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1.
Medicine (Baltimore) ; 99(7): e18894, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049788

RESUMO

Thiamine is an essential co-factor for aerobic metabolism. Both thiamine deficiency and sepsis may be associated with hyperlactatemia and hypotension. We assessed the relationship between thiamine compounds, lactate concentrations and clinical outcomes in septic patients.We undertook a prospective observational single-center study. Erythrocyte levels of total thiamine, free thiamine, thiamine mono, di and triphosphate (TMP, TDP, and TTP respectively), the erythrocyte transketolase activity (ETKA) and the effect of thiamine diphosphate on ETKA were measured in septic patients by high performance liquid chromatography and correlated with arterial lactate. Vital status at the end of intensive care unit stay was recorded.Overall, 28 patients suffering from sepsis were included. Median (interquartile range [IQR]) age was 60 [44-77.3] years, 15 (53.6%) patients were male, median [IQR] simplified acute physiology score II was 40 [27-50]. There was no correlation between total thiamine and lactate levels (P = .33). There was no correlation between free thiamine (P = .81), TMP (P = .71), TDP (P = .31), TTP (P = .86), and lactate levels in our population. There was no correlation between ETKA (P = .58) or the effect of TDP on ETKA (P = .40) and lactate concentration. Total thiamine and TDP concentration were significantly higher in intensive care unit (ICU) survivors than in nonsurvivors (P = .03 and P = .03). The effect of TDP on ETKA was significantly higher in nonsurvivors compared to survivors (P = .04).We found no correlation between thiamine compounds and lactate concentration in sepsis. Thiamine deficiency in sepsis may be associated with ICU-mortality.


Assuntos
Ácido Láctico/sangue , Sepse/sangue , Tiamina/sangue , Adulto , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sepse/mortalidade , Transcetolase/metabolismo
2.
J Surg Res ; 246: 490-498, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31635838

RESUMO

BACKGROUND: Burn patients are at high risk of infection, and as sepsis contributes significantly to morbidity and mortality, early diagnosis is essential. Procalcitonin (PCT) is a biomarker released in response to inflammation and specifically bacterial infection. This study aimed to determine the value of PCT as a diagnostic biomarker of sepsis in burns patients in Johannesburg, South Africa. MATERIALS AND METHODS: All adult patients admitted to two burns intensive care units in Johannesburg over a 3-year study period were included in a retrospective data review. Records of 178 patients were accessible and reviewed. RESULTS: The most significant risk factor for sepsis was percentage total body surface area burned (P = 0.012). A rise in PCT was a significant biomarker for bacterial infection in the early phase after a burn (P = 0.03) but not after day eight. PCT correlated with C-reactive protein as a biomarker for sepsis (P < 0.001), but not with other biomarkers. The mean PCT in patients who died was significantly higher on every study day until death compared with those who remained alive (P < 0.02, consistently). Patients on inotropes also had a significantly increased PCT level (P = 0.0001), as did those who were not discharged from intensive care unit by day 14. CONCLUSIONS: PCT may be useful as an adjunct biomarker of infection in burn patients and has potential as a predictive biomarker of early discharge.


Assuntos
Queimaduras/complicações , Pró-Calcitonina/sangue , Sepse/diagnóstico , Adulto , Biomarcadores/sangue , Queimaduras/sangue , Queimaduras/diagnóstico , Proteína C-Reativa/análise , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Sepse/sangue , Sepse/etiologia , África do Sul , Adulto Jovem
3.
Immunology ; 159(1): 88-95, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31606902

RESUMO

Severe sepsis is often accompanied by a transient immune paralysis, which is associated with enhanced susceptibility to secondary infections and poor clinical outcomes. The functional impairment of antigen-presenting cells is considered to be a major hallmark of this septic immunosuppression, with reduced HLA-DR expression on circulating monocytes serving as predictor of mortality. Unconventional lymphocytes like γδ T-cells have the potential to restore immune defects in a variety of pathologies including cancer, but their use to rescue sepsis-induced immunosuppression has not been investigated. Our own previous work showed that Vγ9/Vδ2+ γδ T-cells are potent activators of monocytes from healthy volunteers in vitro, and in individuals with osteoporosis after first-time administration of the anti-bone resorption drug zoledronate in vivo. We show here that zoledronate readily induces upregulation of HLA-DR, CD40 and CD64 on monocytes from both healthy controls and sepsis patients, which could be abrogated by neutralising the pro-inflammatory cytokines interferon (IFN)-γ and tumour necrosis factor (TNF)-α in the cultures. In healthy controls, the upregulation of HLA-DR on monocytes was proportional to the baseline percentage of Vγ9/Vδ2 T-cells in the peripheral blood mononuclear cell population. Of note, a proportion of sepsis patients studied here did not show a demonstrable response to zoledronate, predominantly patients with microbiologically confirmed bloodstream infections, compared with sepsis patients with more localised infections marked by negative blood cultures. Taken together, our results suggest that zoledronate can, at least in some individuals, rescue immunosuppressed monocytes during acute sepsis and thus may help improve clinical outcomes during severe infection.


