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1.
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
2.
Yonsei Med J ; 61(10): 851-859, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32975059

RESUMO

PURPOSE: Thrombocytopenia (platelet count <150×10³/µL) is associated with poor outcomes in various critical illness settings. However, the prognostic value of platelet count in patients with cardiogenic shock (CS) remains unclear. MATERIALS AND METHODS: We enrolled 1202 patients between January 2014 and December 2018 from a multicenter retrospective-prospective cohort registry of CS. Clinical characteristics and treatment outcomes were compared between the patients with and without thrombocytopenia. RESULTS: At presentation with CS, 244 (20.3%) patients had thrombocytopenia. The patients with thrombocytopenia had lower blood pressure, hemoglobin level, and worse liver and renal functions compared to the patients without. During hospitalization, the patients with thrombocytopenia had more frequent gastrointestinal bleeding (10.5% vs. 3.8%, p=0.009), sepsis (8.3% vs. 2.6%, p=0.013), requirement of renal replacement therapy (36.5% vs. 18.9%, p<0.001), requirement of mechanical ventilation (65.2% vs. 54.4%, p=0.003), longer intensive care unit stay (8 days vs. 4 days, p<0.001), and thirty-day mortality (40.2% vs. 28.5%, p<0.001) compared to those without. In addition, the platelet count was an independent predictor of 30-day mortality (per 103/µL decrease; adjusted hazard ratio: 1.002, 95% confidence interval: 1.000-1.003, p=0.021). CONCLUSION: Thrombocytopenia at CS presentation was associated with worse clinical findings, higher frequencies of complications, and longer stay at the intensive care unit. Also, thrombocytopenia was independently associated with increased 30-day mortality. (Clinical trial registration No. NCT02985008).


Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Choque Cardiogênico , Trombocitopenia , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Estado Terminal , Feminino , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Contagem de Plaquetas , Prevalência , Prognóstico , Estudos Prospectivos , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Sepse/sangue , Sepse/epidemiologia , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/mortalidade , Choque Cardiogênico/terapia , Trombocitopenia/diagnóstico , Trombocitopenia/mortalidade , Trombocitopenia/terapia , Resultado do Tratamento
4.
PLoS One ; 15(9): e0239069, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915919

RESUMO

The diagnosis of leptospirosis remains a challenge due to its non-specific symptoms and the biphasic nature of the illness. A comprehensive diagnosis that includes both molecular (polymerase chain reaction (PCR)) and serology is vital for early detection of leptospirosis and to avoid misdiagnosis. However, not all samples could be subjected to both tests (serology and molecular) due to budget limitation, infrastructure, and technical expertise at least in resource-limited countries. We evaluated the usefulness of testing the clinically suspected leptospirosis cases with both techniques on all samples collected from the patients on the day of admission. Among the 165 patient's blood/serum samples tested (from three hospitals in Central Malaysia), 43 (26%) showed positivity by microscopic agglutination test (MAT), 63 (38%) by PCR, while 14 (8%) were positive by both MAT and PCR. For PCR, we tested two molecular targets (lipL32 by qPCR and 16S rDNA or rrs by nested PCR) and detected lipL32 in 47 (29%) and rrs gene in 63 (38%) patients. The use of more than one target gene for PCR increased the detection rates. Hence, a highly sensitive multiplex PCR targeting more than one diagnostic marker is recommended for the early detection of Leptospira in suspected patients. When the frequencies for positivity detected either by MAT or PCR combined, leptospirosis was diagnosed in a total of 92 (56%) patients, a higher frequency compared to when samples were only tested by a single method (MAT or PCR). The results from this study suggest the inclusion of both serology and molecular methods for every first sample irrespective of the days post-onset of symptoms (DPO) collected from patients for early diagnosis of leptospirosis.


