Search

Your search keyword '"Pietro Maggi"' showing total 48 results
Start Over Author "Pietro Maggi"
48 results on '"Pietro Maggi"'

1. Comparative overview of multi-shell diffusion MRI models to characterize the microstructure of multiple sclerosis lesions and periplaques

Author

Colin Vanden Bulcke, Anna Stölting, Dragan Maric, Benoît Macq, Martina Absinta, and Pietro Maggi

Subjects
Multiple Sclerosis, MRI, Diffusion microstructural modelling, Neuroinflammation, Histopathology, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

In multiple sclerosis (MS), accurate in vivo characterization of the heterogeneous lesional and extra-lesional tissue pathology remains challenging. Marshalling several advanced imaging techniques — quantitative relaxation time (T1) mapping, a model-free average diffusion signal approach and four multi-shell diffusion models — this study investigates the performance of multi-shell diffusion models and characterizes the microstructural damage within (i) different MS lesion types — active, chronic active, and chronic inactive — (ii) their respective periplaque white matter (WM), and (iii) the surrounding normal-appearing white matter (NAWM). In 83 MS participants (56 relapsing-remitting, 27 progressive) and 23 age and sex-matched healthy controls (HC), we analysed a total of 317 paramagnetic rim lesions (PRL+), 232 non-paramagnetic rim lesions (PRL-), 38 contrast-enhancing lesions (CEL). Consistent with previous findings and histology, our analysis revealed the ability of advanced multi-shell diffusion models to characterize the unique microstructural patterns of CEL, and to elucidate their possible evolution into a resolving (chronic inactive) vs smoldering (chronic active) inflammatory stage. In addition, we showed that the microstructural damage extends well beyond the MRI-visible lesion edge, gradually fading out while moving outward from the lesion edge into the immediate WM periplaque and the NAWM, the latter still characterized by diffuse microstructural damage in MS vs HC. This study also emphasizes the critical role of selecting appropriate diffusion models to elucidate the complex pathological architecture of MS lesions and their periplaque. More specifically, multi-compartment diffusion models based on biophysically interpretable metrics such as neurite orientation dispersion and density (NODDI; mean auc=0.8002) emerge as the preferred choice for MS applications, while simpler models based on a representation of the diffusion signal, like diffusion tensor imaging (DTI; mean auc=0.6942), consistently underperformed, also when compared to T1 mapping (mean auc=0.73375).

Published
2024
Full Text
View/download PDF

2. B cell depletion therapy does not resolve chronic active multiple sclerosis lesionsResearch in context

Author

Pietro Maggi, Colin Vanden Bulcke, Edoardo Pedrini, Céline Bugli, Amina Sellimi, Maxence Wynen, Anna Stölting, William A. Mullins, Grigorios Kalaitzidis, Valentina Lolli, Gaetano Perrotta, Souraya El Sankari, Thierry Duprez, Xu Li, Peter A. Calabresi, Vincent van Pesch, Daniel S. Reich, and Martina Absinta

Subjects
Susceptibility-based MRI, Paramagnetic rims, Anti-CD20 treatment, Machine learning, Single cell RNA sequencing, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Chronic active lesions (CAL) in multiple sclerosis (MS) have been observed even in patients taking high-efficacy disease-modifying therapy, including B-cell depletion. Given that CAL are a major determinant of clinical progression, including progression independent of relapse activity (PIRA), understanding the predicted activity and real-world effects of targeting specific lymphocyte populations is critical for designing next-generation treatments to mitigate chronic inflammation in MS. Methods: We analyzed published lymphocyte single-cell transcriptomes from MS lesions and bioinformatically predicted the effects of depleting lymphocyte subpopulations (including CD20 B-cells) from CAL via gene-regulatory-network machine-learning analysis. Motivated by the results, we performed in vivo MRI assessment of PRL changes in 72 adults with MS, 46 treated with anti-CD20 antibodies and 26 untreated, over ∼2 years. Findings: Although only 4.3% of lymphocytes in CAL were CD20 B-cells, their depletion is predicted to affect microglial genes involved in iron/heme metabolism, hypoxia, and antigen presentation. In vivo, tracking 202 PRL (150 treated) and 175 non-PRL (124 treated), none of the treated paramagnetic rims disappeared at follow-up, nor was there a treatment effect on PRL for lesion volume, magnetic susceptibility, or T1 time. PIRA occurred in 20% of treated patients, more frequently in those with ≥4 PRL (p = 0.027). Interpretation: Despite predicted effects on microglia-mediated inflammatory networks in CAL and iron metabolism, anti-CD20 therapies do not fully resolve PRL after 2-year MRI follow up. Limited tissue turnover of B-cells, inefficient passage of anti-CD20 antibodies across the blood–brain-barrier, and a paucity of B-cells in CAL could explain our findings. Funding: Intramural Research Program of NINDS, NIH; NINDS grants R01NS082347 and R01NS082347; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Cariplo Foundation (grant #1677), FRRB Early Career Award (grant #1750327); Fund for Scientific Research (FNRS).

Published
2023
Full Text
View/download PDF

3. BMAT: An open-source BIDS managing and analysis tool

Author

Colin Vanden Bulcke, Maxence Wynen, Jules Detobel, Francesco La Rosa, Martina Absinta, Laurence Dricot, Benoît Macq, Meritxell Bach Cuadra, and Pietro Maggi

Subjects
Neuroimaging, Software, BIDS, Multiple Sclerosis, MRI, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Magnetic Resonance Imaging (MRI) is an established technique to study in vivo neurological disorders such as Multiple Sclerosis (MS). To avoid errors on MRI data organization and automated processing, a standard called Brain Imaging Data Structure (BIDS) has been recently proposed. The BIDS standard eases data sharing and processing within or between centers by providing guidelines for their description and organization. However, the transformation from the complex unstructured non-open file data formats coming directly from the MRI scanner to a correct BIDS structure can be cumbersome and time consuming. This hinders a wider adoption of the BIDS format across different study centers. To solve this problem and ease the day-to-day use of BIDS for the neuroimaging scientific community, we present the BIDS Managing and Analysis Tool (BMAT). The BMAT software is a complete and easy-to-use local open-source neuroimaging analysis tool with a graphical user interface (GUI) that uses the BIDS format to organize and process brain MRI data for MS imaging research studies. BMAT provides the possibility to translate data from MRI scanners to the BIDS structure, create and manage BIDS datasets as well as develop and run automated processing pipelines, and is faster than its competitor. BMAT software propose the possibility to download useful analysis apps, especially applied to MS research with lesion segmentation and processing of imaging contrasts for novel disease biomarkers such as the central vein sign and the paramagnetic rim lesions.

Published
2022
Full Text
View/download PDF

4. Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

Author

Bhagteshwar Singh, Suzannah Lant, Sofia Cividini, Jonathan W. S. Cattrall, Lynsey C. Goodwin, Laura Benjamin, Benedict D. Michael, Ayaz Khawaja, Aline de Moura Brasil Matos, Walid Alkeridy, Andrea Pilotto, Durjoy Lahiri, Rebecca Rawlinson, Sithembinkosi Mhlanga, Evelyn C. Lopez, Brendan F. Sargent, Anushri Somasundaran, Arina Tamborska, Glynn Webb, Komal Younas, Yaqub Al Sami, Heavenna Babu, Tristan Banks, Francesco Cavallieri, Matthew Cohen, Emma Davies, Shalley Dhar, Anna Fajardo Modol, Hamzah Farooq, Jeffrey Harte, Samuel Hey, Albert Joseph, Dileep Karthikappallil, Daniel Kassahun, Gareth Lipunga, Rachel Mason, Thomas Minton, Gabrielle Mond, Joseph Poxon, Sophie Rabas, Germander Soothill, Marialuisa Zedde, Konstantin Yenkoyan, Bruce Brew, Erika Contini, Lucette Cysique, Xin Zhang, Pietro Maggi, Vincent van Pesch, Jérome Lechien, Sven Saussez, Alex Heyse, Maria Lúcia Brito Ferreira, Cristiane N. Soares, Isabel Elicer, Laura Eugenín-von Bernhardi, Waleng Ñancupil Reyes, Rong Yin, Mohammed A. Azab, Foad Abd-Allah, Ahmed Elkady, Simon Escalard, Jean-Christophe Corvol, Cécile Delorme, Pierre Tattevin, Kévin Bigaut, Norbert Lorenz, Daniel Hornuss, Jonas Hosp, Siegbert Rieg, Dirk Wagner, Benjamin Knier, Paul Lingor, Andrea Sylvia Winkler, Athena Sharifi-Razavi, Shima T. Moein, SeyedAhmad SeyedAlinaghi, Saeidreza JamaliMoghadamSiahkali, Mauro Morassi, Alessandro Padovani, Marcello Giunta, Ilenia Libri, Simone Beretta, Sabrina Ravaglia, Matteo Foschi, Paolo Calabresi, Guido Primiano, Serenella Servidei, Nicola Biagio Mercuri, Claudio Liguori, Mariangela Pierantozzi, Loredana Sarmati, Federica Boso, Silvia Garazzino, Sara Mariotto, Kimani N. Patrick, Oana Costache, Alexander Pincherle, Frederikus A. Klok, Roger Meza, Verónica Cabreira, Sofia R. Valdoleiros, Vanessa Oliveira, Igor Kaimovsky, Alla Guekht, Jasmine Koh, Eva Fernández Díaz, José María Barrios-López, Cristina Guijarro-Castro, Álvaro Beltrán-Corbellini, Javier Martínez-Poles, Alba María Diezma-Martín, Maria Isabel Morales-Casado, Sergio García García, Gautier Breville, Matteo Coen, Marjolaine Uginet, Raphaël Bernard-Valnet, Renaud Du Pasquier, Yildiz Kaya, Loay H. Abdelnour, Claire Rice, Hamish Morrison, Sylviane Defres, Saif Huda, Noelle Enright, Jane Hassell, Lucio D’Anna, Matthew Benger, Laszlo Sztriha, Eamon Raith, Krishna Chinthapalli, Ross Nortley, Ross Paterson, Arvind Chandratheva, David J. Werring, Samir Dervisevic, Kirsty Harkness, Ashwin Pinto, Dinesh Jillella, Scott Beach, Kulothungan Gunasekaran, Ivan Rocha Ferreira Da Silva, Krishna Nalleballe, Jonathan Santoro, Tyler Scullen, Lora Kahn, Carla Y. Kim, Kiran T. Thakur, Rajan Jain, Thirugnanam Umapathi, Timothy R. Nicholson, James J. Sejvar, Eva Maria Hodel, The Brain Infections Global COVID-Neuro Network Study Group, Catrin Tudur Smith, and Tom Solomon

Subjects
Medicine, Science
Abstract

Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.

Published
2022

5. Cortical lesions, central vein sign, and paramagnetic rim lesions in multiple sclerosis: Emerging machine learning techniques and future avenues

Author

Francesco La Rosa, Maxence Wynen, Omar Al-Louzi, Erin S Beck, Till Huelnhagen, Pietro Maggi, Jean-Philippe Thiran, Tobias Kober, Russell T Shinohara, Pascal Sati, Daniel S Reich, Cristina Granziera, Martina Absinta, and Meritxell Bach Cuadra

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

The current diagnostic criteria for multiple sclerosis (MS) lack specificity, and this may lead to misdiagnosis, which remains an issue in present-day clinical practice. In addition, conventional biomarkers only moderately correlate with MS disease progression. Recently, some MS lesional imaging biomarkers such as cortical lesions (CL), the central vein sign (CVS), and paramagnetic rim lesions (PRL), visible in specialized magnetic resonance imaging (MRI) sequences, have shown higher specificity in differential diagnosis. Moreover, studies have shown that CL and PRL are potential prognostic biomarkers, the former correlating with cognitive impairments and the latter with early disability progression. As machine learning-based methods have achieved extraordinary performance in the assessment of conventional imaging biomarkers, such as white matter lesion segmentation, several automated or semi-automated methods have been proposed as well for CL, PRL, and CVS. In the present review, we first introduce these MS biomarkers and their imaging methods. Subsequently, we describe the corresponding machine learning-based methods that were proposed to tackle these clinical questions, putting them into context with respect to the challenges they are facing, including non-standardized MRI protocols, limited datasets, and moderate inter-rater variability. We conclude by presenting the current limitations that prevent their broader deployment and suggesting future research directions.

Published
2022
Full Text
View/download PDF

6. RimNet: A deep 3D multimodal MRI architecture for paramagnetic rim lesion assessment in multiple sclerosis

Author

Germán Barquero, Francesco La Rosa, Hamza Kebiri, Po-Jui Lu, Reza Rahmanzadeh, Matthias Weigel, Mário João Fartaria, Tobias Kober, Marie Théaudin, Renaud Du Pasquier, Pascal Sati, Daniel S. Reich, Martina Absinta, Cristina Granziera, Pietro Maggi, and Meritxell Bach Cuadra

Subjects
Multiple sclerosis, Paramagnetic rim lesions, Susceptibility-based MRI, Deep learning, Supervised classification, Multimodal network, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Objectives: In multiple sclerosis (MS), the presence of a paramagnetic rim at the edge of non-gadolinium-enhancing lesions indicates perilesional chronic inflammation. Patients featuring a higher paramagnetic rim lesion burden tend to have more aggressive disease. The objective of this study was to develop and evaluate a convolutional neural network (CNN) architecture (RimNet) for automated detection of paramagnetic rim lesions in MS employing multiple magnetic resonance (MR) imaging contrasts. Materials and methods: Imaging data were acquired at 3 Tesla on three different scanners from two different centers, totaling 124 MS patients, and studied retrospectively. Paramagnetic rim lesion detection was independently assessed by two expert raters on T2*-phase images, yielding 462 rim-positive (rim+) and 4857 rim-negative (rim-) lesions. RimNet was designed using 3D patches centered on candidate lesions in 3D-EPI phase and 3D FLAIR as input to two network branches. The interconnection of branches at both the first network blocks and the last fully connected layers favors the extraction of low and high-level multimodal features, respectively. RimNet’s performance was quantitatively evaluated against experts’ evaluation from both lesion-wise and patient-wise perspectives. For the latter, patients were categorized based on a clinically relevant threshold of 4 rim+ lesions per patient. The individual prediction capabilities of the images were also explored and compared (DeLong test) by testing a CNN trained with one image as input (unimodal). Results: The unimodal exploration showed the superior performance of 3D-EPI phase and 3D-EPI magnitude images in the rim+/- classification task (AUC = 0.913 and 0.901), compared to the 3D FLAIR (AUC = 0.855, Ps

Published
2020
Full Text
View/download PDF

7. Novel marmoset (Callithrix jacchus) model of human Herpesvirus 6A and 6B infections: immunologic, virologic and radiologic characterization.

Author

Emily Leibovitch, Jillian E Wohler, Sheila M Cummings Macri, Kelsey Motanic, Erin Harberts, María I Gaitán, Pietro Maggi, Mary Ellis, Susan Westmoreland, Afonso Silva, Daniel S Reich, and Steven Jacobson

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Human Herpesvirus 6 (HHV-6) is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. HHV-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the CNS. Animal models of HHV-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack CD46, the receptor for cellular entry. Therefore, we investigated the effects of HHV-6 infections in a non-human primate, the common marmoset Callithrix jacchus. We inoculated a total of 12 marmosets with HHV-6A and HHV-6B intravenously and HHV-6A intranasally. Animals were monitored for 25 weeks post-inoculation clinically, immunologically and by MRI. Marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms and generated virus-specific antibody responses, while those inoculated intravenously with HHV-6B were asymptomatic and generated comparatively lower antibody responses. Viral DNA was detected at a low frequency in paraffin-embedded CNS tissue of a subset of marmosets inoculated with HHV-6A and HHV-6B intravenously. When different routes of HHV-6A inoculation were compared, intravenous inoculation resulted in virus-specific antibody responses and infrequent detection of viral DNA in the periphery, while intranasal inoculation resulted in negligible virus-specific antibody responses and frequent detection of viral DNA in the periphery. Moreover, marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms, while marmosets inoculated with HHV-6A intranasally were asymptomatic. We demonstrate that a marmoset model of HHV-6 infection can serve to further define the contribution of this ubiquitous virus to human neurologic disorders.

