Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.056
Filtrar
1.
Cochrane Database Syst Rev ; 5: CD013235, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-34097767

RESUMO

BACKGROUND: Rapid antimicrobial susceptibility tests are expected to reduce the time to clinically important results of a blood culture. This might enable clinicians to better target therapy to a person's needs, and thereby, improve health outcomes (mortality, length of hospital stay), and reduce unnecessary prescribing of broad-spectrum antibiotics; thereby reducing antimicrobial resistance rates. OBJECTIVES: To assess the effects of rapid susceptibility testing versus standard susceptibility testing for bloodstream infections (BSIs). SEARCH METHODS: To identify studies with selected outcomes, we searched the Cochrane Infectious Diseases Group Specialised Register, CENTRAL, MEDLINE, LILACS, and two trials registries, between 1987 and October 2020. We used 'bloodstream infection' and 'antimicrobial susceptibility tests' as search terms. We had no language or publication status limitations. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing rapid antimicrobial susceptibility testing (with a time-to-result of ≤ 8 hours) versus conventional antimicrobial susceptibility testing in people with a BSI caused by any bacteria, as identified by a positive blood culture. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references, full-text reports of potentially relevant studies, extracted data from the studies, and assessed risk of bias. Any disagreement was discussed and resolved with a third review author. For mortality, a dichotomous outcome, we extracted the number of events in each arm, and presented a risk ratio (RR) with 95% confidence interval (CI) to compare rapid susceptibility testing to conventional methods. We used Review Manager 5.4 to meta-analyse the data. For other outcomes, which are time-to-event outcomes (time-to-discharge from hospital, time-to-first appropriate antibiotic change), we conducted qualitative narrative synthesis, due to heterogeneity of outcome measures.  MAIN RESULTS: We included six trials, with 1638 participants. For rapid antimicrobial susceptibility testing compared to conventional methods, there was little or no difference in mortality between groups (RR 1.10, 95% CI 0.82 to 1.46; 6 RCTs, 1638 participants; low-certainty evidence). In subgroup analysis, for rapid genotypic or molecular antimicrobial susceptibility testing compared to conventional methods, there was little or no difference in mortality between groups (RR 1.02, 95% CI 0.69 to 1.49; 4 RCTs, 1074 participants; low-certainty evidence). For phenotypic rapid susceptibility testing compared to conventional methods, there was little or no difference in mortality between groups  (RR 1.37, 95% CI 0.80 to 2.35; 2 RCTs, 564 participants; low-certainty evidence). In qualitative analysis, rapid susceptibility testing may make little or no difference in time-to-discharge (4 RCTs, 1165 participants; low-certainty evidence). In qualitative analysis, rapid genotypic susceptibility testing compared to conventional testing may make little or no difference in time-to-appropriate antibiotic (3 RCTs, 929 participants; low-certainty evidence). In subgroup analysis, rapid phenotypic susceptibility testing compared to conventional testing may improve time-to-appropriate antibiotic (RR -17.29, CI -45.05 to 10.47; 2 RCTs, 564 participants; low-certainty evidence).  AUTHORS' CONCLUSIONS: The theoretical benefits of rapid susceptibility testing have not been demonstrated to directly improve mortality, time-to-discharge, or time-to-appropriate antibiotic in these randomized studies. Future large prospective studies should be designed to focus on the most clinically meaningful outcomes, and aim to optimize blood culture pathways.


Assuntos
Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana/métodos , Sepse/tratamento farmacológico , Viés , Humanos , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/microbiologia , Sepse/mortalidade , Tempo para o Tratamento
2.
Medicine (Baltimore) ; 100(19): e25813, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106618

RESUMO

ABSTRACT: Sepsis is a leading cause of mortality in the intensive care unit. Early prediction of sepsis can reduce the overall mortality rate and cost of sepsis treatment. Some studies have predicted mortality and development of sepsis using machine learning models. However, there is a gap between the creation of different machine learning algorithms and their implementation in clinical practice.This study utilized data from the Medical Information Mart for Intensive Care III. We established and compared the gradient boosting decision tree (GBDT), logistic regression (LR), k-nearest neighbor (KNN), random forest (RF), and support vector machine (SVM).A total of 3937 sepsis patients were included, with 34.3% mortality in the Medical Information Mart for Intensive Care III group. In our comparison of 5 machine learning models (GBDT, LR, KNN, RF, and SVM), the GBDT model showed the best performance with the highest area under the receiver operating characteristic curve (0.992), recall (94.8%), accuracy (95.4%), and F1 score (0.933). The RF, SVM, and KNN models showed better performance (area under the receiver operating characteristic curve: 0.980, 0.898, and 0.877, respectively) than the LR (0.876).The GBDT model showed better performance than other machine learning models (LR, KNN, RF, and SVM) in predicting the mortality of patients with sepsis in the intensive care unit. This could be used to develop a clinical decision support system in the future.