Assuntos
Antígenos HLA-DR/imunologia , Fatores Imunológicos/farmacologia , Monócitos/efeitos dos fármacos , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Sepse/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Ácido Zoledrônico/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Antígenos HLA-DR/metabolismo , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Sepse/sangue , Sepse/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
4.
J Pharm Biomed Anal ; 177: 112883, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31546136

RESUMO

The article is devoted to the application of modern sample preparation technique - microextraction by packed sorbent (MEPS) - in conjunction with non-conventional type of sorbent - hypercrosslinked polystyrene, that was investigated for the first time in this work. Their combination was used to extract phenylcarboxylic acid-type aromatic microbial metabolites from serum samples of a healthy volunteer with following derivatization and GC-MS detection. As barrel insert and needle for MEPS with hypercrosslinked polystyrene is not produced, we designed a device to imitate the commercial MEPS system with packed granular biporous hypercrosslinked polystyrene. Nine aromatic microbial metabolites, including sepsis associated phenyllactic, 4-hydroxyphenyllactic and 4-hydroxyphenylacetic acids, were extracted from serum samples (recoveries were 20-70%) and a linear dependence was revealed in the most clinically significant range of concentrations (0.5-18 µM). The results obtained demonstrate the perspective of the applying of hypercrosslinked polystyrene in commercial devices for MEPS for the future analyses of biological samples, in particular for the early diagnosis of sepsis and treatment effectiveness control.


Assuntos
Bactérias/metabolismo , Fenilacetatos/sangue , Poliestirenos/química , Sepse/diagnóstico , Microextração em Fase Sólida/métodos , Reagentes para Ligações Cruzadas/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Voluntários Saudáveis , Humanos , Limite de Detecção , Fenilacetatos/metabolismo , Sepse/sangue , Sepse/microbiologia
5.
BMC Infect Dis ; 19(1): 1020, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791247

RESUMO

BACKGROUND: Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency. METHODS: We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function. RESULTS: We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver. CONCLUSIONS: Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.


Assuntos
Sepse/sangue , Sepse/complicações , Deficiência de Vitamina D/etiologia , Vitamina D/análogos & derivados , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Fator de Crescimento Insulin-Like I , Rim/efeitos dos fármacos , Testes de Função Renal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hormônio Paratireóideo/sangue , Sepse/fisiopatologia , Transdução de Sinais , Vitamina D/sangue , Vitamina D/metabolismo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/fisiopatologia
6.
Medicine (Baltimore) ; 98(52): e18546, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876752

RESUMO

OBJECTIVE: The predictive accuracies of procalcitonin (PCT) in the diagnosis of catheter-associated bloodstream infection (CABSI) vary widely. This meta-analysis aimed to explore the predictive value of PCT for CABSI. METHODS: We searched PubMed, EMBase, Web of Science, ScienceDirect, Cochrane Library, and studies published up to 10 March 2019. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate PCT predictive value using Stata 14.0 software. RESULTS: The meta-analysis was composed of 7 studies, consisting of 347 subjects. Pooled analysis demonstrated that a high PCT was significantly correlated with CABSI (pooled OR = 23.36, 95%CI 12.43-43.91, P < .001) and medium heterogenicity (I = 36.9%, P = .147). The pooled sensitivity and specificity were 85% (95%CI 0.76-0.91) and 89% (95%CI 0.68-0.97), respectively. Although Begg funnel plot (P = .007) indicated the presence of publication bias among the included studies, the stability of the pooled outcomes was verified by the trim-and-fill method. Furthermore, sensitivity analyses did not show important differences in effect estimation. CONCLUSION: PCT is an effective predictor of CABSI. However, high-quality randomized controlled trials are needed to determine whether PCT could predict CABSI.


