Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.365
Filtrar
1.
Med. intensiva (Madr., Ed. impr.) ; 47(2): 84-89, feb. 2023.
Artigo em Inglês | IBECS | ID: ibc-215029

RESUMO

Objective Survivin is a member of inhibitors of apoptosis proteins family. There are not data about the association between mortality of septic patients and blood survivin concentrations. Therefore, the objective of this study was to determine whether exist that association. Design Observational and prospective study. Setting Three Spanish Intensive Care Units. Patient Patients with sepsis or septic shock according to Sepsis-3 Consensus criteria. Interventions Serum survivin concentrations were determined at moment of sepsis diagnosis. Main variable of interest Mortality at 30 days. Results A total of 204 patients were included in the study, of which 75 (36.8%) died in the first 30 days. Lower age (p<0.001), serum lactic acid levels (p=0.001), rate of septic shock (p=0.001) and SOFA (p<0.001), and higher serum survivin levels (p=0.001) exhibited surviving (n=129) than non-surviving patients (n=75). We found in multiple logistic regression analysis an association between serum survivin concentrations and mortality independently of SOFA, lactic acid, age, INR, activated partial thromboplastin time (aPTT) and empiric antimicrobial treatment adequate (OR=0.968; 95% CI=0.946–0.990; p=0.005), and also independently of APACHE-II, lactic acid, platelet, INR, aPTT and empiric antimicrobial treatment adequate (OR=0.966; 95% CI=0.943–0.989; p=0.004). Conclusions There is an association between septic patient mortality and low blood survivin concentrations (AU)


Objetivo Survivina es un miembro de la familia de proteínas inhibidoras de apoptosis. No existen datos sobre la asociación entre la mortalidad de los pacientes sépticos y las concentraciones de survivina en sangre. Por tanto, el objetivo de este estudio fue determinar si existe esa asociación. Diseño Estudio observacional y prospectivo. Ámbito Tres Unidades de Cuidados Intensivos españolas. Pacientes Pacientes con sepsis o shock séptico según criterios del Consenso Sepsis-3. Intervenciones Se determinaron las concentraciones séricas de survivina en el momento del diagnóstico de la sepsis. Variable de interés principal Mortalidad a los 30 días. Resultados Un total de 204 pacientes se incluyeron en el estudio, 75 (36,8%) de los cuales fallecieron en los primeros 30 días. Menor edad (p<0,001), niveles séricos de ácido láctico (p=0,001), tasa de shock séptico (p=0,001) y SOFA (p<0,001), y mayores niveles de survivina en suero (p=0,001) exhibieron los pacientes supervivientes (n=129) en comparación con los fallecidos (n=75). El análisis de regresión logística múltiple mostró una asociación entre las concentraciones séricas de survivina y la mortalidad independientemente del SOFA, ácido láctico, edad, INR, tiempo de tromboplastina parcial activada (aPTT) y tratamiento antimicrobiano empírico adecuado (OR=0,968; IC 95%=0,946-0,990; p=0,005), y también independientemente del APACHE-II, ácido láctico, plaquetas, INR, aPTT y tratamiento antimicrobiano empírico adecuado (OR=0,966; IC 95%=0,943-0,989; p=0,004). Conclusiones Existe una asociación entre la mortalidad de los pacientes sépticos y las concentraciones bajas de survivina en sangre (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Survivina/sangue , Sepse/sangue , Sepse/mortalidade , Estudos Prospectivos , Biomarcadores/sangue , Curva ROC
2.
Proc Natl Acad Sci U S A ; 119(40): e2209607119, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36161889

RESUMO

Blood stream infections (BSIs) cause high mortality, and their rapid detection remains a significant diagnostic challenge. Timely and informed administration of antibiotics can significantly improve patient outcomes. However, blood culture, which takes up to 5 d for a negative result, followed by PCR remains the gold standard in diagnosing BSI. Here, we introduce a new approach to blood-based diagnostics where large blood volumes can be rapidly dried, resulting in inactivation of the inhibitory components in blood. Further thermal treatments then generate a physical microscale and nanoscale fluidic network inside the dried matrix to allow access to target nucleic acid. The amplification enzymes and primers initiate the reaction within the dried blood matrix through these networks, precluding any need for conventional nucleic acid purification. High heme background is confined to the solid phase, while amplicons are enriched in the clear supernatant (liquid phase), giving fluorescence change comparable to purified DNA reactions. We demonstrate single-molecule sensitivity using a loop-mediated isothermal amplification reaction in our platform and detect a broad spectrum of pathogens, including gram-positive methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteria, gram-negative Escherichia coli bacteria, and Candida albicans (fungus) from whole blood with a limit of detection (LOD) of 1.2 colony-forming units (CFU)/mL from 0.8 to 1 mL of starting blood volume. We validated our assay using 63 clinical samples (100% sensitivity and specificity) and significantly reduced sample-to-result time from over 20 h to <2.5 h. The reduction in instrumentation complexity and costs compared to blood culture and alternate molecular diagnostic platforms can have broad applications in healthcare systems in developed world and resource-limited settings.


