scholarly journals Different Profiles of Cytokines, Chemokines and Coagulation Mediators Associated with Severity in Brazilian Patients Infected with Dengue Virus

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1789
Author(s):  
Victor Edgar Fiestas Solórzano ◽  
Nieli Rodrigues da Costa Faria ◽  
Caroline Fernandes dos Santos ◽  
Gladys Corrêa ◽  
Márcio da Costa Cipitelli ◽  
...  

The incidence of dengue in Latin America has increased dramatically during the last decade. Understanding the pathogenic mechanisms in dengue is crucial for the identification of biomarkers for the triage of patients. We aimed to characterize the profile of cytokines (IFN-γ, TNF-α, IL-1β, IL-6, IL-18 and IL-10), chemokines (CXCL8/IL-8, CCL2/MCP-1 and CXCL10/IP-10) and coagulation mediators (Fibrinogen, D-dimer, Tissue factor-TF, Tissue factor pathway inhibitor-TFPI and Thrombomodulin) during the dengue-4 epidemic in Brazil. Laboratory-confirmed dengue cases had higher levels of TNF-α (p < 0.001), IL-6 (p = 0.005), IL-10 (p < 0.001), IL-18 (p = 0.001), CXCL8/IL-8 (p < 0.001), CCL2/MCP-1 (p < 0.001), CXCL10/IP-10 (p = 0.001), fibrinogen (p = 0.037), D-dimer (p = 0.01) and TFPI (p = 0.042) and lower levels of TF (p = 0.042) compared to healthy controls. A principal component analysis (PCA) distinguished between two profiles of mediators of inflammation and coagulation: protective (TNF-α, IL-1β and CXCL8/IL-8) and pathological (IL-6, TF and TFPI). Lastly, multivariate logistic regression analysis identified high aspartate aminotransferase-to-platelet ratio index (APRI) as independent risk factors associated with severity (adjusted OR: 1.33; 95% CI 1.03–1.71; p = 0.027), the area under the receiver operating characteristics curve (AUC) was 0.775 (95% CI 0.681–0.869) and an optimal cutoff value was 1.4 (sensitivity: 76%; specificity: 79%), so it could be a useful marker for the triage of patients attending primary care centers.

2021 ◽  

Objectives: Postreperfusion significant arrhythmias (PRSA), which is known as part of the diagnostic criteria for postreperfusion syndrome, may serve as a precursor of postreperfusion cardiac arrest (PRCA). Considering the possible relationship between the use of liver grafts with high effluent potassium (eK+) concentrations and PRCA, we aimed to investigate the role of eK+ in PRSA development in deceased liver transplantation (LT). Methods: Using the prospectively collected data from a prior observational study, a retrospective study of 91 adult LT recipients with eK+ measurements between November 2016 and December 2018 was conducted to determine the incidence, predictors, and outcomes of PRSA. Results: PRSA occurred in 46 cases (50.5%), and PRCA occurred in 8 patients (8.8%). Multivariable analysis demonstrated elevated eK+ concentration before reperfusion (odds ratio [OR], 1.425; 95% confidence interval [CI] 1.134–1.790; P = 0.002), and higher serum potassium level at one minute following reperfusion (sK+1) (OR, 3.244; 95% CI 1.668–6.380; P = 0.001) as independent risk factors for PRSA. An eK+ ≥6.9 mmoL/L could predict PRSA with a sensitivity of 71.7% and a specificity of 80.0% (area under the receiver-operating characteristics curve [AUROC], 0.828). In comparison, an sK+1 ≥5.5 mmoL/L could predict PRSA with a sensitivity of 87.0% and a specificity of 64.4% (AUROC, 0.810). PRSA was associated with increased risks of PRCA, postreperfusion vasoplegia, and postoperative early allograft dysfunction. Conclusions: This study has demonstrated that eK+ has the potential to predict PRSA in deceased LT. These findings need confirmation in further studies.


