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Patients undergoing major surgery are often at risk of developing postoperative complications. We investigated whether a preoperative marker of chronic inflammation, soluble urokinase plasminogen activator receptor, can aid in identifying patients at high risk for postoperative complications, morbidity, and mortality. In this prospective observational study (ClinicalTrials.gov identifier: NCT03851965), EDTA blood was collected from consecutive adult White patients scheduled for major noncardiac surgery with expected duration ≥2 hours under general anesthesia. Inclusion criteria were age ≥18 years and American Society of Anesthesiologists physical status I to IV. Plasma soluble urokinase plasminogen activator receptor levels were determined using the suPARnostic quick triage lateral flow assay. The primary endpoint was postoperative complications defined as presence of any complication and/or admission to intensive care unit and/or mortality within the first 90 postoperative days. Preoperative soluble urokinase plasminogen activator receptor had an odds ratio of 1.50 (95% confidence interval: 1.24–1.82) for every ng/mL increase. When including age, sex, American Society of Anesthesiologists score, C-reactive protein, and grouped soluble urokinase plasminogen activator receptor in multivariate analysis, patients with soluble urokinase plasminogen activator receptor between 5.5 and 10 ng/mL had an odds ratio of 11.2 (confidence interval: 3.1–40.8) and patients with soluble urokinase plasminogen activator receptor >10 ng/mL had an odds ratio of 19.9 (95% confidence interval: 4.3–92.9) compared to patients with soluble urokinase plasminogen activator receptor ≤5.5 ng/mL, respectively. Receiver operating characteristic analysis of soluble urokinase plasminogen activator receptor showed an area under the curve of 0.82 (confidence interval: 0.72–0.91). Receiver operating characteristic analysis combining age, sex, C-reactive protein levels, and American Society of Anesthesiologists score and had an area under the curve of 0.71 (95% confidence interval: 0.61–0.82). Adding soluble urokinase plasminogen activator receptor to this model increased the area under the curve to 0.83 (95% confidence interval: 0.74–0.92) (P =.033). Preoperative soluble urokinase plasminogen activator receptor provided strong and independent predictive value on postoperative complications in White patients undergoing major noncardiac surgery. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: IP-10 has potential as a diagnostic marker for infection with Mycobacterium tuberculosis, with comparable accuracy to QuantiFERON-TB Gold In-Tube test (QFT-IT). The aims were to assess the sensitivity and specificity of IP-10, and to evaluate the impact of co-morbidity on IP-10 and QFT-IT. 168 cases with active TB, 101 healthy controls and 175 non-TB patients were included. IP-10 and IFN-γ were measured in plasma of QFT-IT stimulated whole blood and analyzed using previously determined algorithms. A subgroup of 48 patients and 70 healthy controls was tested in parallel with T-SPOT.TB IP-10 and QFT-IT had comparable accuracy. Sensitivity was 81% and 84% with a specificity of 97% and 100%, respectively. Combining IP-10 and QFT-IT improved sensitivity to 87% (p < 0.0005), with a specificity of 97%. T-SPOT.TB was more sensitive than QFT-IT, but not IP-10. Among non-TB patients IP-10 had a higher rate of positive responders (35% vs 27%, p < 0.02) and for both tests a positive response was associated with relevant risk factors. IFN-γ but not IP-10 responses to mitogen stimulation were reduced in patients with TB and non-TB infection. This study confirms and validates previous findings and adds substance to IP-10 as a novel diagnostic marker for infection with M. tuberculosis. IP-10 appeared less influenced by infections other than TB; further studies are needed to test the clinical impact of these findings. [ABSTRACT FROM AUTHOR]

