Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 779
Filtrar
1.
BMC Infect Dis ; 19(1): 760, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470804

RESUMO

BACKGROUND: Early diagnosis of sepsis in pediatric patients is vital but remains a major challenge. Previous studies showed that presepsin is potentially a reliable diagnostic biomarker for sepsis in adult and neonates. However, there is no pooled analysis of its efficacy as a diagnostic biomarker for sepsis in children. The aims of the present meta-analysis were to assess the overall diagnostic accuracy of presepsin in pediatric sepsis and compare it to those for C-reactive protein (CRP) and procalcitonin (PCT). METHODS: A systematic literature search was performed in Medline/Pubmed, Embase, the Cochrane Library, and ISI Web of Science to identify relevant studies reporting the diagnostic accuracy of presepsin in patients with pediatric sepsis. Sensitivities and specificities were pooled by bivariate meta-analysis. Heterogeneity was evaluated by χ2 test. RESULTS: We identified 129 studies in total. Most were disqualified on the basis of their titles/abstracts and duplication. Four studies were included in the final analysis. They comprised 308 patients aged between 1 mo and 18 y. The pooled diagnostic sensitivity and specificity of presepsin were 0.94 (95% confidence interval [CI]: 0.74-0.99) and 0.71 (95% CI: 0.35-0.92), respectively. The pooled diagnostic odds ratio, positive likelihood ratio (LR), and negative LR of presepsin were 32.87 (95% CI: 2.12-510.09), 3.24 (95% CI, 1.14-12.38), and 0.08 (95% CI, 0.01-0.74), respectively. Heterogeneity was found in both sensitivity (χ2 = 11.17; P = 0.011) and specificity (χ2 = 65.78; P < 0.001). No threshold effect was identified among the studies (r = - 0.938). The pooled sensitivity of presepsin (0.94) was higher than that of CRP (0.51) and PCT (0.76), whereas the overall specificity of presepsin (0.71) was lower than that of CRP (0.81) and PCT (0.76). The AUC of presepsin (0.925) was higher than that of CRP (0.715) and PCT (0.820). CONCLUSION: Currently available evidence indicates that presepsin has higher sensitivity and diagnostic accuracy, but lower specificity, than PCT or CRP in detecting sepsis in children. However, these results must be carefully interpreted as the number of studies included was small and the studies were statistically heterogeneous.


Assuntos
Biomarcadores/sangue , Receptores de Lipopolissacarídeos/sangue , Fragmentos de Peptídeos/sangue , Sepse/diagnóstico , Adolescente , Idade de Início , Biomarcadores/análise , Proteína C-Reativa/análise , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Humanos , Lactente , Recém-Nascido , Receptores de Lipopolissacarídeos/análise , Masculino , Fragmentos de Peptídeos/análise , Pró-Calcitonina/análise , Pró-Calcitonina/sangue , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sepse/epidemiologia
2.
Vnitr Lek ; 65(7-8): 490-496, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487992

RESUMO

INTRODUCTION: Presepsin (soluble CD14 subtype) is a new biomarker of infection and sepsis. Correct interpretation is based on the knowledge of analytical reliability, biological variation, decision limits, and diagnostic effectivity. AIM: The aim of the study was to verify analytical precision of presepsin measurements, to assess biological variation in healthy subjects, to verify reference and decision limits, to assess diagnostic effectivity, and to compare data with commonly used septic biomarkers - procalcitonin (PCT), CRP and interleukin 6 (IL6). MATERIAL AND METHODS: Analyti-cal precision (repeatability and intermediate precision) was estimated by repeated measurements of commercial control materials. Biological variation was evaluated in a group of 20 healthy volunteers in a 7-week experi-ment. Reference ranges were extracted from the literature and compared with data from healthy subjects. RESULTS: Precisions of presepsin measurements were 2.0-4.0 % (“within-run”) and 6.1-9.5 % (“between-run”). Intraindividual biological variation of presepsin was 22.3 %, interindividual variation 20.8 %. Index of individuality was 1.07, reference change value (RCV - critical difference) was 72 %. Upper reference limit was around 180 ng/l. CONCLUSION: Ana-lytical quality of presepsin measurement is suitable for clinical use. Biological variation parameters enable the use of reference limits, upper reference limit of presepsin is around 180 ng/l. None of the tested biomarkers has universal cut-off value, multiple biomarkers are needed and repeated measurements are advisable.


