NSABP FB-10: a phase Ib/II trial evaluating ado-trastuzumab emtansine (T-DM1) with neratinib in women with metastatic HER2-positive breast cancer.

Background: We previously reported our phase Ib trial, testing the safety, tolerability, and efficacy of T-DM1 + neratinib in HER2-positive metastatic breast cancer patients. Patients with ERBB2 amplification in ctDNA had deeper and more durable responses. This study extends these observations with in-depth analysis of molecular markers and mechanisms of resistance in additional patients.

Exercise Interventions With Trained Home Helpers for Preventing Loss of Autonomy and Falls in Community-Dwelling Older Adults Receiving Home Heath Physical Therapy T4H: A Randomized Controlled Pilot Study.

Background And Purpose: Older adults at risk for falls live independently in the community in their own home and have rehabilitation needs. However, little is known about whether home coaching of older adults can decrease falls at home. We sought to determine whether a novel program for preventing falls and a loss of exercise capacity, the T4H program, in which home helpers act as exercise coaches by using an information technology (IT) device, was acceptable and feasible.

Neratinib-Plus-Cetuximab in Quadruple-WT () Metastatic Colorectal Cancer Resistant to Cetuximab or Panitumumab: NSABP FC-7, A Phase Ib Study.

Purpose: In metastatic colorectal cancer (mCRC), () gene amplification is implicated in anti-EGFR therapy resistance. We sought to determine the recommended phase II dose (RP2D) and efficacy of neratinib, a pan-ERBB kinase inhibitor, combined with cetuximab, in patients with progressive disease (PD) on anti-EGFR treatment.

Patients And Methods: Twenty-one patients with quadruple-wild-type, refractory mCRC enrolled in this 3+3 phase Ib study.

Correction to: NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2+ breast cancer.

After the publication of this work [1] the authors have reported that in Table 3 The letter "T" in columns 5 and 7 should not be there.

NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2 breast cancer.

Purpose: The primary aim of NSABP FB-7 was to determine the pathologic complete response (pCR) rate in locally advanced HER2-positive (HER2) breast cancer patients treated with neoadjuvant trastuzumab or neratinib or the combination and weekly paclitaxel followed by standard doxorubicin plus cyclophosphamide. The secondary aims include biomarker analyses.

Experimental Design: pCR was tested for association with treatment, gene expression, and a single nucleotide polymorphism (SNP) in the Fc fragment of the IgG receptor IIIa-158V/F (FCGR3A).

Safety and Efficacy of T-DM1 Plus Neratinib in Patients With Metastatic HER2-Positive Breast Cancer: NSABP Foundation Trial FB-10.

Purpose: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer eventually develop resistance to dual-antibody therapy with trastuzumab plus pertuzumab. Mechanisms of resistance have not been well elucidated. We evaluated the safety, tolerability, and efficacy of ado-trastuzumab emtansine (T-DM1) plus neratinib in patients who progressed on trastuzumab plus pertuzumab.

Analysing Time to Event Data in Dementia Prevention Trials: The Example of the GuidAge Study of EGb761.

Time-to-event analysis is frequently used in medical research to investigate potential disease-modifying treatments in neurodegenerative diseases. Potential treatment effects are generally evaluated using the logrank test, which has optimal power and sensitivity when the treatment effect (hazard ratio) is constant over time. However, there is generally no prior information as to how the hazard ratio for the event of interest actually evolves.

Interleukin-10 Production in Response to Amyloid-β Differs between Slow and Fast Decliners in Patients with Alzheimer's Disease.

We investigated IL-10 and IL-6 production in amyloid-β (Aβ) stimulated peripheral blood mononuclear cells (PBMCs) in twenty Alzheimer's disease (AD) patients with slow progression, eleven with fast progression, and twenty age-matched controls. Promoter polymorphisms in IL-10 (position -592, -819, -1082), IL-6 (-174), transforming growth factor-β1 (TGF-β1) (-10, -25), interferon-γ (IFN-γ) (-874), and tumor necrosis factor-α (TNF-α) (-308) genes were analyzed. IL-10 production after Aβ stimulation was high in PBMCs from slow decliners and almost completely abrogated in fast decliners.

Leukocyte Telomere Length in Alzheimer's Disease Patients with a Different Rate of Progression.

Background: Age and short leukocyte telomeres have been associated with a higher risk of Alzheimer's disease (AD). Inflammation is involved in AD and it is suggested that anti-inflammatory interleukin-10 (IL-10) may partly antagonize these processes.

Objective: The aim is to correlate telomere length (TL) in peripheral blood mononuclear cells (PBMC) from patients with AD to disease progression rate.

Fall related to epileptic seizures in the elderly.

It is well known that both falls and epileptic seizures are very frequent and harmful in the elderly. Moreover, although seizures may cause falls, their relationship is poorly documented in this population. We report four women (mean age: 84.

