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1.
Discov Med ; 29(158): 201-209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007195

RESUMO

Sepsis is an important disorder in intensive care medicine, and the emphasis is not on infections but the imbalance in body reactions and life-threatening organ dysfunction. The infection, the imbalance in the body's reaction, and the deadly organ dysfunction are three aspects of sepsis. Currently, there is still a debate on suitable criteria for the diagnosis of patients with sepsis with continuing changes in the guidelines on sepsis management. Here we summarize recent advances on the definitions, diagnosis, and treatment in the clinical practice of sepsis management in the emergency department. We also highlight future research directions on sepsis. In particular, given the global outbreak of coronavirus disease 2019 (COVID-19), we briefly describe the relationship between COVID-19 and sepsis. How to manage sepsis caused by emerging pathogens such as COVID-19 is a new challenge for care professionals in the emergency department.


Assuntos
Betacoronavirus/patogenicidade , Doenças Transmissíveis Emergentes/terapia , Infecções por Coronavirus/terapia , Tratamento de Emergência/métodos , Pneumonia Viral/terapia , Sepse/terapia , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Doenças Transmissíveis Emergentes/complicações , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Serviço Hospitalar de Emergência/organização & administração , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Sepse/diagnóstico , Sepse/virologia , Índice de Gravidade de Doença
2.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33004529

RESUMO

Novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has rapidly spread throughout the world, resulting in a pandemic with high mortality. There are no effective treatments for the management of severe COVID-19 and current therapeutic trials are focused on antiviral therapy and attenuation of hyper-inflammation with anti-cytokine therapy. Severe COVID-19 pneumonia shares some pathological similarities with severe bacterial pneumonia and sepsis. In particular, it disrupts the haemostatic balance, which results in a procoagulant state locally in the lungs and systemically. This culminates in the formation of microthrombi, disseminated intravascular coagulation and multi-organ failure. The deleterious effects of exaggerated inflammatory responses and activation of coagulation have been investigated in bacterial pneumonia and sepsis and there is recognition that although these pathways are important for the host immune response to pathogens, they can lead to bystander tissue injury and are negatively associated with survival. In the past two decades, evidence from preclinical studies has led to the emergence of potential anticoagulant therapeutic strategies for the treatment of patients with pneumonia, sepsis and acute respiratory distress syndrome, and some of these anticoagulant approaches have been trialled in humans. Here, we review the evidence from preclinical studies and clinical trials of anticoagulant treatment strategies in bacterial pneumonia and sepsis, and discuss the importance of these findings in the context of COVID-19.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/sangue , Pneumonia Bacteriana/sangue , Pneumonia Viral/sangue , Sepse/sangue , Biomarcadores/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia
3.
Discov Med ; 29(157): 129-137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002409

RESUMO

Sepsis is a life-threatening clinical condition demanding accurate and rapid diagnosis of the culprit pathogen, thereby to improve prognosis. Pathogen determination through blood culture is the gold standard for diagnosis but has limitations due to low sensitivity. Recently, circulating DNAs derived from pathogenic organisms were found in the plasma of patients with sepsis and were further proved to be more sensitive biomarkers for the diagnosis of the pathogen origin in sepsis. However, the fundamental molecular characteristics of circulating DNA in patients with sepsis remain unclear. Here, we used specific PCR and Sanger sequencing to verify the microbiology culture results via the corresponding plasma circulating DNA. We analyzed the composition and molecular characteristics of circulating DNA in septic patients using next-generation sequencing technology. We showed the presence of pathogen-derived circulating DNA in the plasma of patients with sepsis. The sizes of circulating DNA fragments derived from pathogenic bacteria showed a skewed unimodal distribution, while those derived from host cells showed a normal unimodal distribution. Lengths of fragments at peak concentration for both origins ranged from 150 bp to 200 bp, and reads mapping to pathogenic bacteria genome distributed uniformly on the reference. Our findings have improved our understanding of microbial circulating DNA in patients with sepsis as a potential methodology for the accurate diagnosis of sepsis, especially in light of an urgent need for such a diagnosis associated with the COVID-19 infection.