Assuntos
Testes de Aglutinação , Leptospira/isolamento & purificação , Leptospirose/diagnóstico , Reação em Cadeia da Polimerase , Sepse/diagnóstico , DNA Bacteriano/isolamento & purificação , Erros de Diagnóstico/prevenção & controle , Diagnóstico Precoce , Estudos de Viabilidade , Humanos , Leptospira/genética , Leptospira/imunologia , Leptospirose/sangue , Leptospirose/imunologia , Leptospirose/microbiologia , Malásia , RNA Ribossômico 16S/genética , Sensibilidade e Especificidade , Sepse/sangue , Sepse/imunologia , Sepse/microbiologia , Fatores de Tempo
5.
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
6.
Medicine (Baltimore) ; 99(34): e21893, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846851

RESUMO

We examined the blood concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and citrullinated alpha enolase peptide-1 (CEP-1) antibody in sepsis patients to evaluate their potential diagnostic, classified and prognostic utility together with C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6).Sixty-nine patients admitted at the emergency department with sepsis were studied, on admission, their demographic and clinical information were recorded. Blood levels of CRP, PCT, IL-6, NGAL, and CEP-1 antibody were measured. Relationships between sequential [sepsis-related] organ failure assessment score and blood biomarkers, between acute physiology and chronic health evaluation II score and blood biomarkers were investigated. Additionally, the mutual correlation among CRP, PCT, IL-6, NGAL, and CEP-1 antibody were investigated. Diagnostic and predictive values for clinical outcomes for biomarkers were assessed by receiver operator characteristic curve.Sixty-nine participants (38 sepsis, 31 septic shock) were compared with 40 healthy controls. The levels of CRP, PCT, IL-6, and NGAL were significantly higher in sepsis patients ([59.49 ± 48.88]; 0.71, [0.13-11.72]; 60.46, [33.26-201.20]; 265.61, [185.79-500.96], respectively) compared with healthy controls ([2.05 ± 1.85]; 0.02, [0.02-0.03]; 12.08, [7.22-16.84]; 19.73, [7.66-34.39], respectively) (P < .001). CRP, PCT, IL-6, and NGAL had better discriminatory performance with an area under the receiver operator characteristic curve (AUC) of (0.98; 0.98; 0.90; 0.97, respectively), 95% confidence interval (CI) = ([0.95; 1.00]; [0.96; 1.00]; [0.84; 0.96]; [0.94; 1.00], respectively) (P < .001), with a cut off value of (8.02 mg/L [Se = 88.40%, Sp = 100.00%]; 0.06 ng/mL [Se = 94.20%, Sp = 75.00%]; 30.63 pg/mL [Se = 78.30%, Sp = 95.00%]; 95.72 ng/mL [Se = 99.00%, Sp = 92.00%], respectively). Between the sepsis group and septic shock group, PCT and NGAL were significantly higher in septic shock group (2.44, [0.49-20.36]; 294.65 [203.34-1262.47], respectively) compared with sepsis group (0.41, [0.11-2.63]; 219.94, [146.38-385.24], respectively) (P < .05). Between survivors group and nonsurvivors group, PCT was obviously elevated in nonsurvivors group (2.47, [0.70-12.49]) compare with survivors group (0.41, [0.11-8.16]) (P < .05), with an AUC of 0.69, 95% CI = (0.57; 0.81) (P < .05), while CEP-1 antibody was decreased in nonsurvivors group (14.03, [4.94-17.17]) contrast to survivors group (18.78, [8.08-39.72]) (P < .05), with an AUC of 0.67, 95% CI = (0.54; 0.80) (P < .05). Additionally, CEP-1 antibody demonstrated a negative correlation with either sequential [sepsis-related] organ failure assessment score (r = -0.31, P < .05) or PCT (r = -0.27, P < .05).As CRP, PCT, and IL-6, NGAL was valuable in sepsis diagnosis. With a classificatory value, PCT and NGAL correlated with the degree severity of sepsis. PCT and CEP-1 antibody were meaningful in sepsis prognosis. CEP-1 antibody may be a protective factor for sepsis.