Assuntos
DNA Bacteriano , DNA Fúngico , Teste em Amostras de Sangue Seco , Reação em Cadeia da Polimerase , Sepse , Antibacterianos/farmacologia , Candida albicans/genética , Candida albicans/isolamento & purificação , DNA Bacteriano/sangue , DNA Fúngico/sangue , Teste em Amostras de Sangue Seco/métodos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Heme/química , Humanos , Limite de Detecção , Meticilina/farmacologia , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Sepse/sangue , Sepse/diagnóstico , Sepse/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Células-Tronco
3.
Nagoya J Med Sci ; 84(2): 230-246, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35967939

RESUMO

This study determined prognostic factors by comparing clinico-bacterial factors based on significant elevated serum procalcitonin levels in patients with suspected bloodstream infection (BSI). We retrospectively analyzed the medical records of 1,052 patients (age ≥16 years) with fever (temperature ≥38°C) and serum procalcitonin levels of ≥2.0 ng/mL, and blood culture results. The optimal cutoff value of the significant elevation of procalcitonin was determined using the minimum P-value approach. Clinico-bacterial factors were analyzed per the procalcitonin levels, and significant independent factors for short-term survival were investigated in 445 patients with BSI. Patients with suspected BSI were aged, on average, 72.3 ± 15.1 years, and the incidence of positive blood culture was 42.3%; and the 14-day survival was 83.4%. Procalcitonin ≥100 ng/mL was the most significant predictor for survival. Multivariate analysis in patients with suspected BSI showed that estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and procalcitonin ≥100 ng/mL were significant independent unfavorable prognostic factors. Microorganisms were similar between patients with procalcitonin level 2-99 ng/mL (n=359) and those with ≥100 ng/mL (n=86). Multivariate analysis in patients with BSI showed that eGFR <30 mL/min/1.73 m2, procalcitonin ≥100 ng/mL, and primary infectious foci were significant independent prognostic factors. Patients with foci in the gastrointestinal tract and respiratory system had unfavorable 14-day survival. In conclusions, eGFR <30 mL/min/1.73 m2 and procalcitonin ≥100 ng/mL were significant independent unfavorable prognostic factors for suspected BSI. Primary infectious foci (gastrointestinal tract and respiratory system) were associated with unfavorable short-term survival in patients with positive blood culture.


Assuntos
Bacteriemia , Pró-Calcitonina , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/sangue , Bacteriemia/diagnóstico , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina/sangue , Humanos , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Prognóstico , Precursores de Proteínas , Estudos Retrospectivos , Sepse/sangue , Sepse/diagnóstico
4.
Immunol Res ; 70(5): 698-707, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35732880

RESUMO

Sepsis causes a myriad of immunological reactions that result in life-threatening alterations in the human body. Immunosuppression in sepsis is partly attributed to the programmed death receptor (PD-1) and its associated ligand (PD-L1) via the regulation of lymphocytes and neutrophils. Although the soluble forms of these proteins (i.e., sPD-1 and sPD-L1, respectively) are recognized as possible sepsis biomarkers, their functional implications are yet to be elucidated. Our research assessed the correlation between sPD-1 and sPD-L1 and blood mRNA markers and sepsis outcome. Blood samples of septic patients of urogenital origin versus control patients (both groups: n = 18) were analyzed. Blood serum sPD-1 and sPD-L1 levels were determined using the enzyme-linked immunosorbent assay (ELISA). The whole blood mRNA concentrations of PD-1, PD-L1, neutrophil markers (CEACAM8 and MPO), and T-lymphocyte markers (TCRß, CD4 and CD8) were determined via reverse transcriptase quantitative PCR (RT-qPCR). sPD-L1 levels were significantly increased in septic patients when compared to the controls, whereas sPD-1 levels were unaltered. Patients with high sPD-L1 levels, as dichotomized to the median, had a significantly shorter survival rate than those with low sPD-L1 levels. The sensitivity/specificity characteristics of sPD-L1 proved significant for sepsis detection. Furthermore, sPD-L1 correlated with the mRNA concentrations of PD-L1, CEACAM, and MPO, as well as major inflammatory markers (C-reactive protein and procalcitonin). However, sPD-L1 negatively correlated with TCRß, CD4, and CD8 mRNAs. sPD-L1 was found to be significantly increased in septic patients. Notably, sPD-L1 correlated with PD-L1 mRNA and neutrophil markers and was indicative of adverse outcomes.


Assuntos
Antígeno B7-H1 , Linfócitos , Neutrófilos , Sepse , Antígeno B7-H1/sangue , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Biomarcadores/sangue , Proteína C-Reativa , Humanos , Ligantes , Linfócitos/imunologia , Neutrófilos/imunologia , Pró-Calcitonina , Prognóstico , Receptor de Morte Celular Programada 1/genética , RNA Mensageiro/genética , RNA Mensageiro/imunologia , DNA Polimerase Dirigida por RNA , Receptores de Morte Celular , Sepse/sangue , Sepse/genética , Sepse/imunologia
5.
Int J Infect Dis ; 121: 141-147, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35568360

