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1.
PLoS One ; 15(10): e0239770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052974

RESUMO

Microcirculatory disorders have been consistently linked to the pathophysiology of sepsis. One of the major organs affected is the kidneys, resulting in sepsis-associated acute kidney injury (SA-AKI) that correlates considerably with mortality. However, the potential role of clinical assessment of peripheral perfusion as a possible tool for SA-AKI management has not been established. To address this gap, the purpose of this study was to investigate the prevalence of peripheral hypoperfusion in SA-AKI, its association with mortality, and fluid balance. This observational cohort study enrolled consecutive septic patients in the Intensive Care Unit. After fluid resuscitation, peripheral perfusion was evaluated using the capillary filling time (CRT) and peripheral perfusion index (PI) techniques. The AKI was defined based on both serum creatinine and urine output criteria. One hundred and forty-one patients were included, 28 (19%) in the non-SA-AKI group, and 113 (81%) in the SA-AKI group. The study revealed higher peripheral hypoperfusion rates in the SA-AKI group using the CRT (OR 3.6; 95% CI 1.35-9.55; p < 0.05). However, this result lost significance after multivariate adjustment. Perfusion abnormalities in the SA-AKI group diagnosed by both CRT (RR 1.96; 95% CI 1.25-3.08) and PI (RR 1.98; 95% CI 1.37-2.86) methods were associated to higher rates of 28-day mortality (p < 0.01). The PI's temporal analysis showed a high predictive value for death over the first 72 h (p < 0.01). A weak correlation between PI values and the fluid balance was found over the first 24 h (r = - 0.20; p < 0.05). In conclusion, peripheral perfusion was not different intrinsically between patients with or without SA-AKI. The presence of peripheral hypoperfusion in the SA-AKI group has appeared to be a prognostic marker for mortality. This evaluation maintained its predictive value over the first 72 hours. The fluid balance possibly negatively influences peripheral perfusion in the SA-AKI.


Assuntos
Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/fisiopatologia , Microcirculação/fisiologia , Sepse/fisiopatologia , Lesão Renal Aguda/sangue , Estudos de Coortes , Creatinina/sangue , Feminino , Hidratação/métodos , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Perfusão/métodos , Prognóstico , Sepse/sangue , Sepse/mortalidade , Equilíbrio Hidroeletrolítico/fisiologia
2.
Life Sci ; 261: 118460, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32961234

RESUMO

AIMS: The hyperpermeability of gut-vascular barrier (GVB) plays a role in gut-derived sepsis. The goal of this study was to evaluate if berberine might improve hepatic apolipoprotein M (ApoM) generation and raise plasma ApoM level to protect the compromised GVB. MATERIALS AND METHODS: The compromised GVB was induced by sepsis. Hepatic ApoM mRNA and phosphoenolpyruvate carboxykinase (PEPCK) mRNA and plasma ApoM level were assayed by qRT-PCR and ELISA, respectively. The permeability of intestinal capillary in vivo and of rat intestinal microvascular endothelial cells (RIMECs) in vitro was assayed by FITC-dextran. The blood glucose was detected by a glucometer. Plasma insulin, TNF-α and IL-1ß were assayed by ELISA. The plasmalemma vesicle-associated protein-1 (PV1), ß-catenin and occludin in RIMECs were assayed by Western blot. KEY FINDINGS: Sepsis decreased hepatic ApoM mRNA and plasma ApoM level, but raised hepatic PEPCK mRNA and plasma glucose, insulin, TNF-α, and IL-1ß levels. The increased vascular endothelial permeability was abrogated by recombinant rat ApoM in vivo or ApoM-bound S1P in vitro. ApoM-bound S1P decreased PV1 but increased occludin and ß-catenin expression in LPS-treated RIMECs. Berberine in a dose-dependent manner raised hepatic ApoM mRNA and plasma ApoM level, but decreased septic hyperglycemia, insulin resistance and plasma TNF-α and IL-1ß levels. Berberine reduced sepsis-induced PEPCK and TLR4 mRNA overexpression in the liver. SIGNIFICANCE: This study demonstrated berberine inhibited TLR4-mediated hyperglycemia, insulin resistance and proinflammatory molecule production, thereby increasing ApoM gene expression and plasma ApoM. Berberine protected the damaged GVB via modulation of ApoM/S1P pathway.


