Superoxide dismutase (SOD), advanced oxidation protein products (AOPP), and disease-modifying treatment are related to better relapse recovery after corticosteroid treatment in multiple sclerosis.

OBJECTIVES: The aim of our study was to analyze oxidative stress (OS) markers in multiple sclerosis (MS) patients during relapse and remission and to evaluate the effects of corticosteroid relapse treatment on oxidative status, and also to determine possible relationship between OS markers and relapse disability recovery after corticosteroid treatment. METHODS: Our study included 118 MS patients, (59 relapse/59 remission) 70 females and 48 males, mean age 40.2 ± 9.4 years, and 88 matched healthy controls. Undergoing disease-modifying therapy (DMT) was present in 30.5% of relapse and 88% of remission MS patients. We analyzed in plasma/serum the following: pro-oxidative-antioxidative balance (PAB), nitrates and nitrites (NO3 + NO2), malondialdehyde (MDA), advanced oxidation protein products (AOPP) superoxide dismutase (SOD), catalase (CAT), uric acid, bilirubin, albumin, and transferrin in all patients and additionally after corticosteroid relapse treatment. Neurological disability was measured using the Extended Disability Status Scale (EDSS). RESULTS: Better clinical recovery after relapse treatment was associated with increased baseline SOD, decreased AOPP, and ongoing DMT (all p < 0.05). There was no difference between OS markers in relapse and remission. MS patients had higher MDA, NO3 + NO2, PAB, SOD, CAT, lower AOPP, uric acid, albumin, bilirubin, and transferrin compared to controls (all p < 0.05). Corticosteroids caused significant decrease of all OS markers (all p < 0.05). CONCLUSION: Increased baseline antioxidative activity of SOD and decreased baseline levels of pro-oxidant AOPP along with ongoing DMT were related to better clinical recovery after corticosteroid relapse treatment. Increase of pro-oxidants and antioxidant enzyme activity in relapse and remission confirms ongoing oxidative injury irrelevant of MS clinical presentation.

Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia?

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-platelet count (MPV/PC) ratio are readily available parameters that might have discriminative power regarding outcome. The aim of our study was to assess prognostic value of these biomarkers regarding outcome in critically ill patients with secondary sepsis and/or trauma. METHODS: A total of 392 critically ill and injured patients, admitted to surgical ICU, were enrolled in a prospective observational study. Leukocyte and platelet counts were recorded upon fulfilling Sepsis-3 criteria and for traumatized Injury Severity Score > 25 points. Patients were divided into four subgroups: peritonitis, pancreatitis, trauma with sepsis, and trauma without sepsis. RESULTS: NLR and MPV/PC levels were significantly higher in nonsurvivors (AUC/ROC of 0.681 and 0.592, resp., in the peritonitis subgroup; 0.717 and 0.753, resp., in the pancreatitis subgroup); MLR and PLR did not differ significantly. There was no significant difference of investigated biomarkers between survivors and nonsurvivors in trauma patients with and without sepsis except for PLR in the trauma without sepsis subgroup (significantly higher in nonsurvivors, AUC/ROC of 0.719). Independent predictor of lethal outcome was NLR in the whole cohort and in the peritonitis subgroup as well as MPV in the pancreatitis subgroup. Also, there were statistically significant differences in MPV/PC, MLR, and PLR values regarding nature of bacteremia. In general, the lowest levels had been found in patients with Gram-positive blood cultures. CONCLUSIONS: NLR and MPV were very good independent predictors of lethal outcome. For the first time, we demonstrate that nature of bacteremia influences MPV/PC, MLR, and PLR. In heterogeneous cohort subgroup, analysis is essential.

Tissue and urinary KIM-1 relate to tumor characteristics in patients with clear renal cell carcinoma.

The objective of this prospective follow-up trial was to ascertain whether the urinary kidney injury molecule-1 (uKIM-1) associates with tumor tissue (tKIM-1) expression and with the pathological characteristics of clear renal cell carcinoma (cRCC) in radically nephrectomized (RN) and/or in partially nephrectomized (PN) patients with cRCC, pre- and postoperatively. This clinical study included 40 patients subjected to RN/PN (cRCC group) and 30 healthy volunteers (control group). Urinary KIM-1 was determined by ELISA TIM-1/KIM-1 kit and normalized by urinary creatinine. Immunohistochemical staining (monoclonal anti-human anti-TIM-1/KIM-1/HAVCR antibody) was used for semiquantitative analysis of the tKIM-1 expression and expressed as a score (% KIM-1 positively stained tubules). Both markers were interpreted in terms of the tumor characteristics comprising tumor size, Fuhrman grade, pathological (pT) stage, tumor/nodes/metastasis (TNM) stage, lymphovascular invasion and type of surgery RN/PN. Preoperative uKIM-1 was significantly higher in the cRCC group compared to controls, such as uKIM-1 was statistically higher in RN than in PN patients. Postoperatively, uKIM-1 decreased to control values. Expression of tKIM-1 was documented in all nephrectomized patients. Significant associations were achieved between uKIM-1 and tKIM-1 and with considered tumor characteristics, especially with tumor size and grade. Based on the accomplished associations, we found uKIM-1 as a highly sensitive marker for cRCC diagnosis. The clinical trial registration number: 1110-2012.

Urinary KIM-1 and AQP-1 in patients with clear renal cell carcinoma: Potential noninvasive biomarkers.

BACKGROUND/AIM: Kidney injury molecule-1 (KIM-1) and aquaporin-1 (AQP-1) are potential early urinary biomarkers of clear renal cell carcinoma (cRCC). The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy) in patients with cRCC. METHODS: Urinary concentrations of urinary KIM-1 (uKIM-1) and urinary AQP-1 (uAQP-1) were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. RESULTS: The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ? 1.120 ng/mg urinary creatinine (Ucr)] were significantly greater compared with controls (healthy volunteers) (0.210 +/- 0.082 ng/mgUcr) (p = 0.0227). Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 +/- 0.099 ng/mgUcr vs 0.210 + 0.082 ng/mgUcr, respectively). The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 +/- 0.092 ng/mgUcr) compared with the control group (0.202 +/- 0.078 ng/mgUcr) (p = 0.0014). Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. CONCLUSION: uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy.

Prognostic Value and Daily Trend of Interleukin-6, Neutrophil CD64 Expression, C-Reactive Protein and Lipopolysaccharide-Binding Protein in Critically Ill Patients: Reliable Predictors of Outcome or Not?

BACKGROUND: Severe sepsis and/or trauma complicated by multiple organ dysfunction syndrome are the leading causes of death in critically ill patients. The aim of this prospective single-centre study was to assess the prognostic value and daily trend of interleukin-6 (IL-6), neutrophil CD64 expression, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) regarding outcome in critically ill patients with severe trauma and/or severe sepsis. Outcome measure was hospital mortality. METHODS: One hundred and two critically ill patients admitted to the intensive care unit of a tertiary university hospital were enrolled in this prospective study. Blood samples were collected on admission (day 1), days 2 and 3. RESULTS: CD64 index was 1.6-fold higher on day 1 and 1.78-fold higher on day 2 in non-survivors (p<0.05). The area under the curve (AUC) for the CD64 index on day 1 for outcome was 0.727. At a cut-off level of 2.80 sensitivity was 75% and specificity was 65%. Patients with CD64 index level on day 1 higher than 2.80 had 2.4-fold higher probability of dying. Odds ratio is 2.40; 95% CI 0.60-9.67. CONCLUSIONS: CD64 index on day 1 is a fairly good predictor of outcome. AUCs for IL-6, CRP and LBP were < 0.55, suggesting these biomarkers failed to predict outcome.

Factors influencing antibiotic treatment cost and outcome in critically ill patients: a "real-life" study.

UNLABELLED: BACKGROUND/AIM. Critically ill patients are at very high risk of developing severe infections in intensive care units (ICUs). Procalcitonin (PCT) levels are eleveted in the circulation in patients with bacterial sepsis and PCT might be useful in guiding antibiotic treatment. The aim of this study was to estimate factors influencing patients survival and treatment cost in ICU with special emphasis on the impact of PCT serum levels use in guiding antimicrobial therapy. METHODS: The study was conducted from August 2010 to May 2012 in the Intensive Therapy Unit, Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy (MMA), Belgrade, Serbia. All adult critically ill patients with sepsis and/or trauma admitted in the ICU were included in the study. This study included only the cost of antimicrobial therapy in the ICU and the cost for PCT analysis. We used prices valid in the MMA for the year 2012. PCT in serum was measured by homogeneous immunoassay on a Brahms Kryptor analyzer. RESULTS: A total of 102 patients were enrolled. The mean patients age was 55 ± 19 years and 61.8% of patients were male. The mean length of stay (LOS) in the ICU was 12 ± 21 days. There was a statistically significant difference (p < 0.001) between the sepsis and trauma group regarding outcome (higher mortality rate was in the sepsis group, particularly in the patients with peritonitis who were mostly women). The patients younger than 70 years had better chance of survival. LOS, the use of carbapenems and PCT-measurement influenced the cost of therapy in the ICU. CONCLUSIONS: The obtained results show that age, the diagnosis and gender were the main predictors of survival of critically ill patients in the ICU. The cost of ICU stay was dependent on LOS, use of carbapenems and PCT-measurement although the influence of these three factors on the outcome in the patients did not reach a statistical significance.