Assuntos
Anticorpos/sangue , Lipocalina-2/sangue , Sepse/sangue , Sepse/diagnóstico , Choque Séptico/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anti-Proteína Citrulinada/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Fosfopiruvato Hidratase/metabolismo , Valor Preditivo dos Testes , Pró-Calcitonina/sangue , Prognóstico , Estudos Prospectivos , Sepse/classificação , Sepse/mortalidade , Choque Séptico/sangue
7.
Nat Commun ; 11(1): 3852, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737308

RESUMO

Acute critical illness is often preceded by deterioration of routinely measured clinical parameters, e.g., blood pressure and heart rate. Early clinical prediction is typically based on manually calculated screening metrics that simply weigh these parameters, such as early warning scores (EWS). The predictive performance of EWSs yields a tradeoff between sensitivity and specificity that can lead to negative outcomes for the patient. Previous work on electronic health records (EHR) trained artificial intelligence (AI) systems offers promising results with high levels of predictive performance in relation to the early, real-time prediction of acute critical illness. However, without insight into the complex decisions by such system, clinical translation is hindered. Here, we present an explainable AI early warning score (xAI-EWS) system for early detection of acute critical illness. xAI-EWS potentiates clinical translation by accompanying a prediction with information on the EHR data explaining it.


Assuntos
Lesão Renal Aguda/diagnóstico , Lesão Pulmonar Aguda/diagnóstico , Inteligência Artificial , Registros Eletrônicos de Saúde/estatística & dados numéricos , Sepse/diagnóstico , Doença Aguda , Lesão Renal Aguda/sangue , Lesão Renal Aguda/patologia , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/patologia , Área Sob a Curva , Pressão Sanguínea , Estado Terminal , Diagnóstico Precoce , Frequência Cardíaca , Humanos , Prognóstico , Curva ROC , Sepse/sangue , Sepse/patologia
8.
Crit Care ; 24(1): 493, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778146

RESUMO

BACKGROUND: Administration of dexmedetomidine has been reported to improve inflammatory response in animals. We explored the effects of administering dexmedetomidine on the levels of C-reactive protein (CRP) and procalcitonin, and thus on inflammation, in patients with sepsis enrolled in a randomized clinical trial. METHODS: The DESIRE trial was a multicenter randomized clinical trial in which adult patients with sepsis were sedated with (DEX group) or without (non-DEX group) dexmedetomidine while on mechanical ventilators. As a prespecified sub-analysis, we compared CRP and procalcitonin levels during the first 14 days of treatment between the two groups. The 14-day mortality rate, albumin level, and the number of patients with disseminated intravascular coagulation (DIC) were also assessed. We used generalized linear models to estimate the differences in these outcomes between groups. We also used the Kaplan-Meier method to estimate the 14-day mortality rate and the log-rank test to assess between-group differences. RESULTS: Our study comprised 201 patients: 100 in the DEX group and 101 in the non-DEX group. CRP and procalcitonin levels were lower in the DEX vs. non-DEX group during the 14-day treatment period [CRP-range, 5.6-20.3 vs. 8.3-21.1 mg/dL (P = 0.03); procalcitonin-range, 1.2-37.4 vs. 1.7-52.9 ng/mL (P = 0.04)]. Albumin levels were higher in the DEX group (range, 2.3-2.6 g/dL) than in the non-DEX group (range, 2.1-2.7 g/dL; P = 0.01). The percentage of patients with DIC did not significantly differ between the groups (range, 21-59% and 17-56% for the DEX and non-DEX groups, respectively; P = 0.49). The 14-day mortality rates in the DEX and non-DEX groups were 13 and 21%, respectively (P = 0.16). CONCLUSION: Sedation using dexmedetomidine reduced inflammation in patients with sepsis requiring mechanical ventilation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01760967 . Registered on 4 January 2013.