Published
2013
Full Text
View/download PDF

9. B CELL DEPLETION THERAPY DOES NOT RESOLVE CHRONIC ACTIVE MULTIPLE SCLEROSIS LESIONS

Author

Pietro Maggi, Colin Vanden Bulcke, Edoardo Pedrini, Céline Bugli, Amina Sellimi, Maxence Wynen, Anna Stölting, William A. Mullins, Grigorios Kalaitzidis, Valentina Lolli, Gaetano Perrotta, Souraya El Sankari, Thierry Duprez, Xu Li, Peter A. Calabresi, Vincent van Pesch, Daniel Reich, Martina Absinta, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Abstract

Background Chronic active lesions (CAL) in multiple sclerosis (MS) have been observed even in patients taking high-efficacy disease-modifying therapy, including B-cell depletion. Given that CAL are a major determinant of clinical progression, including progression independent of relapse activity (PIRA), understanding the predicted activity and real-world effects of targeting specific lymphocyte populations is critical for designing next-generation treatments to mitigate chronic inflammation in MS. Methods We analyzed published lymphocyte single-cell transcriptomes from MS lesions and bioinformatically predicted the effects of depleting lymphocyte subpopulations (including CD20 B-cells) from CAL via gene-regulatory-network machine-learning analysis. Motivated by the results, we performed in vivo MRI assessment of PRL changes in 72 adults with MS, 46 treated with anti-CD20 antibodies and 26 untreated, over ~2 years. Findings Although only 4.3% of lymphocytes in CAL were CD20 B-cells, their depletion is predicted to affect microglial genes involved in iron/heme metabolism, hypoxia, and antigen presentation. In vivo, tracking 202 PRL (150 treated) and 175 non-PRL (124 treated), none of the treated paramagnetic rims disappeared at follow-up, nor was there a treatment effect on PRL for lesion volume, magnetic susceptibility, or T1 time. PIRA occurred in 20% of treated patients, more frequently in those with ≥4 PRL (p=0.027). Interpretation Despite predicted effects on microglia-mediated inflammatory networks in CAL and iron metabolism, anti-CD20 therapies do not fully resolve PRL after 2-year MRI follow up. Limited tissue turnover of Bcells, inefficient passage of anti-CD20 antibodies across the blood-brain-barrier, and a paucity of Bcells in CAL could explain our findings.

Published
2023

10. Infrastructure Monitoring for Distributed Tier1: The ReCaS Project Use-Case.

Author

Vania Boccia, L. Carraciuolo, D. Del Prete, Silvio Pardi, Marica Antonacci, Giacinto Donvito, Alfonso Monaco, V. Spinoso, Giuseppe Andronico, Roberto Barbera, Marco Fargetta, Salvatore Monforte, V. Lavorini, Alessandro Tarasio, E. Tassi, Giovanni Battista Barone, Davide Bottalico, Leonardo Merola, S. Naddeo, Giuseppe Scotti, Giorgio Russo, Giorgio Pietro Maggi, and Roberto Bellotti

Published
2014
Full Text
View/download PDF

13. Myelin and axon pathology in multiple sclerosis assessed by myelin water and multi-shell diffusion imaging

Author

Matthias Weigel, Sabine Schaedelin, Thanh D. Nguyen, M. Absinta, Po Jui Lu, Ludwig Kappos, Jens Kuhle, Meritxell Bach Cuadra, Francesco La Rosa, Simona Schiavi, Pascal Sati, Pietro Maggi, Alessandro Daducci, Cristina Granziera, Daniel S. Reich, Muhamed Barakovic, Yi Wang, Ernst Wilhelm Radue, Reza Rahmanzadeh, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie

Subjects
Male, Pathology, Adult, Axons/pathology, Brain/diagnostic imaging, Brain/pathology, Diffusion Magnetic Resonance Imaging/methods, Female, Humans, Image Interpretation, Computer-Assisted/methods, Middle Aged, Multiple Sclerosis/diagnostic imaging, Multiple Sclerosis/pathology, Myelin Sheath/pathology, Neuroimaging/methods, Water, demyelination, diffusion microstructural modelling, multiple sclerosis, myelin water imaging, neurodegeneration, lesions, 030218 nuclear medicine & medical imaging, Myelin, Computer-Assisted, gray-matter, 0302 clinical medicine, Axon, Myelin Sheath, AcademicSubjects/SCI01870, Brain, 3. Good health, medicine.anatomical_structure, medicine.medical_specialty, Multiple Sclerosis, Neurite, injury, Neuroimaging, Grey matter, White matter, 03 medical and health sciences, Image Interpretation, Computer-Assisted, normal-appearing white, medicine, magnetization-transfer ratio, Remyelination, Image Interpretation, disease, business.industry, Multiple sclerosis, Original Articles, medicine.disease, Axons, Hyperintensity, remyelination, Diffusion Magnetic Resonance Imaging, disability, nervous system, AcademicSubjects/MED00310, Neurology (clinical), business, neurite orientation dispersion, 030217 neurology & neurosurgery
Abstract

Damage to the myelin sheath and the neuroaxonal unit is a cardinal feature of multiple sclerosis; however, a detailed characterization of the interaction between myelin and axon damage in vivo remains challenging., We applied myelin water and multi-shell diffusion imaging to quantify the relative damage to myelin and axons (i) among different lesion types; (ii) in normal-appearing tissue; and (iii) across multiple sclerosis clinical subtypes and healthy controls. We also assessed the relation of focal myelin/axon damage with disability and serum neurofilament light chain as a global biological measure of neuroaxonal damage. Ninety-one multiple sclerosis patients (62 relapsing-remitting, 29 progressive) and 72 healthy controls were enrolled in the study., Differences in myelin water fraction and neurite density index were substantial when lesions were compared to healthy control subjects and normal-appearing multiple sclerosis tissue: both white matter and cortical lesions exhibited a decreased myelin water fraction and neurite density index compared with healthy (P < 0.0001) and peri-plaque white matter (P < 0.0001). Periventricular lesions showed decreased myelin water fraction and neurite density index compared with lesions in the juxtacortical region ( P < 0.0001 and P < 0.05). Similarly, lesions with paramagnetic rims showed decreased myelin water fraction and neurite density index relative to lesions without a rim (P < 0.0001). Also, in 75% of white matter lesions, the reduction in neurite density index was higher than the reduction in the myelin water fraction. Besides, normal-appearing white and grey matter revealed diffuse reduction of myelin water fraction and neurite density index in multiple sclerosis compared to healthy controls (P < 0.01). Further, a more extensive reduction in myelin water fraction and neurite density index in normalappearing cortex was observed in progressive versus relapsing-remitting participants. Neurite density index in white matter lesions correlated with disability in patients with clinical deficits (P < 0.01, beta = -10.00); and neurite density index and myelin water fraction in white matter lesions were associated to serum neurofilament light chain in the entire patient cohort (P < 0.01, beta = -3.60 and P < 0.01, beta = 0.13, respectively)., These findings suggest that (i) myelin and axon pathology in multiple sclerosis is extensive in both lesions and normal-appearing tissue; (ii) particular types of lesions exhibit more damage to myelin and axons than others; (iii) progressive patients differ from relapsing-remitting patients because of more extensive axon/myelin damage in the cortex; and (iv) myelin and axon pathology in lesions is related to disability in patients with clinical deficits and global measures of neuroaxonal damage.

Published
2021

15. Paramagnetic Rim Lesions are Specific to Multiple Sclerosis: An International Multicenter 3T MRI Study

Author

Steven Jacobson, Tianxia Wu, Avindra Nath, Pascal Sati, Vincent Van Pesch, Daniel S. Reich, Marie Théaudin, Irene Cortese, Caroline Pot, Massimo Filippi, Vittorio Martinelli, Peter A. Calabresi, Renaud Du Pasquier, M. Absinta, Pietro Maggi, Govind Nair, Roberta Scotti, Gaetano Perrotta, Bryan Smith, Joan Ohayon, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Maggi, Pietro, Sati, Pascal, Nair, Govind, Cortese, Irene C M, Jacobson, Steven, Smith, Bryan R, Nath, Avindra, Ohayon, Joan, van Pesch, Vincent, Perrotta, Gaetano, Pot, Caroline, Théaudin, Marie, Martinelli, Vittorio, Scotti, Roberta, Wu, Tianxia, Du Pasquier, Renaud, Calabresi, Peter A, Filippi, Massimo, Reich, Daniel S, and Absinta, Martina

Subjects
Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Multiple Sclerosis, Neuroimaging, Sensitivity and Specificity, Article, Diagnosis, Differential, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Prevalence, medicine, Humans, Diagnostic biomarker, Aged, Retrospective Studies, medicine.diagnostic_test, Chronic Active, business.industry, Multiple sclerosis, Magnetic resonance imaging, Middle Aged, medicine.disease, Clinical disease, Magnetic Resonance Imaging, Hyperintensity, 030104 developmental biology, Neurology, Female, Neurology (clinical), Nervous System Diseases, Differential diagnosis, business, 030217 neurology & neurosurgery
Abstract

In multiple sclerosis (MS), a subset of chronic active white matter lesions are identifiable on magnetic resonance imaging by their paramagnetic rims, and increasing evidence supports their association with severity of clinical disease. We studied their potential role in differential diagnosis, screening an international multicenter clinical research-based sample of 438 individuals affected by different neurological conditions (MS, other inflammatory, infectious, and non-inflammatory conditions). Paramagnetic rim lesions, rare in other neurological conditions (52% of MS vs 7% of non-MS cases), yielded high specificity (93%) in differentiating MS from non-MS. Future prospective multicenter studies should validate their role as a diagnostic biomarker. ANN NEUROL 2020;88:1034-1042.

Published
2020

17. Immune-mediated neurological syndromes in SARS-CoV-2-infected patients

Author

Sofia Maldonado Slootjes, P. Jacquerye, Amina Sellimi, Vincent Van Pesch, Pietro Maggi, Antoine Capes, Philippe Hantson, Leila Belkhir, Frédéric London, Lucie Pothen, Halil Yildiz, Thierry Duprez, Maroussia Bronchain, Jean-Marc Raymackers, Antoine Guilmot, Ahalieyah Anantharajah, Jean Cyr Yombi, Julien De Greef, Adrian Ivanoiu, Bernard Hanseeuw, Catherine Fillée, Souraya El Sankari, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service de neurologie, UCL - (SLuc) Service de radiologie, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de soins intensifs, UCL - (SLuc) Service de médecine interne générale, UCL - (SLuc) Service de neurologie, UCL - (SLuc) Centre de l'allergie, UCL - SSS/IREC/MBLG - Pôle de Microbiologie médicale, and UCL - (SLuc) Service de microbiologie

Subjects
Adult, Male, Anti-GD1b, medicine.medical_specialty, Neurology, Leukocytosis, Lymphocytic pleocytosis, Clinical Neurology, Neurological examination, Nerve Tissue Proteins, Spinal Puncture, Antibodies, Serology, Cerebrospinal fluid, CSF pleocytosis, Internal medicine, Gangliosides, medicine, Humans, Radiculopathy, Aged, Aged, 80 and over, Neurologic Examination, Original Communication, medicine.diagnostic_test, business.industry, Lumbar puncture, SARS-CoV-2, COVID-19, Delirium, Membrane Proteins, Middle Aged, medicine.disease, Encephalitis, Female, Neurology (clinical), Nervous System Diseases, business
Abstract

Background Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore investigated clinical, serological and CSF features of coronavirus disease 2019 (COVID-19) patients with neurological manifestations. Methods Consecutive COVID-19 patients with neurological manifestations other than isolated anosmia and/or non-severe headache, and with no previous neurological or psychiatric disorders were prospectively included. Neurological examination was performed in all patients and lumbar puncture with CSF examination was performed when not contraindicated. Serum anti-gangliosides antibodies were tested when clinically indicated. Results Of the 349 COVID-19 admitted to our center between March 23rd and April 24th 2020, 15 patients (4.3%) had neurological manifestations and fulfilled the study inclusion/exclusion criteria. CSF examination was available in 13 patients and showed lymphocytic pleocytosis in 2 patients: 1 with anti-contactin-associated protein 2 (anti-Caspr2) antibody encephalitis and 1 with meningo-polyradiculitis. Increased serum titer of anti-GD1b antibodies was found in three patients and was associated with variable clinical presentations, including cranial neuropathy with meningo-polyradiculitis, brainstem encephalitis and delirium. CSF PCR for SARS-CoV-2 was negative in all patients. Conclusions In SARS-Cov-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity.

Published
2021

18. The central vein sign in multiple sclerosis patients with vascular comorbidities

Author

François Guisset, Bernard Dachy, Julie Absil, Pietro Maggi, Vincent Van Pesch, Valentina Lolli, Céline Bugli, Gaetano Perrotta, Marco Pasi, Marie Théaudin, Caroline Pot, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - SSH/LIDAM/SMCS - Support en méthodologie et calcul statistique (plate-forme technologique), and UCL - (SLuc) Service de neurologie

Subjects
medicine.medical_specialty, Multiple Sclerosis, Imaging biomarker, 030204 cardiovascular system & hematology, multiple sclerosis, Veins, 03 medical and health sciences, 0302 clinical medicine, fluids and secretions, Neurologie, medicine, Humans, magnetic resonance imaging, Vein, Central vein sign, Aged, medicine.diagnostic_test, business.industry, cerebral small vessel disease, Multiple sclerosis, Brain, Magnetic resonance imaging, medicine.disease, equipment and supplies, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, vascular risk factors, Cerebral Small Vessel Diseases, Neurology (clinical), Radiology, business, 030217 neurology & neurosurgery, Sign (mathematics)
Abstract

Background: The central vein sign (CVS) is an imaging biomarker able to differentiate multiple sclerosis (MS) from other conditions causing similar appearance lesions on magnetic resonance imaging (MRI), including cerebral small vessel disease (CSVD). However, the impact of vascular risk factors (VRFs) for CSVD on the percentage of CVS positive (CVS+) lesions in MS has never been evaluated. Objective: To investigate the association between different VRFs and the percentage of CVS+ lesions in MS. Methods: In 50 MS patients, 3T brain MRIs (including high-resolution 3-dimensional T2*-weighted images) were analyzed for the presence of the CVS and MRI markers of CSVD. A backward stepwise regression model was used to predict the combined predictive effect of VRF (i.e. age, hypertension, diabetes, obesity, ever-smoking, and hypercholesterolemia) and MRI markers of CSVD on the CVS. Results: The median frequency of CVS+ lesions was 71% (range: 35%–100%). In univariate analysis, age (p < 0.0001), hypertension (p < 0.001), diabetes (p < 0.01), obesity (p < 0.01), smoking (p < 0.05), and the presence of enlarged-perivascular-spaces on MRI (p < 0.005) were all associated with a lower percentage of CVS+ lesions. The stepwise regression model showed that age and arterial hypertension were both associated with the percentage of CVS+ lesions in MS (adjusted R2 = 0.46; p < 0.0001 and p = 0.01, respectively). Conclusion: The proportion of CVS+ lesions significantly decreases in older and hypertensive MS patients. Although this study was conducted in patients with an already established MS diagnosis, the diagnostic yield of the previously proposed 35% CVS proportion-based diagnostic threshold appears to be not affected. Overall these results suggest that the presence of VRF for CSVD should be taken into account during the CVS assessment., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2020

20. RimNet: A deep 3D multimodal MRI architecture for paramagnetic rim lesion assessment in multiple sclerosis

Author

Tobias Kober, Cristina Granziera, Daniel S. Reich, Germán Barquero, Po Jui Lu, Mário João Fartaria, Pietro Maggi, Marie Théaudin, Francesco La Rosa, Matthias Weigel, Renaud Du Pasquier, Hamza Kebiri, Reza Rahmanzadeh, M. Absinta, Meritxell Bach Cuadra, Pascal Sati, UCL - SSS/IONS/NEUR - Clinical Neuroscience, and UCL - (SLuc) Service de neurologie

Subjects
Multimodal network, Computer science, Cognitive Neuroscience, Aggressive disease, Fluid-attenuated inversion recovery, lcsh:Computer applications to medicine. Medical informatics, Imaging data, Convolutional neural network, 050105 experimental psychology, lcsh:RC346-429, Lesion, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Imaging, Three-Dimensional, Radiology Nuclear Medicine and imaging, Neurology, Clinical Neurology, Deep learning, Paramagnetic rim lesions, Supervised classification, Susceptibility-based MRI, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, lcsh:Neurology. Diseases of the nervous system, ComputingMethodologies_COMPUTERGRAPHICS, Retrospective Studies, Lesion detection, medicine.diagnostic_test, business.industry, 05 social sciences, Brain, Magnetic resonance imaging, Regular Article, medicine.disease, Magnetic Resonance Imaging, lcsh:R858-859.7, Neurology (clinical), medicine.symptom, Nuclear medicine, business, 030217 neurology & neurosurgery
Abstract

