Excess adiposity at diagnosis and weight gain during chemotherapy is associated with tumour recurrence and chemotherapy toxicity. We assessed the efficacy of intermittent energy restriction (IER) vs ...continuous energy restriction (CER) for weight control and toxicity reduction during chemotherapy.
One hundred and seventy-two women were randomised to follow IER or CER throughout adjuvant/neoadjuvant chemotherapy. Primary endpoints were weight and body fat change. Secondary endpoints included chemotherapy toxicity, cardiovascular risk markers, and correlative markers of metabolism, inflammation and oxidative stress.
Primary analyses showed non-significant reductions in weight (-1.1 (-2.4 to +0.2) kg, p = 0.11) and body fat (-1.0 (-2.1 to +0.1) kg, p = 0.086) in IER compared with CER. Predefined secondary analyses adjusted for body water showed significantly greater reductions in weight (-1.4 (-2.5 to -0.2) kg, p = 0.024) and body fat (-1.1 (-2.1 to -0.2) kg, p = 0.046) in IER compared with CER. Incidence of grade 3/4 toxicities were comparable overall (IER 31.0 vs CER 36.5%, p = 0.45) with a trend to fewer grade 3/4 toxicities with IER (18%) vs CER (31%) during cycles 4-6 of primarily taxane therapy (p = 0.063).
IER is feasible during chemotherapy. The potential efficacy for weight control and reducing toxicity needs to be tested in future larger trials.
ISRCTN04156504.
Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC ...activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and self-renewal across all molecular subtypes in primary human breast cancer samples. Combined FAK and paclitaxel reduced self-renewal in triple negative cell lines. An invasive breast cancer cohort confirmed high FAK expression correlated with increased risk of recurrence and reduced survival. Co-expression of FAK and CSC markers was associated with the poorest prognosis, identifying a high-risk patient population. Combined FAK and paclitaxel treatment reduced tumour size, Ki67, ex-vivo mammospheres and ALDH+ expression in two triple negative patient derived Xenograft (PDX) models. Combined treatment reduced tumour initiation in a limiting dilution re-implantation PDX model. Combined FAK inhibition with adjuvant therapy has the potential to improve breast cancer survival.
Objective
To assess the effect of early pregnancy on obstetric fistula.
Methods
A prospective observational study was conducted among patients with obstetric fistula caused by a long obstructed labor ...who presented at Selian Lutheran Hospital, Tanzania, or Kitovu Hospital, Uganda, between January 1, 2015, and January 31, 2016. Demographic and clinical variables were evaluated.
Results
Among 270 patients, 162 (60.0%) experienced their first pregnancy up to 2 years after menarche (early group) and 108 (40.0%) experienced their first pregnancy more than 2 years after menarche (late group). No significant differences between the early and late groups were found for median age at presentation (30.0 vs 28.0 years), median parity (both 2.0), stillbirth (n=145 89.5% vs n=95 88.0%), median duration of labor (both 2.0 days), home delivery (n=31 19.1% vs n=17 15.7%), cesarean delivery (n=79 48.8% vs 58 53.7%), median time from obstetric fistula formation to presentation (48.0 vs 24.0 months), and obstetric fistula classifications. Obstetric fistula occurred during the first pregnancy in 99 (61.1%) women in the early group and 71 (65.7%) in the late group (P=0.440).
Conclusion
Frequency of obstetric fistula during the first pregnancy is not increased among women who experience their first pregnancy within 2 years of menarche.
Frequency of obstetric fistula is not increased among women with an early first pregnancy; however, this complication was frequent during first labor, irrespective of age.
Summary
Background
Current published asthma predictive tools have moderate positive likelihood ratios (+LR) but high negative likelihood ratios (−LR) based on their recommended cut‐offs, which limit ...their clinical usefulness.
Objective
To develop a simple clinically applicable asthma prediction tool within a population‐based birth cohort.
Method
Children from the Manchester Asthma and Allergy Study (MAAS) attended follow‐up at ages 3, 8 and 11 years. Data on preschool wheeze were extracted from primary‐care records. Parents completed validated respiratory questionnaires. Children were skin prick tested (SPT). Asthma at 8/11 years (school‐age) was defined as parentally reported (a) physician‐diagnosed asthma and wheeze in the previous 12 months or (b) ≥3 wheeze attacks in the previous 12 months. An asthma prediction tool (MAAS APT) was developed using logistic regression of characteristics at age 3 years to predict school‐age asthma.
Results
Of 336 children with physician‐confirmed wheeze by age 3 years, 117(35%) had school‐age asthma. Logistic regression selected 5 significant risk factors which formed the basis of the MAAS APT: wheeze after exercise; wheeze causing breathlessness; cough on exertion; current eczema and SPT sensitisation(maximum score 5). A total of 281(84%) children had complete data at age 3 years and were used to test the MAAS APT. Children scoring ≥3 were at high risk of having asthma at school‐age (PPV > 75%; +LR 6.3, −LR 0.6), whereas children who had a score of 0 had very low risk(PPV 9.3%; LR 0.2).
Conclusion
MAAS APT is a simple asthma prediction tool which could easily be applied in clinical and research settings.
The purpose of this study was to identify where ultrasmall superparamagnetic particles of iron oxide (USPIO) locate to in myocardium, develop a methodology that differentiates active macrophage ...uptake of USPIO from passive tissue distribution; and investigate myocardial inflammation in cardiovascular diseases.
Myocardial inflammation is hypothesized to be a key pathophysiological mechanism of heart failure (HF), but human evidence is limited, partly because evaluation is challenging. USPIO-magnetic resonance imaging (MRI) potentially allows specific identification of myocardial inflammation but it remains unclear what the USPIO-MRI signal represents.
Histological validation was performed using a murine acute myocardial infarction (MI) model. A multiparametric, multi-time-point MRI methodology was developed, which was applied in patients with acute MI (n = 12), chronic ischemic cardiomyopathy (n = 7), myocarditis (n = 6), dilated cardiomyopathy (n = 5), and chronic sarcoidosis (n = 5).
USPIO were identified in myocardial macrophages and myocardial interstitium. R1 time-course reflected passive interstitial distribution whereas multi-time-point R2* was also sensitive to active macrophage uptake. R2*/R1 ratio provided a quantitative measurement of myocardial macrophage infiltration. R2* behavior and R2*/R1 ratio were higher in infarcted (p = 0.001) and remote (p = 0.033) myocardium in acute MI and in chronic ischemic cardiomyopathy (infarct: p = 0.008; remote p = 0.010), and were borderline higher in DCM (p = 0.096), in comparison to healthy controls, but were no different in myocarditis or sarcoidosis. An R2*/R1 threshold of 25 had a sensitivity and specificity of 90% and 83%, respectively, for detecting active USPIO uptake.
USPIO are phagocytized by cardiac macrophages but are also passively present in myocardial interstitium. A multiparametric multi-time-point MRI methodology specifically identifies active myocardial macrophage infiltration. Persistent active macrophage infiltration is present in infarcted and remote myocardium in chronic ischemic cardiomyopathy, providing a substrate for HF.
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About 40% of foodborne infections are acquired in the home. The aim of the present study was to track contamination of pathogens during domestic food preparation and link the contamination to ...preparation practices. Research participants from 87 households in six European countries were observed and interviewed during shopping and preparation of a chicken and vegetable meal. The presence of Salmonella spp., Campylobacter spp. and norovirus on raw chicken, kitchen surfaces, cloths and sponges was determined.
The prevalence of Campylobacter on raw chicken varied from 8.3% in Norway (NO) to 80% in France (FR) and Portugal (PT), with a mean prevalence of 57%. Campylobacter was found on half of the products that had been frozen and appeared to be less prevalent on chicken from supermarkets than other sources. Salmonella was found in 8.6% of raw chicken samples, exclusively from Hungary (HU).
A relationship between observed practices and spread of pathogens to kitchen surfaces was found only for the use of cutting boards for chicken and/or vegetables. After food preparation, Campylobacter and Salmonella were isolated from 23% (samples derived from HU, RO, UK) and 8.7% (HU), respectively of cutting boards. Research participants in France and Portugal were more likely to buy products that fitted their recipe, with less need for using cutting boards. Using the same board and knife for vegetables after using it for chicken and without washing with detergent was common in Portugal and Romania, but not in the other countries. Contamination with Campylobacter to other kitchen surfaces or washing utensils were found in five households (UK, RO, PT). Rinsing chicken in sinks was common in three countries (PT, HU, RO), and washing vegetables in the same sink was also usual. Prevalence of Norovirus was low, with detection in one out of 451 samples. The participants' awareness of the risk posed by pathogens from raw chicken differed among the six countries, with higher awareness in Norway and the UK than the other countries studied.
In conclusion, practices intended to avoid cross-contamination from chicken to kitchen surfaces and washing utensils are not established among consumers in all European countries. Nevertheless, cross-contamination events that disseminate infectious doses of pathogens seems to be rare, probably due to the relatively low levels of pathogens in food combined with food preferences. Food safety interventions must consider the national food culture, preferences, practices and the prevalence and levels of pathogens in food. Emphasis should be on providing and promoting chicken products with lower risk (prevalence of pathogens, ready-to-cook) and safe use of cutting boards.
•Campylobacter was common in raw poultry and on cutting boards.•Salmonella found in poultry and cutting boards in Hungary•Norovirus was detected in only one of 451 samples.•Country differences in risk perception and high risk behaviour between consumers
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