Assuntos
Apolipoproteínas M/metabolismo , Berberina/uso terapêutico , Permeabilidade Capilar/efeitos dos fármacos , Lisofosfolipídeos/metabolismo , Sepse/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Esfingosina/análogos & derivados , Animais , Berberina/farmacologia , Modelos Animais de Doenças , Trato Gastrointestinal/irrigação sanguínea , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/fisiopatologia , Células Hep G2 , Humanos , Masculino , Ratos Wistar , Sepse/metabolismo , Sepse/fisiopatologia , Esfingosina/metabolismo
3.
PLoS One ; 15(8): e0238039, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853284

RESUMO

Sepsis is a global economic and health burden. Dipeptidyl peptidase 3 (DPP3) is elevated in the plasma of septic patients. The highest levels of circulating DPP3 (cDPP3) are found in non-survivor septic shock patients. The aim of this study was to evaluate the benefits of inhibiting cDPP3 by a specific antibody, Procizumab (PCZ), on cardiac function in an experimental model of sepsis, the caecal ligature and puncture (CLP) model. Rats were monitored by invasive blood pressure and echocardiography. Results are presented as mean ± SD, with p <0.05 considered significant. PCZ rapidly restored left ventricular shortening fraction (from 39 ± 4% to 51 ± 2% before and 30 min after PCZ administration (p = 0.004)). Cardiac output and stroke volume were higher in the CLP + PCZ group when compared to the CLP + PBS group (152 ± 33 mL/min vs 97 ± 25 mL/min (p = 0.0079), and 0.5 ± 0.1 mL vs 0.3 ± 1.0 mL (p = 0.009), respectively) with a markedly reduced plasma DPP3 activity (138 ± 70 U/L in CLP + PCZ group versus 735 ± 255 U/L (p = 0.048) in the CLP + PBS group). Of note, PCZ rapidly reduced oxidative stress in the heart of the CLP + PCZ group when compared to those of the CLP + PBS group (13.3 ± 8.2 vs 6.2 ± 2.5 UI, p = 0.005, 120 min after administration, respectively). Our study demonstrates that inhibition of cDPP3 by PCZ restored altered cardiac function during sepsis in rats.


Assuntos
Dipeptidil Peptidases e Tripeptidil Peptidases/antagonistas & inibidores , Dipeptidil Peptidases e Tripeptidil Peptidases/sangue , Inibidores Enzimáticos/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Sepse/sangue , Sepse/fisiopatologia , Animais , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Masculino , Estudo de Prova de Conceito , Ratos , Ratos Wistar , Sepse/enzimologia , Sístole/efeitos dos fármacos , Sístole/fisiologia
4.
Int J Biol Sci ; 16(14): 2479-2489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32792851

RESUMO

The emergence of SARS-CoV-2 virus and its associated disease COVID-19 have triggered significant threats to public health, in addition to political and social changes. An important number of studies have reported the onset of symptoms compatible with pneumonia accompanied by coagulopathy and lymphocytopenia during COVID-19. Increased cytokine levels, the emergence of acute phase reactants, platelet activation and immune checkpoint expression are some of the biomarkers postulated in this context. As previously observed in prolonged sepsis, T-cell exhaustion due to SARS-CoV-2 and even their reduction in numbers due to apoptosis hinder the response to the infection. In this review, we synthesized the immune changes observed during COVID-19, the role of immune molecules as severity markers for patient stratification and their associated therapeutic options.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Sepse/fisiopatologia , Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Biomarcadores , Transtornos da Coagulação Sanguínea/imunologia , Citocinas/metabolismo , Humanos , Sistema Imunitário , Imunidade Inata , Interferons/metabolismo , Linfopenia/imunologia , Pandemias , Fenótipo , Ativação Plaquetária
5.
PLoS One ; 15(7): e0235207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32629459

RESUMO

BACKGROUND AND AIMS: The effects of physician specialty on the outcome of heart disease remains incompletely understood because of inconsistent findings from some previous studies. Our purpose is to compare the admission outcomes of heart disease in patients receiving care by cardiologists and noncardiologist (NC) physicians. METHODS: Using reimbursement claims data of Taiwan's National Health Insurance from 2008-2013, we conducted a matched study of 6264 patients aged ≥20 years who received a cardiologist's care during admission for heart disease. Using a propensity score matching procedure adjusted for sociodemographic characteristics, medical condition, and type of heart disease, 6264 controls who received an NC physician's care were selected. Logistic regressions were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for complications and mortality during admission for heart disease associated with a cardiologist's care. RESULTS: Patients who received a cardiologist's care had a lower risk of pneumonia (OR = 0.61; 95% CI, 0.53-0.70), septicemia (OR = 0.49; 95% CI, 0.39-0.61), urinary tract infection (OR = 0.76; 95% CI, 0.66-0.88), and in-hospital mortality (OR = 0.37; 95% CI, 0.29-0.47) than did patients who received an NC physician's care. The association between a cardiologist's care and reduced adverse events following admission was significant in both sexes and in patients aged ≥40 years. CONCLUSION: We raised the possibility that cardiologist care was associated with reduced infectious complications and mortality among patients who were admitted due to heart disease.


