Early diagnosis of fungal infections using piezomicrogravimetric and electric chemosensors based on polymers molecularly imprinted with d-arabitol.

An elevated concentration of d-arabitol in urine, especially compared to that of l-arabitol or creatinine, is indicative of a fungal infection. For that purpose, we devised, fabricated, and tested chemical sensors determining d-arabitol. These chemosensors comprised the quartz crystal resonator (QCR) or extended-gate field-effect transistor (EG-FET) transducers integrated with molecularly imprinted polymer (MIP) film recognition units. To this end, we successfully applied a covalent approach to molecular imprinting, which involved formation of weak reversible covalent bonds between vicinal hydroxyl groups of arabitol and boronic acid substituents of the bithiophene functional monomer used. The MIP films were synthesized and simultaneously deposited on gold electrodes of quartz crystal resonators (Au-QCRs) or Au-glass slides by oxidative potentiodynamic electropolymerization. With the QCR and EG-FET chemosensors, the d-arabitol concentration was determined under flow-injection analysis and stagnant-solution binding conditions, respectively. Selectivity with respect to common interferences, and l-arabitol in particular, of the devised chemosensors was superior. Limits of detection and linear dynamic concentration ranges of the QCR and EG-FET chemosensors were 0.15 mM and 0.15 to 1.25 mM as well as 0.12 mM and 0.12 to 1.00 mM, respectively, being lower than the d-arabitol concentrations in urine of patients with invasive candidiasis (>220 µM). Therefore, the devised chemosensors are suitable for early diagnosis of fungal infections caused by Candida sp. yeasts.

Development of chronic myeloid leukaemia in patients treated with anti-VEGF therapies for clear cell renal cell cancer.

Tyrosine kinase inhibitors are novel therapies targeting specific cellular signalling pathways. Sunitinib and sorafenib primarily block tyrosine kinase receptors involved in the progression of many tumours, including clear cell renal cell cancer (ccRCC). Although developed to target selected receptors, it is becoming apparent that they inhibit other kinases; this may result in the development of unexpected side effects. This is potentially dangerous as kinases on noncancerous cells are also inhibited. TKI off-target effects contributing to cardiotoxicity, hypothyroidism, hypertension, fatigue, hair depigmentation, hand-foot syndrome and gastrointestinal perforation have been described. We report three patients (3/412) treated with sunitinib and sorafenib who developed chronic myeloid leukaemia (CML) during treatment for ccRCC, proposing a molecular mechanism of tyrosine kinase inhibitors action on bone marrow cells that might be co-responsible for CML development.

Efficacy of targeted therapy in patients with renal cell carcinoma with pre-existing or new bone metastases.

INTRODUCTION: This single-centre retrospective analysis of data from three randomised studies and two expanded-access studies compared the effect of interferon (IFN)-alfa, sunitinib, and sorafenib on the occurrence and progression of metastatic bone lesions in patients with renal cell carcinoma (RCC). METHODS: The analysis included 292 patients: 107 received sunitinib 50 mg/day in 6-week cycles (Schedule 4/2), 147 received sorafenib 800 mg/day, and 38 received placebo or IFN-alfa 9 MU t.i.w. RESULTS: Pre-existing metastatic bone lesions were reported in 82 patients, of which 30 experienced progression. Twenty-three of 210 patients developed new bone lesions. Overall, sunitinib appeared slightly more effective than sorafenib or IFN-alfa at extending mean time to progression of pre-existing bone lesions (P = 0.057). Compared with sorafenib, sunitinib significantly decreased formation (P = 0.034) and prolonged time to occurrence of new bone lesions (P = 0.047). CONCLUSION: Further evaluation of the effect of these therapies on bone metastases in RCC is warranted.

Blood and marrow transplantation and nutritional support.

INTRODUCTION: Undernourishment on hospital admission has been considered as risk factor for complications and increased relapse/nonrelapse mortality in hematopoietic stem cell transplantation (HSCT) patients. MATERIALS AND METHODS: All patients undergoing HSCT are at an increased risk for malnutrition. The changes in these patients affect mainly protein, energy, and micronutrient metabolism. Nutrition support recommendations are now based on the nutritional status of the individual patient, and total parenteral nutrition is no longer indicated for all HSCT patients. As long as it is possible, an oral route should be use in feeding to avoid complications. When total parenteral nutrition (TPN) should be started is one of the most controversial issues. The following indications for TPN are now generally accepted: severe malnutrition at admission (BMI < 18.5) or weight loss > 10% during treatment or impossibility of oral feeding or failing to meet 60-70% of the requirements over 3 days. Specialized nutritional support containing glutamine or immunomodulatory formulas such as arginine, ω3 polyunsaturated fatty acids, purine/pyrimidines (RNA) may be useful. RESULT: The complications of TPN are divided into metabolic and those related to central venous catheter. TPN should be progressively decreased while increasing feedings by the oral route. When the patients can cover ≥50% of the daily energy requirements orally (for greater than 5 days), withdrawal of TPN may be appropriate. In patients who have suffered from graft-versus-host disease (GvHD) with intestinal involvement, TPN should be used until the stool volume decreases to <500 ml/day for at least 2 days. CONCLUSION: Parenteral nutrition allows better modulation of fluid, electrolytes, and nutrient administration which can be of critical importance when complications such as GvHD or VOD arise.