Vascular calcification and hemodynamical abnormalities lead to reduced arterial elasticity in end stage renal disease. Fibroblast growth factor-23 (FGF23) predicts cardiovascular mortality in advance stages of renal failure possibly indicating more advanced vascular calcification. The relation of FGF23 to arterial stiffness in chronic kidney disease is currently under investigations. The aim of our cross sectional study was to assess the potential associations between FGF23 and arterial distensibility. FGF23 (ELISA), pulse wave velocity (PWV), augmentation index (AI) and central pulse pressure (CPP) (PulsePen), were measured in patients with different stages of renal insufficiency (n = 103, 64.8±13.3 years, 50 males, eGFR 40±21 mL/min/1.73m 2 ). Univariate and multiple linear regression models were used for the statistical analysis. According to our results, logFGF23 showed significant relation with serum phosphate, PTH levels and renal function. There were no significant correlations between FGF23 and PWV or CPP. AI, however, correlated negatively with logFGF23 (r = -0.24, p<0.05). By multiple regressions, serum phosphate, logFGF23, systolic blood pressure and heart rate proved to be the individual predictors of AI. (R 2 = 0.31, ß = 0.31, -0.33, 0.21, -0.27, p<0.05). In the subgroup of patients with <45 mL/min/1.73m 2 eGFR, serum phosphate and logFGF23 remained the significant predictors (R 2 0.21, ß = 0.31, -0.39, p<0.05) FGF23 may be a determinant of peripheral arterial elasticity independently of serum phosphate level especially in advanced stages of chronic kidney disease. (Supported by the Hungarian Kidney Foundation and the Hungarian Society of Hypertension)
Endothelial dysfunction, as assessed by laser-Doppler flowmetry (LDF) is an accepted method to measure microvascular reactivity, which correlates with cardiovascular risk factors in several patient populations. The aim of our prospective cohort study was to assess determinants of LDF parameters and to evaluate their prognostic values in patients with chronic kidney disease (CKD). Ninety four hypertensive, stage 1–5 non-dialysis CKD patients had LDF measurements (iontophoresis of acethylcoline and sodium nitropusside in different doses and postocclusive reactive hyperaemia (PORH)). Baseline associations of these parameters with clinical, hemodynamic and laboratory characteristics were determined by linear regression models. Patients were followed for a median of 43 (37–55) months and the prognostic value of LDF parameters for cardiovascular (CV) events were evaluated by log-rank tests and Cox proportional hazard models. The different LDF parameters did show strong correlation with each other. All iontophoresis parameters were strongly and negatively related to the presence of diabetes or antidiabetic treatment. All PORH parameters were strongly and negatively associated to central pulse pressure and the use of calcium channel blockers. During follow-up 26 CV events occurred. In multivariate analysis, only the presence of diabetes was found to be an independent predictor of CV events (RR: 3.85 (1.66–8.89), p=0.0012). None of the LDF parameters predicted CV outcome. According to our results only the presence of diabetes, but not parameters of microvascular reactivity measured by iontophoresis or PORH have prognostic value for CV events in patients with CKD on conservative therapy. (Supported by Hungarian Kidney Foundation and Hungarian Society of Hypertension).
The etiology of tumors in young age is not precisely known yet, but studies on the topic generally agree that in this group of patients the traditionally known behavioural risk factors (tobacco and alcohol abuse) play no or a significantly less important role. Oral squamous cell carcinoma occurring at a young age is a topic of utmost importance that is extensively and intensively researched as, while the overall incidence of oral cancer is decreasing worldwide, that of squamous cell carcinoma diagnosed in young adults is steadily increasing. The present article aims at presenting the main questions and characteristics of tumors in young adults in Central-Eastern Europe and in developed West European countries as contrasted to tumors found in middle aged and elderly patients. Factors influencing the development of oral cancer include regulatory factors of the cell cycle, the inherited vulnerability of the genetic code of certain proteins and the presence of HPV infection with an oncogenic genotype. The connections of HPV infection and genetic damages are studied intensively. It is known that the prevalence of oral HPV infections is growing with a background of potentially changing sexual habits. It is debated, however, whether smoking and alcohol consumption could have a connection to HPV associated oral cancer and whether the spread of HPV in itself could be an explanation for the growing occurrence of young-age tumors. There is no consensus in the literature as to the prognostic significance of age. Some research groups have found a better life expectancy for young patients, while other authors found a worse prognosis for these patients. It is known that the prognosis of head and neck tumors, the prevalence of HPV infections as well as genetic mutations show regional and ethnic variations. This might be explained by differences in the degree of development of a preventive system, in the quality of care and in the attitudes of young patients towards visiting a doctor. The study is made difficult by incomparable patient selection criteria as well as by the question of the intraoral localisation of tumors as an independent risk factor.