Assuntos
Regras de Decisão Clínica , Árvores de Decisões , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Aprendizado de Máquina , Sepse/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Máquina de Vetores de Suporte , Adulto Jovem
3.
Sci Rep ; 11(1): 10793, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: covidwho-1242045

RESUMO

Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is challenging. This stems from the heterogeneous response of individuals to disease and is reflected in the inter-individual variability of gene expression responses that obscures differential gene expression analysis. Here, we developed an alternative approach that could be applied to dissect the disease-associated molecular changes. We define gene ensemble noise as a measure that represents a variance for a collection of genes encoding for either members of known biological pathways or subunits of annotated protein complexes and calculated within an individual. The gene ensemble noise allows for the holistic identification and interpretation of gene expression disbalance on the level of gene networks and systems. By comparing gene expression data from COVID-19, H1N1, and sepsis patients we identified common disturbances in a number of pathways and protein complexes relevant to the sepsis pathology. Among others, these include the mitochondrial respiratory chain complex I and peroxisomes. This suggests a Warburg effect and oxidative stress as common hallmarks of the immune host-pathogen response. Finally, we showed that gene ensemble noise could successfully be applied for the prediction of clinical outcome namely, the mortality of patients. Thus, we conclude that gene ensemble noise represents a promising approach for the investigation of molecular mechanisms of pathology through a prism of alterations in the coherent expression of gene circuits.


Assuntos
COVID-19/patologia , Expressão Gênica , Influenza Humana/patologia , Sepse/patologia , Área Sob a Curva , COVID-19/complicações , COVID-19/virologia , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Redes Reguladoras de Genes/genética , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/complicações , Influenza Humana/virologia , Estresse Oxidativo/genética , Peroxissomos/genética , Peroxissomos/metabolismo , Modelos de Riscos Proporcionais , Curva ROC , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sepse/complicações , Sepse/genética , Sepse/mortalidade , Índice de Gravidade de Doença , Taxa de Sobrevida , Interface Usuário-Computador
4.
J Am Geriatr Soc ; 69(7): 1713-1721, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33955546

RESUMO

BACKGROUND/OBJECTIVE: Emergency department (ED) visits have declined while excess mortality, not attributable to COVID-19, has grown. It is not known whether older adults are accessing emergency care differently from their younger counterparts. Our objective was to determine patterns of ED visit counts for emergent conditions during the COVID-19 pandemic for older adults. DESIGN: Retrospective, observational study. SETTING: Observational analysis of ED sites enrolled in a national clinical quality registry. PARTICIPANTS: One hundred and sixty-four ED sites in 33 states from January 1, 2019 to November 15, 2020. MAIN OUTCOME AND MEASURES: We measured daily ED visit counts for acute myocardial infarction (AMI), stroke, sepsis, fall, and hip fracture, as well as deaths in the ED, by age categories. We estimated Poisson regression models comparing early and post-early pandemic periods (defined by the Centers for Disease Control and Prevention) to the pre-pandemic period. We report incident rate ratios to summarize changes in visit incidence. RESULTS: For AMI, stroke, and sepsis, the older (75-84) and oldest old (85+ years) had the greatest decline in visit counts initially and the smallest recovery in the post-early pandemic periods. For falls, visits declined early and partially recovered uniformly across age categories. In contrast, hip fractures exhibited less change in visit rates across time periods. Deaths in the ED increased during the early pandemic period, but then fell and were persistently lower than baseline, especially for the older (75-84) and oldest old (85+ years). CONCLUSIONS: The decline in ED visits for emergent conditions among older adults has been more pronounced and persistent than for younger patients, with fewer deaths in the ED. This is concerning given the greater prevalence and risk of poor outcomes for emergent conditions in this age group that are amenable to time-sensitive ED diagnosis and treatment, and may in part explain excess mortality during the COVID-19 era among older adults.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Envelhecimento , COVID-19/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Infarto do Miocárdio , Sepse , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Envelhecimento/psicologia , COVID-19/prevenção & controle , Emergências/epidemiologia , Serviços Médicos de Emergência/métodos , Serviços Médicos de Emergência/estatística & dados numéricos , Humanos , Mortalidade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , SARS-CoV-2 , Sepse/diagnóstico , Sepse/mortalidade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Estados Unidos/epidemiologia
5.
Sci Rep ; 11(1): 10793, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031464

RESUMO

Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is challenging. This stems from the heterogeneous response of individuals to disease and is reflected in the inter-individual variability of gene expression responses that obscures differential gene expression analysis. Here, we developed an alternative approach that could be applied to dissect the disease-associated molecular changes. We define gene ensemble noise as a measure that represents a variance for a collection of genes encoding for either members of known biological pathways or subunits of annotated protein complexes and calculated within an individual. The gene ensemble noise allows for the holistic identification and interpretation of gene expression disbalance on the level of gene networks and systems. By comparing gene expression data from COVID-19, H1N1, and sepsis patients we identified common disturbances in a number of pathways and protein complexes relevant to the sepsis pathology. Among others, these include the mitochondrial respiratory chain complex I and peroxisomes. This suggests a Warburg effect and oxidative stress as common hallmarks of the immune host-pathogen response. Finally, we showed that gene ensemble noise could successfully be applied for the prediction of clinical outcome namely, the mortality of patients. Thus, we conclude that gene ensemble noise represents a promising approach for the investigation of molecular mechanisms of pathology through a prism of alterations in the coherent expression of gene circuits.