Assuntos
Cardiologistas , Clínicos Gerais , Cardiopatias/diagnóstico , Mortalidade Hospitalar/tendências , Pneumonia/diagnóstico , Sepse/diagnóstico , Infecções Urinárias/diagnóstico , Adulto , Idoso , Feminino , Cardiopatias/complicações , Cardiopatias/mortalidade , Cardiopatias/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Admissão do Paciente/estatística & dados numéricos , Pneumonia/complicações , Pneumonia/mortalidade , Pneumonia/fisiopatologia , Pontuação de Propensão , Fatores de Risco , Sepse/complicações , Sepse/mortalidade , Sepse/fisiopatologia , Taiwan/epidemiologia , Infecções Urinárias/complicações , Infecções Urinárias/mortalidade , Infecções Urinárias/fisiopatologia
6.
PLoS One ; 15(7): e0235350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32663203

RESUMO

BACKGROUND: Skin and soft tissue infections (SSTI) are a common but preventable cause of morbidity and mortality among people who inject drugs (PWID). They can be severe, and hospitalisations of PWID with SSTI are rising. The most common SSTI presentations are abscesses and cellulitis. METHODS: We used data from Care & Prevent, a cross-sectional community survey of PWID in London. We reported the lifetime prevalence of SSTI, severity of infections, key risk factors, and associated sequelae. Pictorial questions were used to assess SSTI severity. RESULTS: We recruited 455 PWID. SSTI lifetime prevalence was high: 64% reported an abscess and/or cellulitis. Over one-third (37%) reported a severe infection, 137 (47%) reported hospitalisation. SSTIrisk factors were: aged 35+ years, injecting once or more times a day, subcutaneous or intra-muscular injections, and making four or more attempts to achieve an injection. Those who reported having other health conditions were at higher odds of having an abscess or cellulitis, with risk tending to increase with number of reported conditions. Half (46%) employed self-care for their worst SSTI, and 43% waited for ten or more days before seeking medical care or not seeking medical care at all. CONCLUSIONS: Abscess and cellulitis are very common among PWID in London. We corroborate findings indicating SSTIs are associated with risks, e.g. venous access problems, as well as other co-morbid conditions: septicaemia, endocarditis, DVT, and kidney disease. These co-morbidities may impact SSTIs severity and outcomes. Delayed healthcare seeking potentially exacerbates infection severity, which in turn increases poorer health outcomes and complications.


Assuntos
Abscesso/epidemiologia , Celulite (Flegmão)/epidemiologia , Dermatopatias Infecciosas/epidemiologia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Abscesso/complicações , Abscesso/fisiopatologia , Adulto , Celulite (Flegmão)/complicações , Celulite (Flegmão)/fisiopatologia , Feminino , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Prevalência , Fatores de Risco , Sepse/complicações , Sepse/epidemiologia , Sepse/fisiopatologia , Dermatopatias Infecciosas/complicações , Dermatopatias Infecciosas/fisiopatologia , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/fisiopatologia , Reino Unido/epidemiologia
7.
Medicine (Baltimore) ; 99(29): e21066, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702849

RESUMO

INTRODUCTION: Sepsis is the most common etiology of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Capillary leakage caused by lung endothelial injury is the central cause of ARDS. The results of research in modern medicine in reducing endothelial damage and restoring endothelial functions are limited. In the previous clinical observations, we found that the Fusu mixture not only improves the clinical symptoms but also reduces the leakage of pulmonary capillaries. Therefore, the purpose of this study is to determine the clinical efficacy of the Fusu mixture combined with Western medicine in the treatment of ARDS caused by sepsis and to explore the mechanism of traditional Chinese medicine. METHODS: This is a prospective, single-center, randomized, single-blind, and controlled clinical study involving 620 eligible patients. The patients will be randomly divided into 2 groups: the Western medicine treatment group and the combination of Chinese and Western medicine treatment group. After 14 days of intervention, the clinical efficacy and safety of the Fusu mixture on sepsis-induced ARDS patients will be observed. The primary outcome will be measured as 28-day mortality. The secondary outcome indices include inflammatory markers (CRP, PCT, IL-6, TNF - α), APACHE II score, SOFA score, days without a ventilator, blood gas analysis (Lac, PaO2 / FiO2), intensive care unit hospital stay time, intensive care unit mortality. Simultaneously, the analysis of the exploratory results will be carried out to analyze the possible mechanism of Fusu mixture in the treatment of sepsis-induced ARDS by the high-throughput sequencing and bioinformatics. DISCUSSION: The purpose of this study is to evaluate the clinical efficacy of Fusu mixture in the treatment of sepsis-induced ARDS and explore its possible mechanism of action. If successful, it will provide evidence-based adjuvant therapy for the clinical treatment of ARDS.