Assuntos
Infecções Bacterianas/microbiologia , Ácidos Nucleicos Livres/sangue , DNA Bacteriano/sangue , Sepse/microbiologia , Adulto , Idoso , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Betacoronavirus , Ácidos Nucleicos Livres/análise , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Técnicas de Cultura , DNA Bacteriano/análise , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Pandemias , Pneumonia Viral , Reação em Cadeia da Polimerase , Sepse/complicações , Sepse/diagnóstico , Análise de Sequência de DNA
9.
Pediatr Crit Care Med ; 21(10): 931-932, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33009319
10.
Sci Rep ; 10(1): 16384, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009426

RESUMO

The COVID-19 outbreak is becoming a public health emergency. Data are limited on the clinical characteristics and causes of death. A retrospective analysis of COVID-19 deaths were performed for patients' clinical characteristics, laboratory results, and causes of death. In total, 56 patients (72.7%) of the decedents (male-female ratio 51:26, mean age 71 ± 13, mean survival time 17.4 ± 8.4 days) had comorbidities. Acute respiratory failure (ARF) and sepsis were the main causes of death. Increases in C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer and lactic acid and decreases in lymphocytes were common laboratory results. Intergroup analysis showed that (1) most female decedents had cough and diabetes. (2) The proportion of young- and middle-aged deaths was higher than elderly deaths for males, while elderly decedents were more prone to myocardial injury and elevated CRP. (3) CRP and LDH increased and cluster of differentiation (CD) 4+ and CD8+ cells decreased significantly in patients with hypertension. The majority of COVID-19 decedents are male, especially elderly people with comorbidities. The main causes of death are ARF and sepsis. Most female decedents have cough and diabetes. Myocardial injury is common in elderly decedents. Patients with hypertension are prone to an increased inflammatory index, tissue hypoxia and cellular immune injury.


Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Sepse/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Causas de Morte , China , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Diabetes Mellitus/epidemiologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Cardiopatias/epidemiologia , Humanos , L-Lactato Desidrogenase/sangue , Ácido Láctico/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Sepse/etiologia , Síndrome Respiratória Aguda Grave/etiologia
12.
Rev Assoc Med Bras (1992) ; 66(9): 1252-1257, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33027454

RESUMO

OBJECTIVE: To describe the characteristics of patients treated at a level III surgical Neonatal Intensive Care Unit outside of a maternity service and analyze possible risk factors for mortality in this population. METHODS: A retrospective cohort study evaluating patients admitted to a level III surgical Neonatal Intensive Care Unit from June/2015 to November/2017. Univariate analysis was performed by the Chi-square test and T-student test or Mann-Whitney test. Multivariate analysis by logistic regression was performed including in the model the variables with a P-value <0.2 in univariate analysis. Kaplan-Meier curve and Log-Rank test were performed using the variables that were statistically associated with death in the multivariate analysis. A significance level of a=5% and an error B=80% were adopted. RESULTS: During this period, 246 patients were admitted to this service. 58 (23.8%) patients died, with a mean time until death of 18 days. Half of the patients had a clinical diagnosis of sepsis (50.6%), blood culture was positive in 25.2%, and gram-positive bacteria (48.4%) were the main pathogens isolated. The variables that remained in the final model after multivariate analysis were diagnosis of congenital heart disease (OR = 4.5; p = 0.016), clinical diagnosis of sepsis (OR = 8.1; p = 0.000), and isolation of gram-positive bacteria in blood culture (OR = 3.9; p = 0.006). CONCLUSION: The level III surgical Neonatal Intensive Care Unit outside of a maternity service has a different profile of morbidity and mortality, and death was associated with the diagnosis of congenital heart disease, the clinical diagnosis of sepsis, and the isolation of gram-positive bacteria in the blood culture.


Assuntos
Unidades de Terapia Intensiva Neonatal , Feminino , Humanos , Recém-Nascido , Morbidade , Gravidez , Estudos Retrospectivos , Fatores de Risco , Sepse
13.
BMC Infect Dis ; 20(1): 651, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887563