Assuntos
COVID-19/patologia , Expressão Gênica , Influenza Humana/patologia , Sepse/patologia , Área Sob a Curva , COVID-19/complicações , COVID-19/virologia , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Redes Reguladoras de Genes/genética , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/complicações , Influenza Humana/virologia , Estresse Oxidativo/genética , Peroxissomos/genética , Peroxissomos/metabolismo , Modelos de Riscos Proporcionais , Curva ROC , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sepse/complicações , Sepse/genética , Sepse/mortalidade , Índice de Gravidade de Doença , Taxa de Sobrevida , Interface Usuário-Computador
6.
Medicine (Baltimore) ; 100(21): e26132, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032762

RESUMO

ABSTRACT: We aimed to determine the association between the intensive care unit (ICU) model and in-hospital mortality of patients with severe sepsis and septic shock.This was a secondary analysis of a multicenter prospective observational study conducted in 59 ICUs in Japan from January 2016 to March 2017. We included adult patients (aged ≥16 years) with severe sepsis and septic shock based on the sepsis-2 criteria who were admitted to an ICU with a 1:2 nurse-to-patient ratio per shift. Patients were categorized into open or closed ICU groups, according to the ICU model. The primary outcome was in-hospital mortality.A total of 1018 patients from 45 ICUs were included in this study. Patients in the closed ICU group had a higher severity score and higher organ failure incidence than those in the open ICU group. The compliance rate for the sepsis care 3-h bundle was higher in the closed ICU group than in the open ICU group. In-hospital mortality was not significantly different between the closed and open ICU groups in a multilevel logistic regression analysis (odds ratio = 0.83, 95% confidence interval; 0.52-1.32, P = .43) and propensity score matching analysis (closed ICU, 21.2%; open ICU, 25.7%, P = .22).In-hospital mortality between the closed and open ICU groups was not significantly different after adjusting for ICU structure and compliance with the sepsis care bundle.


Assuntos
Mortalidade Hospitalar , Unidades de Terapia Intensiva/organização & administração , Pacotes de Assistência ao Paciente , Sepse/mortalidade , Sepse/terapia , Choque Séptico/mortalidade , Choque Séptico/terapia , Protocolos Clínicos , Terapia Combinada , Humanos , Estudos Prospectivos , Índice de Gravidade de Doença
7.
Nat Commun ; 12(1): 2745, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980856

RESUMO

In mice, time of day strongly influences lethality in response to LPS, with survival greatest at the beginning compared to the end of the light cycle. Here we show that feeding, rather than light, controls time-of-day dependent LPS sensitivity. Mortality following LPS administration is independent of cytokine production and the clock regulator BMAL1 expressed in myeloid cells. In contrast, deletion of BMAL1 in hepatocytes globally disrupts the transcriptional response to the feeding cycle in the liver and results in constitutively high LPS sensitivity. Using RNAseq and functional validation studies we identify hepatic farnesoid X receptor (FXR) signalling as a BMAL1 and feeding-dependent regulator of LPS susceptibility. These results show that hepatocyte-intrinsic BMAL1 and FXR signalling integrate nutritional cues to regulate survival in response to innate immune stimuli. Understanding hepatic molecular programmes operational in response to these cues could identify novel pathways for targeting to enhance endotoxemia resistance.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Comportamento Alimentar/fisiologia , Fígado/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Sepse/mortalidade , Fatores de Transcrição ARNTL/genética , Animais , Ritmo Circadiano/genética , Modelos Animais de Doenças , Resistência à Doença , Hepatócitos/metabolismo , Hipoglicemia/metabolismo , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Knockout , Receptores Citoplasmáticos e Nucleares/genética , Sepse/induzido quimicamente , Sepse/genética , Sepse/metabolismo , Transdução de Sinais
8.
Biomed Res Int ; 2021: 5535562, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997001

