Survival and mortality analysis in two nephrology centers: A prospective observational study.

BACKGROUND: The prevalence of chronic kidney disease (CKD) requiring dialysis therapy is increasing globally. Survival and mortality data of these patients in Germany are fragmentary since the nationwide registry was terminated in 2006. OBJECTIVE: The objective of this study was to analyze the survival, causes of death, and co-morbidities of dialysis patients in a German population cohort as well as to assess the factors influencing mortality in these patients. MATERIALS AND METHODS: We included adult, prevalent chronic dialysis patients from the German population who underwent hemodialysis and peritoneal dialysis at our centers between 2014 and 2018. We compared the characteristics of living and deceased patients and assessed survival. Patients with and without diabetes mellitus were also examined, and their co-morbidities were analyzed. RESULTS: Of the 425 patients included in our study (m/f: 235/190), 182 died within the observation period. Mean survival of patients with coronary artery disease (CAD) (n = 217), peripheral artery disease (PAD) (n = 128), and cardiorenal syndrome (CRS) (n = 99) was significantly reduced compared to patients without the disease (CAD: 4.2 vs. 6.4 years; PAD: 4.3 vs. 6.5 years; CRS: 3.7 vs. 7.3 years, p < 0.001, respectively). Patients with diabetes mellitus (n = 110) showed no reduced survival compared to patients without the disease (n = 315) (4.8 vs. 4.9 years, p = 0.421). Diastolic blood pressure (DBP) and C-reactive protein (CRP) levels were associated with dialysis time in linear regression analysis (DBP: R = 0.029, p < 0,001; CRP: R = 0.085, p < 0.001). CONCLUSION: Our results provide novel data regarding German CKD patients requiring dialysis and factors influencing mortality, which could serve as a useful reference for further studies.

Evaluation of Grenache, Graciano and Tempranillo grape stilbene content after field applications of elicitors and nitrogen compounds.

BACKGROUND: Stilbenes have a significant biological activity and are one of the most important non-flavonoid contributors to grape and wine health-related properties. The accumulation of this class of compounds could be favored by viticultural practices such as the application of biostimulants. However, stilbene concentration also depends on several factors, including, for example, grape variety. Therefore, the aim of this work was to study the influence of foliar treatments carried out with elicitors (methyl jasmonate (MeJ) and a commercial foliar spray (YD)) and nitrogen compounds (phenylalanine and urea) on the grape stilbene composition of three varieties: Grenache, Graciano and Tempranillo. An ultra-high-pressure liquid chromatographic methodology was validated for stilbene determination. RESULTS: Results showed that, despite the huge influence of the grape variety, YD significantly improved stilbene composition in Grenache and Graciano, while MeJ increased the stilbene content in Graciano and Tempranillo. As for the nitrogen treatments, phenylalanine significantly increased the stilbene concentration in Graciano, while urea treatment increased it in Tempranillo. However, the application of elicitors had a greater effect than the nitrogen compounds. CONCLUSION: Overall, the foliar application of the elicitors could be a suitable practice for increasing the amount of stilbenes in grape and, therefore, its nutraceutical properties. © 2017 Society of Chemical Industry.

Comparison of pretherapeutic and posttherapeutic expression levels of chemotherapy-associated genes in adenocarcinomas of the esophagus treated by 5-fluorouracil- and cisplatin-based neoadjuvant chemotherapy.

We analyzed expression of genes associated with metabolism of chemotherapeutic drugs in locally advanced esophageal adenocarcinomas before and after neoadjuvant chemotherapy to study whether there is a change in gene expression induced by chemotherapy and whether such changes are associated with tumor response or nonresponse. We included 21 patients with locally advanced esophageal adenocarcinomas treated by cisplatin- and 5-fluorouracil (5-FU)-based neoadjuvant chemotherapy before surgery. Messenger RNA was extracted from formalin-fixed, paraffin-embedded preoperative endoscopic esophageal tumor biopsy specimens and tumor tissue specimens after surgical resection. Expression levels of chemotherapy metabolism-associated genes thymidylate synthase (TYMS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), multidrug resistance-associated protein 1 (MRP1), and multidrug-resistance gene 1 (MDR1) were determined by quantitative real-time reverse transcriptase-polymerase chain reaction. There was a significant posttherapeutic reduction in the expression levels of TP (P = .028) and MRP1 (P = .006). Furthermore, down-regulation of MRP1 (P = .041) and TYMS (P = .028) after chemotherapy was associated with tumor response to chemotherapy, assessed clinically and by histopathologic tumor regression. Down-regulation of chemotherapy metabolism-associated genes occurs after neoadjuvant chemotherapy and may modulate tumor response to chemotherapy.

