1,645 results on '"Catholic University of Rome"'
Search Results
2. New advances in addiction medicine
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Catholic University of Rome - Institute of Internal Medicine, University of Virginia - Charlottesville - Department of Psychiatry and Neurobehavioral Sciences, UCL - SST/ELI/ELIM - Applied Microbiology, Addolorato, Giovanni, Ait-Daoud Tiouririne, Nassima, De Witte, Philippe, Catholic University of Rome - Institute of Internal Medicine, University of Virginia - Charlottesville - Department of Psychiatry and Neurobehavioral Sciences, UCL - SST/ELI/ELIM - Applied Microbiology, Addolorato, Giovanni, Ait-Daoud Tiouririne, Nassima, and De Witte, Philippe
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- 2010
3. New Frontiers in Alcohol and Health : - The birth of ERAB- Introduction- Heavy alcohol intake episodes: determinants and interventions- Alcohol and the risk of cancer- Alcoholic liver disease- Alcohol and its effects on the cardiovascular system- Brain, behaviour, genetic findings and pharmacological treatment in alcohol dependence- Conclusion
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UCL - SST/ELI/ELIM - Applied Microbiology, Catholic University of Rome - Italy - Department of Internal Medicine, University of Newcastle - UK - Institute of Cellular Medicine, University of Newcastle - UK - Faculty of Medical Sciences, University of Ulm - Germany - Department of Internal Medicine II - Cardiology, Johns Hopkins Bayview Medical Center - Department of Gastroenterology, Finnish Foundation for Alcohol Studies - Finland - Finnish Foundation for Alcohol Studies, Maastricht University - The Netherlands - Department of Epidemiology, De Witte, Philippe, Addolorato, Giovanni, Day, Chris P., James, Oliver F., Koenig, Wolfgang, Mitchell, Mack C., Poikolainen, Kari, Weijenberg, Matty P., UCL - SST/ELI/ELIM - Applied Microbiology, Catholic University of Rome - Italy - Department of Internal Medicine, University of Newcastle - UK - Institute of Cellular Medicine, University of Newcastle - UK - Faculty of Medical Sciences, University of Ulm - Germany - Department of Internal Medicine II - Cardiology, Johns Hopkins Bayview Medical Center - Department of Gastroenterology, Finnish Foundation for Alcohol Studies - Finland - Finnish Foundation for Alcohol Studies, Maastricht University - The Netherlands - Department of Epidemiology, De Witte, Philippe, Addolorato, Giovanni, Day, Chris P., James, Oliver F., Koenig, Wolfgang, Mitchell, Mack C., Poikolainen, Kari, and Weijenberg, Matty P.
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- 2010
4. Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level
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Van Den Brink, Wim, Addolorato, Giovanni, Aubin, Henri-Jean, Benyamina, Amine, Caputo, Fabio, Dematteis, Maurice, Gual, Antoni, Lesch, Otto-Michael, Mann, Karl, Maremmani, Icro, Nutt, David, Paille, François, Perney, Pascal, Rehm, Jurgen, Reynaud, Michel, Simon, Nicolas, Söderpalm, Bo, Mann, Wolfgang, Walter, Henriette, Mann, Rainer, ANS - Compulsivity, Impulsivity & Attention, Adult Psychiatry, Department of Psychiatry [Amsterdam, The Netherlands], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Department of Internal Medicine, Gastroenterology and Hepatology [Rome, Italy] (Alcohol Use Disorder Unit), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt)-A. Gemelli Hospital [Rome, Italy], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11), Centre de recherche et de traitement de la toxicomanie [AP-HP Hôpital Paul Brousse], Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse, Institute of Internal Medicine, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Centre Hospitalier Universitaire [Grenoble] (CHU), Alcohol Unit, Neurosciences Institute, Hospital Clinic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), University of Vienna [Vienna], Heidelberg University, University of Pisa - Università di Pisa, Department of Experimental Psychology, University of Oxford-University of Oxford, Imperial College London, Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Universitaire de Réadaptation, de Rééducation et d'Addictologie du CHU de Nîmes [Grau-du-Roi] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Public Health and Regulatory Policies, Centre for Addiction and Mental Health [Toronto] (CAMH), Troubles du comportement alimentaire de l'adolescent (UMR_S 669), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 - Faculté des Sciences (UP11 UFR Sciences), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Section of Psychiatry and Neurochemistry [Gothenburg, Sweden] (Institute of Neuroscience and Physiology), University of Gothenburg (GU)-Sahlgrenska Academy at University of Gothenburg [Göteborg], Heidelberg University Hospital [Heidelberg], D&A Pharma supported an Expert Opinion Dossier written by all listed authors with the exception of WHS., Lissalde, Claire, Catholic University of Rome-A. Gemelli Hospital [Rome, Italy], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Catholic University of Rome, University of Pisa [Italy], University of Oxford [Oxford]-University of Oxford [Oxford], and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)