RESUMO

Purpose: Sepsis originates from the host inflammatory response, especially to bacterial infections, and is considered one of the main causes of death in intensive care units. Various agents have been developed to inhibit mediators of the inflammatory response; one prospective agent is ß-sitosterol (ßS), a phytosterol with a structure similar to cholesterol. This study is aimed at evaluating the effects of ßS on the biomarkers of inflammation and liver function in cecal ligation and puncture- (CLP-) induced septic rats. Methods: Thirty male Wistar rats were divided equally into six groups as follows: sham, CLP, CLP+dexamethasone (DX, 0.2 mg/kg), CLP+ßS (1 mg/kg), CLP+imipenem (IMI, 20 mg/kg), and CLP+IMI (20 mg/kg)+ßS (1 mg/kg). Serum levels of IL-1ß, IL-6, IL-10, AST, ALT, and liver glutathione (GSH) were assessed by ELISA. Liver expression levels of TNF-α and NF-κBi mRNAs were evaluated by RT-qPCR. Results: Serum concentrations of IL-1ß, IL-6, IL-10, ALT, and AST and mRNA levels of TNF-α and NF-κBi were all significantly higher in septic rats than in normal rats (p < 0.05). Liver GSH content was markedly lower in the CLP group than that in the sham group. ßS-treated rats had remarkably lower levels of IL-1ß, IL-6, IL-10, TNF-α, NF-κBi, AST, and ALT (51.79%, 62.63%, 41.46%, 54.35%, 94.37%, 95.30%, 34.87%, and 46.53% lower, respectively) and greater liver GSH content (35.71% greater) compared to the CLP group (p < 0.05). Conclusion: ßS may play a protective role in the septic process by mitigating inflammation. This effect is at least partly mediated by inhibition of the NF-κB signaling pathway. Thus, ßS can be considered as a supplementary treatment in septic patients.


Assuntos
Inflamação/metabolismo , Fígado , NF-kappa B/metabolismo , Sepse , Sitosteroides/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Fígado/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Sepse/metabolismo , Sepse/mortalidade , Transdução de Sinais/efeitos dos fármacos
9.
Clin Nephrol ; 95(6): 303-311, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33835014

RESUMO

PURPOSE: Acute kidney injury (AKI) is a common complication of sepsis and has high mortality. The 2017 Acute Disease Quality Initiative (AQDI) workgroup proposed new definitions for AKI - transient AKI and persistent AKI; however, very little is known about the effect of transient and persistent septic AKI on short-term mortality among critically ill patients with sepsis. The purpose of this study was to assess the impact of persistent AKI on mortality and to evaluate whether serum hepcidin can predict the occurrence of persistent AKI in critically ill patients with sepsis. MATERIALS AND METHODS: This prospective observational study was performed in a general hospital mixed surgical-medical ICU in Pudong, China. Consecutive adults with sepsis admitted to the ICU with absence of chronic kidney disease, renal transplant, and AKI were included. AKI was defined according to the KDIGO criteria and classified as transient (< 48-hour duration) or persistent (48-hour duration). Blood samples were obtained within 6 hours from when AKI was diagnosed. RESULTS: A total of 90 patients with sepsis or septic shock were included in the analysis. 44 (48.89%) patients developed AKI during ICU stay: 20 (45.45%) had transient and 24 (54.55%) had persistent AKI. Persistent AKI has a higher mortality than transient AKI (66.7 vs. 30.0%, p = 0.002). Persistent AKI and sequential organ failure assessment (SOFA) scores were an independent predictor of 60-day mortality. Patients with persistent AKI had higher concentrations of serum creatinine (SCr) and hepcidin than transient AKI patients when AKI was diagnosed. Logistic regression indicated that serum hepcidin was an independent predictor of persistent AKI in septic patients, with a fairly predictive value (AUC 0.71, 95% CI: 0.47 - 0.87; p = 0.02). CONCLUSION: Persistent AKI was associated with increased 60-day mortality compared with transient AKI in septic patients. The serum hepcidin levels measured when AKI was diagnosed have a fair predictive value to predict the occurrence of persistent AKI in septic patients.


Assuntos
Injúria Renal Aguda/etiologia , Hepcidinas/sangue , Sepse/mortalidade , Injúria Renal Aguda/sangue , Idoso , Idoso de 80 Anos ou mais , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sepse/sangue , Sepse/complicações
10.
Front Immunol ; 12: 594270, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868224