Assuntos
Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/etiologia , Sepse/complicações , Adulto , Gasometria , Síndrome de Vazamento Capilar/complicações , Síndrome de Vazamento Capilar/etiologia , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Medicina Tradicional Chinesa/normas , Pessoa de Meia-Idade , Estudos Prospectivos , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Sepse/tratamento farmacológico , Sepse/fisiopatologia , Método Simples-Cego , Resultado do Tratamento
8.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32680879

RESUMO

OBJECTIVES: Cardiorespiratory and pulse oximetry monitoring in children who are hospitalized should balance benefits of detecting deterioration with potential harms of alarm fatigue. We developed recommendations for monitoring outside the ICU on the basis of available evidence and expert opinion. METHODS: We conducted a comprehensive literature search for studies addressing the utility of cardiorespiratory and pulse oximetry monitoring in common pediatric conditions and drafted candidate monitoring recommendations based on our findings. We convened a panel of nominees from national professional organizations with diverse expertise: nursing, medicine, respiratory therapy, biomedical engineering, and family advocacy. Using the RAND/University of California, Los Angeles Appropriateness Method, panelists rated recommendations for appropriateness and necessity in 3 sequential rating sessions and a moderated meeting. RESULTS: The panel evaluated 56 recommendations for intermittent and continuous monitoring for children hospitalized outside the ICU with 7 common conditions (eg, asthma, croup) and/or receiving common therapies (eg, supplemental oxygen, intravenous opioids). The panel reached agreement on the appropriateness of monitoring recommendations for 55 of 56 indications and on necessity of monitoring for 52. For mild or moderate asthma, croup, pneumonia, and bronchiolitis, the panel recommended intermittent vital sign or oximetry measurement only. The panel recommended continuous monitoring for severe disease in each respiratory condition as well as for a new or increased dose of intravenous opiate or benzodiazepine. CONCLUSIONS: Expert panel members agreed that intermittent vital sign assessment, rather than continuous monitoring, is appropriate management for a set of specific conditions of mild or moderate severity that require hospitalization.


Assuntos
Eletrocardiografia , Monitorização Fisiológica/métodos , Oximetria , Guias de Prática Clínica como Assunto , Transtornos Respiratórios/fisiopatologia , Testes de Função Respiratória , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacologia , Benzodiazepinas/efeitos adversos , Benzodiazepinas/farmacologia , Criança , Criança Hospitalizada , Técnica Delfos , Relação Dose-Resposta a Droga , Humanos , Oxigenoterapia , Respiração/efeitos dos fármacos , Transtornos Respiratórios/etiologia , Sepse/fisiopatologia
9.
Am J Respir Crit Care Med ; 202(7): 1005-1012, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32614246

RESUMO

Rationale: Tissue Doppler imaging (TDI) is an echocardiographic method that measures the velocity of moving tissue.Objectives: We applied this technique to the diaphragm to assess the velocity of diaphragmatic muscle motion during contraction and relaxation.Methods: In 20 healthy volunteers, diaphragmatic TDI was performed to assess the pattern of diaphragmatic motion velocity, measure its normal values, and determine the intra- and interobserver variability of measurements. In 116 consecutive ICU patients, diaphragmatic excursion, thickening, and TDI parameters of peak contraction velocity, peak relaxation velocity, velocity-time integral, and TDI-derived maximal relaxation rate were assessed during weaning. In a subgroup of 18 patients, transdiaphragmatic pressure (Pdi)-derived parameters (peak Pdi, pressure-time product, and diaphragmatic maximal relaxation rate) were recorded simultaneously with TDI.Measurements and Main Results: In terms of reproducibility, the intercorrelation coefficients were >0.89 for all TDI parameters (P < 0.001). Healthy volunteers and weaning success patients exhibited lower values for all TDI parameters compared with weaning failure patients, except for velocity-time integral, as follows: peak contraction velocity, 1.35 ± 0.34 versus 1.50 ± 0.59 versus 2.66 ± 2.14 cm/s (P < 0.001); peak relaxation velocity, 1.19 ± 0.39 versus 1.53 ± 0.73 versus 3.36 ± 2.40 cm/s (P < 0.001); and TDI-maximal relaxation rate, 3.64 ± 2.02 versus 10.25 ± 5.88 versus 29.47 ± 23.95 cm/s2 (P < 0.001), respectively. Peak contraction velocity was strongly correlated with peak transdiaphragmatic pressure and pressure-time product, whereas Pdi-maximal relaxation rate was significantly correlated with TDI-maximal relaxation rate.Conclusions: Diaphragmatic tissue Doppler allows real-time assessment of the diaphragmatic tissue motion velocity. Diaphragmatic TDI-derived parameters differentiate patients who fail a weaning trial from those who succeed and correlate well with Pdi-derived parameters.