Assuntos
Biomarcadores , Receptores de Lipopolissacarídeos , Fragmentos de Peptídeos , Sepse , Biomarcadores/análise , Proteína C-Reativa , Calcitonina , Humanos , Receptores de Lipopolissacarídeos/análise , Fragmentos de Peptídeos/análise , Valores de Referência , Reprodutibilidade dos Testes , Sepse/diagnóstico
3.
Vnitr Lek ; 65(7-8): 497-505, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487993

RESUMO

Sepsis remains one of the most common causes of death worldwide. It is caused by a complex of inadequate host responses to infection. It is also often difficult to distinguish sepsis from a non-infectious cause of systemic inflammatory response syndrome. Early identification of an infectious origin may dramatically help to improve the outcome and reduce mortality. That is the main reason why clinicians need fast, reliable and specific biomarkers for recognition of sepsis. Presepsin (sCD-14ST) is one of promising biomarkers, the level of which increases in response to a microbial infection in the host. As a glycoprotein expressed in the membranes of monocytes and macrophages, CD14 (cluster of differentiation 14) serves especially as a co-receptor of the lipopolysaccharide-lipopolysaccharide binding protein complexes, and activates the inflammatory cascade. Consequently, during the inflammatory reaction, sCD14-ST, known as presepsin, is cleaved away from plasma. The objective of this article is to determine the diagnostic value of presepsin in the diagnostics of sepsis, assessing its severity, and monitoring the effectiveness of therapeutic interventions, and to establish the prognostic value of this biomarker.


Assuntos
Biomarcadores , Receptores de Lipopolissacarídeos , Fragmentos de Peptídeos , Sepse , Biomarcadores/análise , Humanos , Receptores de Lipopolissacarídeos/análise , Fragmentos de Peptídeos/análise , Prognóstico , Sepse/diagnóstico
4.
J Immunol Res ; 2019: 9782594, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467936

RESUMO

Monocytes are a heterogeneous cell population distinguished into three subsets with distinctive phenotypic and functional properties: "classical" (CD14++CD16-), "intermediate" (CD14++CD16+), and "nonclassical" (CD14+CD16++). Monocyte subsets play a pivotal role in many inflammatory systemic diseases including atherosclerosis (ATS). Only a low number of studies evaluated monocyte behavior in patients affected by cardiovascular diseases, and data about their role in acute aortic dissection (AAD) are lacking. Thus, the aim of this study was to investigate CD14++CD16-, CD14++CD16+, and CD14+CD16++ cells in patients with Stanford-A AAD and in patients with carotid artery stenosis (CAS). Methods. 20 patients with carotid artery stenosis (CAS group), 17 patients with Stanford-A AAD (AAD group), and 17 subjects with traditional cardiovascular risk factors (RF group) were enrolled. Monocyte subset frequency was determined by flow cytometry. Results. Classical monocytes were significantly increased in the AAD group versus CAS and RF groups, whereas intermediate monocytes were significantly decreased in the AAD group versus CAS and RF groups. Conclusions. Results of this study identify in AAD patients a peculiar monocyte array that can partly explain depletion of T CD4+ lymphocyte subpopulations observed in patients affected by AAD.


Assuntos
Aneurisma Dissecante/imunologia , Estenose das Carótidas/imunologia , Monócitos/imunologia , Doença Aguda , Idoso , Aneurisma Dissecante/sangue , Estenose das Carótidas/sangue , Feminino , Citometria de Fluxo , Proteínas Ligadas por GPI/análise , Humanos , Receptores de Lipopolissacarídeos/análise , Masculino , Pessoa de Meia-Idade , Monócitos/classificação , Receptores de IgG/análise , Estudos Retrospectivos
5.
Int J Mol Sci ; 20(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022834

RESUMO

Pneumonia is the leading infectious cause of mortality worldwide and one of the most common lower respiratory tract infections that is contributing significantly to the burden of antibiotic consumption. Due to the complexity of its pathophysiology, it is widely accepted that clinical diagnosis and prognosis are inadequate for the accurate assessment of the severity of the disease. The most challenging task for a physician is the risk stratification of patients with community-acquired pneumonia. Herein, early diagnosis is essential in order to reduce hospitalization and mortality. Procalcitonin and C-reactive protein remain the most widely used biomarkers, while interleukin 6 has been of particular interest in the literature. However, none of them appear to be ideal, and the search for novel biomarkers that will most sufficiently predict the severity and treatment response in pneumonia has lately intensified. Although our insight has significantly increased over the last years, a translational approach with the application of genomics, metabolomics, microbiomics, and proteomics is required to better understand the disease. In this review, we discuss this rapidly evolving area and summarize the application of novel biomarkers that appear to be promising for the accurate diagnosis and risk stratification of pneumonia.


Assuntos
Pneumonia/diagnóstico , Animais , Antibacterianos/uso terapêutico , Biomarcadores/análise , Contagem de Células Sanguíneas , Proteína C-Reativa/análise , Biologia Computacional , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Antígenos HLA-DR/análise , Humanos , Interleucina-6/análise , Receptores de Lipopolissacarídeos/análise , Fragmentos de Peptídeos/análise , Pneumonia/sangue , Pneumonia/tratamento farmacológico , Pró-Calcitonina/análise , Receptores de IgG/análise , Receptor Gatilho 1 Expresso em Células Mieloides/análise
6.
Methods Mol Biol ; 1979: 155-176, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028637

RESUMO

Peripheral blood mononuclear cells (PBMCs) are blood cells that are a critical part of the immune system used to fight off infection. However, due to the complexity of PBMCs, which contain multiple different cell types, studying the function of the individual cell types can be difficult, and often studies rely on bulk measurements. Here, we describe the analysis of PBMCs using single-cell RNA-sequencing in droplets. Data from these studies allow for the identification and quantification of the subpopulation of cells that make up the PBMC sample. In addition, differential gene expression between cell types and samples can be assessed.


Assuntos
Leucócitos Mononucleares/metabolismo , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Contagem de Células/métodos , Separação Celular/métodos , DNA Complementar/genética , Desenho de Equipamento , Sequenciamento de Nucleotídeos em Larga Escala/instrumentação , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Leucócitos Mononucleares/citologia , Receptores de Lipopolissacarídeos/análise , Monócitos/citologia , Monócitos/metabolismo , Transcrição Reversa , Análise de Sequência de RNA/instrumentação , Análise de Célula Única/instrumentação , Fluxo de Trabalho
7.
Int J Mol Sci ; 20(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30979019

RESUMO

Osteoclasts are the sole bone resorbing cell in the body and their over activity is key in the development of osteoporosis. Osteoclastogenesis is mediated by receptor activator of nuclear factor κB ligand (RANKL) signalling pathways. Unsaturated fatty acids (UFA) are known to inhibit osteoclastogenesis by targeting RANKL signalling. However, the mechanisms of action remain unclear. Peroxisome proliferator activated receptors (PPARs) are a family of nuclear receptors, with three known isoforms (PPAR-α, PPAR-ß/δ and PPAR-γ), that are known to bind UFAs and are expressed in osteoclasts. In this study, we aimed to determine how different families of UFAs activate PPARs and how PPAR activation influences osteoclast signalling. Human CD14+ monocytes were seeded into cluster plates with RANKL and macrophage colony stimulating factor (M-CSF) in the presence of PPAR agonists or different types of UFAs. All the PPAR agonists were shown to upregulate the activity of their respective receptors. Polyunsaturated fatty acids increased PPAR-α to a greater extent than monounsaturated fatty acids (MUFAs), which favoured PPAR-ß/δ activation. All PPAR agonists inhibited osteoclastogenesis. The activation of RANKL signalling pathways and expression of key osteoclast genes were downregulated by PPAR agonists. This study reveals that PPAR activation can inhibit osteoclastogenesis through modulation of RANKL signalling.


Assuntos
Ácidos Graxos Insaturados/metabolismo , Receptores de Lipopolissacarídeos/análise , Monócitos/citologia , Osteoclastos/citologia , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais , Adolescente , Adulto , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Masculino , Monócitos/metabolismo , Osteoclastos/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Ligante RANK/metabolismo , Adulto Jovem
8.
BMC Infect Dis ; 19(1): 234, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845929

RESUMO

BACKGROUND: The study of stool microbiota has taken great relevance in the last years, given its role in the maintenance of the intestinal metabolic, physiological, and immunological homeostasis, as well as, its effect over HIV biomarkers levels such as CD4/CD8 ratio, high sensitivity C-Reactive Protein (hs-CRP), related to poor outcomes (rapid progression to AIDS). Several efforts have been made to characterize the gut microbiome. In HIV infection, most of the studies report the presence of a dysbiotic pattern; however, few of them have made an approach in elderly HIV-positive subjects despite the fact that nowadays this subgroup is rising. In this study, we compared the composition of faecal microbiota, Short Chain Fatty Acids (SCFAs), and systemic biomarkers between elderly HIV-positive and HIV-negative subjects. METHODS: A cross-sectional study with 18 HIV-negative controls and 20 HIV-positive patients. The quantification of Bacteroidetes, Firmicutes, Proteobacteria, Actinobacteria, Lactobacillus, Enterobacteriaceae, Bifidobacterium, Escherichia coli, Clostridium leptum, Clostridium coccoides was performed in faecal samples by qPCR. The analysis was performed by calculating the ΔCq of each microorganism using 16S rDNA as a reference gene. Faecal SCFAs were measured by HPLC. The hs-CRP and sCD14 were performed by ELISA. RESULTS: An increase in the Firmicutes/Bacteroidetes ratio, coupled with a significant increase in the proteobacteria phylum was detected in HIV-positive subjects. In contrast, a decrease in the Clostridium leptum group was observed. Nevertheless, these elderly HIV-positive patients showed higher levels of total SCFAs mainly by an augmented propionic acid values, compared to HIV-negative subjects. Whereas high levels of hs-CRP were positively correlated with sCD14 in the HIV-positive group. CONCLUSIONS: Alterations in bacterial communities reveals a dysbiotic state related to an unbalance of faecal SCFAs. Therefore, these intestinal conditions might drive an increase of poor prognostic biomarkers in elderly HIV-positive subjects.


Assuntos
Bactérias/genética , Biomarcadores/análise , Ácidos Graxos Voláteis/análise , Microbioma Gastrointestinal , Infecções por HIV/patologia , Idoso , Bactérias/isolamento & purificação , Proteína C-Reativa/análise , Contagem de Linfócito CD4 , Cromatografia Líquida de Alta Pressão , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Fezes/microbiologia , Feminino , Humanos , Receptores de Lipopolissacarídeos/análise , Masculino , México , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
9.
Virchows Arch ; 474(1): 3-12, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30368555

RESUMO

Macrophages are important for the function of the innate immune system, and in solid tumors, they represent a significant proportion of the tumor mass. Tumor-associated macrophages (TAM) have a M2 phenotype and show a multitude of pro-tumoral functions, promoting tumor cell survival, proliferation, and dissemination. CCL2, synthesized by tumor and stromal cells, initiates a chemokine cascade inducing these processes. We studied by immunohistochemistry (IHC) the frequency of TAMs and CCL2 expressing cells in three groups of primary tumor (PT)-recurrence (R) pairs, where relapse was recorded within 2 years (group 1), between 5 and 10 years (group 2), and after 10 years (group 3). In our study all established breast cancers were heavily infiltrated by CD68 positive cells. Both in PTs and in R lesions the infiltration was more abundant in the peritumoral than in the intratumoral stroma. The mean frequency of M2 marker and CD14 positive cells in the intratumoral stroma and CCL2 expressing tumor cells was higher in the Rs as compared to the corresponding PTs. In PTs, a high frequency of CD14 positive cells and a high expression of CCL2 by tumor cells was associated with an early recurrence. The findings support the current understanding of immune cell orchestrated development, progression and metastatic spread of breast cancer. Our study showed that a high frequency of CCL2 positive tumor cells and CD14 positive TAMs are significant risk factors for rapid tumor recurrence. Potential targets for intervention are discussed.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/imunologia , Movimento Celular , Quimiocina CCL2/análise , Receptores de Lipopolissacarídeos/análise , Macrófagos/imunologia , Recidiva Local de Neoplasia , Biópsia por Agulha , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Macrófagos/patologia , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Fatores de Risco , Células Estromais/imunologia , Células Estromais/patologia , Fatores de Tempo , Resultado do Tratamento
10.
J Infect Chemother ; 25(3): 170-174, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30473180

RESUMO

Therapeutic outcomes for septic arthritis vary greatly depending on the span of time between disease-onset and surgery. The most important factor is making an early and definitive diagnosis; however, some cases may be difficult to diagnose. We investigated presepsin, a biomarker of sepsis, to determine whether or not presepsin in synovial fluid would be useful for the diagnosis of septic arthritis. We selected 18 patients with septic arthritis including periprosthetic joint infections (SA group) and 28 patients with osteoarthritis (OA group). We measured the concentrations of synovial fluid presepsin, blood presepsin and procalcitonin (PCT) in the two groups. We compared the sensitivities and specificities of synovial fluid presepsin, blood presepsin and PCT. Synovial fluid and blood presepsin and blood PCT were all significantly higher in the SA group. Synovial fluid presepsin exhibited both 100% sensitivity and 100% specificity in the SA group, which were higher rates than those for blood presepsin and PCT. We found that synovial fluid presepsin is markedly elevated in case of septic arthritis, and therefore, it has potential as a new biomarker of septic arthritis.


Assuntos
Artrite Infecciosa/diagnóstico , Receptores de Lipopolissacarídeos/análise , Fragmentos de Peptídeos/análise , Líquido Sinovial/química , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Arterioscler Thromb Vasc Biol ; 39(1): 25-36, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30580568

RESUMO

Objective- Three distinct human monocyte subsets have been identified based on the surface marker expression of CD14 and CD16. We hypothesized that monocytes were likely more heterogeneous in composition. Approach and Results- We used the high dimensionality of mass cytometry together with the FlowSOM clustering algorithm to accurately identify and define monocyte subsets in blood of healthy human subjects and those with coronary artery disease (CAD). To study the behavior and functionality of the newly defined monocyte subsets, we performed RNA sequencing, transwell migration, and efferocytosis assays. Here, we identify 8 human monocyte subsets based on their surface marker phenotype. We found that 3 of these subsets fall within the CD16+ nonclassical monocyte population and 4 subsets belong to the CD14+ classical monocytes, illustrating significant monocyte heterogeneity in humans. As nonclassical monocytes are important in modulating atherosclerosis in mice, we studied the functions of our 3 newly identified nonclassical monocytes in subjects with CAD. We found a marked expansion of a Slan+CXCR6+ nonclassical monocyte subset in CAD subjects, which was positively correlated with CAD severity. This nonclassical subset can migrate towards CXCL16 and shows an increased efferocytosis capacity, indicating it may play an atheroprotective role. Conclusions- Our data demonstrate that human nonclassical monocytes are a heterogeneous population, existing of several subsets with functional differences. These subsets have changed frequencies in the setting of severe CAD. Understanding how these newly identified subsets modulate CAD will be important for CAD-based therapies that target myeloid cells.