RESUMO

Objectives: The mortality rate of sepsis remains very high. Metabolomic techniques are playing increasingly important roles in diagnosis and treatment in critical care medicine. The purpose of our research was to use untargeted metabolomics to identify and analyze the common differential metabolites among patients with sepsis with differences in their 7-day prognosis and blood PD-1 expression and analyze their correlations with environmental factors. Methods: Plasma samples from 18 patients with sepsis were analyzed by untargeted LC-MS metabolomics. Based on the 7-day prognoses of the sepsis patients or their levels of PD-1 expression on the surface of CD4+ T cells in the blood, we divided the patients into two groups. We used a combination of multidimensional and monodimensional methods for statistical analysis. At the same time, the Spearman correlation analysis method was used to analyze the correlation between the differential metabolites and inflammatory factors. Results: In the positive and negative ionization modes, 16 and 8 differential metabolites were obtained between the 7-day death and survival groups, respectively; 5 and 8 differential metabolites were obtained between the high PD-1 and low PD-1 groups, respectively. We identified three common differential metabolites from the two groups, namely, PC (P-18:0/14:0), 2-ethyl-2-hydroxybutyric acid and glyceraldehyde. Then, we analyzed the correlations between environmental factors and the common differences in metabolites. Among the identified metabolites, 2-ethyl-2-hydroxybutyric acid was positively correlated with the levels of IL-2 and lactic acid (Lac) (P < 0.01 and P < 0.05, respectively). Conclusions: These three metabolites were identified as common differential metabolites between the 7-day prognosis groups and the PD-1 expression level groups of sepsis patients. They may be involved in regulating the expression of PD-1 on the surface of CD4+ T cells through the action of related environmental factors such as IL-2 or Lac, which in turn affects the 7-day prognosis of sepsis patients.


Assuntos
Metaboloma , Metabolômica , Receptor de Morte Celular Programada 1/metabolismo , Sepse/metabolismo , Sepse/mortalidade , Adulto , Idoso , Biomarcadores , Feminino , Expressão Gênica , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/genética , Curva ROC , Sepse/diagnóstico , Sepse/etiologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
11.
Hematology ; 26(1): 328-339, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33818297

RESUMO

OBJECTIVE: The aim of this study was to investigate the data of HSCT patients who were admitted to our Hematology ICU due to infections or infectious complications. MATERIALS AND METHODS: HSCT patients who were admitted to our Hematology ICU between 01 January 2014 and 01 September 2017 were analyzed retrospectively. RESULTS: 62 HSCT patients were included in this study. The median age was 55.5 years and 58% of the patients were allogeneic HSCT patients. Major underlying hematologic disorders were multiple myeloma (29%) and lymphoma (27.4%). The most common reasons for ICU admission were sepsis/septic shock (61.3%) and acute respiratory failure (54.8%). Overall ICU mortality rate was 45.2%. However, a lot of factors were related with ICU mortality of HSCT patients in univariate analysis, only APACHE II score was found to be an independent risk factor for ICU mortality. While there was infection in 58 patients at ICU admission, new infections developed in 38 patients during ICU stay. The most common new infection was pneumonia/VAP, while the most frequently isolated bacteria were Acinetobacter baumannii. Length of ICU stay, sepsis/septic shock as a reason for ICU admission and the presence of urinary catheter at ICU admission were determined factors for ICU-acquired infections. There was no difference between autologous and allogeneic stem cell transplant patients in terms of ICU morbidities and mortality. However, pneumonia/VAP developed in the ICU was higher in autologous HSCT patients, while bloodstream/catheter-related bloodstream infection was higher in allogeneic HSCT patients. CONCLUSION: It was concluded that early or late post-HSCT infections and related complications (sepsis, organ failure, etc.) constituted a major part of the reasons for ICU admission, ICU mortality and ICU morbidities.


Assuntos
Infecções Bacterianas/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Micoses/etiologia , APACHE , Infecções por Acinetobacter/etiologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/isolamento & purificação , Adulto , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Infecções/etiologia , Infecções/microbiologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Micoses/mortalidade , Estudos Retrospectivos , Sepse/etiologia , Sepse/microbiologia , Sepse/mortalidade
12.
Oxid Med Cell Longev ; 2021: 6667074, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33927797

RESUMO

Sepsis-induced myocardial dysfunction considerably increases mortality risk in patients with sepsis. Previous studies from our group have shown that sepsis alters the expression of structural proteins in cardiac cells, resulting in cardiomyocyte degeneration and impaired communication between cardiac cells. Caveolin-3 (CAV3) is a structural protein present in caveolae, located in the membrane of cardiac muscle cells, which regulates physiological processes such as calcium homeostasis. In sepsis, there is a disruption of calcium homeostasis, which increases the concentration of intracellular calcium, which can lead to the activation of potent cellular enzymes/proteases which cause severe cellular injury and death. The purpose of the present study was to test the hypotheses that sepsis induces CAV3 overexpression in the heart, and the regulation of L-type calcium channels directly relates to the regulation of CAV3 expression. Severe sepsis increases the expression of CAV3 in the heart, as immunostaining in our study showed CAV3 presence in the cardiomyocyte membrane and cytoplasm, in comparison with our control groups (without sepsis) that showed CAV3 presence predominantly in the plasma membrane. The administration of verapamil, an L-type calcium channel inhibitor, resulted in a decrease in mortality rates of septic mice. This effect was accompanied by a reduction in the expression of CAV3 and attenuation of cardiac lesions in septic mice treated with verapamil. Our results indicate that CAV3 has a vital role in cardiac dysfunction development in sepsis and that the regulation of L-type calcium channels may be related to its expression.


