Search

Your search keyword '"Gidaro, A"' showing total 123 results
Start Over Author "Gidaro, A" Topic medicine.disease
123 results on '"Gidaro, A"'

1. Concomitant use of Tyrosine-Kinase Inhibitor and Mepolizumab in Asthma Secondary to Chronic Myeloid Leukemia with Hypereosinophilia

Author

Roberto Castelli, Antonio Gidaro, Maria Cristina Carraro, Emanuele Salvi, and Roberta Simona Rossi

Subjects
Pharmacology, business.industry, medicine.drug_class, Immunology, Myeloid leukemia, Hypereosinophilia, Imatinib, General Medicine, medicine.disease, Tyrosine-kinase inhibitor, hemic and lymphatic diseases, Eosinophilic, medicine, Immunology and Allergy, medicine.symptom, business, Bosutinib, Mepolizumab, Asthma, medicine.drug
Abstract

Introduction: Asthma and hypereosinophilia have been treated with different therapeutics in the past. Some of them appear to be more effective in symptoms resolution and decreasing eosinophilic count. Case Presentation: We report here an unusual case of asthma with hypereosinophilia secondary to Chronic Myeloid Leukemia (CML) with high prevalence of eosinophilic infiltrate, treated simultaneously with an anti-IL-5 antibody (Mepolizumab) and Tyrosine-kinase Inhibitors (TKI: Imatinib and Bosutinib) for three years. The patient showed a promising reduction of pulmonary exacerbations and good control of CML without developing side effects. Conclusion: We hope that this finding could inspire further studies on the efficacy and safety of the concomitant use of anti-IL-5 and TKI.

Published
2021

2. Risk-tailored treatment of splenic marginal zone lymphoma

Author

Roberta Simona Rossi, Monica Balzarotti, Giorgio Lambertenghi Deliliers, Emanuele Salvi, Luigi Bergamaschini, Roberto Castelli, and Antonio Gidaro

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Lymphocytosis, Anemia, medicine.medical_treatment, Splenectomy, Receptors, Antigen, B-Cell, Antineoplastic Agents, Risk Assessment, Antineoplastic Agents, Immunological, Risk Factors, Internal medicine, Tumor Microenvironment, Humans, Medicine, Pharmacology (medical), Receptor, Notch2, Splenic marginal zone lymphoma, Precision Medicine, Neoplasm Staging, Pharmacology, Chemotherapy, business.industry, Splenic Neoplasms, NF-kappa B, Lymphoma, B-Cell, Marginal Zone, Hepatitis B, medicine.disease, Hepatitis C, Lymphoma, medicine.anatomical_structure, Disease Progression, Rituximab, Lymphoma, Large B-Cell, Diffuse, Bone marrow, medicine.symptom, business, Signal Transduction, medicine.drug
Abstract

Splenic marginal zone lymphoma (SMZL) is a rare lymphoproliferative disease involving B-cells and affecting elderly patients. SMZL plague peripheral blood and bone marrow, spleen. Lymph nodes are generally spared. SMZL is due to a protracted antigen stimulation of B lymphocytes and of microenvironment leading B-cell to polyclonal and then oligoclonal/monoclonal growth, promoting lymphoproliferation. Integration of the NOTCH2 and NFk-B signaling has been recently identified as the primary mechanism of neoplastic proliferation in SMZL. In total 20% of cases carry mutations in NOTCH2. Although SMZL has an indolent course, progression to diffuse large B-cell lymphoma occurs in about 10-15% of patients. Establishing the prognosis is a key step in disease management, depending on both individual risk and patients' health status. This review discusses tailored treatment of SMZL patients. Progression risk factors include nodal and extra-nodal involvement, peripheral lymphocytosis, anemia and thrombocytopenia. Patients with two or more score points have a median survival of

Published
2021

3. Hereditary angioedema due to C1 inhibitor deficiency in Belarus: epidemiology, access to diagnosis and seven novel mutations in SERPING1 gene

Author

Antonio Gidaro, Irina E. Guryanova, Marco Cicardi, Debora Parolin, Francesca Perego, Mikhail Belevtsev, Yulia Zharankova, Natalya Konoplya, Sonia Caccia, Chiara Suffritti, Ekaterina A. Polyakova, Andrea Zanichelli, and Nastassia Ishchanka

Subjects
lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Pediatrics, Allergy, Immunology, C1-inhibitor, SERPING1 variants, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, Immunology and Allergy, Molecular Biology, 030304 developmental biology, 0303 health sciences, Hematology, C1 inhibitor, biology, Angioedema, business.industry, Research, Belarus, medicine.disease, 030228 respiratory system, Hereditary angioedema (HAE), Hereditary angioedema, biology.protein, medicine.symptom, business, lcsh:RC581-607, Rare disease, Tranexamic acid, medicine.drug
Abstract

Background Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease. Few states in developing countries have an adequate management of HAE, but none of them belongs to the former USSR area. This study analyses data from C1-INH-HAE patients from Belarus. Methods Data about clinical characteristics, genetics, access to diagnosis and treatment were collected from 2010 by the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology in Minsk. A questionnaire about attacks, prophylactic (LTP) and on-demand therapy (ODT) was administered to patients. Results We identified 64 C1-INH-HAE patients belonging to 26 families, 27 (42.2%) of which were diagnosed in the last 3 years. The estimated minimal prevalence was 1:148,000. Median age at diagnosis was 29 years, with diagnostic delay of 19 years. Thirty-eight patients answered a questionnaire about therapy. Eleven patients did not use any treatment to resolve HAE attacks. Twenty-seven patients underwent ODT: 9 with appropriate treatments, and 18 with inappropriate treatments. Nine patients used LTP with attenuated androgens and 1 with tranexamic acid. Thirty-two patients answered a questionnaire about attacks and triggers: 368 angioedema attacks were reported, with an average of 10 attacks per year. We found 24 different SERPING1 variants: 9 missenses, 6 in splice sites, 6 small deletions, 2 nonsense, 1 large deletion; 7 have not been previously described. De novo variants were found in 11 patients. Conclusions C1-INH-HAE diagnosis and management in Belarus is improved as seen from the high number of new diagnosis in the last 3 years. Next steps will be to reduce the diagnostic delay and to promote the LTP and ODT.

Published
2021

4. Natural history of Type 2 and 3 spinal muscular atrophy: 2‐year NatHis‐SMA study

Author

Jean-Yves Hogrel, Myriam Ly-Le Moal, A. Daron, Teresa Gidaro, Timothy Seabrook, Laurent Servais, Carole Vuillerot, Vincent Laugel, Emmanuel Fournier, Pierre G. Carlier, Ulrike Schara, Yann Péréon, Nicole Hellbach, Andreea Mihaela Seferian, Claude Cances, Ksenija Gorni, M. Annoussamy, Linda Lowes, C. Lilien, Ricardo Hermosilla, Christian Czech, Liesbeth De Waele, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), SYSNAV, Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre de reference des maladies neuromusculaires Nantes-Angers, CHU d'Angers et Nantes, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Hospitals Leuven [Leuven], KU Leuven Campus Kulak Kortrijk [Belgium], CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], University of Duisburg-Essen, University of Oxford, Nationwide Children's Hospital, Hoffman-La Roche Ltd, Translational Medicine, Neuroscience, Institut ROCHE [Boulogne-Billancourt], Roche S.A.S, Roche Innovation Center [Basel, Switzerland], Pfizer, Gestionnaire, Hal Sorbonne Université, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), CHU Toulouse [Toulouse], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, University of Oxford [Oxford], and Universität Duisburg-Essen = University of Duisburg-Essen [Essen]

Subjects
0301 basic medicine, Vital capacity, Time Factors, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Medizin, MESH: Respiratory Function Tests, NASAL INSPIRATORY PRESSURE, Severity of Illness Index, Pulmonary function testing, MESH: Magnetic Resonance Imaging, Disability Evaluation, 0302 clinical medicine, MESH: Muscular Atrophy, Spinal, MESH: Child, Longitudinal Studies, MESH: Nerve Tissue Proteins, Child, MESH: Longitudinal Studies, Research Articles, VALUES, General Neuroscience, MESH: Muscle Strength, MESH: Disability Evaluation, RNA-Binding Proteins, SMA, Magnetic Resonance Imaging, MESH: Motor Activity, Respiratory Function Tests, medicine.anatomical_structure, MESH: Young Adult, Child, Preschool, Anesthesia, Disease Progression, Upper limb, MESH: Disease Progression, Erratum, Life Sciences & Biomedicine, RC321-571, Research Article, Adult, Adolescent, Clinical Neurology, Neurosciences. Biological psychiatry. Neuropsychiatry, Nerve Tissue Proteins, Motor Activity, Muscular Atrophy, Spinal, Upper Extremity, Young Adult, 03 medical and health sciences, FEV1/FVC ratio, Statistical significance, MESH: Severity of Illness Index, medicine, Humans, Muscle Strength, RC346-429, MESH: Adolescent, Science & Technology, MESH: Humans, business.industry, MESH: Time Factors, MESH: Child, Preschool, Neurosciences, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Survival of motor neuron, MESH: Adult, Spinal muscular atrophy, MESH: Upper Extremity, medicine.disease, 030104 developmental biology, MESH: RNA-Binding Proteins, Neurology. Diseases of the nervous system, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery
Abstract

OBJECTIVE: To characterize the natural history of spinal muscular atrophy (SMA) over 24 months using innovative measures such as wearable devices, and to provide evidence for the sensitivity of these measures to determine their suitability as endpoints in clinical trials. METHODS: Patients with Type 2 and 3 SMA (N = 81) with varied functional abilities (sitters, nonsitters, nonambulant, and ambulant) who were not receiving disease-modifying treatment were assessed over 24 months: motor function (Motor Function Measure [MFM]), upper limb strength (MyoGrip, MyoPinch), upper limb activity (ActiMyo® ), quantitative magnetic resonance imaging (fat fraction [FFT2 ] mapping and contractile cross-sectional area [C-CSA]), pulmonary function (forced vital capacity [FVC], peak cough flow, maximum expiratory pressure, maximum inspiratory pressure, and sniff nasal inspiratory pressure), and survival of motor neuron (SMN) protein levels. RESULTS: MFM32 scores declined significantly over 24 months, but not 12 months. Changes in upper limb activity could be detected over 6 months and continued to decrease significantly over 12 months, but not 24 months. Upper limb strength decreased significantly over 12 and 24 months. FVC declined significantly over 12 months, but not 24 months. FFT2 increased over 12 and 24 months, although not with statistical significance. A significant increase in C-CSA was observed at 12 but not 24 months. Blood SMN protein levels were stable over 12 and 24 months. INTERPRETATION: These data demonstrate that the MFM32, MyoGrip, MyoPinch, and ActiMyo® enable the detection of a significant decline in patients with Type 2 and 3 SMA over 12 or 24 months. ispartof: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY vol:8 issue:2 pages:359-373 ispartof: location:United States status: published

Published
2020

5. Circulating endothelial progenitors are increased in COVID‐19 patients and correlate with SARS‐CoV‐2 RNA in severe cases

Author

Patrizia Mancuso, Luca Gusso, Antonio Gidaro, Francesco Bertolini, Jessica Quarna, Stefano Rusconi, Andrea Giacomelli, Paola Cremonesi, Sonia Caccia, Chiara Cogliati, Alessandro Raveane, and Giuliana Gregato

Subjects
Male, Endothelial cells, Apoptosis, Disease, 030204 cardiovascular system & hematology, Circulating Endothelial Progenitors, medicine.disease_cause, Polymerase Chain Reaction, Severity of Illness Index, Gastroenterology, SARS‐CoV‐2, 0302 clinical medicine, Endothelial Progenitor Cells, Coronavirus, Covid‐19, Aged, 80 and over, medicine.diagnostic_test, Brief Report, Liter, Hematology, Middle Aged, Viral Load, Flow Cytometry, COVID-19 Nucleic Acid Testing, Host-Pathogen Interactions, cardiovascular system, RNA, Viral, CD146, Female, Circulating Endothelial Cells, Adult, medicine.medical_specialty, CD146 Antigen, Flow cytometry, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Humans, Progenitor cell, Aged, SARS-CoV-2, business.industry, COVID-19, Cancer, medicine.disease, Kinetics, Case-Control Studies, Brief Reports, business, Biomarkers
Abstract

Background During the course of COVID-19, the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thrombotic phenomena and/or diffuse vascular damage are frequent, and viral elements have been observed within endothelial cells. Objectives CD146 + circulating endothelial cells (CD146 + CECs) and their progenitors (CEPs) are increased in cardiovascular, thrombotic, infectious, and cancer diseases. The present study was designed to investigate their kinetics in novel coronavirus (COVID-19) patients. Methods We used a validated flow cytometry procedure to enumerate viable and apoptotic CD146 + CECs and CEPs in COVID-19 patients during the course of the disease and in patients who recovered. Results Viable CEPs per milliliter were significantly increased in COVID-19 patients compared with healthy controls. This increase was observed in patients with mild symptoms and not further augmented in patients with severe symptoms. In patients who recovered, CEPs decreased, but were in a range still significantly higher than normal controls. Regarding mature CD146 + CECs, in COVID-19 patients, their absolute number was similar to those observed in healthy controls, but the viable/apoptotic CD146 + CEC ratio was significantly different. Both mild and severe COVID-19 patients had significantly less apoptotic CD146 + CECs compared with healthy controls. Patients who recovered had significantly less CD146 + CECs per milliliter when compared with controls as well as to mild and severe COVID-19 patients. A positive correlation was found between the copies of SARS-CoV-2 RNA in the cellular fraction and apoptotic CEPs per milliliter in severe COVID-19 patients. Conclusions CD146 + CECs and CEPs might be investigated as candidate biomarkers of endothelial damage in COVID-19 patients.

Published
2020

6. Complement activation in patients with immune thrombocytopenic purpura according to phases of disease course

Author

Roberto Castelli, G Lambertenghi Delilliers, Luigi Bergamaschini, Antonio Gidaro, and Marco Cicardi

Subjects
Adult, Blood Platelets, Male, 0301 basic medicine, Adolescent, medicine.medical_treatment, Immunology, Pathogenesis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Immune system, immune system diseases, hemic and lymphatic diseases, medicine, Humans, Immunology and Allergy, Platelet, Complement Activation, Autoantibodies, Purpura, Thrombocytopenic, Idiopathic, biology, business.industry, Bone marrow failure, Complement System Proteins, Original Articles, Middle Aged, medicine.disease, Thrombocytopenic purpura, Complement system, 030104 developmental biology, Cytokine, Disease Progression, biology.protein, Female, Antibody, business, 030215 immunology
Abstract

Summary Immune thrombocytopenic purpura (ITP) is an autoimmune thrombocytopenia with shortened platelet survival and relative bone marrow failure. The pathogenesis involves antibody production, cytokine release, T cell impairment, complement activation and clearance of platelets. We measured plasma levels of C3, C4, C1q and sC5b-9 in 80 ITP patients in acute phase, 50 ITP patients in complete (CR) or partial (PR) remission and 50 age- and sex-matched healthy volunteers. Statistical analyses showed that acute ITP patients had higher plasma levels of sC5b-9 and C1q than CR or PR patients (median = sC5b-9: 200 versus 98 mg/dl, P-value

Published
2020

7. ASC‐1 Is a Cell Cycle Regulator Associated with Severe and Mild Forms of Myopathy

Author

Teresa Gidaro, Julien Durigneux, Emma Pierce-Hoffman, Fabio Catervi, Johann Böhm, Alan H. Beggs, Adnan Yuksel, Montse Olivé, Casie A. Genetti, Raul Juntas-Morales, Isabelle Duband-Goulet, Nicolas Deconinck, Norma B. Romero, Eva Cabet, Rocío-Nur Villar-Quiles, Asuman Koparir, Ana Ferreiro, Jocelyn Laporte, Xavière Lornage, Mireille Cossée, John Rendu, Sandra Coppens, Lara Servais, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Département de neurologie [Montpellier], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Biruni University, Children's University Hospital Queen Fabiola [Bruxelles, Belgium], Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA, Partenaires INRAE, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des Maladies Neuromusculaires AOC, Groupe d'imagerie neurofonctionnelle (GIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Children's Hospital and Harvard Medical School, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Mühendislik ve Doğa Bilimleri Fakültesi

Subjects
Male, TRANSCRIPTION COACTIVATOR, 0301 basic medicine, Pathology, animal diseases, [SDV]Life Sciences [q-bio], Cardiomyopathy, Muscle Proteins, medicine.disease_cause, SIGNAL COINTEGRATOR 1, 0302 clinical medicine, Fibroblasts -- physiology, Amyotrophic lateral sclerosis, Child, Cells, Cultured, Mutation, ABNORMALITIES, Cell Cycle -- physiology, Cell Cycle, PROLIFERATION, hemic and immune systems, Sciences bio-médicales et agricoles, Middle Aged, MUSCLE, Pedigree, 3. Good health, Phenotype, Neurology, Child, Preschool, Female, Transcription Factors -- genetics, medicine.symptom, tissues, D3, G1 phase, Adult, endocrine system, medicine.medical_specialty, Amino Acid Transport System y+, DISORDERS, Muscle Proteins -- genetics, Muscle, Skeletal -- pathology -- physiopathology, Article, 03 medical and health sciences, Muscular Diseases, Neurologie, medicine, Humans, Amino Acid Transport System y+ -- metabolism -- physiology, Muscle, Skeletal, Cell Cycle Protein, Myopathy, business.industry, Infant, Spinal muscular atrophy, Fibroblasts, medicine.disease, GENE, Congenital myopathy, eye diseases, MUSCULAR-DYSTROPHY, ADIPOGENESIS, 030104 developmental biology, Muscular Diseases -- genetics -- physiopathology, Neurology (clinical), business, 030217 neurology & neurosurgery, Transcription Factors
Abstract

Objective: Recently, the ASC-1 complex has been identified as a mechanistic link between amyotrophic lateral sclerosis and spinal muscular atrophy (SMA), and 3 mutations of the ASC-1 gene TRIP4 have been associated with SMA or congenital myopathy. Our goal was to define ASC-1 neuromuscular function and the phenotypical spectrum associated with TRIP4 mutations. Methods: Clinical, molecular, histological, and magnetic resonance imaging studies were made in 5 families with 7 novel TRIP4 mutations. Fluorescence activated cell sorting and Western blot were performed in patient-derived fibroblasts and muscles and in Trip4 knocked-down C2C12 cells. Results: All mutations caused ASC-1 protein depletion. The clinical phenotype was purely myopathic, ranging from lethal neonatal to mild ambulatory adult patients. It included early onset axial and proximal weakness, scoliosis, rigid spine, dysmorphic facies, cutaneous involvement, respiratory failure, and in the older cases, dilated cardiomyopathy. Muscle biopsies showed multiminicores, nemaline rods, cytoplasmic bodies, caps, central nuclei, rimmed fibers, and/or mild endomysial fibrosis. ASC-1 depletion in C2C12 and in patient-derived fibroblasts and muscles caused accelerated proliferation, altered expression of cell cycle proteins, and/or shortening of the G0/G1 cell cycle phase leading to cell size reduction. Interpretation: Our results expand the phenotypical and molecular spectrum of TRIP4-associated disease to include mild adult forms with or without cardiomyopathy, associate ASC-1 depletion with isolated primary muscle involvement, and establish TRIP4 as a causative gene for several congenital muscle diseases, including nemaline, core, centronuclear, and cytoplasmic-body myopathies. They also identify ASC-1 as a novel cell cycle regulator with a key role in cell proliferation, and underline transcriptional coregulation defects as a novel pathophysiological mechanism. ANN NEUROL 2020;87:217–232., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019

8. Ataluren delays loss of ambulation and respiratory decline in nonsense mutation Duchenne muscular dystrophy patients

Author

Craig M McDonald, Francesco Muntoni, Vinay Penematsa, Joel Jiang, Allan Kristensen, Francesco Bibbiani, Elizabeth Goodwin, Heather Gordish-Dressman, Lauren Morgenroth, Christian Werner, James Li, Richard Able, Panayiota Trifillis, Már Tulinius, M Ryan, K Jones, N Goemans, C Campbell, JK Mah, K Selby, B Chabrol, Y Pereon, T Voit, T Gidaro, U Schara, JB Kirschner, Y Nevo, GP Comi, E Bertini, E Mercuri, J Colomer, A Nascimento, JJ Vilchez, M Tulinius, T Sejersen, F Muntoni, K Bushby, and M Guglieri

Subjects
medicine.medical_specialty, Vital capacity, nonsense mutation Duchenne muscular dystrophy, Duchenne muscular dystrophy, Nonsense mutation, efficacy, Walking, dystrophin, chemistry.chemical_compound, respiratory function, Internal medicine, loss of ambulation, medicine, Humans, Respiratory function, Respiratory system, Oxadiazoles, business.industry, Health Policy, ataluren, medicine.disease, Ataluren, Muscular Dystrophy, Duchenne, chemistry, Codon, Nonsense, Propensity score matching, Ambulatory, Study 019, business, Research Article
Abstract

Aim: We investigated the effect of ataluren plus standard of care (SoC) on age at loss of ambulation (LoA) and respiratory decline in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) versus patients with DMD on SoC alone. Patients & methods: Study 019 was a long-term Phase III study of ataluren safety in nmDMD patients with a history of ataluren exposure. Propensity score matching identified Study 019 and CINRG DNHS patients similar in disease progression predictors. Results & conclusion: Ataluren plus SoC was associated with a 2.2-year delay in age at LoA (p = 0.0006), and a 3.0-year delay in decline of predicted forced vital capacity to ClinicalTrials.gov registration : NCT01557400 .