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Adult ,Male ,Adolescent ,Settore MED/12 - GASTROENTEROLOGIA ,alcohol dependence ,heavy drinking ,drinking risk level ,NO ,nalrexone ,Young Adult ,acamprosate ,acamprosate, nalrexone, nalmefene, heavy drinking ,Secondary Prevention ,Humans ,acamprosate, nalrexone, nalmefene, heavy drinking, alcohol dependence, alcoholism, drinking risklevel, gamma-hydroxybutyric acid, GHB, sodium oxybate ,drinking risklevel ,Clinical Trials as Topic ,alcoholism ,Middle Aged ,nalmefene ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,gamma-hydroxybutyric acid ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,GHB ,sodium oxybate ,Alcohol Deterrents - Abstract
International audience; Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to meth-odological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol-dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90 000 alcohol-dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. 2018). A promising new medication for this population is sodium oxybate, a compound that acts on GABA B receptors and extrasynaptic GABA A receptors resulting in alcohol-mimetic effects. In this article, a European expert group of alcohol researchers and clini-cians summarizes data (a) from published trials, (b) from two new-as yet unpublished-large clinical trials (GATE 2 (n = 314) and SMO032 (n = 496), (c) from post hoc subgroup analyses of patients with different WHO-defined DRLs and (d) from multiple meta-analyses. These data provide convergent evidence that sodium oxybate is effective especially in a subgroup of alcohol-dependent patients with VH DRLs. Depending on the study, abstinence rates are increased up to 34 percent compared with placebo with risk ratios up to 6.8 in favor of sodium oxybate treatment. These convergent data are supported by the clinical use of sodium oxybate in Austria and Italy for more than 25 years. Sodium oxybate is the sodium salt of γ-hydroxybutyric acid that is also used as a recreational (street) drug suggestive of abuse potential. However, a pharmacovigilance database of more than 260 000 alcohol-dependent patients treated with sodium oxybate reported very few adverse side effects and only few cases of abuse. We therefore conclude that sodium oxybate is an effective, well-tolerated and safe treatment for withdrawal and relapse prevention treatment, especially in alcohol-dependent patients with VH DRL.
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- 2018
- Full Text
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5. CT and MR imaging prior to transcatheter aortic valve implantation
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Marco Francone, Luigi Natale, Matthias Gutberlet, Jens Bremerich, Ricardo P.J. Budde, Alban Redheuil, Gianluca Pontone, Christian Loewe, Rodrigo Salgado, Kostantin Nikolaou, Florian Wolf, Jean-Nicolas Dacher, Rozemarijn Vliegenthart, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Basel (Unibas), Service d'imagerie médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), CHU Rouen, Medizinische Universität Wien = Medical University of Vienna, Catholic University of Rome, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Groningen [Groningen], Universität Leipzig [Leipzig], Antwerp University Hospital [Edegem] (UZA), Radiology & Nuclear Medicine, Gestionnaire, Hal Sorbonne Université, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), and Cardiovascular Centre (CVC)
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[SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery ,[INFO.INFO-IM] Computer Science [cs]/Medical Imaging ,Heart Valve Diseases ,Settore MED/11 - Malattie dell'Apparato Cardiovascolare ,VALVULAR HEART-DISEASE ,030204 cardiovascular system & hematology ,Aortic valve stenosis ,030218 nuclear medicine & medical imaging ,CORONARY OBSTRUCTION ,0302 clinical medicine ,Bicuspid Aortic Valve Disease ,ELDERLY-PATIENTS ,Neuroradiology ,medicine.diagnostic_test ,valvular heart disease ,Calcinosis ,Interventional radiology ,General Medicine ,3. Good health ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,REPLACEMENT ,Aortic Valve ,POTENTIAL ROLE ,MULTIDETECTOR COMPUTED-TOMOGRAPHY ,Radiology ,Cardiac ,medicine.medical_specialty ,Consensus ,Transcatheter aortic ,Magnetic Resonance Imaging, Cine ,Mistake ,[SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery ,AMERICAN-COLLEGE ,STENOSIS ,Magnetic resonance imaging ,Multidetector computed tomography ,Transcatheter aortic valve replacement ,03 medical and health sciences ,Imaging, Three-Dimensional ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Preoperative Care ,medicine ,[INFO.INFO-IM]Computer Science [cs]/Medical Imaging ,MANAGEMENT ,Humans ,Radiology, Nuclear Medicine and imaging ,Computer. Automation ,business.industry ,Correction ,medicine.disease ,Stenosis ,Quality of Life ,business ,Tomography, X-Ray Computed ,TASK-FORCE - Abstract