Assuntos
Infecções Relacionadas a Cateter/sangue , Pró-Calcitonina/sangue , Sepse/sangue , Biomarcadores/sangue , Infecções Relacionadas a Cateter/diagnóstico , Humanos , Valor Preditivo dos Testes , Sepse/diagnóstico , Sepse/etiologia
7.
Res Vet Sci ; 127: 122-129, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31704497

RESUMO

Gram positive bacteria are a cause of sepsis in human preterm infants, and associates with high mortality and hemostatic dysfunction. It is unknown whether bovine colostrum may protect against sepsis and prevent hemostatic dysfunction. The current study was part of an overall sepsis study investigating Staphylococcus epidermidis (SE) induced sepsis in premature pigs including investigation of the effect of feeding bovine colostrum. The specific hypothesis of this study was that the hemostatic response would be hypercoagulable in septic pigs compared to non-infected controls, and that feeding bovine colostrum would increase the hypercoagulant response. Thromboelastography, activated partial thromboplastin time, prothrombin time and fibrinogen concentration were characterized in SE infected pigs, SE infected pigs fed bovine colostrum, and uninfected controls. All pigs were followed for 24 h. In addition, the same parameters were evaluated in a group of premature pigs and a group of full born pigs all followed for 11 days. SE septic premature pigs were characterized by increased clot strength and decreased fibrinolysis, significantly low platelet count and high fibrinogen concentration. Feeding bovine colostrum did not affect the hemostatic response. Compared to full born pigs, preterm newborn pigs demonstrated reduced clot strength, prolonged prothrombin time and low fibrinogen concentration. In all pigs, the fibrinogen concentration increased 11 days post-partum. To conclude, SE induced sepsis in premature pigs resulted in hypercoagulability. Bovine colostrum did not mitigate the hemostatic response. A hypocoagulable hemostatic response was present in healthy preterm pigs compared to full born pigs, similar to previous reports in infants.


Assuntos
Colostro/fisiologia , Nascimento Prematuro/veterinária , Sepse/veterinária , Infecções Estafilocócicas/veterinária , Staphylococcus epidermidis/fisiologia , Doenças dos Suínos/sangue , Trombofilia/veterinária , Animais , Bovinos , Feminino , Gravidez , Sepse/sangue , Infecções Estafilocócicas/sangue , Suínos , Trombofilia/sangue
8.
Medicine (Baltimore) ; 98(46): e18029, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725679

RESUMO

Neutrophil-to-lymphocyte ratio (NLR) has been reported to serve as a prognostic marker in inflammatory diseases. The purpose of this study was to evaluate the association of NLR at admission with in-hospital mortality in patients with sepsis presenting to emergency department.This was a secondary analysis based on a single-center, retrospective, cohort study. Patients with sepsis admitted to an academic emergency department between January 2010 and January 2015 were enrolled. NLR of patients was analyzed from the hospital's electronic health record (EHR) system. A total of 174 adult patients, of which 80 (46.0%) died in hospital. The primary outcome was in-hospital mortality. Secondary outcome was 28-day mortality.Contrary to previous studies, a larger NLR was found to have less odds of in-hospital mortality, as well as the presence of bacteremia. Patients who has severe/shock or had a history of chronic heart failure (CHF) had larger odds of death during hospital. Multivariate logistic regression analysis indicated that low NLR was an independent predictor of in-hospital mortality (OR = -0.98; 95% CI -0.96 to -0.99; P = .022). However, no correlation was found between the NLR and 28-day hospital mortality in patients with sepsis (P = .988). As a predictor of in-hospital survival, the area under curve (AUC) of the NLR was 0.622 (95%CI 0.54-0.71; P = .006) and the cut-off value was 9.11 with 0.551 sensitivity and 0.707 specificity.NLR at admission was an independent predictor of in-hospital mortality of sepsis patients.