Graphical abstract, Highlights • RimNet, an automated method to detect paramagnetic rim in Multiple Sclerosis lesions. • Different rim detection ability of 3D FLAIR and 3D EPI (T2* & Phase) MRI. • RimNet performance is close to experts’ at lesion and patient-wise levels. • Automated rim analysis is feasible with one single 3D EPI MR acquisition. • Excellent RimNet performance is maintained in inter-hospital evaluation., Objectives In multiple sclerosis (MS), the presence of a paramagnetic rim at the edge of non-gadolinium-enhancing lesions indicates perilesional chronic inflammation. Patients featuring a higher paramagnetic rim lesion burden tend to have more aggressive disease. The objective of this study was to develop and evaluate a convolutional neural network (CNN) architecture (RimNet) for automated detection of paramagnetic rim lesions in MS employing multiple magnetic resonance (MR) imaging contrasts. Materials and methods Imaging data were acquired at 3 Tesla on three different scanners from two different centers, totaling 124 MS patients, and studied retrospectively. Paramagnetic rim lesion detection was independently assessed by two expert raters on T2*-phase images, yielding 462 rim-positive (rim+) and 4857 rim-negative (rim-) lesions. RimNet was designed using 3D patches centered on candidate lesions in 3D-EPI phase and 3D FLAIR as input to two network branches. The interconnection of branches at both the first network blocks and the last fully connected layers favors the extraction of low and high-level multimodal features, respectively. RimNet’s performance was quantitatively evaluated against experts’ evaluation from both lesion-wise and patient-wise perspectives. For the latter, patients were categorized based on a clinically relevant threshold of 4 rim+ lesions per patient. The individual prediction capabilities of the images were also explored and compared (DeLong test) by testing a CNN trained with one image as input (unimodal). Results The unimodal exploration showed the superior performance of 3D-EPI phase and 3D-EPI magnitude images in the rim+/- classification task (AUC = 0.913 and 0.901), compared to the 3D FLAIR (AUC = 0.855, Ps

Published
2020
Full Text
View/download PDF

21. The 'central vein sign' in patients with diagnostic 'red flags' for multiple sclerosis: A prospective multicenter 3T study

Author

Luca Massacesi, Gaetano Perrotta, Reto Meuli, Martina Absinta, Marie Théaudin, Pascal Sati, Massimo Filippi, Pietro Maggi, Renaud Du Pasquier, Bernard Dachy, Caroline Pot, Daniel S. Reich, Maggi, Pietro, Absinta, Martina, Sati, Pascal, Perrotta, Gaetano, Massacesi, Luca, Dachy, Bernard, Pot, Caroline, Meuli, Reto, Reich, Daniel S, Filippi, Massimo, Pasquier, Renaud Du, Théaudin, Marie, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Article, 030218 nuclear medicine & medical imaging, Diagnosis, Differential, Young Adult, 03 medical and health sciences, red flags, 0302 clinical medicine, Predictive Value of Tests, Neurologie, medicine, Humans, Prospective Studies, Vein, Central vein sign, Aged, business.industry, Multiple sclerosis, Middle Aged, equipment and supplies, medicine.disease, Cerebral Veins, Magnetic Resonance Imaging, White Matter, MS diagnosis, medicine.anatomical_structure, Neurology, Female, Neurology (clinical), Radiology, Differential diagnosis, business, 030217 neurology & neurosurgery, Sign (mathematics), Red flags
Abstract

Background: The central vein sign (CVS) has been shown to help in the differential diagnosis of multiple sclerosis (MS), but most prior studies are retrospective. Objectives: To prospectively assess the diagnostic predictive value of the CVS in diagnostically difficult cases. Methods: In this prospective multicenter study, 51 patients with suspected MS who had clinical, imaging, or laboratory “red flags” (i.e. features atypical for MS) underwent 3T fluid-attenuated inversion recovery (FLAIR*) magnetic resonance imaging (MRI) for CVS assessment. After the diagnostic work-up, expert clinicians blinded to the results of the CVS assessment came to a clinical diagnosis. The value of the CVS to prospectively predict an MS diagnosis was assessed. Results: Of the 39 patients who received a clinical diagnosis by the end of the study, 27 had MS and 12 received a non-MS diagnosis that included systemic lupus erythematosus, sarcoidosis, migraine, Sjögren disease, SPG4-spastic-paraparesis, neuromyelitis optica, and Susac syndrome. The percentage of perivenular lesions was higher in MS (median = 86%) compared to non-MS (median = 21%; p < 0.0001) patients. A 40% perivenular lesion cutoff was associated with 97% accuracy and a 96% positive/100% negative predictive value. Conclusion: The CVS detected on 3T FLAIR* images can accurately predict an MS diagnosis in patients suspected to have MS, but with atypical clinical, laboratory, and imaging features., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2020

22. Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies

Author

Pascal Sati, Vittorio Martinelli, Matteo Grammatico, Gregorio Spagni, Alessandro Barilaro, Luca Massacesi, Giovanna Carlucci, Anna Maria Repice, Roberta Scotti, Niloufar Sadeghi, Pietro Maggi, Martina Absinta, Domenico Prisco, Gaetano Perrotta, Bernard Dachy, Daniel S. Reich, Lorenzo Emmi, Giacomo Emmi, Massimo Filippi, and Luisa Vuolo

Subjects
Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Multiple sclerosis, Magnetic resonance imaging, medicine.disease, Hyperintensity, 030218 nuclear medicine & medical imaging, Lesion, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Neurology, medicine, Biomarker (medicine), Neurology (clinical), Differential diagnosis, medicine.symptom, Vein, Vasculitis, business, 030217 neurology & neurosurgery
Abstract

Objectives In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). Methods In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. Results MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behcet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjogren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. Interpretation The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294.

Published
2018

24. Magnetic resonance imaging of experimental autoimmune encephalomyelitis in the common marmoset

Author

Luca Massacesi, Pascal Sati, Pietro Maggi, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Encephalomyelitis, Autoimmune, Experimental, Immunology, Central nervous system, Disease, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Species Specificity, biology.animal, medicine, Animals, Humans, Immunology and Allergy, Pathological, Multiple sclerosis,Experimental autoimmune encephalomyelitis, Marmoset, Magnetic resonance imaging, Brain, Inflammation, Demyelination, Inflammation, Mri techniques, Experimental autoimmune encephalomyelitis, biology, medicine.diagnostic_test, Brain, Marmoset, Callithrix, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Neurology, Neurology (clinical), Demyelination, Neuroscience, 030217 neurology & neurosurgery
Abstract

Magnetic resonance imaging (MRI) is an invaluable tool for the diagnosis and monitoring of patients with multiple sclerosis (MS) as well as for the study of the disease pathophysiology. Because of its strong clinical, radiological and histopathological similarities with the human disease, experimental autoimmune encephalomyelitis (EAE) in the common marmoset has been studied more intensively over the past several years. Here, we review the current knowledge on MRI in the marmoset EAE, and we outline the physiopathological significance and translational values of these studies with respect to MS. Accumulating evidences suggest that the application of conventional, as well as non-conventional, MRI techniques in the marmoset EAE is a promising approach to elucidate the pathological processes underlying the development of inflammatory demyelinated lesions in the central nervous system, potentially improving the identification and development of new therapeutics.

Published
2017

25. Human Leukocyte Antigen Genotype as a Marker of Multiple Sclerosis Prognosis

Author

Thibo Billiet, Andreas Lysandropoulos, Gaetano Perrotta, Caroline Pot Kreis, Annemie Ribbens, Pietro Maggi, Marie Théaudin, Renaud Du Pasquier, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Adolescent, Genotype, Human leukocyte antigen, Fluid-attenuated inversion recovery, Verbal learning, HLA-B8 Antigen, HLA-B44 Antigen, 03 medical and health sciences, HLA-B7 Antigen, Young Adult, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, HLA-A2 Antigen, medicine, HLA-DQ beta-Chains, Humans, Aged, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Multiple sclerosis, Histocompatibility Antigens Class I, Magnetic resonance imaging, General Medicine, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Prognosis, Magnetic Resonance Imaging, 030104 developmental biology, Neurology, Disease Progression, Biomarker (medicine), Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Objective:In a previous pilot monocentric study, we investigated the relation between human leukocyte antigen (HLA) genotype and multiple sclerosis (MS) disease progression over 2 years. HLA-A*02 allele was correlated with better outcomes, whereas HLA-B*07 and HLA-B*44 were correlated with worse outcomes. The objective of this extension study was to further investigate the possible association of HLA genotype with disease status and progression in MS as measured by sensitive and complex clinical and imaging parameters.Methods:Hundred and forty-six MS patients underwent HLA typing. Over a 4-year period of follow-up, we performed three clinical and magnetic resonance imaging (MRI) assessments per patient, which respectively included Expanded Disability Status Scale, Multiple Sclerosis Severity Scale, Timed-25-Foot-Walk, 9-Hole Peg Test, Symbol Digit Modalities Test, Brief Visual Memory Test, California Verbal Learning Test-II, and whole-brain atrophy, fluid-attenuated inversion recovery (FLAIR) lesion volume change and number of new FLAIR lesions using icobrain. We then compared the clinical and MRI outcomes between predefined HLA patient groups.Results:Results of this larger study with a longer follow-up are in line with what we have previously shown. HLA-A*02 allele is associated with potentially better MS outcomes, whereas HLA-B*07, HLA-B*44, HLA-B*08, and HLA-DQB1*06 with a potential negative effect. Results for HLA-DRB1*15 are inconclusive.Conclusion:In the era of MS treatment abundance, HLA genotype might serve as an early biomarker for MS outcomes to inform individualized treatment decisions.

Published
2019

26. Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies

Author

Pietro, Maggi, Martina, Absinta, Matteo, Grammatico, Luisa, Vuolo, Giacomo, Emmi, Giovanna, Carlucci, Gregorio, Spagni, Alessandro, Barilaro, Anna Maria, Repice, Lorenzo, Emmi, Domenico, Prisco, Vittorio, Martinelli, Roberta, Scotti, Niloufar, Sadeghi, Gaetano, Perrotta, Pascal, Sati, Bernard, Dachy, Daniel S, Reich, Massimo, Filippi, Luca, Massacesi, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Maggi, Pietro, Absinta, Martina, Grammatico, Matteo, Vuolo, Luisa, Emmi, Giacomo, Carlucci, Giovanna, Spagni, Gregorio, Barilaro, Alessandro, Repice, Anna Maria, Emmi, Lorenzo, Prisco, Domenico, Martinelli, Vittorio, Scotti, Roberta, Sadeghi, Niloufar, Perrotta, Gaetano, Sati, Pascal, Dachy, Bernard, Reich, Daniel S., Filippi, Massimo, and Massacesi, Luca

Subjects
Adult, Male, Brain, Neuroimaging, Middle Aged, Aged, Brain/diagnostic imaging, Brain/pathology, Diagnosis, Differential, Female, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging/methods, Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting/pathology, Neuroimaging/methods, Vasculitis, Central Nervous System/diagnostic imaging, Vasculitis, Central Nervous System/pathology, Young Adult, Magnetic Resonance Imaging, Multiple Sclerosis, Relapsing-Remitting, Neurology, Neurologie, Neurology (clinical), Vasculitis, Central Nervous System, Research Articles, Research Article
Abstract

Objectives: In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the “central vein sign”) improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). Methods: In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing–remitting MS, 3-dimensional T2*-weighted and T2–fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. Results: MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. Interpretation: The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283–294., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

28. Myelin-specific T cells carry and release magnetite PGLA-PEG COOH nanoparticles in the mouse central nervous system

Author

Mario Milco D'Elios, Roberta Amoriello, D. Saer, Costanza Ravagli, Elena Bonechi, Clara Ballerini, Barbara Valtancoli, Laura Cappiello, Giovanni Baldi, Alessandra Flori, Luca Menichetti, Alessandra Aldinucci, Andrea Bencini, Luca Conti, Pietro Maggi, Marisa Benagiano, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
medicine.drug_class, General Chemical Engineering, Multiple sclerosis, Central nervous system, Experimental autoimmune encephalomyelitis, 02 engineering and technology, General Chemistry, 021001 nanoscience & nanotechnology, medicine.disease, Monoclonal antibody, In vitro, Cell biology, 03 medical and health sciences, chemistry.chemical_compound, Myelin, 0302 clinical medicine, medicine.anatomical_structure, chemistry, Drug delivery, medicine, Chemistry (all), Chemical Engineering (all), 0210 nano-technology, 030217 neurology & neurosurgery, Iron oxide nanoparticles
Abstract

Progress in nanotechnology has determined new strategies concerning drug delivery into the central nervous system for the treatment of degenerative and inflammatory diseases. To date, brain targeting through systemic drug administration, even in a nano-composition, is often unsuccessful. Therefore, we investigated the possibility of loading T lymphocytes with PGLA–PEG COOH magnetite nanoparticles (30 nm), which can be built up to easily bind drugs and monoclonal antibodies, and to exploit the ability of activated T cells to cross the blood–brain barrier and infiltrate the brain parenchyma. Iron oxide nanoparticles have been widely used in biomedical applications due to their theranostic properties and are therefore a well-established nanomaterial. The magnetite core is easily hybridized with polymeric compounds that may enhance the possibility of the nanoparticles entering cells with low phagocytic properties. Taking advantage of these material characteristics, after in vitro assessment of the viability and functionality of nano-loaded MOG35–55 specific T cells, we transferred cells containing the nano-cargo into naïve mice affected by experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. By means of histological and immunohistological methods, we were able to identify the nano-loaded T cells in the central nervous system. Our data demonstrated that T cells containing nanomaterials hold the possibility of carrying and releasing nanoparticles in the brain.

Published
2017

29. The formation of inflammatory demyelinated lesions in cerebral white matter

Author

Sheila Cummings Sm Macri, Luca Massacesi, Afonso C. Silva, Steven Jacobson, Susan V. Westmoreland, Tianxia T Wu, Pietro Maggi, Heather Hl Knight, Daniel S. Reich, Mary M Ellis, Emily C. Leibovitch, María I. Gaitán, and Jillian Je Wholer

Subjects
Pathology, medicine.medical_specialty, medicine.diagnostic_test, Microglia, business.industry, Multiple sclerosis, Experimental autoimmune encephalomyelitis, Magnetic resonance imaging, Vascular permeability, medicine.disease, Blood–brain barrier, Lesion, White matter, medicine.anatomical_structure, Neurology, Immunology, medicine, Neurology (clinical), medicine.symptom, business
Abstract

Objective Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. Methods By 7T magnetic resonance imaging (MRI), T1 maps, proton density, and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood–brain barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. Results On average, BBB permeability increased 3.5-fold (p

Published
2014

30. Massive subdural haematoma and dementia: a 'yin and yang' paradigm

Author

Jean Christophe Bier, Pietro Maggi, Sandra De Breucker, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Aged, 80 and over, Male, medicine.medical_specialty, business.industry, Treatment outcome, Subdural haematoma, General Medicine, medicine.disease, Decompression, Surgical, Yin and yang, Surgery, Tomography x ray computed, Hematoma, Subdural, Treatment Outcome, Pick Disease of the Brain, Medicine, Dementia, Humans, Yin-Yang, business, Tomography, X-Ray Computed
Abstract

n/a

Published
2016

31. SWI enhances vein detection using gadolinium in multiple sclerosis

Author

Matteo Grammatico, Marco Moretti, Luca Massacesi, Stefano Chiti, Lorenzo Nicola Mazzoni, Pietro Maggi, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Pathology, medicine.medical_specialty, magnetic resonance imaging (MRI), business.industry, Multiple sclerosis, Gadolinium, chemistry.chemical_element, Case Report, General Medicine, Sciences bio-médicales et agricoles, Fluid-attenuated inversion recovery, medicine.disease, White matter, Central nervous system (CNS), medicine.anatomical_structure, chemistry, inflammation, Neurologie, brain/brain stem, Parenchyma, Susceptibility weighted imaging, medicine, Vein, business
Abstract

Susceptibility weighted imaging (SWI) combined with the FLAIR sequence provides the ability to depict in vivo the perivenous location of inflammatory demyelinating lesions - one of the most specific pathologic features of multiple sclerosis (MS). In addition, in MS white matter (WM) lesions, gadolinium-based contrast media (CM) can increase vein signal loss on SWI. This report focuses on two cases of WM inflammatory lesions enhancing on SWI images after CM injection. In these lesions in fact the CM increased the contrast between the parenchyma and the central vein allowing as well, in one of the two cases, the detection of a vein not visible on the same SWI sequence acquired before CM injection., info:eu-repo/semantics/published

Published
2015

32. Nanomaterial applications in multiple sclerosis inflamed brain

Author

Pietro Maggi, Giovanni Baldi, Alessandra Aldinucci, Clara Ballerini, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Diagnostic Imaging, Multiple Sclerosis, Inflammatory response, Immunology, Pharmacology toxicology, Neuroscience (miscellaneous), Pharmacology, Nanomaterials, Drug Delivery Systems, medicine, Immunology and Allergy, Humans, Inflammation, business.industry, Multiple sclerosis, Brain, medicine.disease, Wide field, Nanostructures, Nanomedicine, Drug delivery, Translational science, business, Neuroscience
Abstract

In the last years scientific progress in nanomaterials, where size and shape make the difference, has increased their utilization in medicine with the development of a promising new translational science: nanomedicine. Due to their surface and core biophysical properties, nanomaterials hold the promise for medical applications in central nervous system (CNS) diseases: inflammatory, degenerative and tumors. The present review is focused on nanomaterials at the neuro-immune interface, evaluating two aspects: the possible CNS inflammatory response induced by nanomaterials and the developments of nanomaterials to improve treatment and diagnosis of neuroinflammatory diseases, with a focus on multiple sclerosis (MS). Indeed, nanomedicine allows projecting new ways of drug delivery and novel techniques for CNS imaging. Despite the wide field of application in neurological diseases of nanomaterials, our topic here is to review the more recent development of nanomaterials that cross blood brain barrier (BBB) and reach specific target during CNS inflammatory diseases, a crucial strategy for CNS early diagnosis and drug delivery, indeed the main challenges of nanomedicine.