2001 ◽  
Vol 86 (12) ◽  
pp. 1573-1577 ◽  
Author(s):  
Perenlei Enkhbaatar ◽  
Mitsuhiro Uchiba ◽  
Hirotaka Isobe ◽  
Hiroaki Okabe ◽  
Kenji Okajima

SummaryExcessive production of nitric oxide (NO) by the inducible form of NO synthase (iNOS) plays a key role in the development of endotoxin shock. Tumor necrosis factor-α (TNF-α) induces iNOS, thereby contributing to the development of shock. We recently reported that recombinant tissue factor pathway inhibitor (r-TFPI), an important inhibitor of the extrinsic pathway of the coagulation system, inhibits TNF-α production by monocytes. In this study, we investigated whether r-TFPI could ameliorate hypotension by inhibiting excessive production of NO in rats given lipopolysaccharide (LPS). Pretreatment of animals with r-TFPI prevented LPS-induced hypotension. Recombinant TFPI significantly inhibited the increases in both the plasma levels of NO2 -/NO3 - and lung iNOS activity 3 h after LPS administration. Expression of iNOS mRNA in the lung was also inhibited by intravenous administration of r-TFPI. However, neither DX-9065a, a selective inhibitor of factor Xa, nor an inactive derivative of factor VIIa (DEGR-F.VIIa) that selectively inhibits factor VIIa activity, had any effect on LPS-induced hypotension despite their potent anticoagulant effects. Moreover, neither the plasma levels of NO2 -/NO3 - nor lung iNOS activity were affected by administration of DX-9065a and DEGR-F.VIIa. These results suggested that r-TFPI ameliorates LPS-induced hypotension by reducing excessive production of NO in rats given LPS and this effect was not attributable to its anticoagulant effects, but to the inhibition of TNF-α production.


2021 ◽  
Author(s):  
Ming Li ◽  
Haifeng Sun ◽  
Suochun Xu ◽  
Yang Yan ◽  
Haichen Wang ◽  
...  

Abstract Background: The aim of this study was to analyze the predictive value of biomarkers related to preoperative inflammatory and coagulation in the prognosis of patients with type A acute aortic dissection (AAD). Methods: A total of 206 patients with type A AAD who had received surgical treatment were enrolled. Patients were divided into two groups according to whether they died during hospitalization. Peripheral blood samples were collected before anesthesia induction. Preoperative levels of D-dimer, fibrinogen (FIB), platelet (PLT), white blood cells (WBC) and neutrophil (NEU) between the two groups were compared. Univariate and multivariate logistic regression analysis were utilized to identify the independent risk factors for postoperative in-hospital deaths of patients with type A AAD. Receiver operating characteristic (ROC) curve were used to analyze the predictive value of D-dimer, FIB, PLT, WBC, NEU and CRP in the prognosis of the patients. Results: Univariate logistic regression analysis showed that the P values of the five parameters including D-dimer, FIB, PLT, WBC and NEU were all less than 0.1, which may be risk factors for postoperative in-hospital deaths of patients with type A AAD. Further multivariate logistic regression analysis indicated that higher preoperative D-dimer and WBC levels were independent risk factors for in-hospital deaths of patients with type A AAD. ROC curve analysis indicated that FIB+PLT combination is provided with the highest predictive value for in-hospital deaths.Conclusion: Both preoperative D-dimer and WBC in patients with type A AAD may be used as independent risk factors for the prognosis of such patients. Combined use of FIB and PLT may improve the accuracy and accessibility of clinical prognostic assessment.


Author(s):  
Yumeng Yao ◽  
Jiatian Cao ◽  
Qingqing Wang ◽  
Kai Liu ◽  
Zhe Luo ◽  
...  

Abstract Background: Over 240000 cases of coronavirus disease-19 (COVID-19) has been reported since Dec. 2019. We aim to assess the use of D-dimer as a biomarker for disease severity and clinical outcome in COVID-19 patients.Methods: We retrospectively analyzed the clinical, laboratory, and radiological characteristics of 248 consecutive cases of COVID-19 in Renmin Hospital of Wuhan University, Wuhan, China from Jan 28 to Mar 08, 2020. Correlations of D-dimer upon admission with clinical staging, radiological staging, and in-hospital mortality were analyzed. Receiver operating characteristics curve was used to determine the optimal cutoff level for D-dimer that discriminated those survivors versus non-survivors during hospitalization. Results: D-dimer elevation (≥0.50mg/L) was seen in 74.6% (185/248) of the patients. Pulmonary embolism and deep vein thrombosis were ruled out in patients with high probability of thrombosis. D-dimer levels significantly increased with increasing severity of COVID-19 as determined by clinical staging (Kendall's tau_b = 0.374, P=0.000) and chest CT staging (Kendall's tau_b = 0.378, P=0.000). In-hospital mortality rate was 6.9%. Median D-dimer level in non-survivors (n=17) was significantly higher than in survivors (n=231) [6.21 (3.79-16.01) mg/L versus 1.02 (0.47-2.66) mg/L, P=0.000]. D-dimer level of >2.14 mg/L predicted in-hospital mortality with a sensitivity of 88.2% and specificity of 71.3% (AUC 0.85; 95% CI=0.77-0.92).Conclusions: D-dimer is commonly elevated in patients with COVID-19. D-dimer levels correlate with disease severity and is a reliable prognostic marker for in-hospital mortality in patients admitted for COVID-19.


2016 ◽  
Vol 44 (6) ◽  
pp. 1483-1491 ◽  
Author(s):  
Xingrui Xie ◽  
Li Chen ◽  
Jinsheng Zeng ◽  
Chao Qin ◽  
Daobin Cheng ◽  
...  

Objective To identify the unique clinical features and biological markers of lung cancer-associated stroke. Methods We recruited 102 patients with lung cancer plus stroke, 102 with lung cancer, and 102 with stroke. Detailed information was analysed and compared among groups. Results The groups were age-matched. Patients with lung cancer plus stroke showed multiple lesions involving multiple cerebral artery territories on magnetic resonance imaging, compared with stroke-alone patients. These patients also had a poorer modified Rankin Scale score at 30 days, and high mortality (18.6%). Patients with lung cancer plus stroke had a higher incidence of metastasis, and higher blood levels of D-dimer, CA125 and CA199 compared with patients with lung cancer alone. Multivariate logistic regression analysis showed that levels of D-dimer, CA125 and CA199 were independently related to lung cancer-associated stroke. Conclusion Elevated plasma D-dimer, CA125 and CA199 may be independent risk factors for and biomarkers of lung cancer-associated stroke.


2012 ◽  
Vol 302 (11) ◽  
pp. H2352-H2362 ◽  
Author(s):  
Yoshihiro Higuchi ◽  
Toru Kubota ◽  
Masamichi Koyanagi ◽  
Toyoki Maeda ◽  
Arthur M. Feldman ◽  
...  

Heart failure (HF) has been recognized as a hypercoagulable state. However, the natural anticoagulation systems in the failing heart have not been studied. Recent experimental and clinical data have indicated that not only the thrombomodulin (TM)/protein C (PC) pathway but also the protein S (PS)/tissue factor pathway inhibitor (TFPI) system function as potent natural anticoagulants. To investigate the balance between procoagulant and anticoagulant activities in the failing heart, we measured the cardiac expression of tissue factor (TF), type 1 plasminogen activator inhibitor (PAI-1), TM, PC, PS, and TFPI by RT-PCR and/or Western blot analysis in male transgenic (TG) mice with heart-specific overexpression of TNF-α. Both procoagulant (TF and PAI-1) and anticoagulant (PS and TFPI) factors were upregulated in the myocardium of 24-wk-old TG (end-stage HF) but not in that of 4-wk-old TG (early decompensated HF) compared with the wild-type mice. Both factors were also upregulated in the infarcted myocardium at 3 days after coronary ligation in the wild-type mice. The expression of TM was downregulated in the TG heart, and PC was not detected in the hearts. The transcript levels of PS orphan receptors, Mer and Tyro3, but not Axl, were significantly upregulated in the TG heart. Double immunohistochemical staining revealed that myocardial infiltrating CD3-positive T cells may produce PS in the TG myocardium. In conclusion, the PS/TFPI was upregulated in the myocardium of a different etiological model of HF, thus suggesting a role for the PS/TFPI system in the protection of the failing heart under both inflammatory and hypercoagulable states.