Assuntos
Estado Terminal , Diafragma/diagnóstico por imagem , Contração Muscular/fisiologia , Ultrassonografia Doppler/métodos , Desmame do Respirador , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos , Coma/fisiopatologia , Coma/terapia , Diafragma/fisiologia , Diafragma/fisiopatologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/fisiopatologia , Traumatismo Múltiplo/terapia , Procedimentos Neurocirúrgicos , Período Pós-Operatório , Pressão , Reprodutibilidade dos Testes , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Sepse/fisiopatologia , Sepse/terapia , Resultado do Tratamento
10.
PLoS One ; 15(6): e0234039, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555710

RESUMO

Sepsis is characterized by organ dysfunction due to a dysregulated immune response to infection. Currently, no effective treatment for sepsis exists. Platelets are recognized as mediators of the immune response and may be a potential therapeutic target for the treatment of sepsis. We previously demonstrated that NLRP3 inflammasome activation in sepsis-induced activated platelets was associated with multi-organ injury in the cecal-ligation puncture (CLP) rat model of sepsis. In this study, we tested the hypothesis that inhibition of NLRP3 would inhibit platelet activation and attenuate multi-organ injury in the CLP rat. CLP (n = 10) or Sham (n = 10) surgery were performed in male and female Sprague-Dawley rats. A subset of CLP rats were treated with MCC950 (50mg/kg/d), a specific NLRP3 inhibitor (CLP+MCC950, n = 10). At 72 hrs. post-CLP, blood and organs were harvested for analysis of platelet activation, NLRP3 activation, inflammation and end organ damage. Platelet activation increased from 8±0.8% in Sham to 16±1% in CLP, and was reduced to 9±1% in CLP+M rats (p<0.05). NLRP3 activation was also increased in platelets of CLP vs Sham. NLRP3 expression was unchanged in kidney and lung after CLP, but Caspase 1 expression and IL-1ß were increased. MCC950 treatment attenuated NLRP3 activation in platelets. Plasma, kidney, and lung levels of NLRP3 inflammasome associated cytokines, IL-1ß and IL-18, were significantly increased in CLP compared to Sham rats. Inhibition of NLRP3 normalized cytokine levels. Glomerular injury, pulmonary edema, and endothelial dysfunction markers were increased in CLP rats vs Sham. MCC950 treatment significantly decreased renal and pulmonary injury and endothelial dysfunction in CLP+M. Our results demonstrate a role for NLRP3 in contributing to platelet activation and multi-organ injury in sepsis.


Assuntos
Ceco/cirurgia , Inflamassomos/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Ativação Plaquetária/efeitos dos fármacos , Punções/efeitos adversos , Sepse/tratamento farmacológico , Sepse/fisiopatologia , Animais , Caspase 1/metabolismo , Citocinas/metabolismo , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Ligadura/efeitos adversos , Masculino , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Sepse/metabolismo
11.
Med Clin North Am ; 104(4): 573-585, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32505253

RESUMO

Sepsis and septic shock are major causes of mortality among hospitalized patients. The sepsis state is due to dysregulated host response to infection, leading to inflammatory damage to nearly every organ system. Early recognition of sepsis and appropriate treatment with antibiotics, fluids, and vasopressors is essential to reducing organ system injury and mortality. This review summarizes the current understanding of the epidemiology, pathophysiology, diagnosis, and treatment of sepsis and septic shock.


Assuntos
Tomada de Decisão Clínica , Escores de Disfunção Orgânica , Sepse/diagnóstico , Choque Séptico/diagnóstico , Pressão Sanguínea/efeitos dos fármacos , Serviço Hospitalar de Emergência , Mortalidade Hospitalar , Humanos , Classificação Internacional de Doenças , Taxa Respiratória , Sensibilidade e Especificidade , Sepse/fisiopatologia , Sepse/terapia , Choque Séptico/fisiopatologia , Choque Séptico/terapia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Terminologia como Assunto , Vasoconstritores/uso terapêutico
13.
Ann Emerg Med ; 76(4): 427-441, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32593430