RESUMO

BACKGROUND: Risk factors related to mortality due to invasive pneumococcal disease (IPD) have been unveiled previously, but early clinical manifestations of IPD based on prognosis remain uncovered. METHODS: The demographic characteristics, clinical features, serotype, antibiotic susceptibility, and outcomes of 97 hospitalized children with laboratory-confirmed IPD from Suzhou, China, were collected and analyzed retrospectively. RESULTS: The median age was 0.69 (0.49-1.55) years in the non-survivor group compared with 2.39 (0.90-3.81) years in the survivor group. The mortality of 97 children with laboratory-confirmed IPD was 17.5% (17/97), and 53.6% of them were aged less than 2 years. Pathogens were mainly from the blood and cerebrospinal fluid, and sepsis was the most frequent type. Statistically significant differences were found in hyperpyrexia, vomiting, anorexia, lethargy, poor perfusion of extremities, Hb level, and Plt count between the nonsurvival and survival groups. Further, the multivariate regression analysis showed that early signs, including hyperpyrexia, vomiting, anorexia, lethargy, and poor perfusion of extremities, were independent risk factors for the in-hospital mortality of children with laboratory-confirmed IPD. The mortality was also associated with antimicrobial sensitivity in pneumococcal isolates. The microbes in 1/17 (5.9%) children who were prescribed an antibiotic showed antimicrobial sensitivity in the nonsurvival group, compared with 21/80 (26.3%) children who survived. The most common serotypes identified were 6B (35.3%, 6/17), 14 (23.5%, 4/17), 19F (23.5%, 4/17), 19A (5.9%, 1/17), 23F (5.9%, 1/17), and 20 (5.9%, 1/17) in the nonsurvival group. The coverage of IPD serotypes of the 7-valent pneumococcal conjugate vaccine (PCV7) was 88.2% (15/17), while that of the 13-valent S. pneumoniae vaccine (PCV13) was 94.1% (16/17) of the coverage in the nonsurvival group. CONCLUSIONS: Recurrent hyperpyrexia, vomiting, anorexia, lethargy, and poor perfusion of extremities in the early stage were independent predictors for the in-hospital mortality of children with laboratory-confirmed IPD. Appropriate use of antibiotics and PCV immunization were the keys to improve the outcome of IPD.


Assuntos
Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/mortalidade , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pré-Escolar , Feminino , Vacina Pneumocócica Conjugada Heptavalente/uso terapêutico , Mortalidade Hospitalar , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sepse/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Cobertura Vacinal
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(4): 468-476, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895098

RESUMO

Objective To establish an improved animal model of sepsis induced by cecal ligation and puncture(CLP). Methods Ninety-six male Sprague-Dawley rats were randomly divided into sham operation group(n=24),intubation group(n=24),CLP group(n=24),and CLP+intubation group(n=24).The mortality rate,abdominal cavity condition,pathological changes and pathological scores of heart,lungs,liver,and kidneys of rats in each group were observed after modeling.Blood samples were obtained from the inferior vena cava for measuring the whole blood cells(WBC)and platelets(PLT)counts and analyzing serum interleukin(IL)-6,tumor necrosis factor(TNF)-α,serum troponin T(cTnT),creatine kinase-MB(CK-MB),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),creatinine(CREA),and blood urea nitrogen(BUN)levels.Blood gas analysis of the aorta was also performed. Results The mortality rates 24 h after modeling were 0 in sham operation group and intubation group,20.8% in CLP group,and 54.2% in CLP+intubation group.Pathologically,swelling and inflammatory cell infiltration in the heart,lungs,liver,and kidneys were seen in the CLP+intubation group,inflammatory cell infiltration in a single organ was seen in most rats in the CLP group,and no obvious swelling and infiltration of inflammatory cells was observed in the sham-operation group and intubation group.The myocardial histopathology score,lung tissue injury pathology score,and kidney tissue injury pathology score in both the sham-operation group and the intubation group were significantly lower than those in the CLP group and the CLP+intubation group(all P=0.000).TNF-α,PaO2,CK-MB,cTnT,AST,TBIL,BUN,and CREA were significantly different between sham-operation group and intubation group/CLP group/CLP+intubation group and between intubation group and CLP group/CLP+intubation group(all P=0.000).The pH level was significantly different between sham operation group and intubation group/CLP group,between intubation group and CLP group/CLP+intubate group(all P=0.000). Conclusions Although both CLP and CLP+intubation can well mimic the pathophysiological mechanism of sepsis in rats,multiple organ dysfunction occurs in the latter.Thus,CLP+intubation can establish animal models of multiple organ dysfunction caused by sepsis induced by clinically effective abdominal infection.