Summary: Objective: We have recently shown that the level of soluble urokinase plasminogen activator receptor (suPAR), which is associated with the immune status of HIV-infected patients undergoing highly active antiretroviral therapy (HAART), correlates with the insulin action of such patients. Here we extend these findings by investigating the association of suPAR to glucose metabolic insufficiency during an oral glucose challenge (OGTT). Methods: In 16 HIV-infected patients with lipodystrophy and 15 HIV-infected patients without lipodystrophy, glucose tolerance, insulin sensitivity (ISIcomposite), prehepatic insulin secretion, proinsulin level and suppression of free fatty acids (FFA) were determined during an OGTT. Stability of suPAR was tested in 6 HIV-infected patients during a 3h OGTT. Results: Lipodystrophy was associated with a 70% increase in plasma suPAR (P <0.05). During the OGTT, plasma suPAR correlated inversely with ISIcomposite and positively with 2h plasma glucose, fasting insulin secretion, fasting intact proinsulin and FFA level during the OGTT (all P <0.05). In multiple regression analyses, in which anthropometric measures (BMI, limbadiposity and fat mass), immune markers (CD4, HIV-RNA, duration of HIV infection), and dyslipidemia (plasma total cholesterol, triglyceride and free fatty acid level during the OGTT) were included, suPAR remained a significant marker of glucose tolerance and insulin sensitivity. Plasma suPAR exhibited a small CV (11%) during the 3h OGTT. Conclusions: suPAR associated to important glucose metabolic aberrations in HIV-infected patients on HAART. Moreover, suPAR was stable after a glucose challenge. Future research is required to confirm these findings and explore the potential of suPAR as marker of dysmetabolism in HIV-infected patients. [Copyright &y& Elsevier]

Background & Aims: Recently, full viral life cycle hepatitis C virus (HCV) cell culture systems were developed for strain JFH1 (genotype 2a) and an intragenotypic 2a/2a genome (J6/JFH). We aimed at exploiting the unique JFH1 replication characteristics to develop culture systems for genotype 3a, which has a high prevalence worldwide. Methods: Huh7.5 cells were transfected with RNA transcripts of an intergenotypic 3a/JFH1 recombinant with core, E1, E2, p7, and NS2 of the 3a reference strain S52, and released viruses were passaged. Cultures were examined for HCV core and/or NS5A expression (immunostaining), HCV RNA titers (real-time PCR), and infectivity titers (50% tissue culture infectious dose). The role of mutations identified by sequencing of recovered S52/JFH1 viruses was analyzed by reverse genetics studies. Results: S52/JFH1 and J6/JFH viruses passaged in Huh7.5 cells showed comparable growth kinetics and similar peak HCV RNA and infectivity titers. However, analysis of S52/JFH1 viruses identified 9 putative adaptive mutations in core, E2, p7, NS3, and NS5A. All 7 S52/JFH1 recombinants with an amino acid change in p7 combined with a change in NS3 or NS5A, but only 2 of 9 recombinants with individual mutations (in p7 and NS3, respectively) were fully viable without the requirement for additional mutations. The biological relevance of our system was shown by studying dependence of 3a/JFH1 infection on CD81, and its impact on distribution of intracellular lipids. Conclusions: We developed a robust intergenotypic recombinant cell culture system for HCV genotype 3a, providing a valuable tool for studies of 3a core-NS2 and related therapeutics. [Copyright &y& Elsevier]

• SuPAR was a strong prognostic biomarker of non-cardiac mortality after STEMI. • The suPAR level was independent of sampling time < 12 h after revascularization. • SuPAR may identify patients in risk of non-cardiac mortality prior to discharge. Identification of patients at high risk of non-cardiac mortality following ST-segment elevation myocardial infarction (STEMI) could guide clinicians to identify patients who require attention due to serious non-cardiac conditions after the acute phase of STEMI. The purpose of this study was to evaluate if the non-specific and prognostic biomarker of inflammation and comorbidity, soluble urokinase receptor (suPAR), could predict non-cardiac mortality in a cohort of STEMI patients. SuPAR was measured in 1,190 STEMI patients who underwent primary percutaneous coronary intervention (pPCI). The primary endpoint was non-cardiac mortality, secondary endpoints were cardiac mortality, all-cause mortality, reinfarction and periprocedural acute kidney injury. Backwards elimination of potential confounders significantly associated with the respective outcome was used to adjust associations. Patients were followed for a median of 3.0 years (interquartile range 2.5– 3.6 years). Multivariate cox regression revealed that a plasma suPAR level above 3.70 ng mL−1 was associated with non-cardiac and cardiac mortality at hazard ratios 3.33 (95% confidence interval 1.67–6.63, p = 0.001, adjusted for age) and 0.99 (0.18–5.30, p = 0.98, adjusted for previous myocardial infarction and left ventricular ejection fraction), respectively. In patients with pPCI treated STEMI, suPAR was an independent prognostic biomarker of non-cardiac but not cardiac mortality and may identify patients with high risk of non-cardiac mortality. [ABSTRACT FROM AUTHOR]

Objective The main objective of this study was to investigate the association between two markers of low-grade inflammation; soluble urokinase plasminogen activator receptor (suPAR) and high-sensitive C-reactive protein (hs-CRP); and coronary artery calcification (CAC) score detected by cardiac computed tomography (CT) scan. Design A cross sectional study of 1126 randomly sampled middle-aged men and women. Methods CAC score was measured by a non-contrast cardiac CT scan and total 10-year cardiovascular mortality risk was estimated using the Systematic Coronary Risk Evaluation (SCORE). Plasma samples were analysed for suPAR and hs-CRP. The association of suPAR and hs-CRP to CAC was evaluated by logistic regression analyses adjusting for categorised SCORE. The additive effect of suPAR to SCORE was evaluated by comparing area under curve (AUC) and net reclassification improvement (NRI). Results The odds of being in a higher CAC category, i.e. having more severe CAC, increased 16% (odds ratio (OR) 1.16, p = 0.02) when plasma suPAR concentration increased 1 ng/ml, and this was more pronounced in women (OR 1.30, p = 0.01) than in men (OR 1.15, p = 0.05). In comparison, hs-CRP was not associated with CAC category (OR 1.00, p = 0.90). When adding suPAR to categorised SCORE, AUC increased from 0.66 to 0.70 ( p = 0.04) in women and from 0.65 to 0.68 ( p = 0.03) in men. NRI was significant in men (NRI 19.3%, 95% CI 6.1–32.6, p = 0.004) as well as in women (NRI 20.8%, 95%CI 1.0–40.7, p = 0.04), without significant gender difference. Conclusions suPAR, but not hs-CRP, appeared to be associated with CAC score independently of SCORE. The association was strongest in women. [ABSTRACT FROM AUTHOR]

Soluble urokinase plasminogen activator receptor (suPAR) is associated with faster decline in kidney function and the pathogenesis of diabetic nephropathy. However, little is known about the impact of treatment on plasma and urinary levels of suPAR. We aimed to investigate the impact of renin angiotensin system (RAS) single and dual blockade on suPAR levels in patients with type 2 diabetes and albuminuria. We conducted a post-hoc analysis of a randomized controlled crossover trial. Urine and plasma samples were analyzed for suPAR levels. The placebo period was considered reference and all treatment periods were compared to placebo. Patients (n = 22) were treated for 2-month periods with either placebo, irbesartan 300 mg once daily, aliskiren 300 mg once daily or irbesartan/aliskiren combination in random order. Placebo geometric mean plasma (SEM) levels of suPAR were 3.3 ng/mL (1.1) and urine levels were 4.0 ng/mL (1.1). None of the treatments had significant effects on plasma levels of suPAR compared to placebo. Compared to placebo, irbesartan and combination treatment decreased urinary levels of suPAR significantly (-1.3 ng/mL), while aliskiren did not. In patients with type 2 diabetes urinary levels of suPAR were reduced during RAS blockade treatment, which may contribute to renoprotection. [ABSTRACT FROM AUTHOR]