Published
2014

33. Perivenular brain lesions in a primate multiple sclerosis model at 7-tesla magnetic resonance imaging

Author

Steven Jacobson, Ismael Il Calandri, Jillian E. Wohler, Pascal Sati, Luca Massacesi, Daniel S. Reich, Afonso C. Silva, Pietro Maggi, Emily C. Leibovitch, María I. Gaitán, Hellmut Merkle, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
medicine.medical_specialty, Pathology, medicine.diagnostic_test, business.industry, Multiple sclerosis, Experimental autoimmune encephalomyelitis, Clinical Neurology, Magnetic resonance imaging, medicine.disease, Lesion, White matter, medicine.anatomical_structure, Neurology, Susceptibility weighted imaging, Medicine, Histopathology, Neurology (clinical), medicine.symptom, Subarachnoid space, business
Abstract

Background Magnetic resonance imaging (MRI) can provide in vivo assessment of tissue damage, allowing evaluation of multiple sclerosis (MS) lesion evolution over time – a perspective not obtainable with postmortem histopathology. Relapsing–remitting experimental autoimmune encephalomyelitis (EAE) is an experimental model of MS that can be induced in the common marmoset, a small new world primate, and that causes perivenular white matter (WM) lesions similar to those observed in MS. Methods Brain lesion development and evolution were studied in vivo and postmortem in four marmosets with EAE through serial T2- and T2*-weighted scans at 7-tesla. Supratentorial WM lesions were identified and characterized. Results Of 97 lesions observed, 86 (88%) were clearly perivenular, and 62 (72%) developed around veins that were visible even prior to EAE induction. The perivenular configuration was confirmed by postmortem histopathology. Most affected veins, and their related perivascular Virchow-Robin spaces, passed into the subarachnoid space rather than the ventricles. Conclusion As in human MS, the intimate association between small veins and EAE lesions in the marmoset can be studied with serial in vivo MRI. This further strengthens the usefulness of this model for understanding the process of perivenular lesion development and accompanying tissue destruction in MS.

Published
2014

34. Degenerative Lumbar Instability. Stabilization and Interspinous Device Positioning

Author

Tommaso Scarabino, Michele Santoro, Pietro Maggi, Carmen Bruno, and Angela Lorusso

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Lumbar instability, medicine, Back pain, Interventional radiology, medicine.symptom, equipment and supplies, business, Low back pain, Surgery
Abstract

Patient with low back pain in vertebral instability treated by stabilization through L4–L5 screws, bars, and previously by interspinous device (X-Stop).

Published
2013

35. Pathology

Author

Saverio Pollice, Pietro Maggi, Tullia Garribba, Saverio Lorusso, and Tommaso Scarabino

Published
2013

36. Lumbar Stenosis and Degenerative Instability Posterior Rigid Stabilization

Author

Angela Lorusso, Raniero Mignini, Tommaso Scarabino, Pietro Maggi, and Carmen Bruno

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Interventional radiology, medicine.disease, Prosthesis, Surgery, Posterior stabilization, Stenosis, Lumbar stenosis, Lumbar interbody fusion, medicine, business
Abstract

Patient with low-back pain in stenosis and vertebral in stability treated by rigid posterior stabilization and intervertebral prosthesis posteriorly placed with trans-foraminal approach (Transforaminal Lumbar Interbody Fusion Surgery, TLIF).

Published
2013

37. Cervical Traumatic Fracture Vertebral Removal

Author

Francesco Paradiso, Michele Santoro, Pietro Maggi, Angela Lorusso, and Tommaso Scarabino

Subjects
Traumatic fracture, medicine.medical_specialty, medicine.diagnostic_test, business.industry, mental disorders, medicine, Interventional radiology, business, psychological phenomena and processes, Surgery
Abstract

Patient with C5 traumatic fracture treated by drawing and cage positioning (fixed to C4–C6).

Published
2013

38. Spontaneous rupture of urinary bladder: a case report and review

Author

Giuseppe, Albino, Francesco, Bilardi, Domenico, Gattulli, Pietro, Maggi, Antonio, Corvasce, and Ettore Cirillo, Marucco

Subjects
Male, Rupture, Spontaneous, Urinary Bladder Diseases, Humans, Aged
Abstract

Spontaneous rupture of the bladder is a rare event. The clinical presentation shows the signs and symptoms of peritonitis, but the diagnosis is made at the operating table. This event is burdened with a high mortality rate. We present a case report of a 73-year-old man who came to our observation. He was a chronic carrier of urinary catheter, at least 7 times removed traumatically by himself. At the time of admission he showed drastic reduction in urine output, absence of hydronephrosis, normal functioning of the catheter, a tense and widely meteoric abdomen, the presence of air-fluid levels, normal kidneys, absence of free fluid in the abdomen. The CT showed a fluid collection of about 7 cm diameter between the bladder and rectum. The explorative laparotomy found a small fissuration of the posterior wall of the bladder. For his severe conditions, the patient died a few hours after surgery, in intensive care unit. Although it is a rare event, since 1980, 177 cases of spontaneous rupture of the bladder are reported in the literature. Their causes may be essentially divided into two groups: for increase of intravesical pressure; or for weakening of the bladder wall. In most cases, the spontaneous rupture of the bladder takes place in presence of a urothelial neoplasm or after radiation therapy of the pelvic organs. The etiology of spontaneous rupture of the bladder in our case does not relate to a bladder tumor or radiotherapy. It may have been caused by repeated episodes of acute retention of urine with extreme bladder distension up to 3 liters. It is not easy to think of a bladder perforation in patients presenting signs of peritonitis without a history of bladder cancer or pelvic radiotherapy. A CT with intravesical contrast medium could help the diagnostic orientation.

Published
2013

39. Seven-tesla phase imaging of acute multiple sclerosis lesions: A new window into the inflammatory process : MS Lesions at 7T Phase Imaging

Author

Pascal Sati, Irene Cortese, María I. Gaitán, Massimo Filippi, Daniel S. Reich, Martina Absinta, Pietro Maggi, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Multiple sclerosis, Magnetic resonance imaging, Lesion types, medicine.disease, Phase image, Neurology, In vivo, Phase imaging, medicine, Neurology (clinical), business, Pathological, Process (anatomy)
Abstract

Objective In multiple sclerosis (MS), accurate, in vivo characterization of dynamic inflammatory pathological changes occurring in newly forming lesions could have major implications for understanding disease pathogenesis and mechanisms of tissue destruction. Here, we investigated the potential of ultrahigh-field magnetic resonance imaging (MRI; 7T), particularly phase imaging combined with dynamic contrast enhancement, to provide new insights in acute MS lesions. Methods Sixteen active MS patients were studied at 7T. Noncontrast, high-resolution T2* magnitude and phase scans, T1 scans before/after gadolinium contrast injection, and dynamic contrast-enhanced (DCE) T1 scans were acquired. T2*/phase features and DCE pattern were determined for acute and chronic lesions. When possible, 1-year follow-up 7T MRI was performed. Results Of 49 contrast-enhancing lesions, 44 could be analyzed. Centrifugal DCE lesions appeared isointense or hypointense on phase images, whereas centripetal DCE lesions showed thin, hypointense phase rims that clearly colocalized with the initial site of contrast enhancement. This pattern generally disappeared once enhancement resolved. Conversely, in 43 chronic lesions also selected for the presence of hypointense phase rims, the findings were stable over time, and the rims were typically thicker and darker. These considerations suggest different underlying pathological processes in the 2 lesion types. Interpretation Ultrahigh-field MRI and, especially, phase contrast, are highly sensitive to tissue changes in acute MS lesions, which differ from the patterns seen in chronic lesions. In acute lesions, the hypointense phase rim reflects the expanding inflammatory edge and may directly correspond to inflammatory byproducts and sequelae of blood–brain barrier opening. Ann Neurol 2013;74:669–678

Published
2013

40. 'And if a one night a renal colic...' the strange case of renal vein thrombosis without renal cancer

Author

Giuseppe, Albino, Ettore Cirillo, Marucco, and Pietro, Maggi

Subjects
Diagnosis, Differential, Male, Humans, Thrombosis, Renal Colic, Renal Veins, Aged
Abstract

It is common experience to all urologists to manage many patients admitted at night from the casualty ward with a diagnosis of "therapy-resistant renal colic". However not all the patients with flank pain really suffer for renal colic, although painful somatic irradiation refers to the same areas.A seventy years old male patient was admitted from the casualty ward for left renal colic. Laboratory tests showed normal creatinine, mild reduction of albuminemia, elevated triglycerides and cholesterol at the upper limit of normal. The pain had risen sharply a few hours before. For some years the patient suffered nocturia, but he never made an urologic consultation. Ultrasonography performed in the casualty ward demonstrated normal findings with no hydronephrosis but the presence of left perirenal extravasation with "casting-like" aspect and extending to the pelvis. Contrast-enhanced computed tomography (CT) revealed the presence of left renal vein thrombosis and acute segmental pulmonary embolism. The left kidney, apart from increased volume and reduced parenchymal impregnation, showed no neoplastic nodule. The case presented as unusual according to the opinion of consulted nephrologists, vascular surgeons and urologists (also from others hospitals and universities). After informed consent of the patient (stressing seriousness and singularity of his condition), we decided to treat him as a deep vein thrombosis. We administered an heparin bolus (80UI/kg), followed by the infusion of heparin (18UI/kg/h) using a peristaltic pump for 14 days.CT performed after 14 days of treatment showed the full resolution of renal vein thrombus and of pulmonary embolism. Thereafter a nephrotic syndrome was diagnosed and the patient was took in care by the nephrologist. Nephrotic syndrome preceded the hospital admission of the patient and was the etiological cause of renal vein thrombosis.The well known causes of acute flank pain reported in textbooks include renal and perirenal inflammatory processes, renal cell or transitional cell cancers of the kidney or of the urinary tract, obstruction of the urinary tract by stones or stenosis, hydronephrosis of different etiology whereas vascular causes are not often mentioned.After the diagnosis of left renal vein thrombosis, the more probable associated urological is a renal cell carcinoma. Excluding renal cancer other possible causes of thrombosis are medical conditions such as amyloidosis, multiple myeloma, nephrotic syndrome, thrombophlebitis.

Published
2011

41. Teleradiologia

Author

Tommaso Scarabino, Pietro Maggi, Tullia Garribba, and Alberto Maggialetti

Published
2010

44. Novel Marmoset (Callithrix jacchus) Model of Human Herpesvirus 6A and 6B Infections: Immunologic, Virologic and Radiologic Characterization

Author

Sheila Cummings Sm Macri, Jillian J Wohler, Pietro Maggi, Erin E Harberts, Mary M Ellis, Kelsey K Motanic, Steven Jacobson, María I. Gaitán, Emily C. Leibovitch, Daniel S. Reich, Afonso C. Silva, Susan V. Westmoreland, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Brain -- pathology -- virology, Herpesvirus 6, Human, viruses, lcsh:QH301-705.5, Immune Response, biology, Viral Immune Evasion, Spinal Cord -- pathology -- virology, Brain, virus diseases, Marmoset, Callithrix, Animal Models, Sciences bio-médicales et agricoles, Magnetic Resonance Imaging, DNA, Viral -- analysis, Viral Persistence and Latency, Spinal Cord, Roseolovirus Infections, Injections, Intravenous, Human herpesvirus 6, medicine.symptom, Research Article, lcsh:Immunologic diseases. Allergy, Neurovirulence, Immunology, Neuroimaging, Nervous System Diseases -- diagnosis -- immunology -- virology, Microbiology, Asymptomatic, Virus, Herpesvirus 6, Human -- pathogenicity -- physiology, Roseolovirus Infections -- diagnosis -- immunology -- virology, Model Organisms, Immune system, Callithrix -- physiology, Virology, biology.animal, Genetics, medicine, Animals, Humans, Biology, Molecular Biology, Administration, Intranasal, Multiple sclerosis, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, medicine.disease, Animal Models of Infection, Viral Disease Diagnosis, Disease Models, Animal, lcsh:Biology (General), DNA, Viral, Parasitology, Nervous System Diseases, lcsh:RC581-607, Viral Transmission and Infection, Neuroscience
Abstract

Human Herpesvirus 6 (HHV-6) is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. HHV-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the CNS. Animal models of HHV-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack CD46, the receptor for cellular entry. Therefore, we investigated the effects of HHV-6 infections in a non-human primate, the common marmoset Callithrix jacchus. We inoculated a total of 12 marmosets with HHV-6A and HHV-6B intravenously and HHV-6A intranasally. Animals were monitored for 25 weeks post-inoculation clinically, immunologically and by MRI. Marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms and generated virus-specific antibody responses, while those inoculated intravenously with HHV-6B were asymptomatic and generated comparatively lower antibody responses. Viral DNA was detected at a low frequency in paraffin-embedded CNS tissue of a subset of marmosets inoculated with HHV-6A and HHV-6B intravenously. When different routes of HHV-6A inoculation were compared, intravenous inoculation resulted in virus-specific antibody responses and infrequent detection of viral DNA in the periphery, while intranasal inoculation resulted in negligible virus-specific antibody responses and frequent detection of viral DNA in the periphery. Moreover, marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms, while marmosets inoculated with HHV-6A intranasally were asymptomatic. We demonstrate that a marmoset model of HHV-6 infection can serve to further define the contribution of this ubiquitous virus to human neurologic disorders., info:eu-repo/semantics/published

Published
2013

45. Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation In Autologous Hematopoietic Stem Cell Transplantation (HSCT) for Severe Multiple Sclerosis (MS)

Author

Massimo Di Gioia, Pietro Maggi, Luca Massacesi, Maria Pia Amato, Filippo Fani, Alberto Bosi, Elisabetta Andreoli, Chiara Nozzoli, Stefano Guidi, Antonella Gozzini, Riccardo Saccardi, and A. Repice

Subjects
Ganciclovir, Foscarnet, Cyclophosphamide, business.industry, medicine.medical_treatment, Immunology, Immunosuppression, Cell Biology, Hematology, Hematopoietic stem cell transplantation, Biochemistry, Transplantation, Medicine, Rituximab, business, Viral load, medicine.drug
Abstract

Abstract 4537 INTRODUCTION. Autologous HSCT is currently under investigation for the treatment of refractory, progressive MS. A better selection of patients and the use of less aggressive regimens resulted in a significant drop of Transplant-related Mortality (TRM), which is mostly related to immunosuppression. CMV and EBV tend to reactivate in ATG-treated allogeneic HSCT. We investigated the frequency of CMV/EBV viral load in a consecutive cohort of MS patients who underwent HSCT in our Center following BEAM and Anti-T Lymphocyte Globulin (ATG) conditioning regimen. PATIENTS AND METHODS. Thirty-one patients underwent auto-HSCT for severe MS in our Institution from 1999 to 2010. All patients were mobilized by Cyclophosphamide 4 g/sqm + G-CSF and conditioned with BEAM plus rabbit ATG (Thymoglobulin©) at a dose ranging between 7.5 and 10 mg/Kg. Monitoring of CMV/EBV DNA by quantitative PCR on either circulating Mononuclear Cells (MNC) or Whole Blood (WB) was performed in 29 pts. In 18 patients ≥2 tests were available for both CMV and EBV from +20 and +120 days. In 2006, following a case of severe CMV infection, a specific protocol was developed, aimed at monitoring on a weekly basis the viral load in case reactivation until complete negativisation. Pre-emptive treatment was administered in case of viral DNA load >1×103 copies/105MNC or >1×1044 copies/ml WB in two subsequent determinations. RESULTS. Overall 84 and 95 tests were carried out for CMV and EBV, respectively. 10/29 patients (34.5%) were shown positive for CMV at a median of 33,5 days from HSCT (28-47), whereas 11/29 patients (37.9%) were positive for EBV at a median of 29 days from HSCT (20-109). Five patients resulted positive for both viruses. According to the ongoing protocols, 20% of CMV+ patients and 18% of EBV+ patients received a pre-emptive treatment with a fast drop of viral load. In the other patients the reactivation was self-limiting in 2–3 weeks from the first positive determination. One patient developed a severe CMV infection at + 47 days successfully treated the iv administration of Gancyclovir and Foscarnet. One EBV+ patient developed fever which responded promptly after treatment with rituximab. Moreover, in 16/29 patients a sporadic assessment of CMV/EBV was performed at early (between +5 and + 20) and late phases (beyond 120 days) without any evidence of viral reactivation. CONCLUSIONS. Autologous HSCT with BEAM/ATG can be safely performed in MS patients. A significant reactivation of both CMV and EBV can occur in the 3 months following HSCT, possibly related to the ATG administration. Monitoring of viral load and, whenever necessary, pre-emptive anti-viral treatment should be performed in order to improve safety of HSCT in this subset of non-neoplastic patients. Disclosures: No relevant conflicts of interest to declare.

