Utility of brain parenchyma density measurement and computed tomography perfusion imaging in predicting brain death.

PURPOSE: To assess the utility of brain parenchyma density measurement on unenhanced computed tomography (CT) in predicting brain death (BD), in order to evaluate the added value of CT perfusion (CTP). MATERIAL AND METHODS: A total of 77 patients who were clinically diagnosed as BD and had both CT angiography (CTA) and CTP imaging in the same session were retrospectively reviewed. On unenhanced phase of CTA, density measurement was performed from 23 regions of interests (ROIs) which were located in the following areas: level of basal ganglia (caudate nucleus, putamen, corpus callosum, posterior limb of internal capsule), level of brainstem, grey- white matters on levels of centrum semiovale (CS), high convexity (HC), and cerebellum. CTP images were evaluated qualitatively and independently. Grey matter (GM), white matter (WM), density, and GM/WM density ratio of BD patients were compared with control subjects. RESULTS: Comparing with the normal control group, the GM and WM density at each level and GM/WM density ratio of CS, HC, and cerebellum level were significantly lower in brain-dead patients (p = 0.019 for HC-WM, p < 0.001 for other areas). Using ROC analysis, the highest value of area under curve (AUC) for the GM/WM density ratio was found at the HC level (AUC = 0.907). The sensitivity of the GM/WM density ratio at the HC level was found to be 90% when the cut-off value of 1.25 was identified. Evaluating the GM/WM density ratio together with the CTP results increased the sensitivity further to 98%. CONCLUSIONS: The GM/WM density ratio at the HC level on unenhanced CT may be a useful finding to predict BD. Also, the addition of CTP increases the sensitivity of this method.

Preoperative Magnetic Resonance Volumetry in Predicting Myometrial Invasion, Lymphovascular Space Invasion, and Tumor Grade: Is It Valuable in International Federation of Gynecology and Obstetrics Stage I Endometrial Cancer?

OBJECTIVE: The aim of this retrospective single-center study was to evaluate the relationship between maximum tumor size, tumor volume, tumor volume ratio (TVR) based on preoperative magnetic resonance (MR) volumetry, and negative histological prognostic parameters (deep myometrial invasion [MI], lymphovascular space invasion, tumor histological grade, and subtype) in International Federation of Gynecology and Obstetrics stage I endometrial cancer. METHODS/MATERIALS: Preoperative pelvic MR imaging studies of 68 women with surgical-pathologic diagnosis of International Federation of Gynecology and Obstetrics stage I endometrial cancer were reviewed for assessment of MR volumetry and qualitative assessment of MI. Volume of the tumor and uterus was measured with manual tracing of each section on sagittal T2-weighted images. Tumor volume ratio was calculated according to the following formula: TVR = (total tumor volume/total uterine volume) × 100. Receiver operating characteristics curve was performed to investigate a threshold for TVR associated with MI. The Mann-Whitney U test, Kruskal-Wallis test, and linear regression analysis were applied to evaluate possible differences between tumor size, tumor volume, TVR, and negative prognostic parameters. RESULTS: Receiver operating characteristics curve analysis of TVR for prediction of deep MI was statistically significant (P = 0.013). An optimal TVR threshold of 7.3% predicted deep myometrial invasion with 85.7% sensitivity, 46.8% specificity, 41.9% positive predictive value, and 88.0% negative predictive value. Receiver operating characteristics curve analyses of TVR, tumor size, and tumor volume for prediction of tumor histological grade or lymphovascular space invasion were not significant. The concordance between radiologic and pathologic assessment for MI was almost excellent (κ value, 0.799; P < 0.001). Addition of TVR to standard radiologic assessment of deep MI increased the sensitivity from 90.5% to 95.2%. CONCLUSIONS: Tumor volume ratio, based on preoperative MR volumetry, seems to predict deep MI independently in stage I endometrial cancer with insufficient sensitivity and specificity. Its value in clinical practice for risk stratification models in endometrial cancer has to be studied in larger cohort of patients.

Evaluation of nephrotoxicity and prognosis in patients treated with colistin due to hospital-acquired pneumonia.