Published
2021

9. Home-based gait analysis as an exploratory endpoint during a multicenter phase 1 trial in limb girdle muscular dystrophy type R2 and facioscapulohumeral muscular dystrophy

Author

Erwan Gasnier, David Vissiere, Laurent Servais, Tahseen Mozaffar, Gennyne Walker, Kathryn R. Wagner, John Vissing, Teresa Gidaro, M. Annoussamy, Sanjay S. Shukla, Stanley Iyadurai, and Shahram Attarian

Subjects
musculoskeletal diseases, medicine.medical_specialty, Physiology, STRIDE, Walking, Cellular and Molecular Neuroscience, Physical medicine and rehabilitation, Physiology (medical), medicine, Facioscapulohumeral muscular dystrophy, Humans, Gait, business.industry, Stride length, medicine.disease, Home based, Muscular Dystrophy, Facioscapulohumeral, Clinical trial, Muscular Dystrophies, Limb-Girdle, Gait analysis, Neurology (clinical), business, Gait Analysis, human activities, Limb-girdle muscular dystrophy
Abstract

INTRODUCTION/AIMS Limb girdle muscular dystrophy type 2B (LGMDR2) and facioscapulohumeral muscular dystrophy (FSHD) are genetic muscular dystrophies with an increasing number of potential therapeutic approaches. The aim of this study is to report the data of exploratory digital outcomes extracted from wearable magneto-inertial sensors used in a non-controlled environment for ambulant patients with FSHD and LGMDR2 in a short-term, multicenter clinical study. METHODS Digital outcomes (stride length, stride speed, and walk parameters in a non-controlled environment) were used as exploratory outcomes in the open-label study ATYR1940-C-004 in ambulant patients during the 3 mo of ATYR1940 treatment and 1 mo of follow-up. Activity and gait variables were calculated from the data recorded in 30-day sub-periods using the sensors. For each sub-period, activity and gait parameters were compared between FSHD and LGMDR2 patients. Change from baseline over the 4-mo study period was assessed. RESULTS Ten patients (5 FSHD, 5 LGMDR2) were ambulant and compliant for analysis. Gait parameters, but not activity variables, were significantly lower in LGMDR2 compared to FSHD patients at baseline. Longitudinal analyses showed a slight but significant decrease in stride speed at month 4 for all subjects. Activity variables such as total number of strides per day were highly variable from month to month in individual patients, and no visit effects were found for this variable. DISCUSSION The present study suggests that home-recorded stride speed constitutes a precise and sensitive outcome in ambulant patients with FSHD and LGMDR2.

Published
2021

10. Prothrombotic and Inflammatory Markers in Elderly Patients with Non-Alcoholic Hepatic Liver Disease before and after Weight Loss: A Pilot Study

Author

Antonio Gidaro, Alessandro P Delitala, Roberto Castelli, Gianpaolo Vidili, Luigi Bergamaschini, Emanuele Salvi, and Roberto Manetti

Subjects
TAFI, medicine.medical_specialty, Cirrhosis, slimming, Fibrinogen, Gastroenterology, digestive system, Article, Liver disease, Von Willebrand factor, Diabetes mellitus, Internal medicine, insulin resistance, medicine, von Willebrand factor (VWF), biology, medicine.diagnostic_test, business.industry, plasminogen activator inhibitor-1 (PAI-1), Fatty liver, nutritional and metabolic diseases, General Medicine, medicine.disease, factor VII (FVII), digestive system diseases, biology.protein, Medicine, Steatohepatitis, weight loss, business, Lipid profile, protein S, non-alcoholic fatty liver disease (NAFLD), medicine.drug
Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a pathological condition, ranging from fatty liver to chronic steatohepatitis (NASH), liver cirrhosis, and eventually to hepatocellular carcinoma. Recent findings suggest that patients with NAFLD have an increased risk of cardiovascular events and thromboembolism, which is independent of metabolic diseases that are frequently associated with NAFLD, such as diabetes, hyperlipidemia, and obesity. Methods: We evaluated 30 NAFLD patients, before and after weight loss. Plasma levels of C-reactive protein (CRP), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (VWF), homocysteine, coagulation protein S, Thrombin activable fibrinolysis inhibitor (TAFI), and factor VII (FVII) were assessed to evaluate whether they should be responsible of the prothrombotic state of NAFLD after weight loss. Results: At baseline, patients affected by NAFLD had a significantly higher levels of CRP, fibrinogen, PAI-1, VWF antigen, and FVII levels. After weight reduction, we observed a significant drop of inflammatory and prothrombotic markers, as well as glucometabolic, lipid profile. Conclusion: These findings provide evidence for a link between NAFLD/NASH and thromboembolism. The association seems to be linked with primitive thrombotic state and hypercoagulation due to increased levels of coagulation factors and reduced levels of PAI-1. This hypercoagulation state might explain increased levels of thrombosis and splanchnic thrombosis observed in NASH correlated cirrhosis.

Published
2021

11. Life expectancy in Italian patients with hereditary angioedema due to C1-inhibitor deficiency

Author

Marco Cicardi, Chiara Frigerio, Riccardo Senter, Maria Domenica Guarino, Itaca, Antonio Gidaro, Maria Bova, Francesco Arcoleo, Andrea Zanichelli, Tiziana De Pasquale, Mauro Cancian, Mariangela Lo Pizzo, Piergiorgio Duca, and Francesca Perego

Subjects
Pediatrics, medicine.medical_specialty, C1 inhibitor deficiency, business.industry, Angioedemas, Hereditary, Complement C1 Inactivator Proteins, medicine.disease, Life Expectancy, Italy, Hereditary angioedema, medicine, Life expectancy, Humans, Immunology and Allergy, business, Complement C1 Inhibitor Protein
Published
2020

12. Incidence and outcome of delirium during helmet CPAP treatment in COVID-19 patients

Author

Federica Samartin, Stella Ingrassia, Anna Maria Brambilla, Antonio Gidaro, Emanuele Salvi, and Alessandro Torre

Subjects
medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, MEDLINE, behavioral disciplines and activities, law.invention, law, mental disorders, Internal Medicine, medicine, Intubation, Dementia, Cpap treatment, Humans, education, education.field_of_study, Continuous Positive Airway Pressure, business.industry, SARS-CoV-2, Mortality rate, Incidence (epidemiology), Incidence, COVID-19, Delirium, Ce - Letter to Editor, medicine.disease, Intensive care unit, nervous system diseases, Cohort, Emergency medicine, Emergency Medicine, medicine.symptom, business, Respiratory Insufficiency
Abstract

It is estimated that almost one-third of patients with COVID-19 develop delirium in the course of disease, actually it may be the only presenting symptom, especially in dementia patients. In COVID-19 patients delirium is associated with higher mortality rate, increased length of stay and a greater rate of admission in Intensive Care Unit and ventilator utilisation. We hypothesized a greater rate of delirium in Helmet CPAP COVID-19 ventilated patients because many known risk factors for delirium co-exist in these kind of patients (i.e. isolation, noise, dehydration). The first aim of our study is to investigate the incidence of delirium occurring during Helmet CPAP therapy in COVID-19 patients. Moreover, we wanted to verify if there are predictable risk factors for delirium and to determine if delirium increases the risk of adverse outcomes (need of endotracheal intubation and death). The cohort of CPAP ventilated COVID-19 patients were composed by 194 patients. Of them, 57 patients (29.3%) developed delirium during CPAP, more than two third in the first 48h. Age over 70 years, previous diagnosis of dementia or psychiatric condition, P/F < 150 after starting CPAP and Gr/Lys >8 resulted risk factors for delirium. Delirium group had a significantly higher mortality rate (47% vs 23%) and lower intubation rate (12% vs 26%) compared to non-delirious ones. Despite many potential predisposing factors are common in CPAP ventilated patients, delirium incidence in our population seems not to differ from what reported by other studies. Moreover, the occurrence of delirium seems not to be related to prolonged CPAP treatment, indeed no correlation between time spent in CPAP and delirium onset was found.

Published
2021

13. Bendamustine in association with rituximab for first-line treatment of diffuse large B-cell lymphoma in frail patients ineligible for R-CHOP/R-CHOP-like treatments

Author

Antonio Gidaro, Giorgio Lambertenghi Deliliers, Luigi Bergamaschini, and Roberto Castelli

Subjects
0301 basic medicine, Bendamustine, Oncology, Male, Cancer Research, Vincristine, medicine.medical_specialty, Cyclophosphamide, Frail Elderly, Antineoplastic Agents, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Prednisone, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Bendamustine Hydrochloride, Humans, Pharmacology (medical), neoplasms, Aged, Pharmacology, Aged, 80 and over, Performance status, business.industry, Standard treatment, medicine.disease, Progression-Free Survival, 030104 developmental biology, 030220 oncology & carcinogenesis, Rituximab, Female, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, medicine.drug
Abstract

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) has been considered the standard of care for diffuse large B cell lymphoma (DLBCL) patients, including in the elderlies, and represent the current standard treatment. Ineligibility for R-CHOP-like treatments seems to be associated with shorter survival. Recent studies have shown that bendamustine and rituximab is linked, in elderly patients affected by DLBCL. Here we report our experience with BR in 40 elderly frail patients affected by DLBCL ineligibles for R-CHOP. The OOR was 77.5%, with 22 complete responses and 9 partial responses statistical analysis showed no significant difference in overall survival (OS) between patients aged 80 years and older and patients younger than 80 years (6·4 vs. 10·2 months, respectively, P = 0·43). Complete responders were more likely patients with good performance status, (ECOG 0-1) 13 patients (60%), 9 patients (40%) were ECOG 2; of the 9 patients who achieved partial response, 7 patients had ECOG 0-1 and 2 patients had ECOG 2. Four patients had stable disease. Progression-free survival (PFS) median PFS was 13.5 months. These preliminary results showed that bendamustine and rituximab has been associated with high response rates, acceptable toxicity in frail DLBCL patients and high rate of OSS. In older patients with advanced IPI scores, no significant difference in OS were observed between patients aged 80 years and older and patients younger than 80 years. We conclude that bendamustine and rituximab seems to be a reasonable alternative for frail DLBCL patients.

Published
2021

14. Risdiplam-Treated Infants with Type 1 Spinal Muscular Atrophy versus Historical Controls

Author

Darras, Basil T, Masson, Riccardo, Mazurkiewicz-Bełdzińska, Maria, Rose, Kristy, Xiong, Hui, Zanoteli, Edmar, Baranello, Giovanni, Bruno, Claudio, Vlodavets, Dmitry, Wang, Yi, El-Khairi, Muna, Gerber, Marianne, Gorni, Ksenija, Khwaja, Omar, Kletzl, Heidemarie, Scalco, Renata S, Fontoura, Paulo, Servais, Laurent, Joseph J, Volpe, John, Posner, Armin, Koch, Ulrich, Kellner, Rosaline, Quinlivan, Nicolas, Deconinck, Irina, Balikova, Patricia, Delbeke, Inge, Joniau, Valentine, Tahon, Sylvia, Wittevrongel, Elke De Vos, Rodrigo de Holanda Mendonça, Ciro Matsui Jr, Ana Letícia Fornazieri Darcie, Cleide, Machado, Maria Kiyoko Oyamada, Daniel de Souza Costa, Joyce, Martini, Graziela, Polido, Juliana Rodrigues Iannicelli, Juliana Caires de Oliveira Achili Ferreira, Chaoping, Hu, Yiyun, Shi, Shuizhen, Zhou, Xiaomei, Zhu, Chen, Qian, Shen, Li, Ying, Xiao, Zhenxuan, Zhou, Hui, Li, Sujuan, Wang, Tian, Sang, Cuijie, Wei, Jing, Wen, Yiwen, Cao, Wenzhu, Li, Lun, Qin, Nina, Barisic, Ivan, Celovec, Martina, Martina, Galiot, Delic, Petra Kristina Ivkić, Nenad, Vukojević, Ivana, Kern, Boris, Najdanovic, Marin, Skugor, Odile, Boespflug-Tanguy, Teresa, Gidaro, Andrea, Seferian, Emmanuel, Barreau, Elodie Da Cunha, Céline, Lambotin, Nabila, Mnafek, Helene, Peche, Stephanie, Gilabert, Allison, Grange, Charlotte, Lilien, Darko, Milascevic, Ariadna, Perticari, Shotaro, Tachibana, Emanuela, Pagliano, Stefania Bianchi Marzoli, Diletta, Santarsiero, Myriam Garcia Sierra, Gemma, Tremolada, Maria Teresa Arnoldi, Marta, Vigano, Riccardo, Zanin, Noemi, Brolatti, Marina, Pedemonte, Enrico, Priolo, Giuseppe, Rao, Enrica, Spaletra, Lorenza, Sposetti, Elisa, Tassara, Simone, Morando, Paola, Tacchetti, Giacomo Pietro Comi, Alessandra, Govoni, Silvia Gabriella Osnaghi, Valeria, Minorini, Francesca, Abbati, Federica, Fassini, Michaela, Foa, Amalia, Lopopolo, Elisa, Minuti, Mercuri, Eugenio Maria, Pane, Marika, Concetta, Palermo, Pera, Maria Carmela, Amorelli, Giulia Maria, Costanza, Barresi, Gugliemo, D'Amico, Orazi, Lorenzo, Coratti, Giorgia, De Sanctis, Roberto, Yasuhiro, Takeshima, Fumi, Gomi, Naoki, Kimura, Takanobu, Morimatsu, Mana, Okamoto, Toru, Furukawa, Mateusz, Koberda, Natalia, Kubiak, Urszula, Stodolska-Koberda, Agnieszka, Waśkowska, Jagoda, Kolendo, Agnieszka, Sobierajska-Rek, Svetlana, Artemyeva, Evgenia, Melnik, Natalya, Leppenen, Nataliya, Yupatova, Elena, Litvinova, Anastasya, Monakhova, Yulia, Papina, Olga, Shidlovsckaia, Andrea, Klein, Cornelia, Enzmann, Elea, Galiart, Konstantin, Gugleta, Patricia, Siems, Verena, Kreiliger, Christine Wondrusch Haschke, Haluk, Topaloglu, Ibrahim, Oncel, Didem, Ardicli, Nesibe Eroglu Ertugrul, Hizal, Gharibzadeh, Ceren, Gunbey, Bahadir, Konuskan, Selen Serel Arslan, Elams Ebru Yalcin, Fatma Gokcem Yildiz Sarikaya, Bora, Eldem, Sibel, Kadayıfçılar, Ipek, Alemdaroglu, Aynur Ayse Karaduman, Oznur Tunca Yilmaz, Robert, J Graham, Partha, Ghosh, David, Casavant, Brian, Snyder, Alexis, Levine, Rachael, Titus, Amanda, Engelbrekt, Lucia, Ambrosio, Anne, Fulton, Anna Maria Baglieri, Courtney, Dias, Elizabeth, Maczek, Elizabeth, Mirek, Amy, Pasternak, John, W Day, Shannon, Beres, Tina, Duong, Richard, Gee, Sally, Young, Darras, Basil T, Masson, Riccardo, Mazurkiewicz-Bełdzińska, Maria, Rose, Kristy, Xiong, Hui, Zanoteli, Edmar, Baranello, Giovanni, Bruno, Claudio, Vlodavets, Dmitry, Wang, Yi, El-Khairi, Muna, Gerber, Marianne, Gorni, Ksenija, Khwaja, Omar, Kletzl, Heidemarie, Scalco, Renata S, Fontoura, Paulo, Servais, Laurent, and Ambrosio, Lucia

Subjects
Male, medicine.medical_specialty, Neuromuscular disease, Risdiplam, Type 1 Spinal Muscular Atrophy, treated infants, historical controls, MEDLINE, Spinal Muscular Atrophies of Childhood, Severity of Illness Index, Text mining, Settore MED/39 - NEUROPSICHIATRIA INFANTILE, Internal medicine, Severity of illness, medicine, Humans, Progression-free survival, 610 Medicine & health, business.industry, Historically Controlled Study, Infant, General Medicine, Spinal muscular atrophy, SMA, medicine.disease, Progression-Free Survival, Settore MED/26 - NEUROLOGIA, Pyrimidines, Neuromuscular Agents, Motor Skills, Female, business, Azo Compounds
Abstract

BACKGROUND Type 1 spinal muscular atrophy (SMA) is a progressive neuromuscular disease characterized by an onset at 6 months of age or younger, an inability to sit without support, and deficient levels of survival of motor neuron (SMN) protein. Risdiplam is an orally administered small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein in blood. METHODS We conducted an open-label study of risdiplam in infants with type 1 SMA who were 1 to 7 months of age at enrollment. Part 1 of the study (published previously) determined the dose to be used in part 2 (reported here), which assessed the efficacy and safety of daily risdiplam as compared with no treatment in historical controls. The primary end point was the ability to sit without support for at least 5 seconds after 12 months of treatment. Key secondary end points were a score of 40 or higher on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; range, 0 to 64, with higher scores indicating better motor function), an increase of at least 4 points from baseline in the CHOP-INTEND score, a motor-milestone response as measured by Section 2 of the Hammersmith Infant Neurological Examination (HINE-2), and survival without permanent ventilation. For the secondary end points, comparisons were made with the upper boundary of 90% confidence intervals for natural-history data from 40 infants with type 1 SMA. RESULTS A total of 41 infants were enrolled. After 12 months of treatment, 12 infants (29%) were able to sit without support for at least 5 seconds, a milestone not attained in this disorder. The percentages of infants in whom the key secondary end points were met as compared with the upper boundary of confidence intervals from historical controls were 56% as compared with 17% for a CHOP-INTEND score of 40 or higher, 90% as compared with 17% for an increase of at least 4 points from baseline in the CHOP-INTEND score, 78% as compared with 12% for a HINE-2 motor-milestone response, and 85% as compared with 42% for survival without permanent ventilation (P