Summary: Mycobacterium tuberculosis (Mtb) and the human immunodeficiency virus (HIV) are both life-threatening pathogens in their own right, but their synergic effects on the immune system during co-infection markedly enhance their effect on the host. This review focuses on the bidirectional interaction between HIV and Mtb and discusses the relevance of sputum smear examination, CD4+ counts, viral load at baseline and after initiation of anti-retroviral therapy, as well as additional existing and new potential immune correlates of disease progression and prognosis. These markers include β2-microglobulin, neopterin, tumor necrosis factor receptor II (TNFRII), CD8+/CD38+, soluble urokinase plasminogen activator receptor (suPAR) and CXCL10 (or IP-10). [Copyright &y& Elsevier]

Background: Severe acute respiratory syndrome coronavirus 2 (The Covid-19 pandemic) strains health care capacity. Better risk stratification, with discharge of patients with a predicted mild disease trajectory, can ease this burden. Elevated blood-soluble urokinase plasminogen activator receptor (suPAR) has previously been shown to be associated with risk of intubation in confirmed COVID-19 patients.Objective: To evaluate whether point-of-care measures of suPAR in patients presenting to the emergency department (ED) with symptoms of COVID-19 can identify patients that can be safely discharged.Methods: Observational cohort study including all patients in the ED with symptoms of COVID-19 from March 19 to April 3, 2020. SuPAR was measured at first presentation. Review of electronic patient records 14 days after admission was used to assess disease trajectory. Primary endpoints were mild, moderate, severe, or very severe trajectory. The predictive value of suPAR, National Early Warning Score (NEWS), C-reactive protein (CRP), and duration of symptoms was calculated using receiver operating characteristics (ROC).Results: Of 386 patients, 171 (44%) had a mild disease trajectory, 79 (20%) a moderate, 63 (16%) a severe, and 73 (19%) a very severe disease trajectory. Low suPAR was a strong marker of mild disease trajectory. Results suggest a cut-off for discharge for suPAR < 2.0 ng/mL if suPAR is used as a single parameter, and <3.0 ng/mL when combined with NEWS ≤ 4 and CRP < 10 mg/L.Conclusion: suPAR is a potential biomarker for triage and safe early discharge of patients with COVID-19 symptoms in the ED. suPAR can be used even before SARS-CoV-2 status is known. [ABSTRACT FROM AUTHOR]

• The DOC is a cancer diagnostics program for patients with non-specific symptoms. • The inflammatory biomarker suPAR was elevated in cancer and non-malignant disease. • Patients without incident disease had significantly lower suPAR at baseline. • Patients who died within 1 year had higher suPAR at baseline compared to survivors. • However, the predictive value of suPAR for ruling out disease was low. Accurate first-line diagnostics are essential for early recognition of cancer but also to identify patients free of disease. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in patients with cancer or non-malignant disease compared to disease-free patients. We tested if low suPAR could be used to identify disease-free patients in an accelerated cancer diagnostics program, including ruling out cancer. Patients with serious nonspecific symptoms and signs of cancer (NSSC) were included at the Diagnostic Outpatient Clinic, Copenhagen University Hospital Hvidovre, Denmark. Data from a clinical examination, including blood tests and imaging, was combined with national registry data on diagnoses and mortality. The association between blood suPAR and the primary outcome of disease-free (i.e., absence of incident disease and mortality) within 1-year follow-up was analysed with logistic regression analysis. Of 1583 patients included, 349 (22.0%) were diagnosed with cancer, 837 (52.9%) with non-malignant disease, and 392 (25.8%) were disease-free within one year. Admission suPAR was significantly lower in disease-free patients compared to patients with cancer or non-malignant disease (P < 0.001), area under the curve 0.67 (95% confidence interval (CI): 0.64–0.70). The highest positive predictive value (PPV) for the outcome of disease-free was 0.55 (95% CI: 0.41–0.68) at a suPAR of 1.65 ng/mL. Patients who died had significantly higher suPAR compared to patients who survived in all disease subgroups. The AUC of suPAR for 1-year mortality was 0.80 (95% CI: 0.77–0.83). suPAR was significantly lower in disease-free individuals compared to patients with cancer or other conditions, but the PPV was not sufficiently high to terminate further clinical investigation with appropriate safety. Elevated suPAR may be a useful prognostic marker for adverse outcomes. [ABSTRACT FROM AUTHOR]