Quantification of stilbenoids in grapevine canes and grape cluster stems with a focus on long-term storage effects on stilbenoid concentration in grapevine canes.

On the one hand there is an enormous amount of underutilized side-streams rich in bioactives during wine-production, while on the other hand there is a growing demand for promising phytochemicals for e.g. dietary and pharmaceutical purposes. In the present study we analyzed the stilbenoid contents of grape canes and grape cluster stems collected in Germany. Likewise we investigated the effect of long-term post-harvest storage on stilbenoid levels in grape canes and also the variability of stilbenoids in grape cluster stems during growth cycle. The predominant stilbenoids in either canes or stems were trans-resveratrol and trans-ε-viniferin. The contents in canes ranged from 441 to 7532 and 1218 to 5341mg/kgDW for trans-resveratrol and trans-ε-viniferin, respectively, depending on variety, vintage and storage time. Within storage of 6 months the content in canes increased by up to a factor of fourteen. Stilbenoid contents in grapevine cluster stems varied from 16 to 289 and 23 to 253mg/kgDW for trans-resveratrol and trans-ε-viniferin, respectively, depending on vintage and wine-growing area.

Association of pretherapeutic expression of chemotherapy-related genes with response to neoadjuvant chemotherapy in Barrett carcinoma.

PURPOSE: We analyzed pretherapeutic gene expression patterns of patients with locally advanced adenocarcinomas of the esophagus with regard to response to neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: Pretherapeutic, paraffin-embedded, formalin-fixed endoscopic esophageal tumor biopsies of 38 patients with locally advanced esophageal adenocarcinomas (Barrett adenocarcinoma) were included. All patients underwent two cycles of cisplatin and 5-fluorouracil (5-FU) therapy with or without additional paclitaxel followed by abdominothoracal esophagectomy. RNA expression levels of 5-FU metabolism-associated genes thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase, MAP7, and ELF3, of platinum- and taxane-related genes caldesmon, ERCC1, ERCC4, HER-2/neu, and GADD45, and of multidrug resistance gene MRP1 were determined using real-time reverse transcriptase-PCR. Expression levels were correlated with response to chemotherapy, histopathologically assessed in surgically resected specimens. RESULTS: Responding patients showed significantly higher pretherapeutic expression levels of MTHFR (P = 0.012), caldesmon (P = 0.016), and MRP1 (P = 0.007). In addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival benefit after surgery (P = 0.013 and P = 0.015, respectively). Additionally, investigation of intratumoral heterogeneity of gene expression of relevant genes (MTHFR, caldesmon, HER-2/neu, ERCC4, and MRP1), verified in nine untreated Barrett adenocarcinomas by examination of five distinct tumor areas, revealed no significant heterogeneity in gene expression indicating that expression profiles obtained from biopsy material may yield a representative genetic expression profile of total tumor tissue. CONCLUSIONS: Our results indicate that determination of mRNA levels of few genes may be useful for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with locally advanced Barrett adenocarcinoma.

Chemical Characterization, Free Radical Scavenging, and Cellular Antioxidant and Anti-Inflammatory Properties of a Stilbenoid-Rich Root Extract of Vitis vinifera.

Dietary stilbenoids are receiving increasing attention due to their potential health benefits. However, most studies concerning the bioactivity of stilbenoids were conducted with pure compounds, for example, resveratrol. The aim of this study was to characterize a complex root extract of Vitis vinifera in terms of its free radical scavenging and cellular antioxidant and anti-inflammatory properties. HPLC-ESI-MS/MS analyses of the root extract of Vitis vinifera identified seven stilbenoids including two monomeric (resveratrol and piceatannol), two dimeric (trans-ɛ-viniferin and ampelopsin A), one trimeric (miyabenol C), and two tetrameric (r-2-viniferin = vitisin A and r-viniferin = vitisin B) compounds which may mediate its biological activity. Electron spin resonance and spin trapping experiments indicate that the root extract scavenged 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, galvinoxyl, and superoxide free radicals. On a cellular level it was observed that the root extract of Vitis vinifera protects against hydrogen peroxide-induced DNA damage and induces Nrf2 and its target genes heme oxygenase-1 and γ-glutamylcysteine synthetase. Furthermore, the root extract could induce the antiatherogenic hepatic enzyme paraoxonase 1 and downregulate proinflammatory gene expression (interleukin 1ß, inducible nitric oxide synthase) in macrophages. Collectively our data suggest that the root extract of Vitis vinifera exhibits free radical scavenging as well as cellular antioxidant and anti-inflammatory properties.