Assuntos
Mortalidade Hospitalar , Contagem de Leucócitos/métodos , Sepse/sangue , Sepse/mortalidade , Centros Médicos Acadêmicos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Comorbidade , Feminino , Humanos , Modelos Logísticos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Estudos Retrospectivos
9.
Medicine (Baltimore) ; 98(48): e18025, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770216

RESUMO

INTRODUCTION: Sepsis is a physiological, pathological, and biochemical syndrome caused by infection. Acupuncture may be useful for sepsis. This systematic review aims to assess the efficacy and safety of acupuncture as a complementary therapy for sepsis. METHODS AND ANALYSIS: We will search PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Wan Fang Database, Chinese Biomedicine (CBM) database, VIP database, and TCM Literature Analysis and Retrieval Database from inception to October 31, 2019 to identify any eligible study. We include all randomized controlled trials (RCTs) without any limitation of blinding or publication language, exclude cohort studies and case reports. Two reviewers will independently select studies, extract and manage data. The primary outcomes include the mortality at 28 days, acute physiology, and chronic health evaluation II scores. The secondary outcomes include the tumor necrosis factor α (TNF-α) counts, interleukin 6 (IL-6) counts, interleukin 10 (IL-10) counts, procalcitonin (PCT), lactic acid, the level of T cell subsets (CD3+, CD4+, CD8+, CD4+/CD8+), monocytes of human leukocyte antigen DR (HLA-DR), C-reactive protein (CRP), the numeration of leukocyte, intra-abdominal pressure, and adverse events or reactions. Statistical analyses will be performed using the Review Manager V.5.3 and R packages Metafor. We will use the Cochrane risk of bias tool for randomized trials to assess the risk of bias of included studies. ETHICS AND DISSEMINATION: This study will not involve personal information. Ethical approval will not be required. We will publish the results in a peer-reviewed journal. PROSPERO TRIAL REGISTRATION NUMBER: CRD42019141491.


Assuntos
Terapia por Acupuntura/métodos , Sepse/terapia , APACHE , Proteína C-Reativa/análise , Antígenos HLA-DR/sangue , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Ácido Láctico/sangue , Contagem de Leucócitos , Metanálise como Assunto , Pró-Calcitonina/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Sepse/sangue , Sepse/mortalidade , Revisão Sistemática como Assunto , Subpopulações de Linfócitos T/metabolismo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
10.
J Vet Emerg Crit Care (San Antonio) ; 29(6): 593-603, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31637812

RESUMO

OBJECTIVE: To quantify plasma cytokine concentrations in dogs with sepsis and noninfectious systemic inflammation and to evaluate the association between plasma cytokines and outcome in dogs with sepsis. DESIGN: Prospective, observational cohort study. SETTING: University teaching hospital. ANIMALS: Forty-five dogs with sepsis, 10 dogs with noninfectious systemic inflammation (nSIRS), and 15 healthy controls were consecutively enrolled from June 2015 to February 2016 and followed to hospital discharge. Dogs with sepsis satisfied ≥2 SIRS criteria and had a documented or highly suspected bacterial infection. Dogs with nSIRS satisfied ≥2 SIRS criteria but had no evidence of infection. Dogs <3 kg and those with documented coagulopathy were excluded. INTERVENTIONS: Measurement of inflammatory cytokines and high-mobility group box-1 (HMGB-1) was performed on each group. MEASUREMENTS AND MAIN RESULTS: High-mobility group box-1 concentrations were analyzed by ELISA. Plasma concentrations of 13 cytokines were measured in singlet using multiplex magnetic bead assays. Kruskal-Wallis with Dunn's multiple comparison tests were used to compare biomarker concentrations between groups. Mann-Whitney U-tests were used to compare biomarker concentrations between survivors and nonsurvivors. Associations between biomarkers were evaluated using Spearman's correlation coefficients. Independent outcome predictors were identified using multivariable logistic regression. Alpha was set at 0.05. Concentrations of interleukin (IL)-6, C-X-C motif chemokine (CXCL)-8, keratinocyte-derived chemokine (KC)-like, C-C motif chemokine ligand 2 (CCL2), and HMGB-1 were significantly greater in dogs with sepsis versus healthy controls (all P ≤ 0.034). In dogs with sepsis, only CCL2 was independently associated with survival (odds ratio [OR] 0.996, 95% CI 0.993-0.999, P = 0.004). A cut-off of 385 pg/mL for CCL2 was 80% sensitive and 91.4% specific for nonsurvival (area under the ROC curve [AUROC] 0.866). CONCLUSIONS: Dogs with sepsis have significantly increased concentrations of HMGB-1 and inflammatory cytokines, including IL-6, CXCL8, and KC-like. Increased CCL2 concentration is a negative prognostic indicator in dogs with sepsis. These findings should be confirmed using duplicate analyses in larger, distinct populations of dogs with sepsis before applying them to clinical patients.


Assuntos
Citocinas/metabolismo , Doenças do Cão/sangue , Sepse/veterinária , Síndrome de Resposta Inflamatória Sistêmica/veterinária , Animais , Biomarcadores/sangue , Estudos de Coortes , Citocinas/genética , Cães , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação/metabolismo , Inflamação/veterinária , Masculino , Prognóstico , Estudos Prospectivos , Sepse/sangue , Síndrome de Resposta Inflamatória Sistêmica/sangue
11.
Dis Markers ; 2019: 8792640, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612071

RESUMO

Background: Calreticulin has been identified to play a critical role in innate and adaptive immune responses. However, little is known about the role of calreticulin in sepsis with a characteristic of immune disorder. This study was aimed at investigating whether plasma calreticulin level increases in sepsis and its association with sepsis severity. Methods: This retrospective analysis evaluated sepsis patients who were admitted to the intensive care unit (ICU). Healthy subjects were also included as controls. Plasma samples were collected from the patients within 48 h after ICU admission as well as the healthy subjects. Plasma calreticulin levels were measured via the enzyme-linked immunosorbent assay. Results: In total, 127 sepsis patients and 40 healthy controls were included. Calreticulin was significantly increased in sepsis patients than in healthy controls. Furthermore, the level of plasma calreticulin was significantly higher in nonsurvivors than in survivors. Patients with calreticulin levels > 343.5 pg/ml showed lower cumulative survival than those with levels < 343.5 pg/ml. Conclusion: Calreticulin level was positively correlated with the severity of sepsis. High calreticulin level indicated poor prognosis of sepsis patients.


Assuntos
Calreticulina/sangue , Sepse/sangue , Sepse/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Sepse/mortalidade , Sepse/patologia , Índice de Gravidade de Doença , Análise de Sobrevida
12.
Int J Mol Sci ; 20(19)2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31569348

RESUMO

Sepsis represents a major global health burden. Early diagnosis of sepsis as well as guiding early therapeutic decisions in septic patients still represent major clinical challenges. In this context, a whole plethora of different clinical and serum-based markers have been tested regarding their potential for early detection of sepsis and their ability to stratify patients according to their probability to survive critical illness and sepsis. Adipokines represent a fast-growing class of proteins that have gained an increasing interest with respect to their potential to modulate immune responses in inflammatory and infectious diseases. We review current knowledge on the role of different adipokines in diagnostic work-up and risk stratification of sepsis as well as critical illness. We discuss recent data from animal models as well as from clinical studies and finally highlight the limitations of these analyses that currently prevent the use of adipokines as biomarkers in daily practice.


Assuntos
Adipocinas/sangue , Biomarcadores , Estado Terminal , Sepse/sangue , Animais , Estudos de Casos e Controles , Diagnóstico Precoce , Humanos , Prognóstico , Sepse/diagnóstico
13.
Tissue Cell ; 60: 33-37, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31582016

RESUMO

Cell-based therapy provides a promising approach for the treatment of sepsis and related disorders. Fate determination of transplanted cells is the most essential issue for cell therapist. Optical imaging is the reliable, time and cost-effective system for cell tracking. The present study was aimed to apply an optical imaging system for monitoring of GFP-labeled unrestricted somatic stem cells in the sepsis animal model. In vivo imaging showed the most accumulation of intravenously injected cells into the lungs and liver of septic mice. Thereafter, the imaging data were more approved by flow cytometry and immunohistochemistry staining. Cellular localization in septic lungs and liver that observed by optical imaging technique may offer beneficial evidence for designing of sepsis clinical trials.


Assuntos
Células-Tronco Adultas , Proteínas de Fluorescência Verde , Sepse/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Genes Reporter , Microscopia Intravital , Camundongos , Camundongos Endogâmicos C57BL , Sepse/sangue , Sepse/terapia , Transplante de Células-Tronco
14.
Dis Markers ; 2019: 1089107, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583025

