenerative central nervous system disorder that often impairs motor skills, speech and other functions. We discovered a large Chinese family showing primarily parkinsonism symptoms with autosomal dominant inheritance. Six affected individuals in the family showed typical parkinsonism symptoms, including pill-rolling tremor. Two other affected individuals showed cerebellar ataxia symptoms. A whole-genome scan using the 50K single nucleotide polymorphism array with three different linkage methods detected two positive regions on chromosome 12q24.1 and 5q13.3. The ATXN2 gene, responsible for spinocerebellar ataxia type 2 (SCA2) was located precisely in the center of the positive region on chromosome 12. Further analysis of SCA2 revealed heterozygous pathological CAG expansions in the family. The affected individuals' symptoms were typical of parkinsonism, but complex. Inverse correlation between CAG repeat size and age of onset is not obvious in this pedigree. This parkinsonism-predominant SCA2 family shared the same disease gene locus with other 'standard' SCA2 families, but it is possible that variations in one or more modifier genes might account for the parkinsonism-predominant SCA2 predisposition observed in this pedigree.


Assuntos
Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 5/genética , Doença de Parkinson/genética , Doença de Parkinson/patologia , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/patologia , /genética , Ataxinas , Cerebelo/patologia , Expansão das Repetições de DNA/genética , Genes Dominantes/genética , Ligação Genética , Humanos , Imageamento por Ressonância Magnética , Proteínas do Tecido Nervoso/genética , Linhagem , Polimorfismo de Nucleotídeo Único/genética
20.
Mol Cells ; 27(2): 159-66, 2009 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-19277497

RESUMO

Myocardial ischemia-reperfusion injury is a medical problem occurring as damage to the myocardium following blood flow restoration after a critical period of coronary occlusion. Oxygen free radicals (OFR) are implicated in reperfusion injury after myocardial ischemia. The antioxidant enzyme, Cu, Zn-superoxide dismutase (Cu, Zn-SOD, also called SOD1) is one of the major means by which cells counteract the deleterious effects of OFR after ischemia. Recently, we reported that a PEP-1-SOD1 fusion protein was efficiently delivered into cultured cells and isolated rat hearts with ischemia-reperfusion injury. In the present study, we investigated the protective effects of the PEP-1-SOD1 fusion protein after ischemic insult. Immunofluorescecnce analysis revealed that the expressed and purified PEP-1-SOD1 fusion protein injected into rat tail veins was efficiently transduced into the myocardium with its native protein structure intact. When injected into Sprague-Dawley rat tail veins, the PEP-1- SOD1 fusion protein significantly attenuated myocardial ischemia-reperfusion damage; characterized by improving cardiac function of the left ventricle, decreasing infarct size, reducing the level of malondialdehyde (MDA), decreasing the release of creatine kinase (CK) and lactate dehydrogenase (LDH), and relieving cardiomyocyte apoptosis. These results suggest that the biologically active intact forms of PEP-1-SOD1 fusion protein will provide an efficient strategy for therapeutic delivery in various diseases related to SOD1 or to OFR.


Assuntos
Cisteamina/análogos & derivados , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/enzimologia , Peptídeos/metabolismo , Proteínas Recombinantes de Fusão/administração & dosagem , Superóxido Dismutase/metabolismo , Animais , Apoptose , Creatina Quinase/metabolismo , Cisteamina/metabolismo , Imunofluorescência , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase-1
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...