Assuntos
Dexmedetomidina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Inflamação/prevenção & controle , Respiração Artificial , Sepse/terapia , Idoso , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Sepse/sangue , Resultado do Tratamento
9.
JCI Insight ; 5(17)2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32706339

RESUMO

BACKGROUNDElevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare with those observed in critically ill patients with acute respiratory distress syndrome (ARDS) or sepsis due to other causes.METHODSWe used a Luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1ß, IL-1RA, IL-6, IL-8, IL-18, and TNF-α) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis.RESULTSFifteen hospitalized COVID-19 patients, 9 of whom were critically ill, were compared with critically ill patients with ARDS (n = 12) or sepsis (n = 16). There were no statistically significant differences in baseline levels of IL-1ß, IL-1RA, IL-6, IL-8, IL-18, and TNF-α between patients with COVID-19 and critically ill controls with ARDS or sepsis.CONCLUSIONLevels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 may be unwarranted.FUNDINGFunding was received from NHLBI K23 HL125663 (AJR); The Bill and Melinda Gates Foundation OPP1113682 (AJR and CAB); Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687 NIH/NIAID U19AI057229-16; Stanford Maternal Child Health Research Institute; and Chan Zuckerberg Biohub (CAB).


Assuntos
Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Citocinas/imunologia , Pneumonia Viral/imunologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Sepse/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Infecções por Coronavirus/sangue , Síndrome da Liberação de Citocina/sangue , Citocinas/sangue , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/sangue , Proteína Antagonista do Receptor de Interleucina 1/imunologia , Interleucina-18/sangue , Interleucina-18/imunologia , Interleucina-1beta/sangue , Interleucina-1beta/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Interleucina-8/sangue , Interleucina-8/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Síndrome do Desconforto Respiratório do Adulto/sangue , Sepse/sangue , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
10.
Medicine (Baltimore) ; 99(28): e20272, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664056

RESUMO

This study aimed to determine the role of survivin in sepsis patients.Serum samples of 288 sepsis patients and 290 healthy individuals (as healthy controls) were collected 24 hours within enrollment. Serum survivin and inflammatory cytokines were detected by enzyme-linked immunosorbent assay, and biochemical indexes were recorded. In sepsis patients, acute pathologic and chronic health evaluation II score and sequential organ failure assessment score were evaluated, and 28-day mortality was recorded.Survivin was greatly decreased in sepsis patients compared to healthy controls (P < .001) and it predicted decreased sepsis risk (area under curve (AUC): 0.921, 95% confidence interval (CI): 0.900-0.942). For clinical characteristics of sepsis patients, survivin was negatively correlated with acute pathologic and chronic health evaluation II score (P < .001), score and sequential organ failure assessment score (P < .001), serum creatinine (P < .001), white blood cell (P = .037), C-reactive protein (P < .001), tumor necrosis factor-α (P < .001), interleukin (IL)-1ß (P < .001), IL-6 (P < .001), and IL-8 (P < .001), while positively correlated with albumin (P < .001). For prognosis of sepsis patients, survivin was decreased in deaths compared to survivors (P < .001), and it predicted decreased death risk (AUC: 0.625, 95% CI: 0.558-0.692). Meanwhile, accumulating mortality was decreased in survivin high patients compared to survivin low patients (P = .006). However, multivariate logistic regression revealed survivin was not an independent predictive factor for 28-day mortality, indicating it might interact with other independent factors to affect prognosis of sepsis patients.Survivin was decreased in sepsis patients and predicted decreased sepsis risk. Meanwhile, survivin was correlated with declined inflammation, reduced disease severity, and favorable prognosis in sepsis patients.


Assuntos
Sepse/sangue , Survivina/sangue , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sepse/diagnóstico , Sepse/mortalidade
11.
Clin Appl Thromb Hemost ; 26: 1076029620938149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32677459