RESUMO

OBJECTIVES: Vascular hyperpermeability by loss of endothelial barrier integrity is a hallmark of sepsis. Vimentin is involved in the regulation of the endothelial function and inflammatory response. However, the serum level of vimentin and its clinical relevance in pediatric severe sepsis (PSS) remain unknown. METHODS: We conducted a prospective study of PSS cases who were admitted to the pediatric intensive care unit (PICU) from January 2018 to December 2020. RESULTS: A total of 108 patients with PSS with a median age of 19.5 month were enrolled. The hospital mortality rate was 19.44% (21/108). Comparing with healthy controls, serum vimentin levels on PICU admission were significantly higher in patients with PSS (P < 0.001). The area under the ROC curve for vimentin to predict the hospital mortality was 0.712 (95% CI: 0.578-846) with a sensitivity of 71.43% and a specificity of 70.11%. Moreover, hospital mortality was significantly higher in patients with vimentin level over the cutoff value of 24.53 ng/ml than in patients with vimentin level below 24.53 ng/ml (P < 0.001). CONCLUSIONS: Serum vimentin level as an indicator of endothelial injury is associated with the prognosis of PSS, and serum vimentin level ≥24.53 ng/ml on PICU admission predicts high risk for hospital mortality in PSS.


Assuntos
Sepse , Vimentina , Criança , Humanos , Unidades de Terapia Intensiva Pediátrica , Prognóstico , Estudos Prospectivos , Curva ROC , Sepse/sangue , Vimentina/sangue
6.
J Clin Lab Anal ; 36(6): e24392, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35441408

RESUMO

BACKGROUND: Sepsis is a highly life-threatening disease. Long non-coding RNA urothelial carcinoma associated 1 (lncRNA UCA1) participates in the processes of inflammation and organ injury in several diseases, whereas its role in sepsis patients is still unclear. The aim was to explore the clinical value of lncRNA UCA1 in sepsis patients. METHODS: One hundred seventy-four sepsis patients and 100 age and gender-matched controls were enrolled. LncRNA UCA1 in peripheral blood mononuclear cell samples was examined, and the level of inflammatory cytokines in serum samples was assessed. RESULTS: LncRNA UCA1 was highly expressed in sepsis patients compared with controls. LncRNA UCA1 was positively correlated with tumor necrosis factor-α, interleukin (IL)-6, IL-17, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in sepsis patients, while it was not correlated with these inflammatory cytokines in controls. lncRNA UCA1 upregulation was related to raised APACHE II score and SOFA score in sepsis patients. Moreover, lncRNA UCA1 was increased in sepsis deaths compared with sepsis survivors and was independently correlated with increased 28-day sepsis mortality risk. Further receiver operating characteristic curves presented that lncRNA UCA1 had a good value to predict 28-motality risk, while its combination with other independent factors (including age, history of chronic kidney disease, G+ bacterial infection, Fungus infection, C-reactive protein, and APACHE II score) exerted a great predictive value for 28-day mortality risk. CONCLUSION: LncRNA UCA1 is upregulated and correlates with multiple pro-inflammatory cytokines, terrible disease severity, and poor prognosis in sepsis patients.


Assuntos
RNA Longo não Codificante , Sepse , Estudos de Casos e Controles , Citocinas/sangue , Citocinas/imunologia , Humanos , Interleucina-6 , Leucócitos Mononucleares/patologia , Prognóstico , RNA Longo não Codificante/sangue , RNA Longo não Codificante/genética , RNA Longo não Codificante/imunologia , Sepse/sangue , Sepse/genética , Sepse/imunologia , Regulação para Cima
7.
Diagn Microbiol Infect Dis ; 103(3): 115694, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35427887

RESUMO

Granzyme B could be released from cytotoxic T lymphocytes producing apoptosis activation. The objective of our study was to determine whether an association between septic patient mortality and blood granzyme B concentrations exist. We recruited septic patients admitted in 3 Intensive Care Units. We recorded mortality at 30 days and we determined serum granzyme B concentrations at moment of sepsis diagnosis. We found higher rate of history of diabetes mellitus (P = 0.02), serum granzyme B concentrations (P < 0.001), age (P = 0.001), serum lactic acid levels (P = 0.001) and sepsis-related organ failure assessment (P < 0.001) exhibited non-surviving patients (n = 67) than surviving ones (n = 110). We found in multiple logistic regression analysis an association of serum granzyme B concentrations with mortality (odds ratio = 1.223; 95% confidence interval = 1.104-1.355; P < 0.001) controlling for diabetes mellitus, sepsis-related organ failure assessment, lactic acid and age. That we know, our study is the first reporting the existence of an association of high serum granzyme B concentrations with high septic patients mortality.


