Alena Tichá

Polypharmacy and malnutrition.

Purpose of reviewMalnutrition and polypharmacy increase with age and polymorbidity and their relationship is based on a number of mechanisms. The occurrence of malnutrition in both in-patients and out-patients and its dependence on polymorbidity and age are well known, but the interrelation of polypharmacy and malnutrition has been far less investigated. The countries with the highest occurrence of polypharmacy in Europe include the Czech Republic and Finland, whereas the lowest prevalence of polypharmacy is found in Norway and the Netherlands. Recent findingsThe occurrence, consequences and mutual relationship of malnutrition and polypharmacy are described. Up-to-date knowledge regarding the influence of drugs on nutritional status is summarized. SummaryThe effect of polypharmacy on nutrition is suggested from the observations that problems with nutrition occur mostly in elderly patients, and that such patients are more frequently subject to polypharmacy. It is known that about 65% of hospitalized patients have a worse nutritional status than their healthy contemporaries. A worsened nutritional status may adversely influence the process of treatment.

Intestinal permeability in patients with metastatic colon cancer treated with patupilone.

Abstract Background: Only a limited number of cytotoxic drugs have shown activity in metastatic colorectal carcinoma. Patupilone is a novel agent with promising activity in this common cancer. Diarrhea represents the dose-limiting toxicity of patupilone. Measurement of intestinal permeability is one of the potential methods of non-invasive laboratory assessment of gastrointestinal toxicity. Methods: We have assessed intestinal permeability by measuring absorption of lactulose, mannitol and xylose in 27 previously treated patients with metastatic colorectal cancer enrolled in a phase I trial of patupilone. Results: Lactulose/mannitol and lactulose/xylose ratios increased after the treatment. Significantly higher lactulose/mannitol ratio was observed in patients who had severe diarrhea. Moreover, patients who subsequently had an adverse event of grade 3 or higher had significantly higher baseline lactulose/mannitol or lactulose/xylose ratios. Conclusions: Measurement of intestinal permeability using the lactulose/mannitol test may represent a biomarker for the monitoring, or even prediction of toxicity of cytotoxic drugs, including patupilone.

Markers of Perioperative Bowel Complications in Colorectal Surgery Patients

Colorectal cancer is a clinical condition whose treatment often involves intestinal resection. Such treatment frequently results in two major gastrointestinal complications after surgery: anastomotic leakage and prolonged ileus. Anastomotic leakage is a serious complication which, more often than not, is diagnosed late; to date, C-reactive protein is the only available diagnostic marker. A monocentric, prospective, open case-control study was performed in patients (n = 117) undergoing colorectal surgery. Intestinal fatty acid binding protein (i-FABP), citrulline, D-lactate, exhaled hydrogen, Escherichia coli genomic DNA, and ischemia modified albumin (IMA) were determined preoperatively, postoperatively, and on the following four consecutive days. Bacterial DNA was not detected in any sample, and i-FABP and D-lactate lacked any distinct potential to detect postoperative bowel complications. Exhaled breath hydrogen content showed unacceptably low sensitivity. However, citrulline turned out to be a specific marker for prolonged ileus on postoperative days 3-4. Using a cut-off value of 20 μmol/L, a sensitivity and specificity of ~75% was achieved on postoperative day 4. IMA was found to be an efficient predictor of anastomosis leak by calculating the difference between preoperative and postoperative values. This test had 100% sensitivity and 80% specificity and 100% negative and 20% positive predictive value.

Disease specific substrates in cancer cachexia - Reality and anticipation.

In recent years, the concept of nutrition in patients with tumour diseases has been changing very significantly. The article discusses the pathogenesis of tumour cachexia and sarcopenia, which have been intensively studied, particularly in the last ten years. The possibilities and modern approaches in nutritional support in oncology are reviewed with a special emphasis on the group of elderly patients. Also, a detailed list of the most frequently used pharmaconutrients in oncology is presented. The recommendations for nutritional care of elderly oncological patients are given and discussed.