[Needs, uses, cons-pros, good practices and opportunities about walker in elderly with loss of autonomy].

Non-use of the walker may be secondary to an initial inappropriate prescribing, a lack of adequate training, a lack of monitoring and side effects of using. Improving both stability and mobility in users is due to several biomechanical mechanisms. The benefits of walker are: general physiological effects, more confidence, better social life and decrease in the burden of care.

Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council.

Guidance synthesis. Medical research for and with older people in Europe: proposed ethical guidance for good clinical practice: ethical considerations.

Introduction: In Europe the population is ageing rapidly. Older people are taking many medicinal products daily and these may not necessarily be suitable for them. Publications show that older patients are underrepresented in clinical trials, especially those over 75 years, with multiple co-morbidities, concomitant treatments and/or frailty.

Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98.

Purpose: Previous preclinical and clinical data suggest that the immune system influences prognosis and response to chemotherapy (CT); however, clinical relevance has yet to be established in breast cancer (BC). We hypothesized that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic CT-in this case, anthracycline-only CT-in selected BC subtypes.

Patients And Methods: We investigated the relationship between quantity and location of lymphocytic infiltrate at diagnosis with clinical outcome in 2009 node-positive BC samples from the BIG 02-98 adjuvant phase III trial comparing anthracycline-only CT (doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin plus cyclophosphamide followed by CMF) versus CT combining doxorubicin and docetaxel (doxorubicin plus docetaxel followed by CMF or doxorubicin followed by docetaxel followed by CMF).

[Clinical pharmacology and aging].

Clinicians must be aware that aging can lead to changes in the pharmacokinetics and pharmacodynamics of many drugs. Drug distribution may be modified with aging secondarily to the decrease of serum albumin and to modifications of body composition (increase in the proportion of fat mass and decrease of lean mass). Hepatic metabolism of several drugs is reduced with age, especially drugs which depend of hepatic blood flow or P450 cytochroms.

Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial.

Background: Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints.

Methods: In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France.

A short-term, multicomponent infection control program in nursing homes: a cluster randomized controlled trial.

Objectives: To assess the impact of a hygiene-encouragement program on reducing infection rates (primary end point) by 5%.

Design: A cluster randomized study was carried out over a 5-month period.

Settings And Participants: Fifty nursing homes (NHs) with 4345 beds in France were randomly assigned by stratified-block randomization to either a multicomponent intervention (25 NHs) or an assessment only (25 NHs).

Is there a cold shock response in the Antarctic psychrophile Pseudoalteromonas haloplanktis?

The growth behavior and the proteomic response after a cold shock were investigated in the psychrophilic Antarctic bacterium Pseudoalteromonas haloplanktis. Remarkably, no cold-induced proteins were observed in the proteome, whereas some key proteins were repressed. This suggests noticeable differences in the cold shock response between a true psychrophile and mesophiles.

Correlation between quantitative HER-2 protein expression and risk for brain metastases in HER-2+ advanced breast cancer patients receiving trastuzumab-containing therapy.

Background: Patients with human epidermal growth factor receptor (HER)-2+ breast cancer are at particularly high risk for brain metastases; however, the biological basis is not fully understood. Using a novel HER-2 assay, we investigated the correlation between quantitative HER-2 expression in primary breast cancers and the time to brain metastasis (TTBM) in HER-2+ advanced breast cancer patients treated with trastuzumab.

Methods: The study group included 142 consecutive patients who were administered trastuzumab-based therapy for HER-2+ metastatic breast cancer.

[Management of pneumonia in the elderly].

Pneumonias in elderly are frequent and severe. They require an accurate assessment following clinical, biological and radiological steps. Each of them can contribute to give answers to the following questions: does this patient need emergency hospitalisation? Is the infection really bacterial and pulmonary? Should antibiotics be started? Which others treatments should be associated for the infection itself and for comorbid conditions? Concerning prevention, every effort must be done to decrease the incidence of these infections, especially vaccination.

Swallowing disorders, pneumonia and respiratory tract infectious disease in the elderly.

Swallowing disorders (or dysphagia) are common in the elderly and their prevalence is often underestimated. They may result in serious complications including dehydration, malnutrition, airway obstruction, aspiration pneumonia (infectious process) or pneumonitis (chemical injury caused by the inhalation of sterile gastric contents). Moreover the repercussions of dysphagia are not only physical but also emotional and social, leading to depression, altered quality of life, and social isolation.

HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer: a meta-analysis of individual patient data.

Background: Prediction of response to anthracycline-based therapy for breast cancer is challenging. We aimed to assess the value of HER2 and TOP2A as predictive markers of response to anthracycline-based adjuvant therapy in patients with early breast cancer.

Methods: We did a meta-analysis of individual patient data from five randomised adjuvant trials that compared anthracycline-based regimens with cyclophosphamide, methotrexate, and fluorouracil (CMF) regimens.