RESUMO

The focus of sepsis has shifted from inflammation to organ dysfunction on the basis of a recent definition based on the sequential organ failure score (SOFA). A diagnostic and prognostic marker is necessary under this definition but is currently unknown. We enrolled 80 sepsis patients consecutively admitted to an intensive care unit through the emergency department and 80 healthy control patients who received routine health check-ups from August 2018 to January 2019. SEPSIS-3 criteria were used for the diagnosis of patients based on SOFA score ≥ 2 from the baseline along with evidence of infection. Concentrations of 28 cytokines, eight chemokines, and nine growth factors were measured on the day of diagnosis. Hierarchical cluster analysis was performed for molecules. The majority of infections were pneumonia (45% of patients) and urinary tract infections (40% of patients). Most of the measured molecules were increased in patients with sepsis. Area under receiver operating characteristic curve (AUROC) values were found to be as follows: hepatic growth factor (HGF), 0.899; interleukin-1 receptor antagonist (IL-1RA), 0.893; C-C motif ligand 5 (CCL5) 5, 0.887; C-X-C motif chemokine 10 (CXCL10), 0.851; CCL2, 0.840; and IL-6, 0.830. IL-1RA, IL-6, IL-8, IL-15, and CCL11 concentrations correlated with SOFA score with statistical significance. Prognosis multivariate analysis revealed an odds ratio of 0.968 for epidermal growth factor (EGF). Three clusters were formed, of which Clusters 2 and 3 were associated with nonsurvivors. Diagnosis of sepsis was performed using cytokines, chemokines, and growth factors. HGF revealed the highest diagnostic capability, and EGF predicted favorable prognosis among the tested molecules.


Assuntos
Citocinas/sangue , Fator de Crescimento de Hepatócito/sangue , Pneumonia/diagnóstico , Sepse/diagnóstico , Infecções Urinárias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Estudos de Casos e Controles , Fator de Crescimento Epidérmico/sangue , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Razão de Chances , Escores de Disfunção Orgânica , Pneumonia/sangue , Pneumonia/mortalidade , Pneumonia/patologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Sepse/sangue , Sepse/mortalidade , Sepse/patologia , Análise de Sobrevida , Infecções Urinárias/sangue , Infecções Urinárias/mortalidade , Infecções Urinárias/patologia
15.
Adv Clin Exp Med ; 28(11): 1561-1567, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31596557

RESUMO

Fibronectin (FN) is a widely distributed glycoprotein which is present in different bodily fluids, on the surface of cells and in the extracellular matrix (ECM). It plays roles in various processes, including cell adhesion, migration, growth, proliferation, and tissue repair. Fibronectin exists in 2 forms: a soluble, inactive molecule, called plasma FN (pFN), which is synthesized by hepatocytes in the liver, and an insoluble cellular form (cFN), which is produced locally by different types of cells and is a key component of the ECM. Fibrinogen fibrils ensure structural support for cell adhesion and promote cell migration, proliferation and apoptosis. Additionally, FN controls the availability of growth factors. The plasma form of FN is a crucial component of the fibrin clot in the early wound-healing response, while the cellular form of FN supports efficient platelet adhesion, activation, aggregation, and procoagulant activity. Alternative splicing of the FN gene results in the generation of protein variants which contain the additional isoforms - extra domain A of FN (EDA) and extra domain A of FN (EDB); these are associated with, e.g., tissue remodeling, fibroblast differentiation, inflammation, and tumor progression. Fibronectin also serves as a target for a large number of bacterial proteins, and as part of a 3-component bridge (FN, integrin and FN-binding proteins - FnBPs) it contributes to bacterial colonization of endothelial and epithelial cells. Fibronectin has been identified in sepsis in humans as a negative acute-phase protein, and a low level of FN seems to be a marker of a poor prognosis for a patient. Here, the role of FN in inflammatory processes and sepsis is presented.


Assuntos
Fibronectinas/sangue , Sepse/diagnóstico , Biomarcadores/sangue , Humanos , Inflamação/sangue , Inflamação/imunologia , Isoformas de Proteínas , Sepse/sangue
16.
Nat Commun ; 10(1): 4116, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511522

RESUMO

Damage-associated molecular patterns (DAMPs) are molecules that can be actively or passively released by injured tissues and that activate the immune system. Here we show that nicotinate phosphoribosyltransferase (NAPRT), detected by antibody-mediated assays and mass spectrometry, is an extracellular ligand for Toll-like receptor 4 (TLR4) and a critical mediator of inflammation, acting as a DAMP. Exposure of human and mouse macrophages to NAPRT activates the inflammasome and NF-κB for secretion of inflammatory cytokines. Furthermore, NAPRT enhances monocyte differentiation into macrophages by inducing macrophage colony-stimulating factor. These NAPRT-induced effects are independent of NAD-biosynthetic activity, but rely on NAPRT binding to TLR4. In line with our finding that NAPRT mediates endotoxin tolerance in vitro and in vivo, sera from patients with sepsis contain the highest levels of NAPRT, compared to patients with other chronic inflammatory conditions. Together, these data identify NAPRT as a endogenous ligand for TLR4 and a mediator of inflammation.