Assuntos
Granzimas , Sepse , Granzimas/sangue , Granzimas/imunologia , Humanos , Unidades de Terapia Intensiva , Ácido Láctico/sangue , Prognóstico , Estudos Prospectivos , Sepse/sangue , Sepse/imunologia , Sepse/mortalidade , Choque Séptico/sangue , Choque Séptico/imunologia , Choque Séptico/mortalidade
8.
J Clin Lab Anal ; 36(5): e24358, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35334494

RESUMO

BACKGROUND: For investigating the expression of miR-320-3p in children with sepsis-induced acute kidney injury (AKI) and its prognostic value. METHODS: A total of 142 patients were grouped into a survival group (n = 95) and death group (n = 47), which was based on their 28-day survival. Serum degrees of miR-320-3p, neutrophil gelatinase-associated lipid carrier protein (NGAL) and kidney injury molecule-1 (KIM-1) were detected. The Acute Physiology and Chronic Health scoring system Ⅱ (APACHE Ⅱ) marks were recorded. Target gene forecast and functional enrichment discussion of miR-320-3p were performed, and a protein-protein interaction (PPI) network diagram was plotted by applying bioinformatics methods. Multivariate logistic regression, ROC curve and Pearson correlation analysis were applied. RESULTS: The death group showed greatly higher serum levels of miR-320-3p, KIM-1 and APACHE Ⅱ scores than the survival group (p < 0.01). Multivariate logistic regression analysis showed that levels of miR-320-3p, NGAL, KIM-1 and APACHE Ⅱ scores were independent risk elements for death in sepsis children with AKI (p < 0.01). According to ROC curve analysis, the region under the curve (0.963, 95% CI: 0.908-0.996) of miR-320-3p, NGAL, KIM-1 levels and APACHE Ⅱ scores combined to forecast the death of kids suffering from sepsis and AKI were the biggest. According to correlation analysis, the expression degree of serum miR-320-3p in the death group was positively correlated with NGAL, KIM-1 and APACHE Ⅱ scores (all p < 0.01). CONCLUSIONS: The expression level of serum miR-320-3p in children with sepsis-induced AKI was significantly increased, and the combination of NGAL, KIM-1 and APACHE Ⅱ scores has good value for prognosis prediction in children.


Assuntos
Injúria Renal Aguda , MicroRNAs , Sepse , Injúria Renal Aguda/sangue , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Biomarcadores , Criança , Feminino , Humanos , Lipocalina-2/genética , Masculino , MicroRNAs/biossíntese , MicroRNAs/sangue , MicroRNAs/genética , Prognóstico , Curva ROC , Sepse/sangue , Sepse/genética , Sepse/patologia
9.
Eur J Med Res ; 27(1): 39, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35272698

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common and critical complication of sepsis, and is associated with unacceptable morbidity and mortality. Current diagnostic criteria for AKI was insensitive for early detection. Novel biomarkers including cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), klotho and fibroblast growth factor-23 (FGF-23) can predict AKI earlier and allow immediate interventions. We aimed to determine the diagnostic performance of these biomarkers for detecting AKI in sepsis patients. METHODS: This prospective observational study was conducted between May 2018 and November 2020, enrolling 162 sepsis patients eventually. The AKI was defined in accordance with 2012 KDIGO criteria and we divided patients into non-AKI (n = 102) and AKI (n = 60) groups. Serum levels of several AKI biomarkers were detected by ELISA. The relationship between biomarker levels on admission of AKI was analyzed and discrimination performances comparison were performed. RESULTS: AKI incidence was up to 37.0% (60/162) during hospitalization. Compared with non-AKI group, both serum cystatin C, KIM-1, NGAL and FGF-23 were significantly elevated at admission in septic AKI patients. The areas under the receiver operating curves demonstrated that serum cystatin C had modest discriminative powers for predicting AKI after sepsis, and cystatin C combined with serum creatinine in the prediction of septic AKI increased the diagnostic sensitivity prominently. CONCLUSION: Serum cystatin C, KIM-1, NGAL and FGF-23 levels were both increased in septic AKI patients. Our study provided reliable evidence that cystatin C solely and combined with serum creatinine may accurately and sensitively predict septic AKI of patients on admission.


Assuntos
Injúria Renal Aguda/sangue , Cistatina C/sangue , Diagnóstico Precoce , Fator de Crescimento de Fibroblastos 23/sangue , Receptor Celular 1 do Vírus da Hepatite A/sangue , Proteínas Klotho/sangue , Lipocalina-2/sangue , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Idoso , Biomarcadores/sangue , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Sepse/sangue , Sepse/complicações
10.
Acta Biochim Pol ; 69(1): 113-117, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35225489

RESUMO

OBJECTIVE: Sepsis is a host response with life-threatening organ dysfunction caused by an infection. Although the overall mortality rate has increased from 30% to 37% by the surviving sepsis campaign, it is still not acceptable. Early identification, accurate stratification and appropriate intervention can improve the prognosis. In this study we assessed the risk stratification and prognostic value of serum neutrophil gelatinase-associated lipocalin (sNGAL) as a biomarker in sepsis patients. METHODS: A total of 112 sepsis patients (38 patients with sepsis, 41 patients with severe sepsis, 33 patients with septic shock) and 25 healthy controls were enrolled in this study. Serum samples of all patients were collected and frozen before testing. Basic patient information was collected, including age, gender, primary infection, complications, and so on. Results of serum calcitonin, lactic acid, and SOFA score were followed up for 28 days. RESULTS: Levels of serum procalcitonin (PCT), serum lactate, Sequential Organ Failure Assessment (SOFA) score and sNGAL of sepsis patients were significantly higher (p<0.05) than those of controls. The sNGAL level in sepsis patients who were alive on the 28th day of follow-up was significantly lower (p<0.05) than that of sepsis patients who had died before the 28th day of follow-up. Multiple logistic regression analysis showed that sNGAL-0h and lactates were independent risk factors of death due to sepsis within 28 days. At cut-off value of 250 ng/mL, the sensitivity and specificity sNGAL-0h predicting the 28-day mortality in septic patients were 0.838 and 0.827, respectively. The sNGAL level in sepsis patients with acute kidney injury (AKI) was significantly higher (p<0.05) than in sepsis patients without AKI. CONCLUSION: Serum NGAL may contribute to the assessment of the severity of sepsis. Serum NGAL and lactate can be independent risk factors for 28-day mortality in sepsis patients. Serum NGAL has potential of predicting septic-AKI.