Assuntos
Caveolina 3/metabolismo , Coração/efeitos dos fármacos , Sepse/tratamento farmacológico , Verapamil/uso terapêutico , Animais , Canais de Cálcio Tipo L , Humanos , Masculino , Camundongos , Sepse/mortalidade , Sepse/patologia , Análise de Sobrevida , Verapamil/farmacologia
13.
Int J Mol Sci ; 22(6)2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33804806

RESUMO

Peritoneal resident macrophages play a key role in combating sepsis in the peritoneal cavity. We sought to determine if peritoneal transplantation of embryonic Myb- "peritoneal-like" macrophages attenuate abdominal fecal sepsis. Directed differentiation of rodent pluripotent stem cells (PSCs) was used in factor-defined media to produce embryonic-derived large "peritoneal-like" macrophages (Ed-LPM) that expressed peritoneal macrophage markers and demonstrated phagocytic capacity. Preclinical in vivo studies determined Ed-LPM efficacy in rodent abdominal fecal sepsis with or without Meropenem. Ex vivo studies explored the mechanism and effects of Ed-LPM on host immune cell number and function, including phagocytosis, reactive oxygen species (ROS) production, efferocytosis and apoptosis. Ed-LPM reduced sepsis severity by decreasing bacterial load in the liver, spleen and lungs. Ed-LPM therapy significantly improved animal survival by ~30% and reduced systemic bacterial burden to levels comparable to Meropenem therapy. Ed-LPM therapy decreased peritoneal TNFα while increasing IL-10 concentrations. Ed-LPMs enhanced peritoneal macrophage phagocytosis of bacteria, increased macrophage production of ROS and restored homeostasis via apoptosis and efferocytosis-induced clearance of neutrophils. In conclusion, Ed-LPM reduced systemic sepsis severity, improved survival and reduced bacterial load by enhancing peritoneal macrophage bacterial phagocytosis and killing and clearance of intra-peritoneal neutrophils. Macrophage therapy may be a potential strategy to address sepsis.


Assuntos
Carga Bacteriana , Macrófagos/imunologia , Macrófagos/metabolismo , Proteínas Proto-Oncogênicas c-myb/deficiência , Sepse/etiologia , Sepse/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Contagem de Leucócitos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fagocitose/imunologia , Prognóstico , Ratos , Sepse/diagnóstico , Sepse/mortalidade , Índice de Gravidade de Doença
14.
Pan Afr Med J ; 38: 78, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33889244

RESUMO

Introduction: the use of chlorhexidine antiseptic gel for umbilical cord care in unhygienic settings has been shown to reduce infection and neonatal mortality in Asia, leading to the revision of WHO guidelines. However, few studies exist in the African context and none have been undertaken in conflict-affected settings. We aimed to assess the effectiveness of applying chlorhexidine gel to the umbilical cord stump on cord sepsis and neonatal mortality rates in the Republic of South Sudan. Methods: our pre/post quasi-experimental study recruited 3,143 pregnant women from six rural communities in Jubek County, South Sudan: 1,825 women in the treatment group and 1,318 women in the control group. Neonates in the treatment group had chlorhexidine applied to the umbilical cord stump within 24 hours of birth and daily for seven days. No chlorhexidine gel was applied in the control group, instead they were encouraged to practice dry cord care. Data was collected at enrolment and at each antenatal visit at 3, 7, 14 and 28 days. Our primary outcomes of interest were incidence of neonatal umbilical cord sepsis and neonatal mortality, which were analyzed on an intention-to-treat basis. The study is registered with Pan African Clinical Trial Registry, Number PACTR201808694484456. Results: the neonatal cord infection rate among the treatment group was 17.0%, compared to 38.9% in the control group (P<0.05), which was statistically significant. Neonatal mortality was least in the intervention (1.3%) and highest in the control (13.3%) group, which was also statistically significant. Conclusion: our evidence showed that chlorhexidine gel application contributed to the reduction of cord sepsis and neonatal mortality in conflict-affected South Sudan where the majority of births happen at home in unsanitary conditions. Chlorhexidine gel should be added to the essential medicines list in South Sudan and a costed plan for scale-up of chlorhexidine gel application should be developed by the Ministry of Health.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Clorexidina/administração & dosagem , Sepse/prevenção & controle , Cordão Umbilical/efeitos dos fármacos , Adolescente , Adulto , Feminino , Géis , Humanos , Incidência , Lactente , Mortalidade Infantil , Recém-Nascido , Masculino , Gravidez , Cuidado Pré-Natal , População Rural , Sepse/mortalidade , Sudão do Sul , Fatores de Tempo , Cordão Umbilical/microbiologia , Adulto Jovem
15.
Medicine (Baltimore) ; 100(15): e25483, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847655

RESUMO

BACKGROUND: Emerging evidence has indicated that interleukin-8 (IL-8) gene-251A/T polymorphism may affect individual susceptibility to sepsis. However, the results of published studies are inconclusive. The aim of this meta-analysis was to elucidate the association between this polymorphism and the risk and mortality of sepsis. METHODS: Relevant publications were searched from PubMed, EmBase, and Web of Science databases up to January 31, 2021, with studies only in English. The reference lists of the retrieved studies were investigated as well. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to figure out the relationship between IL-8-251 A/T polymorphisms and the risk and mortality of sepsis. All of the data were analyzed with Stata 16.0. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This meta-analysis will summarize the relationship between IL-8-251 A/T polymorphism and the risk and mortality of sepsis.