Published
2021

15. Risdiplam in Type 1 Spinal Muscular Atrophy

Author

Baranello, Giovanni, Darras, Basil T, Day, John W, Deconinck, Nicolas, Klein, Andrea, Masson, Riccardo, Mercuri, Eugenio Maria, Rose, Kristy, El-Khairi, Muna, Gerber, Marianne, Gorni, Ksenija, Khwaja, Omar, Kletzl, Heidemarie, Scalco, Renata S, Seabrook, Timothy, Fontoura, Paulo, Servais, Laurent, FIREFISH Working Group: Joseph, J Volpe, John, Posner, Armin, Koch, Ulrich, Kellner, Rosaline, Quinlivan, Irina, Balikova, Patricia, Delbeke, Inge, Joniau, Valentine, Tahon, Sylvia, Wittevrongel, Elke De Vos, Edmar, Zanoteli, Rodrigo de Holanda Mendonça, Ciro Matsui Jr, Ana Letícia Fornazieri Darcie, Cleide, Machado, Maria Kiyoko Oyamada, Daniel de Souza Costa, Joyce, Martini, Graziela, Polido, Juliana Rodrigues Iannicelli, Juliana Caires de Oliveira Achili Ferreira, Wang, Yi, Chaoping, Hu, Yiyun, Shi, Shuizhen, Zhou, Xiaomei, Zhu, Chen, Qian, Shen, Li, Ying, Xiao, Zhenxuan, Zhou, Hui, Li, Sujuan, Wang, Hui, Xiong, Tian, Sang, Cuijie, Wei, Jing, Wen, Yiwen, Cao, Wenzhu, Li, Lun, Qin, Nina, Barisic, Ivan, Celovec, Martina Galiot Delic, Petra Kristina Ivkić, Nenad, Vukojević, Ivana, Kern, Boris, Najdanovic, Marin, Skugor, Odile, Boespflug-Tanguy, Teresa, Gidaro, Andrea, Seferian, Emmanuel, Barreau, Elodie Da Cunha, Céline, Lambotin, Nabila, Mnafek, Helene, Peche, Stephanie, Gilabert, Allison, Grange, Charlotte, Lilien, Darko, Milascevic, Ariadna, Perticari, Shotaro, Tachibana, Emanuela, Pagliano, Bianchi Marzoli, Stefania, Diletta, Santarsiero, Myriam Garcia Sierra, Gemma, Tremolada, Maria Teresa Arnoldi, Marta, Vigano, Riccardo, Zanin, Bissoli, Claudio Bruno, Noemi, Brolatti, Marina, Pedemonte, Enrico, Priolo, Giuseppe, Rao, Enrica, Spaletra, Lorenza, Sposetti, Elisa, Tassara, Simone, Morando, Paola, Tacchetti, Giacomo Pietro Comi, Alessandra, Govoni, Silvia Gabriella Osnaghi, Valeria, Minorini, Francesca, Abbati, Federica, Fassini, Michaela, Foa, Amalia, Lopopolo, Elisa, Minuti, Pane, Marika, Concetta, Palermo, Pera, Maria Carmela, Amorelli, Giulia Maria, Costanza, Barresi, Gugliemo, D'Amico, Orazi, Lorenzo, Coratti, Giorgia, De Sanctis, Roberto, Yasuhiro, Takeshima, Fumi, Gomi, Naoki, Kimura, Takanobu, Morimatsu, Mana, Okamoto, Toru, Furukawa, Maria, Mazurkiewicz-Bełdzińska, Mateusz, Koberda, Natalia, Kubiak, Urszula, Stodolska-Koberda, Agnieszka, Waśkowska, Jagoda, Kolendo, Agnieszka, Sobierajska-Rek, Dmitry, Vlodavets, Svetlana, Artemyeva, Evgenia, Melnik, Natalya, Leppenen, Nataliya, Yupatova, Elena, Litvinova, Anastasya, Monakhova, Yulia, Papina, Olga, Shidlovsckaia, Cornelia, Enzmann, Elea, Galiart, Konstantin, Gugleta, Patricia, Siems, Verena, Kreiliger, Christine Wondrusch Haschke, Haluk, Topaloglu, Ibrahim, Oncel, Didem, Ardicli, Nesibe Eroglu Ertugrul, Hizal, Gharibzadeh, Ceren, Gunbey, Bahadir, Konuskan, Selen Serel Arslan, Elams Ebru Yalcin, Fatma Gokcem Yildiz Sarikaya, Bora, Eldem, Sibel, Kadayıfçılar, Ipek, Alemdaroglu, Aynur Ayse Karaduman, Oznur Tunca Yilmaz, Lucia, Ambrosio, Anne, Fulton, Anna Maria Baglieri, Courtney, Dias, Elizabeth, Maczek, Elizabeth, Mirek, Amy, Pasternak, Shannon, Beres, Tina, Duong, Richard, Gee, Sally, Young, Giovanni, Baranello, Basil T, Darra, John W, Day, Nicolas, Deconinck, Andrea, Klein, Riccardo, Masson, Eugenio, Mercuri, Kristy, Rose, Muna, El-Khairi, Marianne, Gerber, Ksenija, Gorni, Omar, Khwaja, Heidemarie, Kletzl, Renata S, Scalco, Timothy, Seabrook, Paulo, Fontoura, Laurent, Servai, and Ambrosio, Lucia

Subjects
Male, Oral, Neuromuscular disease, RNA Splicing, Administration, Oral, 030204 cardiovascular system & hematology, Spinal Muscular Atrophies of Childhood, Bioinformatics, Dose-Response Relationship, 03 medical and health sciences, 0302 clinical medicine, Settore MED/39 - NEUROPSICHIATRIA INFANTILE, medicine, Humans, Risdiplam, Type 1 Spinal Muscular Atrophy, 030212 general & internal medicine, Progression-free survival, 610 Medicine & health, Respiratory Tract Infections, Dose-Response Relationship, Drug, business.industry, Infant, Survival of motor neuron, General Medicine, Spinal muscular atrophy, medicine.disease, Survival of Motor Neuron 1 Protein, Progression-Free Survival, Clinical trial, Dose–response relationship, Settore MED/26 - NEUROLOGIA, Pyrimidines, nervous system, Neuromuscular Agents, RNA splicing, Administration, Female, Drug, business, Respiratory Insufficiency, Azo Compounds
Abstract

Background: Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein. Methods: We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds. Results: A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study. Conclusions: In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.).

Published
2021

16. Correlation between continuous Positive end-expiratory pressure (PEEP) values and occurrence of Pneumothorax and Pneumomediastinum in SARS-CoV2 patients during non-invasive ventilation with Helmet

Author

Anna Maria Brambilla, Antonio Gidaro, Chiara Cogliati, Marco Schiuma, Cecilia Bonino, Stella Ingrassia, Stefano Rusconi, Jaqueline Curra, Antonio Brucato, Viola Cupiraggi, Francesco Banfi, Andrea Giacomelli, Federica Samartin, and Emanuele Salvi

Subjects
Original Article: Clinical Research, medicine.medical_treatment, Population, Pneumomediastinum, CPAP, Medicine, Continuous positive airway pressure, education, PEEP, education.field_of_study, business.industry, Mortality rate, Pneumothorax, COVID-19, respiratory system, medicine.disease, respiratory tract diseases, Pneumonia, Anesthesia, SARS-CoV2, Breathing, business, Complication, circulatory and respiratory physiology
Abstract

Background Acute Hypoxemic Respiratory Failure (AHRF) is a common complication of Covid-19 related pneumonia, for which non-invasive ventilation (NIV) with Helmet Continuous Positive Airway Pressure (CPAP) is widely used. During past epidemics of SARS and MERS pneumomediastinum (PNM) and pneumothorax (PNX) were common complications (respectively 1.7-12% and 16,4%) either spontaneous or associated to ventilation. Methods Aim of our retrospective study was to investigate the incidence of PNX/PNM in COVID-19 pneumonia patients treated with CPAP. Moreover, we examined the correlation between PNX/PNM and Positive end-expiratory pressure (PEEP) values. We collected data from patients admitted to “Luigi Sacco” University Hospital of Milan from 21/02/2020 to 06/05/2020 with COVID-19 pneumonia requiring CPAP. Results One-hundred-fifty-four patients were enrolled. During hospitalization 3 PNX and 2 PNM occurred (3.2%). Out of these five patients 2 needed invasive ventilation after PNX, two died. In the overall population, 42 patients (27%) were treated with High-PEEP (>10 cmH2O), and 112 with Low-PEEP (≤10 cmH2O). All the PNX/PNM occurred in the High-PEEP group (5/37 vs 0/112, p Conclusion The incidence of PNX appears to be lower in COVID-19 than SARS and MERS, but their occurrence is accompanied by high mortality and worsening of clinical conditions. Considering the association of PNX/PNM with high PEEP we suggest using the lower PEEP as possible to prevent these complications. “Key messages” box Section 1: What is already known on this subject Elevated incidence of pneumomediastinum (PNM) and pneumothorax (PNX) occurring during SARS and MERS pneumonia (respectively 1.7-12%9,10 and 16,4%11), either spontaneous or associated to ventilation.Conversely, these complications have not been reported when NIV was used for the treatment of common pneumonia patients6,7. Some cases of PNX and PNM have been recently reported in patients with COVID-19 pneumonia, most of them spontaneous12-14, in some cases related to NIV15,16 or endotracheal intubation (ETI)17,18. Section 2: What this study adds Incidence of PNX/PNM is lower in COVID19 pneumonia patients during CPAP (3,2%) than SARS and MERS. Considering mortality rate and need of ETI, occurrence of PNX/PNM worsens prognosis. All the PNX/PNM occurred in the High-PEEP (>10 cmH2O) group (5/37 vs 0/112, p Considering the association of high PEEP (>10 cmH2O) with PNX/PNM, the use of low PEEP values has to be taken into consideration.

Published
2020

17. Global versus individual muscle segmentation to assess quantitative MRI-based fat fraction changes in neuromuscular diseases

Author

Olivier Benveniste, Benjamin Marty, Julien Le Louër, Brenda L. Wong, Yves Allenbach, Teresa Gidaro, P. Baudin, Jean-Marc Boisserie, Harmen Reyngoudt, Pierre G. Carlier, Cedi Koumako, Anthony Behin, Laurent Servais, Tanya Stojkovic, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire RMN AIM-CEA, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Division of Pediatric Neurology, Cincinnati Children's Hospital Medical Center, CHU Pitié-Salpêtrière [AP-HP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and University of Oxford

Subjects
medicine.medical_specialty, Dysferlinopathy, Neuromuscular disease, [SDV]Life Sciences [q-bio], Duchenne muscular dystrophy, Thigh, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Muscular dystrophy, Muscle, Skeletal, business.industry, Muscles, Skeletal muscle, General Medicine, Spinal muscular atrophy, Neuromuscular Diseases, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Adipose Tissue, Muscular Dystrophies, Limb-Girdle, 030220 oncology & carcinogenesis, Cardiology, Radiology, Inclusion body myositis, business
Abstract

Magnetic resonance imaging (MRI) constitutes a powerful outcome measure in neuromuscular disorders, yet there is a broad diversity of approaches in data acquisition and analysis. Since each neuromuscular disease presents a specific pattern of muscle involvement, the recommended analysis is assumed to be the muscle-by-muscle approach. We, therefore, performed a comparative analysis of different segmentation approaches, including global muscle segmentation, to determine the best strategy for evaluating disease progression. In 102 patients (21 immune-mediated necrotizing myopathy/IMNM, 21 inclusion body myositis/IBM, 10 GNE myopathy/GNEM, 19 Duchenne muscular dystrophy/DMD, 12 dysferlinopathy/DYSF, 7 limb-girdle muscular dystrophy/LGMD2I, 7 Pompe disease, 5 spinal muscular atrophy/SMA), two MRI scans were obtained at a 1-year interval in thighs and lower legs. Regions of interest (ROIs) were drawn in individual muscles, muscle groups, and the global muscle segment. Standardized response means (SRMs) were determined to assess sensitivity to change in fat fraction (ΔFat%) in individual muscles, muscle groups, weighted combinations of muscles and muscle groups, and in the global muscle segment. Global muscle segmentation gave high SRMs for ΔFat% in thigh and lower leg for IMNM, DYSF, LGMD2I, DMD, SMA, and Pompe disease, and only in lower leg for GNEM and thigh for IBM. Global muscle segment Fat% showed to be sensitive to change in most investigated neuromuscular disorders. As compared to individual muscle drawing, it is a faster and an easier approach to assess disease progression. The use of individual muscle ROIs, however, is still of interest for exploring selective muscle involvement. • MRI-based evaluation of fatty replacement in muscles is used as an outcome measure in the assessment of 1-year disease progression in 8 different neuromuscular diseases. • Different segmentation approaches, including global muscle segmentation, were evaluated for determining 1-year fat fraction changes in lower limb skeletal muscles. • Global muscle segment fat fraction has shown to be sensitive to change in lower leg and thigh in most of the investigated neuromuscular diseases.

Published
2020

18. Viable circulating endothelial cells and their progenitors are increased in Covid-19 patients

Author

Francesco Bertolini, Luca Gusso, Antonio Gidaro, Chiara Cogliati, Jessica Quarna, Alessandro Raveane, Sonia Caccia, Patrizia Mancuso, Paola Cremonesi, and Giuliana Gregato

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.diagnostic_test, business.industry, Cancer, Disease, medicine.disease_cause, medicine.disease, Gastroenterology, Flow cytometry, Apoptosis, Internal medicine, cardiovascular system, medicine, In patient, Progenitor cell, business, Coronavirus
Abstract

During the course of Covid-19, the disease caused by the new Coronavirus SARS-CoV-2, thrombotic phenomena and/or diffuse vascular damage are frequent, and viral elements have been observed within endothelial cells. Circulating endothelial cells (CECs) and their progenitors (CEPs) are increased in cardiovascular, thrombotic, infectious and cancer diseases. Using a validated flow cytometry procedure, we found that viable CEPs/mL were significantly increased in Covid-19 patients compared to healthy controls. This increase was observed in patients with mild symptoms and not further augmented in patients with severe symptoms. In patients who recovered, CEPs decreased, but were in a range still significantly higher than normal controls. Regarding mature CECs, in Covid-19 patients their absolute number was similar to those observed in healthy controls, but the viable/apoptotic CEC ratio was significantly different. Both mild and severe Covid-19 patients had significantly more viable CECs compared to healthy controls. Patients who recovered had significantly less CECs/mL when compared to controls as well as to mild and severe Covid-19 patients. A positive correlation was found between the copies of SARS-CoV-2 RNA in the cellular fraction and apoptotic CEPs/mL in severe Covid-19 patients. These findings suggest that CECs and CEPs might be investigated as candidate biomarkers of endothelial damage in Covid-19 patients.

Published
2020

19. Risk Of Thrombosis In Elderly Immune Primary Trombocytopenic Patients Treated with Thrombopoietin Receptors Agonists

Author

Roberto Castelli, Giorgio Lambertenghi Deliliers, and Antonio Gidaro

Subjects
Male, medicine.medical_specialty, MEDLINE, Bioinformatics, Immune system, Risk Factors, Internal medicine, medicine, Humans, Receptor, Thrombopoietin, Aged, Aged, 80 and over, Purpura, Thrombocytopenic, Idiopathic, Hematology, Primary (chemistry), business.industry, Thrombosis, Middle Aged, medicine.disease, Female, Cardiology and Cardiovascular Medicine, business, Receptors, Thrombopoietin
Published
2020

20. Mild clinical presentation in KLHL40-related nemaline myopathy (NEM 8)

Author

John Rendu, Julien Fauré, Laurent Pelletier, Pierre G. Carlier, Laurent Servais, Norma B. Romero, Andreea Mihaela Seferian, Véronique Forin, Edoardo Malfatti, Teresa Gidaro, Jessica Taytard, E. Gargaun, C Bosson, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de référence des maladies rares neuromusculaires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unit of Neuromuscular Morphology [CHU Pitié-Salpêtrière], Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de réhabilitation pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), NMR Laboratory, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Institut de Myologie (U153 Inserm - IM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Centre de référence des maladies rares neuromusculaires [CHU Pitié-Salpétriêre], and HAL-UPMC, Gestionnaire

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Muscle Proteins, KLHL40, Biology, medicine.disease_cause, Myopathies, Nemaline, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Nemaline myopathy, medicine, Humans, Nemaline bodies, Child, Muscle, Skeletal, Genetics (clinical), Sanger sequencing, Mutation, Muscle biopsy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, Genetic heterogeneity, medicine.disease, Hypotonia, 3. Good health, 030104 developmental biology, Phenotype, Neurology, Pediatrics, Perinatology and Child Health, symbols, Female, Neurology (clinical), Presentation (obstetrics), medicine.symptom, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Nemaline myopathies are clinically and genetically heterogeneous muscle diseases characterized by the presence of nemaline bodies (rods) in muscle fibers. Mutations in the KLHL40 (kelch-like family member 40) gene (NEM 8) are common cause of severe/lethal nemaline myopathy. We report an 8-year-old girl born to consanguineous Moroccan parents, who presented with hypotonia and poor sucking at birth, delayed motor development, and further mild difficulties in walking and fatigability. A muscle biopsy revealed the presence of nemaline bodies. KLHL40 gene Sanger sequencing disclosed a never before reported pathogenic homozygous mutation which resulted in absent KLHL40 protein expression in the muscle. This further expands the phenotypical spectrum of KLHL40 related nemaline myopathy.

Published
2020

21. DMD and West syndrome

Author

N. Butoianu, Teresa Gidaro, E. Gargaun, Svetlana Gataullina, Ruxandra Cardas, Laurent Servais, Thierry Bienvenu, Dana Craiu, Juliette Nectoux, Catrinel Iliescu, and Andreea Mihaela Seferian

Subjects
musculoskeletal diseases, Central Nervous System, Male, Pediatrics, medicine.medical_specialty, Duchenne muscular dystrophy, Dystrophin, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Seizures, 030225 pediatrics, medicine, Humans, Protein Isoforms, Muscular dystrophy, Genetics (clinical), biology, Seizure types, business.industry, Infant, West Syndrome, medicine.disease, Hypsarrhythmia, Muscular Dystrophy, Duchenne, Epileptic spasms, Neurology, Child, Preschool, Pediatrics, Perinatology and Child Health, Mutation, biology.protein, Neurology (clinical), medicine.symptom, business, Spasms, Infantile, 030217 neurology & neurosurgery
Abstract

Duchenne Muscular Dystrophy (DMD) is the most frequent muscular dystrophy in childhood, with a worldwide incidence of one in 5000 live male births. It is due to mutations in the dystrophin gene leading to absence of full-length dystrophin protein. Central nervous system involvement is well-known in Duchenne Muscular Dystrophy. The multiple dystrophin isoforms expressed in brain have important roles in cerebral development and functioning. The association of Duchenne Muscular Dystrophy with seizures has been reported, and there is a higher prevalence of epilepsy in Duchenne Muscular Dystrophy patients (between 6.3% and 12.3%) than in the general pediatric population (0.5–1%). Duchenne Muscular Dystrophy patients may present with focal seizures, generalized tonic-clonic seizures or absences. We report on two boys in whom Duchenne Muscular Dystrophy is associated with epileptic spasms and hypsarrhythmia that fulfil the criteria for West syndrome, thus extending the spectrum of seizure types described in Duchenne Muscular Dystrophy patients.

Published
2020

22. Normalized grip strength is a sensitive outcome measure through all stages of Duchenne muscular dystrophy

Author

Volker Straub, Valeria Ricotti, Jean-Yves Hogrel, Laurent Servais, Thomas Voit, Andreea Mihaela Seferian, Imelda J. M. de Groot, Marie De Antonio, Teresa Gidaro, Valérie Decostre, Erik H. Niks, Francesco Muntoni, Isabelle Ledoux, Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Leiden University Medical Center (LUMC), Radboud University Medical Center [Nijmegen], University College of London [London] (UCL), Centre Hospitalier Universitaire de Liège (CHU-Liège), University of Oxford [Oxford], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universiteit Leiden, University of Oxford, and Gestionnaire, Hal Sorbonne Université

Subjects
Duchenne muscular dystrophy, Adult, Male, medicine.medical_specialty, Adolescent, Normal values, Muscle Strength Dynamometer, Outcome measures, 03 medical and health sciences, Grip strength, Young Adult, 0302 clinical medicine, Physical medicine and rehabilitation, [SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Outcome Assessment, Health Care, medicine, Humans, In patient, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030212 general & internal medicine, Child, Glucocorticoids, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hand Strength, business.industry, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Reproducibility of Results, medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Muscular Dystrophy, Duchenne, Neurology, Child, Preschool, Cohort, Ambulatory, Disease Progression, Ceiling effect, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract

Contains fulltext : 220816.pdf (Publisher’s version ) (Closed access) OBJECTIVE: The main aim was to explore the changes in hand-grip strength in patients with Duchenne muscular dystrophy (DMD) aged 5-29 years. Secondary aims were to test the effect of mutation, ambulatory status and glucocorticoid use on grip strength and its changes over time and to compute the number of subjects needed for a clinical trial to stabilize grip strength. METHODS: The analysis was performed on data collected during five international natural history studies on a cohort of DMD patients. Two hundred and two patients with genetically proven DMD were pooled from five different natural history studies. Excepting 13 patients with only one visit, the mean duration of follow-up was 2.2 +/- 1.6 years. A total of 977 measurement points were collected. Grip strength was measured on the dominant side with a high precision dynamometer. The analysis was performed using absolute values and normalized values expressed in percentage of predicted values for age. RESULTS: For absolute values, grip strength typically increased in ambulatory boys and decreased in non-ambulatory patients. However, when normalized, grip strength was already reduced at age 5 years and thereafter continued to fall away from normal values. The weaker the patients, the less strength they are prone to lose over again. INTERPRETATION: Grip strength constitutes a sensitive and continuous outcome measure that can be used across all stages of DMD. Its measurement is easy to standardized, can be used in ambulatory and non-ambulatory patients and does not present any floor or ceiling effect. It is thus attractive as an outcome measure in therapeutic trials.