RESUMO

The novel coronavirus infection (COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as adult respiratory syndrome, sepsis, coagulopathy, and death in a proportion of patients. Among other factors and direct viral effects, the increase in the vasoconstrictor angiotensin II, the decrease in the vasodilator angiotensin, and the sepsis-induced release of cytokines can trigger a coagulopathy in COVID-19. A coagulopathy has been reported in up to 50% of patients with severe COVID-19 manifestations. An increase in d-dimer is the most significant change in coagulation parameters in severe COVID-19 patients, and progressively increasing values can be used as a prognostic parameter indicating a worse outcome. Limited data suggest a high incidence of deep vein thrombosis and pulmonary embolism in up to 40% of patients, despite the use of a standard dose of low-molecular-weight heparin (LMWH) in most cases. In addition, pulmonary microvascular thrombosis has been reported and may play a role in progressive lung failure. Prophylactic LMWH has been recommended by the International Society on Thrombosis and Haemostasis (ISTH) and the American Society of Hematology (ASH), but the best effective dosage is uncertain. Adapted to the individual risk of thrombosis and the d-dimer value, higher doses can be considered, especially since bleeding events in COVID-19 are rare. Besides the anticoagulant effect of LMWH, nonanticoagulant properties such as the reduction in interleukin 6 release have been shown to improve the complex picture of coagulopathy in patients with COVID-19.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Trombofilia/etiologia , Trombose/prevenção & controle , Angiotensina II/metabolismo , Arteriopatias Oclusivas/sangue , Arteriopatias Oclusivas/epidemiologia , Arteriopatias Oclusivas/etiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/etiologia , Surtos de Doenças , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/prevenção & controle , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Incidência , Inflamação , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Prognóstico , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Risco , Sepse/sangue , Sepse/complicações , Síndrome Respiratória Aguda Grave/sangue , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/epidemiologia , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Trombose/sangue , Trombose/epidemiologia , Trombose/etiologia , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/prevenção & controle , Ativador de Plasminogênio Tecidual/uso terapêutico
12.
Medicine (Baltimore) ; 99(22): e20274, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481394

RESUMO

Sepsis is a life-threatening disease in the intensive care unit (ICU). The current diagnostic criteria for sequential organ failure assessment (SOFA) scores do not reflect the current understanding of sepsis. We developed a novel and convenient score to aid early prognosis.Retrospective multivariable regression analysis of 185 infected emergency ICU (EICU) patients was conducted to identify independent variables associated with death, to develop the new "STAPLAg" score; STAPLAg was then validated in an internal cohort (n = 106) and an external cohort (n = 78) and its predictive efficacy was compared with that of the initial SOFA score.Age, and initial serum albumin, sodium, PLR, troponin, and lactate tests in the emergency department were independent predictors of death in infected EICU patients, and were used to establish the STAPLAg score (area under the curve [AUC] 0.865). The initial SOFA score on admission was predictive of death (AUC 0.782). Applying the above categories to the derivation cohort yielded mortality risks of 7.7% for grade I, 56.3% for grade II, and 75.0% for grade III. Internal (AUC 0.884) and external (AUC 0.918) cohort validation indicated that the score had good predictive power.The STAPLAg score can be determined early in infected EICU patients, and exhibited better prognostic capacity than the initial SOFA score on admission in both internal and external cohorts. STAPLAg constitutes a new resource for use in the clinical diagnosis of sepsis and can also predict mortality in infected EICU patients. REGISTRATION NUMBER:: ChinCTR-PNC-16010288.


Assuntos
Escore de Alerta Precoce , Unidades de Terapia Intensiva , Escores de Disfunção Orgânica , Sepse/diagnóstico , Fatores Etários , Idoso , Feminino , Humanos , Ácido Láctico/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Sepse/sangue , Sepse/mortalidade , Albumina Sérica/análise , Sódio/sangue , Troponina/sangue
13.
Medicine (Baltimore) ; 99(22): e19754, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481361