Assuntos
Lipocalina-2/sangue , Sepse/sangue , Injúria Renal Aguda/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Ácido Láctico/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Gravidade do Paciente , Prognóstico , Medição de Risco , Fatores de Risco , Sepse/mortalidade , Choque Séptico/sangue
11.
Mol Med Rep ; 25(4)2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35137927

RESUMO

Myocardial injury occurs in the majority of patients with sepsis and is associated with early mortality. MicroRNAs (miRs) transported by exosomes have been implicated in numerous diseases, such as tumors, acute myocardial infarction and cardiovascular disease. Human serum albumin (hsa)­miR­1262 has been shown to serve a role in sepsis; however, its role in exosomes isolated from patients with sepsis and septic myocardial injury remains unclear. In the present study, serum exosomes were isolated via ultracentrifugation. Solute carrier family 2 member 1 (SLC2A1), an essential mediator in energy metabolism, was silenced and overexpressed in the human myocardial AC16 cell line using lentiviral plasmids containing either SLC2A1­targeting short interfering RNAs or SLC2A1 cDNA, respectively. Cell apoptosis was analyzed using flow cytometry, and the extracellular acidification rate and oxygen consumption rate of AC16 cells were determined using an XFe24 Extracellular Flux Analyzer. Furthermore, the dual­luciferase reporter assay was used to evaluate the interaction between hsa­miR­1262 and SLC2A1. Finally, reverse transcription­quantitative PCR and western blotting were used to evaluate gene and protein expression levels, respectively. Exosomes isolated from the blood of patients with sepsis (Sepsis­exo) markedly reduced aerobic glycolysis activity, but significantly promoted the apoptosis of human AC16 cells in a time­dependent manner. Moreover, Sepsis­exo significantly increased hsa­miR­1262 expression levels, but significantly decreased SLC2A1 mRNA expression levels in a time­dependent manner. Bioinformatics analysis indicated that hsa­miR­1262 bound to the 3' untranslated region of SLC2A1 to negatively regulate its expression. The silencing of SLC2A1 promoted apoptosis and suppressed glycolysis in AC16 cells, whereas SLC2A1 overexpression resulted in the opposite effects. Therefore, the present study demonstrated that exosomes derived from patients with sepsis may inhibit glycolysis and promote the apoptosis of human myocardial cells through exosomal hsa­miR­1262 via its target SLC2A1. These findings highlighted the importance of the hsa­miR­1262/SLC2A1 signaling pathway in septic myocardial injury and provided novel insights into therapeutic strategies for septic myocardial depression.


Assuntos
Apoptose , Exossomos/metabolismo , Transportador de Glucose Tipo 1/metabolismo , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Sepse/sangue , Albumina Sérica Humana/metabolismo , Regiões 3' não Traduzidas/genética , Linhagem Celular , Transportador de Glucose Tipo 1/genética , Glicólise , Traumatismos Cardíacos/genética , Traumatismos Cardíacos/metabolismo , Humanos , MicroRNAs/genética , Miócitos Cardíacos/efeitos dos fármacos , Transdução de Sinais/genética , Fatores de Tempo
12.
Cell ; 185(5): 916-938.e58, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35216673

RESUMO

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19.


Assuntos
Biomarcadores/sangue , COVID-19/patologia , Proteoma/análise , Adulto , Proteínas Sanguíneas/metabolismo , COVID-19/sangue , COVID-19/virologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Feminino , Humanos , Influenza Humana/sangue , Influenza Humana/patologia , Linfócitos/imunologia , Linfócitos/metabolismo , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Proteína Quinase 14 Ativada por Mitógeno/genética , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Análise de Componente Principal , SARS-CoV-2/isolamento & purificação , Sepse/sangue , Sepse/patologia , Índice de Gravidade de Doença , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo
13.
Dis Markers ; 2022: 5176915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35178128

RESUMO

PURPOSE: DDX3X acts as the critical checkpoint of death in stressed cells. The purpose of this study was to evaluate the mRNA expression level of DDX3X in T cells in peripheral blood of patients with sepsis and to explore its correlation with the prognosis of sepsis. METHODS: Seventy-nine patients with traumatic sepsis were enrolled in this prospective cohort study. Blood samples were collected within 24 hours after the diagnosis of sepsis or septic shock, and the mRNA expression level of DDX3X in T cells was detected by PCR. RESULTS: The level of DDX3X mRNA in T cells was significantly increased in septic patients as well as in septic shock patients. The level of DDX3X mRNA was negatively correlated with T cell count and positively correlated with acute physiological and chronic health assessment (APACHE) score and sequential organ failure assessment (SOFA) score (P < 0.01). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.79 (95% confidence interval (CI), 0.68-0.90). A Cox proportional hazard model identified an association between an increased DDX3X mRNA level (≥1.575) and the risk of 28-day mortality (hazard ratio = 9.540, 95% CI, 2.452-37.108). CONCLUSIONS: High level of DDX3X mRNA in T cells in sepsis is associated with the severity of sepsis and the mortality of patients with sepsis.