Hemodiafiltration and plasma levels of axitinib in a patient with metastatic renal clear cell carcinoma

BACKGROUND The standard treatment for metastatic renal cancer is based on vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTor) inhibitors. Compared to other advanced tumors, the treatment of renal cancer is highly affected by impaired renal function; therefore, patients with severe renal insufficiency, including patients on hemodialysis, are generally excluded from clinical trials. CASE REPORT In the present manuscript we present the case of a renal cancer patient who underwent bilateral nephrectomy and received two lines of treatment. We hypothesized that axitinib, a tyrosine kinase inhibitor, would have a similar plasma concentration to patients without hemodialysis and that the levels before and after hemodiafiltration will not differ significantly, as observed in other targeted therapies. CONCLUSION The observed axitinib concentrations were at least an order of magnitude lower than expected based on the literature and measurements in other patients. The present case report indicates a potential risk of axitinib underdosing in patients on hemodiafiltration with the standard dose; therefore, drug dosage may need to be corrected based on the plasma levels of axitinib.

Changes in cholesterol metabolism during acute upper gastrointestinal bleeding: liver cirrhosis and non cirrhosis compared

BACKGROUND Cholesterol is derived via de novo synthesis and dietary absorption. Both processes can be monitored by determination of non-cholesterol sterol concentrations (lathosterol for synthesis; sitosterol and campesterol for absorption). The hypocholesterolemia that occurs during acute illness is a result of a multifactorial inability to compensate for the increased needs for this metabolite. The aim of this study was to examine the plasma cholesterol profile and both processes of cholesterol acquisition during acute upper gastrointestinal haemorrhage with emphasis on liver cirrhosis. MATERIAL AND METHODS Thirty five patients with acute upper gastrointestinal bleeding (cirrhosis n=14, non-cirrhosis n=21) were evaluated over a 6 day period. The control cohort consisted of 100 blood donors. Serum concentrations of total, LDL (low-density lipoprotein) and HDL (high-density lipoprotein) cholesterol were measured enzymatically. Sterol concentrations were analysed using gas chromatography, data were statistically analysed. RESULTS In all patients, we found lower plasma levels of total cholesterol (P<0.001) and decrease of LDL and HDL cholesterol. Patients had also significantly lower plasma levels of sterol concentrations. While the differences in cholesterol profile between cirrhotic and non-cirrhotic bleeding were significant only in HDL cholesterol (P<0.001), comparison of non-cholesterol sterols was statistically significant (P<0.001) in all measured parameters. CONCLUSION Our results showed substantial abnormalities in the cholesterol plasma profile including both the processes of cholesterol acquisition in patients with upper acute gastrointestinal bleeding. The patients with or without liver cirrhosis had similar trends in cholesterol plasma levels. Depression of cholesterol synthesis was, however, prolonged in the cirrhotic group and the data also suggest a different phytosterol metabolism.

Selected Risk Nutritional Factors for Chemotherapy-Induced Polyneuropathy

The present study seeks to identify the nutritional risk factors involved in the development of neuropathies induced by chemotherapeutic treatments. Unlike the gastrointestinal or hematological adverse effects of chemotherapy there is no protective treatment strategy for polyneuropathy. The aim of this study was to find possible deficiencies in nutritional factors, which can be used for supplementation in the future for prevention of chemotherapy-induced neuropathy development. We analyzed 70 patients undergoing paclitaxel chemotherapy and evaluated the risk factors involved in chemotherapy-induced peripheral neuropathy (CIPN). Several risk factors were considered in the development of CIPN, including deficiency of vitamin B1, B6, and D and fatty acids. The occurrence of CIPN complication in 60% cases was observed. We found significant differences in vitamin D and saturated fatty acid concentration. Vitamin D levels in the group without CIPN were estimated to be 38.2 (24.95, 47.63) nmol/L, whereas in the group with CIPN it was determined to be 25.6 (19.7, 32.55) nmol/L, p = 0.008. The level of total saturated fatty acids in the group without CIPN was of 32.613 Area % (31.322; 36.262), whereas in the group with CIPN it was of 34.209 Area % (32.86; 39.386), p = 0.01. The obtained results suggest a diet lower in saturated fatty acid content during chemotherapy. The most significant finding was that supplementation of vitamin D before chemotherapy could be an efficient neuroprotective in CIPN prophylaxis, as significantly lower levels 25OH derivative of vitamin D were observed in the CIPN group throughout the study period.