Assuntos
Citometria de Fluxo/métodos , Monócitos/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Aterosclerose/etiologia , Movimento Celular , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/etiologia , Humanos , Receptores de Lipopolissacarídeos/análise , Camundongos , Pessoa de Meia-Idade , Monócitos/imunologia , Receptores de IgG/análise
12.
Pathog Dis ; 76(8)2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30445573

RESUMO

Infection with Mycobacterium tuberculosis (Mtb) is characterized by an inflammatory response resulting in the formation of granulomas. These tight aggregates of immune cells play an important role in bacterial containment and in the eventual outcome of infection. Monocytes are a major component of the early immune response to Mtb and contribute to the cellular matrix of the newly forming granuloma. Therefore, defining which monocyte subset is the target of mycobacterial infection is critical. Here, we describe a flow-cytometry-based assay to analyze infectivity in vitro of monocyte subsets by Mycobacterium bovis BCG before granuloma formation. We identified CD14+CD16- monocytes as the main target of infection in peripheral blood mononuclear cells from six healthy donors. CD14+CD16+ monocytes displayed the lowest infection rates and remained uninfected in some donors. We found that a longer infection time resulted in an increase of the percentage of monocytes infected and of the number of granulomas produced. We did not observe changes in monocyte cell death or subset expansion upon infection. Future experiments with our in vitro method could help define Mtb infectivity of monocyte subsets. Our study provides a platform to investigate how early infection of different monocyte subsets may alter granuloma formation and outcomes of Mtb infection.


Assuntos
Receptores de Lipopolissacarídeos/análise , Monócitos/imunologia , Monócitos/microbiologia , Mycobacterium bovis/crescimento & desenvolvimento , Receptores de IgG/análise , Citometria de Fluxo , Voluntários Saudáveis , Humanos , Imunofenotipagem , Monócitos/química
13.
BMC Pulm Med ; 18(1): 176, 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30470216

RESUMO

BACKGROUND: We aimed to determine the presepsin concentration in pleural fluid from patients with pleural effusions of different aetiologies and to compare its diagnostic value with that of pleural fluid C-reactive protein (CRP) and procalcitonin (PCT). METHODS: We enrolled 132 patients with pleural effusion who underwent diagnostic evaluation, and we classified them into six categories: empyema, parapneumonic effusion, tuberculous effusion, malignant effusion, paramalignant effusion, and transudate effusion. Additionally, all pleural effusions were categorised as infectious or non-infectious effusions. RESULTS: Receiver operating characteristic analysis was used to evaluate diagnostic performance. When diagnosing empyema, the marker with the highest sensitivity was pleural fluid presepsin (cut-off: 754 pg/mL; sensitivity: 90.9%, specificity: 74.4%) and that with the highest specificity was pleural fluid CRP (cut-off: 4.91 mg/dL; sensitivity: 63.6%, specificity: 89.3%). Pleural fluid PCT tended to be lower in patients with empyema than in those with parapneumonic effusion, but this was not useful for the diagnosis of empyema. When diagnosing infectious pleural effusion, a combination of pleural fluid CRP (cut-off: 2.59 mg/dL) and presepsin (cut-off: 680 pg/mL) produced the highest diagnostic accuracy (83.3%). CONCLUSIONS: Pleural fluid presepsin was found at high levels in patients with empyema and parapneumonic effusion. This pattern closely resembles the previously reported pattern of pleural fluid CRP. Some combinations of pleural fluid inflammatory markers may be more clinically useful than these markers in isolation.


Assuntos
Proteína C-Reativa/análise , Exsudatos e Transudatos/química , Receptores de Lipopolissacarídeos/análise , Fragmentos de Peptídeos/análise , Derrame Pleural/etiologia , Pró-Calcitonina/análise , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/diagnóstico , Curva ROC
14.
Crit Care ; 22(1): 316, 2018 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-30463590

RESUMO

BACKGROUND: Sepsis is an important cause of neonatal morbidity and mortality; therefore, the early diagnosis of neonatal sepsis is essential. METHOD: Our aim was to compare the diagnostic accuracy of procalcitonin (PCT), C-reactive protein (CRP), procalcitonin combined with C-reactive protein (PCT + CRP) and presepsin in the diagnosis of neonatal sepsis. We searched seven databases to identify studies that met the inclusion criteria. Two independent reviewers performed data extraction. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under curve (AUC), and corresponding 95% credible interval (95% CI) were calculated by true positive (TP), false positive (FP), false negative (FN), and true negative (TN) classification using a bivariate regression model in STATA 14.0 software. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, and corresponding 95% CI were the primary outcomes. Secondary outcomes included the sensitivity and specificity in multiple subgroup analyses. RESULTS: A total of 28 studies enrolling 2661 patients were included in our meta-analysis. The pooled sensitivity of CRP (0.71 (0.63, 0.78)) was weaker than that of PCT (0.85 (0.79, 0.89)), PCT + CRP (0.91 (0.84, 0.95)) and presepsin (0.94 (0.80, 0.99)) and the pooled NLR of presepsin (0.06 (0.02, 0.23)) and PCT + CRP (0.10 (0.05, 0.19)) were less than CRP (0.33 (0.26, 0.42)), and the AUC for presepsin (0.99 (0.98, 1.00)) was greater than PCT + CRP (0.96 (0.93, 0.97)), CRP (0.85 (0.82, 0.88)) and PCT (0.91 (0.89, 0.94)). The results of the subgroup analysis showed that 0.5-2 ng/mL may be the appropriate cutoff interval for PCT. A cut-off value > 10 mg/L for CRP had high sensitivity and specificity. CONCLUSIONS: The combination of PCT and CRP or presepsin alone improves the accuracy of diagnosis of neonatal sepsis. However, further studies are required to confirm these findings.


Assuntos
Proteína C-Reativa/análise , Receptores de Lipopolissacarídeos/análise , Sepse Neonatal/diagnóstico , Fragmentos de Peptídeos/análise , Pró-Calcitonina/análise , Área Sob a Curva , Biomarcadores/análise , Biomarcadores/sangue , Humanos , Recém-Nascido , Doenças do Recém-Nascido/sangue , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/fisiopatologia , Receptores de Lipopolissacarídeos/sangue , Sepse Neonatal/sangue , Sepse Neonatal/fisiopatologia , Razão de Chances , Pediatria/métodos , Fragmentos de Peptídeos/sangue , Pró-Calcitonina/sangue , Curva ROC
15.
PLoS Negl Trop Dis ; 12(10): e0006887, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30346948

RESUMO

BACKGROUND: Chronic infection with Trypanosoma cruzi leads to a constant stimulation of the host immune system. Monocytes, which are recruited in response to inflammatory signals, are divided into classical CD14hiCD16-, non-classical CD14loCD16+ and intermediate CD14hiCD16+ subsets. In this study, we evaluated the frequencies of monocyte subsets in the different clinical stages of chronic Chagas disease in comparison with the monocyte profile of seronegative heart failure subjects and seronegative healthy controls. The effect of the anti-parasite drug therapy benznidazole on monocyte subsets was also explored. METHODOLOGY/PRINCIPAL FINDINGS: The frequencies of the different monocyte subsets and their phenotypes were measured by flow cytometry. Trypanosoma cruzi-specific antibodies were quantified by conventional serological tests. T. cruzi-infected subjects with mild or no signs of cardiac disease and patients suffering from dilated cardiomyopathy unrelated to T. cruzi infection showed increased levels of non-classical CD14loCD16+ monocytes compared with healthy controls. In contrast, the monocyte profile in T. cruzi-infected subjects with severe cardiomyopathy was skewed towards the classical and intermediate subsets. After benznidazole treatment, non-classical monocytes CD14loCD16+ decreased while classical monocytes CD14hiCD16-increased. CONCLUSIONS/SIGNIFICANCE: The different clinical stages of chronic Chagas disease display distinct monocyte profiles that are restored after anti-parasite drug therapy. T. cruzi-infected subjects with severe cardiac disease displayed a profile of monocytes subsets suggestive of a more pronounced inflammatory environment compared with subjects suffering from heart failure not related to T. cruzi infection, supporting that parasite persistence might also alter cell components of the innate immune system.


Assuntos
Cardiomiopatia Dilatada/patologia , Doença de Chagas/patologia , Monócitos/imunologia , Fenótipo , Trypanosoma cruzi/imunologia , Adulto , Idoso , Anticorpos Antiprotozoários/sangue , Feminino , Citometria de Fluxo , Proteínas Ligadas por GPI/análise , Humanos , Imunofenotipagem , Receptores de Lipopolissacarídeos/análise , Masculino , Pessoa de Meia-Idade , Monócitos/classificação , Receptores de IgG/análise , Adulto Jovem
16.
Clin Exp Immunol ; 194(3): 350-360, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30101536

