Neutrophil–lymphocyte ratio dynamics during concurrent chemo-radiotherapy for glioblastoma is an independent predictor for overall survival

Elevated neutrophil–lymphocyte ratio (NLR) may predict worse outcomes in cancer, including glioblastoma (GBM). This study assessed whether change in NLR during focal radiotherapy and concomitant temozolomide (RT-TMZ) provides further prognostic information. This was a retrospective review of patients treated with RT-TMZ for histologically confirmed GBM from January 2004 to September 2010. Variables assessed included age, ECOG performance status (PS), dexamethasone use and extent of surgery. Hematological results were collected at baseline, during and 4 weeks post RT-TMZ. Kaplan–Meier method was used to calculate overall survival (OS). Multivariable analysis (MVA) assessed for joint effect of covariates on OS and Pearson Correlation Coefficients assessed for association between dexamethasone dose and NLR change. With a median age of 55 (range 18–70), 369 patients were included. Median follow up was 15.1 month (range 1.6–134.6). The OS was 66.1% (95% CI 61.2–70.6) and 31.4 (95% CI 26.8–36.1) at 1 and 2 years, respectively. On univariate analysis, both decrease in NLR post RT-TMZ (HR 0.641, p?<?0.0001) and baseline NLR?<?7.5 (HR 0.628, p?<?0.0001) were associated with longer OS. On MVA decrease in NLR (HR 0.727, 95% CI 0.578–0.915), age (HR 1.025, 95% CI 1.012–1.038), baseline neutrophil (<8) (HR 0.689, 95% CI 0.532–0.891), total TMZ cycles (HR 0.89, 95% CI 0.867–0.913) and PS (HR 0.476, 95% CI 0.332–0.683) were independent predictors of OS. These findings suggest that a decrease in NLR during RT-TMZ, accounting for known prognostic factors, is an independent prognostic factor for survival in GBM.     

Resveratrol rescues cAMP-dependent anionic transport in the cystic fibrosis pancreatic cell line CFPAC1

BACKGROUND AND PURPOSE

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent chloride channel in the plasma membrane of epithelia whose mutation is the cause of the genetic disease cystic fibrosis (CF). The most frequent CFTR mutation is deletion of Phe⁵⁰⁸ and this mutant protein (delF508CFTR) does not readily translocate to the plasma membrane and is rapidly degraded within the cell. We hypothesized that treating epithelial cells with resveratrol, a natural polyphenolic, phyto-ooestrogenic compound from grapes, could modulate both the expression and localization of CFTR.

EXPERIMENTAL APPROACH

Cells endogenously expressing CFTR (MDCK1 and CAPAN1 cells) or delF508CFTR (CFPAC1 and airway epithelial cells, deriving from human bronchial biopsies) were treated with resveratrol for 2 or 18 h. The effect of this treatment on CFTR and delF508CFTR expression and localization was evaluated using RT-PCR, Western blot and immunocytochemistry. Halide efflux was measured with a fluorescent dye and with halide-sensitive electrodes. Production of interleukin-8 by these cells was assayed by ELISA.

KEY RESULTS

Resveratrol treatment increased CFTR expression or maturation in immunoblotting experiments in MDCK1 cells or in CFPAC1 cells. Indirect immunofluorescence experiments showed a shift of delF508CFTR localization towards the (peri)-membrane area in CFPAC1 cells and in human airway epithelial cells. A cAMP-dependent increase in membrane permeability to halide was detected in resveratrol-treated CFPAC1 cells, and was inhibited by a selective inhibitor of CFTR.

CONCLUSION AND IMPLICATIONS

These results show that resveratrol modulated CFTR expression and localization and could rescue cAMP-dependent chloride transport in delF508CFTR cells.     

A diet rich in long chain omega-3 fatty acids modulates satiety in overweight and obese volunteers during weight loss

Long chain omega-3 fatty acids (LC n-3 FA) are considered nutritional factors with a potential to modulate food intake. Thus, the aim of the current study was to determine whether appetite could be affected by LC n-3 FA when included in a calorie-restricted diet to treat overweight or obesity. Appetite was explored in volunteers (31+/-5 years; BMI: 28.3+/-1.5kg/m(2)) during the last 2 weeks of an 8-week energy-restricted balanced diet (weight loss=-5.9+/-3.1%) providing either a low (<260mg/day; n=112) or a high amount (>1300mg/day; n=121) of LC n-3 FA. Erythrocyte membrane fatty acids were measured to detect diet-related changes in fatty acids and a validated visual analogue scale (VAS) was used to measure hunger sensations directly after and 2h after a test dinner. The LC n-3 FA content in erythrocyte membrane was lower in the low LC n-3 FA group (10.5+/-2.5% vs. 12.5+/-2.6%; p<0.001) after the intervention. The VAS assessment revealed lower hunger sensations in the high LC n-3 FA group immediately after the test dinner (fullness: p=0.045) and after 120min (fullness: p=0.008; hunger: p=0.039). Correlation analysis showed a positive relation between n-3FA/n-6 FA ratio in erythrocyte membrane and fullness 2h postprandial (r=0.139; p=0.032). In conclusion, LC n-3 FA intake modulates postprandial satiety in overweight and obese volunteers during weight loss. Further research is needed to investigate whether LC n-3 FA improve compliance to the nutritional treatment of overweight and obesity as well as weight loss maintenance.     

