Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial.

Background: The benefit of extending aromatase inhibitor therapy beyond 5 years in the context of previous aromatase inhibitors remains controversial. We aimed to compare extended therapy with letrozole for 5 years versus the standard duration of 2-3 years of letrozole in postmenopausal patients with breast cancer who have already received 2-3 years of tamoxifen.

Methods: This multicentre, open-label, randomised, phase 3 trial was done at 69 hospitals in Italy.

Netupitant/palonosetron (NEPA) and dexamethasone for prevention of emesis in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide: a multi-cycle, phase II study.

Background: NEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor antagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against chemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent chemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The study also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on day 6 through 21 (very late period) in each cycle.

The impact of progesterone receptor expression on prognosis of patients with rapidly proliferating, hormone receptor-positive early breast cancer: a analysis of the IBIS 3 trial.

Background: In the Italian Breast Cancer Intergroup Studies (IBIS) 3 phase III trial, we compared cyclophosphamide, methotrexate, 5-fluorouracil (CMF) alone to sequential epirubicin/CMF regimens in patients with rapidly proliferating early breast cancer (RPEBC). We performed a analysis in the subgroup of patients with hormone-receptor-positive RPEBC on the prognostic role of progesterone receptor (PgR) status.

Methods: RPEBC was defined by thymidine labeling index (TLI) >3% or grade 3 or S-phase >10% or Ki67 >20%.

Validation of the AJCC prognostic stage for HER2-positive breast cancer in the ShortHER trial.

Background: The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial.

Methods: The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy.

Metformin plus chemotherapy versus chemotherapy alone in the first-line treatment of HER2-negative metastatic breast cancer. The MYME randomized, phase 2 clinical trial.

Purpose: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC).

Methods: Non-diabetic women with HER2-negative MBC were randomized to receive non-pegylated liposomal doxorubicin (NPLD) 60 mg/m + cyclophosphamide (C) 600 mg/m × 8 cycles Q21 days plus M 2000 mg/day (arm A) versus NPLD/C (arm B). The primary endpoint was progression-free survival (PFS).

Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study‡.

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy.

The Promher Study: An Observational Italian Study on Adjuvant Therapy for HER2-Positive, pT1a-b pN0 Breast Cancer.

Background: The management of pT1a-b pN0 HER2-positive breast cancer is controversial and no data about the efficacy of trastuzumab in this setting are available from randomized clinical trials. The aims of this retrospective study were to assess how patients are managed in clinical practice in Italy, which clinical or biological characteristics influenced the choice of adjuvant systemic therapy and the outcome of patients.

Methods: Data of consecutive patients who underwent surgery from January 2007 to December 2012 for HER2-positive, pT1a-b pN0 M0 breast cancer were retrospectively collected from 28 Italian centres.

Time to initiation of adjuvant chemotherapy in patients with rapidly proliferating early breast cancer.

Aim: To evaluate the optimal time interval from definitive surgery to commencing chemotherapy in early breast cancer (EBC).

Patients And Methods: The relationship between time to initiation of adjuvant chemotherapy (TTC), calculated in weeks, and disease-free (DFS) or overall survival (OS), was assessed in 921 EBC patients with rapidly proliferating tumours (thymidine labelling index >3% or G3 or Ki67 >20%), randomised in a phase III clinical trial (NCT01031030) to receive chemotherapy with or without anthracyclines (epirubicin→cyclophosphamide, methotrexate and fluorouracil (CMF) versus CMF→epirubicin versus CMF). DFS, OS and 95% confidence intervals (95% confidence interval (CI)) were calculated by the Kaplan-Meier method.

Randomized phase III trial of adjuvant epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) versus CMF followed by epirubicin in patients with node-negative or 1-3 node-positive rapidly proliferating breast cancer.

Adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) have proven highly effective in rapidly proliferating breast cancer (RPBC). It has also been seen that sequential administration of doxorubicin and CMF is superior to their alternation, especially in indolent tumors. In a phase III study, we evaluated whether adjuvant epirubicin (E) followed by CMF is superior to the inverse sequence in RPBC.

Efficacy of azathioprine on multiple sclerosis new brain lesions evaluated using magnetic resonance imaging.

Background: Azathioprine is an immunosuppressive agent that reduces relapse rates in patients with multiple sclerosis (MS), but its efficacy in suppressing new brain lesions has never been evaluated.

Objective: To evaluate the efficacy of azathioprine therapy on new brain lesion suppression in MS.

Design: Open-label treatment vs baseline study.

Temozolomide and interferon-alpha in metastatic melanoma: a phase II study of the Italian Melanoma Intergroup.

Temozolomide (TMZ) is a new oral alkylating agent which has proven to be as active as dacarbazine (DTIC) in the treatment of melanoma, but with a lower toxicity. A multicentric phase II trial was conducted in an out-patient setting to determine the therapeutic activity and safety of TMZ in combination with interferon-alpha (IFN-alpha). From June 2000 to July 2001, 41 patients were recruited to receive TMZ 200 mg/m orally on days 1-5 every 28 days and with 5 MU IFN-alpha subcutaneously three times a week, continuously for eight cycles or until disease progression occurred.

Epidemiology of dementias.

The increasing and widespread interest in age-associated dementias originated because of the rapid aging of the world population. Considering the rapid demographic changes and current epidemiologic data indicating a steep increase in the frequency of dementia with advancing age, several authors have introduced the concept of an "epidemic of dementia". Epidemiological research gives the opportunity to provide both scientific data and background information for health policy makers.

Lifestyle-related risk factors for Parkinson's disease: a population-based study.

Objectives: To investigate the association of major lifestyle-related risk factors with the prevalent cases of Parkinson's disease (PD) identified by the Italian Longitudinal Study on Aging.

Methods: A total of 5632 individuals randomly selected from the population registers of eight centers were screened for parkinsonism using both a questionnaire and a neurologic examination. Screened positives underwent a structured clinical work-up for the diagnosis of parkinsonism and parkinsonism subtypes.

Stroke in an elderly population: incidence and impact on survival and daily function. The Italian Longitudinal Study on Aging.

Background: Epidemiological data are essential to estimate the burden of stroke. We evaluated stroke incidence in older Italians and the effect of first-ever stroke on survival and activities of daily living (ADL).

Methods: The analysis was performed in the Italian Longitudinal Study on Aging (ILSA) sample, consisting of 5,632 individuals aged 65-84.

Incidence of dementia, Alzheimer's disease, and vascular dementia in Italy. The ILSA Study.

Objectives: To estimate the incidence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in older Italians and evaluate the relationship of age, gender, and education to developing dementia.

Design: Cohort incidence study in the context of the Italian Longitudinal Study on Aging.

Setting: Population sample from eight Italian municipalities.

Maurice Ravel and right-hemisphere musical creativity: influence of disease on his last musical works?

The problem of finding correspondence between a particular neuronal organization and a specific function of the human brain remains a central question of neuroscience. It is sometimes thought that language and music are two sides of the same intellectual coin, but research on brain-damaged patients has shown that the loss of verbal functions (aphasia) is not necessarily accompanied by a loss of musical abilities (amusia). Amusia without aphasia has also been described.

Parkinson's disease and parkinsonism in a longitudinal study: two-fold higher incidence in men. ILSA Working Group. Italian Longitudinal Study on Aging.

Objective: To determine the incidence of parkinsonism and PD in the Italian elderly, and to explore the relation with age and gender.

Methods: In eight Italian municipalities, a population-based, parkinsonism-free cohort was followed for an average of 3 years. At the end of the follow-up, the cohort survivors were directly contacted (screening and clinical examination).

Cognitive impairment without dementia in older people: prevalence, vascular risk factors, impact on disability. The Italian Longitudinal Study on Aging.

Objectives: To investigate prevalence of "cognitive impairment, no dementia" (CIND) in the Italian older population, evaluating the association with cardiovascular disease and the impact on activities of daily living (ADL). CIND may provide pathogenic clues to dementia and independently affect ADL.

Design: Cross-sectional examination in the context of the Italian Longitudinal Study on Aging.

Magnetic resonance measures in Alzheimer disease: their utility in early diagnosis and evaluating disease progression.

We sought to identify the most reliable magnetic resonance (MR) measures for the diagnosis and staging of Alzheimer disease (AD) in a clinical setting and to estimate, for different degrees of dementia, the rate of change of cerebral atrophy in certain regions of interest (ROIs). Forty-two probable AD patients and eight normal controls underwent MR brain scans, neurological examinations, and neuropsychological testing. We computed each subject's corpus callosum width, ventricular size, right and left temporal lobe areas, interuncal distance, and assessed the degree of cortical atrophy.

Influence of different screening procedures on the stroke prevalence estimates: the Italian Longitudinal Study on Aging.

Stroke prevalence surveys are more and more needed for health care and facility planning. Prevalence estimates and costs of the definition procedure may vary depending on different screening strategies. We evaluated the impact of these different strategies on the overall diagnostic procedure and on stroke prevalence estimates in the Italian Longitudinal Study on Aging.

Validity of different linguistic versions of the Alzheimer's Disease Assessment Scale in an international multicentre Alzheimer's disease trial.

Owing to the involvement of Italian Centres in a multicentre, German-Italian therapeutical trial with Alzheimer's dementia patients, to be assessed with the Alzheimer's Disease Assessment Scale (ADAS), it was decided that the Italian centres would use an Italian version of the scale, derived from that used by the German centres. However, the lists of words for exploring verbal memory are not merely translated from the German version, but are composed of selective Italian words chosen according to linguistic criteria. This Italian version was validated following the same procedure adopted for validating the German version.

Dementia is a major predictor of death among the Italian elderly. ILSA Working Group. Italian Longitudinal Study on Aging.

Background: Neurologic diseases are rarely listed on death certificates because death is more often attributed to cardiovascular and pneumonic events occurring during terminal stages.

Objective: To evaluate the effect of major age-associated neurologic and non-neurologic diseases on survival in a cohort of Italian elderly.

Methods: A population-based multicenter survey, carried out in eight Italian municipalities, with a sample of 5,632 individuals aged 65 to 84 years.

Rates and risk factors for dementia and Alzheimer's disease: results from EURODEM pooled analyses. EURODEM Incidence Research Group and Work Groups. European Studies of Dementia.

Objective: To investigate the risk of AD associated with a family history of dementia, female gender, low levels of education, smoking, and head trauma.

Background: These putative factors have been identified in cross-sectional studies. However, those studies are prone to bias due to systematic differences between patients and control subjects regarding survival and how risk factors are recalled.