2021 ◽  
Author(s):  
Qiuyue Feng ◽  
Jingjing Hao ◽  
Ang Li ◽  
Zhaohui Tong

Abstract Background: This study was to create nomogram models for precise prediction of mortality risk of NHIV-PJP and HIV-PJP cases.Methods: A retrospective study was performed over a 10-year period to evaluate the clinical characteristics and outcomes of NHIV-PJP at Beijing Chaoyang Hospital and HIV-PJP at Beijing Ditan Hospital in China from 2010 to 2019. Univariate and multivariate logistic regression analysis were used to screen out mortality risk factors for creating nomograms. Nomogram models were evaluated by using a bootstrapped concordance index, calibration plots and receiver operating characteristics (ROCs) curve.Results: A total of 167 NHIV-PJP cases and 193 HIV-PJP cases were included in the study. Pneumothorax, febrile days after admission, CD4+ T cells≤100cells/ul and sulfa combine CAS treatment were identified as independent risk factors that could be combined for accurate prediction of mortality result in NHIV-PJP group. We created a nomogram for mortality risk by using these variables. The area under the curve was 0.865 (95% confidence interval 0.799-0.931). The nomogram had a C-index of 0.865 and was well calibrated. Independent risk factors contained in the nomogram in HIV-PJP group included pneumothorax, PLT≤80×109/L, HGB≤90g/L, ALB, CMV co-infection and sulfa combine CAS treatment. The nomogram showed good discrimination, with a C-index of 0.904 and good calibration. The area under the curve was 0.910 (95% confidence interval 0.850-0.970). Conclusions: Our nomograms were useful tools for evaluating the poor prognosis in both NHIV-PJP and HIV-PJP cases.


2010 ◽  
Vol 104 (08) ◽  
pp. 207-212 ◽  
Author(s):  
Pamela Lutsey ◽  
Aaron Folsom ◽  
Susan Heckbert ◽  
Mary Cushman ◽  
Neil Zakai

SummaryTissue factor pathway inhibitor (TFPI) inhibits tissue factor, a potent coagulation initiator. Limited evidence suggests that low TFPI levels are associated with increased risk of venous thromboembolism (VTE). We measured total TFPI in a nested case-control study in the Longitudinal Investigation of Thromboembolism Etiology. Control subjects were frequency matched 2:1 to cases on age, sex, race, and cohort. Odds ratios (ORs) for VTE by TFPI levels were computed using logistic regression models adjusting for age, race, sex, coagulation factors (factors VII, VIII, IX, XI, D-dimer), and body mass index (BMI). To evaluate for greater than additive interactions, we calculated the percent relative excess risk due to interaction between TFPI and other VTE risk factors. A total of 534 cases of VTE occurred and matched to 1,091 controls. Mean baseline TFPI in ng/ml (standard deviation) in those who developed VTE and controls was 36.4 (12.8) and 35.0 (11.1), respectively. Higher TFPI was associated with male sex, age, BMI, factors VII, VIII, IX, XI, and D-dimer. TFPI level did not differ by ethnicity, factor V Leiden, or pro-thrombin G20210A. Compared with those in the upper 95%, the bottom 5% of TFPI had an age-, sex-, race-, and study-adjusted OR (95% CI) of 1.35 (0.86, 2.12) for VTE. Adjusting for factors VII, VIII, IX, and XI the OR was 1.93 (1.05, 3.53). Further addition of D-dimer and BMI to this model decreased the OR to 1.70 (0.98, 2.93). Low TFPI did not demonstrate greater than additive interaction with other VTE risk factors.


2019 ◽  
Vol 24 (3) ◽  
pp. 275-285
Author(s):  
Sara H. Bollens ◽  
Robert A. Fox

A first-line screening instrument, the Preschool Inventory of Trauma Symptoms (PITS), was developed to assess trauma symptoms with a diverse sample of 150 toddlers and preschoolers ( M = 2.49 years; SD = 1.12). Items reflected the current trauma literature, assessment measures, and diagnostic criteria for very young children. A principal component analysis produced a 34-item, four-factor model: Arousal and Hyper-Reactivity, Fearful Attachment, Intrusion and Re-Experiencing, and Avoidance and Negative Cognition and Mood. One validity scale, Response Style, was also developed. All scales significantly correlated ( r = .45 to .81; p < .01) with preestablished trauma measures and demonstrated adequate internal consistency (α = .68 − .87). A receiver operating characteristics curve analysis identified a cut-score with good discrimination ability (.88), sensitivity (.81), and specificity (.81). In a preliminary pilot study, PITS also was found to be sensitive to trauma symptom change following participation in an evidence-based trauma informed treatment program. A copy of the PITS is included in the Appendix for free use by qualified professionals.


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