RESUMO

BACKGROUND: Previous studies have indicated the association of microRNA-146a/b (miR-146a/miR-146b) with pro-inflammatory cytokines production, lipopolysaccharide-mediated injuries and organ dysfunction, however, the correlation of miR-146a/miR-146b with disease risk, disease severity, biochemical indices, inflammatory cytokines and mortality of sepsis has not been explored, which was investigated in the present study. METHODS: In total, 180 sepsis patients and 180 healthy controls were enrolled. The peripheral blood samples were collected from sepsis patients within 24 hour after admission and from healthy controls at enrolment. Furthermore, MiR-146a/miR-146b expressions in plasma were detected by reverse transcription quantitative polymerase chain reaction. RESULTS: MiR-146a and miR-146b expressions were higher in sepsis patients compared to healthy controls. MiR-146a (AUC: 0.774, 95%CI: 0.727-0.820) and miR-146b (AUC: 0.897, 95%CI: 0.865-0.929) were both of good value in predicting increased sepsis risk, among which miR-146b presented a superior predictive value. In sepsis patients, MiR-146a expression was positively associated with miR-146b expression. Besides, MiR-146a and miR-146b expressions were positively correlated with acute pathologic and chronic health evaluation II score, sequential organ failure assessment score, serum creatinine, C-reactive protein, tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-17, while negatively correlated with albumin. Based on the survival status in 28-day follow-up, MiR-146a and miR-146b expression were both increased in survivors compared to deaths. miR-146b presented relatively good predictive for increased 28-day mortality risk (AUC: 0.703, 95%CI: 0.617-0.788), but MiR-146a was of poor value in predicting increased 28-day mortality risk (AUC: 0.599, 95%CI: 0.511-0.688). CONCLUSION: MiR-146b presents superior potential as a prognostic biomarker in sepsis patients compared to MiR-146a, which implies the clinical application of miR-146b in disease management of sepsis.


Assuntos
MicroRNAs/sangue , Sepse/sangue , APACHE , Idoso , Estudos de Casos e Controles , China/epidemiologia , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sepse/mortalidade
14.
Med Leg J ; 88(2): 78-80, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32490726

RESUMO

Viral sepsis is rare, and its real incidence is not known. SARS-CoV-2 infection causes the release of a significant amount of pro-inflammatory cytokines that aggravates interstitial pneumonia and evolves in viral sepsis with prominent hypercoagulability. We believe it is useful and advisable to establish early immunomodulator therapy and the prophylaxis anticoagulant therapy should be rethought.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Citocinas/sangue , Pneumonia Viral/complicações , Sepse/virologia , Trombose/virologia , Fatores Etários , Anticoagulantes/uso terapêutico , Biomarcadores/sangue , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Imunossupressores/uso terapêutico , Pandemias , Pneumonia Viral/tratamento farmacológico , Sepse/sangue , Trombose/prevenção & controle
15.
Medicine (Baltimore) ; 99(25): e20756, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569219

RESUMO

The prognostic value of 3 types (total, bioavailable, and free) of 25-hydroxy vitamin D [25(OH)D] and vitamin D binding protein (VDBP) in patients with sepsis is unknown. The aim of this study was to evaluate the association of levels of those 3 types of 25(OH) D and VDBP with 30-day mortality in patients with sepsis. From March to December 2018, patients diagnosed with sepsis and admitted to the medical intensive care unit were enrolled, prospectively. We measured total 25(OH)D and VDBP levels, performed GC genotyping for the polymorphisms rs4588 and rs7041, and calculated bioavailable and free 25(OH)D levels. Total, bioavailable, and free 25(OH)D levels did not differ in 30-days nonsurvivors and survivors. Serum VDBP level was significantly higher in survivors than nonsurvivors (138.6 ug/mL vs 108.2 ug/mL, P = .023) and was associated with 30-day mortality in univariate but not multivariate analysis. VDBP polymorphisms and allele frequencies were not statistically different between the groups. Serum VDBP level was significantly higher in survivors than nonsurvivors over 30-days mortality in septic patients. However, 3 types (total, bioavailable, and free) of 25(OH)D levels did not differ between the survivors and nonsurvivors group.


Assuntos
Sepse/mortalidade , Proteína de Ligação a Vitamina D/sangue , Vitamina D/sangue , Idoso , Idoso de 80 Anos ou mais , Disponibilidade Biológica , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Sepse/sangue , Sepse/complicações , Sepse/genética , Vitamina D/metabolismo , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/mortalidade , Proteína de Ligação a Vitamina D/genética , Proteína de Ligação a Vitamina D/metabolismo
16.
Clin Chim Acta ; 509: 22-24, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32504637