Maternal mortality and the rising cesarean rate

ObjectiveTo review maternal mortality in a large stand-alone maternity hospital in a European city and to determine whether the increased cesarean rate was associated with an increase in maternal deaths.MethodsThe details of maternal deaths at Coombe Women and Infants University Hospital, Dublin, Ireland, as published in the hospital's Annual Clinical Reports for 1995–2009, were reviewed. Maternal mortality ratio was defined as the number of maternal deaths per 100 000 live births.ResultsOver 15 years, 112 326 women delivered 114 170 infants weighing at least 500 g. The cesarean rate increased from 14.1% in 1995 to 26.5% in 2009 (20.0% overall). The maternal mortality ratio was low at 2.7 per 100 000 live births. There were 2 maternal deaths following cesarean, neither of which was attributable to the operation.ConclusionIn Ireland, a large stand-alone maternity hospital can achieve a low maternal mortality ratio, according to international standards, despite an increase in cesarean rate over the past 2 decades. There was no evidence that the increased cesarean rate had an adverse impact on maternal mortality ratio.     

Time Costs Associated with Informal Care for Colorectal Cancer: An Investigation of the Impact of Alternative Valuation Methods

Background

A societal perspective in economic evaluation necessitates that all resources associated with a disease or intervention should be valued; however, informal care time costs are rarely considered.

Objective

We estimated time allocated to care by informal carers of colorectal cancer survivors; and investigated the impact of applying alternative valuation methods to this time.

Methods

Colorectal cancer cases (ICD10 C18-C20) diagnosed 6–30 months previously and identified from the National Cancer Registry Ireland were invited to provide details of informal carers. Carers completed a postal questionnaire. Time estimates per week associated with hospital-related and domestic-related care activities were collected for two phases: diagnosis and initial treatment (initial 3 months) and ongoing care (previous 30 days). Seven valuation scenarios, based on variants of the opportunity cost approach (OCA), and the proxy good approach (PGA), were considered. The base-case was OCA with all carer time valued at the average national wage.

Results

We received 154 completed questionnaires (response rate = 68 %). Average weekly time allocated to caring was 42.5 h in the diagnosis and initial treatment phase and 16.9 h in the ongoing care phase. Under the base-case, average weekly time costs were €295 (95 % CI 255–344) for hospital-related activities and €630 (95 % CI 543–739) for domestic-related activities in the diagnosis and initial treatment phase and €359 (95 % CI 293–434) in the ongoing care phase. PGA estimates were 23 % below the base-case. Only one alternative scenario (occupation and gender-specific wages for carers in paid work and replacement wages for non-working carers) surpassed base-case costs, and the difference was modest.

Conclusions

Overall, significant time is associated with informal caring in colorectal cancer. Different time valuation methods can produce quite different cost estimates. A standardised methodology for estimating informal care costs would facilitate better integration of these into economic evaluations.     

The influence of maternal body composition on birth weight

Objective

To identify the maternal body composition parameters that independently influence birth weight.

Study design

A longitudinal prospective observational study in a large university teaching hospital. One hundred and eighty-four non-diabetic caucasian women with a singleton pregnancy were studied. In early pregnancy maternal weight and height were measured digitally in a standardised way and the body mass index (BMI) was calculated. At 28 and 37 weeks’ gestation maternal body composition was assessed using segmental multifrequency bioelectrical impedance analysis. At delivery the baby was weighed and the clinical details were recorded.

Results

Of the women studied, 29.2% were overweight and 34.8% were obese. Birth weight did not correlate with maternal weight or BMI in early pregnancy. Birth weight correlated with gestational weight gain (GWG) before the third trimester (r = 0.163, p = 0.027), but not with GWG in the third trimester. Birth weight correlated with maternal fat-free mass, and not fat mass at 28 and 37 weeks gestation. Birth weight did not correlate with increases in maternal fat and fat-free masses between 28 and 37 weeks.

Conclusions

Contrary to previous reports, we found that early pregnancy maternal BMI in a non-diabetic population does not influence birth weight. Interestingly, it was the GWG before the third trimester and not the GWG in the third trimester that influenced birth weight. Our findings have implications for the design of future intervention studies aimed at optimising gestational weight gain and birth weight.

Condensation

Maternal fat-free mass and gestational weight gain both influence birth weight.