Published
2010

46. Autologous HSCT Induce a Sustained Inhibition of New MRI Lesions in Severe Refractory Multiple Sclerosis. Long Term Results of a Prospective Multicenter Trial

Author

Alberto Bosi, Paolo Bartolomeo, Amedea Donelli, Pietro Maggi, Riccardo Saccardi, Massimo Filippi, Maria Pia Sormani, Federico Papineschi, Alberto M. Marmont, Maria A. Rocca, Luisa Vuolo, Angelo Guerrasio, Giorgio La Nasa, Massimo Di Gioia, Gianluigi Mancardi, and Francesca Gualandi

Subjects
Cerebral atrophy, medicine.medical_specialty, business.industry, Multiple sclerosis, Immunology, Cell Biology, Hematology, Filgrastim, medicine.disease, Biochemistry, Surgery, Transplantation, Atrophy, Median follow-up, Multicenter trial, Medicine, business, Prospective cohort study, medicine.drug
Abstract

Abstract 1221 Poster Board I-243 Introduction A subset of Multiple Sclerosis (MS) patients shows a clinical trend to a fast deterioration of disability despite the use of approved drugs. New immunosuppressive agents are currently employed only in the early phase of the disease but in almost 10% of patients they either do not show any clinical/ radiological improvement or have to be halted for different reasons. Autologous HSCT has been reported as a promising approach for MS patients unresponsive to the available therapies but long term clinical and laboratory follow-up with a stringent MRI monitoring are not yet available. We report here the long term follow-up of a prospective phase II multicenter trial of the Italian GITMO-Neuro cooperative network. Method 21 MS patients (4 Relapsing Remitting and 17 Secondary Progressive) were enrolled between 1999 and 2004 in a prospective trial, aimed to monitor both clinical outcome and MRI imaging. Patients were shown to be refractory to conventional treatments, had a EDSS between 5.0 and 6.5 and at least 1 Gadolinium (Gd) enhancing area in brain MRI. PBSC were mobilized with Cyclophosphamide (4g/m2 ) and Filgrastim; patients were conditioned with BEAM plus rabbit ATG (Thymoglobulin®, Genzyme) and infused with unmanipulated graft. The effect of HSCT was evaluated with serial monthly Gd-enhanced brain MRI for a pretreatment period of 3 months and compared with serial monthly Gd-enhanced MRI imaging for the following 6 months. Subsequently, MRI scans were carried out at, +9, +12, +18 + 24 and at the last follow-up. Clinical outcome was evaluated by both EDSS assessment and number of clinical relapses after the transplant. The same MRI scanning protocol was used at each neuroradiological examination: T1 and T2 total lesion load, new T2 lesions, new hypointense lesions, Gd enhancing activity and progression of brain atrophy were evaluated. Results All patients showed a sustained engraftment with modest early side effects, as previously reported (Saccardi R. et al. Blood 2005 105:2601-07). At a median follow up of 7 years (range 4-10 years) no late effects were reported. Two patients had a clinical relapse 5 years after the HSCT, spontaneously recovered. Nine patients showed a clinical progression at a median of 30 months (16 – 66) after transplant, while the others are either stable (7) or improved (5), as compared with baseline. No patients received any immunosuppressive treatment after HSCT. At MRI examination total lesion load assessed by T2 and T1 sequences remained stable through the follow-up, and only 5 new T2 lesions appeared after HSCT. No Gd enhancing activity was ever observed after transplantation in the examined cases. Brain atrophy progression was higher in the first 2 years after transplantation and then decreased significantly in the following years Conclusions The clinical and MRI results of this prospective study are extremely positive, considering that the majority of cases remained stable at a median of 7 years after transplantation. MRI activity, as evaluated with Gd enhancing areas and the appearance of new lesions, was absent or negligible. Also brain atrophy, rapidly progressing early after the transplant probably due to the suppression of the inflammation, was thereafter shown to be in the range of MS patients. The duration of the follow-up and the stringent MRI methodology provide an evidence of the efficacy of this procedure in this subset of aggressive MS patients. Disclosures No relevant conflicts of interest to declare.