Published
2020

23. Rimeporide as a first- in-class NHE-1 inhibitor: Results of a phase Ib trial in young patients with Duchenne Muscular Dystrophy

Author

Joana Domingos, Delphine Labolle, Teresa Gidaro, Francesco Muntoni, Florence Porte Thomé, Camilla Johansson, Stefano C. Previtali, Jordi Díaz-Manera, Pietro Spitali, Julian Gray, Mirko Signorelli, Stephanie Carnesecchi, Jacqueline Pitchforth, Alberto Zambon, Cristina Al-Khalili Szigyarto, Pascale Roux-Lombard, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospital de la Santa Creu i Sant Pau, CIBER de Enfermedades Raras (CIBERER), Université de Genève (UNIGE), Geneva University Hospital (HUG), Leiden University Medical Center (LUMC), Royal Institute of Technology [Stockholm] (KTH ), Science for Life Laboratory [Solna], University College of London [London] (UCL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Genève = University of Geneva (UNIGE), and Universiteit Leiden

Subjects
Male, 0301 basic medicine, musculoskeletal diseases, Cardiomyopathy, Duchenne muscular dystrophy, Administration, Oral, Pharmacokinetic, Duchenne Muscular Dystrophy, Pharmacology, ddc:616.07, Models, Biological, Drug Administration Schedule, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacokinetics, Rimeporide, medicine, Humans, In patient, Child, Muscle, Skeletal, NHE-1, ComputingMethodologies_COMPUTERGRAPHICS, ddc:616, Sodium-Hydrogen Exchanger 1, business.industry, medicine.disease, Pathophysiology, 3. Good health, Europe, Muscular Dystrophy, Duchenne, Treatment Outcome, 030104 developmental biology, Neuromuscular Agents, chemistry, 030220 oncology & carcinogenesis, Pharmacodynamics, Heart failure, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Safety, business
Abstract

Graphical abstract, Rimeporide, a first-in-class sodium/proton exchanger Type 1 inhibitor (NHE-1 inhibitor) is repositioned by EspeRare for patients with Duchenne Muscular Dystrophy (DMD). Historically, NHE-1 inhibitors were developed for cardiac therapeutic interventions. There is considerable overlap in the pathophysiological mechanisms in Congestive Heart Failure (CHF) and in cardiomyopathy in DMD, therefore NHE-1 inhibition could be a promising pharmacological approach to the cardiac dysfunctions observed in DMD. Extensive preclinical data was collected in various animal models including dystrophin-deficient (mdx) mice to characterise Rimeporide’s anti-fibrotic and anti-inflammatory properties and there is evidence that NHE-1 inhibitors could play a significant role in modifying DMD cardiac and also skeletal pathologies, as the NHE-1 isoform is ubiquitous. We report here the first study with Rimeporide in DMD patients. This 4-week treatment, open label phase Ib, multiple oral ascending dose study, enrolled 20 ambulant boys with DMD (6–11 years), with outcomes including safety, pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers. Rimeporide was safe and well-tolerated at all doses. PK evaluations showed that Rimeporide was well absorbed orally reaching pharmacological concentrations from the lowest dose, with exposure increasing linearly with dose and with no evidence of accumulation upon repeated dosing. Exploratory PD biomarkers showed positive effect upon a 4-week treatment, supporting its therapeutic potential in patients with DMD, primarily as a cardioprotective treatment, and provide rationale for further efficacy studies.

Published
2020

24. Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps

Author

Teresa Gidaro and Laurent Servais

Subjects
030506 rehabilitation, Pediatrics, medicine.medical_specialty, Oligonucleotides, MEDLINE, SMN1, Approved drug, Muscular Atrophy, Spinal, 03 medical and health sciences, 0302 clinical medicine, Developmental Neuroscience, medicine, Milestone (project management), Animals, Humans, Drug Approval, business.industry, Spinal muscular atrophy, medicine.disease, SMA, Expanded access, Pediatrics, Perinatology and Child Health, Nusinersen, Neurology (clinical), 0305 other medical science, business, 030217 neurology & neurosurgery, Central Nervous System Agents
Abstract

Spinal muscular atrophy (SMA) is a recessive disorder caused by a mutation in the survival motor neuron 1 gene (SMN1); it affects 1 in 11 000 newborn infants. The most severe and most common form, type 1 SMA, is associated with early mortality in most cases and severe disability in survivors. Nusinersen, an antisense oligonucleotide, promotes production of full-length protein from the pseudogene SMN2. Nusinersen treatment prolongs survival of patients with type 1 SMA and allows motor milestone acquisition. Patients with type 2 SMA also show progress on different motor scales after nusinersen treatment. Nusinersen was recently approved by the European Medicines Agency and the US Food and Drug Administration; it is now reimbursed in several European countries and in the USA. In Australia, the transition from expanded access programme to commercial availability is coming soon. In New Zealand, an expanded access programme is opened, and in Canada price negotiation for the treatment is in progress. In this review we exemplify the clinical benefit of nusinersen in subgroups of patients with SMA. Nusinersen represents the first efficacious marked approved drug in type 1 and type 2 SMA. Different knowledge gaps, such as results in older patients, in patients with permanent ventilation, in patients with neonatal forms, or in patients after spinal fusion, still need to be addressed. WHAT THIS PAPER ADDS: Identifies gaps in knowledge about the efficacy of nusinersen in broader populations of patients with spinal muscular atrophy. Identifies open questions in populations of patients where proof of efficacy is available.

Published
2018

25. X-linked myotubular myopathy: A prospective international natural history study

Author

A. Hernandez, Andrea Gangfuß, V. Chê, Adele D'Amico, Rémi Bellance, Laurent Servais, Capucine de Lattre, Basil T. Darras, E. Gargaun, James J. Dowling, Teresa Gidaro, C. Lilien, Ulrike Schara, A. Daron, Ana Buj-Bello, H. Landy, Jean-Marie Cuisset, Carole Vuillerot, Jean-Yves Hogrel, S. Fontaine, Jean-Michel Arnal, Valérie Biancalana, Michèle Mayer, M. Annoussamy, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Advanced BC.org, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Neuromuscular Physiology and Evaluation Laboratory, Service of Clinical Trials and Databases, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Adult, Male, Vital capacity, medicine.medical_specialty, Neuromuscular disease, Adolescent, [SDV]Life Sciences [q-bio], Population, Medizin, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, Longitudinal Studies, Prospective Studies, education, Prospective cohort study, Child, education.field_of_study, business.industry, Exhalation, Infant, Middle Aged, medicine.disease, X-linked myotubular myopathy, 3. Good health, 030104 developmental biology, Phenotype, Child, Preschool, Breathing, Disease Progression, Neurology (clinical), business, 030217 neurology & neurosurgery, Natural history study, Follow-Up Studies, Myopathies, Structural, Congenital
Abstract

ObjectivesBecause X-linked myotubular myopathy (XLMTM) is a rare neuromuscular disease caused by mutations in the MTM1 gene with a large phenotypic heterogeneity, to ensure clinical trial readiness, it was mandatory to better quantify disease burden and determine best outcome measures.MethodsWe designed an international prospective and longitudinal natural history study in patients with XLMTM and assessed muscle strength and motor and respiratory functions over the first year of follow-up. The humoral immunity against adeno-associated virus serotype 8 was also monitored.ResultsForty-five male patients aged 3.5 months to 56.8 years were enrolled between May 2014 and May 2017. Thirteen patients had a mild phenotype (no ventilation support), 7 had an intermediate phenotype (ventilation support less than 12 hours a day), and 25 had a severe phenotype (ventilation support 12 or more hours a day). Most strength and motor function assessments could be performed even in very weak patients. Motor Function Measure 32 total score, grip and pinch strengths, and forced vital capacity, forced expiratory volume in the first second of exhalation, and peak cough flow measures discriminated the 3 groups of patients. Disease history revealed motor milestone loss in several patients. Longitudinal data on 37 patients showed that the Motor Function Measure 32 total score significantly decreased by 2%. Of the 38 patients evaluated, anti–adeno-associated virus type 8 neutralizing activity was detected in 26% with 2 patients having an inhibitory titer >1:10.ConclusionsOur data confirm that XLMTM is slowly progressive for male survivors regardless of their phenotype and provide outcome validation and natural history data that can support clinical development in this population.ClinicalTrials.gov identifierNCT02057705.

Published
2019

26. P.200 Feasibility and baseline values of continuous movement measurement in patients with centronuclear myopathy by using ActiMyo®

Author

J.Y. Hogrel, H. Landy, Ulrike Schara, V. Chê, Teresa Gidaro, Alessandra D'Amico, Andreea Mihaela Seferian, C. Lilien, L. Servais, M. Annoussamy, Jonathan Baets, Chris Freitag, M. Grelet, Anna Buj-Bello, A. Hernandez, Dominique Duchene, C. de Lattre, Anthony Behin, A. Grangé, and E. Gasnier

Subjects
Baseline values, medicine.medical_specialty, business.industry, Movement measurement, Medizin, medicine.disease, Neurology, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, Cardiology, In patient, Neurology (clinical), Centronuclear myopathy, business, Genetics (clinical)
Published
2019

27. Il ritmo dialitico bisettimanale può essere utilizzato in pazienti selezionati all’avvio del trattamento emodialitico cronico

Author

Valentina Martina, Bianca Visciano, Maria Meneghini, Barbara Gidaro, Antonella Stasi, Luca di Toma, Annalisa Neri, Francesco Cosa, Carlo Guastoni, and Marina Cornacchiari

Subjects
lcsh:Internal medicine, business.industry, Renal function, Patient survival, General Medicine, medicine.disease, Body weight, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, Obstructive lung disease, Pulmonary oedema, Pericarditis, Diabetes mellitus, Anesthesia, medicine, Pharmacology (medical), business, lcsh:RC31-1245, Urine output
Abstract

In recent years, several studies have evaluated the differences in survival and residual renal function between patients who underwent two times weekly haemodialysis (HDB) and three times weekly haemodialysis (HDT). In most cases, these studies have taken into account only the patient survival but not the time into treatment or “technique survival”. In our centre we have retrospectively evaluated the incident patients that were treated with HDB for at least three months between 01 January 2013 and 01 November 2015, focusing on the HDB technique survival. During the follow-up, 35 patients started treatment with HDB, while 13 with HDT. On average, patients treated with HDT were younger than HDB patients (60.9±15.9 years vs. 77.8±9.6 years, p=0.01), and body weight was higher in HDT patients (71±8 kg vs. 63±13 kg, p=0.01). HDT patients were more frequently affected by two or more comorbidities (diabetes, peripheral vasculopathy, cardiac disease, chronic obstructive lung disease) than patients treated by HDB. The creatinine clearance (CrCl) evaluated at the beginning of treatment was similar in the two groups (7.48±5 mL/min in HDB vs 5.4±5 mL/min in HDT, p=NS). Urine output at the beginning of the study was higher in the HDB than the HDT group (1,785±480 mL/24 h vs. 530±500 mL/24 h, p=0.001). Results. The mean survival of the HDB was 14.9±1.5 months (ranging from 12 to 17.9 months, median 14±2.4 months). During the follow-up period, 12 patients switched from HDB to HDT due to the presence of signs of fluid overload in ten of them. In these patients the CrCl and the urine output were significantly reduced by the end of the treatment (CrCl was 3.4±1.9 mL/min vs 6.8±2 mL/min, p=0.01; urine output was 995±567 mL/24h vs 1400±400 mL/24h, p = 0.02). No hospital admissions for uremic symptoms (pericarditis, pulmonary oedema, severe hyperkalaemia) were recorded throughout the follow-up period in HDB patients. Conclusions. Our study shows that HDB can be proposed in selected patients for a considerable period. Decrease of urine output and presence of symptoms related to fluid overload are the two main factors leading to the switch to HDT treatment.

Published
2018

28. Treatment with Ataluren for Duchene Muscular Dystrophy

Author

Mercuri, E, Muntoni, F, Osorio, An, Tulinius, M, Buccella, F, Morgenroth, Lp, Gordish-Dressman, H, Jiang, J, Trifillis, P, Zhu, J, Kristensen, A, Santos, Cl, Henricson, Ek, Mcdonald, Cm, Desguerre, I, Bernert, G, Gosk-Tomek, M, Ille, A, Kellersmann, A, Weiss, S, Pilshofer, V, Balintovà, Z, Danhofer, P, Fabulovà, P, Jurıkovà, L, Fuchsovà, P, Haberlovà, J, Laffargue, F, Sarret, C, Pontier, B, Bellance, R, Sarrazin, E, Sabouraud, P, Magot, A, Mercier, S, Péréon, Y, Cuisset, J-M, Coopman-Degryse, S, Enaud, E, Jacquemont, M-L, Perville, A, Renouil, M, Trommsdorff, V, Verheulpen, D, Fontaine-Carbonnel, S, Vuillerot, C, Peudenier, S, Ropars, J, Audic, F, Chabrol, B, Chabrier, S, Gousse, G, Lagrue, E, Aragon, K, Barnerias, C, Brande, Lv, De Lucia, S, Gidaro, T, Seferian, A, Servais, L, Laugel, V, Espil-Taris, C, Mecili, H, Raffo, E, Ragot-Mandry, S, Borrell, S, Kirschner, J, Gangfuss, A, Henrich, M, Kolbel, H, Schara, U, Sponemann, N, Temme, E, Seeger, J, Hirsch, A, Denecke, J, Johannsen, J, Neu, A, Osinski, D, Rugner, S, Schussler, S, Trollmann, R, Kaindl, A, Schneider, Jb, Stoltenburg, C, Weiss, C, Schreiber, G, Hahn, A, Grzybowski, M, Pavlidou, E, Pavlou, E, Dobner, S, Liptai, Z, Dor, T, Brogna, C, Catteruccia, M, D’Amico, A, Pane, E, Bello, L, Pegoraro, E, Semplicini, C, Albamonte, E, Baranello, G, Comi, G, Govoni, A, Lerario, A, Magri, F, Masson, R, Mauri, E, Sansone, V, Brusa, C, Mongini, T, Ricci, F, Vacchetti, M, Bruno, C, Paniucci, C, Pedemonte, M, Giannotta, M, Pini, A, Messina, S, Sframeli, M, Vita, Gl, Vita, G, Ruggiero, L, Santoro, L, Craiu, D, Motoescu, C, Sandu, C, Teleanu, R, Vasile, D, Hughes, I, Childs, A-M, Alhaswani, Z, Roper, H, Parasuraman, D, Degoede, C, Gowda, V, Manzur, A, Munot, P, Sarkokzy, A, Charlesworth, C, Lemon, J, Turner, L, Spinty, S, Dubrovsky, A, Kornberg, A, Ryan, M, Webster, R, Biggar, Wd, Mcadam, Lc, Mah, Jh, Kolski, H, Vishwanathan, V, Chidambaranathan, S, Nevo, Y, Gorni, K, Carlo, J, Abresch, Rt, Joyce, Nc, Cnaan, A, Leshner, R, Tesi-Rocha, C, Thangarajh, M, Duong, T, Clemens, Pr, Abdel-Hamid, H, Connolly, Am, Pestronk, A, Teasley, J, Harper, A, Bertorini, Te, Kuntz, N, Driscoll, S, Day, Jw, Karachunski, P, and Lotze, T.

Subjects
safety, medicine.medical_specialty, nonsense mutation Duchenne muscular dystrophy, Duchenne muscular dystrophy, Neurosurgery, STRIDE, effectiveness, Duchenne Muscular Dystrophy, Pediatrics, Dystrophin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Child Development, STRIDE Registry, International database, Internal medicine, medicine, Humans, In patient, Registries, Child, 030304 developmental biology, Pediatric, 0303 health sciences, Brain Diseases, Oxadiazoles, business.industry, Health Policy, Disease progression, Infant, ataluren, medicine.disease, Ataluren, Muscular Dystrophy, Duchenne, Treatment Outcome, chemistry, Neurology, Muscle Disorders, Codon, Nonsense, Neuromuscular, Propensity score matching, dystrophin, Nervous System Diseases, business, 030217 neurology & neurosurgery, Natural history study, Research Article
Abstract

Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype–phenotype/–ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan–Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p ≤ 0.05). There were no DMD genotype–phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.

Published
2020

29. The Senhance™ surgical robotic system ('Senhance') for total hysterectomy in obese patients: a pilot study

Author

Emanuele Perrone, Stefano Gidaro, Giovanni Scambia, Salvatore Gueli Alletti, Stefano Cianci, Giuseppe Vizzielli, Cristiano Rossitto, S. Pizzacalla, Giorgia Monterossi, Gueli Alletti, S., Rossitto, C., Cianci, S., Perrone, E., Pizzacalla, S., Monterossi, G., Vizzielli, G., Gidaro, S., and Scambia, G.

Subjects
medicine.medical_specialty, Ileus, medicine.medical_treatment, Operative Time, Health Informatics, Gynecologic oncology, Telelap ALF-X, Hysterectomy, Surgeon, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Robotic Surgical Procedures, Laparotomy, medicine, Humans, Endometrial Neoplasm, Obesity, Prospective Studies, Laparoscopy, Aged, Senhance, Surgeons, medicine.diagnostic_test, business.industry, Endometrial cancer, Perioperative, Middle Aged, medicine.disease, Surgery, Robotic, Endometrial Neoplasms, Prospective Studie, Robotic systems, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Postoperative Complication, business, Learning Curve, Human
Abstract

This pilot study was aimed to value the feasibility and safety of Senhance Robotic Platform for hysterectomy in obese patients. Ten obese patients (30&nbsp

Published
2017

30. Characterization of pulmonary function in 10–18 year old patients with Duchenne muscular dystrophy

Author

Ulrike Schara, Diana Castro, T. Gidaro, S. Lutz, Ksenija Gorni, Janbernd Kirschner, Antonella Taglia, V. Doppler, F. Knipp, Christian Rummey, Jan J.G.M. Verschuuren, Thomas Meier, Gihan Tennekoon, J.J. Vílchez Padilla, E. Falcier, Luisa Politano, Craig M. McDonald, Chiara S. M. Straathof, S. Borell, S. Coopman, Matthew J. Will, Pierre-Yves Jeannet, Nathalie Goemans, Paolo Spagnolo, Jean-Marie Cuisset, Carsten G. Bönnemann, R.C. Richardson, G. Bernert, Thomas Sejersen, N. Muelas Gómez, Maria Grazia D'Angelo, Erika Brighina, Thomas Voit, S. Gandossini, Mika Leinonen, Susan T. Iannaccone, Oscar H. Mayer, Gunnar M. Buyse, Clemens Bloetzer, M. van den Hauwe, Susan D. Apkon, Richard S. Finkel, G. Buyse, P. D’Ambrosio, Erik K Henricson, Nanette C. Joyce, M. Hovmöller, Van den Hauwe, M, Meier, Thoma, Rummey, Christian, Leinonen, Mika, Spagnolo, Paolo, Mayer, Oscar H., Buyse, Gunnar M., Bernert, G., Knipp, F., Buyse, G. M., Goemans, N., Van den Hauwe, M., Voit, T., Doppler, V., Gidaro, T., Cuisset, J. -. M., Coopman, S., Schara, U., Lutz, S., Kirschner, J., Borell, S., Will, M., D'Angelo, M. G., Brighina, E., Gandossini, S., Gorni, K., Falcier, E., Politano, L., D'Ambrosio, P., Taglia, A., Verschuuren, J. J. G. M., Straathof, C. S. M., Vílchez Padilla, J. J., Muelas Gómez, N., Sejersen, T., Hovmã¶ller, M., Jeannet, P. -. Y., Bloetzer, C., Iannaccone, S., Castro, D., Tennekoon, G., Finkel, R., Bã¶nnemann, C., Mcdonald, C., Henricson, E., Joyce, N., Apkon, S., and Richardson, R. C.