RESUMO

The objective of this study was to conduct an analysis of peripheral blood Th17 cells with the ability to home to gut mucosa (CD4+ Th17+ ß7+ ) during recent or chronic human immunodeficiency virus (HIV) infections. The relationship between HIV load and systemic inflammation markers was studied. Twenty-five patients with recent (n = 10) or chronic (n = 15) untreated HIV infections; 30 treated HIV-infected patients with undetectable HIV load at the time of inclusion and 30 healthy controls were included. Bacterial translocation markers (16S rDNA), soluble CD14 (sCD14) and interleukin (IL)-6 monocyte activation parameters, CD4/CD8 ratio and T helper type 17 (Th17) subpopulations [CD4+ Th17+ expressing the IL-23 receptor (IL-23R) or ß7] were analysed at baseline and after 6 and 12 months of anti-retroviral therapy (ART). 16S rDNA was detected in all patients. Significantly increased serum levels of sCD14 and IL-6 and a decreased CD4/CD8 ratio were observed in patients. Similar percentages of CD4+ IL-23R+ and CD4+ Th17+ ß7+ cells were observed in healthy controls and patients at baseline. After 12 months of therapy, patients with a recent HIV infection showed significant increases of CD4+ IL-23R+ and CD4+ Th17+ ß7+ cell percentages and a decrease in IL-6 levels, although 16S rDNA continued to be detectable in all patients. No significant differences were observed in Th17 subpopulations in patients with chronic HIV infection after therapy. Early initiation of ART helps to increase the number of Th17 cells with the ability to home to the intestinal mucosa and to partially restore gut mucosal homeostasis. These results provide a rationale for initiating ART during the acute phase of HIV infection.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/imunologia , HIV-1/imunologia , Cadeias beta de Integrinas/biossíntese , Mucosa Intestinal/imunologia , Células Th17/metabolismo , Adulto , Antirretrovirais/uso terapêutico , Relação CD4-CD8 , DNA Ribossômico/análise , Feminino , Infecções por HIV/virologia , Humanos , Interleucina-6/análise , Mucosa Intestinal/citologia , Receptores de Lipopolissacarídeos/análise , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina/biossíntese , Células Th17/imunologia , Carga Viral
17.
J Investig Clin Dent ; 9(4): e12353, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30062853

RESUMO

AIM: In the present study, we evaluated the effect of systemic long-term, low-dose aspirin on the periodontal status and gingival crevicular fluid (GCF) concentrations of aspirin-triggered lipoxins (ATL) and soluble CD14 (sCD14). METHODS: The study group consisted of 45 patients who were on long-term, low-dose aspirin therapy, and the control group included patients not on aspirin therapy. Mean bleeding index, plaque index (PI), probing depth (PD), and clinical attachment loss (CAL) were recorded. GCF samples were analyzed for concentrations of ATL, and sCD14 using enzyme-linked immunosorbent assay method. RESULTS: The means of PI, PD, and CAL were higher for the control group compared to the study group. The mean concentration of ATL was significantly higher for the study group (49.13 ± 37.39 ng/mL). The mean concentration of sCD14 was higher in the control group (5.75 ± 3.91 µg/mL). There was a negative correlation in the study group between concentrations of ATL with PD (r = -0.54) and CAL (r = -0.123). There was a positive correlation between sCD14 and CAL (r = 0.047) in the study group. A negative correlation was also observed between concentrations of sCD14 and ATL (r = -0.134) in the study group. CONCLUSION: The results indicate better periodontal status among long-term aspirin users compared to non-aspirin users.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Periodontite Crônica/tratamento farmacológico , Líquido do Sulco Gengival/efeitos dos fármacos , Receptores de Lipopolissacarídeos/análise , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Estudos de Casos e Controles , Periodontite Crônica/metabolismo , Índice de Placa Dentária , Feminino , Líquido do Sulco Gengival/química , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/tratamento farmacológico , Índice Periodontal
18.
J Leukoc Biol ; 104(6): 1049-1059, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29791013

RESUMO

HIV infection of the CNS causes neuroinflammation and damage that contributes to the development of HIV-associated neurocognitive disorders (HAND) in greater than 50% of HIV-infected individuals, despite antiretroviral therapy (ART). Opioid abuse is a major risk factor for HIV infection. It has been shown that opioids can contribute to increased HIV CNS pathogenesis, in part, by modulating the function of immune cells. HIV enters the CNS within two weeks after peripheral infection by transmigration of infected monocytes across the blood brain barrier (BBB). CD14+ CD16+ monocytes are a mature subpopulation that is increased in number in the peripheral blood of HIV-infected people. Mature monocytes can be productively infected with HIV, and they transmigrate preferentially across the BBB in response to CCL2, a chemokine elevated in the CNS and CSF of HIV-infected people even with ART. Buprenorphine, an opioid derivate, is an opioid replacement therapy for heroin addiction. It is a partial agonist of µ-opioid receptor and full antagonist of κ-opioid receptor. The effects of buprenorphine on CCL2-mediated CD14+ CD16+ monocytes transmigration across the BBB, a critical mechanism that promotes neuroinflammation and HAND, have not been characterized. We showed for the first time that buprenorphine decreases several steps of CCL2-mediated human mature monocyte transmigration. We propose that buprenorphine treatment in the context of HIV infection could serve a dual purpose, to treat opioid addiction and also to reduce neuroinflammation. Additionally, buprenorphine may be used as a treatment for HAND not only in the context of opioid abuse.


Assuntos
Buprenorfina/farmacologia , Quimiocina CCL2/fisiologia , Monócitos/efeitos dos fármacos , Receptores Opioides mu/agonistas , Migração Transendotelial e Transepitelial/efeitos dos fármacos , Complexo AIDS Demência/imunologia , Complexo AIDS Demência/prevenção & controle , Buprenorfina/uso terapêutico , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Quimiotaxia de Leucócito/efeitos dos fármacos , Proteínas Ligadas por GPI/análise , Humanos , Inflamação/tratamento farmacológico , Molécula 1 de Adesão Intercelular/metabolismo , Receptores de Lipopolissacarídeos/análise , Monócitos/citologia , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Receptores de IgG/análise , Receptores Opioides kappa/antagonistas & inibidores , Células THP-1 , Molécula 1 de Adesão de Célula Vascular/metabolismo
19.
Khirurgiia (Mosk) ; (5): 58-66, 2018.
Artigo em Russo | MEDLINE | ID: mdl-29798993

RESUMO

AIM: To compare diagnostic value of molecular biomarkers of sepsis in patients with surgical infection in screening via Sepsis-2 (Surviving Sepsis Campaign 2012, SSC 2012) and Sepsis-3 (The Third International Consensus Definitions for Sepsis and Septic Shock) criteria. MATERIAL AND METHODS: Septic patients according to Sepsis-2 and Sepsis-3 criteria were identified from general population with surgical infection. Logistic regression models quality was the criterion for assessment of diagnostic value of molecular biomarkers. Risk factors importance was estimated via odds ratios (OR) calculation. RESULTS: Sepsis-3 ROC-AUC for procalcitonin increased up to 0.933, cut-off value 2.35 ng/ml (Sepsis-2 AUC 0.768 (p=0.004), cut-off 1.72 ng/ml). Sepsis-3 ROC-AUC for presepsin increased up to 0.932, cut-off value - 772 pg/ml (Sepsis-2 AUC 0.865, cut-off 567 pg/ml). The highest risk of sepsis was observed in systemic response to inflammation combined with organ dysfunction (OR 69.667, S 0.636; 95% CI 20.03-242.4) (Sepsis-2 - OR 9.25, S 0.548; 95% CI 3.2-27.1, p<0.001). Increased levels of both biomarkers significantly increased the risk of sepsis (OR 22.5, S 0.794; 95% CI 4.74-106.6 and OR 20.97, S 0.58; 95% CI 6.705-65.6, respectively). CONCLUSION: Organ dysfunction assessment by Sepsis-3 criteria improves diagnostic possibilities in patients with suspected sepsis. Maximum predictive value is observed for systemic inflammation response combined with organ dysfunction. In these patients procalcitonin and presepsin are characterized by equivalent high diagnostic potential for evidence of infectious nature of the disease. Increased level of these markers can serve as a basis for antimicrobial therapy administration.


Assuntos
Anti-Infecciosos/uso terapêutico , Calcitonina , Receptores de Lipopolissacarídeos , Fragmentos de Peptídeos , Sepse , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Infecção da Ferida Cirúrgica/complicações , Síndrome de Resposta Inflamatória Sistêmica , Biomarcadores/análise , Biomarcadores/sangue , Calcitonina/análise , Calcitonina/sangue , Feminino , Humanos , Receptores de Lipopolissacarídeos/análise , Receptores de Lipopolissacarídeos/sangue , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Sepse/diagnóstico , Sepse/etiologia , Sepse/imunologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia
20.
Mycopathologia ; 183(4): 709-716, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29736739

RESUMO

Coccidioidomycosis is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. These fungi are endemic in the southern USA and northern Mexico. Immunocompromised patients are susceptible to develop severe forms of this fungal infection. Cytokines play an important role in controlling the fungal infection, but little is known about the predominant immunological environment in human lung tissue from fatal cases. Our aim was to analyze the pro-inflammatory and anti-inflammatory cytokines and monocyte/macrophages markers (CD14 and CD206) in the granulomas of six fatal cases of coccidioidomycosis. Cytokines and surface markers were higher in coccidioidomycosis cases when compared to control (P < 0.05). CD14 positive cells were increased inside the coccidioidal granuloma when compared to the outside (P < 0.05). No differences were found in the number of CD206+ cells inside the granuloma when compared to the outer population (P > 0.05). Interestingly, an analysis of stain intensity signals showed an increased signaling of CD14, CD206, IL-10 and TNFα inside the granuloma when compared to the outside (P < 0.05). iNOS and IL-12 gene expression were not detected in coccidioidomycosis cases, while IL-10, IL-6 and TGFß gene expression were detected, but the differences when compared to healthy lungs were not significant (P > 0.05). TNFα gene expression was lower in coccidioidomycosis cases when compared to healthy lung (P = 0.05). In conclusion, pro- and anti-inflammatory responses co-exist inside of the granulomas of fatal cases of coccidioidomycosis and the absent of iNOS and IL-12 gene expression may be related with patient's outcome.


Assuntos
Coccidioidomicose/parasitologia , Granuloma/patologia , Pulmão/patologia , Idoso , Citocinas/análise , Histocitoquímica , Humanos , Lectinas Tipo C/análise , Receptores de Lipopolissacarídeos/análise , Lectinas de Ligação a Manose/análise , México , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/análise , Receptores de Superfície Celular/análise , Estudos Retrospectivos , Estados Unidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA