Forty-four patients with advanced gastric cancer were treated with a combination including 5-fluorouracil, 4-epi-doxorubicin and mitomycin C. 4-Epi-doxorubicin was substituted for adriamycin in ...MacDonald's original schedule. The combined treatment involved 600 mg/m2 i.v. of 5-fluorouracil on days 1, 8, 29 and 36; 80 mg/m2 i.v. of 4-epi-doxorubicin on days 1 and 29; and 10 g/m2 i.v. of mitomycin C on day 1. The cycle was repeated on day 57 after the start of treatment. Out of 44 patients, 39 were evaluable. Thirteen partial remissions (33%) were achieved. The average duration of remission was 7 months (range, 3-12 months). The average survival of the responders was 9 months, and that of nonresponders 3.5 months. Toxicity was moderate, well-tolerated and, as compared with the FAM schedule, less pronounced, particularly as regards myelotoxicity. Thus, the substitution of 4-epi-doxorubicin for adriamycin in the original schedule of MacDonald et al. (1980) did not improve treatment results, but the observed toxicity was less pronounced.
The synergistic activity we have observed in vitro in V-79 hamster lung cells after treatment with cis-platinum combined with irradiation, stimulated a pilot study of 31 patients with inoperable ...locoregionally advanced squamous cell esophageal cancer. The 27 evaluable cases (22 men and 5 women--mean age 59 years) had undergone no prior radiation or cytostatic drug therapy. Histological evidence of the tumor (26 squamous cell, 1 adenocarcinoma) was obtained by endoscopy in all patients before treatment began. The patients were irradiated in two opposite thoracic fields with a total dosage of 3,000-4,000 cGy (200 cGy daily, 1,000 weekly) concurrently with 2 cycles of cis-platinum in the dosage of 30 mg/m2 iv. daily X 4 (120 mg/m2 per cycle). The results showed that cis-platinum combined with radiation showed an evident antitumor activity which included 4 complete clinical remissions and 11 partial remissions with a response rate of 56% (15/27). In two complete responders even a pathologic remission was evident (biopsy specimen) and they are now 16+ and 18+ months free of the disease. The median remission duration has been 8+ months (14+ months in complete responders) and the median survival period for the entire group is 10+ months (for responders 15+ months, p less than 0.05). Toxicity was moderate and reversible, and mainly accounted for radiation mucositis, retrosternal pain and vomiting. A mild bone marrow suppression was observed. In 2 cases esophagotracheal fistulae occurred. The results of this study show that the combination of cis-platinum and radiation might constitute successful palliative or neoadjuvant treatment for squamous cell esophageal cancer.
During the last 20 years, multiple sclerosis (MS) disease has seen major changes with new diagnostic criteria, a better identification of disease phenotypes, individualization of disease prognosis ...and the appearance of new therapeutic options in relapsing remitting as well as progressive MS. As a result, the management of MS patients has become more complex and challenging. The objective of these consensus recommendations was to review how the disease should be managed in Argentina to improve long-term outcomes in MS patients.
A panel of 36 experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2018 and 2019 to carry out a consensus recommendation on the management of MS patients in Argentina. To achieve consensus, the methodology of “formal consensus-RAND/UCLA method” was used.
Recommendations focused on diagnosis, disease prognosis, tailored treatment, treatment failure identification and pharmacovigilance process.
The recommendations of these consensus guidelines attempt to optimize the health care and management of patients with MS in Argentina.
•The objective of these consensus was to review how MS should be managed in Argentina•Recommendations focused on diagnosis, tailored treatment, treatment failure and pharmacovigilance•An early and individualized specific treatment for MS should be used on every patient.•Neurologists who follow MS patients are responsible for the prescription of the specific treatment•Patients with suspected MS should be evaluated in an MS care unit and/or by trained MS neurologist
One of the biggest challenges in multiple sclerosis (MS) is the definition of treatment response/failure in order to optimize treatment decisions in affected patients. The objective of this consensus ...was to review how disease activity should be assessed and to propose recommendations on the identification of treatment failure in RRMS patients in Argentina.
A panel of experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2016 and 2017 to carry out a consensus recommendation on the identification of treatment failure in RRMS patients. To achieve consensus, the methodology of “formal consensus-RAND/UCLA method” was used.
Recommendations were established based on published evidence and the expert opinion. Recommendations focused on disease management, disease activity markers and treatment failure identification were determined. Main consensus were: ≥2 relapses during the first year of treatment and/or ≥3 new or enlarged T2 or T1 GAD+ lesions and/or sustained increase of ≥2 points in EDSS or ≥100% in T25FW defines treatment failure in RRMS patients.
The recommendations of this consensus guidelines attempts to optimize the health care and management of patients with MS in Argentina.
•The objective of this consensus was to treatment failure in RRMS patients in Argentina.•43 experts from all Argentina defined the treatment failure by formal consensus.•≥2 relapses during the first year of treatment defines treatment failure.•≥3 new or enlarged T2 or T1 GAD+ lesions, defines treatment failure.•Sustained increase of ≥2 points in EDSS or ≥100% in T25FW defines treatment failure.
Summary Background In a 12-month phase 3 study in patients with relapsing-remitting multiple sclerosis (RRMS), TRANSFORMS, fingolimod showed greater efficacy on relapse rates and MRI outcomes ...compared with interferon beta-1a. We had two aims in our extension: to compare year 2 with year 1 in the switched patients to assess the effect of a change from interferon beta-1a to fingolimod, and to compare over 24 months the treatment groups as originally randomised to assess the effect of delaying the start of treatment with fingolimod. Methods Patients randomly assigned to receive 0·5 mg or 1·25 mg daily oral fingolimod in the core study continued with the same treatment in our extension; patients who originally received 30 μg weekly intramuscular interferon beta-1a were randomly reassigned (1:1) to receive either 0·5 mg or 1·25 mg fingolimod. The initial randomisation and dose of fingolimod assigned for the extension remained masked to the patients and investigators. As in the core study, re-randomisation was done centrally in blocks of six and stratified according to site. Our efficacy endpoints were annualised relapse rate (ARR), disability progression, and MRI outcomes. Our within-group analyses were based on the intention-to-treat and safety populations that entered our extension study. Our between-group analyses were based on the intention-to-treat and safety populations from the core study. This study is registered with ClinicalTrials.gov , number NCT00340834. Findings 1027 patients entered our extension and received the study drug, and 882 completed 24 months of treatment. Patients receiving continuous fingolimod showed persistent benefits in ARR (0·5 mg fingolimod n=356, 0·12 95% CI 0·08–0·17 in months 0–12 vs 0·11 0·08–0·16 in months 13–24; 1·25 mg fingolimod n=330, 0·15 0·10–0·21 vs 0·11 0·08–0·16; however, in patients who initially received interferon beta-1a, ARR was lower after switching to fingolimod compared with the previous 12 months (interferon beta-1a to 0·5 mg fingolimod n=167, 0·31 95% CI 0·22–0·43 in months 0–12 vs 0·22 0·15–0·31, in months 13–24 p=0·049; interferon beta-1a to 1·25 mg fingolimod n=174, 0·29 0·20–0·40 vs 0·18 0·12–0·27, p=0·024). After switching to fingolimod, numbers of new or newly enlarging T2 and gadolinium (Gd)-enhancing T1 lesions were significantly reduced compared with the previous 12 months of interferon beta-1a therapy (p<0·0001 for T2 lesions at both doses; p=0·002 for T1 at 0·5 mg; p=0·011 for T1 at 1·25 mg), and the pattern of adverse events shifted towards that typical for fingolimod. Over 24 months, in continuous fingolimod groups compared with the group that switched from interferon beta-1a to fingolimod, we recorded lower ARRs (0·18 95% CI 0·14–0·22 for 0·5 mg; 0·20 0·16–0·25 for 1·25 mg; 0·33 0·27–0·39 for the switch group; p<0·0001 for both comparisons), fewer new or newly enlarged T2 lesions (p=0·035 for 0·5 mg, p=0·068 for 1·25 mg), and fewer patients with Gd-enhancing T1 lesions (p=0·001 for 0·5 mg fingolimod vs switch group; p=0·002 for 1·25 mg fingolimod vs switch group). There was no benefit on disability progression. Interpretation Switching from interferon beta-1a to fingolimod led to enhanced efficacy with no unexpected safety concerns. Compared with patients switched from interferon beta-1a to fingolimod, continuous treatment with fingolimod for 2 years provides a sustained treatment effect with improved clinical and MRI outcomes. Funding Novartis Pharma AG.
Objective Susac syndrome (SuS), multiple sclerosis (MS), and primary angiitis of the central nervous system (PACNS) present diagnostic challenges due to overlapping clinical features. We aimed to ...enhance diagnostic precision by developing the SPAMS (SuS, PACNS, MS) score, a practical radiological tool. Methods This multicenter study included 99 patients (43 SuS, 37 MS, 19 PACNS) from South American countries. Relevant MRI features were identified through an elastic‐net model determined key variables. Results The SPAMS score assigned 2 points for snowball lesions, 1 point for spokes‐like lesions, or if there are more than 4 lesions in the corpus callosum, corpus callosum involvement, or cerebellar involvement. It subtracted 1 point if gadolinium‐enhancing lesions or 4 points if Dawson's fingers are present. Bootstrapping validated the optimal cutoff at 2 points, exhibiting a diagnostic performance of area under the curve = 0.931, sensitivity = 88%, specificity = 89%, positive predictive value = 88%, negative predictive value = 89%, and accuracy = 88%. Interpretation When specific MRI findings coexisted, the SPAMS score differentiated SuS from MS and PACNS. Access to MRI and standard protocol sequences makes it a valuable tool for timely diagnosis and treatment, potentially preventing disability progression and severe clinical outcomes. ANN NEUROL 2024
The EA-QOL questionnaire measures quality-of-life specifically for children born with esophageal atresia (EA) aged 8-18 and was completed in Sweden and Germany. This study aimed to describe an ...international collaborative initiative to establish a semantically equivalent linguistic version of the EA-QOL questionnaires in 12 new countries. The 24-item EA-QOL questionnaire was translated into the target languages and the translated questionnaire was evaluated through cognitive debriefing interviews with children with EA aged 8-18 and their parents in each new country. Participants rated an item as to whether an item was easy to understand and sensitive/uncomfortable to answer. They could choose not to reply to a non-applicable/problematic item and provide open comments. Data were analyzed using predefined psychometric criteria; item clarity ≥80%, item sensitive/uncomfortable to answer ≤20%, item feasibility(missing item responses ≤5%). Decision to improve any translation was made by native experts-patient stakeholders and the instrument developer. Like in Sweden and Germany, all items in the cross-cultural analysis of child self-report (
= 82, 4-10 children/country) met the criteria for item clarity in all 12 new countries, and in parent-report (
= 86, 5-10 parents/country) in 8/12 countries. All items fulfilled the criteria for sensitive/uncomfortable to answer (child-report 1.2-9.9%; parent-report 0-11.6%) and item feasibility. Poor translations were resolved. Hence, this study has established semantically equivalent linguistic versions of the EA-QOL questionnaire for use in children aged 8-18 with repair of EA in and across 14 countries.
The identification, diagnosis, follow-up, and treatment of patients with secondary progressive multiple sclerosis (SPMS) show significant differences between health care professionals in Argentina.
...To provide consensus recommendations on the management of patients with SPMS in Argentina to optimize patient care.
A panel of expert neurologists from Argentina dedicated to the diagnosis and care of multiple sclerosis patients gathered during 2019 and 2020 to carry out a consensus recommendation on the diagnosis and treatment of SPMS patients in Argentina. To achieve consensus, the methodology of 'formal consensus-RAND/UCLA method' was used. Recommendations were established based on published evidence and the expert opinion. Recommendations focused on how to define SPMS and how to follow SPMS patients.
The recommendations of this consensus guidelines attempt to optimize the care of SPMS patients in Argentina.
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