INTRODUCTION: Colistimethate sodium (CMS) is frequently used in the treatment of nosocomial multidrug-resistant gram-negative infections. Nephrotoxicity is the most important side effect. The aim of this study is to evaluate the effect of colistin on nephrotoxicity and to assess prognosis in patients treated with CMS due to hospital-acquired pneumonia (HAP). MATERIALS AND METHODS: Patients treated with CMS for HAP due to multidrug-resistant Pseudomonas aeruginosa or Acinetobacter baumannii were included in this cohort study. RESULT: We evaluated 281 patients treated with two different brands of CMS whose administration dose is different: imported (n= 58, low dose/kg) and domestic (n= 223, high dose/kg). Nephrotoxicity developed in 175 patients (62.3%). The median age (73 vs. 66 years, p= 0.004) and mortality rates were higher (66.9% vs. 52.8%, p= 0.022) in patients having nephrotoxicity. The patients receiving high dose/kg had higher nephrotoxicity rate (67.7% vs. 41.4%, p< 0.001). The clinical, bacteriological response and mortality rates of the whole group were 52.0%, 61.0%, 61.6%, respectively. The clinical and bacteriological response rates were similar in the different dose groups. Multivariate analysis showed that nephrotoxicity was associated with domestic brand depending on use of high dose (OR= 3.97), advanced age (ß= 0.29, p= 0.008), male gender (OR= 2.60), hypertension (OR= 2.50), red blood cells transfusion (OR= 2.54), absence of acute kidney injury (OR= 10.19), risk stage of RIFLE (OR= 11.9). CONCLUSIONS: Nephrotoxicity is associated with the use of high dose colistin, age, gender, hypertension, red blood cells replacement and RIFLE stage. The mortality rate is higher in patients developing nephrotoxicity.

ERCC1 expression does not predict survival and treatment response in advanced stage non-small cell lung cancer cases treated with platinum based chemotherapy.

BACKGROUND: ERCC1 is considered as a promising molecular marker that may predict platinum based chemotherapy response in non small cell lung cancer patients. We therefore investigated whether its expression is indeed associated with clinical outcomes in advanced stage NSCLC patients. MATERIALS AND METHODS: Pretreatment tumor biopsy samples of 83 stage 3B and 4 non-small cell lung cancer patients treated with platinum based chemotherapy were retrospectively analyzed for immunohistochemical ERCC1 expression. None of the patients received curative surgery or radiotherapy. RESULTS: By calculating H- scores regarding the extent and intensity of immunohistochemical staining of tumor biopsy samples, ERCC1 expression was found to be positive in 50 patients (60.2%). ERCC1 positive and negative groups had no statistically significant differences regarding treatment response, progression free survival and overall survival (respectively p=0.161; p=0.412; p=0.823). CONCLUSIONS: In our study we found no association between ERCC1 expression and survival or treatment response. The study has some limitations, such as small sample size and retrospective analysis method. There is need of more knowledge for use of ERCC1 guided chemotherapy regimens in advanced stage NSCLC.

Do cardiac risk factors affect the homocysteine and asymmetric dimethylarginine relationship in patients with coronary artery diseases?

OBJECTIVES: Elevated homocysteine (Hcy) concentrations have been shown to be a risk factor for atherosclerotic vascular disease and thrombosis. Increased asymmetric dimethylarginine (ADMA) levels have been implicated in the pathogenesis of numerous conditions affecting the cardiovascular system. In this study, the influence of cardiovascular risk factors and other variables on Hcy and ADMA relationship in patients with coronary artery disease (CAD) was investigated. DESIGN AND METHODS: Seventy-five patients with CAD were divided into three tertiles according to their Hcy levels. The effect of age, gender, blood pressure, lipid profile, renal function, and the presence of diabetes, insulin resistance, heart failure, inflammation, overweight, smoking and severity of coronary atherosclerosis on Hcy and ADMA relationship was evaluated. RESULTS: ADMA concentrations of patients in the middle and highest Hcy tertiles were significantly higher than the patients in the lowest tertile. When ADMA concentrations were adjusted for demographic, clinical and laboratory variables, the significant differences in ADMA concentrations between the tertiles were preserved. ADMA levels positively correlated with Hcy. Homocysteine levels positively correlated with serum creatinine and NT-proBNP concentrations and negatively correlated with glomerular filtration rates. Stepwise multiple regression analysis revealed Hcy as the unique predictor of ADMA levels. CONCLUSION: Homocysteine concentration has an effect on ADMA levels. There is a strong correlation between Hcy and ADMA. Cardiovascular risk factors do not have an influence on this relationship.

Metabolic syndrome, insulin resistance, fibrinogen, homocysteine, leptin, and C-reactive protein in obese patients with obstructive sleep apnea syndrome.

OBJECTIVE: The prevalence of obstructive sleep apnea syndrome (OSAS) and metabolic syndrome is increasing worldwide, in part linked to epidemic of obesity. The purposes of this study were to establish the rate of metabolic syndrome and to compare fibrinogen, homocysteine, high-sensitivity C-reactive protein (hsCRP), leptin levels, and homeostasis model assessment insulin resistance (HOMA-IR) in the obese patients with and without OSAS. METHODS: The study population included 36 consecutive obese patients with OSAS (23 males; mean age, 50.0 ±19.7 years), and 34 obese patients without OSAS (17 males; mean age, 49.7±11.1 years) were enrolled as control group. Metabolic syndrome was investigated; fibrinogen, homocysteine, CRP, and leptin levels were measured, and IR was assessed. RESULTS: Metabolic syndrome was found in 17 (47.2%) obese OSAS patients, whereas only 29.4% of obese subjects had metabolic syndrome (P > 0.05). Obese patients with OSAS had significantly higher mean levels of triglyceride (P < 0.001), total-cholesterol (P = 0.003), low-density lipoprotein-cholesterol (P = 0.001), fasting glucose (P = 0.01), HOMA-IR (P <0.001), thyroid-stimulating hormone (P = 0.03), fibrinogen (P < 0.003), hsCRP (P <0.001), and leptin (P = 0.03) than control group . Besides, leptin level was positively correlated with waist (r = 0.512, P = 0.03) and neck circumferences (r = 0.547, P = 0.03), and fasting glucose (r = 0.471, P = 0.04) in OSAS patients, but not in obese subjects. CONCLUSION: This study demonstrated that obese OSAS patients may have an increased rate of metabolic syndrome and higher levels of serum lipids, fasting glucose, IR, leptin, fibrinogen, and hsCRP than obese subjects without sleep apnea. Thus, clinicians should be encouraged to systematically evaluate the presence of metabolic abnormalities in OSAS and vice versa.

The relationship between the myocardial T2* value and left ventricular volumetric and functional parameters in thalassemia major patients.

PURPOSE: Cardiac involvement in thalassemia major (TM) is mainly characterized by left ventricular dysfunction caused by iron overload. Cardiovascular magnetic resonance imaging (MRI) including myocardial T2* measurement is becoming increasingly popular for quantitatively evaluating myocardial iron overload. The aim of this study was to evaluate the relationship between the myocardial T2* value and left ventricular functional parameters and to examine the associations between the degree of cardiac iron load and various clinical parameters. MATERIALS AND METHODS: A retrospective analysis of 47 patients (25 males and 22 females; mean age, 23.0±5.4 years) with TM was performed. Myocardial iron load was assessed by T2* measurements, and volumetric functions were analyzed using the steady state free precession sequence. RESULTS In patients with myocardial iron deposition (T2* < 20 ms), the mean left ventricular ejection fraction (LVEF) was 64.73±4.94%. The LVEF of patients with myocardial siderosis was significantly lower than that of patients without myocardial siderosis (r=0.35, P = 0.014). Inverse and significant correlations between both the left ventricular (LV) end-systolic volume index and the LV end-diastolic volume index and the myocardial T2* value (r=-0.32, P = 0.027 and r=-0.29, P = 0.046, respectively) were observed. There was an inverse correlation between the myocardial T2* value and the liver iron concentration (r=-0.31, P = 0.037). Cardiac T2* was not associated with serum ferritin levels, pre-transfusion hemoglobin levels or the annual red cell consumption rate. CONCLUSION: Myocardial iron load assessed by cardiac MRI (T2*) is associated with deterioration in left ventricular function. Thalassemia major patients with myocardial siderosis may have LVEF values within normal limits, but this result must be interpreted cautiously.