Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial

Background and purpose Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. Methods This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed. Results Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60. Conclusions The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation

Psychopathological Impact in Patients with History of Rheumatic Fever with or without Sydenham's Chorea: A Multicenter Prospective Study

Sydenham's chorea (SC) is a post-streptococcal autoimmune disorder of the central nervous system, and it is a major criterium for the diagnosis of acute rheumatic fever (ARF). SC typically improves in 12-15 weeks, but patients can be affected for years by persistence and recurrencies of both neurological and neuropsychiatric symptoms. We enrolled 48 patients with a previous diagnosis of ARF, with or without SC, in a national multicenter prospective study, to evaluate the presence of neuropsychiatric symptoms several years after SC's onset. Our population was divided in a SC group (n = 21), consisting of patients who had SC, and a nSC group (n = 27), consisting of patients who had ARF without SC. Both groups were evaluated by the administration of 8 different neuropsychiatric tests. The Work and Social Adjustment Scale (WSAS) showed significantly (p = 0.021) higher alterations in the SC group than in the nSC group. Furthermore, 60.4% (n = 29) of the overall population experienced neuropsychiatric symptoms other than choreic movements at diagnosis and this finding was significantly more common (p = 0.00) in SC patients (95.2%) than in nSC patients (33.3%). The other neuropsychiatric tests also produced significant results, indicating that SC can exert a strong psychopathological impact on patients even years after its onset

Efficacy of canakinumab in patients with Still's disease across different lines of biologic therapy: real-life data from the International AIDA Network Registry for Still's Disease

Introduction: The effectiveness of canakinumab may change according to the different times it is used after Still's disease onset. This study aimed to investigate whether canakinumab (CAN) shows differences in short- and long-term therapeutic outcomes, according to its use as different lines of biologic treatment.Methods: Patients included in this study were retrospectively enrolled from the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to Still's disease. Seventy-seven (51 females and 26 males) patients with Still's disease were included in the present study. In total, 39 (50.6%) patients underwent CAN as a first-line biologic agent, and the remaining 38 (49.4%) patients were treated with CAN as a second-line biologic agent or subsequent biologic agent.Results: No statistically significant differences were found between patients treated with CAN as a first-line biologic agent and those previously treated with other biologic agents in terms of the frequency of complete response (p =0.62), partial response (p =0.61), treatment failure (p >0.99), and frequency of patients discontinuing CAN due to lack or loss of efficacy (p =0.2). Of all the patients, 18 (23.4%) patients experienced disease relapse during canakinumab treatment, 9 patients were treated with canakinumab as a first-line biologic agent, and nine patients were treated with a second-line or subsequent biologic agent. No differences were found in the frequency of glucocorticoid use (p =0.34), daily glucocorticoid dosage (p =0.47), or concomitant methotrexate dosage (p =0.43) at the last assessment during CAN treatment.Conclusion: Canakinumab has proved to be effective in patients with Still's disease, regardless of its line of biologic treatment

Preface of the 31st Italian Symposium on Advanced Database Systems

This volume contains the proceedings of the 31st Italian Symposium on Advanced Database Systems (SEBD - Sistemi Evoluti per Basi di Dati), held in Galzinagno Terme (Padua, Italy) from 2 to 5 July 2023.</p

Preface of the 31st Italian Symposium on Advanced Database Systems

This volume contains the proceedings of the 31st Italian Symposium on Advanced Database Systems (SEBD - Sistemi Evoluti per Basi di Dati), held in Galzinagno Terme (Padua, Italy) from 2 to 5 July 2023.</p

Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Clinical and laboratory features associated with macrophage activation syndrome in Still's disease: data from the international AIDA Network Still's Disease Registry

: To characterize clinical and laboratory signs of patients with still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. patients with still's disease classified according to internationally accepted criteria were enrolled in the autoInflammatory disease alliance (AIDA) still's disease registry. clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p = 0.003), liver involvement (p = 0.04), hepatomegaly (p = 0.02), hepatic failure (p = 0.01), axillary lymphadenopathy (p = 0.04), pneumonia (p = 0.03), acute respiratory distress syndrome (p &lt; 0.001), platelet abnormalities (p &lt; 0.001), high serum ferritin levels (p = 0.009), abnormal liver function tests (p = 0.009), hypoalbuminemia (p = 0.002), increased LDH (p = 0.001), and LDH serum levels (p &lt; 0.001). at multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9-52.6, p = 0.007) and monoarthritis (OR 15.8, 95% CI 2.9-97.1, p = 0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4-0.9, p = 0.045), a normal platelet count (OR 0.1, 95% CI 0.01-0.8, p = 0.034) or thrombocytosis (OR 0.01, 95% CI 0.0-0.2, p = 0.008) resulted to be protective. clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data

Cuidando a quienes cuidan, experiencias del servicio de contención virtual en tiempos de pandemia COVID19

Este trabajo tiene como objetivo describir las características del dispositivo creado para la contención y el acompañamiento de profesionales de la salud en tiempos de pandemia por el Coronavirus Covid-19, promoviendo la salud y el bienestar emocional. Se detalla la conformación del equipo de trabajo y la implementación de la atención remota como así también los datos estadísticos obtenidos. Luego de las medidas implementadas por el Gobierno de la Nación, en marco de emergencia sanitaria mundial por el Coronavirus (COVID-19), el 26 de Marzo de 2020 se pone en marcha el servicio. El equipo de trabajo brinda orientación, acompañamiento y contención psicológica a los efectores/efectoras de la Salud que trabajan en diversas instituciones públicas y privadas de nuestra provincia y a docentes y no docentes que se desempeñan en dependencias de la UNC. Desde la Facultad de Psicología de la Universidad Nacional de Córdoba, el Ministerio de Salud, la Secretaría de Salud Mental de la Provincia de Córdoba y la Municipalidad de Córdoba, se gestiona este este servicio surge como un dispositivo de intervención virtual para el cuidado de quienes cuidan la salud de la población y los que brindan transferencia de conocimiento a alumnos de la UNC.publishedVersionFil: López, Nahuel. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Chávez, Lorena Paola. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Salvetti, Marcela Alejandra. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Ré, Ana Carolina. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Scorza, Diana Rita. Ministerio de Salud de la Provincia de Córdoba. Secretaría de Salud Mental; Argentina.Fil: Irueste, Paula. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Serena, Florencia. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Figueroa, Maximiliano Rubén. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Pavan, María Avila. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Alvo, Carolina. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Moreno Andueza, Mayra. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Neme Villarroel, Yanina. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Colombo, Judith J. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Cabanillas, José Ignacio. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Moreno Frías, Ana Virginia. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Espeche, Ana Beatriz. Ministerio de Salud de la Provincia de Córdoba. Secretaría de Salud Mental; Argentina.Fil: Estrada, Ezequiel Matías. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Zandivarez, Paola Fátima. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Wortley, Ana Carolina. Universidad Nacional de Córdoba. Facultad de Psicología. Servicio Cuidando a Quienes Cuidan: Servicio de Contención Virtual para Efectores/as de la Salud, Docentes y No docentes; Argentina.Fil: Waigel, Vanina Alejandra. Ministerio de Salud de la Provincia de Córdoba. Secretaría de Salud Mental; Argentina.Fil: Simonini, Claudia. Ministerio de Salud de la Provincia de Córdoba. Secretaría de Salud Mental; Argentina.Fil: Tumas, Paula. Municipalidad de Córdoba. Secretaría de Salud; Argentina

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p &lt; 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p &lt; 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths