Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial.

BACKGROUND: Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial. PATIENTS AND METHODS: Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board. RESULTS: The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P + T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m2, baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%). CONCLUSIONS: Dual blockade with P + T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors.

The association of healthy lifestyle behaviors with mental health indicators among adolescents of different family affluence in Belgium.

BACKGROUND: Healthy lifestyles may contribute to better mental health, which is particularly important in adolescence, an age at which half of all mental health problems first occur. This association may be even more relevant in adolescents of low family affluence, who show more mental health problems, as well as more unhealthy lifestyles. This study investigated healthy lifestyle behaviors, namely sufficient sleep and physical activity, daily breakfast intake, low levels of alcohol use or smoking, in relation to mental health and symptoms of mental health problems (feelings of depression, anxiety, stress and self-esteem) among adolescents from different family affluence. Furthermore, the moderating role of family affluence was examined in those relations. METHODS: Adolescents aged 12-18y were recruited via a random sample of schools in Flanders, Belgium. A total of 1037 adolescents participated (mean age = 15.2, 49.8% female). Independent samples t-tests, Mann Whitney U-tests and χ2-tests determined the differences in healthy lifestyle behaviors and mental health indicators between adolescents of low-medium and high family affluence. Regression analyses assessed the association between healthy lifestyles and mental health outcomes and the moderating role of family affluence. RESULTS: All healthy lifestyle behaviors were associated with at least one mental health outcome, with the exception of alcohol consumption. Adolescents from low-medium family affluence had lower levels of physical activity, less often took breakfast, had lower levels of alcohol consumption and reported lower self-esteem than adolescents from high family affluence. The results showed no moderating effect of family affluence for the association between healthy lifestyle and mental health. CONCLUSION: These findings support the value of integrating healthy lifestyle behaviors in interventions for mental health promotion, for both youth of low-medium and high family affluence.

Content validity and methodological considerations in ecological momentary assessment studies on physical activity and sedentary behaviour: a systematic review.

BACKGROUND: Ecological momentary assessment (EMA) is a method of collecting real-time data based on repeated measures and observations that take place in participant's daily environment. EMA has many advantages over more traditional, retrospective questionnaires. However, EMA faces some challenges to reach its full potential. The aims of this systematic review are to (1) investigate whether and how content validity of the items (i.e. the specific questions that are part of a larger EMA questionnaire) used in EMA studies on physical activity and sedentary behaviour was assessed, and (2) provide an overview of important methodological considerations of EMA in measuring physical activity and sedentary behaviour. METHODS: Thirty papers (twenty unique studies) were systematically reviewed and variables were coded and analysed within the following 4 domains: (1) Content validity, (2) Sampling approach, (3) Data input modalities and (4) Degree of EMA completion. RESULTS: Only about half of the studies reported the specific items (n = 12) and the source of the items (n = 11). None of the studies specifically assessed the content validity of the items used. Only a minority (n = 5) of the studies reported any training, and one tested the comprehensibility of the EMA items. A wide variability was found in the design and methodology of the EMA. A minority of the studies (n = 7) reported a rationale for the used prompt frequency, time selection, and monitoring period. Retrospective assessment periods varied from 'now' to 'in the last 3.5 hours'. In some studies there was a possibility to delay (n = 6) or deactivate (n = 10) the prompt, and some provided reminders after the first prompt (n = 9). CONCLUSIONS: Almost no EMA studies reported the content validation of the items used. We recommend using the COSMIN checklist (COnsensus-based Standards for the selection of health Measurement INstruments) to report on the content validity of EMA items. Furthermore, as often no rationale was provided for several methodological decisions, the following three recommendations are made. First, provide a rationale for choosing the sampling modalities. Second, to ensure assessment 'in the moment', think carefully about the retrospective assessment period, reminders, and deactivation of the prompt. Third, as high completion rates are important for representativeness of the data and generalizability of the findings, report completion rates. TRIAL REGISTRATION: This review is registered in PROSPERO, the International prospective register of systematic reviews (registration number: CRD42017077996).

Pelvic salvage (SBRT) radiotherapy based on 68Ga-PSMA PET/CT: About a case.

Very few patients with a biochemical failure after radical prostatectomy respond to prostatic bed irradiation. In this setting, 68Ga-PSMA PET/CT seems to be a useful tool for the detection of lesions remaining occult to conventional imaging work-up, changing the treatment strategy in a significant percentage of patients. we report the case of a patient in whom the PSMA PET allowed orientation of the SBRT. To date the patient has no recurrence.

Psychometric data of a questionnaire to measure cyberbullying bystander behavior and its behavioral determinants among adolescents.

.This paper describes the items, scale validity and scale reliability of a self-report questionnaire that measures bystander behavior in cyberbullying incidents among adolescents, and its behavioral determinants. Determinants included behavioral intention, behavioral attitudes, moral disengagement attitudes, outcome expectations, self-efficacy, subjective norm and social skills. Questions also assessed (cyber-)bullying involvement. Validity and reliability information is based on a sample of 238 adolescents (M age=13.52 years, SD=0.57). Construct validity was assessed using Confirmatory Factor Analysis (CFA) or Exploratory Factor Analysis (EFA) in Mplus7 software. Reliability (Cronbach Alpha, α) was assessed in SPSS, version 22. Data and questionnaire are included in this article. Further information can be found in DeSmet et al. (2018) [1].

Which healthy lifestyle factors are associated with a lower risk of suicidal ideation among adolescents faced with cyberbullying?

