Aleksandar Urošević, Olga Dulović, Branko Milošević, Nebojša Maksić, Nataša Popović, Ivana Milošević, Dragan Delić, Djordje Jevtović, Jasmina Poluga, Jelena Jordović, Sanja Peruničić and Goran Stevanović
Background: West Nile virus neuroinvasive disease (WNND) occurs in less than 1% of infected people. Leukocytosis with lymphocytopenia, mild anaemia, thrombocytopenia, elevated liver and muscle enzymes and hyponatremia are occasionally present in patients with WNND. Cerebrospinal fluid (CSF) findings resemble other viral neuroinfections. The purpose of this study is to present some of the most important laboratory findings of our patients with WNND and to evaluate their correlation with fatal outcome.
Methods: The study included 161 patients with WNND. Their blood and CSF samples were cytobiochemically analysed and the obtained variables were then tested for predictive significance of the disease outcome, or used for differentiation between two clinical syndromes (encephalitis vs meningitis).
Results: West Nile encephalitis was present in 127 (78.9%) patients and West Nile meningitis was diagnosed in 34 (21.1%) cases. Leukocytosis was found in 45.9% patients. CRP level higher than 100 mg/L was registered only in those with encephalitis (p=0.020). CSF leukocyte count was 146±171 per microlitre, with slight lymphocytic predominance (mean 52%). Hypoglycorrhachia was registered in 9.3% of our patients with WNND. Twenty-eight (17.4%) patients died and all of them had encephalitis. Independent predictors of fatal outcome in WNND were serum CRP > 100 mg/L (p=0.011) and CSF proteins > 1 g/L (p=0.002).
Conclusions: WNND usually affects older males. Prolonged neutrophilic predominance in CSF can occasionally be present, as well as hypoglycorrhachia. Patients with encephalitis, high serum CRP and high CSF protein level have a higher risk of fatal outcome.
Olga Vasović, Katarina Lalić, Danijela Trifunović, Nataša Milić, Ivan Jevremović, Ljiljana Popović, Dalibor Paspalj, Aleksandra Milićević-Kalasić, Goran Ševo, Nebojša Despotović, Predrag Erceg and Dragoslav P. Milosevic
Background: We investigated the traditional and new bio- markers as predictors of cardiovascular mortality in the func- tionally disabled elderly who are living in a community.
Methods: This prospective study included 253 participants (78.3% women) aged 65 and over who were monitored for 32 months. Receiver operating curve analysis and the Cox proportional hazard model were used to identify univariate and multivariate predictors of cardiovascular mortality. The Kaplan-Meier survival curve and Log rank test were used for survival analysis.
Results: During the study, 43.1% participants died from car- diovascular diseases. Cutoff points of multivariate predictors were used to build a score system. The risk score was positive in patients with three or more of the following predictors: albumin <40 g/L, body mass index <25 kg/m2, total serum bilirubin <10.5 (imol/L, blood urea nitrogen >6.5 mmol/L and high-sensitivity C-reactive protein >2.25 mg/L. The rel- ative risk for cardiovascular mortality for someone with a positive vs. negative score was 3.91 (95% Cl: 2.55-5.98; P< 0.001). There was no change in risk after adjustment for age; sex, traditional cardiovascular risk factors, comorbidities and a number of disabilities.
Conclusions: Presence of lo* grade inflammation, malnulri tion and early signs of renal dy sfunction are essential for car- diovascular risk among the functional disabled elderly and may be assessed using the proposed new inflammatory m3lnuhffion-renal involved score (1MRIS).
Goran Milosevic, Nikola Kotur, Nada Krstovski, Jelena Lazic, Branka Zukic, Biljana Stankovic, Dragana Janic, Theodora Katsila, George P. Patrinos, Sonja Pavlovic and Lidija Dokmanovic
Acute lymphoblastic leukemia is the most common childhood malignancy. Optimal use of anti leukemic drugs has led to less toxicity and adverse reactions, and a higher survival rate. Thiopurine drugs, including 6-mercaptopurine, are mostly used as antileukemic medications in the maintenance phase of treatment for children with acute lymphoblastic leukemia. For those patients, TPMT genotype- tailored 6-mercaptopurine therapy is already implemented in the treatment protocols. We investigated the role of TPMT, ITPA, ABCC4 and ABCB1 genetic variants as predictors of outcome and 6-mercaptopurine induced toxicity during the maintenance phase of treatment in pediatric acute lymphoblastic leukemia. Sixty-eight children with acute lymphoblastic leukemia were enrolled in this study. Patients have been treated according to ALL IC-BFM 2002 or ALL IC-BFM 2009 protocols. Toxicity and adverse events have been monitored via surrogate markers (off-therapy weeks, episodes of leu - ko penia and average 6-mercaptopurine dose) and a prob- abilistic model was employed to predict overall 6-mercaptopurine related toxicity. We confirmed that patients with acute lymphoblastic leukemia that carry inactive TPMT allele(s) require 6- mercaptopurine dose reduction. ITPA and ABCC4 genetic variants failed to show an association with 6-mercapto - purine induced toxicity during the maintenance phase. Carriers of ABCB1 variant allele experienced greater hepatotoxicity. The probabilistic model Neural net which considered all the analysed genetic variants was assessed to be the best prediction model. It was able to discriminate ALL patients with good and poor 6-mercaptopurin tolerance in 71% of cases (AUC=0.71). This study contributes to the design of a panel of pharmacogenetic markers for predicting thiopurineinduced toxicity in pediatric ALL.
Vladimir Gasic, Biljana Stankovic, Branka Zukic, Dragana Janic, Lidija Dokmanovic, Nada Krstovski, Jelena Lazic, Goran Milosevic, Marianna Lucafò, Gabriele Stocco, Giuliana Decorti, Sonja Pavlovic and Nikola Kotur
Long non-coding RNA growth arrest-specific 5 (GAS5) is deregulated in many cancers because of its role in cell growth arrest and apoptosis. Additionally, GAS5 interacts with glucocorticoid receptor, making it a potential pharmacotranscription marker of glucocorticoid (GC) therapy. In this study, we aimed at analysing GAS5 expression in the remission induction therapy phase of childhood acute lymphoblastic leukemia (ALL), in which GCs are mandatorily used, and to correlate it with therapy response.
GAS5 expression was measured in peripheral blood mononuclear cells taken from 29 childhood ALL patients at diagnosis, on day 15 and day 33 of remission induction therapy using RT-qPCR methodology.
Our results have shown interindividual differences in GAS5 expression at all time points. For each ALL patient, GAS5 expression was higher on day 15 in comparison to its level at diagnosis (p<0.0005). On day 33, the level of GAS5 expression decreased in comparison with day 15 (p<0.0005), but it was still significantly higher than at diagnosis for the majority of patients (p=0.001). Patients whose number of blasts on day 8 was below 100 per μL of peripheral blood had a higher GAS5 expression at diagnosis (p=0.016), and lower ratio day 15/diagnosis (p=0.009).
Our results suggest that the expression level of GAS5 could be a potential marker of therapy response in remission induction therapy of childhood ALL.