Transcatheter aortic valve replacement (TAVR) is a minimally invasive alternative to conventional aortic valve replacement in symptomatic patients with severe aortic stenosis and contraindications to surgery. The procedure has shown to improve patient’s quality of life and prolong short- and mid-term survival in high-risk individuals, becoming a widely accepted therapeutic option which has been integrated into current clinical guidelines for the management of valvular heart disease. Nevertheless, not every patient at high-risk for surgery is a good candidate for TAVR. Besides clinical selection, which is usually established by the Heart Team, certain technical and anatomic criteria must be met as, unlike in surgical valve replacement, annular sizing is not performed under direct surgical evaluation but on the basis of non-invasive imaging findings. Present consensus document was outlined by a working group of researchers from the European Society of Cardiovascular Radiology (ESCR) and aims to provide guidance on the utilisation of CT and MR imaging prior to TAVR. Particular relevance is given to the technical requirements and standardisation of the scanning protocols which have to be tailored to the remarkable variability of the scanners currently utilised in clinical practice; recommendations regarding all required pre-procedural measurements and medical reporting standardisation have been also outlined, in order to ensure quality and consistency of reported data and terminology. Key Points • To provide a reference document for CT and MR acquisition techniques, taking into account the significant technological variation of available scanners. • To review all relevant measurements that are required and define a step-by-step guided approach for the measurements of different structures implicated in the procedure. • To propose a CT/MR reporting template to assist in consistent communication between various sites and specialists involved in the procedural planning. Electronic supplementary material The online version of this article (10.1007/s00330-019-06357-8) contains supplementary material, which is available to authorized users.
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- 2020
- Full Text
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6. Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study
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Chappell, E., Riordan, A., Jourdain, G., Soriano-Arandes, A., Ene, L., Scherpbier, H., Warszawski, J., Collins, I., Smit, C., Marques, L., Klein, N., Guillén, S., Judd, A., Thorne, C., Goodall, R., Königs, C., Spoulou, V., Prata, F., Goetghebuer, T., Chiappini, E., Galli, L., Naver, L., Giaquinto, C., Gibb, D., Marczynska, M., Okhonskaia, L., Klimkait, T., Lallemant, M., Ngo-Giang-Huong, N., Kiseleva, G., Malyuta, R., Volokha, A., Hainaut, M., Delforge, M., Le Chenadec, J., Ramos, E., Dialla, O., Wack, T., Laurent, C., Ait Si Selmi, L., Leymarie, I., Ait Benali, F., Brossard, M., Boufassa, L., Floch-Tudal, C., Firtion, G., Hau, I., Chace, A., Bolot, P., Blanche, S., Levine, M., Bicëtre, L., Fourcade, C., Heller-Roussin, B., Runel-Belliard, C., Tricoire, J., Chirouze, C., Reliquet, V., Brouard, J., Kebaili, K., Fialaire, P., Lalande, M., Schultze-Strasser, S., Baumann, U., Niehues, T., Neubert, J., Kobbe, R., Berlin, C., Feiterna-Sperling, C., Buchholz, B., Notheis, G., de Martino, M., Angelo Tovo, P., Patrizia, O., Larovere, D., Ruggeri, M., Faldella, G., Baldi, F., Badolato, R., Montagnani, C., Venturini, E., Lisi, C., Di Biagio, A., Taramasso, L., Giacomet, V., Erba, P., Esposito, S., Lipreri, R., Salvini, F., Tagliabue, C., Cellini, M., Bruzzese, E., Lo Vecchio, A., Rampon, O., Donà, D., Romano, A., Dodi, I., Maccabruni, A., Consolini, R., Bernardi, S., Tchidjou Kuekou, H., Genovese, O., Olmeo, P., Cristiano, L., Mazza, A., Gabiano, C., Garazzino, S., Pellegatta, A., Pajkrt, D., Weijsenfeld, A., de Boer CG, Jurriaans, S., Back, N., Zaaijer, H., Berkhout, B., Cornelissen, M., Schinkel, C., Wolthers, K., Fraaij, P., van Rossum AMC, van der Knaap LC, Visser, E., Koopmans, M., van Kampen JJA, Pas, S., Henriet, S., van de Flier, M., van Aerde, K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F., Schölvinck, E., de