RESUMO

INTRODUCTION: Interesting results regarding the contribution of MDW (Monocyte Distribution Width) in the Infectious Disease Unit have been reported. An observational study is ongoing at San Donato Hospital with the aim to evaluate the contribution of MDW in the diagnostic pathway in adult patients entering in the ED setting and tested for SARS-CoV-2. MATERIAL AND METHOD: COVID-19 symptomatic and paucisymptomatic patients presenting to ED (Emergency Department), have been enrolled consecutively. Whole blood venous samples have been collected on K2 EDTA for MDW determination, at the same time a nasopharyngeal swab for SARS-CoV-2 RNA detection have been collected. RESULTS: One hundred six patients were negative for SARS-CoV-2 with MDW mean value of 20.3 ± 3.3, while forty-one were positive for SARS-CoV-2 with higher MDW mean value of 27.3 ± 4.9 (P < 0.005). The ROC curve analysis has been evaluated showing MDW AUC of 0.91. Finally twenty-three patients hospitalized in high-intensity care unit showed an MDW value higher than the eighteen patients presenting few symptoms [28.8 ± 5.3 vs 25.4 ± 3.6 respectively, P < 0.05]. DISCUSSION: Monocytic population, in Covid19 disease, are the first elements of innate immunity to be involved, these changes are the basis of the modification of the MDW, with evident efficacy in term of sensitivity, particularly in the studied Covid19 patients. Moreover the patients hospitalized in high-intensity care unit showed significantly elevated MDW respects to middle or low symptomatic one, suggest including this parameter as prognostic marker or of therapy efficacy, integrated with other laboratory findings.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Monócitos/metabolismo , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Sepse/sangue , Sepse/diagnóstico , Adulto , Idoso , Betacoronavirus/isolamento & purificação , Tamanho Celular , Técnicas de Laboratório Clínico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Pandemias
18.
Int J Infect Dis ; 97: 260-266, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32497803

RESUMO

OBJECTIVES: Related innate immune system activation and diagnostic factors of sepsis are not fully understood. The aim of this study was to analyze the clinical value of full-length tryptophanyl-tRNA synthetase (WRS) induced through inflammatory stimuli for the detection of sepsis and prediction of mortality in critically ill patients. METHODS: This was a retrospective analysis of blood samples collected prospectively from patients in the medical intensive care unit (ICU) at Yonsei University College of Medicine, from March 2015 to June 2018. The ability of WRS to detect sepsis and predict mortality were compared to those of procalcitonin (PCT), C-reactive protein (CRP), and interleukin 6 (IL-6), and with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. RESULTS: A total of 241 study patients were enrolled, of whom 190 (78.8%) had been diagnosed with sepsis on ICU admission. The areas under the receiver operating characteristics curves (AUROCs) for sepsis discrimination with WRS, PCT, CRP, and IL-6 levels, and SOFA and APACHE II scores were 0.864, 0.727, 0.625, 0.651, 0.840, and 0.754, respectively. The prediction of 28-day mortality in patients with sepsis using WRS levels was possible and non-inferior to that with the SOFA score. CONCLUSIONS: WRS secreted early in sepsis may be useful not only for the early detection of sepsis, but also for the prediction of mortality in critically ill patients.


Assuntos
Sepse/diagnóstico , Triptofano-tRNA Ligase/sangue , APACHE , Idoso , Proteína C-Reativa/metabolismo , Estado Terminal , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Pró-Calcitonina/sangue , Prognóstico , Estudos Retrospectivos , Sepse/sangue , Sepse/enzimologia , Triptofano-tRNA Ligase/genética , Universidades
19.
Medicine (Baltimore) ; 99(25): e20729, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569211