• Routine biomarkers can accurately predict mortality in acutely admitted patients. • Simple and easily calculated blood test score. • Potential to increase risk stratification when combining blood tests with triage. This study aimed to improve early risk stratification in the emergency department by creating a simple blood test score based on routine biomarkers and assess its predictive ability for 30-day mortality of acutely admitted patients. This was a secondary analysis of data from the TRIAGE II study. It included unselected acutely admitted medical and surgical patients, who had albumin, C-reactive protein, creatinine, haemoglobin, leukocytes, potassium, sodium and thrombocytes levels analysed upon admission. Patients were classified according to the number of biomarker results outside the reference range into four risk groups termed "very low", "low", "intermediate", and "high" with 0–1, 2–3, 4–5 and 6–8 abnormal biomarker results, respectively. Logistic regression was used to calculate odds ratios for 30-day mortality and receiver operating characteristic was used to test the discriminative value. The primary analysis was done in patients triaged with ADAPT (Adaptive Process Triage). Subsequently, we analysed two other cohorts of acutely admitted patients. The TRIAGE II cohort included 17,058 eligible patients, 30-day mortality was 5.2%. The primary analysis included 7782 patients. Logistic regression adjusted for age and sex showed an OR of 24.1 (95% CI 14.9–41.0) between the very low- and the high-risk group. The area under the curve (AUC) was 0.79 (95% CI 0.76–0.81) for the blood test score in predicting 30-day mortality. The subsequent analyses confirmed the results. A blood test score based on number of routine biomarkers with an abnormal result was a predictor of 30-day mortality in acutely admitted patients. [ABSTRACT FROM AUTHOR]

Background Dyslipidemia and low-grade inflammation are integral in the pathogenesis of atherosclerosis. We aim to compare the effects of a considerable weight loss and intensive exercise training on lipid atherogenicity and low-grade inflammation in a high-risk population with coronary artery disease (CAD). Methods Seventy non-diabetic participants with CAD, BMI 28–40 kg/m 2 , age 45–75 years were randomized to 12 weeks' aerobic interval training (AIT) at 85–90% of peak heart rate three times/week or a low energy diet (LED, 800–1000 kcal/day) for 8–10 weeks followed by 2–4 weeks' weight maintenance diet. Lipid profile atherogenicity was described using lipoprotein particle size and density profiling. Low-grade inflammation was evaluated by tumor necrosis factor alpha (TNFα), C-reactive protein, interleukin 6 and soluble urokinase plasminogen activator receptor. Results Twenty-six (74%) AIT and 29 (83%) LED participants completed intervention per protocol. AIT and LED decreased total (AIT: −518 {−906;−129},P = 0.011, LED: −767 {−1128:−406},P < 0.001) and low-density lipoprotein (LDL, AIT: −186 {−306;−65},P = 0.004, LED: −277 {−433;−122},P < 0.001) assessed as the area under the density profile curve. LED was superior to AIT in decreasing atherogenicity reflected by increased LDL (between-group: 1.0 Å {0.4; 1.7},P = 0.003) and high-density lipoprotein (between-group: 1.2 Å {0.2; 2.4},P = 0.026) particle size and a decreased proportion of total lipoprotein constituted by the small, dense LDL 5 subfraction (between-group: −5.0% {−8.4;−1.7},P = 0.004). LED decreased TNFα (9.5% {−15.8;−2.6},P = 0.009). No changes were seen following AIT. Conclusion LED and AIT decreased total and LDL lipoprotein. LED was superior in decreasing atherogenicity assessed by a shift in density profile and increased particle size. Effect on low-grade inflammation was limited. [ABSTRACT FROM AUTHOR]

