A double‐blind,randomized, controlled trial on N‐acetylcysteine for the prevention of acute kidney injury in patients undergoing allogeneic hematopoietic stem cell transplantation

Acute kidney injury (AKI) is one of the complications of hematopoietic stem cell transplantation and is associated with increased mortality. N‐acetylcysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties that has been investigated for the prevention of AKI in several clinical settings. In the present study, we evaluated the effects of intravenous NAC on the prevention of AKI in allogeneic hematopoietic stem cell transplantation patients. A double‐blind randomized placebo‐controlled trial was conducted, and 80 patients were recruited to receive 100 mg/kg/day NAC or placebo as intermittent intravenous infusion from day ?6 to day +15. AKI was determined on the basis of the Risk–Injury–Failure–Loss–End‐stage renal disease and AKI Network criteria as the primary outcome. We assessed urine neutrophil gelatinase‐associated lipocalin (uNGAL) on days ?6, ?3, +3, +9 and +15 as the secondary outcome. Moreover, transplant‐related outcomes and NAC adverse reactions were evaluated during the study period. Statistical analysis was performed using appropriate parametric and non‐parametric methods including Kaplan–Meier for AKI and generalized estimating equation for uNGAL. At the end of the trial, data from 72 patients were analysed (NAC: 33 patients and placebo: 39 patients). Participants of each group were not different considering baseline characteristics. AKI was observed in 18% of NAC recipients and 15% of placebo group patients, and the occurrence pattern was not significantly different (p = 0.73). Moreover, no significant difference was observed between groups for uNGAL measures (p = 0.10). Transplant‐related outcomes were similar for both groups, and all patients had successful engraftment. Three patients did not tolerate NAC because of abdominal pain, shortness of breath and rash with pruritus and were dropped from the intervention group before transplantation. However, the frequency of adverse reactions was not significantly different between groups. In conclusion, our findings could not show any clinical benefits from high‐dose NAC particularly for AKI prevention in allogeneic hematopoietic stem cell transplantation patients. Copyright © 2014 John Wiley & Sons, Ltd.     

Efficacy of l-carnitine supplementation for management of blood lipids: A systematic review and dose-response meta-analysis of randomized controlled trials

Background and aiml-carnitine has an important role in fatty acid metabolism and could therefore act as an adjuvant agent in the improvement of dyslipidemia. The purpose of present systematic review and meta-analysis was to critically assess the efficacy of l-carnitine supplementation on lipid profiles.Methods and resultsWe performed a systematic search of all available randomized controlled trials (RCTs) in the following databases: Scopus, PubMed, ISI Web of Science, The Cochrane Library. Mean difference (MD) of any effect was calculated using a random-effects model.In total, there were 55 eligible RCTs included with 58 arms, and meta-analysis revealed that l-carnitine supplementation significantly reduced total cholesterol (TC) (56 arms-MD: ?8.53 mg/dl, 95% CI: ?13.46, ?3.6, I²: 93%), low-density lipoprotein-cholesterol (LDL-C) (47 arms-MD: ?5.48 mg/dl, 95% CI: ?8.49, ?2.47, I²: 94.5) and triglyceride (TG) (56 arms-MD: ?9.44 mg/dl, 95% CI: ?16.02, ?2.87, I²: 91.8). It also increased high density lipoprotein-cholesterol (HDL-C) (51 arms-MD:1.64 mg/dl, 95% CI:0.54, 2.75, I²: 92.2). l-carnitine supplementation reduced TC in non-linear fashion based on dosage (r = 21.11). Meta-regression analysis indicated a linear relationship between dose of l-carnitine and absolute change in TC (p = 0.029) and LDL-C (p = 0.013). Subgroup analyses showed that l-carnitine supplementation did not change TC, LDL-C and TG in patients under hemodialysis treatment. Intravenous l-carnitine and lower doses (>2 g/day) had no effect on TC, LDL-C and triglycerides.Conclusionl-carnitine supplementation at doses above 2 g/d has favorable effects on patients' lipid profiles, but is modulated on participant health and route of administration.     