Assuntos
RNA Helicases DEAD-box/genética , RNA Mensageiro , Sepse/genética , Sepse/mortalidade , Linfócitos T , Adulto , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Mensageiro/biossíntese , Sepse/sangue , Índice de Gravidade de Doença , Linfócitos T/metabolismo
14.
PLoS One ; 17(2): e0262938, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35176042

RESUMO

INTRODUCTION: Extended differential parameters (EDPs) are generated with the automated differential count by Sysmex XN-series automated hematology analysers, and include the immature granulocyte count (IG%), the neutrophil fluorescent light intensity (NE-SFL) and the neutrophil fluorescent light distribution width (NE-WY). These have been proposed as early biomarkers of bacteremia. This study aimed to evaluate the NE-SFL, NE-WY and IG% in comparison to neutrophil CD64 (nCD64) expression (as a high quality sepsis biomarker) among patients with suspected bacterial sepsis at the Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa. METHODS: A daily search of the laboratory information system identified samples submitted for a blood culture (BC) and a concurrent full blood count (FBC). Automated differential counts using a Sysmex XN-9000 haematology analyser and neutrophil CD64 expression by flow cytometry were assessed on the residual FBC samples. RESULTS: A total of 151 samples were collected, of which 83 were excluded due to equivocal results with regards to the presence of bacterial infection. The remaining 68 samples included 23 with bacteremia, 28 with evidence of non-bacteremic bacterial infection, 13 with no evidence of bacterial infection and 4 with Tuberculosis. HIV status was documented in 90 of the patients, with a seropositivity rate of 57.8%. The EDPs were all significantly higher among patients with bacteremia as compared to those without bacterial infection, but on ROC curve analyses, only the NE-SFL showed good performance (AUC>0.8) for discriminating cases with bacteremia from those without bacterial infection at a cut-off value of 49.75. In comparison to the nCD64, the NE-SFL showed moderate agreement (kappa = 0.5). On stratification of the ROC analysis by HIV status, the NE-SFL showed superior performance among persons with HIV infection (AUC = 1), while the automated IG% showed better performance among the patients without HIV infection (AUC = 0.9). CONCLUSION: In this study, EDPs showed differential performance as biomarkers for bacteremia according to HIV-status in the South African setting, with the most promising results seen with the NE-SFL and IG% parameters among people with and without HIV infection, respectively. Further assessment of these parameters without pre-selection of patients likely to have infection is required to further determine their clinical utility, particularly among patients with underlying inflammatory conditions or malignancy.


Assuntos
Bacteriemia/diagnóstico , Bactérias/isolamento & purificação , Biomarcadores/sangue , Infecções por HIV/complicações , HIV/isolamento & purificação , Sepse/diagnóstico , Centros Médicos Acadêmicos/estatística & dados numéricos , Adolescente , Adulto , Bacteriemia/sangue , Bacteriemia/etiologia , Hemocultura , Criança , Pré-Escolar , Feminino , Infecções por HIV/virologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Curva ROC , Sepse/sangue , Sepse/etiologia , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
15.
Int J Mol Sci ; 23(3)2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35163743

RESUMO

Inflammation and thrombosis are closely intertwined in numerous disorders, including ischemic events and sepsis, as well as coronavirus disease 2019 (COVID-19). Thrombotic complications are markers of disease severity in both sepsis and COVID-19 and are associated with multiorgan failure and increased mortality. Immunothrombosis is driven by the complement/tissue factor/neutrophil axis, as well as by activated platelets, which can trigger the release of neutrophil extracellular traps (NETs) and release further effectors of immunothrombosis, including platelet factor 4 (PF4/CXCL4) and high-mobility box 1 protein (HMGB1). Many of the central effectors of deregulated immunothrombosis, including activated platelets and platelet-derived extracellular vesicles (pEVs) expressing PF4, soluble PF4, HMGB1, histones, as well as histone-decorated NETs, are positively charged and thus bind to heparin. Here, we provide evidence that adsorbents functionalized with endpoint-attached heparin efficiently deplete activated platelets, pEVs, PF4, HMGB1 and histones/nucleosomes. We propose that this elimination of central effectors of immunothrombosis, rather than direct binding of pathogens, could be of clinical relevance for mitigating thrombotic complications in sepsis or COVID-19 using heparin-functionalized adsorbents.