Published
2009

47. First evidence for off-shell production of the Higgs boson and measurement of its width

Author

Tumasyan, Armen, Wolfgang Adam, Andrejkovic, Janik Walter, Thomas Bergauer, Suman Chatterjee, Damanakis, Konstantinos, Marko Dragicevic, Alberto Escalante del Valle, Fruehwirth, Rudolf, Manfred Jeitler, Krammer, Natascha, Lukas Lechner, Liko, Dietrich, Mikulec, Ivan, Paulitsch, Peter, Pitters, Florian Michael, Jochen Schieck, Schoefbeck Robert, Schwarz, Dennis, Sebastian Templ, Wolfgang Waltenberger, Claudia-Elisabeth Wulz, Chekhovsky, Vladimir, Litomin, Aliaksandr, Vladimir Makarenko, Darwish, Mohamed Rashad, Wolf, Eddi A., Tahys Janssen, Kello, Tomas, Aleksandra Lelek, Rejeb Sfar, Haifa, Pierre Van Mechelen, Putte, Senne, Nick van Remortel, Emil Sørensen Bols, Hondt, Jorgen D., Moor, Alexandre, Delcourt, Martin, Hesham El Faham, Steven Lowette, Seth Moortgat, Alexander Morton, Denise Müller, Abanti Ranadhir Sahasransu, Stefaan Tavernier, Doninck, Walter, David Vannerom, Beghin, Diego, Bugra Bilin, Barbara Clerbaux, Lentdecker, Gilles, Laurent Favart, Amandeep Kaur Kalsi, Lee, Kyeongpil, Mahdavikhorrami, Mostafa, Inna Makarenko, Santiago Paredes Saenz, Pétré, Laurent, Andrey Popov, Postiau, Nicolas, Elizabeth Rose Starling, Laurent Thomas, Vanden Bemden, Max, Catherine Vander Velde, Pascal Vanlaer, Tom Cornelis, Dobur, Didar, Joscha Knolle, Lambrecht, Luka, Mestdach, Gianny, Marek Niedziela, Rendón, César, Roskas, Christos, Samalan, Amrutha, Kirill Skovpen, Michael Tytgat, Den Bossche, Niels, Vermassen, Basile, Wezenbeek, Liam, Benecke, Anna, Agni Bethani, Bruno, Giacomo, Florian Bury, Claudio Caputo, Pieter David, Christophe Delaere, Izzeddin Suat Donertas, Andrea Giammanco, Jaffel, Khawla, Sandhya Jain, Lemaitre, Vincent, Kuntal Mondal, Prisciandaro, Jessica, Taliercio, Angela, Maksym Teklishyn, Tran, Tu Thong, Pietro Vischia, Sébastien Wertz, Gilvan Alves, Hensel, Carsten, Arthur Moraes, Rebello Teles, P., Walter Luiz Aldá Júnior, Miguel Pereira, Barroso Ferreira Filho, Mapse, Brandao Malbouisson, Helena, Wagner de Paula Carvalho, Chinellato, Jose, Eliza Melo da Costa, Da Silveira, G. G., Dilson De Jesus Damiao, Dos Santos Sousa, Vitor, Fonseca de Souza Sandro, Maria Clemencia Mora Herrera, Mota Amarilo, Kevin, Mundim, L., Nogima, Helio, Santoro, Alberto, Sheila Silva do Amaral, Andre Sznajder, Thiel, Mauricio, Felipe Araujo, Antonio Vilela Pereira, Cesar Augusto Bernardes, Luigi Calligaris, Thiago Rafael Fernandez Perez Tomei, Eduardo de Moraes Gregores, Dener de Souza Lemos, Pedro Galli Mercadante, Sergio Novaes, Padula, Sandra S., Aleksandrov, Aleksandar, Gueorgui Antchev, Hadjiiska, Roumyana, Iaydjiev, Plamen, Misheva, Milena, Rodozov, Mircho, Shopova, Mariana, Sultanov, Georgi, Dimitrov, Anton, Ivanov, Todor, Leandar Litov, Pavlov, Borislav, Petkov, Peicho, Petrov, Anton, Tongguang Cheng, Javaid, Tahir, Mittal, Monika, Wang, Hanwen, Yuan, Li, Muhammad Ahmad, Bauer, Gerry, Candan Dozen, Zhen Hu, Jordan Martins, Wang, Yi, Yi, Kai, Émilien Chapon, Guoming Chen, Hesheng Chen, Mingshui Chen, Iemmi, Fabio, ANSHUL KAPOOR, Leggat, Duncan, Liao, Hongbo, Zhenan Liu, Vukasin Milosevic, fabio monti, Ram Krishna Sharma, Junquan Tao, Thomas-Wilsker, Joshuha, Jin Wang, Huaqiao Zhang, Jingzhou Zhao, Agapitos, Antonis, An, Ying, Ban, Yong, Chen, Cheng, Andrew Levin, Qiang Li, Lyu, Xudong, Mao, Yajun, Qian, Si-Jin, Dayong Wang, Xiao, Jie, Yang, Heng, Lu, Meng, Zhengyun You, Gao, Xuyang, Hideki Okawa, Yu Zhang, Meng Xiao, Carlos Arturo Ávila Bernal, Andres Leonardo Cabrera Mora, Carlos Andrés Flórez, Fraga, Jorge, Mejia Guisao, Jhovanny, Ramirez, Felipe, Jose Ruiz, Giljanovic, Duje, Nikola Godinovic, Damir Lelas, Ivica Puljak, Antunovic, Zeljko, Kovac, Marko, Toni Sculac, Vuko Brigljević, Dinko Ferencek, Devdatta Majumder, Roguljic, Matej, Andrey Starodumov, Tatjana Susa, Alexandros Attikis, Christoforou, Konstantinos, Gouranga Kole, Kolosova, Marina, Konstantinou, Sotiroulla, Jehad.Mousa, Nicolaou, Charalambos, Fotios Ptochos, Razis, Panos A., Rykaczewski, Hans, Halil Saka, Finger, Miroslav, michael finger, Kveton, Antonin, Ayala, Edy, Carrera Jarrin, E., Hassan Abdalla, Salama, Elsayed, Mohammed Attia Mahmoud, yasser mohammed, Sandeep Bhowmik, Ram Krishna Dewanjee, Ehataht, Karl, Kadastik, Mario, Nandan, Saswati, Nielsen, Christine, Pata, Joosep, Martti Raidal, Tani, Laurits, Veelken, Christian, Paula Anna-Maria Eerola, Henning Kirschenmann, Kenneth Mikael Österberg, Mikko Voutilainen, Bharthuar, Shudhashil, Jens Erik Brucken, Francisco Ignacio Garcia Fuentes, Joona Havukainen, Min Suk Kim, Kinnunen, Ritva, Lampén, Tapio, Kati Lassila-Perini, Sami Lehti, Lindén, Tomas, Lotti, Mikko, Martikainen, Laura, Myllymäki, Mikael, Jennifer Ott, Rantanen, Milla-Maarit, Siikonen, Hannu, Eija Maarit Tuominen, Tuominiemi, Jorma, Panja Luukka, Petrow, Henri, Tuuva, Tuure, Chiara Amendola, Besancon, Marc, Fabrice Couderc, Dejardin, Marc, Denegri, Daniel, Faure, Jean-Louis, Federico Ferri, Ganjour, Serguei, Gras, Philippe, Gautier Hamel de Monchenault, Jarry, Patrick, Bruno Lenzi, Malcles, Julie, Rander, John, André Rosowsky, Mehmet Özgür Sahin, Savoy-Navarro, Aurore, Simkina, Polina, Maxim Titov, Geum Bong Yu, Sudha Ahuja, Florian Beaudette, Matteo Bonanomi, Buchot Perraguin, Axel, Busson, Philippe, Cappati, Alessandra, Charlot, Claude, Davignon, Olivier, Diab, Batoul, Guillaume Falmagne, Fontana Santos Alves, Bruno Afonso, Ghosh, Shamik, Raphael Granier de Cassagnac, Hakimi, Alexandre, Inna Kucher, Motta, Jona, Matthew Nguyen, Christophe Ochando, Pascal Paganini, Rembser, Jonas, Roberto Salerno, UTTIYA SARKAR, Jean-Baptiste Sauvan, Yves Sirois, Tarabini, Alessandro, Zabi, Alexandre, Amina Zghiche, Agram, Jean-Laurent, Andrea, Jeremy, Apparu, Dylan, Daniel Bloch, Bourgatte, Guillaume, Brom, Jean-Marie, Chabert, Eric Christian, Caroline Collard, Darej, Douja, Fontaine, Jean-Charles, Goerlach, Ulrich, Grimault, Clément, Le Bihan, Anne-Catherine, Emery Nibigira, Pierre Van Hove, Asilar, Ece, Stephanie Beauceron, Colin Bernet, Boudoul, Gaelle, Camen, Camille, Carle, Aurélien, Nicolas Chanon, Contardo, Didier, Pierre Depasse, El Mamouni, Houmani, Fay, Jean, Susan Gascon-Shotkin, Maxime Gouzevitch, Ille, Bernard, Laktineh, Imad Baptiste, Hugues Lattaud, Antoine Lesauvage, Morgan Lethuillier, Mirabito, Laurent, Perries, Stephane, Shchablo, Konstantin, Viola Sordini, Touquet, Gaël, Vander Donckt, Muriel, Viret, Sébastien, Lomidze, Irakli, Toriashvili, Tengizi, Tsamalaidze, Zviad, Botta, Valeria, Lutz Feld, Klein, Katja, Lipinski, Martin, Meuser, Danilo, Pauls, Alexander, Röwert, Nicolas, Schulz, Johannes, Marius Teroerde, Dodonova, Alena, Eliseev, Dmitry, Martin Erdmann, Peter Fackeldey, Fischer, Benjamin, Thomas Hebbeker, Hoepfner, Kerstin, Ivone, Francesco, Mastrolorenzo, Luca, Markus Merschmeyer, Arnd Meyer, Mocellin, Giovanni, Mondal, Spandan, Swagata Mukherjee, Dennis Noll, Novak, Andrzej, Andrey Pozdnyakov, Rath, Yannik, Reithler, Hans, Alexander Schmidt, Schuler, Simon Christoph, Archana Sharma, Vigilante, Lorenzo, Wiedenbeck, Sebastian, Zaleski, Shawn, Dziwok, Christian, Flügge, Günter, Wael Haj Ahmad, Hlushchenko, Olena, Kress, Thomas, Andreas Nowack, Pooth, Oliver, Dennis Roy, Achim Stahl, Tim Ziemons, Zotz, Alexander, Aarup Petersen, Henriette, Aldaya Martin, Maria, Asmuss, Paul, Baxter, Samuel, Bayatmakou, Maryam, Behnke, Olaf, Bermúdez Martínez, Armando, Bhattacharya, Soham, Afiq Anuar, Freya Blekman, Borras, Kerstin, Brunner, David, Alan Campbell, Andrea Cardini, Cheng, Chun, Colombina, Federica, Sandra Consuegra Rodriguez, Correia Silva, Gilson, Silva, Malinda, Didukh, Leonid, Eckerlin, Guenter, Eckstein, Doris, Luis Ignacio Estevez Banos, Oleg Filatov, Gallo, Elisabetta, Geiser, Achim, Giraldi, Angela, Greau, Guillaume, Alexander Grohsjean, Guthoff, Moritz, Abideh Jafari, Nur Zulaiha Jomhari, Hannes Jung, Ashraf Mohamed, Matthias Kasemann, hessamoddin kaveh, Claus Kleinwort, Roman Kogler, Dirk Krücker, Lange, Wolfgang, Lipka, Katerina, Lohmann, Wolfgang, Mankel, Rainer, Isabell-Alissandra Melzer-Pellmann, Mendizabal Morentin, Mikel, Metwally, Josry, Meyer, Andreas B., Mareike Meyer, Joachim Mnich, Mussgiller, Andreas, Nürnberg, Andreas, Otarid, Younes, Danyer Pérez Adán, Pitzl, Daniel, Raspereza, Alexei, Ribeiro Lopes, Beatriz, Rübenach, Jonas, Alessia Saggio, Andrej Saibel, Mykola Savitskyi, Scham, Moritz, Scheurer, Valerie, Schnake, Simon, Schütze, Paul, Christian Schwanenberger, Shchedrolosiev, Mykyta, Rafael Eduardo Sosa Ricardo, Stafford, Dominic, Nicolas Tonon, Merijn van de Klundert, Federico Vazzoler, Roberval Walsh, Walter, David, Qun Wang, Yiwen Wen, Wichmann, Katarzyna, Wiens, Lucas, Wissing, Christoph, Sebastian Wuchterl, Aggleton, Robin, Steffen Albrecht, Samuel Bein, Lisa Benato, Patrick Connor, Ksenia de Leo, Eich, Melanie, El Morabit, Karim, Feindt, Finn, Fröhlich, Alexander, Christoph Garbers, Erika Garutti, Gunnellini, Paolo, Hajheidari, Mohammadtaghi, Johannes Haller, Andreas Hinzmann, Kasieczka, Gregor, Robert Klanner, Kramer, Tobias, Kutzner, Viktor, Johannes Lange, Torben Lange, Artur Lobanov, Andrea Malara, Matthies, Christopher, ANKITA MEHTA, Louis Moureaux, Nigamova, Aliya, Pena Rodriguez, Karla Josefina, Marcel Rieger, Rieger, Oliver, Schleper, Peter, Matthias Schröder, Joern Schwandt, Jory, Stadie, Hartmut, Steinbrück, Georg, Tews, Alexandra, Irene Zoi, Janek Bechtel, Brommer, Sebastian, Burkart, Maximilian, Erik Butz, Rene Caspart, Chwalek, Thorsten, Boer, Wim, Dierlamm, Alexander, Droll, Alexander, Nils Faltermann, Giffels, Manuel, Gosewisch, Jan-Ole, Gottmann, Artur, Frank Hartmann, Heidecker, Christoph, Ulrich Husemann, Keicher, Philip, Koppenhöfer, Roland, Maier, Stefan, Soureek Mitra, Müller, Thomas, Neukum, Max, Günter Quast, Klaus Rabbertz, Rauser, Johann, Daniel Savoiu, Schnepf, Matthias, Seith, David, Shvetsov, Ivan, Simonis, Hans-Jürgen, Ralf Ulrich, Linden, Jan, Cube, Ralf Florian, Wassmer, Michael, Marc Weber, Wieland, Sebastian, Roger Wolf, Wozniewski, Sebastian, Wunsch, Stefan, Anagnostou, Georgios, Daskalakis, Georgios, Kyriakis, Aristotelis, Loukas, Demetrios, Anna Stakia, Diamantopoulou, Magda, Karasavvas, Dimitrios, Pantelis Kontaxakis, Koraka, Charis Kleio, Manousakis-Katsikakis, Arkadios, Panagiotou, Apostolos, Papavergou, Ioanna, Niki Saoulidou, Konstantinos Theofilatos, Eirini Tziaferi, Vellidis, Konstantinos, Vourliotis, Emmanouil, Bakas, Georgios, Konstantinos Kousouris, Papakrivopoulos, Ioannis, Tsipolitis, Georgios, Zacharopoulou, Anna, Adamidis, Kosmas, Bestintzanos, Ioannis, Ioannis Evangelou, Foudas, Costas, Gianneios, Paraskevas, Katsoulis, Panagiotis, Kokkas, Panagiotis, Manthos, Nikolaos, Ioannis Papadopoulos, John Strologas, Mate Csanad, Farkas, Krisztián, Mahmoud Moussa Abdelkhalek Gadallah, Sandor Lokos, Major, Péter, Koushik Mandal, Gabriella Pásztor, Rádl, Attila József, Surányi, Olivér, Gabor Veres, Márton Bartók, Bencze, Gyorgy, Csaba Hajdu, Dezso Horvath, Ferenc Siklér, Viktor Veszprémi, Czellar, Sandor, Daniele Fasanella, Francesco Fienga, János Karancsi, Molnar, Jozsef, Szillasi, Zoltan, Teyssier, Daniel, Raics, Peter, Zoltan Trocsanyi, Ujvari, Balazs, Tamas Csorgo, Nemes, Frigyes, Novak, Tamas, Seema Bahinipati, Chandiprasad Kar, Mal, Prolay, Tribeni Mishra, Muraleedharan Nair Bindhu, Vinaya Krishnan, Aruna Kumar Nayak, Saha, Prafulla, Nairit Sur, Swain, Sanjay Kumar, Vats, Diwakar, Sunil Bansal, Beri, Suman Bala, Vipin Bhatnagar, Geetanjali Chaudhary, SUSHIL SINGH CHAUHAN, Nitish Dhingra, Gupta, Rajat, Kaur, Amandeep, Kaur, Harjot, Kaur, M., Priyanka Kumari, Meena, Meena, Kaur Sandeep, Singh, J. B., Amandeep Kaur, Ahmed, Asar, Ashutosh Bhardwaj, brajesh choudhary, Gola, Mohit, Sumit Keshri, Ashok Kumar, Md Naimuddin, Priyanka, Ranjan, Kirti, Saumya, Saumya, Aashaq Shah, Bharti, Monika, Bhattacharya, Rajarshi, satyaki bhattacharya, Bhowmik, Debabrata, Dutta, Shubham, Dutta, Suchandra, bhawna gomber, Maity, Manas, Pritam Palit, PRASANT KUMAR ROUT, Saha, Gourab, Bisnupriya Sahu, Sarkar, Subir, Sharan, Manoj, Prafulla Kumar Behera, Behera, Subash Chandra, Pritam Kalbhor, Jyothsna Rani Komaragiri, Kumar, Deepak, Muhammad, Alibordi, Lata Panwar, Pradhan, Raghunath, Pujahari, Prabhat Ranjan, ashish sharma, Sikdar, Anup Kumar, Praveen Chandra Tiwari, Naskar, Kousik, Aziz, Tariq, Dugad, Shashikant, Kumar, Mintu, Mohanty, Gagan B., sudeshna banerjee, Chudasama, Ruchi, Guchait, Monoranjan, Karmakar, Saikat, Kumar, Sanjeev, Majumder, Gobinda, Mazumdar, Kajari, Soumya Mukherjee, Alpana, Alpana, Sourabh Dube, Kansal, Bhumika, Laha, Arnab, Shubham Pandey, Angira Rastogi, Seema Sharma, Bakhshiansohi, Hamed, Khazaie, Elham, Zeinali, Maryam, Chenarani, Shirin, seyed Mohsen Etesami, Mohsen Khakzad, Mojtaba Mohammadi Najafabadi, Martin Grunewald, Marcello Abbrescia, Reham Aly, Aruta, Caterina, Anna Colaleo, Donato Maria Creanza, Nicola De Filippis, Mauro De Palma, Di Florio, Adriano, Di Pilato, Antonio, Walaa Elmetenawee, Filippo Errico, Luigi Fiore, giuseppe Iaselli, Merve Ince Lezki, Samet Lezki, Giorgio Pietro Maggi, Marcello Maggi, Margjeka, Ilirjan, Vincenzo Mastrapasqua, Salvatore My, Salvatore Nuzzo, Pellecchia, Antonello, Pompili, Alexis, Gabriella Pugliese, Ramos, Dayron, Antonio Ranieri, Giovanna Selvaggi, Silvestris, L., Federica Maria Simone, Sözbilir, Ümit, Rosamaria Venditti, Piet Verwilligen, Giovanni Abbiendi, Carlo Battilana, Daniele Bonacorsi, Borgonovi, Lisa, Brigliadori, Luca, Renato Campanini, Paolo Capiluppi, Andrea Castro, Francesca Romana Cavallo, Claudia Ciocca, Cuffiani, Marco, Gaetano Marco Dallavalle, Tommaso Diotalevi, Fabrizio Fabbri, Alessandra Fanfani, Paolo Giacomelli, Luca Giommi, Claudio Grandi, Guiducci, Luigi, Lo Meo, Sergio, Lunerti, Leonardo, Stefano Marcellini, Gianni Masetti, Francesco Luigi Navarria, Andrea Perrotta, Federica Primavera, Antonio Maria Rossi, Tiziano Rovelli, Gian Piero Siroli, Sebastiano Albergo, Salvatore Costa, Alessandro Di Mattia, Potenza, Renato, Alessia Rita Tricomi, Tuve, Cristina, Giuseppe Barbagli, Antonio Cassese, Ceccarelli, Rudy, Vitaliano Ciulli, Carlo Civinini, Alessandro, Raffaello D., Ettore Focardi, Giuseppe Latino, Piergiulio