Management of Hyperlipidemia in Very High and Extreme Risk Patients in Croatia: an observational study of treatment patterns and lipid control.

Our observational study evaluated current management of elevated low-density lipoprotein cholesterol (LDL-C) in adult secondary prevention patients (all very high risk (VHR) by European guidelines) attending specialist clinics across Croatia. Data were collected retrospectively from patient records for the preceding 12 months. The subset judged to be at extreme risk (ER; American Association of Clinical Endocrinologists (AACE) criteria; n=48) were compared with the remaining patients (VHR group; n=41). All patients were receiving statins (75.6% VHR/81.3% ER at high-intensity), with only a minority receiving concomitant lipid-lowering treatment (7.3% VHR/16.7% ER). Median (Q1, Q3) LDL-C levels at the last visit were 1.9 (1.6, 2.4) mmol/L for VHR and 2.1 (1.5, 3.1) mmol/L for ER, with only 41.5% (95% CI 26.3-57.9) of VHR patients and 27.1% (15.3-41.9) of ER patients attaining their LDL-C targets (<1.8 mmol/L and <1.42 mmol/L, respectively). Thus, we found that a substantial proportion of VHR and ER secondary prevention patients being treated across Croatia had LDL-C levels exceeding the targets recommended in the European and newer AACE guidelines, but not all were receiving high-intensity statins. Identification of ER patients and their lipid patterns may help optimize usage of high-intensity statin treatment, alone or along with newer treatments, for better control of elevated LDL-C.

The role of p53 isoforms' expression and p53 mutation status in renal cell cancer prognosis.

OBJECTIVES: To analyze p53 mutations and gene expression of p53, ∆40p53, and ∆133p53 isoforms in renal cell cancer (RCC) tissues and normal adjacent tissue (NAT) and to associate them to clinical features and outcome. PATIENTS AND METHODS: Forty-one randomly selected patients, with primary, previously untreated RCC, with complete clinicopathohistological data were analyzed. NAT samples were available for 37 cases. Expression of p53, ∆40p53 and ∆133p53 was determined using RT-qPCR. A functional yeast-based assay was performed to analyze p53 mutations. RESULTS: More than half (56.1%) of patients harbored functional p53 mutations, and they were significantly younger than those with wild type (WT) p53 (P = 0.032). Expression of p53, ∆40p53, and ∆133p53 was upregulated in mutant (MT) p53 RCC compared to WT p53 RCC tissues. However, there was no difference in expression of these isoforms between MT p53 RCC tissues and NAT. Expression of ∆133p53 was significantly downregulated in WT p53 tissues compared to NAT (P = 0.006). Patients that harbored functional p53 mutation had better overall survival (hazard ratio 4.32, 95% confidence interval 1.46-18.82, P = 0.006). Multivariate analysis demonstrated that tumor stage and p53 mutation might be used as independent prognostic marker for overall survival in RCC patients. CONCLUSIONS: Our findings support the specific events in the carcinogenesis of RCC. p53 isoforms can be differentially expressed depending on p53 mutational status.