Subjects
Duchenne muscular dystrophy, medicine.medical_specialty, Vital capacity, Adolescent, peak expiratory flow, Respiratory Tract Diseases, Medizin, Clinical Neurology, Pulmonary insufficiency, Placebo group, Pediatrics, Pulmonary function testing, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, forced vital capacity, Internal medicine, medicine, Humans, In patient, Genetics(clinical), Pediatrics, Perinatology, and Child Health, Longitudinal Studies, Muscular Dystrophy, Child, Genetics (clinical), Old patients, business.industry, pulmonary function, respiratory system, Perinatology and Child Health, medicine.disease, Duchenne, Cross-Sectional Studies, Muscular Dystrophy, Duchenne, Respiratory Function Tests, Pediatrics, Perinatology and Child Health, Neurology, Neurology (clinical), Surgery, respiratory tract diseases, 030228 respiratory system, Cardiology, business, 030217 neurology & neurosurgery, circulatory and respiratory physiology
Abstract

Pulmonary function loss in patients with Duchenne muscular dystrophy (DMD) is progressive and leads to pulmonary insufficiency. The purpose of this study in 10-18 year old patients with DMD is the assessment of the inter-correlation between pulmonary function tests (PFTs), their reliability and the association with the general disease stage measured by the Brooke score. Dynamic PFTs (peak expiratory flow [PEF], forced vital capacity [FVC], forced expiratory volume in one second [FEV1]) and maximum static airway pressures (MIP, MEP) were prospectively collected from 64 DMD patients enrolled in the DELOS trial (ClinicalTrials.gov, number NCT01027884). Baseline PEF percent predicted (PEF%p) was

Published
2017

31. Longitudinal functional and NMR assessment of upper limbs in Duchenne muscular dystrophy

Author

Gwenn Ollivier, Aurélie Canal, Laurent Servais, Jean-Yves Hogrel, Valérie Decostre, Noura Azzabou, Teresa Gidaro, Isabelle Ledoux, Anne Gaelle Le Moing, C. Lilien, Pierre G. Carlier, M. Annoussamy, Nacera Reguiba, Thomas Voit, Amélie Moraux, Ruxandra Cardas, Claire Wary, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and DESSAIVRE, Louise

Subjects
Male, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Adolescent, [SDV]Life Sciences [q-bio], Duchenne muscular dystrophy, Fat infiltration, Article, 030218 nuclear medicine & medical imaging, Phosphocreatine, Upper Extremity, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Longitudinal Studies, Muscular dystrophy, Sensitivity to change, Child, business.industry, Nuclear magnetic resonance spectroscopy, medicine.disease, [SDV] Life Sciences [q-bio], Muscular Dystrophy, Duchenne, medicine.anatomical_structure, chemistry, Ambulatory, Cardiology, Upper limb, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

International audience; Objective:To explore the value of nuclear magnetic resonance (NMR) and functional assessments for follow-up of ambulatory and nonambulatory patients with Duchenne muscular dystrophy (DMD).Methods:Twenty-five 53-skippable patients with DMD were included in this study; 15 were nonambulatory at baseline. All patients underwent clinical and functional assessments every 6 months using the Motor Function Measure (MFM), hand grip and key pinch strength, MoviPlate, and NMR spectroscopy and imaging studies.Results:Upper limb distal strength decreased in nonambulatory patients over the period of 1 year; ambulatory patients showed improvement during the same period. The same applied for several NMRS indices, such as phosphocreatine/adenosine triphosphate, which decreased in older patients but increased in younger ambulatory patients. Fat infiltration in the upper limbs increased linearly with age. Almost all NMR and functional assessment results correlated.Conclusions:Our results underscore complementarity of functional and NMR assessments in patients with DMD. Sensitivity to change of various indices may differ according to disease stage.

Published
2016

32. Sitting in patients with spinal muscular atrophy type 1 treated with nusinersen

Author

Aragon-Gawinska, K, Daron, A, Ulinici, A, Vanden Brande, L, Seferian, A, Gidaro, T, Scoto, M, Deconinck, N, Servais, L, and Group, SMA-Registry Study

Subjects
Male, 030506 rehabilitation, Pediatrics, medicine.medical_specialty, Oligonucleotides, Clinical Neurology, Neurological examination, Spinal Muscular Atrophies of Childhood, Baseline level, Sitting, 03 medical and health sciences, 0302 clinical medicine, Developmental Neuroscience, Neurologie, mental disorders, medicine, Humans, In patient, Pediatrics, Perinatology, and Child Health, Registries, Child, Neurologic Examination, Sitting Position, medicine.diagnostic_test, business.industry, Motor Skills -- drug effects -- physiology, Infant, Mean age, Spinal muscular atrophy, Sciences bio-médicales et agricoles, medicine.disease, Perinatology, and Child Health, Motor Skills, Child, Preschool, Pediatrics, Perinatology and Child Health, Oligonucleotides -- pharmacology -- therapeutic use, Nusinersen, Female, Neurology (clinical), Spinal Muscular Atrophies of Childhood -- drug therapy -- physiopathology, 0305 other medical science, business, 030217 neurology & neurosurgery, After treatment
Abstract

To determine factors associated with acquisition of a sitting position in patients with spinal muscular atrophy type 1 (SMA1) treated with nusinersen., info:eu-repo/semantics/published

Published
2020

33. The role of intraoperative stroke volume variation on bleeding during functional endoscopic sinus surgery

Author

Santo Di Lorenzo, Fabiana Lucci, Mario Dauri, Roberta Di Mauro, Eleonora Gidaro, Nicola Toschi, Federica Martino, Stefano Di Girolamo, and Maria Beatrice Silvi

Subjects
Adult, Male, medicine.medical_specialty, Blood Loss, Surgical, Hemodynamics, Settore MED/41 - Anestesiologia, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, Monitoring, Intraoperative, medicine, Coagulopathy, Humans, Prospective Studies, Sinusitis, 030223 otorhinolaryngology, Prospective cohort study, Aged, Rhinitis, medicine.diagnostic_test, business.industry, Endoscopy, Stroke Volume, Stroke volume, Functional endoscopic sinus surgery, Middle Aged, medicine.disease, Surgery, Anesthesiology and Pain Medicine, Chronic Disease, Female, Supraventricular tachycardia, business
Abstract

Background Functional endoscopic sinus surgery (FESS) is a minimally-invasive surgical technique for patients with paranasal sinus pathology. Surgical bleeding reduces operative field visibility and increases the incidence of serious complications. Epinephrine injection into the nasal mucosa and controlled hypotension are used to minimize bleeding. Hypotension carries risks and sometimes does not reduce surgical bleeding. The goal of this study is to discover which hemodynamic parameter better correlates with surgical bleeding. Methods We enrolled 55 patients undergoing FESS. Inclusion criteria: male or female with chronic rhinosinusitis (CRS), older than 18 years, ASA I to III and primary surgery. Exclusion criteria: ASA>III, cerebrovascular and cardiac disorders, supraventricular tachycardia, renal or hepatic diseases, non-treated arterial hypertension, beta-blocking agent therapy, platelet-inhibiting agent or anticoagulant therapy, coagulopathy, pregnancy, clotting disorders, presence of neoplastic lesions and history of cranio-facial surgery. We used standard ASA plus ClearSight to assess hemodynamic parameters. Surgical procedures were performed by one surgeon and divided in ten surgical times (from T0 to T9). Intraoperative bleeding was assessed using the Fromme-Boezaart Scale. Results Analysis between all the hemodynamic parameters registered and the Fromme-Boezaart Score showed a negative correlation between surgical bleeding and stroke volume variation (SVV) only. When dichotomizing according to Fromme-Boezaart Score (above or below 2), SVV was the only parameter which showed significant differences between groups. A cut-off of 12.5% in SVV is optimal to distinguish the group with the better surgical visibility from the group with the worst one. Conclusions Targeting SVV larger than 12% achieves a possible reduction of the intraoperative bleeding in patients undergoing FESS.

Published
2018

34. Adherence to antibiotic treatment guidelines and outcomes in the hospitalized elderly with different types of pneumonia

Author

Rossio, R, Franchi, C, Ardoino, I, Djade, Cd, Tettamanti, M, Pasina, L, Salerno, F, Marengoni, A, Corrao, S, Marcucci, M, Peyvandi, F, Biganzoli, Em, Nobili, A, Mannucci, Pm, Mannucci, M, Sparacio, E, Alborghetti, S, Di Costanzo, R, Eldin, Tk, Prisco, D, Silvestri, E, Cenci, C, Barnini, T, Delitala, G, Carta, S, Atzori, S, Guarnieri, G, Zanetti, M, Spalluti, A, Serra, Mg, Bleve, Ma, Vanoli, M, Grignani, G, Casella, G, Gasbarrone, L, Maniscalco, G, Gunelli, M, Tirotta, D, Brucato, A, Ghidoni, S, Di Corato, P, Bernardi, M, Li Bassi, S, Santi, L, Agnelli, G, Iorio, A, Marchesini, E, Mannarino, E, Lupattelli, G, Rondelli, P, Paciullo, F, Fabris, F, Carlon, M, Turatto, F, Baroni, Mc, Zardo, M, Manfredini, R, Molino, C, Pala, M, Fabbian, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Paolisso, G, Rizzo, Mr, Laieta, Mt, Salvatore, T, Sasso, Fc, Utili, R, Durante Mangoni, E, Pinto, D, Olivieri, O, Stanzial, Am, Fellin, R, Volpato, S, Fotini, S, Barbagallo, M, Dominguez, L, Plances, L, D'Angelo, D, Rini, G, Mansueto, P, Pepe, I, Licata, G, Calvo, L, Valenti, M, Borghi, C, Strocchi, E, Rinaldi, Er, Zoli, M, Fabbri, E, Magalotti, D, Auteri, A, Pasqui, Al, Puccetti, L, Laghi Pasini, F, Capecchi, Pl, Bicchi, M, Sabbà, C, Vella, Fs, Marseglia, A, Luglio, Cv, Palasciano, G, Modeo, Me, Aquilino, A, Pugliese, S, Capobianco, C, Postiglione, A, Barbella, Mr, De Stefano, F, Fenoglio, L, Brignone, C, Bracco, C, Giraudo, A, Musca, G, Cuccurullo, O, Cricco, L, Fiorentini, A, Cappellini, Md, Fabio, G, Seghezzi, S, De Amicis, Mm, Fargion, S, Bonara, P, Bulgheroni, M, Lombardi, R, Magrini, F, Massari, F, Tonella, T, Tedeschi, A, Moreo, G, Ferrari, B, Roncari, L, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Mari, D, Rossi, Pd, Damanti, S, Prolo, S, Lilleri, Ms, Micale, G, Podda, M, Selmi, C, Meda, F, Accordino, S, Conca, A, Monti, V, Corazza, Gr, Miceli, E, Lenti, Mv, Padula, D, Balduini, Cl, Bertolino, G, Provini, S, Quaglia, F, Murialdo, G, Bovio, M, Dallegri, F, Ottonello, L, Quercioli, A, Barreca, A, Secchi, Mb, Ghelfi, D, Chin, Ws, Carassale, L, Caporotundo, S, Anastasio, L, Sofia, L, Carbone, M, Di Carlo, S, Traisci, G, De Feudis, L, Davì, G, Guagnano, Mt, Sestili, S, Bergami, E, Rizzioli, E, Cagnoni, C, Bertone, L, Manucra, A, Buratti, A, Tognin, T, Liberato, Nl, Bernasconi, G, Nardo, B, Bianchi, Gb, Giaquinto, S, Benetti, G, Quagliolo, M, Centenaro, Gr, Purrello, F, Di Pino, A, Piro, S, Mancuso, G, Calipari, D, Bartone, M, Gullo, F, Cortellaro, M, Magenta, M, Perego, F, Meroni, Mr, Cicardi, M, Gidaro, A, Sacco, A, Bonelli, A, Dentamaro, G, Rozzini, R, Falanga, L, Giordano, A, Perin, Pc, Lorenzati, B, Gruden, G, Bruno, G, Montrucchio, G, Greco, E, Tizzani, P, Fera, G, Di Luca, Ml, Renna, D, Perciccante, A, Coralli, A, Tassara, R, Melis, D, Rebella, L, Menardo, G, Bottone, S, Sferrazzo, E, Ferri, C, Striuli, R, Scipioni, R, Salmi, R, Gaudenzi, P, Gamberini, S, Ricci, F, Morabito, C, Fava, R, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Bolondi, L, Rasciti, L, Serio, I, Masala, C, Mammarella, A, Raparelli, V, Rossi Fanelli, F, Delfino, M, Amoroso, A, Violi, F, Basili, S, Perri, L, Serra, P, Fontana, V, Falcone, M, Landolfi, R, Grieco, A, Gallo, A, Zuccalà, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, Bellusci, M, Setti, D, Pedrazzoli, F, Romanelli, G, Pirali, C, Amolini, C, Rosei, Ea, Rizzoni, D, Castoldi, L, Picardi, A, Gentilucci, Uv, Mazzarelli, C, Gallo, P, Guasti, Luigina, Castiglioni, Luana, Maresca, ANDREA MARIA, Squizzato, Alessandro, Contini, Sara, Molaro, Marta, Annoni, G, Corsi, M, Zazzetta, S, Bertolotti, M, Mussi, C, Scotto, R, Ferri, Ma, Veltri, F, Arturi, F, Succurro, E, Sesti, G, Gualtieri, U, Perticone, F, Sciacqua, A, Quero, M, Bagnato, C, Loria, P, Becchi, Ma, Martucci, G, Fantuzzi, A, Maurantonio, M, Corinaldesi, R, De Giorgio, R, Serra, M, Grasso, V, Ruggeri, E, Carozza, Lm, Pignatti, F., Rossio, Raffaella, Franchi, Carlotta, Ardoino, Ilaria, Djade, Codjo D., Tettamanti, Mauro, Pasina, Luca, Salerno, Francesco, Marengoni, Alessandra, Corrao, Salvatore, Marcucci, Maura, Peyvandi, Flora, Biganzoli, Elia M., Nobili, Alessandro, Mannucci, Pier Mannuccio, Sparacio, Eleonora, Alborghetti, Stefania, Di Costanzo, Rosa, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Barnini, Tommaso, Delitala, Giuseppe, Carta, Stefano, Atzori, Sebastiana, Guarnieri, Gianfranco, Zanetti, Michela, Spalluti, Annalisa, Serra, Maria Grazia, Bleve, Maria Antonietta, Vanoli, Massimo, Grignani, Giulia, Casella, Gianluca, Gasbarrone, Laura, Maniscalco, Giorgio, Gunelli, Massimo, Tirotta, Daniela, Brucato, Antonio, Ghidoni, Silvia, Di Corato, Paola, Bernardi, Mauro, Li Bassi, Silvia, Santi, Luca, Agnelli, Giancarlo, Iorio, Alfonso, Marchesini, Emanuela, Mannarino, Elmo, Lupattelli, Graziana, Rondelli, Pamela, Paciullo, Francesco, Fabris, Fabrizio, Carlon, Michela, Turatto, Francesca, Baroni, Maria Cristina, Zardo, Marianna, Manfredini, Roberto, Molino, Christian, Pala, Marco, Fabbian, Fabio, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Laieta, Maria Teresa, Salvatore, Teresa, Sasso, Ferdinando Carlo, Utili, Riccardo, Mangoni, Emanuele Durante, Pinto, Daniela, Olivieri, Oliviero, Stanzial, Anna Maria, Fellin, Renato, Volpato, Stefano, Fotini, Siouli, Barbagallo, Mario, Dominguez, Ligia, Plances, Lidia, D'Angelo, Daniela, Rini, Giovanbattista, Mansueto, Pasquale, Pepe, Ilenia, Licata, Giuseppe, Calvo, Luigi, Valenti, Maria, Borghi, Claudio, Strocchi, Enrico, Rinaldi, Elisa Rebecca, Zoli, Marco, Fabbri, Elisa, Magalotti, Donatella, Auteri, Alberto, Pasqui, Anna Laura, Puccetti, Luca, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Bicchi, Maurizio, Sabbà, Carlo, Vella, Francesco Saverio, Marseglia, Alessandro, Luglio, Chiara Valentina, Palasciano, Giuseppe, Modeo, Maria Ester, Aquilino, Annamaria, Raffaele, Pallante, Pugliese, Stefania, Capobianco, Caterina, Postiglione, Alfredo, Barbella, Maria Rosaria, De Stefano, Francesco, Fenoglio, Luigi, Brignone, Chiara, Bracco, Christian, Giraudo, Alessia, Musca, Giuseppe, Cuccurullo, Olga, Cricco, Luigi, Fiorentini, Alessandra, Cappellini, Maria Domenica, Fabio, Giovanna, Seghezzi, Sonia, De Amicis, Margherita Migone, Fargion, Silvia, Bonara, Paola, Bulgheroni, Mara, Lombardi, Rosa, Magrini, Fabio, Massari, Ferdinando, Tonella, Tatiana, Tedeschi, Alberto, Moreo, Guido, Ferrari, Barbara, Roncari, Luisa, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Magnini, Maria, Mari, Daniela, Rossi, Paolo Dionigi, Damanti, Sarah, Prolo, Silvia, Lilleri, Maria Sole, Micale, Giuliana, Podda, Mauro, Selmi, Carlo, Meda, Francesca, Accordino, Silvia, Conca, Alessio, Monti, Valentina, Corazza, Gino Roberto, Miceli, Emanuela, Lenti, Marco Vincenzo, Padula, Donatella, Balduini, Carlo L., Bertolino, Giampiera, Provini, Stella, Quaglia, Federica, Murialdo, Giovanni, Bovio, Marta, Dallegri, Franco, Ottonello, Luciano, Quercioli, Alessandra, Barreca, Alessandra, Secchi, Maria Beatrice, Ghelfi, Davide, Chin, Wu Sheng, Carassale, Laura, Caporotundo, Silvia, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Traisci, Giancarlo, De Feudis, Lucrezia, Di Carlo, Silvia, Davì, Giovanni, Guagnano, Maria Teresa, Sestili, Simona, Bergami, Elisabetta, Rizzioli, Emanuela, Cagnoni, Carlo, Bertone, Luca, Manucra, Antonio, Buratti, Alberto, Tognin, Tiziana, Liberato, Nicola Lucio, Bernasconi, Giordano, Nardo, Barbara, Bianchi, Giovanni Battista, Benetti, Giampiero, Quagliolo, Michela, Centenaro, Giuseppe Riccardo, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Gullo, Francesco, Cortellaro, Michele, Magenta, Marina, Perego, Francesca, Meroni, Maria Rachele, Cicardi, Marco, Magenta, Antonio Gidaro Marina, Sacco, Andrea, Bonelli, Antonio, Dentamaro, Gaetano, Rozzini, Renzo, Falanga, Lina, Giordano, Alessandro, Perin, Paolo Cavallo, Lorenzati, Bartolomeo, Gruden, Gabriella, Bruno, Graziella, Montrucchio, Giuseppe, Greco, Elisabetta, Tizzani, Pietro, Fera, Giacomo, Di Luca, Maria Loreta, Renna, Donatella, Perciccante, Antonio, Coralli, Alessia, Tassara, Rodolfo, Melis, Deborah, Rebella, Lara, Menardo, Giorgio, Bottone, Stefania, Sferrazzo, Elsa, Ferri, Claudio, Striuli, Rinaldo, Scipioni, Rosa, Salmi, Raffaella, Gaudenzi, Piergiorgio, Gamberini, Susanna, Ricci, Franco, Morabito, Cosimo, Fava, Roberto, Semplicini, Andrea, Gottardo, Lucia, Vendemiale, Gianluigi, Serviddio, Gaetano, Forlano, Roberta, Bolondi, Luigi, Rasciti, Leonardo, Serio, Ilaria, Masala, Cesare, Mammarella, Antonio, Raparelli, Valeria, Fanelli, Filippo Rossi, Delfino, Massimo, Amoroso, Antonio, Violi, Francesco, Basili, Stefania, Perri, Ludovica, Serra, Pietro, Fontana, Vincenzo, Falcone, Marco, Landolfi, Raffaele, Grieco, Antonio, Gallo, Antonella, Zuccalà, Giuseppe, Franceschi, Francesco, De Marco, Guido, Chiara, Cordischi, Marta, Sabbatini, Bellusci, Martino, Setti, Donatella, Pedrazzoli, Filippo, Romanelli, Giuseppe, Pirali, Caterina, Amolini, Claudia, Rosei, Enrico Agabiti, Rizzoni, Damiano, Castoldi, Luana, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Mazzarelli, Chiara, Gallo, Paolo, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Contini, Sara, Molaro, Marta, Annoni, Giorgio, Corsi, Maurizio, Zazzetta, Sara, Bertolotti, Marco, Mussi, Chiara, Scotto, Roberto, Ferri, Maria Alice, Veltri, Francesca, Arturi, Franco, Succurro, Elena, Sesti, Giorgio, Gualtieri, Umberto, Perticone, Francesco, Sciacqua, Angela, Quero, Michele, Bagnato, Chiara, Loria, Paola, Becchi, Maria Angela, Martucci, Gianfranco, Fantuzzi, Alessandra, Maurantonio, Mauro, Corinaldesi, Roberto, De Giorgio, Roberto, Serra, Mauro, Grasso, Valentina, Ruggeri, Eugenio, Carozza, Lorenzo Mauro, Pignatti, Fabio, Raffaella Rossio, Carlotta Franchi, Ilaria Ardoino, Codjo D. Djade, Mauro Tettamanti, Luca Pasina, Francesco Salerno, Alessandra Marengoni, Salvatore Corrao, Maura Marcucci, Flora Peyvandi, Elia M. Biganzoli, Alessandro Nobili, Pier Mannuccio Mannucci, REPOSI Investigators [.., Mauro Bernardi, Claudio Borghi, Marco Zoli, Luigi Bolondi, Roberto Corinaldesi, Roberto De Giorgio, ], Rossio, R, Franchi, C, Ardoino, I, Djade, C, Tettamanti, M, Pasina, L, Salerno, F, Marengoni, A, Corrao, S, Marcucci, M, Peyvandi, F, Biganzoli, E, Nobili, A, Mannucci, P, Mannucci, M, Sparacio, E, Alborghetti, S, Di Costanzo, R, Eldin, T, Prisco, D, Silvestri, E, Cenci, C, Barnini, T, Delitala, G, Carta, S, Atzori, S, Guarnieri, G, Zanetti, M, Spalluti, A, Serra, M, Bleve, M, Vanoli, M, Grignani, G, Casella, G, Gasbarrone, L, Maniscalco, G, Gunelli, M, Tirotta, D, Brucato, A, Ghidoni, S, Di Corato, P, Bernardi, M, Li Bassi, S, Santi, L, Agnelli, G, Iorio, A, Marchesini, E, Mannarino, E, Lupattelli, G, Rondelli, P, Paciullo, F, Fabris, F, Carlon, M, Turatto, F, Baroni, M, Zardo, M, Manfredini, R, Molino, C, Pala, M, Fabbian, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Paolisso, G, Rizzo, M, Laieta, M, Salvatore, T, Sasso, F, Utili, R, Durante Mangoni, E, Pinto, D, Olivieri, O, Stanzial, A, Fellin, R, Volpato, S, Fotini, S, Barbagallo, M, Dominguez, L, Plances, L, D’Angelo, D, Rini, G, Mansueto, P, Pepe, I, Licata, G, Calvo, L, Valenti, M, Borghi, C, Strocchi, E, Rinaldi, E, Zoli, M, Fabbri, E, Magalotti, D, Auteri, A, Pasqui, A, Puccetti, L, Laghi Pasini, F, Capecchi, P, Bicchi, M, Sabbà, C, Vella, F, Marseglia, A, Luglio, C, Palasciano, G, Modeo, M, Aquilino, A, Pugliese, S, Capobianco, C, Postiglione, A, Barbella, M, De Stefano, F, Fenoglio, L, Brignone, C, Bracco, C, Giraudo, A, Musca, G, Cuccurullo, O, Cricco, L, Fiorentini, A, Cappellini, M, Fabio, G, Seghezzi, S, De Amicis, M, Fargion, S, Bonara, P, Bulgheroni, M, Lombardi, R, Magrini, F, Massari, F, Tonella, T, Tedeschi, A, Moreo, G, Ferrari, B, Roncari, L, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Mari, D, Rossi, P, Damanti, S, Prolo, S, Lilleri, M, Micale, G, Podda, M, Selmi, C, Meda, F, Accordino, S, Conca, A, Monti, V, Corazza, G, Miceli, E, Lenti, M, Padula, D, Balduini, C, Bertolino, G, Provini, S, Quaglia, F, Murialdo, G, Bovio, M, Dallegri, F, Ottonello, L, Quercioli, A, Barreca, A, Secchi, M, Ghelfi, D, Chin, W, Carassale, L, Caporotundo, S, Anastasio, L, Sofia, L, Carbone, M, Di Carlo, S, Traisci, G, De Feudis, L, Davì, G, Guagnano, M, Sestili, S, Bergami, E, Rizzioli, E, Cagnoni, C, Bertone, L, Manucra, A, Buratti, A, Tognin, T, Liberato, N, Bernasconi, G, Nardo, B, Bianchi, G, Giaquinto, S, Benetti, G, Quagliolo, M, Centenaro, G, Purrello, F, Di Pino, A, Piro, S, Mancuso, G, Calipari, D, Bartone, M, Gullo, F, Cortellaro, M, Magenta, M, Perego, F, Meroni, M, Cicardi, M, Gidaro, A, Sacco, A, Bonelli, A, Dentamaro, G, Rozzini, R, Falanga, L, Giordano, A, Perin, P, Lorenzati, B, Gruden, G, Bruno, G, Montrucchio, G, Greco, E, Tizzani, P, Fera, G, Di Luca, M, Renna, D, Perciccante, A, Coralli, A, Tassara, R, Melis, D, Rebella, L, Menardo, G, Bottone, S, Sferrazzo, E, Ferri, C, Striuli, R, Scipioni, R, Salmi, R, Gaudenzi, P, Gamberini, S, Ricci, F, Morabito, C, Fava, R, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Bolondi, L, Rasciti, L, Serio, I, Masala, C, Mammarella, A, Raparelli, V, Rossi Fanelli, F, Delfino, M, Amoroso, A, Violi, F, Basili, S, Perri, L, Serra, P, Fontana, V, Falcone, M, Landolfi, R, Grieco, A, Gallo, A, Zuccalà, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, Bellusci, M, Setti, D, Pedrazzoli, F, Romanelli, G, Pirali, C, Amolini, C, Rosei, E, Rizzoni, D, Castoldi, L, Picardi, A, Gentilucci, U, Mazzarelli, C, Gallo, P, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Contini, S, Molaro, M, Annoni, G, Corsi, M, Zazzetta, S, Bertolotti, M, Mussi, C, Scotto, R, Ferri, M, Veltri, F, Arturi, F, Succurro, E, Sesti, G, Gualtieri, U, Perticone, F, Sciacqua, A, Quero, M, Bagnato, C, Loria, P, Becchi, M, Martucci, G, Fantuzzi, A, Maurantonio, M, Corinaldesi, R, De Giorgio, R, Grasso, V, Ruggeri, E, Carozza, L, Pignatti, F, DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, Facolta' di MEDICINA e CHIRURGIA, Da definire, AREA MIN. 06 - Scienze mediche, DOMINGUEZ RODRIGUEZ, Ligia Juliana, and Reposi, Investigators