Assuntos
Predisposição Genética para Doença/genética , Interleucina-8/genética , Polimorfismo de Nucleotídeo Único/genética , Sepse/genética , Sepse/mortalidade , Humanos , Metanálise como Assunto , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Fatores de Risco , Revisões Sistemáticas como Assunto
16.
Artigo em Inglês | MEDLINE | ID: mdl-33852709

RESUMO

Sepsis is the organ dysfunction resulting from an infection associated with an unregulated host inflammatory response, which generates high mortality rates in Brazil. The aim of this stydy was to analyze the trend of early, late and post-neonatal mortality rates due to sepsis in Brazilian regions, from 2009 to 2018. This is an ecological study of time series. The trend of infant mortality from sepsis was analyzed using the International Classification of Diseases (ICD10) according to the place of residence (North, Northeast, Southeast, South and Midwest). Death Certificate data were collected from the Mortality Information System database. The temporal trend was analyzed using the Prais-Winsten estimate, interpreted as increasing, decreasing or stable, through the dependent variable (logarithm of mortality rates) and interdependent variables (years of the historical series). The Stata 14.0 statistical software was used. There were 39,867 infant deaths due to sepsis (78.67% for unspecified bacterial sepsis of the neonate ). Most of the children were male, had mixed ethnicity (black and white) , were born preterm with low birth weight and most mothers were 20-34 years old. There were decreasing trends in mortality rates from 2009 to 2018: early neonatal, in the Southeast (-3.57%), North (-3.33%) and South (-2.91%); late neonatal, in the South (-4.12%), Southeast (-4.53%), North (-4.55%) and Midwest (-6.21%); and post-neonatal, in the Northeast (-1.84%), North (-3.62%), Southeast (-3.83%) and Midwest (-5.81%). The Northeast showed a stable trend in early and late neonatal mortality rates. It was concluded that most regions showed a decreasing trend in mortality rates from sepsis in all age components, despite regional differences.


Assuntos
Mortalidade Infantil/tendências , Sepse/mortalidade , Adulto , Brasil/epidemiologia , Criança , Humanos , Lactente , Recém-Nascido , Masculino , Sepse/microbiologia , Adulto Jovem
17.
J Int Med Res ; 49(4): 3000605211004221, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33823636

RESUMO

OBJECTIVE: Sepsis is the leading cause of death in patients admitted to adult intensive care units (ICUs). We aimed to determine the predictive value of red blood cell distribution width (RDW) in patients with sepsis in a large cohort. METHODS: This retrospective observational study used data from the eICU Collaborative Research Database. The prognostic value of RDW was investigated using the receiver operating characteristic (ROC) curve, multiple logistic regression model, integrated discriminatory index (IDI), and net reclassification index (NRI). RESULTS: In total, 9743 patients were included. The area under the ROC curve of the RDW for predicting hospital mortality was 0.631 (95% confidence interval [CI]: 0.616-0.645). Based on the multiple logistic regression model, an RDW of ≥14.5% was correlated with hospital mortality, regardless of Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) scores (odds ratio [OR]: 1.838, 95% CI: 1.598-2.119). Using SOFA and APACHE IV scores as reference, the IDI and continuous NRI of RDW for hospital mortality was about 0.3 and 0.014, respectively. CONCLUSIONS: The RDW may be useful in predicting hospital mortality in patients with sepsis, offering extra prognostic value beyond SOFA and APACHE IV scores.


Assuntos
Índices de Eritrócitos , Mortalidade Hospitalar , Sepse , APACHE , Adulto , Humanos , Unidades de Terapia Intensiva , Prognóstico , Curva ROC , Estudos Retrospectivos , Sepse/diagnóstico , Sepse/mortalidade
18.
Biochem Biophys Res Commun ; 551: 86-92, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33721834

RESUMO

Radiotherapy is the most common strategy in the treatment of cancer. However, radiation-induced acute complications, in particular sepsis, render patients in a life-threatening status or lead to delay of therapy that largely influences patients' overall responses. The understanding of sepsis in radiotherapy is currently scant and effective medicine is not available by far. Here, with WT mice as control, we challenged mice deficient to cGas, Caspase-11, Gsdmd or Asc with cecal ligation and puncture (CLP, a sepsis model) after a treatment of thorax irradiation. We found that radiation robustly upgraded caspase-11 pathway in irradiated region and consequently deteriorated lung injury and mortality in the sepsis model. cGas knockout markedly attenuated radiation-upgraded caspase-11 and restored sepsis. Deficiency of non-canonical inflammasome, caspase-11 and the downstream GSDMD, rather than an AIM2 inflammasome component, ASC, dramatically protected against radiation-promoted injury and mortality in septic mice. The protection may attribute to the inhibition of caspase-11-mediated pyroptosis in endothelial cells of the lung. Thus, blocking cGAS/caspase-11 signaling would be an adjuvant treatment strategy for preventing sepsis in radiotherapy of cancer.