Cyberbullying is associated with negative mental health outcomes including adolescent suicidal ideation. This requires effective and accessible preventive efforts. Healthy lifestyles are factors adolescents themselves can modify that may lower their risk of suicidal ideation. The aim of this study was to examine associations between physical activity, (outdoor) sport participation, a healthy diet, higher sleep duration and low levels of smoking and alcohol use, and suicidal ideation when faced with cyberbullying. A cross-sectional survey was administered in 2014-2015 to 1037 adolescents (12-18 years, M age = 15; 50% girls) in Flanders, Belgium. Logistic regression analyses were conducted to assess direct effects of cyberbullying involvement (victim, perpetrator, bystander) on suicidal ideation, and interaction effects between cyberbullying involvement, healthy lifestyles and suicidal ideation. Results showed that cyberbullying victimization, perpetration and bystanding were associated with higher suicidal ideation, but that the association with cyberbullying perpetration disappeared when corrected for other cyberbullying involvement forms. More physical activity, sleeping longer, more often taking a healthy diet and lower levels of smoking were associated with lower suicidal ideation. Some associations of healthy lifestyles with suicidal ideation disappeared at higher levels of cyberbullying involvement. Low alcohol consumption and (outdoor) sport participation were not associated with suicidal ideation, and sport participation was even associated with higher suicidal ideation at low levels of cyberbullying involvement. These findings suggest a novel approach to suicide prevention may be warranted, by strengthening healthy lifestyles as factors that adolescents themselves can modify to increase their resilience and reduce suicidal ideation.

Fructose consumption impairs serotonergic signaling in the murine enteric nervous system.

The intake of free fructose has increased substantially since the development of high-fructose corn syrup. This has not only been associated with metabolic disorders but recent evidence also indicates that chronic fructose consumption can affect neuronal and cognitive function. In this study we investigated the effects of fructose consumption on serotonergic signaling and neuronal activity in the mouse submucous plexus. Male mice were put on a control or fructose (23% solution) diet for 6 weeks or were assigned to a recovery group that received normal water (2 weeks) after 4 weeks of fructose. At the end of the diet, gene expressions and enteric neuronal activity, after depolarization with high K(+) and 5-HT, were measured using Ca(2+) imaging and RT-qPCR, respectively. Even in the lack of gain weight and the absence of changes in duodenal permeability, the total number of 5-HT-responding neurons and the depolarization and 5-HT-evoked Ca(2+) amplitudes were significantly lower after fructose consumption. Expression of synaptobrevin CaV 2.1 and CaV 2.2 mRNA did not differ after fructose intake; however, CaV 2.1 mRNA levels were significantly higher in the recovery animals. SERT mRNA concentration, isolated from submucosal plexus containing mucosal epithelium, was significantly decreased after fructose consumption. Chronic fructose consumption impairs serotonergic signaling in the mouse submucous plexus, prior to weight gain and detectable intestinal permeability problems.

Distinct subcellular localization of the neuronal marker HuC/D reveals hypoxia-induced damage in enteric neurons.

BACKGROUND: Correct neuronal identification is essential to study neurons in health and disease. Although commonly used as pan-neuronal marker, HuC/D's expression pattern varies substantially between healthy and (patho)physiological conditions. This heterogenic labeling has received very little attention. We sought to investigate the subcellular HuC/D localization in enteric neurons in different conditions. METHODS: The localization of neuronal RNA-binding proteins HuC/D was investigated by immunohistochemistry in the mouse myenteric plexus using different toxins and caustic agents. Preparations were also stained with Sox10 and glial fibrillary acidic protein (GFAP) antibodies to assess enteric glial cell appearance. KEY RESULTS: Mechanically induced tissue damage, interference with the respiratory chain and oxygen (O2 ) deprivation increased nuclear HuC/D immunoreactivity. This effect was paralleled by a distortion of the GFAP-labeled glial network along with a loss of Sox10 expression and coincided with the activation of a non-apoptotic genetic program. Chemically induced damage and specific noxious stimuli did not induce a change in HuC/D immunoreactivity, supporting the specific nature of the nuclear HuC/D localization. CONCLUSIONS & INFERENCES: HuC/D is not merely a pan-neuronal marker but its subcellular localization also reflects the condition of a neuron at the time of fixation. The functional meaning of this change in HuC/D localization is not entirely clear, but disturbance in O2 supply in combination with the support of enteric glial cells seems to play a crucial role. The molecular consequence of changes in HuC/D expression needs to be further investigated.

[What's about overactive lifestyle in fibromyalgia and chronic fatigue syndrome]. / Place du style de vie "hyperactif" dans les syndromes de fibromyalgie et de fatigue chronique.

Fibromyalgia and chronic fatigue syndrome are clinical conditions different but they share common components, particularly multifactorial aetiology. High level of action proneness and "overactive" lifestyle can be considered as predisposing risk factors and perpetuating factors for these somatic functional syndromes. For the clinicians managing complex situations, only a holistic, circular and biopsychosocial approach could restore a new equilibrium (allostasis) with strategies of coping with chronic pain and planification of activities.

A diagnostic-ratio approach to measuring beliefs about the leadership abilities of male and female managers.

This study departed from previous research on gender stereotyping in the leadership domain by adopting a more comprehensive view of leadership and using a diagnostic-ratio measurement strategy. One hundred and fifty-one managers (95 men and 56 women) judged the leadership effectiveness of male and female middle managers by providing likelihood ratings for 14 categories of leader behavior. As expected, the likelihood ratings for some leader behaviors were greater for male managers, whereas for other leader behaviors, the likelihood ratings were greater for female managers or were no different. Leadership ratings revealed some evidence of a same-gender bias. Providing explicit verification of managerial success had only a modest effect on gender stereotyping. The merits of adopting a probabilistic approach in examining the perception and treatment of stigmatized groups are discussed.