First-Line Chemotherapy for HER-2–Negative Metastatic Breast Cancer Patients Who Received Anthracyclines as Adjuvant Treatment

Learning Objectives After completing this course, the reader will be able to: Discuss the value of retreatment with anthracyclines for HER-2–negative metastatic breast cancer patients who received anthracyclines as adjuvant treatment.Discuss the role of liposomal anthracyclines, taxanes, and combinations without anthracyclines and taxanes, or innovative treatments, including target-based agents.Comment on the weakness and quality of available evidence. Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.co

Psychological factors may impacton postmenopausal women fracture risk

Anxiety and osteoporosis are common diseases and major public health problems. The association between  anxiety levels and bone loss was poorly investigated, thus we aimed to explore whether anxiety severity could be considered as an independent fracture risk. In a setting of postmenopausal women we measured anxiety levels by Hamilton Anxiety Rating Scale (HAMA), depressive symptoms by Beck Depression Inventory and evaluated quality of life by the 36-Item Short Form Health Survey (SF-36) questionnaire. Women with higher anxiety levels showed lower BMD at lumbar spine and femoral neck, and exhibited a poorer quality of life after grouping our population in tertiles of HAMA score. Anxiety levels were predictive of reduced BMD after correcting for other known clinical risk of fractures

Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial

<p>Abstract</p> <p>Background</p> <p>To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer.</p> <p>Methods</p> <p>Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed.</p> <p>Results</p> <p>From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm.</p> <p>Conclusions</p> <p>In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00540800">NCT00540800</a>.</p

Vinorelbine plus 3-weekly trastuzumab in metastatic breast cancer: a single-centre phase 2 trial

BACKGROUND: After two studies reporting response rates higher than 70% in HER2-positive metastatic breast cancer with weekly trastuzumab and vinorelbine, we planned a phase 2 study to test activity of the same combination, with trastuzumab given every 3 weeks. METHODS: Patients with HER2-positive metastatic breast cancer (3+ at immunohistochemistry or positive at fluorescence in situ hybridization), PS ≤2, normal left-ventricular ejection fraction (LVEF) and no more than one chemotherapy line for metastatic disease were eligible. Vinorelbine (30 mg/m(2)) was given on days 1&8 every 21 and trastuzumab (8 mg/kg day 1, then 6 mg/kg) every 21 days). A single-stage phase 2 design, with p(0 )= 0.45, p(1 )= 0.65, type I and II error = 0.10, was applied; 22 objective responses were required in 39 patients. RESULTS: From Nov 2002 to May 2005, 50 patients were enrolled, with a median age of 54 years (range 31–81). Among 40 patients eligible for response assessment, there were 7 complete and 13 partial responses (overall response rate 50%; 95% exact CI 33.8–66.2); 11 patients had disease stabilization, lasting more than 6 months in 10 cases. Response rate did not vary according to patients and tumor characteristics, type and amount of previous chemotherapy. Within the whole series, median progression-free survival was 9.6 months (95% CI 7.3–12.3), median overall survival 22.7 months (95% CI 19.5-NA). Fifteen patients (30%) developed brain metastases at a median time of 12 months (range 1–25). There was one toxic death due to renal failure in a patient receiving concomitant pamidronate. Twenty-three patients (46%) had grade 3–4 neutropenia, 2 (4%) grade 3 anemia, 4 (8%) febrile neutropenia. Two patients stopped treatment because of grade 2 decline of LVEF and one patient because of grade 2 liver toxicity concomitant with a grade 1 decline of LVEF. One patient stopped trastuzumab after 50 cycles because of grade 1 decline of LVEF. CONCLUSION: Although lower than in initial studies, activity of 3-weekly trastuzumab plus vinorelbine fell within the range of results reported with weekly schedules. Toxicity was prevalently manageable. This combination is safe and active for metastatic breast cancer patients who received adjuvant taxanes with anthracyclines

Endocrine features of Prader-Willi syndrome: a narrative review focusing on genotype-phenotype correlation

Prader-Willi syndrome (PWS) is a complex genetic disorder caused by three different types of molecular genetic abnormalities. The most common defect is a deletion on the paternal 15q11-q13 chromosome, which is seen in about 60% of individuals. The next most common abnormality is maternal disomy 15, found in around 35% of cases, and a defect in the imprinting center that controls the activity of certain genes on chromosome 15, seen in 1-3% of cases. Individuals with PWS typically experience issues with the hypothalamic-pituitary axis, leading to excessive hunger (hyperphagia), severe obesity, various endocrine disorders, and intellectual disability. Differences in physical and behavioral characteristics between patients with PWS due to deletion versus those with maternal disomy are discussed in literature. Patients with maternal disomy tend to have more frequent neurodevelopmental problems, such as autistic traits and behavioral issues, and generally have higher IQ levels compared to those with deletion of the critical PWS region. This has led us to review the pertinent literature to investigate the possibility of establishing connections between the genetic abnormalities and the endocrine disorders experienced by PWS patients, in order to develop more targeted diagnostic and treatment protocols. In this review, we will review the current state of clinical studies focusing on endocrine disorders in individuals with PWS patients, with a specific focus on the various genetic causes. We will look at topics such as neonatal anthropometry, thyroid issues, adrenal problems, hypogonadism, bone metabolism abnormalities, metabolic syndrome resulting from severe obesity caused by hyperphagia, deficiencies in the GH/IGF-1 axis, and the corresponding responses to treatment

Correction to: Neuropsychological Assessment in Elderly Men with Benign Prostatic Hyperplasia Treated with Dutasteride

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Quality of life in postmenopausal women: which role for vitamin D?

Quality of life (QoL) represents a dramatic issue in an aging population. Vitamin D has been consistently associated with several diseases. Thus, vitamin D may be considered a hallmark of health status. Our aim was to investigate whether vitamin D could be a determinant of self-perceived quality of life. The 36-Item Short Form Health Survey (SF-36) for quality of life, the Hamilton Anxiety Rating Scale (HAM-A), the Beck Depression Inventory II edition (BDI-II), in addition with multiple clinical risk factors for fractures and FRAX score, BMD at lumbar spine and femoral neck, were evaluated in a group of 177 postmenopausal women referring to an outpatients clinic for the prevention of osteoporosis. Serum levels of vitamin D [25(OH)D], indicative of vitamin D status, were detected by high-performance liquid chromatography. Scores of each dimension of the SF-36 were significantly related with the measurements of anxiety and depression by HAM-A and BDI-II respectively. Moreover role emotional, vitality, general health and bodily pain were significantly associated with vitamin D status. However, at a stepwise multiple regression analysis the physical component summary, obtained from SF-36, was not independently predicted from vitamin D. In conclusion we found an association between vitamin D status and QoL, thus we suggest physicians to consider vitamin D levels as a marker of QoL. Further studies testing the impact of vitamin D administration in improving QoL over time are needed

A General Procedure to Study Subcellular Models of Transsynaptic Signaling at Inhibitory Synapses

Computational modeling of brain circuits requires the definition of many parameters that are difficult to determine from experimental findings. One way to help interpret these data is to fit them using a particular kinetic model. In this paper, we propose a general procedure to fit individual synaptic events recorded from voltage clamp experiments. Starting from any given model description (mod file) in the NEURON simulation environment, the procedure exploits user-defined constraints, dependencies, and rules for the parameters of the model to fit the time course of individual spontaneous synaptic events that are recorded experimentally. The procedure, implemented in NEURON, is currently available in ModelDB. A Python version is installed, and will be soon available for public use, as a standalone task in the Collaboratory Portal of the Human Brain Project. To illustrate the potential application of the procedure, we tested its use with various sets of experimental data on GABAergic synapses; gephyrin and gephyrin-dependent pathways were chosen as a suitable example of a kinetic model of synaptic transmission. For individual spontaneous inhibitory events in hippocampal pyramidal CA1 neurons, we found that gephyrin-dependent subcellular pathways may shape synaptic events at different levels, and can be correlated with cell- or event-specific activity history and/or pathological conditions

Feasibility, Safety, and Effectiveness of Telerehabilitation in Mild-to-Moderate Parkinson's Disease

Introduction: Parkinson's disease (PD) patients frequently engage in rehabilitation to ameliorate symptoms. During the Coronavirus disease 2019 (COVID-19) pandemic, access to rehabilitation programs has been markedly limited, consequently, telerehabilitation gained popularity. In this prospective, open-label, and pilot study, we aimed to investigate feasibility, safety, and efficacy of telerehabilitation in mild-to-moderate PD patients. Materials and Methods: Twenty-three PD patients, with Hoehn and Yahr stage &lt;3, without gait disturbances or dementia and capable of using the televisit platform, were recruited for a 5-week telerehabilitation program, consisting of 1 remote visit with a therapist and a minimum of two sessions of &gt;30-min of self-conducted exercises per week. Patients received video tutorials of exercises and were asked to keep a diary of sessions. At baseline (T0), at the end of the intervention (T1), and 1 month after the end of treatment (T2), patients were remotely assessed with MDS-UPDRS part I-III, PDQ-39, Functional Independence Measure (FIM), and Frontal Assessment Battery scales, respectively. Acceptable compliance to the program was defined as &gt;60% matching of frequency and duration of sessions, whereas optimal compliance was set at &gt;80% matching. Results: The dropout rate was 0%. Over 85% of patients reached acceptable adherence cut-off and around 70% reached optimal one. No adverse events were reported during sessions. The repeated measure analysis of variance (rANOVA) showed a significant effect of factor “time” for MDS-UPDRS-III (p &lt; 0.0001) with a mean reduction of 4.217 points between T0 and T1 and return to baseline at T2. No significant effect was found for other outcome measures. Conclusion: Our findings demonstrate that telerehabilitation is safe, feasible, and effective on motor symptoms in mild-to-moderate PD patients

Board Resources and Firm Performance in SMEs

The objective of this paper is to analyse whether the knowledge, experience and capabilities of the board of directors aid the expansion of growth-oriented SMES. The sample consists of 200 board members of 32 firms listed on Spain’s alternative investment market. Our results show that average board tenure, educational level and CEO experience all affect firm growth. This article highlights the particular importance of human capital for these firms and how it can improve their performance