Lenzi, Lizzo, Mattia, Marco Meschini, Simone Paoletti, Seidita, Roberto, Giacomo Sguazzoni, Lorenzo Viliani, Luigi Benussi, stefano bianco, Davide Piccolo, Marco Bozzo, Fabrizio Ferro, Mulargia, Roberto, Enrico Robutti, Silvano Tosi, Andrea Davide Benaglia, Boldrini Giacomo, Brivio, Francesco, Cetorelli, Flavia, Federico De Guio, Mauro Emanuele Dinardo, Paolo Dini, simone gennai, Alessio Ghezzi, Pietro Govoni, LUCA GUZZI, Marco Toliman Lucchini, Malberti, Martina, Sandra Malvezzi, Andrea Massironi, Dario Livio Menasce, Luigi Moroni, Marco Paganoni, Daniele Pedrini, Pinolini, Bianca Sofia, Stefano Ragazzi, Nicola Redaelli, Tommaso Tabarelli de Fatis, Valsecchi, Davide, Davide Zuolo, Salvatore Buontempo, Carnevali, Francesco, Nicola Cavallo, Agostino De Iorio, Francesco Fabozzi, Alberto Orso Maria Iorio, Luca Lista, Sabino Meola, Pierluigi Paolucci, Biagio Rossi, Crisostomo Sciacca, Patrizia Azzi, nicola bacchetta, Dario Bisello, Pierluigi Bortignon, Alberto Bragagnolo, Roberto Carlin, Paolo Checchia, Tommaso Dorigo, Umberto Dosselli, Fabrizio Gasparini, Ugo Gasparini, Grosso, Gaia, Layer, Lukas, Enrico Lusiani, Martino Margoni, Marini, Filippo, Anna Teresa Meneguzzo, Jacopo Pazzini, Paolo Ronchese, Rossin, Roberto, Franco Simonetto, Giles Strong, Mia Tosi, Yarar, Hevjin, Marco Zanetti, Pierluigi Zotto, Alberto Zucchetta, Gianni Zumerle, Aimè, Chiara, Alessandro Braghieri, Calzaferri, Simone, Davide Fiorina, Montagna, Paolo, Ratti, Sergio P., Valerio Re, Cristina Riccardi, Paola Salvini, Ilaria Vai, Paolo Vitulo, Patrick Asenov, Gian Mario Bilei, Diego Ciangottini, Livio Fano', Magherini, Matteo, Mantovani, Giancarlo, Mariani, Valentina, Mauro Menichelli, Francesco Moscatelli, ANDREA PICCINELLI, Matteo Presilla, Alessandro Rossi, Attilio Santocchia, Daniele Spiga, Tommaso Tedeschi, Paolo Azzurri, Giuseppe Bagliesi, Valerio Bertacchi, Lorenzo Bianchini, Tommaso Boccali, Edoardo Bossini, Rino Castaldi, maria agnese ciocci, Amante, Valeria D., Roberto Dell'Orso, Maria Rosaria Di Domenico, Silvio Donato, Alessandro Giassi, Franco Ligabue, Elisabetta Manca, GIULIO MANDORLI, Matos Figueiredo, Diego, Alberto Messineo, Musich, Marco, Fabrizio Palla, Parolia, Shubhi, Ramirez-Sanchez, Gabriel, Andrea Rizzi, Rolandi, G., Roy Chowdhury, Suvankar, Scribano, Angelo, negin shafiei, Paolo Spagnolo, Roberto Tenchini, Guido Emilio Tonelli, Nicola Turini, Andrea Venturi, Piero Giorgio Verdini, Patrizia Barria, Campana, Mattia, Francesca Cavallari, Daniele Del Re, Emanuele Di Marco, Marcella Diemoz, Egidio Longo, Paolo Meridiani, Giovanni Organtini, Pandolfi, Francesco, Riccardo Paramatti, Quaranta, Claudio, Shahram Rahatlou, Chiara Ilaria Rovelli, Francesco Santanastasio, Livia Soffi, Tramontano, Raffaella, Nicola Amapane, Roberta Arcidiacono, Stefano Argiro', Michele Arneodo, Nazar Bartosik, Riccardo Bellan, Andrea Bellora, Jorge Berenguer Antequera, Cristina Biino, nicolo cartiglia, marco costa, Roberto Covarelli, Natale Demaria, Grippo, Michael, Muhammad Bilal Kiani, Federica Legger, Chiara Mariotti, Silvia Maselli, Mecca, Alberto, Ernesto Migliore, Ennio Monteil, Marco Monteno, Maria Margherita Obertino, Ortona, Giacomo, Luca Pacher, Nadia Pastrone, Mario Pelliccioni, Marta Ruspa, Ksenia Shchelina, federico siviero, Valentina Sola, Ada Maria Solano, Dario Soldi, Amedeo Staiano, Tornago, Marta, Daniele Trocino, Umoret, Giulio, Vagnerini, Antonio, Stefano Belforte, Vieri Candelise, Massimo Casarsa, Fabio Cossutti, Da Rold, Alessandro, Della Ricca, G., Sorrentino, Giulia, Sunil Manohar Dogra, Changgi Huh, Kim, Bobae, Dong Hee Kim, Guinyun Kim, Kim, Jiwoong, Lee, Jeongeun, Sehwook Lee, Chang-Seong Moon, Young Do Oh, Pak, Sang Il, Sezen Sekmen, Yang, Yu Chul, Hyunchul Kim, Dong Ho Moon, Brieuc Francois, Tae Jeong Kim, Jiwon Park, Cho, Sungwoong, Suyong Choi, Byungsik Hong, Lee, Kisoo, Kyong Sei Lee, Lim, Jaehoon, Park, Jaebeom, Park, Sung Keun, Yoo, Jaehyeok, Junghwan Goh, Gurtu, Atul, Hyunsoo Kim, Kim, Yongsun, Almond, John, Bhyun, Ji Hwan, Choi, Junho, Jeon, Sihyun, Kim, Junho, Kim, Jae Sung, Ko, Sanghyun, Kwon, Hyejin, Haneol Lee, Lee, Sangeun, Oh, Byung Hun, Minseok Oh, Oh, Sung Bin, Hyon-San Seo, Yang, Unki, INSEOK YOON, Jang, Woojin, Kang, Da Young, Kang, Yechan, Kim, Seulgi, Ko, Byeonghak, Jason Sang Hun Lee, Lee, Yunjae, Merlin, Jeremie Alexandre, Park, Inkyu, Roh, Youn, Ryu, Min Sang, Song, Donghyun, Watson, Ian J., Yang, Seungjin, Ha, Seungkyu, Yoo, Hwi Dong, Choi, Minuk, Lee, Heewon, Lee, Yonghoon, Intae Yu, Beyrouthy, Taha, Maghrbi, Yasser, Karlis Dreimanis, Viesturs Veckalns, Ambrozas, Marijus, Alexandra Carvalho, Andrius Juodagalvis, Aurelijus Rinkevicius, Gintautas Tamulaitis, Nurfikri Norjoharuddeen, Siew Yan Hoh, Zolkapli, Zukhaimira, Benitez, J. F., Alfredo Castaneda Hernandez, Encinas Acosta, Hedwin Aaron, Gallegos Maríñez, Luis Gabriel, León Coello, Moisés, Javier Alberto Murillo Quijada, Sehrawat, Ashish, Lizardo Valencia Palomo, Ayala, Gabriel, Castilla-Valdez, Heriberto, Eduard De La Cruz Burelo, Ivan Heredia de la Cruz, Lopez-Fernandez, Ricardo, Mondragon Herrera, Cesar Atzin, Perez Navarro, Daniel Alejandro, Reyes-Almanza R., Alberto Sanchez-Hernandez, Carrillo Moreno, Salvador, Cristina Oropeza Barrera, Vazquez Valencia, Fabiola, Pedraza, Isabel, Salazar Ibarguen, Humberto Antonio, Uribe Estrada, Cecilia, Bubanja, Itana, Mijuskovic, Jelena, Raicevic, Natasa, David Krofcheck, Philip Butler, Ahmad, Ashfaq, Asghar, Muhammad Irfan, Awais, Ali, Awan, Muhammad Imran Malik, Muhammad Gul, Hoorani, Hafeez R., Khan, Wajid Ali, Shah, Mehar Ali, Muhammad Shoaib, Muhammad Waqas, Avati, Valentina, Grzanka, Leszek, Malawski, Maciej, Bialkowska, Helena, Michal Bluj, Bożena Boimska, Górski, Maciej, Kazana, Malgorzata, Michał Szleper, Zalewski, Piotr, Bunkowski, Karol, Doroba, Krzysztof, Artur Kalinowski, Marcin Konecki, Jan Krolikowski, Araujo, Mariana, Pedrame Bargassa, Bastos, Diogo, Alessio Boletti, Pietro Faccioli, Michele Gallinaro, Jonathan Hollar, Nuno Leonardo, Niknejad, Tahereh Sadat, Pisano, Matteo, Seixas, J., Oleksii Toldaiev, Joao Varela, Afanasiev, Serguei, Budkouski, Dzmitry, Golutvin, Igor, Ilya Gorbunov, Karjavine, Vladimir, Vladimir Korenkov, Lanev, Alexander, Malakhov, Alexander, Matveev, Viktor, Palichik, Vladimir, Perelygin, Victor, Savina, Maria, Shalaev, Vladislav, Shmatov, Sergey, Shulha, Siarhei, Smirnov, Vitaly, Teryaev, Oleg, Voytishin, Nikolay, Yuldashev, Bekhzod S., Zarubin, Anatoli, Zhizhin, Ilia, Gennadii Gavrilov, Golovtcov, Victor, Ivanov, Yury, Victor Kim, Kuznetsova, Ekaterina, Murzin, Victor, Oreshkin, Vadim, Smirnov, Igor, Dmitry Sosnov, Sulimov, Valentin, Uvarov, Lev, Volkov, Serguei, Vorobyev, Alexey, Yuri Andreev, Dermenev, Alexander, Sergei Gninenko, Golubev, Nikolai, Anton Karneyeu, Dmitry Kirpichnikov, Kirsanov, Mikhail, Krasnikov, Nikolai, Pashenkov, Anatoli, Grigorii Pivovarov, Toropin, Alexander, Aushev, Tagir, Epshteyn, Vladimir, Gavrilov, Vladimir, Lychkovskaya, Natalia, Nikitenko, Alexander, Popov, Vladimir, Stepennov, Anton, Toms, Maria, Vlasov Evgueni, Zhokin, Alexander, Bychkova, Oksana, Ruslan Chistov, Mikhail Danilov, Oskin, Andrei, Parygin, Pavel, Sergey Polikarpov, Andreev, Vladimir, Azarkin, Maksim, Igor Dremin, Kirakosyan, Martin, Terkulov, Adel, Belyaev, Andrey, Eduard Boos, Bunichev, Viacheslav, Mikhail Dubinin, Lev Dudko, Ershov, Alexander, Vyacheslav Klyukhin, Olga Kodolova, Igor Lokhtin, Obraztsov, Stepan, Perfilov, Maxim, Petrushanko, Sergey, Savrin, Viktor, Blinov, Vladimir, Dimova, Tatyana, Kardapoltsev, Leonid, Kozyrev, Aleksei, Ovtin, Ivan, Radchenko, Olesia, Yuri Skovpen, Igor Azhgirey, Bayshev, Igor, Elumakhov, Dmitry, Kachanov, Vassili, Dmitri Konstantinov, Petr Mandrik, Petrov, Vladimir, Ryutin, Roman, Sergei, Sobol, Andrei, Sergey Troshin, Tyurin, Nikolay, Uzunian, Andrey, Volkov, Alexey, Babaev, Anton, Okhotnikov, Vitalii, Borshch, Vladislav, Vladimir Ivanchenko, Evgueni Tcherniaev, Petar Adzic, Milos Dordevic, Predrag Milenovic, Jovan Milosevic, Aguilar-Benitez, Manuel, JUAN ALCARAZ MAESTRE, Álvarez Fernández, Adrian, Bachiller, Irene, Barrio Luna, Mar, Cristina Fernández Bedoya, C.A. Carrillo Montoya, Maria Cepeda, Cerrada, Marcos, Nicanor Colino, La Cruz, Begona, Antonio Delgado Peris, Juan Pablo Fernández Ramos, Josep Flix, Maria Cruz Fouz Iglesias, Oscar Gonzalez Lopez, Silvia Goy Lopez, José María Hernández Calama, Isabel Josa Mutuberria, Jaime Leon Holgado, Moran, Dermot, Álvaro Navarro-Tobar, Perez Dengra, Carlos, Antonio Perez-Calero Yzquierdo, Jesus Puerta Pelayo, Ignacio Redondo, Romero, Luciano, Sánchez Navas, Sergio, Lourdes Urda, Willmott, Carlos, Trocóniz, Jorge F., Barbara Alvarez Gonzalez, Javier Cuevas, Javier Fernandez Menendez, Santiago Folgueras, Isidro González Caballero, González Fernández, Juan Rodrigo, Jose Enrique Palencia Cortezon, Ramón Álvarez, Clara, Víctor Rodríguez Bouza, Soto Rodríguez, Alejandro, Trapote, Andrea, Nicolò Trevisani, Vico Villalba, Carlos, Javier Andres Brochero Cifuentes, Cabrillo, Iban Jose, Alicia Calderon, Jordi Duarte-Campderrós, Marcos Fernandez Garcia, Celia Fernández Madrazo, Pedro Fernández Manteca, García Alonso, Andrea, Gomez, Gervasio, Martinez Rivero, Celso, Pablo Martinez Ruiz del Arbol, Francisco Matorras, Pablo Matorras, Jonatan Piedra, Prieels, Cédric, Alberto Ruiz Jimeno, Luca Scodellaro, Vila, Ivan, Jesus Manuel Vizan Garcia, Malagalage, Kithsiri, Kailasapathy, Balashangar, Sonnadara, Don Upul Jayasiri, Dhammage, Deshitha Chamikara Wickramarathna, Dharmaratna, W. G. D., Liyanage, Kalpanie, Perera, Nimantha, Wickramage, Nadeesha, Thea Aarrestad, Abbaneo, Duccio, Juliette Alimena, Auffray, Etiennette, Auzinger, Georg, Baechler, Joachim, Baillon, Paul, David Barney, Bendavid, Joshua, Michele Bianco, Andrea Bocci, Caillol, Cécile, Camporesi, Tiziano, Mar Capeans, Cerminara, Gianluca, Nadezda Chernyavskaya, Simranjit Singh Chhibra, Choudhury, Somnath, Marco Cipriani, Leonardo Cristella, Enterria, David D., Anne Evelyn Dabrowski, André David, Albert De Roeck, Matteo Maria Defranchis, Mario Deile, Dobson, Marc, Marc Duenser, Dupont, Niels, Elliott-Peisert, Anna, Fallavollita, Francesco, alice florent, Laurent Forthomme, Giovanni Franzoni, Funk, Wolfgang, Saranya Ghosh, Giani, Simone, Gigi, Dominique, Gill, Karl, Glege, Frank, Loukas Gouskos, Katya Govorkova, Mykyta Haranko, Jeroen Hegeman, Vincenzo, James, Thomas, Patrick Janot, Jan Kašpar, Jan Kieseler, Matthias Komm, Kratochwil, Nicolaus, Clemens Lange, Laurila, Santeri, Lecoq, Paul, Lintuluoto, Adelina, Carlos Lourenco, Maier, Benedikt, Luca Malgeri, Mallios, Stavros, Mannelli, Marcello, Meijers, Frans, Stefano Mersi, Emilio Meschi, Filip Moortgat, Martijn Mulders, Orfanelli, Styliani, Orsini, Luciano, Felice Pantaleo, Perez, Emmanuel, Marco Peruzzi, Petrilli, Achille, Giovanni Petrucciani, Andreas Pfeiffer, Maurizio Pierini, Piparo, Danilo, Michael Pitt, Huilin Qu, Quast, Thorben, Dinyar Rabady, Racz, Attila, Reales Gutiérrez, Guillermo, Rovere, Marco, Sakulin, Hannes, Scarfi, Simone, Schwick, Christoph, Michele Selvaggi, Sharma, Archana, Pedro Manuel Vieira de Castro Ferreira da Silva, Walter Snoeys, Paraskevas Sphicas, Sioni Summers, Vittorio Raoul Tavolaro, Treille, Daniel, Tropea, Paola, Tsirou, Andromachi, Wanczyk, Joanna, Wozniak, Kinga Anna, Zeuner, Wolfram Dietrich, Lea Caminada, Aliakbar Ebrahimi, Erdmann, Wolfram, Horisberger, Roland, Ingram, Quentin, Kaestli, Hans-Christian, Kotlinski, Danek, Langenegger, Urs, Marino Missiroli, Noehte, Lars, Rohe, Tilman, Konstantin Androsov, Malte Backhaus, Berger, Pirmin, Calandri Alessandro, Cosa, Annapaola, Guenther Dissertori, Dittmar, Michael, Donegà, Mauro, Christian Dorfer, Eble, Florian, Gedia, Krunal, Glessgen, Franz, Alejandro Gomez Espinosa, Christophorus Grab, Hits, Dmitry, Lustermann, Werner, Lyon, Anne-Mazarine, Riccardo Andrea Manzoni, Luigi Marchese, Martin Perez, Cristina, Meinhard, Maren Tabea, Nessi-Tedaldi, Francesca, Jeremi Niedziela, Pauss, Felicitas, Perovic, Vasilije, Simone Pigazzini, Maria Giulia Ratti, Reichmann, Michael, Reissel, Christina, Reitenspiess, Thomas, Branislav Ristic, Ruini, Daniele, Sanz-Becerra, Diego A., Stampf, Vinzenz, Jan Steggemann, Rainer Wallny, Claude Amsler, Bärtschi, Pascal, Cristina Botta, Brzhechko, Danyyl, Florencia Canelli, Cormier, Kyle, Adinda de Wit, Del Burgo, Riccardo, Jaana Heikkilä, Huwiler, Marc, Jin, Weijie, Arash Jofrehei, Benjamin Kilminster, Stefanos Leontsinis, Liechti, Sascha Pascal, Anna Macchiolo, Meiring, Peter, Vinicius Mikuni, Molinatti, Umberto, Neutelings, Izaak, Reimers, Arne, Robmann, Peter, Sergio Sanchez Cruz, Korbinian Schweiger, Senger, Matias, Yuta Takahashi, Adloff, Catherine, Kuo, Chia-Ming, Lin, Willis, Ashim Roy, Tanmay Sarkar, Yu, Shin-Shan, Ceard, Ludivine, Chao, Yuan, KAI-FENG CHEN, Po-Hsun Chen, Chen, Pu-Sheng, Huajie Cheng, Wei-Shu Hou, Li, You-Ying, Lu, Rong-Shyang, Stathes Paganis, Psallidas, Andreas, Steen, Arnaud, Wu, Hsin-Yeh, Efe Yazgan, Yu, Pei-Rong, Burin Asavapibhop, Chayanit Asawatangtrakuldee, Norraphat Srimanobhas, Fatma Boran, Damarseckin, Serdal, Zuhal Seyma Demiroglu, furkan dolek, İSA DUMANOGLU, Eskut, Eda, Guler, Y., EMINE GÜRPINAR GÜLER, Isik, Candan, Kara, Ozgun, Kayis Topaksu, Aysel, Ugur Kiminsu, Onengut, Gulsen, Ozdemir, Kadri, Polatoz, Ayse, Ali Eren Simsek, Tali, Bayram, Given Names Deactivated Family Name Deactivated, Turkcapar, Semra, Ibrahim Soner Zorbakir, Karapinar, Guler, Kadir Ocalan, Metin Yalvac, Akgun, Bora, ismail okan atakisi, Erhan Gülmez, mithat kaya, Kaya, Ozlem, Özçelik, Özlem, Tekten, Sevgi, Elif Asli Yetkin, Altan Cakir (ITU), KEREM CANKOÇAK, Komurcu, Yildiray, Sercan Sen, Cerci, Salim, Hos, Ilknur, Isildak, Bora, Kaynak, Berkan, Ozkorucuklu, Suat, Hale Sert, Simsek, Cagdas, Deniz Sunar Cerci, Zorbilmez, Caglar, Grynyov, Boris, Leonid Levchuk, Anthony, David, Eshwen Bhal, Bologna, Simone, Jim Brooke, Aaron Bundock, Emyr Clement, David Cussans, Henning Flaecher, Glowacki, Maciej, Joel Goldstein, Heath, Greg P., Helen Heath, Luke Kreczko, Benjamin Krikler, Paramesvaran, Sudarshan, Seif El Nasr-Storey, Sarah, Smith, Vincent J., Nicolas Stylianou, Walkingshaw Pass, Katie, White, Robert, Bell, Ken W., Alexander Belyaev, Chris