RESUMO

STUDY OBJECTIVE: Debate exists about the mortality benefit of administering antibiotics within either 1 or 3 hours of sepsis onset. We performed this meta-analysis to analyze the effect of immediate (0 to 1 hour after onset) versus early (1 to 3 hours after onset) antibiotics on mortality in patients with severe sepsis or septic shock. METHODS: This review was consistent with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searched databases included PubMed, EMBASE, Web of Science, and Cochrane Library, as well as gray literature. Included studies were conducted with consecutive adults with severe sepsis or septic shock who received antibiotics within each period and provided mortality data. Data were extracted by 2 independent reviewers and pooled with random effects. Two authors independently assessed quality of evidence across all studies with Cochrane's Grading of Recommendations Assessment, Development and Evaluation methodology and risk of bias within each study, using the Newcastle-Ottawa Scale. RESULTS: Thirteen studies were included: 5 prospective longitudinal and 8 retrospective cohort ones. Three studies (23%) had a high risk of bias (Newcastle-Ottawa Scale). Overall, quality of evidence across all studies (Grading of Recommendations Assessment, Development and Evaluation) was low. Pooling of data (33,863 subjects) showed no difference in mortality between patients receiving antibiotics in immediate versus early periods (odds ratio 1.09; 95% confidence interval 0.98 to 1.21). Analysis of severe sepsis studies (8,595 subjects) found higher mortality in immediate versus early periods (odds ratio 1.29; 95% confidence interval 1.09 to 1.53). CONCLUSION: We found no difference in mortality between immediate and early antibiotics across all patients. Although the quality of evidence across studies was low, these findings do not support a mortality benefit for immediate compared with early antibiotics across all patients with sepsis.


Assuntos
Antibacterianos/administração & dosagem , Sepse/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Antibacterianos/uso terapêutico , Humanos , Sepse/fisiopatologia
14.
Life Sci ; 255: 117849, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32473249

RESUMO

AIMS: The associations between colorectal neoplasia differentially expressed (CRNDE), a novel long non-coding RNA (lncRNA), and inflammation and cell apoptosis have been underscored recently. However, its function in sepsis-induced myocardial injury remains undetermined. The current study sets to examine the putative mechanism of CRNDE in myocardial injury evoked by sepsis. MATERIALS AND METHODS: Firstly, the rat model of sepsis was developed and verified. Subsequently, differentially expressed lncRNAs in myocardial tissues of septic rats were determined. Afterwards, CRNDE overexpression or knockdown was introduced into the myocardial tissues of rats. Then, H9c2 cells were induced by lipopolysaccharide (LPS) and transfected with overexpression of CRNDE and sirtuin 1 (SIRT1), si-CRNDE or microRNA (miR)-29a mimic. Apoptosis, Caspase-3 activity, secretion of inflammatory factors, and intracellular reactive oxygen species (ROS) content were subsequently measured in rat tissues and transfected cells. Finally, the NF-κB/PARP-1 signaling activity in rat myocardial tissues and cells was detected. KEY FINDINGS: CRNDE expression was reduced in the myocardial tissues of rats with sepsis, and CRNDE restoration alleviated following myocardial injury. Additionally, overexpression of CRNDE inhibited cardiomyocyte apoptosis, ROS content, Caspase-3 activity, nuclear NF-κB p65 phosphorylation and PARP-1 expression. Dual-luciferase assays showed that the CRNDE/miR-29a/SIRT1 network regulated sepsis-induced myocardial injury. Moreover, miR-29a mimic attenuated the protective effect of CRNDE overexpression on LPS-induced cardiomyocytes. SIGNIFICANCE: CRNDE protects the myocardial tissues against sepsis-induced cardiomyocyte apoptosis and oxidative damage by inhibiting the post-transcriptional regulatory function of miR-29a on SIRT1.


Assuntos
MicroRNAs/genética , Miocárdio/patologia , RNA Longo não Codificante/genética , Sepse/fisiopatologia , Sirtuína 1/genética , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Inflamação/genética , Inflamação/patologia , Lipopolissacarídeos , Masculino , Miócitos Cardíacos/patologia , NF-kappa B/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Sepse/genética
15.
Life Sci ; 255: 117821, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32445759

RESUMO

Human sepsis is the result of a multifaceted pathological process causing marked dysregulation of cardiovascular responses. A more sophisticated understanding of the pathogenesis of sepsis is certainly prerequisite. Evidence from studies provide further insight into the role of inducible nitric oxide synthase (iNOS) isoform. Results on inhibition of iNOS in sepsis models remain inconclusive. Concern has been devoted to improving our knowledge and understanding of the role of iNOS. The aim of this review is to define the role of iNOS in redox homeostasis disturbance, the detailed mechanisms linking iNOS and posttranslational modifications (PTMs) to cardiovascular dysfunctions, and their future implications in sepsis settings. Many questions related to the iNOS and PTMs still remain open, and much more work is needed on this.