Subjects
Male, Antibiotic regimen, Guidelines adherence, Settore MED/09 - Medicina Interna, Antibiotics, Logistic regression, Elderly, Community-acquired pneumonia, 80 and over, Elderly people, Age Factor, Hospital Mortality, Aged, 80 and over, Treatment regimen, Medicine (all), Age Factors, Optimal management, Mortality, Pneumonia, Re-hospitalization, Aged, Anti-Bacterial Agents, Female, Humans, Logistic Models, Practice Guidelines as Topic, Treatment Outcome, Guideline Adherence, Hospitalization, Internal Medicine, Human, medicine.medical_specialty, Logistic Model, medicine.drug_class, Socio-culturale, antibiotic treatment, guidelines, pneumonia, elderly, Internal medicine, Anti-Bacterial Agent, medicine, elderly, pmeumonia, antibiotics, guidelines adherence, mortality, re-hospitalization, pmeumonia, Intensive care medicine, business.industry, Settore MED/09 - MEDICINA INTERNA, Antibiotic, medicine.disease, business
Abstract

none 22 no Background: Few studies evaluated the clinical outcomes of Community Acquired Pneumonia (CAP), Hospital-Acquired Pneumonia (HAP) and Health Care-Associated Pneumonia (HCAP) in relation to the adherence of antibiotic treatment to the guidelines of the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) in hospitalized elderly people (65 years or older). Methods: Data were obtained from REPOSI, a prospective registry held in 87 Italian internal medicine and geriatric wards. Patients with a diagnosis of pneumonia (ICD-9 480-487) or prescribed with an antibiotic for pneumonia as indication were selected. The empirical antibiotic regimen was defined to be adherent to guidelines if concordant with the treatment regimens recommended by IDSA/ATS for CAP, HAP, and HCAP. Outcomes were assessed by logistic regression models. Results: A diagnosis of pneumonia was made in 317 patients. Only 38.8% of them received an empirical antibiotic regimen that was adherent to guidelines. However, no significant association was found between adherence to guidelines and outcomes. Having HAP, older age, and higher CIRS severity index were the main factors associated with in-hospital mortality. Conclusions: The adherence to antibiotic treatment guidelines was poor, particularly for HAP and HCAP, suggesting the need for more adherence to the optimal management of antibiotics in the elderly with pneumonia. none Raffaella Rossio; Carlotta Franchi; Ilaria Ardoino; Codjo D. Djade; Mauro Tettamanti; Luca Pasina; Francesco Salerno; Alessandra Marengoni; Salvatore Corrao; Maura Marcucci; Flora Peyvandi; Elia M. Biganzoli; Alessandro Nobili; Pier Mannuccio Mannucci; REPOSI Investigators [...; Mauro Bernardi; Claudio Borghi; Marco Zoli; Luigi Bolondi; Roberto Corinaldesi; Roberto De Giorgio;...] Raffaella Rossio; Carlotta Franchi; Ilaria Ardoino; Codjo D. Djade; Mauro Tettamanti; Luca Pasina; Francesco Salerno; Alessandra Marengoni; Salvatore Corrao; Maura Marcucci; Flora Peyvandi; Elia M. Biganzoli; Alessandro Nobili; Pier Mannuccio Mannucci; REPOSI Investigators [..; Mauro Bernardi; Claudio Borghi; Marco Zoli; Luigi Bolondi; Roberto Corinaldesi; Roberto De Giorgio;..]

Published
2015

35. Costs and effects of on-demand treatment of hereditary angioedema in Italy: a prospective cohort study of 167 patients

Author

Carlo Federici, Antonio Gidaro, Ludovica Borsoi, Francesca Perego, Marco Cicardi, Rosanna Tarricone, Valentina Crosta, and Andrea Zanichelli

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Cost-Benefit Analysis, PDC1-INH, COST-ANALYSIS, HEALTH ECONOMICS, HEREDITARY ANGIOEDEMA, ICATIBANT, Bradykinin, 03 medical and health sciences, Indirect costs, chemistry.chemical_compound, Plasma, 0302 clinical medicine, Health Economics, PDC1-INH, Icatibant, medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Dosing, Prospective Studies, Prospective cohort study, cost-analysis, Angioedema, business.industry, Incidence (epidemiology), Research, icatibant, Angioedemas, Hereditary, General Medicine, Middle Aged, medicine.disease, hereditary angioedema, Treatment Outcome, 030228 respiratory system, chemistry, Italy, Hereditary angioedema, Cohort, Female, medicine.symptom, business, Complement C1 Inhibitor Protein
Abstract

ObjectivesTo explore treatment behaviours in a cohort of Italian patients with hereditary angioedema due to complement C1-inhibitor deficiency (C1-INH-HAE), and to estimate how effects and costs of treating attacks in routine practice differed across available on-demand treatments.DesignCost analyses and survival analyses using attack-level data collected prospectively for 1 year.SettingNational reference centre for C1-INH-HAE.Participants167 patients with proved diagnosis of C1-INH-HAE, who reported data on angioedema attacks, including severity, localisation and duration, treatment received, and use of other healthcare services.InterventionsAttacks were treated with either icatibant, plasma-derived C1-INH (pdC1-INH) or just supportive care.Main outcome measuresTreatment efficacy in reducing attack duration and the direct costs of acute attacks.ResultsOverall, 133 of 167 patients (79.6%) reported 1508 attacks during the study period, with mean incidence of 11 attacks per patient per year. Only 78.9% of attacks were treated in contrast to current guidelines. Both icatibant and pdC1-INH significantly reduced attack duration compared with no treatment (median times from onset 7, 10 and 47 hours, respectively), but remission rates with icatibant were 31% faster compared with pdC1-INH (HR 1.31, 95% CI 1.14 to 1.51). However, observed treatment behaviours suggest patterns of suboptimal dosing for pdC1-INH. The average cost per attack was €1183 (SD €789) resulting in €1.58 million healthcare costs during the observation period (€11 912 per patient per year). Icatibant was 54% more expensive than pdC1-INH, whereas age, sex and prophylactic treatment were not associated to higher or lower costs.ConclusionsBoth icatibant and pdC1-INH significantly reduced attack duration compared with no treatment, however, icatibant was more effective but also more expensive. Treatment behaviours and suboptimal dosing of pdC1-INH may account for the differences, but further research is needed to define their role.

Published
2018

36. Nusinersen in patients older than 7 months with spinal muscular atrophy type 1: A cohort study

Author

Juliette Ropars, Karolina Aragon-Gawinska, Andreea Mihaela Seferian, Jessica Taytard, Laurent Servais, Jerome Rambaud, Carole Vuillerot, Chiara Marini-Bettolo, Teresa Gidaro, Claude Cances, M. Annoussamy, Mariacristina Scoto, Mondher Chouchane, Inge Cuppen, A. Daron, E. Gargaun, Imelda Hughes, and Marjorie Illingworth

Subjects
0301 basic medicine, Male, Pediatrics, medicine.medical_specialty, DNA Copy Number Variations, Movement, Oligonucleotides, Phases of clinical research, Spinal Muscular Atrophies of Childhood, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Severity of illness, medicine, Humans, Longitudinal Studies, Stage (cooking), Child, Injections, Spinal, business.industry, Respiration, Infant, Spinal muscular atrophy, medicine.disease, Clinical trial, Survival of Motor Neuron 2 Protein, 030104 developmental biology, Treatment Outcome, Expanded access, Child, Preschool, Nusinersen, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study
Abstract

ObjectiveTo evaluate the safety and clinical efficacy of nusinersen in patients older than 7 months with spinal muscular atrophy type 1 (SMA1).MethodsPatients with SMA1 were treated with nusinersen by intrathecal injections as a part of the Expanded Access Program (EAP; NCT02865109). We evaluated patients before treatment initiation (M0) and at 2 months (M2) and 6 months (M6) after treatment initiation. Survival, respiratory, and nutritional data were collected. Motor function was assessed with the modified Hammersmith Infant Neurologic Examination Part 2 (HINE-2) and physiotherapist scales adjusted to patient age (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders and the Motor Function Measure 20 or 32).ResultsWe treated 33 children ranging in age from 8.3 to 113.1 months between December 2016 and May 2017. All patients were alive and were continuing treatment at M6. Median progress on the modified HINE-2 score was 1.5 points after 6 months of treatment (p < 0.001). The need for respiratory support significantly increased over time. There were no statistically significant differences between patients presenting with 2 and those presenting with 3 copies of the survival motor neuron 2 (SMN2) gene.ConclusionsOur results are in line with the phase 3 study for nusinersen in patients with SMA1 treated before 7 months of age and indicate that patients benefit from nusinersen even at a later stage of the disease.ClinicalTrials.gov identifier:NCT02865109.Classification of evidenceThis study provides Class IV evidence that for patients with SMA1 who are older than 7 months, nusinersen is beneficial.

Published
2018

37. Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy : Baseline data NatHis-SMA study

Author

Aurélie Chabanon, Andreea Mihaela Seferian, Aurore Daron, Yann Péréon, Claude Cances, Carole Vuillerot, Liesbeth De Waele, Jean-Marie Cuisset, Vincent Laugel, Ulrike Schara, Teresa Gidaro, Stéphanie Gilabert, Jean-Yves Hogrel, Pierre-Yves Baudin, Pierre Carlier, Emmanuel Fournier, Linda Pax Lowes, Nicole Hellbach, Timothy Seabrook, Elie Toledano, Mélanie Annoussamy, Laurent Servais, NatHis-SMA study group, and Group, NatHis-SMA Study

Subjects
0301 basic medicine, Male, Longitudinal study, Muscle Physiology, Muscle Functions, Physiology, Medizin, HEALTHY-SUBJECTS, lcsh:Medicine, CHILDREN, Disease, Spinal Muscular Atrophies of Childhood, NASAL INSPIRATORY PRESSURE, Biochemistry, Pulmonary function testing, Diagnostic Radiology, Fats, 6-MINUTE WALK TEST, MUSCLE STRENGTH, 0302 clinical medicine, Medicine and Health Sciences, Longitudinal Studies, Child, lcsh:Science, Lung, Musculoskeletal System, Forearms, Multidisciplinary, Muscle Weakness, VALUES, Radiology and Imaging, Muscle Analysis, Wrist, SMA, Magnetic Resonance Imaging, Lipids, Multidisciplinary Sciences, Arms, Bioassays and Physiological Analysis, Child, Preschool, Science & Technology - Other Topics, Female, Anatomy, CLINICAL-TRIALS, Natural history study, Muscle Electrophysiology, Research Article, Adult, medicine.medical_specialty, Adolescent, Imaging Techniques, NEUROMUSCULAR DISEASES, MOTOR FUNCTION MEASURE, Research and Analysis Methods, 03 medical and health sciences, Young Adult, Physical medicine and rehabilitation, Diagnostic Medicine, medicine, Humans, Muscle Strength, Science & Technology, business.industry, Limbs (Anatomy), Electrophysiological Techniques, lcsh:R, Electromyoneurography, Biology and Life Sciences, OUTCOME MEASURES, Spinal muscular atrophy, medicine.disease, Clinical trial, 030104 developmental biology, lcsh:Q, business, 030217 neurology & neurosurgery, Psychomotor Performance, Biomarkers
Abstract

UNLABELLED: Spinal muscular atrophy (SMA) is a monogenic disorder caused by loss of function mutations in the survival motor neuron 1 gene, which results in a broad range of disease severity, from neonatal to adult onset. There is currently a concerted effort to define the natural history of the disease and develop outcome measures that accurately capture its complexity. As several therapeutic strategies are currently under investigation and both the FDA and EMA have recently approved the first medical treatment for SMA, there is a critical need to identify the right association of responsive outcome measures and biomarkers for individual patient follow-up. As an approved treatment becomes available, untreated patients will soon become rare, further intensifying the need for a rapid, prospective and longitudinal study of the natural history of SMA Type 2 and 3. Here we present the baseline assessments of 81 patients aged 2 to 30 years of which 19 are non-sitter SMA Type 2, 34 are sitter SMA Type 2, 9 non-ambulant SMA Type 3 and 19 ambulant SMA Type 3. Collecting these data at nine sites in France, Germany and Belgium established the feasibility of gathering consistent data from numerous and demanding assessments in a multicenter SMA study. Most assessments discriminated between the four groups well. This included the Motor Function Measure (MFM), pulmonary function testing, strength, electroneuromyography, muscle imaging and workspace volume. Additionally, all of the assessments showed good correlation with the MFM score. As the untreated patient population decreases, having reliable and valid multi-site data will be imperative for recruitment in clinical trials. The pending two-year study results will evaluate the sensitivity of the studied outcomes and biomarkers to disease progression. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02391831). ispartof: PLOS ONE vol:13 issue:7 ispartof: location:United States status: published