Assuntos
Espaço Extracelular/metabolismo , Inflamação/enzimologia , Pentosiltransferases/metabolismo , Receptor 4 Toll-Like/metabolismo , Diferenciação Celular , Líquido Extracelular/enzimologia , Humanos , Inflamação/genética , Inflamação/patologia , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/metabolismo , Monócitos/citologia , Células Mieloides/metabolismo , Nicotinamida Fosforribosiltransferase/química , Nicotinamida Fosforribosiltransferase/metabolismo , Pentosiltransferases/sangue , Pentosiltransferases/química , Ligação Proteica , Fatores de Risco , Sepse/sangue , Sepse/enzimologia
17.
Scand J Immunol ; 90(6): e12823, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31489646

RESUMO

Sepsis is associated with significant mortality. Early diagnosis and prognosis of patients with sepsis is still a difficult clinical challenge. In this study, the ability of plasma PTX3 (pentraxin 3), MCP1 (monocyte chemoattractant protein 1) and Ang (angiopoietin)1/2 was investigated to evaluate the severity of sepsis. Blood samples were obtained from 43 patients with sepsis. A total of 33 post-surgery patients with infections and 25 healthy individuals served as controls. The results showed that plasma PTX3, MCP1 and Ang2 significantly increased in patients on the first day of septic shock onset, while sepsis patients had significantly higher Ang2 level, compared with controls. Furthermore, PTX3, MCP1 and Ang2 had high AUROC values in patients with septic shock on the first day of sepsis onset. The findings suggest that PTX3, MCP1 and Ang2 maybe early predictors to evaluate the severity of sepsis and septic shock with the latest Sepsis 3.0 definitions.


Assuntos
Angiopoietina-2/sangue , Proteína C-Reativa , Quimiocina CCL2/sangue , Sepse/sangue , Sepse/diagnóstico , Componente Amiloide P Sérico , Choque Séptico/sangue , Choque Séptico/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estudos de Casos e Controles , Humanos , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Sepse/terapia , Índice de Gravidade de Doença , Choque Séptico/terapia
18.
BMC Infect Dis ; 19(1): 780, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492102

RESUMO

BACKGROUND: Sepsis is still a common critical disease with high morbidity and mortality in intensive care unit. Despite published guidelines for sepsis, development of antibiotic therapy and advanced organ support technologies, the mortality of sepsis patients is still 25% or more. It is necessary to distinguish the subtypes of sepsis, and the targeted therapy for the patients need to be explored. Platelets have various biological functions in hemostasis and thrombosis, host defense, inflammatory/immune responses and tissue repair/regeneration. Moreover, severe thrombocytopenia or sustained thrombocytopenia was closely associated with multiply organ dysfunction and higher mortality in sepsis patients. The clinical therapies for thrombocytopenia are platelet transfusion and platelet-elevating drugs. However, platelet transfusion has many defects in clinical practice in sepsis patients, and the impact of platelet-elevating drugs for sepsis patients is still unclear. RESCUE trial is aim to explore the effect of a platelet-elevating drug, recombinant human thrombopoietin (rhTPO), as an effective rescue therapy on sepsis patients with acute severe thrombocytopenia. METHODS: It is a randomized, open-label, multi-center, controlled trial in 5 tertiary academic hospitals including medical, surgical or general ICUs. In this study, a total of 200 sepsis patients with severe thrombocytopenia will be randomly assigned in a 1:1 ratio to the control and rhTPO group. The patients will be followed up to 28 days after randomization. All patients in two groups receive the same treatment based on the guideline of Surviving Sepsis Campaign. Primary outcome is 28-day mortality. Secondary outcomes are the changes of PCs, blood transfusion, biomarkers of infection and organ function, days free from advanced organ support, drug-related adverse events, the length of ICU and hospital stay. DISCUSSION: RESCUE trial is the first randomized controlled trial to explore the impact of rhTPO for severe thrombocytopenia in sepsis patients diagnosed by sepsis-3.0 standard. Furthermore, RESCUE trial results will be of significant clinical value on the targeted therapy and add clinical evidence that rhTPO is an effective rescue therapy for these sepsis patients. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02707497. Registered Date: March 3rd, 2016. Protocol Version 3. Protocol Date: January 25th, 2019.