RESUMO

We aimed to investigate the predictive value of microRNA 103 (MIR103) and microRNA 107 (MIR107) for acute respiratory distress syndrome (ARDS) risk, as well as their correlations with overall disease severity and prognosis in sepsis patients.Plasma samples were collected from 196 sepsis patients within 24 hours after enrollment and from 196 healthy individuals (as healthy controls (HCs)) at enrollment. Plasma MIR103 and MIR107 were detected by reverse transcription-quantitative polymerase chain reaction.MIR103 and MIR107 were both decreased in ARDS sepsis patients and non-ARDS sepsis patients compared to HCs, and were reduced in ARDS sepsis patients than non-ARDS sepsis patients. Decreased MIR103 (area under curve (AUC): 0.727, 95% confidence interval (CI): 0.619-0.835) and MIR107 (AUC: 0.694, 95% CI: 0.577-0.811) predicted increased ARDS risk in sepsis patients. Meanwhile, MIR103 and MIR107 were negatively correlated with acute pathologic and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, serum creatinine, C-reactive protein, tumor necrosis factor, interleukin 1ß, interleukin 6 and interleukin 8, while positively correlated with albumin in sepsis patients. For prognosis, 28-day mortality was increased in ARDS sepsis patients compared to non-ARDS sepsis patients. Finally, MIR103 and MIR107 were reduced in deaths than survivors of sepsis patients, and decreased MIR103 (AUC: 0.704, 95% CI: 0.626-0.782) as well as MIR107 (AUC: 0.649, 95% CI: 0.569-0.729) predicted increased 28-day mortality risk in sepsis patients.MiR-103 and MIR107 were predictive biomarkers for risks of ARDS and 28-day mortality in sepsis patients, which might improve the management of sepsis.


Assuntos
MicroRNAs/sangue , Síndrome do Desconforto Respiratório do Adulto/sangue , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Sepse/sangue , Sepse/mortalidade , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco
20.
PLoS One ; 15(6): e0234656, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559761

RESUMO

BACKGROUND: The incidence of many infections is seasonal e.g. surgical site infections, urinary tract infection and bloodstream infections. We questioned whether there is seasonal variation even in climate-controlled hospitalized patients, and analyzed the influence of climate parameters on nosocomial bloodstream infections. METHODS AND FINDINGS: The retrospective cohort study is based on two databases: The German national surveillance system for nosocomial infections in intensive care units (ICU-KISS) from 2001 to 2015 and aggregated monthly climate data. Primary bloodstream infection (PBSI) is defined as a positive blood culture with one (or more) pathogen(s) which are not related to an infection on another site and which were not present at admission. Monthly infection data were matched with postal code, calendar month and corresponding monthly climate and weather data. All analyses were exploratory in nature. 1,196 ICUs reported data on PBSI to KISS. The ICUs were located in 779 hospitals and in 728 different postal codes in Germany. The majority of the 19,194 PBSI were caused by gram-positive bacteria. In total, the incidence density of BSI was 17% (IRR 1.168, 95%CI 1.076-1.268) higher in months with high temperatures (≥20°C) compared to months with low temperatures (<5°C). The effect was most prominent for gram-negatives; more than one third (38%) higher followed by gram-positives with 13%. Fungi reached their highest IRR at moderately warm temperatures between 15-20°C. At such temperatures fungi showed an increase of 33% compared to temperatures below 5°C. PBSI spiked in summer with a peak in July and August. PBSI differed by pathogen: The majority of bacteria increased with rising temperatures. Enterococci showed no seasonality. S. pneumoniae reached a peak in winter time. The association of the occurrence of PBSI and temperatures ≥20°C was stronger when the mean monthly temperature in the month prior to the occurrence of BSI was considered instead of the temperature in the month of the occurrence of BSI. High average temperatures ≥20°C increased the risk of the development of a PBSI by 16% compared with low temperatures <5°C. CONCLUSIONS: Most nosocomial infections are endogenous in nature; the microbiome plays a crucial role in host health. If gut and skin microbiome varies with season, environmental parameters will contribute to the observed incidence patterns. Similarly, the impact of global warming on both local weather patterns and extreme weather events may influence the acquisition of pathogens. A better understanding of the etiology of these infections is needed to provide guidance for future infection control strategies.


Assuntos
Infecção Hospitalar/sangue , Estações do Ano , Sepse/sangue , Luz Solar , Temperatura , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Humanos , Incidência , Unidades de Terapia Intensiva , Vigilância da População , Sepse/epidemiologia
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