Published
2018

38. Nusinersen versus sham control in later-onset spinal muscular atrophy

Author

Vogt, Sibylle, Krueger, Marcus, Pechmann, Astrid, Rippberger, Bianca, Eckenweiler, Matthias, Schara, Ulrike, Koelbel, Heike, Andres, Barbara, Rupprich, Katrin, Gangfuss, Andrea, Jachertz, Philipp, Della Marina, Adela, Sponemann, Nina, Pane, Markia, Palermo, Concetta, Piastra, Marco, Fanelli, Lavinia, de Sanctis, Roberto, Genovese, Orazio, Antonaci, Laura, Pera, Maria Carmela, Lamendola, Priscilla, Messina, Sonia, Vita, Gianluca, Di Bella, Vincenzo, Sframeli, Maria, Rosa, Matteo, Barcellona, Costanza, Distefano, Maria Grazia, Cavallaro, Filippo, Versaci, Antonio, de Luca, Francesco, Vita, Giuseppe, Nacimento Osorio, Andres, Tizzano, Eduardo, Ortez Gonzalez, Carlos Ignacio, Ortigoza Escobar, Juan Dario, Colomer Oferil, Juame, Medina Cantillo, Julita, Febrer Rotger, Anna, Vigo Morancho, Meritxell, Eldblom, Johanneh, Darin, Niklas, Kroksmark, Anna Karin, Lindstedt, Asa, Michael, Eva, Kimber, Eva, Wahlgren, Lisa, Chan, Sophelia Hoi-Shan, Chim, Stella, Chiu, Joseph, Ho, Alvin Chi Chung, Ip, Jing Kun Janice, Lam, Wendy Wai Man, Ng, Maggie Chui-San, Wan, Connie, Wong, Virginia Chun Nei, Yue, Yvonne, Arakawa, Reiko, Yamauchi, Akemi, Nagata, Satoru, Ito, Yasushi, Nakatsukasa, Hidetsugu, Takeshita, Akiko, Hirasawa, Kyoko, Ikai, Tetsuo, Eto, Kaoru, Otamni, Yui, Takeshima, Yasuhiro, Fukuda, Noroki, Tanaka, Yasuhiro, Shimomura, Hideki, Lee, Tomoko, Shibano, Takayuki, Mercuri, E., Tachikawa, Tomohiro, Darras, B. T., Chae, Jong-Hee, Chiriboga, C. A., Lim, Byung Chan, Day, J. W., Shin, Hyung-Ik, Campbell, C., Kim, Soo Yeon, Connolly, A. M., Choi, Sun Ah, Iannaccone, S. T., Son, Woo Sung, Kirschner, J., Jo, Hyemi, Kuntz, N. L., Chun, Seong Min, Saito, K., Kim, Hyuna, Shieh, P. B., Tulinius, M., Mazzone, E. S., Montes, J., Bishop, K. M., Yang, Q., Foster, R., Gheuens, S., Bennett, C. F., Farwell, W., Schneider, E., de Vivo, D. C., Finkel, R. S., Bradley, Walter G., Kaufmann, Petra, Dickson, Patricia I., Reingold, Stephen C., Davis, Charles S., Arredondo, Kristen, Castro, Diana, Cowie, Margaret, Farrow-Gillespie, Alan, Hebert, Andrew, Kauk, Melissa, Miller, Nancy, Nelson, Leslie, Spain, Thomas, Cappell, Joshua, Constantinescu, Andrei, Cruz, Rosangel, Dastgir, Jahannaz, de Vivo, Darryl, Dunaway, Sally, Engelstad, Kristin, Khandji, Alexander G., Kramer, Samantha, Marra, Jonathan, Popolizio, Molly, Salazar, Rachel, Weimer, Louis H., Aziz-Zaman, Sonya, Lamarca, Nicole, Ghosh, Partha, Al-Ghamdi, Fouad, Liew, Wendy, Graham, Robert, Berde, Charles, Sethna, Navil, Koka, Anjali, Wang, Luke, Laine, Regina, Souris, Michelle, Ordonez, Grace, Harrington, Timothy, Szelag, Heather, Pasternak, Amy, Mirek, Elizabeth, Quigley, Janet, Finkel, Richard, Berry, Debbie, Civitello, Matthew, Endsley, Julie Duke, Eden, Candace, Leon, Wendy, O'Reardon, Kathleen, Sigurdardottir, Laufey, Johnson, Craig, Turner, Jenna, Vega, Melisa, Weber-Guzman, Fabiola, Zinn, Matthias, Rocha, Ana Carolina Tesi, Watson, Karolina, d'Souza, Genevieve, Ramamurthi, R. J., Gee, Richard, Kitsuwa-Lowe, Janis, Hagerman, Katharine, Crasta, Sheela, Welsh, Lesly, Paulose, Shirley, Mcfall, Danielle, Perez, Jennifer, Patnaik, Swetapadma, Sanjanwala, Bharati, Sakamuri, Sarada, Proud, Crystal, Purse, Bona Park, Duong, Trinh Tina, Sampson, Jacinda, Tennekoon, Gihan, Brandsema, John, Glanzman, Allan, Flickinger, Jean, Toms, Michele, Adang, Laura, Stanford, Delores, Mayer, Oscar, Zigmont, Joshua, Chadehumbe, Madeline, Kichula, Elizabeth, Finanger, Erika, Russman, Barry, Roberts, Colin, Frank, Andrea, Benjamin, Danielle, Zilke, Kirsten, Golumbek, Paul T., Zaidman, Craig M., Anand, Pallavi, Gadeken, Rebecca, Siener, Catherine, Kuntz, Nancy, Epstein, Leon, Krueger, Jena, Goldman, Stewart, Krosschell, Kristin, Blomgren, Colleen, Choi, Hyoung Won, Kurz, Jonathan, Parsons, Julie, Janas, Joanne, Yang, Michele, Ballard, Alison, Carry, Terri, Shea, Stephanie, Bielsky, Alan, Booker, Kaylee, Camuto, Alicia, Lord-Halvorson, Sierra, Gibbons, Melissa, Zimmerman, Carl, Allen, Victoria, Fuhr, Peter, Johnson, Hannah, Tran, Vi, Vanderveen, Gina, Shieh, Perry, Fowler, Eileen, Parziale, Nicholas, Rao, Lekha, Skura, Christy, Kelley, Carolyn, Shu, Francy, Oskoui, Maryam, Zielinski, David, Poulin, Chantal, Ingelmo, Pablo Mauricio, Desilets, Sarah Turgeon, Dinunzio, Pamela, Rivera, Gonzalo, Srour, Myriam, Arpin, Stephanie, Goobie, Sharan, Gibson, Paul, Scholtes, Cheryl, Mcdonald, Wendy, Zapata, Eugenio, Nguyen, Cam-Tu Emilie, Servais, Laurent, Gargaun, Elena, Le Moing, Anne-Gaelle, Gidaro, Teresa, Vialle, Raphael, Guye, Marie-Laurence, Lilien, Charlotte, Olliver, Gwenn, Gilabert, Stephanie, Borell, Sabine, Wider, Sabine, Stein, Sabine, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Department of Paediatrics, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Vall d'Hebron University Hospital [Barcelona], CIBER de Enfermedades Raras (CIBERER), Handicaps génétiques de l'enfant (Inserm U393), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Seoul National University Hospital, Max-Planck-Institut für Mikrostrukturphysik (MPI-HALLE), Max-Planck-Gesellschaft, The University of Tokyo (UTokyo), Institut de Chimie Organique et Analytique (ICOA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institute of Plasma Physics, Chinese Academy of Sciences (ASIPP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de mécanique des solides (LMS), École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), CureSMA [Elk Grove Village, IL, USA], Harvard Medical School [Boston] (HMS), Institute for Marine and Antarctic Studies [Hobart] (IMAS), University of Tasmania [Hobart, Australia] (UTAS), The Hospital for sick children [Toronto] (SickKids), University of Toronto, The Open University [Milton Keynes] (OU), Department of Pediatrics, Feinberg School of Medicine, Northwestern University [Evanston]-Northwestern University [Evanston]-Northwestern University, University Hospital Basel [Basel], McGill University Health Center [Montreal] (MUHC), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service of Clinical Trials and Databases, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Groupe de Recherche sur l'Analyse Multimodale de la Fonction Cérébrale - UMR INSERM_S 1105 (GRAMFC), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Oxford, Schara, Ulrike (Beitragende*r), Koelbel, Heike (Beitragende*r), Rupprich, Katrin (Beitragende*r), Gangfuss, Andrea (Beitragende*r), Della Marina, Adela (Beitragende*r), and Sponemann, Nina (Beitragende*r)

Subjects
0301 basic medicine, Male, [SDV]Life Sciences [q-bio], spinal, Medizin, Oligonucleotides, Spinal Muscular Atrophies of Childhood, Pediatrics, law.invention, Age of Onset, Child, Child, Preschool, Double-Blind Method, Female, Humans, Infant, Injections, Spinal, Least-Squares Analysis, Motor Skills, Oligonucleotides, Antisense, Medicine (all), 0302 clinical medicine, age of onset, Randomized controlled trial, law, Clinical endpoint, inglese, injections, Motor skill, motor skills, General Medicine, SMA, Settore MED/26 - NEUROLOGIA, medicine.anatomical_structure, female, Anesthesia, Nusinersen, Spinal, antisense, preschool, Injections, 03 medical and health sciences, least-squares analysis, Settore MED/39 - NEUROPSICHIATRIA INFANTILE, Settore MED/41 - ANESTESIOLOGIA, medicine, Antisense, Preschool, business.industry, Spinal muscular atrophy, Motor neuron, medicine.disease, 030104 developmental biology, Age of onset, business, 030217 neurology & neurosurgery
Abstract

Background: Nusinersen is an antisense oligonucleotide drug that modulates pre–messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). Methods: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale–Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills. Results: In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by –1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P Conclusions: Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials.gov number, NCT02292537. opens in new tab.)

Published
2018

39. P.107Clinical changes over time in patients with centronuclear myopathy due to mutations in DNM2 gene enrolled in a European prospective natural history study

Author

C. Lilien, Nicol C. Voermans, A. Grangé, Teresa Gidaro, L. Servais, V. Chê, Andreea Mihaela Seferian, Jonathan Baets, Anthony Behin, W. De Ridder, M. Annoussamy, C. Freitag, L. Thielemans, Marc Bitoun, K. Paradis, J.Y. Hogrel, S. Van Rooijen, and D. Duchene

Subjects
medicine.medical_specialty, business.industry, medicine.disease, DNM2, Neurology, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, In patient, Neurology (clinical), Centronuclear myopathy, business, Gene, Genetics (clinical), Natural history study
Published
2019

40. P.240ASC-1 related myopathy: phenotypic spectrum and pathophysiology of an emerging congenital myopathy

Author

L. Servais, Nicolas Deconinck, Teresa Gidaro, Montse Olivé, Johann Böhm, E. Pierce-Hoffman, A. Koparir, Ana Ferreiro, R. Juntas-Morales, Casie A. Genetti, Isabelle Duband-Goulet, L. Davignon, Alan H. Beggs, Eva Cabet, A. Yuksel, Rocío-Nur Villar-Quiles, Mireille Cossée, and Sandra Coppens

Subjects
Pathology, medicine.medical_specialty, business.industry, medicine.disease, Congenital myopathy, Phenotype, Pathophysiology, Neurology, Pediatrics, Perinatology and Child Health, Medicine, Neurology (clinical), medicine.symptom, business, Myopathy, Genetics (clinical)
Published
2019

41. Telelap Alf-X–Assisted Laparoscopy for Ovarian Cyst Enucleation: Report of the First 10 Cases

Author

Giovanni Scambia, Barbara Costantini, Giorgia Monterossi, Anna Fagotti, Francesco Fanfani, Stefano Gidaro, Cristiano Rossitto, Luigi Selvaggi, and Salvatore Gueli Alletti

Subjects
Adult, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Enucleation, Gynecologic oncology, Benign Ovarian Cyst, ovarian cyst, Gynecologic Surgical Procedures, Postoperative Complications, Robotic Surgical Procedures, Laparotomy, telelap alf-x, Humans, Medicine, Robotic surgery, Prospective Studies, Laparoscopy, Aged, Ovarian cyst, medicine.diagnostic_test, business.industry, Obstetrics and Gynecology, Perioperative, Middle Aged, medicine.disease, Surgery, Ovarian Cysts, Treatment Outcome, Settore MED/40 - GINECOLOGIA E OSTETRICIA, Female, business
Abstract

This prospective single-institutional clinical trial sought to assess the safety and feasibility of laparoscopic benign ovarian cyst enucleation with a novel robotic-assisted laparoscopic system. Here we report a series of 10 patients treated using the Telelap ALF-X system in the first clinical application on patients at the Division of Gynecologic Oncology, Catholic University of the Sacred Heart of Rome. The primary inclusion criterion was the presence of monolateral ovarian cyst without a preoperative assessment suspicious for malignancy. Intraoperative data, including docking time, operative time, estimated blood loss, intraoperative and perioperative complications, and conversion to either standard laparoscopy or laparotomy, were collected. The cysts were removed with an ovary-sparing technique with respect to conservative surgical principles. The median operative time was 46.3 minutes, and patients without postoperative complications were discharged at 1 or 2 days after the procedure. Telelap ALF-X laparoscopic enucleation of benign ovarian cysts with an ovary-sparing technique is feasible, safe, and effective; however, more clinical data are needed to determine whether this approach can offer any other benefits over other minimally invasive surgical techniques.

Published
2015

42. Invited review: Stem cells and muscle diseases: advances in cell therapy strategies

Author

Vincent Mouly, Gillian Butler-Browne, Anne Bigot, Elisa Negroni, Capucine Trollet, and Teresa Gidaro

Subjects
Histology, Cell, Biology, medicine.disease, Embryonic stem cell, 3. Good health, Pathology and Forensic Medicine, Transplantation, Cell therapy, medicine.anatomical_structure, Neurology, Physiology (medical), Immunology, medicine, Myocyte, Neurology (clinical), Stem cell, Muscular dystrophy, Induced pluripotent stem cell, Neuroscience
Abstract

Despite considerable progress to increase our understanding of muscle genetics, pathophysiology, molecular and cellular partners involved in muscular dystrophies and muscle ageing, there is still a crucial need for effective treatments to counteract muscle degeneration and muscle wasting in such conditions. This review focuses on cell-based therapy for muscle diseases. We give an overview of the different parameters that have to be taken into account in such a therapeutic strategy, including the influence of muscle ageing, cell proliferation and migration capacities, as well as the translation of preclinical results in rodent into human clinical approaches. We describe recent advances in different types of human myogenic stem cells, with a particular emphasis on myoblasts but also on other candidate cells described so far [CD133+ cells, aldehyde dehydrogenase-positive cells (ALDH+), muscle-derived stem cells (MuStem), embryonic stem cells (ES) and induced pluripotent stem cells (iPS)]. Finally, we provide an update of ongoing clinical trials using cell therapy strategies.

Published
2015

43. Posizionamento Di Un Catetere Venoso Centrale Permanente Nella Trombosi Della Vena Cava Superiore

Author

Antonia Stasi, Barbara Gidaro, Luca di Toma, Roberto Ferraresi, Carlo Guastoni, Marina Cornacchiari, Marco Mereghetti, and Maria Giuseppina Ponticelli

Subjects
lcsh:Internal medicine, medicine.medical_specialty, Emodialisi, business.industry, medicine.medical_treatment, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, medicine.disease, Thrombosis, Surgery, Clinical Practice, Stenosis, Superior vena cava, Catetere venoso centrale permanente, medicine, Pharmacology (medical), Trombosi, Clinical case, Hemodialysis, lcsh:RC31-1245, business, Vena cava superiore, Central venous catheter
Abstract

È sempre più frequente l’utilizzo di cateteri posizionati nei vasi venosi centrali per il trattamento emodialitico, la terapia infusiva, la nutrizione parenterale e la chemioterapia. Anche i cardiologi ricorrono sempre più spesso all’impianto di cateteri venosi centrali per l’elettrostimolazione e la cardioversione elettrica. Il risultato è la possibilità di comparsa dell’occlusione di tali vene a causa della presenza di questi dispositivi. Questo articolo descrive il caso clinico di un’ampia trombosi coinvolgente la vena cava superiore e la modalità di posizionamento di un catetere venoso centrale, unica possibilità per poter effettuare un trattamento dialitico nel paziente.

Published
2014

44. Clinical Severity, Age, and Sex Overcome Cardiometabolic Morbidities but Not Stroke as Predictors of Mortality in Elderly Inpatients: Data From the REgistro POliterapie Società Italiana di Medicina Interna Registry

Author

Salvatore, Corrao, Alessandra, Marengoni, Giuseppe, Natoli, Alessandro, Nobili, Piermannuccio, Mannucci, Francesco, Perticone, Domenico, Prisco, Elena, Silvestri, Caterina, Cenci, Tommaso, Barnini, Giuseppe, Delitala, Stefano, Carta, Sebastiana, Atzori, Gianfranco, Guarnieri, Michela, Zanetti, Annalisa, Spalluti, Maria Grazia Serra, Maria Antonietta Bleve, Massimo, Vanoli, Giulia, Grignani, Gianluca, Casella, Laura, Gasbarrone, Giorgio, Maniscalco, Massimo, Gunelli, Daniela, Tirotta, Antonio, Brucato, Silvia, Ghidoni, Paola Di Corato, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giancarlo, Agnelli, Emanuela, Marchesini, Elmo, Mannarino, Graziana, Lupattelli, Pamela, Rondelli, Francesco, Paciullo, Fabrizio, Fabris, Michela, Carlon, Francesca, Turatto, Maria Cristina Baroni, Marianna, Zardo, Manfredini, Roberto, Christian, Molino, Marco, Pala, Fabbian, Fabio, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Giuseppe, Paolisso, Maria Rosaria Rizzo, Maria Teresa Laieta, Teresa, Salvatore, Ferdinando Carlo Sasso, Riccardo, Utili, Emanuele Durante Mangoni, Daniela, Pinto, Oliviero, Olivieri, Anna Maria Stanzial, Renato, Fellin, Volpato, Stefano, Sioulis, Fotini, Mario, Barbagallo, Ligia, Dominguez, Lidia, Plances, Daniela, D’Angelo, Giovanbattista, Rini, Pasquale, Mansueto, Ilenia, Pepe, Giuseppe, Licata, Luigi, Calvo, Maria, Valenti, Claudio, Borghi, Enrico, Strocchi, Elisa, Rebecca, Marco, Zoli, Elisa, Fabbri, Donatella, Magalotti, Alberto, Auteri, Anna Laura Pasqui, Luca, Puccetti, Franco Laghi Pasini, Pier Leopoldo Capecchi, Maurizio, Bicchi, Carlo, Sabbà, Francesco Saverio Vella, Alessandro, Marseglia, Chiara Valentina Luglio, Giuseppe, Palasciano, Maria Ester Modeo, Annamaria, Aquilino, Raffaele, Pallante, Stefania, Pugliese, Caterina, Capobianco, Alfredo, Postiglione, Maria Rosaria Barbella, Francesco De Stefano, Luigi, Fenoglio, Chiara, Brignone, Christian, Bracco, Alessia, Giraudo, Giuseppe, Musca, Olga, Cuccurullo, Luigi, Cricco, Alessandra, Fiorentini, Maria Domenica Cappellini, Giovanna, Fabio, Sonia, Seghezzi, Margherita Migone De Amicis, Silvia, Fargion, Paola, Bonara, Mara, Bulgheroni, Rosa, Lombardi, Marianna, Porzio, Giulia, Periti, Fabio, Magrini, Ferdinando, Massari, Tatiana, Tonella, Flora, Peyvandi, Alberto, Tedeschi, Raffaella, Rossio, Guido, Moreo, Barbara, Ferrari, Luisa, Roncari, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Maria, Magnini, Daniela, Mari, Paolo Dionigi Rossi, Sarah, Damanti, Silvia, Prolo, Maria Sole Lilleri, Giuliana, Micale, Mauro, Podda, Carlo, Selmi, Francesca, Meda, Francesco, Salerno, Silvia, Accordino, Alessio, Conca, Valentina, Monti, Gino Roberto Corazza, Emanuela, Miceli, Marco Vincenzo Lenti, Donatella, Padula, Balduini, Carlo L., Giampiera, Bertolino, Stella, Provini, Federica, Quaglia, Giovanni, Murialdo, Marta, Bovio, Franco, Dallegri, Luciano, Ottonello, Alessandra, Quercioli, Alessandra, Barreca, Maria Beatrice Secchi, Davide, Ghelfi, Wu Sheng Chin, Laura, Carassale, Silvia, Caporotundo, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Giancarlo, Traisci, Lucrezia De Feudis, Silvia Di Carlo, Giovanni, Davì, Maria Teresa Guagnano, Simona, Sestili, Elisabetta, Bergami, Emanuela, Rizzioli, Carlo, Cagnoni, Luca, Bertone, Antonio, Manucra, Alberto, Buratti, Tiziana, Tognin, Nicola Lucio Liberato, Giordano, Bernasconi, Barbara, Nardo, Giovanni Battista Bianchi, Sabrina, Giaquinto, Giampiero, Benetti, Michela, Quagliolo, Giuseppe Riccardo Centenaro, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Francesco, Gullo, Michele, Cortellaro, Marina, Magenta, Francesca, Perego, Maria Rachele Meroni, Marco, Cicardi, Antonio Gidaro Marina Magenta, Andrea, Sacco, Antonio, Bonelli, Gaetano, Dentamaro, Renzo, Rozzini, Lina, Falanga, Alessandro, Giordano, Paolo Cavallo Perin, Bartolomeo, Lorenzati, Gabriella, Gruden, Graziella, Bruno, Giuseppe, Montrucchio, Elisabetta, Greco, Pietro, Tizzani, Giacomo, Fera, Maria Loreta Di Luca, Donatella, Renna, Antonio, Perciccante, Alessia, Coralli, Rodolfo, Tassara, Deborah, Melis, Lara, Rebella, Giorgio, Menardo, Stefania, Bottone, Elsa, Sferrazzo, Claudio, Ferri, Rinaldo, Striuli, Rosa, Scipioni, Raffaella, Salmi, Piergiorgio, Gaudenzi, Susanna, Gamberini, Franco, Ricci, Cosimo, Morabito, Roberto, Fava, Andrea, Semplicini, Lucia, Gottardo, Gianluigi, Vendemiale, Gaetano, Serviddio, Roberta, Forlano, Luigi, Bolondi, Leonardo, Rasciti, Ilaria, Serio, Cesare, Masala, Antonio, Mammarella, Valeria, Raparelli, Filippo Rossi Fanelli, Massimo, Delfino, Antonio, Amoroso, Francesco, Violi, Stefania, Basili, Ludovica, Perri, Pietro, Serra, Vincenzo, Fontana, Marco, Falcone, Raffaele, Landolfi, Antonio, Grieco, Antonella, Gallo, Giuseppe, Zuccalà, Francesco, Franceschi, Guido De Marco, Cordischi, Chiara, Sabbatini, Marta, Martino, Bellusci, Donatella, Setti, Filippo, Pedrazzoli, Giuseppe, Romanelli, Caterina, Pirali, Claudia, Amolini, Enrico Agabiti Rosei, Damiano, Rizzoni, Luana, Castoldi, Antonio, Picardi, Umberto Vespasiani Gentilucci, Chiara, Mazzarelli, Paolo, Gallo, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Sara, Contini, Marta, Molaro, Giorgio, Annoni, Maurizio, Corsi, Sara, Zazzetta, Marco, Bertolotti, Chiara, Mussi, Roberto, Scotto, Maria Alice Ferri, Francesca, Veltri, Franco, Arturi, Elena, Succurro, Giorgio, Sesti, Umberto, Gualtieri, Angela, Sciacqua, Michele, Quero, Chiara, Bagnato, Paola, Loria, Maria Angela Becchi, Gianfranco, Martucci, Alessandra, Fantuzzi, Mauro, Maurantonio, Roberto, Corinaldesi, Roberto De Giorgio, Mauro, Serra, Valentina, Grasso, Eugenio, Ruggeri, Lorenzo Mauro Carozza, Fabio, Pignatti, Corrao, S., Marengoni, A., Natoli, G., Nobili, A., Mannucci, P., and Perticone, F.