Assuntos
Proteínas Sanguíneas/isolamento & purificação , Heparina/farmacologia , Tromboinflamação/tratamento farmacológico , Coagulação Sanguínea/fisiologia , Plaquetas/metabolismo , Proteínas Sanguíneas/metabolismo , COVID-19/metabolismo , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Proteínas HMGB/isolamento & purificação , Proteínas HMGB/metabolismo , Proteína HMGB1/isolamento & purificação , Proteína HMGB1/metabolismo , Heparina/metabolismo , Histonas/isolamento & purificação , Histonas/metabolismo , Humanos , Neutrófilos/metabolismo , Ativação Plaquetária/imunologia , Fator Plaquetário 4/isolamento & purificação , Fator Plaquetário 4/metabolismo , SARS-CoV-2/patogenicidade , Sepse/sangue , Sepse/metabolismo , Tromboplastina/metabolismo , Trombose/tratamento farmacológico
16.
BMC Nephrol ; 23(1): 52, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35109818

RESUMO

BACKGROUND: Albumin (ALB) levels are negatively associated with mortality in patients with sepsis. However, among sepsis patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT), there has been no similar study on the correlation between ALB levels and mortality alone. This study tested the hypothesis that ALB levels are negatively associated with mortality among such patients. METHODS: We conducted a secondary analysis of 794 septic patients who were diagnosed with AKI and underwent CRRT in South Korea. For the Kaplan-Meier survival analysis, Cox proportional hazards models were used to study the hypotheses, with adjustments for the pertinent covariables. We also explore the possible nonlinear relationship and conducted sensitivity analyses including subgroup analyses and tests for interactions to investigate the association further. Additionally, ALB was used to construct model and we then compared the performance of ALB with that of APACHE II and SOFA in predicting mortality. RESULTS: The ALB level was an independent prognostic factor for death at 28 and 90 days after CRRT initiation (HR = 0.75, 95% CI: 0.62-0.90, P = 0.0024 for death at 28 days and HR = 0.73, 95% CI: 0.63-0.86, P < 0.0001 for death at 90 days). A nonlinear association was not identified between ALB levels and the endpoints. Subgroup analyses and tests for interactions indicated that HCO3 and CRP played an interactive role in the association. ROC analysis indicated ALB, SOFA and APACHE-II were separately inadequate for clinical applications. CONCLUSION: A 1 g/dL increase in ALB levels was independently associated with a 25 and 27% decrease in the risk of death at 28 and 90 days, respectively. However, this conclusion needs to be taken with caution as this study has several limitations.


Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Terapia de Substituição Renal Contínua , Sepse/sangue , Sepse/mortalidade , Albumina Sérica/análise , Injúria Renal Aguda/complicações , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Sepse/complicações , Análise de Sobrevida
17.
Dis Markers ; 2022: 3893653, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35126786

RESUMO

OBJECTIVE: The effect of serum magnesium on the prognosis of children with sepsis in the pediatric intensive care unit (PICU) is unclear. This study was designed to assess the risk of inpatient mortality for children with sepsis in the PICU based on serum magnesium levels at admission. METHODS: We collected patients' clinical information from the Pediatric Intensive Care database and then performed locally weighted scatterplot smoothing (LOWESS) analysis, Kaplan-Meier analysis, and multivariate logistic regression to determine the relationship between admission serum magnesium and inpatient mortality in children with sepsis. RESULTS: A total of 974 critically ill children with sepsis were included, with 246 patients in the hypomagnesemia group, 666 in the normal group, and 62 in the hypermagnesemia group. The chi-square test suggested that the hypermagnesemia group had higher in-hospital mortality than the normal group (14.5% vs. 2.4%, P < 0.001). Kaplan-Meier curves revealed that the 30-day overall survival rate was lower in the hypermagnesaemia group than in the normal group (P < 0.001). The multivariate logistic regression model revealed that hypermagnesaemia was a risk factor related to inpatient mortality (odds ratio 4.22, 95% CI 1.55-11.50), while hypomagnesaemia was not a significant factor for inpatient mortality (odds ratio 0.78, 95% CI 0.26-2.32). CONCLUSION: Hypermagnesaemia, but not hypomagnesaemia, is a predictor of inpatient mortality in critically ill children with sepsis.


Assuntos
Magnésio/sangue , Sepse/sangue , Sepse/mortalidade , Criança , Pré-Escolar , Estado Terminal , Feminino , Mortalidade Hospitalar , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Prognóstico
18.
Oxid Med Cell Longev ; 2022: 3990607, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35126812

RESUMO

Neutrophils release chromatin and antimicrobial proteins to trap and kill microbes, which is termed as neutrophil extracellular trap (NET) formation. NETs play a pivotal role in host defense against infection. However, emerging evidence indicated that NETs also contribute to an exaggerated inflammatory response and organic injuries in sepsis. Zingerone, a natural compound extracted from Zingiber officinale, exerts antioxidant, anti-inflammatory, and antioncogenic properties. In this study, we found that treatment with zingerone reduced organ injury and improved the outcome in a cecal ligation puncture- (CLP-) induced polymicrobial sepsis model. Administration of zingerone also alleviates reactive oxygen species (ROS) accumulation and systematic inflammation in septic mice and inhibits neutrophil extracellular traps (NETs) formation in vivo and in vitro. Furthermore, inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2) with its specific antagonist significantly counteracted the suppressive effects of zingerone on ROS and NETs and retarded the protective role of zingerone against sepsis-associated organ injury. In addition, exposure to zingerone does not affect phagocytic activity of neutrophils in vitro and bacterial dissemination in vivo. Above all, our results indicate that zingerone treatment obviously attenuates NET formation and inflammatory response via Nrf2-mediated ROS inhibition, thus providing a novel therapeutic strategy against sepsis-induced injury.


Assuntos
Armadilhas Extracelulares/metabolismo , Guaiacol/análogos & derivados , Fator 2 Relacionado a NF-E2/metabolismo , Neutrófilos/metabolismo , Substâncias Protetoras/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Sepse/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Doadores de Sangue , Células Cultivadas , Citocinas/sangue , Modelos Animais de Doenças , Armadilhas Extracelulares/efeitos dos fármacos , Guaiacol/administração & dosagem , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Sepse/sangue , Resultado do Tratamento
19.
Biomolecules ; 12(2)2022 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-35204801

RESUMO

Chemerin, a novel adipokine, is a potent chemoattractant molecule with antimicrobial properties, implicated in immune responses. Our aim was to investigate circulating chemerin and its kinetics, early in sepsis in critically ill patients and its association with severity and prognosis. Serum chemerin was determined in a cohort of 102 critically ill patients with sepsis during the first 48 h from sepsis onset and one week later, and in 102 age- and gender-matched healthy controls. Patients were followed for 28 days and their outcomes were recorded. Circulating chemerin was significantly higher in septic patients at onset compared to controls (342.3 ± 108.1 vs. 200.8 ± 40.1 µg/L, p < 0.001). Chemerin decreased significantly from sepsis onset to one week later (342.3 ± 108.1 vs. 308.2 ± 108.5 µg/L, p < 0.001), but remained higher than in controls. Chemerin was higher in patients presenting with septic shock than those with sepsis (sepsis onset: 403.2 ± 89.9 vs. 299.7 ± 99.5 µg/L, p < 0.001; one week after: 374.9 ± 95.3 vs. 261.6 ± 91.9 µg/L, p < 0.001), and in nonsurvivors than survivors (sepsis onset: 427.2 ± 96.7 vs. 306.9 ± 92.1 µg/L, p < 0.001; one week after: 414.1 ± 94.5 vs. 264.2 ± 79.9 µg/L, p < 0.001). Moreover, patients with septic shock and nonsurvivors, presented a significantly lower absolute and relative decrease in chemerin one week after sepsis onset compared to baseline (p < 0.001). Based on ROC curve analyses, the diagnostic performance of chemerin (AUC 0.78, 95% CI 0.69-0.87) was similar to C-reactive protein (CRP) (AUC 0.78, 95% CI 0.68-0.87) in discriminating sepsis severity. However, increased chemerin at sepsis onset and one week later was an independent predictor of 28-day mortality (sepsis onset: HR 3.58, 95% CI 1.48-8.65, p = 0.005; one week after: HR 10.01, 95% CI 4.32-23.20, p < 0.001). Finally, serum chemerin exhibited significant correlations with the severity scores, white blood cells, lactate, CRP and procalcitonin, as well as with biomarkers of glucose homeostasis, but not with cytokines and soluble urokinase-type plasminogen activator receptor (suPAR). Circulating chemerin is increased early in sepsis and its kinetics may have diagnostic and prognostic value in critically ill patients. Further studies are needed to shed light on the role of chemerin in sepsis.


Assuntos
Quimiocinas , Sepse , Choque Séptico , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Quimiocinas/sangue , Estado Terminal , Humanos , Prognóstico , Estudos Prospectivos , Sepse/sangue , Sepse/diagnóstico , Choque Séptico/sangue , Choque Séptico/diagnóstico
20.
FASEB J ; 36(3): e22179, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35182399

RESUMO

The value of plasma fibronectin (pFN) in the diagnosis and prognosis of sepsis has not been fully established. Previous studies finding that pFN is significantly reduced in sepsis, however, whether reduced pFn affects the prognosis of sepsis has not been clarified. Here, we detected and analyzed pFN and other conventional inflammatory markers in advanced sepsis patients and performed correlation analysis with SOFA score. We also used Fn gene conditional knockout mice which were performed by cecum ligation and puncture (CLP) to investigate the effect of FN deficiency on sepsis prognosis. We found, compared with procalcitonin, c-reactive protein, and interleukin-6, pFN was more correlated with SOFA score in advanced sepsis patients (r -.720, p < .001). In animal experiments, Fn gene knockout mice showed significantly greater mortality after CLP compared with the control group because of inhibited phagocytosis and bacterial clearance ability of macrophages, with double cytokine storm. Furthermore, FN can regulate macrophages through the integrin α5ß1/Fak/Src signaling pathway. Overall, we found pFN can more accurately reflect the severity and prognosis of advanced sepsis. The absence of FN altered the cytokine storm and phagocytic function of macrophages, suggesting that FN could be a potential therapeutic target in sepsis.


Assuntos
Citocinas/metabolismo , Fibronectinas/metabolismo , Macrófagos/metabolismo , Sepse/metabolismo , Animais , Células Cultivadas , Fibronectinas/sangue , Fibronectinas/genética , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Integrina alfa5beta1/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Sepse/sangue , Quinases da Família src/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...