Dose-finding study of epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer

Background: Anthracyclines and taxanes are the most active drugs against breast cancer and the search after their optimal combination is under intensive investigation in both the advanced and early disease settings. A dose-finding study of epidoxorubicin (E) and docetaxel (D) was conducted in advanced breast cancer (ABC) to define the maximum tolerated dose (MTD) of the combination with and without granulocyte colony-stimulating factor (G-CSF) support and to characterise its toxicity and activity profile. Patients and methods: Forty-two patients who received neither palliative chemotherapy nor adjuvant anthracyclines (55% with dominant visceral disease and 66% with ≥2 sites involved) with measurable/evaluable lesions, were treated at four dose levels starting from E 75 mg/m2 and D 75 mg/m2 to E 120 mg/m2 and D 85 mg/m2. A maximum of four cycles of the combination was given every three weeks and four additional cycles of single agent D were allowed in responding patients. Cardiac function was monitored at baseline and at every second course by echocardiography. Results: Febrile neutropenia (two patients) and prolonged, severe neutropenia (absolute neutrophil count (ANC) <0.1 times 109/l for more than three days; one patient) defined the MTD of the combination without G-CSF support at E 90 mg/m2and D 75 mg/m2. G-CSF was then routinely administered from the subsequent dose level of E 120 mg/m2 and D 75 mg/m2. The MTD with G-CSF support was established at E 120 mg/m2 and D 85 mg/m2 (one patient with neutropenic fever together with failure of ANC recovery at day 21, three patients with ANC less than 0.1 × 109l for more than three days, one patient with both and one patient with grade 4 thrombocytopenia and toxic death from typhlitis while neutropenic). No severe neurotoxicity, mucositis, or fluid retention were observed and there were no clinical signs of cardiotox-icity. Antitumour activity was not a primary endpoint of the study: the overall response rate (ORR) in 40 evaluable patients was 60% (95% confidence interval: 43%-75%, 58% in liver disease, 84% in soft tissue) with no apparent dose-related effect. After a median follow-up of 19 months (range 2-30$), the overall time to progression (TTP) in nine patients without maintenance hormonal therapy was five months. Conclusions: The combination of E and D proved to be an effective and safe regimen in poor- prognosis patients with ABC. G-CSF support allowed higher doses to be delivered safely but dose escalation did not translate into improved response rates (RR). The MTD without growth factors support was used, in a phase II trial, which also included patients with previous anthracycline-containing adjuvant regimen

Cognitive impairment in multiple sclerosis: An exploratory analysis of environmental and lifestyle risk factors

BACKGROUND:Many potentially modifiable risk factors for MS are investigated. It is not known, however, if these factors also apply to MS-related cognitive impairment (CI), a frequent consequence of MS. OBJECTIVE:The aim of our study was to assess risk factors for CI in MS patients, focusing on environmental exposures, lifestyle and comorbidities. METHODS:We included MS patients referring to MS Centers in Florence and Barletta between 2014 and 2017. Neuropsychological performance was assessed through the Rao's battery and Stroop test, cognitive reserve (premorbid intelligence quotient-IQ) was evaluated using the National Adult Reading Test (NART). Potential risk factors were investigated through a semi-structured questionnaire. RESULTS:150 patients were included. CI was detected in 45 (30%) subjects and was associated with older age (p<0.005), older age at MS onset (p = 0.016), higher EDSS score (p<0.005), progressive disease course (p = 0.048) and lower premorbid IQ score (p<0.005). As for risk factors, CI was related with lower physical activity in childhood-adolescence (p<0.005). In women, hormonal therapy resulted to be protective against CI (p = 0.041). However, in the multivariable analysis, the only significant predictors of CI were older age (p<0.05; OR 1.06, 95% CI 1.02-1.10) and lower premorbid IQ (p<0.05; OR 0.93, 95% CI: 0.88-0.98). Removing IQ from the model, CI was associated with higher EDSS (p = 0.030; OR 1.25, 95% CI 1.02-1.53) and, marginally, previous physical activity (p = 0.066; OR 0.49, 95% CI: 0.23-1.05). CONCLUSIONS:Our findings suggest that physical activity in childhood-adolescence could be a contributor to cognitive reserve building, thus representing a potential protective factors for MS-related CI susceptible to preventive strategies

The brief international cognitive assessment for multiple sclerosis (BICAMS): Normative values with gender, age and education corrections in the Italian population

Background: BICAMS (Brief International Cognitive Assessment for Multiple Sclerosis) has been recently developed as brief, practical and universal assessment tool for cognitive impairment in MS subjects. It includes the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-2 (CVLT2) and the Brief Visuospatial Memory Test-Revised (BVMT-R) . In this study we aimed at gathering regression based normative data for the BICAMS battery in the Italian population.Methods: Healthy subjects were consecutively recruited among patient friends and relatives. Corrections for demographics were calculated using multivariable linear regression models. Test-retest reliability was assessed using the Pearson correlation coefficient.Results: The BICAMS battery was administered to 273 healthy subjects (180 women, mean age 38.9 ± 13.0&nbsp;years, mean education 14.9 ± 3.0&nbsp;years). Test-retest reliability was good for all the tests.Conclusions: The study provided normative data of the BICAMS for the Italian population confirming good test-retest reliability which can facilitate the use of the battery in clinical practice, also for longitudinal patient assessments

The Italian multiple sclerosis register

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups

The Italian multiple sclerosis register

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups

Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine–Induced Immune Thrombotic Thrombocytopenia

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. Design, setting, and participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. Main outcomes and measures: Clinical characteristics and mortality rate. Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. Conclusions and relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.info:eu-repo/semantics/publishedVersio