Assuntos
Sepse , Animais , Aspartato Aminotransferases , Modelos Animais de Doenças , Ligadura , Masculino , Punções , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa
16.
Crit Care ; 24(1): 534, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867859

RESUMO

BACKGROUND: Sepsis represents a major worldwide healthcare burden. However, how body-mass index (BMI) is related to the long-term risk of sepsis-related mortality in low- and middle-income countries remains uncertain. METHODS: We examined the associations of sepsis-related mortality with both baseline BMI and waist circumference (WC) using data from China Kadoorie Biobank, a prospective cohort recruited during 2004-2008 and followed up to December 2016. After excluding participants with chronic obstructive pulmonary disease, tuberculosis, cancer, heart disease, and stroke, and omitting the first 3 years of follow-up, 440,763 participants remained for analysis. RESULTS: During a median follow-up of 10.0 years, 1957 sepsis-related deaths (3,134,870 person-years) were included for analysis. Compared with reference BMI of 22.5 to < 25.0 kg/m2, the multivariable-adjusted hazard ratios (HRs) for sepsis-related mortality were 2.42 (95% CIs 2.07-2.84) for BMI of < 18.5, 1.59 (1.36-1.85) for 18.5 to < 20.0, 1.21 (1.06-1.38) for 20.0 to < 22.5, 0.97 (0.83-1.13) for 25.0 to < 27.5, 0.98 (0.80-1.21) for 27.5 to < 30.0, and 1.22 (0.93-1.60) for ≥ 30.0 kg/m2. Further adjustment for WC led to slightly augmentation of the effect size for the lower BMI groups and null association in the obese group. In the association analysis between WC and sepsis-related mortality, compared with the middle quintile group, only the highest quintile group showed an increased risk of sepsis-related mortality after adjusted for BMI (HR = 1.54; 95% CI 1.28-1.84). CONCLUSIONS: Underweight, lower normal weight, and abdominal obesity are associated with increased future risk of sepsis-related mortality over 10 years in the Chinese population. The double burden of underweight and obesity indicates a heavy sepsis burden faced by low- and middle-income countries.


Assuntos
Índice de Massa Corporal , Sepse/mortalidade , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Medição de Risco
18.
Eur Rev Med Pharmacol Sci ; 24(16): 8606-8620, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32894568

RESUMO

OBJECTIVE: COVID-19 immune syndrome is a multi-systemic disorder induced by the COVID-19 infection. Pathobiological transitions and clinical stages of the COVID-19 syndrome following the attack of SARS-CoV-2 on the human body have not been fully explored. The aim of this review is to outline the three critical prominent phase regarding the clinicogenomics course of the COVID-19 immune syndrome. MATERIALS AND METHODS: In the clinical setting, the COVID-19 process presents as "asymptomatic/pre-symptomatic phase", "respiratory phase with mild/moderate/severe symptoms" and "multi-systemic clinical syndrome with impaired/disproportionate and/or defective immunity". The corresponding three genomic phases include the "ACE2, ANPEP transcripts in the initial phase", "EGFR and IGF2R transcripts in the propagating phase" and the "immune system related critical gene involvements of the complicating phase". RESULTS: The separation of the phases is important since the genomic features of each phase are different from each other and these different mechanisms lead to distinct clinical multi-systemic features. Comprehensive genomic profiling with next generation sequencing may play an important role in defining and clarifying these three unique separate phases for COVID-19. From our point of view, it is important to understand these unique phases of the syndrome in order to approach a COVID-19 patient bedside. CONCLUSIONS: This three-phase approach may be useful for future studies which will focus on the clinical management and development of the vaccines and/or specific drugs targeting the COVID-19 processes. ANPEP gene pathway may have a potential for the vaccine development. Regarding the specific disease treatments, MAS agonists, TXA127, Angiotensin (1-7) and soluble ACE2 could have therapeutic potential for the COVID-19 course. Moreover, future CRISPR technology can be utilized for the genomic editing and future management of the clinical course of the syndrome.


Assuntos
Doenças Assintomáticas , Infecções por Coronavirus/patologia , Sistema Imunitário/metabolismo , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação da Expressão Gênica , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/patologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Prognóstico , Receptor IGF Tipo 2/genética , Receptor IGF Tipo 2/metabolismo , Sepse/complicações , Sepse/patologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
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