Genomic analysis of clonal eosinophils by CGH arrays reveals new genetic regions involved in chronic eosinophilia

To assess the presence of genetic imbalances in patients with myeloproliferative neoplasms (MPNs), 38 patients with chronic eosinophilia were studied by array comparative genomic hybridization (aCGH): seven had chronic myelogenous leukaemia (CML), BCR‐ABL1 positive, nine patients had myeloproliferative neoplasia Ph? (MPN‐Ph?), three had a myeloid neoplasm associated with a PDGFRA rearrangement, and the remaining two cases were Lymphoproliferative T neoplasms associated with eosinophilia. In addition, 17 patients had a secondary eosinophilia and were used as controls. Eosinophilic enrichment was carried out in all cases. Genomic imbalances were found in 76% of all MPN patients. Losses on 20q were the most frequent genetic abnormality in MPNs (32%), affected the three types of MPN studied. This study also found losses at 11q13.3 in 26% of patients with MPN‐Ph? and in 19p13.11 in two of the three patients with an MPN associated with a PDGFRA rearrangement. In addition, 29% of patients with CML had losses on 8q24. In summary, aCGH revealed clonality in eosinophils in most MPNs, suggesting that it could be a useful technique for defining clonality in these diseases. The presence of genetic losses in new regions could provide new insights into the knowledge of these MPN associated with eosinophilia.     

Vitamin D-Loaded Nanostructured Lipid Carrier (NLC): A New Strategy for Enhancing Efficacy of Doxorubicin in Breast Cancer Treatment

The dangerous dose-dependent side effects of anticancer agents triggered the finding of new approaches for elevated chemotherapy efficacy. This study investigated the potential application of nanostructured lipid careers (NLCs) in increasing vitamin D₃ (VitD) effectiveness in breast cancer cell (MCF-7) in concurrent administration with doxorubicin (Dox). VitD-loaded NLCs were characterized by particle size, zeta potential, Fourier transform infrared spectroscopy, and scanning electron microscope. Cytotoxicity and molecular effects of formulation were evaluated by MTT, DAPI staining, flow cytometry, and real-time quantitative PCR assays. The formulation revealed mean particle size of 87±5 nm with a polydispersity index of 0.24 confirmed by SEM images. The IC₅₀ values for VitD and Dox were 1.3 ± 0.04 and 0.65 ± 0.05 µM, respectively. VitD-loaded NLCs decreased the percentage of cell proliferation from 49 ± 7.2% to 37 ± 5.1% (P < 0.05). Cotreatment of the cells with VitD-loaded NLCs and Dox caused over a twofold increase in the percentage of apoptosis (P < 0.05). Gene expression profile demonstrated a significant decrease in antiapoptotic factor survivin along with increase in proapoptotic factor Bax mRNA levels. Overall, our results introduced the NLC technology as a novel strategy to elevate the efficacy of chemotherapeutics in breast cancer.     

Diagnostic du cancer du sein après 74 ans : information donnée par les structures de gestion du dépistage organisé à la sortie de la tranche d’âge concernée

BackgroundBreast cancer among older women is a major and increasing public health issue. No clear recommendation has been established in France after 74 years, the age limit for state-organised screening program. A survey was performed among all regional agencies in charge of the breast screening to analyse which information is delivered to women reaching the age of 75 years.MethodsA postal survey sent to 91 French organised cancer screening agencies.ResultsAmong the 89 agencies that answered, only 22 deliver a systematic written information. Twelve suggest that mammographic screening should be continued, and five mention clinical examination. Twenty agencies dispatch the screening to general practitionners or gynaecologists. Two information letters insist on the ongoing risk of breast cancer. Most of the written information is given with the last mammography report. No impact study has ever been performed.ConclusionIn our study, only 25% of the screening agencies give systematic information to women. The modalities and the substance of this information are heterogeneous. A better information seems to be a key-point for earlier clinical breast cancer diagnosis among older women, for whom there is little direct evidence of the benefit of systematic mammographic screening.