ABSTRACT
BACKGROUND: Metabolic toxicities of mTOR inhibitors (mTORi) are well characterized. The purpose of the study was to investigate the relationship between these metabolic toxicities and mTORi efficacy. METHODS: From 2007 to 2011, metabolic toxicities were retrospectively collected in patients treated with an mTORi (everolimus, temsirolimus) for a metastatic renal cell carcinoma (mRCC) in a single institution. Patients were eligible if they have received an mTORi for at least 28 days. Changes in the following parameters were analyzed: lymphocytes, serum creatinine, glycemia, serum phosphate, liver transaminases, cholesterol, and triglycerides. The efficacy was assessed by progression-free survival (PFS) and tumor response. RESULTS: Data were collected from seventy-five patients (everolimus = 44 patients; temsirolimus = 31 patients). Six patients exhibited a partial response, 42 a stable disease and 15 had a progressive disease (12 missing). After a median follow-up of 12.8 months, the median PFS was 6.7 months (95% confidence interval: 4.0-9.1 months). Patients with CB had a statistically more severe absolute increase of glycemia and absolute decrease in phosphatemia (p = 0.002 and p = 0.02 respectively). The Progression Free Survival was significantly higher with the onset rate of hypophosphatemia (p = 0.03) and hyperglycemia (p = 0.001) and lower with the onset rate of lymphopenia (p = 0.004). CONCLUSIONS: Hyperglycemia, hypophosphatemia and lymphopenia, were significantly associated with tumor response and/or PFS. Those events, as well as their onset rate, should be prospectively monitored as predictors of response to mTORi.
Subject(s)
Carcinoma, Renal Cell/drug therapy , Everolimus/adverse effects , Kidney Neoplasms/drug therapy , Sirolimus/analogs & derivatives , TOR Serine-Threonine Kinases/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biomarkers , Biomarkers, Tumor , Disease-Free Survival , Everolimus/pharmacology , Everolimus/therapeutic use , Female , France , Humans , Male , Middle Aged , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Sirolimus/adverse effects , Sirolimus/pharmacology , Sirolimus/therapeutic use , Treatment OutcomeABSTRACT
We demonstrate a high-power cladding-pumped Er-Yb codoped fiber laser with 74% efficiency. A pump-limited output power of 264 W is obtained using in-band pumping at 1535 nm. We compare the efficiency of 1480 and 1535 nm pumping through numerical simulations and experimental measurements.
ABSTRACT
BACKGROUND: To evaluate the correlation and agreement between central venous saturation (ScvO(2)) and mixed venous saturation (SvO(2)) during cardiopulmonary bypass. METHODS: Twenty-two consecutive patients scheduled for coronary artery surgery were prospectively included. Paired measurements of ScvO(2) and SvO(2) were performed 5 minutes after aortic cross-clamping, after each cardioplegia dose and after de-clamping of the aortic cross-clamp. ScvO(2) and SvO(2) were measured, respectively, by a fibreoptic catheter in the superior vena cava and on blood samples from the venous return line of the extracorporeal circuit, using a blood gas analyser RESULTS: Ninety-five paired measurements of venous saturation were obtained. Correlation between the measurements was associated with an r = 0.55. The mean bias was 2.2 [Limits of agreement: -13.6%, +18%]. Changes in oxygen saturation over time showed an r = 0.4 and a mean bias of 0.2 [Limits of agreement: -17.9%, +18.3%]. Multivariate analysis identified the oxygen consumption index as the only factor explaining this variability. CONCLUSIONS: Although mean biases between the measurements were low, limits of agreement were too large to provide a clinically acceptable estimation of SvO(2) by ScvO(2) in these conditions. Variations in regional oxygen consumption seem to be the main factor worsening the relationship.