Abstract: Background: The inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR) and C-reactive protein (CRP) independently predict cardiovascular disease (CVD). The prognostic implications of suPAR and CRP combined with Framingham Risk Score (FRS) have not been determined. Methods: From 1993 to 1994, baseline levels of suPAR and CRP were obtained from 2315 generally healthy Danish individuals (mean [SD] age: 53.9 [10.6] years) who were followed for the composite outcome of ischemic heart disease, stroke and CVD mortality. Results: During a median follow-up of 12.7years, 302 events were recorded. After adjusting for FRS, women with suPAR levels in the highest tertile had a 1.74-fold (95% confidence interval [CI]: 1.08–2.81, p=0.027) and men a 2.09-fold (95% CI: 1.37–3.18, p<0.001) increase in risk compared to the lowest tertile. Including suPAR and CRP together resulted in stronger risk prediction with a 3.30-fold (95% CI: 1.36–7.99, p<0.01) increase for women and a 3.53-fold (1.78–7.02, p<0.001) increase for men when both biomarkers were in the highest compared to the lowest tertile. The combined extreme tertiles of suPAR and CRP reallocated individuals predicted to an intermediate 10-year risk of CVD of 10–20% based on FRS, to low (<10%) or high (>20%) risk categories, respectively. This was reflected in a significant improvement of C statistics for men (p=0.034) and borderline significant for women (p=0.054), while the integrated discrimination improvement was highly significant (P≤0.001) for both genders. Conclusions: suPAR provides prognostic information of CVD risk beyond FRS and improves risk prediction substantially when combined with CRP in this setting. [Copyright &y& Elsevier]

Abstract: Background: Low-grade inflammation is a marker for cardiovascular disease (CVD). The inflammatory biomarkers C-reactive protein (CRP) and soluble urokinase plasminogen activator receptor (suPAR) independently predict CVD. We tested the hypothesis that these biomarkers reflect different aspects of the inflammation associated with CVD. Methods: We studied 2273 subjects without CVD. Log-transformed CRP and suPAR were included in general linear and logistic regression models to compare associations with measures of anthropometry and subclinical organ damage (SOD). Owing to interactions on body mass index (BMI) (P<0.0001), the population was stratified by gender and smoking concerning anthropometry. Results: In both genders, independent of smoking, log-CRP was positively associated with BMI (β: 0.28 to 0.40, P<0.001) and waist circumference (WC) (β: 0.27 to 0.42, P<0.001). In contrast, in smoking women and men, log-suPAR was negatively associated with BMI and WC (β: −0.09 to −0.19, P<0.05). In non-smoking women, log-suPAR was positively associated with BMI and WC (β: 0.14 and 0.16, P<0.001), whereas no associations were found in non-smoking men. No interactions were found on SOD. Adjusted for age, sex, smoking, and physical activity, log-suPAR was associated with an increased urine albumin/creatinine ratio (standardized odds ratio (95% confidence interval (CI)) for highest vs. lower quartiles: 1.36 (1.21–1.52), whereas log-CRP was not (1.10 (0.99–1.22))), and extent of atherosclerosis (standardized proportional odds ratio (95% CI) for carotid plaques 0, 1≤ to ≤3, >3: 1.31 (1.16–1.47), whereas log-CRP was not (1.00 (0.89–1.11))). Conclusions: CRP is positively associated with anthropometric measures, whereas suPAR is linked to endothelial dysfunction and atherosclerosis. [Copyright &y& Elsevier]

The plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is an independent predictor of cardiovascular disease and all-cause mortality in healthy subjects. The prognostic capability of suPAR, its temporal course, and its relation to plasma C-reactive protein (CRP) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention (PCI) is unknown. Therefore, the plasma suPAR and CRP levels were measured in 296 consecutive patients with ST-segment elevation myocardial infarction admitted for primary PCI at baseline and every 6 to 8 hours thereafter until the cardiac biomarker levels had peaked. The end points were all-cause mortality and fatal or nonfatal recurrent myocardial infarction (MI). During a median follow-up period of 5.75 years, 69 deaths and 48 nonfatal and 14 fatal recurrent MIs occurred. All-cause mortality increased significantly from 8.1% to 41.5% across increasing quartiles of suPAR levels at the end of follow-up (log-rank p <0.0001). After adjustment for other independent prognostic factors, a highly significant increase was seen in all-cause mortality (hazard ratio 1.45, 95% confidence interval, 1.19 to 1.76; p <0.001) and recurrent MI (hazard ratio 1.53, 95% confidence interval 1.16 to 2.01; p <0.01) for each standard deviation increment of suPAR levels). In contrast to plasma CRP, the suPAR levels remained stable after primary PCI. Furthermore, CRP did not predict mortality or reinfarction after adjustment for age and gender (p = 0.34). In conclusion, suPAR is a stable plasma biomarker after ST-segment elevation myocardial infarction treated with primary PCI that predicts all-cause mortality and recurrent MI. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Elevated soluble urokinase-type plasminogen activator receptor (suPAR) indicates an inflammatory state caused by conditions such as HIV and cancer. Recently suPAR was identified as an indicator of cardiovascular disease (CVD). CVD is highly prevalent in black South Africans, but the potential role of suPAR is unknown. We investigated suPAR as a possible marker of arterial stiffness in Africans and Caucasians. Methods: This study involved 207 Africans and 314 Caucasians (aged 20–70yrs). C-reactive protein (CRP) and suPAR were determined in fasting blood samples. We measured blood pressure, pulse wave velocity (PWV) and Windkessel arterial compliance (Cwk). Results: Africans displayed higher suPAR, CRP, PWV and lower Cwk (p<0.001) compared to Caucasians. SuPAR was elevated in Africans irrespective of gender and smoking. We found strong relationships between PWV and suPAR (r=0.27; p<0.001) and Cwk and suPAR (r=−0.39; p<0.001) in the whole group, but found no independent relationship of any arterial stiffness measure and suPAR in Africans after adjustment for confounders. Caucasian men indicated a weak significant independent association between Cwk and suPAR (β=−0.09; p=0.028). Conclusion: Africans had higher levels of suPAR and arterial stiffness than Caucasians (p<0.001), but there was no independent relationship between arterial stiffness and suPAR in the Africans. It is speculated that due to the inflammatory role of suPAR, it will have stronger relationships with atherosclerosis, which has not yet manifested in this relatively young population group. SuPAR may therefore not be an ideal early marker of cardiovascular dysfunction, but may rather indicate established CVD. [Copyright &y& Elsevier]

Abstract: IFN-γ responses to Mycobacterium tuberculosis specific antigens are used as in vitro diagnostic tests for tuberculosis infection. The tests are sensitive and specific for latent and active tuberculosis disease, but sensitivity may be reduced during immunosuppression. The objective of the study was to explore new ways to improve the diagnosis of tuberculosis infection using CXCL10 and IL-2 as alternative markers to IFN-γ. CXCL10, IL-2, and IFN-γ responses to stimulation with ESAT-6/CFP10/TB7.7 were assessed in 12 Quantiferon positive, 8 Quantiferon negative tuberculosis patients and 11 Quantiferon negative controls. CXCL10 and IL-2 were determined by multiplex and IFN-γ by the Quantiferon ELISA. The median antigen specific CXCL10, IFN-γ, and IL-2 responses in patients with tuberculosis were 870pg/ml (range 261–1576pg/ml), 217pg/ml (81–1273pg/ml), 59pg/ml (14–276pg/ml) respectively, and the CXCL10 responses were significantly higher than any of the other cytokines measured (p =0.001). In 4/7 individuals with a negative (n =6) or indeterminate (n =1) Quantiferon test, antigen specific CXCL10 responses were detectable at high levels ranging from 196–532pg/ml. In conclusion CXCL10 was strongly induced after M. tuberculosis specific stimulation and sensitivity appeared superior to the Quantiferon test. Our findings suggest that CXCL10 may serve as an alternative or additional marker for the immunodiagnosis of tuberculosis. [Copyright &y& Elsevier]