Assuntos
Caspases Iniciadoras/metabolismo , Neoplasias/radioterapia , Nucleotidiltransferases/metabolismo , Radioterapia/efeitos adversos , Sepse/etiologia , Sepse/metabolismo , Transdução de Sinais , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/enzimologia , Neoplasias/metabolismo , Nucleotidiltransferases/deficiência , Nucleotidiltransferases/genética , Sepse/mortalidade
19.
Front Immunol ; 12: 592303, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692779

RESUMO

A complicated clinical course for critically ill patients admitted to the intensive care unit (ICU) usually includes multiorgan dysfunction and subsequent death. Owing to the heterogeneity, complexity, and unpredictability of the disease progression, ICU patient care is challenging. Identifying the predictors of complicated courses and subsequent mortality at the early stages of the disease and recognizing the trajectory of the disease from the vast array of longitudinal quantitative clinical data is difficult. Therefore, we attempted to perform a meta-analysis of previously published gene expression datasets to identify novel early biomarkers and train the artificial intelligence systems to recognize the disease trajectories and subsequent clinical outcomes. Using the gene expression profile of peripheral blood cells obtained within 24 h of pediatric ICU (PICU) admission and numerous clinical data from 228 septic patients from pediatric ICU, we identified 20 differentially expressed genes predictive of complicated course outcomes and developed a new machine learning model. After 5-fold cross-validation with 10 iterations, the overall mean area under the curve reached 0.82. Using a subset of the same set of genes, we further achieved an overall area under the curve of 0.72, 0.96, 0.83, and 0.82, respectively, on four independent external validation sets. This model was highly effective in identifying the clinical trajectories of the patients and mortality. Artificial intelligence systems identified eight out of twenty novel genetic markers (SDC4, CLEC5A, TCN1, MS4A3, HCAR3, OLAH, PLCB1, and NLRP1) that help predict sepsis severity or mortality. While these genes have been previously associated with sepsis mortality, in this work, we show that these genes are also implicated in complex disease courses, even among survivors. The discovery of eight novel genetic biomarkers related to the overactive innate immune system, including neutrophil function, and a new predictive machine learning method provides options to effectively recognize sepsis trajectories, modify real-time treatment options, improve prognosis, and patient survival.


Assuntos
Suscetibilidade a Doenças , Leucócitos/imunologia , Leucócitos/metabolismo , Aprendizado de Máquina , Sepse/epidemiologia , Sepse/etiologia , Transcriptoma , Biomarcadores , Mapeamento Cromossômico , Biologia Computacional/métodos , Cuidados Críticos , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Curva ROC , Reprodutibilidade dos Testes , Sepse/mortalidade , Fatores de Tempo
20.
Clin Ter ; 172(2): 134-137, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33763682

RESUMO

Objectives: Sepsis is a "life-threatening organ dysfunction caused by a dysregulated host response to infection", which is identified by a >2 point increase from patient baseline in the Sequential Organ Failure Assessment score (SOFAs). The prevalence and outcome of patients with sepsis has been mainly assessed in ICU patients, while few data are available for patients admitted to internal medicine wards. Our purpose was to evaluate the prevalence and the clinical outcome of patients with sepsis in an internal medicine-ward. Design: This is a single-center retrospective observational study evaluating all patients admitted over a 2-month period (October and Novembre 2015) in the internal medicine ward of the San Giovanni di Dio Hospital in Florence. Patients with clinical and/or instrumental signs of bacterial infection were evaluated with SOFAs and divided into patients with and without sepsis. Results: 635 patients were evaluated, and 279 of them (43.9%) were diagnosed with a bacterial infection. The diagnosis of sepsis was made in 93 patients (14.6%). In-hospital mortality and transfer to ICU were observed in 16% of patients with sepsis and in 2.5% of patients without sepsis (p<0.0001). A SOFAs value <2 had a negative predic-tive value of 97.5%, and increasing values of SOFAs were associated with a worse prognosis. Conclusions: The results suggest that: a) a high proportion of patients hospitalized in an internal medicine ward are affected by sepsis; b) these patients are burdened with high in-hospital mortality or transfer to ICU; c) SOFA score has a high prognostic power.


Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Sepse/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prevalência , Prognóstico , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...