Assuntos
Doenças Cardiovasculares/etiologia , Óxido Nítrico Sintase Tipo II/metabolismo , Sepse/complicações , Animais , Doenças Cardiovasculares/enzimologia , Humanos , Oxirredução , Processamento de Proteína Pós-Traducional , Sepse/enzimologia , Sepse/fisiopatologia
16.
Life Sci ; 254: 117819, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32442451

RESUMO

AIMS: Vascular dysfunction plays a key role in sepsis but the role of perivascular adipose tissue (PVAT) in this condition is relatively unknown. MAIN METHODS: Sepsis was induced by cecal ligation and puncture (CLP). The responses of the aorta and superior mesenteric artery to norepinephrine in the presence or absence of PVAT were evaluated. Fluorescent probes measured the production of nitric oxide (NO) and reactive oxygen species (ROS). NO synthases (NOS) and ß3-adrenoceptor expression were detected by immunofluorescence and S-nitrosylation by the biotin switch assay. KEY FINDINGS: Aorta and superior mesenteric arteries from septic animals with intact PVAT showed a worsened response to the vasoconstrictor compared to vessels without PVAT. PVAT from the aorta (APVAT) produced NO and ROS whereas PVAT from the superior mesenteric artery (MPVAT) produced only ROS. Septic APVAT exhibited a higher density of NOS-1 and NOS-3. S-nitrosylation was found in APVAT. Donor (PVAT obtained from normal or septic rats):Host (normal vessel without PVAT) experiments showed that L-NAME, ODQ and ß3-adrenergic receptor antagonist blocked the septic APVAT anti-contractile effect. None of these compounds affected MPVAT; tempol, but not apocynin, blocked its anti-contractile effect. SIGNIFICANCE: PVAT contributes to the anti-contractile effect in the aorta and mesenteric artery of septic rats through different pathways. ß3-Adrenergic receptor and NO appear to be key mediators of this effect in APVAT, but not in MPVAT where ROS seem to be a relevant mediator. Therefore, PVAT is a relevant player of sepsis vascular dysfunction.


Assuntos
Aorta/metabolismo , Artérias Mesentéricas/metabolismo , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Adrenérgicos beta 3/fisiologia , Sepse/fisiopatologia , Acetofenonas/farmacologia , Tecido Adiposo/metabolismo , Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Animais , Óxidos N-Cíclicos/farmacologia , Feminino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/metabolismo , Norepinefrina/farmacologia , Oxidiazóis/farmacologia , Fenótipo , Quinoxalinas/farmacologia , Ratos , Receptores Adrenérgicos beta 3/biossíntese , Marcadores de Spin , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia
17.
Life Sci ; 255: 117841, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32454156

RESUMO

AIMS: Trefoil factor 3 (TFF3) is a gut mucosal protective molecule that is secreted by intestinal goblet cells. The dimeric structure of TFF3 enables it to function in intestinal mucosal repair and to maintain its own stability. Protein disulfide isomerase a1 (PDIA1) can directly catalyze the formation, isomerization and reduction of disulfide bonds in proteins and may play an important role in the formation of TFF3 dimer. In this study, we focused on the specific molecular mechanism of TFF3 dimerization by PDIA1 and the changes during sepsis. METHODS: We examined the changes of PDIA1 and TFF3 in sepsis rats and cell models and used a variety of experimental techniques to investigate the specific molecular mechanism of PDIA1-catalyzed TFF3 dimerization. KEY FINDINGS: We found that PDIA1 can directly catalyze the dimerization of TFF3. Our MD model proposed that two TFF3 monomers form hydrogen bonds with the region b' of PDIA1 through two stepwise reactions. Furthermore, we propose that the Cys24-Cys27 active site at the region a' of PDIA1 mediates disulfide bond formation between the Cys79 residues of each of the two TFF3 monomers via deprotonation and nucleophilic attack. During sepsis, PDIA1 is downregulated and the excessive release of nitric oxide (NO) promoted PDIA1 nitrosylation. This modification reduced PDIA1 activity, which resulted in the corresponding decrease of TFF3 dimerization and compromised TFF3 dimer function. SIGNIFICANCE: Our study revealed a novel mechanism for the inhibition of intestinal mucosal repair during sepsis and revealed novel targets for the prevention and treatment of sepsis.


Assuntos
Mucosa Intestinal/metabolismo , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Sepse/fisiopatologia , Fator Trefoil-3/metabolismo , Animais , Dimerização , Modelos Animais de Doenças , Regulação para Baixo , Masculino , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Óxido Nítrico/metabolismo , Pró-Colágeno-Prolina Dioxigenase/genética , Isomerases de Dissulfetos de Proteínas/genética , Ratos , Ratos Sprague-Dawley
18.
Curr Cardiol Rep ; 22(5): 35, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32377972

RESUMO

PURPOSE OF REVIEW: To briefly review epidemiology and pathophysiology of SICM and provide a more extensive review of the data on diagnostic and management strategies. RECENT FINDINGS: SICM is likely underdiagnosed and that has mortality implications. Current evidence supports speckle tracking echocardiography to identify decreased contractility irrespective of left ventricular ejection fraction for the diagnosis of SICM. There continues to be a dearth of large clinical trials evaluating the treatment of SICM and current consensus focuses on supportive measures such as vasopressors and inotropes. Sepsis is a significant cause of mortality, and sepsis-induced cardiomyopathy has both prognostic and management implications for these patients. Individualized work-up and management of these patients is crucial to improving outcomes.