Brew, Brown, Robert M., Cockerill, David Ja, Cooke, Charlotte, Ellis, Katherine Victoria, Harder, Kristian, Harper, Sam, Holmberg, Mei-Li, Jacob Linacre, Manolopoulos, Konstantinos, David Newbold, Olaiya, Emmanuel, Petyt, David, Thomas Reis, Schuh, Thomas, Shepherd-Themistocleous, Claire, Tomalin, Ian R., Thomas Williams, Robert Bainbridge, Bloch, Philippe, Bonomally, Shameena, Johan Borg, Breeze, Shane, Buchmuller, Oliver, Vilius Cepaitis, Gurpreet Singh Chahal, Colling, David, Paul Dauncey, Gavin Davies, Michel Della Negra, Fayer, Simon, Giacomo Fedi, Geoffrey Hall, Hassanshahi, Mohammad Hassan, Iles, Gregory, Langford, Jonathon, Lyons, Louis, Magnan, Anne-Marie, Malik, Sarah, Arabella Martelli, Monk, David Gabriel, Jordan Nash, Pesaresi, Mark, Radburn-Smith, Benjamin Charles, Raymond, David Mark, Richards, Alexander, Rose, Andrew, Edward Scott, Seez, Christopher, Shtipliyski, Antoni, Alexander Tapper, Uchida, Kirika, Tejinder Virdee, Milos Vojinovic, Nicholas Wardle, Samuel Webb, Winterbottom, Daniel, Coldham, Kathryn, Joanne Cole, Khan, Akram, Paul Kyberd, Ivan Reid, Teodorescu, Liliana, Sema Zahid, Salavat Abdullin, Andrew Brinkerhoff, Bryan Caraway, Jay Dittmann, Kenichi Hatakeyama, Kanuganti, Ankush Reddy, Brooks McMaster, Mark Saunders, Sawant, Siddhesh, Sutantawibul, Chosila, Jonathan Wilson, Rachel Bartek, Aaron Dominguez, Rishabh uniyal, Vargas Hernandez, Andres Mateus, Andrew Buccilli, Seth Cooper, Davide Di Croce, Sergei Gleyzer, Conor Henderson, Cilicia Uzziel Perez, Paolo Rumerio, Christopher West, Alp Akpinar, Andreas Albert, Dan, Christopher Cosby, Zeynep Demiragli, Carlos Francisco Erice Cid, Fontanesi, Elisa, Gastler, Daniel, Samuel May, James Rohlf, Kaitlin Salyer, Sperka, David, Daniel Spitzbart, Indara Suarez, Tsatsos, Anna, Yuan, Siqi, Zou, David, Gabriele Benelli, Bjorn Burkle, Coubez, Xavier, David Cutts, Mary Hadley, Ulrich Heintz, Julie Hogan, Kwon, Taeun, Greg Landsberg, Ka Tung Lau, Li, Daniel, Lukasik, Michael, Jingyu Luo, Narain, Meenakshi, Pervan, Nikolas, Sinan Sagir, Simpson, Farrah, Emanuele Usai, Wong, Wing Yan, Xuli Yan, David Yu, Zhang, Wenyu, Johan Bonilla, Christopher Brainerd, Breedon, Richard, Calderon La Barca Sanchez, Manuel, Maxwell Chertok, John Conway, Cox, Peter Timothy, Erbacher, Robin, Haza, Grace, Frank Jensen, Kukral, Ota, Lander, Richard, Michael Mulhearn, Pellett, Dave, Brendan Regnery, Devin Taylor, Yao Yao, Fengwangdong Zhang, Michail Bachtis, Cousins, Robert D., Abhisek Datta, Hamilton, David, Jay Hauser, Ignatenko, Mikhail, Iqbal, Muhammad Ansar, Lam, Tyler, Nash, William Arthur, Simon Regnard, David Saltzberg, Stone, Brent, Viatcheslav Valuev, Chen, Yuan, Robert Clare, John Gary, Gordon, Michael, Gail Hanson, Georgia Karapostoli, Owen Long, Manganelli, Nicholas, Weinan Si, Wimpenny, Stephen, Zhang, Yi, Branson, James G., Philip Chang, Cittolin, Sergio, Stephane Cooperstein, Daniel Diaz, Javier Mauricio Duarte, Raffaele Gerosa, Leonardo Giannini, Guiang, Jonathan, Raghav Kansal, Vyacheslav Krutelyov, Lee, Robert, JAMES LETTS, Mario Masciovecchio, Mokhtar, Farouk, Marco Pieri, Balaji Venkat Sathia Narayanan, Vivek Sharma, Tadel, Matevz, Frank Wuerthwein, Yifan Xiang, avi yagil, Amin, Nick, Claudio Campagnari, Matthew Citron, Giulia Collura, Dorsett, Alex, Valentina Dutta, Joseph Incandela, Matthew Kilpatrick, Jaebak Kim, Marsh, Bennett, Mei, Hualin, Oshiro, Michael, Melissa Quinnan, Richman, Jeffrey, Ulascan Sarica, Setti, Francesco, Sheplock, James, Siddireddy, Prasanna, Stuart, David, Sicheng Wang, Adi Bornheim, Cerri, Olmo, Irene Dutta, Jay Lawhorn, Nan Lu, Mao, Jiajing, Harvey Newman, Nguyen, Thong Q., Maria Spiropulu, jean-roch vlimant, Christina Wang, Si Xie, Zhicai Zhang, Ren-Yuan Zhu, John Alison, Sitong An, Andrews, Michael Benjamin, Patrick Bryant, Thomas Ferguson, Harilal, Abhirami, Liu, Chuyuan, Tanmay Mudholkar, Manfred Paulini, Sanchez, Alejandro, Terrill, Wesley, JOHN CUMALAT, WILLIAM FORD, Hassani, Abbas, Karathanasis, George, Macdonald, Emily, Patel, Rishi, Alexx Perloff, Savard, Claire, Schonbeck, Nicolas, KEVIN STENSON, KEITH ULMER, STEPHEN WAGNER, Zipper, Noah, James Alexander, Samuel Bright-Thonney, Xuan Chen, Yangyang Cheng, Derek Cranshaw, Fan, Xingchen, Hogan, Shaun, Jose Andres Monroy Montanez, Ritchie Patterson, J., Dan Quach, Joseph Reichert, Michael Reid, Ryd, Anders, Werner Sun, Julia Thom-Levy, Peter Wittich, Rui Zou, Michael Albrow, Maral Alyari, Apollinari, Giorgio, Artur Apresyan, Aram Apyan, Bauerdick, Lothar A. T., Douglas Berry, Jeffrey Berryhill, Bhat, Pushpalatha C., Kevin Burkett, Butler, Joel Nathan, Canepa, Anadi, Giuseppe Cerati, Harry Cheung, Chlebana, Frank, Karri Folan Di Petrillo, Jennet Dickinson, Daniel Elvira, V., Feng, Yongbin, Freeman, Jim, Abhijith Gandrakota, Gecse, Zoltan, Gray, Lindsey, Green, Dan, Stefan Gruenendahl, Oliver Gutsche, Harris, Robert M., Heller, Ryan, Theodor Christian Herwig, James Hirschauer, Bodhitha Jayatilaka, Jindariani, Sergo, Johnson, Marvin, Joshi, Umesh, Thomas Klijnsma, Boaz Klima, Kwok, Ka Hei Martin, Stephan Lammel, Don Lincoln, Lipton, Ron, Liu, Tiehui, Madrid, Christopher, Maeshima, Kaori, Cristina Mantilla, Mason, David, Patricia McBride, Merkel, Petra, Stephen Mrenna, Steve Nahn, Jennifer Ngadiuba, Papadimitriou, Vaia, Pastika, Nathaniel, Kevin Pedro, Peña, Cristián H., Fabio Ravera, Allison Reinsvold Hall, Luciano Ristori, Elizabeth Sexton-Kennedy, Nicholas Smith, Aron Soha, Spiegel, Leonard, Stoyan Stoynev, James Strait, Lucas Taylor, Tkaczyk, Slawek, Nhan Tran, Lorenzo Uplegger, Eric Vaandering, Hannsjörg Weber, Avery, Paul, Dimitri Bourilkov, Luca Cadamuro, Cherepanov, Vladimir, Field, Richard D., Guerrero, Daniel, Kim, Mugeon, Koenig, Evan, Jacobo Konigsberg, Korytov, Andrey, Lo, Kin Ho, Konstantin Matchev, Nicholas Menendez, Guenakh Mitselmakher, Muthirakalayil Madhu, Arun, Rawal, Neha, Rosenzweig, Daniel, Rosenzweig, Suzanne, kun shi, Jian Wang, Zhenbin Wu, Efe Yigitbasi, Zuo, Xunwu, Adams, T., Andrew Askew, Redwan Habibullah, Hagopian, Vasken, Johnson, Kurtis F., Khurana, Raman, Ted Kolberg, Martinez, German, Harrison Prosper, Schiber, Catherine, Oleksandr Viazlo, Rachel, Zhang, Jingyu, Marc Baarmand, Butalla, Stephen, Tamer Elkafrawy, Marcus Hohlmann, Ravindra Kumar Verma, Daniel Noonan, Rahmani, Mehdi, Francisco Yumiceva, Adams, Mark Raymond, Hugo, Richard Cavanaugh, Dittmer, Susan, Olga Evdokimov, Cecilia Elena Gerber, David Hofman, Merritt, Anna Henckel, Corrinne Mills, Geonhee Oh, Roy, Titas, Rudrabhatla, Sahithi, Marguerite Tonjes, Nikos Varelas, Jussi Viinikainen, Wang, Xiao, Zhenyu Ye, Mohammad Alhusseini, Kamuran Dilsiz, Emediato, Luiz, Reddy Pratap Gandrajula, Ohannes Kamer Koseyan, Merlo, Jean-Pierre, Mestvirishvili, Alexi, Nachtman, Jane, Hasan Ogul, Yasar Onel, Penzo, Aldo, Snyder, Christina, Emrah Tiras, Oz Amram, Barry Blumenfeld, Lucas Corcodilos, Davis, Jeffrey, Andrei Gritsan, Kyriacou, Savvas, Petar Maksimovic, Jeffrey Roskes, Swartz, Morris, Tamas Almos Vami, Abreu, Andrés, Anguiano, Justin, Cristian Baldenegro Barrera, Philip Baringer, Alice Bean, Flowers, Zachary, Isidori, Tommaso, Sadia Khalil, King, Jack, Georgios Konstantinos Krintiras, Anna Kropivnitskaya, Lazarovits, Margaret, Le Mahieu, Cole, Lindsey, Cole, Marquez, Juan, Nicola Minafra, Michael Murray, Nickel, Matthew, Christopher Rogan, Royon, Christophe, Riccardo Salvatico, Sanders, Stephen, Schmitz, Erich, Caleb Smith, Quan Wang, Warner, Zachary, Justin Williams, Wilson, Graham W., Duric, Senka, Andrew Ivanov, Ketino Kaadze, Kim, Doyeong, Yurii Maravin, Mitchell, Tyler, Modak, Atanu, Nam, Kyungwook, Rebassoo, Finn, Wright, Douglas, Adams, Eric, Baden, Drew, Baron, Owen, Alberto Belloni, Sarah Eno, Nicholas Hadley, Shabnam Jabeen, Kellogg, Richard G., Koeth, Timothy, Lai, Yihui, Lascio, Samuel, Mignerey, Alice, Nabili, Sara, Christopher Palmer, Markus Seidel, Andris Skuja, Wang, Long, Kak Wong, Abercrombie, Daniel, Andreassi, Guido, Bi, Ran, Cali, Ivan Amos, Yi Chen, Alfonso, Mariarosaria D., Eysermans, Jan, Chad Freer, Gomez Ceballos, Guillelmo, Goncharov, Maxim, Harris, Philip, Hu, Miao, Dmytro Kovalskyi, Krupa, Jeffrey, Yen-Jie Lee, KENNETH LONG, Dylan Rankin, Christof Roland, Roland, Gunther, Zhaozhong Shi, Stephans, George S. F., Wang, Jing, Zhangqier Wang, Boleslaw Wyslouch, Chatterjee, Rajdeep Mohan, Andrew Evans, Hiltbrand, Joshua, Shilpi Jain, Joshi, B. M., Krohn, Michael, Kubota, Yuichi, Jeremiah Mans, Revering, Michael, Roger Rusack, Saradhy, Rohith, Neil Schroeder, Nadja Strobbe, Wadud, Mohammad Abrar, Kenneth Bloom, Bryson, Miranda, Shubhanshu Chauhan, Claes, Daniel R., Fangmeier, Caleb, Linda Finco, Frank Golf, Joo, Changwoo, Ilya Kravchenko, Reed, Ian, Siado, Joaquin Emilo, Snow, Gregory R., Tabb, William, Wightman, Andrew, Yan, Furong, Zecchinelli, Angelo Giacomo, Garvita Agarawal, Hirak Bandyopadhyay, Lauren Hay, Ia Iashvili, Kharchilava, Avto, Christine McLean, Nguyen, Duong, Juska Pekkanen, Salvatore Rappoccio, Ac, Williams, George Alverson, Barberis, Emanuela, Yacine Haddad, Han, Yixiao, Hortiangtham, Apichart, Krishna, Amrutha, Jingyan Li, Jindrich Lidrych, Madigan, Gabriel, Badder Marzocchi, David Michael Morse, Nguyen, Vivan, Toyoko Orimoto, Parker, Ashley, Louise Skinnari, Tishelman-Charny, Abraham, Wamorkar, Tanvi, Bingran Wang, Wisecarver, Andrew, Darien Wood, Saptaparna, Bueghly, James, Ziheng Chen, Andrew Gilbert, Thoth Gunter, Hahn, Kristan Allan, Liu, Yihan, Odell, Nathaniel, Michael Schmitt, Velasco, Mayda, Reyer Band, Bucci, Rachael, Cremonesi, Matteo, Abhishek Das, Nabarun Dev, Reza Goldouzian, Hildreth, Michael, Kenyi Hurtado Anampa, Jessop, Colin P., Kevin Lannon, Lawrence, John, Nikitas Loukas, Lutton, Dylan, Mariano, Joseph, Marinelli, Nancy, Mcalister, Ian, Thomas McCauley, Mcgrady, Christopher, Mohrman, Kelci, Moore, Connor, Musienko, Yuri, Ruchti, Randy, Townsend, Austin, Wayne, Mitchell, Mateusz Zarucki, Zygala, Lara, Bylsma, Ben, Durkin, L. S., Brian Francis, Christopher Hill, Estefany, Wei, Kai, Winer, Brian L., Brent Yates, Francesca Maria Addesa, Brandon Bonham, Pallabi Das, Dezoort, Gage, Peter Elmer, Andre Frankenthal, Bennett Greenberg, Haubrich, Nicholas, Higginbotham, Samuel, Alexis Kalogeropoulos, Kopp, Gillian, Stephanie Kwan, Lange, David, Daniel Marlow, Kelvin Mei, Ojalvo, Isabel, James Olsen, David Stickland, Tully, C. G., Sudhir Malik, Norberg, Scarlet, Bakshi, Amandeep Singh, Virgil Barnes, Ridhi Chawla, Souvik Das, Gutay, Laszlo, Timothy Matthew Jones, Andreas Jung, Dmitry Kodratyev, Koshy, Abraham Mathew, Liu, Miaoyuan, Negro, Giulia, Norbert Neumeister, Paspalaki, Garyfallia, Stefan Piperov, Purohit, Arnab, Jan-Frederik Schulte, Stojanovic, Milan, Thieman, Jason R., Fuqiang Wang, Rui Xiao, Wei Xie, James Dolen, Parashar, Neeti, Darin Acosta, Carnahan, Taylor, Decaro, Matthew, Sven Dildick, Karl Ecklund, Freed, Sarah, Gardner, Parker, Frank Geurts, Arun Kumar, Li, Wei, Paul Padley, Redjimi, Radia, Rotter, John, Wei Shi, Andre Govinda Stahl Leiton, Shuai Yang, Zhang, Liuyao, Yousen Zhang, Arie Bodek, Barbaro, Pawel, Regina Demina, Joseph Dulemba, Fallon, Colin, Tom Ferbel, Galanti, Mario, Aran Garcia-Bellido, Otto Hindrichs, Khukhunaishvili, Aleko, Ranken, Evan, Taus, Rhys, Gerrit Van Onsem, Goulianos, Konstantin, Chiarito, Brandon, John Paul Chou, Yuri Gershtein, Eva Halkiadakis, Hart, Andrew, Maximilian Heindl, Olena Karacheban, Laflotte, Ian, Amitabh Lath, Montalvo, Roy, Nash, Kevin, Osherson, Marc, Sevil Salur, Schnetzer, Steve, Sunil Somalwar, Stone, Robert, Steffie Ann Thayil, Thomas, Scott, Hui Wang, Acharya, Himal, Delannoy, Andres G., Sara Fiorendi, Tova Holmes, Luke Moore, Othmane Bouhali, Mykhailo Dalchenko, Andrea Delgado, Eusebi, Ricardo, Gilmore, Jason, Huang, Tao, Kamon, Teruki, Hyunyong Kim, Sifu Luo, Malhotra, Shivali, Mueller, Ryan, Overton, David, Denis Rathjens, Alexei Safonov, Akchurin, Nural, Damgov, Jordan, Hegde, Vinay, Lamichhane, Kamal, Sung-Won Lee, Mengke, Tielige, Samila Muthumuni, Timo Peltola, Volobouev, Igor, Wang, Zhixing, Whitbeck, Andrew, Eric Appelt, Greene, Senta, Alfredo Gurrola, Johns, Willard, Melo, Andrew, Klaas Padeken, Francesco Romeo, Paul Sheldon, Tuo, Shengquan, Julia Velkovska, Michael Arenton, Cardwell, Bryan, Bradley Cox, Grace Cummings, John Hakala, Robert Hirosky, Matthew Joyce, Alexander Ledovskoy, Li, Ang, Christopher Neu, Carlos Eugenio Perez Lara, Benjamin Tannenwald, Sebastian White, Nabin Poudyal, Banerjee, Sunanda, Kevin Black, Tulika Bose, Sridhara Dasu, Isabelle De Bruyn, Pieter Everaerts, Galloni, Camilla, He, He, Matthew Herndon, Herve, Alain, Hussain, Usama, Lanaro, Armando, Loeliger, Andrew, Loveless, Richard, Jithin Madhusudanan Sreekala, Mallampalli, Abhishikth, Mohammadi, Abdollah, Pinna, Deborah, Savin, Alexander, Shang, Victor, Varun Sharma, Smith, Wesley H., Teague, Dylan, Trembath-Reichert, Stephen, and Wren Vetens

48. Debate: Should statin be used in patients with heart failure?

Author

Pietro Maggioni Aldo

Subjects
cholesterol, clinical trials, heart failure, statins, Medicine (General), R5-920
Abstract

Abstract Statins reduce mortality of patients with coronary artery disease (CAD). However, by protocol, trials have excluded patients with chronic heart failure. Since the prevalent etiology of heart failure is CAD, preventing CAD may prevent heart failure progression. Statins may have other beneficial effects besides cholesterol lowering, such as anti-inflammatory properties and improvement of endothelial function. On the contrary, high levels of cholesterol can be beneficial in heart failure patients on the basis of the ability of serum lipoproteins to modulate inflammatory response. Furthermore, statins affecting mitochondrial function can have a deleterious effect on skeletal or cardiac muscles. Despite all these conflicting data, there is no evidence from trials on the effects of statins in patients with heart failure. For this reason, the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI) investigators planned a controlled trial testing the effect of statins in patients with heart failure of different etiology.

Published
2001
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results