Assuntos
Sepse/complicações , Sepse/tratamento farmacológico , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológico , Trombopoetina/uso terapêutico , Doença Aguda , Adulto , Idoso , Transfusão de Sangue/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Contagem de Plaquetas , Proteínas Recombinantes/uso terapêutico , Terapia de Salvação , Sepse/sangue , Sepse/mortalidade , Índice de Gravidade de Doença , Trombocitopenia/sangue , Trombocitopenia/mortalidade , Resultado do Tratamento , Adulto Jovem
19.
BMC Res Notes ; 12(1): 560, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488211

RESUMO

OBJECTIVE: Our immediate objective is to determine whether infectivity of lytic podophage T3 has a relatively high persistence in the blood of a mouse, as suggested by previous data. Secondarily, we determine whether the T3 surface has changed during this mouse passage. The surface is characterized by native agarose gel electrophoresis (AGE). Beyond our current data, the long-term objective is optimization of phages chosen for therapy of all bacteremias and associated sepsis. RESULTS: We find that the persistence of T3 in mouse blood is higher by over an order of magnitude than the previously reported persistence of (1) lysogenic phages lambda and P22, and (2) lytic phage T7, a T3 relative. We explain these differences via the lysogenic character of lambda and P22, and the physical properties of T7. For the future, we propose testing a new, AGE-based strategy for rapidly screening for high-persistence, lytic, environmental podophages that have phage therapy-promoting physical properties.


Assuntos
Bacteriemia/terapia , Bacteriófago T3/fisiologia , Terapia por Fagos/métodos , Sepse/terapia , Animais , Bacteriemia/sangue , Bacteriólise , Bacteriófago T7/fisiologia , Feminino , Camundongos Endogâmicos C57BL , Sepse/sangue
20.
Crit Care ; 23(1): 267, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370866

RESUMO

BACKGROUND: Data that indicate vitamin A status in critically ill children with sepsis are sparse. The association between serum vitamin A levels and the clinical outcomes of sepsis has not been well assessed. The aim of this study was to assess the prevalence of vitamin A deficiency in critically ill children with sepsis and its association with clinical outcomes. METHODS: Critically ill children with sepsis admitted to the pediatric intensive care unit were engaged in this prospective study. Sex- and age-matched approximate-health children from the Department of Pediatric Surgery were enrolled as the control group. Blood samples were collected from all patients in the first 24 h of admission for the measurement of serum vitamin A status. We compared vitamin A status between the sepsis group and the control group. In addition, we compared the clinical characteristics of the two subgroups of septic patients with vitamin A deficiency and those without vitamin A deficiency. Univariate and multivariable methods were used to evaluate the association between vitamin A deficiency and septic shock. RESULTS: One hundred sixty septic children and 49 approximate-health children were enrolled in this study. Vitamin A deficiency was found in 94 (58.8%) subjects in the study group and 6 (12.2%) subjects in the control group (P < 0.001). In septic patients, 28-day mortality and hospital mortality in patients with vitamin A deficiency were not significantly higher than that in patients without vitamin A deficiency (P > 0.05). However, vitamin A levels were inversely associated with higher PRISM scores in septic children with VAD (r = - 0.260, P = 0.012). Vitamin A deficiency was associated with septic shock with an unadjusted odds ratio (OR) of 3.297 (95% confidence interval (CI), 1.169 to 9.300; P = 0.024). In a logistic model, vitamin A deficiency (OR, 4.630; 95% CI, 1.027-20.866; P = 0.046), procalcitonin (OR, 1.029; 95% CI, 1.009-1.048; P = 0.003), and the Pediatric Risk of Mortality scores (OR, 1.132; 95% CI, 1.009-1.228; P = 0.003) were independently associated with septic shock. CONCLUSION: The prevalence of vitamin A deficiency was high in children with sepsis. Vitamin A deficiency may be a marker of mortality in critically ill children with sepsis. TRIAL REGISTRATION: Clinicaltrials.gov , NCT03598127.


Assuntos
Sepse/complicações , Deficiência de Vitamina A/fisiopatologia , Vitamina A/análise , Adolescente , Biomarcadores/análise , Biomarcadores/sangue , Criança , Pré-Escolar , China/epidemiologia , Estado Terminal/epidemiologia , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Sepse/sangue , Sepse/fisiopatologia , Vitamina A/sangue
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