Subjects
Male, Pediatrics, medicine.medical_specialty, REPOSI study, Clinical severity, age, stroke, risk factors, elderly, REPOSI study, Socio-culturale, 030204 cardiovascular system & hematology, Age and sex, elderly, Severity of Illness Index, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Metabolic Diseases, medicine, risk factors, Humans, Clinical severity, Hospital Mortality, Registries, 030212 general & internal medicine, Stroke, Aged, Aged, 80 and over, Inpatients, business.industry, Age Factors, medicine.disease, age, Italy, Cardiovascular Diseases, Female, Morbidity, Geriatrics and Gerontology, business
Published
2016

45. First experience in colorectal surgery with a new robotic platform with haptic feedback

Author

G. David, Isacco Montroni, Antonino Spinelli, Matteo Sacchi, Stefano Gidaro, Marco Montorsi, and Michele Carvello

Subjects
medicine.medical_specialty, medicine.diagnostic_test, Colorectal cancer, business.industry, General surgery, medicine.medical_treatment, Gastroenterology, Perioperative, Single Center, medicine.disease, Colorectal surgery, Surgery, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Laparotomy, medicine, Diverticular disease, 030211 gastroenterology & hepatology, Robotic surgery, Laparoscopy, business
Abstract

The use of robotic techniques is increasing in colorectal surgery. Recently, the Senhance™ surgical robotic system was introduced as a novel robotic platform designed to overcome some of the limits of standard laparoscopy. This study describes the initial, single center experience, evaluating feasibility and safety of the new robotic system in performing colorectal surgical procedures. Methods From June 2015 to November 2016, perioperative data of the first 45 patients who underwent robotic colorectal surgery with the SenhanceTM surgical robotic system were collected and analyzed. Indications for surgery included inflammatory bowel disease, colorectal cancer, endoscopically unresectable adenomas and complicated diverticular disease. Results The median age was 57 years (18-92) and the median BMI was 24 Kg/m2 (16-30). Surgical indications were colorectal cancer (66%), complicated inflammatory bowel disease (18%), diverticular disease (11%) and endoscopically unresectable adenoma (4.4%). The median operative time was 256 minutes; the median docking time 10.7 min (range 2-25). There were 3 conversions to standard laparoscopy, and none to laparotomy. All patients operated on for malignancy (28 adenocarcinoma, 2 neuroendocrine tumors) underwent an appropriate oncological procedure. The median time to discharge was 5 days (range 3-19). The incidence of post-operative complications was 35.5% (Clavien-Dindo I/II-14 patients, III-2 patients). One patient was readmitted in the postoperative period. No patient required reoperation. Conclusion The results of this audit suggest that adoption of The Senhance™ surgical robotic system in colorectal surgery is feasible and safe. More clinical data are needed to determine whether this approach can offer any other benefits over other minimally invasive surgical techniques. This article is protected by copyright. All rights reserved.

Published
2017

46. Longitudinal data of the European prospective natural history study of patients with type 2 and 3 spinal muscular atrophy

Author

Claude Cances, Jean-Marie Cuisset, Linda Lowes, Vincent Laugel, Laurent Servais, Teresa Gidaro, A. Chabanon, M. Annoussamy, Ulrike Schara, A. Daron, Omar Khwaja, Carole Vuillerot, Ricardo Hermosilla, J.Y. Hogrel, Andreea Mihaela Seferian, Nathalie Goemans, E. Gargaun, Yann Péréon, Pierre G. Carlier, and Christian Czech

Subjects
0301 basic medicine, medicine.medical_specialty, Longitudinal data, business.industry, Medizin, Spinal muscular atrophy, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Physical medicine and rehabilitation, Neurology, Pediatrics, Perinatology and Child Health, Physical therapy, medicine, Neurology (clinical), business, 030217 neurology & neurosurgery, Genetics (clinical), Natural history study
Published
2017

47. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy

Author

S. Richardson, E. Kimber, H. Kim, Diana Castro, H. Johnson, A. C. Tesi Rocha, Matthias Eckenweiler, C. Manzitti, John W. Day, R. De Sanctis, M. Gormley, Mar Tulinius, Mirac Yildirim, C. M. Temucin, M. Gratacos Vinola, S. Matsumaru, F. Weber-Guzman, J. Kitsuwa-Lowe, Lavinia Fanelli, T. Sato, W. C. Virginia, J. H. Hsu, S. Nagata, A. Michoulas, Sally Dunaway, Mariacristina Scoto, R. Shell, R. Laine, D. DiBella, C. King, Jacqueline Montes, Haluk Topaloglu, Maryam Oskoui, Didem Ardicli, K. Rupprich, C. Stella, F. Dorban, Alan C Farrow-Gillespie, S. A. Choi, T. Ikai, W. C. Liang, N. Matsushima, PH Lister, Arnaud Vanlander, N. Rausch, T. T. Duong, Marika Pane, Melissa Gibbons, M. M. Homi, A. K. Kroksmark, B. Andres, Kristin J. Krosschell, S. Patnaik, L. Welsh, Eduardo F. Tizzano, M. Gallardo, Michèle Mayer, Sarada Sakamuri, W. Liew, T. Spain, M. Yang, Kayoko Saito, Edward C. Smith, L. Sanabria, Astrid Pechmann, H. Kaneko, Leslie Nelson, Basil T. Darras, C. Milleson, Janbernd Kirschner, R. Arakawa, Margot Morrison, Y. Kaburagi, P. Dinunzio, C. K.W. Joseph, M. Chadehumbe, Craig M. Zaidman, S. Nicolarsen, Hyung Ik Shin, Alberto Garaventa, James J. Dowling, J. S. Lee, K. Booker, A. Takeshita, D. McElroy, K. Carroll, D. Vens, Y. Chiba, L. Wand, C. Kelly, Luke Smith, H. Shimomura, M. Srour, J. B. Bodensteriner, B. Rippberger, A. Herbert, Eugenio Mercuri, H. Jo, J. Turner, A. Camuto, N. Parziale, J. O'Brien, N. Nelson, E. Serdaroglu, Jong-Hee Chae, V. Tahon, E. Toro Tamargo, L. Weimer, T. Voit, L. W.M. Wendy, J. Rambaud, G. Gilbert, C. Zimmerman, S. Kramer, D. McFall, Jennifer Perez, N. Berthon-Jones, Jessica Taytard, Marco Luigetti, J. Pisco Domingos, R. Van Der Looven, Genevieve D'Souza, C. Berde, E. Roland, M. de Los Angeles Tormos Munoz, J. Zigmont, S. Baily, S. Gilabert, H. Nakatsukasa, S. Trest, Bahadır Konuşkan, H. A. Ferreira Sampaio, Z. John Zhong, G. VanderVeen, V. Allen, C. Aguilar, N. Taniguchi, G. Ordonez, Elizabeth Kichula, F. Shu, M. N. Chui-San, M. Zinn, Anne M. Connolly, Ian R. Woodcock, Ayşe Karaduman, R. Haldenby, K. Hirasawa, F. Munell Casadesus, L.D.M. Peña, Vamshi K. Rao, Allan M. Glanzman, Claudia A. Chiriboga, A. Martinez Bermejo, John F. Brandsema, S. Epinosa Garcia, M. K. Schroth, T. Shibano, Richard Gee, Valeria Ricotti, Y. Ito, Y. Tanaka, S. Arpin, C. S. Yan, L. Schottlaender, Marco Piastra, M. Kauk, Francesco Muntoni, K. Sugimoto, Öznur Yilmaz, K. DeCock, Kathryn Selby, T. Yanagishita, Concetta Palermo, H. W. Chung, B. Taicher, Jiri Vajsar, K. Zilke, R. Gadeken, A. Yamauchi, Marta Bertoli, Nancy L. Kuntz, T. Tachikawa, C. Johnson, A. Mayhew, Jahannaz Dastgir, Y. J. Jong, P. C. Chou, G. Rivera, T. N. Shun, Y. H. Ju, N. Holuba La Marca, M. Toms, Matthew Civitello, Eugene Schneider, C. Lilien, S. Ito, C. Skura, Y. Yvonne, K. O'Reardon, Barry S. Russman, Janet Quigley, J. W. Said, B. Planas Pascual, R. J. Ramamurthi, Wildon Farwell, V. Selby, W. Y. Connie, M. Souris, Nicholas E. Johnson, M. Miki, N. Sponemann, Andrei Constantinescu, K. Mayne, H. H. Shih, B. Sanjanwala, Teresa Gidaro, D. Berry, Gihan Tennekoon, A. G. Le Moing, Danielle Ramsey, C. Poulin, S. Goldman, K. Watson, H. L. Teoh, N. J. Palacios, Tai-Heng Chen, A. C. Chung, Terri Carry, J. Coates, D. Zielinski, R. Vialle, F. G. Yildiz Sarikaya, Marcus Krüger, M. del Mar Garcia Romero, E. Michael, E. D. Austin, J. Janas, K. Engelstad, S. Y. Kim, M. Alavarez Molinero, Leon G. Epstein, Monique M. Ryan, Jean Flickinger, D. Benjamin, S. Wider, C. S. Davis, Jena M. Krueger, I. J.K. Janice, Darryl C. De Vivo, M. del Mar Melendez Plumed, Y. Takeshima, C. Gunbey, Serena Sivo, A. Christiaens, Q. Ollievier, Elizabeth Mirek, D. Stanford, Susan T. Iannaccone, Jonathan E. Kurz, D. Cook, C. S. Ng, A. Koka, V. Chau, M. del Pilar Tirado Requero, M. B. Gomez Garcia de la Banda, E. M. Yiu, Amy Pasternak, Rosangel Cruz, S. So, S. I. Pascual Pascual, V. G. Haliloglu, E. S. Schroers, P. Jachertz, C. Ortiz-Miller, Sandra Coppens, J. Lee, M. Popolizio, Michael Doumit, Rachel Salazar, Michelle A. Farrar, Peter G. Fuhr, M. Pedermonte, L. S. Lord-Halvorson, W. Leon, Y. S. Zeng, L. D'Argenzio, Russell J. Butterfield, C. Blomgren, Erika Finanger, S. Shea, Paola Tacchetti, N. Y. Ki, H. W. Choi, K. Oriyama, S. Wittevrongel, Catherine Siener, K. Mizuochi, M. Cowie, R. Van Coster, E. Gargaun, S. M. Scuplak, Sibylle Vogt, S. Stein, Tim Harrington, P. M. Ingelmo, J. Wootton, M. Tanyildiz, A. F. Rucian, Jonathan Marra, C. Frank Bennett, Claire L Wood, Nicolas Deconinck, Adnan Y. Manzur, Helene Verhelst, B. Purse, P. L. Léger, J. Cappell, S. Aziz-Zaman, H. Y. Wang, Claudio Bruno, S. Garcia Guixot, Robert Muni Lofra, Federica Trucco, S. M. Chun, Catherine E. Roberts, Ulrike Schara, Walter G. Bradley, K. L. De Valle, E. De Vos voor, S. Borell, A. Lim, Sophelia H. S. Chan, L. Rao, M. Shichiji, S. Rooze, T. M. Newcomb, Fouad Al-Ghamdi, Chiara Fiorillo, J. D. Endsley, L. Y. Sigurdardottir, Pallavi Anand, A. Zuffi, Julie A. Parsons, M. Kasper, A. Nishikawa, Sarah Gheuens, S. Turgeon-Desilet, T. Fujino, L. Staudt, Y. C. Wu, Jacinda B. Sampson, Paola Lanteri, Stephanie DeArmey, Partha S. Ghosh, Alexandra C. Ross, L. Adang, Laurent Servais, V. Tran, Alan Bielsky, Y. Otani, Navil F. Sethna, J. Hen, Perry B. Shieh, N. Fukuda, N. Miller, K. Eto, S. Paulose, Niklas Darin, C. Sabapathy, Robert J. Graham, Christopher Proud, Richard S. Finkel, Alexander G. Khandji, A. Della Marina, Adrian Murphy, Kathie M. Bishop, Tejaswi Kandula, Valentina Lanzillotta, Heather Szelag, Kalliopi Sofou, Y. H. Chou, Heike Koelbel, J. Eldblom, T. Lee, M. M. Martinez Moreno, Volker Straub, Laura E. Case, A. Lindstedt, G. Gili, A. Frank, H. C.C. Alvin, A. Ganfuss, Karen Herbert, Paul T. Golumbek, D. Villano, B. Wenderickx, B. C. Lim, W. S. Son, Schara, Ulrike (Beitragende*r), Ganfuss, Andrea (Beitragende*r), Koelbel, Heike (Beitragende*r), Rupprich, Katrin (Beitragende*r), Schroers, Ester Sarah (Beitragende*r), Sponemann, Nina (Beitragende*r), and Çocuk Sağlığı ve Hastalıkları

Subjects
Male, 0301 basic medicine, Pathology, Movement disorders, animal diseases, Messenger, Oligonucleotides, Medizin, Spinal Muscular Atrophies of Childhood, 0302 clinical medicine, Age of Onset, Disease-Free Survival, Double-Blind Method, Female, Humans, Infant, Injections, Spinal, Motor Skills, Oligonucleotides, Antisense, RNA, Messenger, Respiration, Artificial, Survival Analysis, Survival of Motor Neuron 2 Protein, Medicine (all), Respiration, General Medicine, Settore MED/26 - NEUROLOGIA, medicine.anatomical_structure, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Artificial, Nusinersen, medicine.symptom, medicine.medical_specialty, Spinal, Injections, 03 medical and health sciences, Atrophy, General & Internal Medicine, Settore MED/41 - ANESTESIOLOGIA, medicine, Antisense, Survival analysis, business.industry, Spinal muscular atrophy, Motor neuron, medicine.disease, nervous system diseases, 030104 developmental biology, nervous system, RNA, Infantile onset, Age of onset, business, 030217 neurology & neurosurgery
Abstract

Background: Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. Methods: We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. Results: In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P Conclusions: Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug.

Published
2017

48. Congenital muscular dystrophy phenotype with neuromuscular spindles excess in a 5-year-old girl caused by HRAS mutation

Author

Anamaria Bolocan, Dominique P. Germain, Susana Quijano-Roy, Michel Fardeau, Teresa Gidaro, Nathalie Blin, Brigitte Estournet, Anne-Gaëlle Le Moing, Robert Carlier, Laurent Servais, Andreea Mihaela Seferian, Valérie Allamand, Hélène Cavé, Pascale Richard, C. Gartioux, Thomas Voit, Norma B. Romero, and Clarisse Baumann

Subjects
Ullrich congenital muscular dystrophy, DNA Mutational Analysis, Muscular Dystrophies, Amino Acyl-tRNA Synthetases, medicine, Humans, Missense mutation, HRAS, Muscle Spindles, Kyphoscoliosis, Genetics (clinical), Muscle biopsy, medicine.diagnostic_test, business.industry, Skeletal muscle, Anatomy, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, Child, Preschool, Mutation, Pediatrics, Perinatology and Child Health, Congenital muscular dystrophy, Female, Neurology (clinical), Differential diagnosis, business
Abstract

We report on a 5-year-old girl who presented with an association of symptoms reminiscent of an Ullrich-like congenital muscular dystrophy including congenital hypotonia, proximal joint contractures, hyperlaxity of distal joints, normal cognitive development, and kyphoscoliosis. There was an excess of neuromuscular spindles on the skeletal muscle biopsy. This very peculiar feature on muscle biopsy has been reported only in patients with mutations in the HRAS gene. Sequence analysis of the subject's HRAS gene from blood leukocytes and skeletal muscle revealed a previously described heterozygous missense mutation (c.187G>A, p. Glu63Lys). The present report thus extends the differential diagnosis of congenital muscular dystrophy with major "retractile" phenotypes and adds congenital muscular dystrophy to the clinical spectrum of HRAS-related disorders.

Published
2014

49. Continuous Venovenous Hemofiltration After Coronary Procedures for the Prevention of Contrast-Induced Acute Kidney Injury in Patients With Severe Chronic Renal Failure

Author

Maurizio D'Urbano, Seveso G, Patrizia Covella, Matteo Mariani, Carlo Guastoni, Fabrizio Poletti, Nicoletta Bellotti, Stefano De Servi, Barbara Gidaro, and Antonella Stasi

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, medicine.medical_treatment, Population, Contrast Media, Renal function, Coronary Angiography, Iopamidol, Internal medicine, medicine, Humans, Renal replacement therapy, Acute Coronary Syndrome, education, Dialysis, Aged, Aged, 80 and over, Kidney, education.field_of_study, business.industry, Acute kidney injury, Acute Kidney Injury, medicine.disease, Coronary Vessels, medicine.anatomical_structure, Cardiology, Kidney Failure, Chronic, Female, Hemofiltration, Cardiology and Cardiovascular Medicine, business, Glomerular Filtration Rate, medicine.drug
Abstract

Continuous venovenous hemofiltration (CVVH) is a renal replacement therapy that has been successfully used in patients with severe chronic renal failure to prevent contrast-induced acute kidney injury (CI-AKI). In this study, we present a consecutive experience using a new CVVH protocol that has also been applied to patients with acute coronary syndrome (ACS). CVVH was performed in consecutive patients with estimated glomerular filtration rate30 ml/min/1.73 m(2) (mean ± SD, 21.1 ± 7.3 ml/min/1.73 m(2)) undergoing diagnostic or interventional coronary procedures starting after the angiographic procedures. Iopamidol was used as a contrast agent. In the first 6 patients, iopamidol removal by the CVVH hemofilter and kidney was calculated by measuring iopamidol concentrations in the blood, urine, and ultrafiltrate collected during the 6-hour CVVH session. In the second phase, the protocol was applied to 47 additional patients meeting the inclusion criteria. Six-hour CVVH resulted in iopamidol removal comparable with that of 12-hour diuresis (43 ± 12% vs 42 ± 15% of administered, p = NS). CI-AKI occurred in 7.5% of patients in the whole population and no patients had acute pulmonary edema, need for dialysis, or any major bleeding. In conclusion, in a population including patients with ACS with severe chronic renal failure undergoing coronary angiographic procedures, 6-hour CVVH performed only after contrast medium exposure was able to remove an amount of contrast medium similar to that removed by the kidneys in 12 hours and resulted in a low rate of CI-AKI.

Published
2014

Catalog

Books, media, physical & digital resources
See catalog results