Background The incidence of fractures is substantially increased in patients with chronic kidney disease (CKD) compared to the general population. The factors associated with increased bone fracture in this population are not well understood. Vitamin D deficiency has been associated with decreased bone mass and higher incidence of fractures in the general population. In this study, we aimed to assess the association between fracture and vitamin D status and other factors potentially associated with fracture in patients on maintenance hemodialysis. Methods One hundred and forty-four patients were assessed and interviewed about previous low-trauma fractures. Evidence of fracture was obtained from medical records and also through patient interviews. Routine laboratory results were collected from medical records. Serum intact PTH (iPTH) and 25(OH) vitamin D 3 were measured. All patients underwent bone densitometry of the lumbar spine, femoral neck and distal radius. Bone quality was also assessed with quantitative bone ultrasound (QUS). Descriptive statistics, logistic regression models were used to analyze factors associated with fractures. Results One hundred and thirty patients were included in the final analysis. Patients with fractures ( n = 21) had lower 25(OH) vitamin D 3 levels (15.8 nmol/l (interquartile range, IQR: 27) vs. 30.0 nmol/l (IQR: 28.5), P = 0.029), were more likely females, had longer duration of end-stage kidney disease, and lower bone mineral density (BMD) at the distal radius. QUS parameters were not associated with fractures. Multivariate analyses revealed that serum 25(OH) vitamin D 3 concentration, BMD at the radius, iPTH less than 100 pg/ml and history of fractures were independent predictors of new bone fracture after the initiation of dialysis therapy. Conclusion Increased bone fragility in dialysis patients is associated with vitamin D deficiency and relative hypoparathyroidism in addition to reduced BMD at the radius. Further studies are needed to determine whether patients with vitamin D deficiency benefit from vitamin D supplementation to reduce fracture risk.
The relationship between parathyroid function, an important determinant of bone turnover, and bone mineral density (BMD) in patients with chronic kidney disease is not fully understood. We wanted to analyze the association between BMD and parathyroid function in hemodialysis patients in details.
Adherent and tight junction molecules have been described to contribute to carcinogenesis and tumor progression. Additionally, the group of claudin-low tumors have recently been identified as a molecular subgroup of breast carcinoma. In our study, we examined the expression pattern of claudins, beta-catenin and E-cadherin in invasive ductal (IDCs) and lobular (ILCs) carcinomas and their corresponding lymph node metastases (LNMs). Tissue microarrays of 97 breast samples (60 invasive ductal carcinomas, 37 invasive lobular carcinomas) and their corresponding LNMs have been analyzed immunohistochemically for claudin-1, -2, -3, -4, -5, -7, beta-catenin and E-cadherin expression. The stained slides were digitalized with a slide scanner and the reactions were evaluated semiquantitatively. When compared to LNMs, in the IDC group beta-catenin and claudin-2, -3, -4 and -7 protein expression showed different pattern while claudin-1, -2, -3, -4 and -7 were differently expressed in the ILC group. Lymph node metastases developed a notable increase of claudin-5 expression in both groups. Decrease or loss of claudin-1 and expression of claudin-4 in lymph node metastases correlated with reduced disease-free survival in our patients. According to our observations, the expression of epithelial junctional molecules, especially claudins, is different in primary breast carcinomas compared to their lymph node metastases as demonstrated by immunohistochemistry. Loss of claudin junctional molecules might contribute to tumor progression, and certain claudin expression pattern might be of prognostic relevance.