Assuntos
Cardiomiopatias/etiologia , Coração/fisiopatologia , Sepse/fisiopatologia , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Ecocardiografia , Coração/diagnóstico por imagem , Humanos , Sepse/complicações , Sepse/diagnóstico por imagem , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda , Função Ventricular Esquerda
19.
Trop Doct ; 50(3): 186-190, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32216538

RESUMO

Information concerning the clinical outcome of severe sepsis and septic shock among the burden of tropical infections in children is limited, particularly in low-income settings. We conducted a prospective consecutive cohort study in all children aged 1 month to 16 years needing paediatric intensive care between 1 January 2017 and 31 December 2018. Demographic details, presenting symptoms and duration, associated co-morbidity and organ dysfunction were recorded. Clinical and laboratory parameters discriminating between survivors and non-survivors were evaluated. Most presented with respiratory or central nervous system derangement along with cardiovascular dysfunction. Haematological involvement was almost invariably found on diagnostic evaluation. Those children with ≥3 systems involved had higher odds of mortality. Dengue was seen in half the patients, being the commonest tropical infection. Not surprisingly, non-survivors were younger, had rapid progression of illness and needed ventilation more often within the first hour of admission. However, in multivariable regression analysis, only procalcitonin levels were associated with increased risk of mortality. We conclude that that tropical infections causing severe sepsis and septic shock are an important cause of mortality. There are, however, no clinical parameters which differentiate reliably between survivors and non-survivors.


Assuntos
Estado Terminal/mortalidade , Sepse/mortalidade , Choque Séptico/mortalidade , Adolescente , Criança , Pré-Escolar , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Índia/epidemiologia , Lactente , Masculino , Estudos Prospectivos , Fatores de Risco , Sepse/etiologia , Sepse/patologia , Sepse/fisiopatologia , Choque Séptico/etiologia , Choque Séptico/patologia , Choque Séptico/fisiopatologia
20.
PLoS One ; 15(3): e0229563, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32155161

RESUMO

BACKGROUND: Sepsis-induced cardiomyopathy (SIC) is known to show cardiac dysfunction in patients with sepsis. Both a decrease or an increase in ejection fraction (EF), an indicator of cardiac function, can occur. The purpose of this study was to identify factors associated with abnormal left ventricular (LV) function measured by EF in patients with sepsis in the intensive care unit (ICU). METHODS: This was a retrospective study performed from November 2016 to December 2018. Three-hundred and sixty-six patients (mean age, 73 ± 13 years; 191 [52%] men) admitted to the ICU with sepsis were included. Patients were classified into three categories according to LV EF (group 1 -[EF<50%, n = 36], group 2 -[50≤EF<70%, n = 252], and group 3 -[EF≥70%, n = 78]). Echocardiographic assessment was performed within 48 hours of diagnosis of sepsis. We analyzed clinical factors including mortality, echocardiographic findings, and laboratory parameters. RESULTS: Decreased LV EF occurred in 36 (10%) patients and hyper-dynamic EF developed in 78 (21%) patients. Of 366 patients, 103 (28%) patients died. Baseline characteristics were similar in the three groups, except female sex an indicator of abnormal EF. Mortality rates were also similar in the three groups; however, mortality rates were significantly higher in patients with abnormal EF (decreased or increased vs. normal). Echocardiographic parameters were significantly different in the three groups, in terms of LV systolic parameters and chamber size. Small left atrium (LA) and small LV were significantly associated with abnormal EF (especially in patients with increased EF). High brain natriuretic peptide was associated with decreased EF. Among these factors, female sex and small LA were significantly associated with abnormal EF in the multiple regression analysis. CONCLUSION: Our findings highlight that female sex and small cardiac size are associated with abnormal EF, and therefore, death. Therefore, female patients and patients with small LA should be monitored closely when they present with sepsis.


Assuntos
Sepse/fisiopatologia , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Função Atrial/fisiologia , Diástole , Ecocardiografia , Feminino , Átrios do Coração/fisiopatologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Sístole , Disfunção Ventricular Esquerda/metabolismo , Função Ventricular Esquerda/fisiologia
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