Groot-de Jonge, H., Niesters, H., van Leer-Buter CC, Knoester, M., Bont, L., Geelen, S., Wolfs, T., Nauta, N., Ang, C., van Houdt, R., Pettersson, A., Vandenbroucke-Grauls, C., Reiss, P., Bezemer, D., van Sighem AI, Wit, F., Boender, T., Zaheri, S., Hillebregt, M., de Jong, A., Bergsma, D., Grivell, S., Jansen, A., Raethke, M., Meijering, R., de Groot, L., van den Akker, M., Bakker, Y., Claessen, E., El Berkaoui, A., Koops, J., Kruijne, E., Lodewijk, C., Munjishvili, L., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Rutkens, T., Schoorl, M., Timmerman, A., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Woudstra, T., Tuk, B., Popielska, J., Pokorska-Śpiewak, M., Ołdakowska, A., Zawadka, K., Coupland, U., DorobaLaura Marques, M., Teixeira, C., Fernandes, A., Voronin, E., Miloenko, M., Labutina, S., Tomás Ramos, J., Prieto, L., Luisa Navarro, M., Saavedra, J., Santos, M., Angeles Muñoz, M., Ruiz, B., Mc Phee CF, de Ory SJ, Alvarez, S., Ángel Roa, M., Beceiro, J., Martínez, J., Badillo, K., Apilanez, M., Pocheville, I., Garrote, E., Colino, E., Gómez Sirvent, J., Garzón, M., Román, V., Montesdeoca, A., Mateo, M., José Muñoz, M., Angulo, R., Neth, O., Falcón, L., Terol, P., Luis Santos, J., Moreno, D., Lendínez, F., Grande, A., José Romero, F., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Guerrero, C., Collado, P., Antonio Couceiro, J., Pérez, A., Isabel Piqueras, A., Bretón, R., Segarra, I., Gavilán, C., Jareño, E., Montesinos, E., Dapena, M., Álvarez, C., Gloria Andrés, A., Marugán, V., Ochoa, C., Alfayate, S., Isabel Menasalvas, A., de Miguel, E., Aebi-Popp, K., Asner, S., Aubert, V., Battegay, M., Baumann, M., Bernasconi, E., Böni, J., Brazzola, P., Bucher, H., Calmy, A., Cavassini, M., Ciuffi, A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C., Grawe, C., Günthard, H., Haerry, D., Hasse, B., Hirsch, H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., de Tejada BM, Metzner, K., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Polli, C., Posfay-Barbe, K., Rauch, A., Rudin, C., Schmid, P., Scherrer, A., Speck, R., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Wyler, C., Yerly, S., Techakunakorn, P., Hansudewechakul, R., Kham, C., Wanchaitanawong, V., Theansavettrakul, S., Sai, M., Nanta, S., Ngampiyaskul, C., Phanomcheong, S., Hongsiriwon, S., Karnchanamayul, W., Kwanchaipanich, R., Kanjanavanit, S., Kamonpakorn, N., Nantarukchaikul, M., Layangool, P., Mekmullica, J., Lucksanapisitkul, P., Watanayothin, S., Lertpienthum, N., Warachit, B., Hanpinitsak, S., Potchalongsin, S., Thanasiri, P., Krikajornkitti, S., Attavinijtrakarn, P., Srirojana, S., Bunjongpak, S., Puangsombat, A., Na-Rajsima, S., Ananpatharachai, P., Akarathum, N., Phuket, V., Lawtongkum, W., Kheunjan, P., Suriyaboon, T., Saipanya, A., Than-In-At, K., Jaisieng, N., Suaysod, R., Chailoet, S., Naratee, N., Kawilapat, S., Kaleeva, T., Baryshnikova, Y., Soloha, S., Bashkatova, N., Raus, I., Glutshenko, O., Ruban, Z., Prymak, N., Bailey, H., Bamford, A., Butler, K., Doerholt, K., Doherty, C., Foster, C., Francis, K., Harrison, I., Kenny, J., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Peters, H., Prime, K., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Turkova, A., Welch, S., Jeannie Collins, I., Cook, C., Crichton, S., Dobson, D., Fairbrother, K., M Gibb D, Harper, L., Le Prevost, M., Van Looy, N., Walsh, A., Thrasyvoulou, L., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Sloper, K., Fidler, K., Hague, R., Price, V., Clapson, M., Flynn, J., Cardoso, A., Abou-Rayyah, M., Gurtin, D., Yeadon, S., Segal, S., Ball, C., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Clough, S., Anguvaa, L., Conway, S., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, B., Pope, S., Cliffe, L., Smyth, A., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Rogahn, D., Clarke, L., Jones, L., Offerman, B., Greenberg, M., Benson, C., Ibberson, L., Faust, S., Hancock, J., Sharland, M., Lyall, H., Monrose, C., Seery, P., Menson, E., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., Yannoulias, A., Critchton, S., Duff, C., Gomezpena, D., Lundin, R., Mangiarini, L., Nardone, A., Posfay Barbe, Klara, Universidad de Alcalá - University of Alcalá (UAH), Department of Sciences for Woman and Child's Health, Università degli Studi di Firenze = University of Florence (UniFI), Épidémiologie clinique, santé mère-enfant et VIH en Asie du Sud-Est (IRD_PHPT), Harvard University-Chiang Mai University (CMU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Saint-Denis [Ile-de-France], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service de maladies infectieuses CHU J Minjoz Besancon, Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'hématologie : Immuno-Hématologie pédiatrique et transplantation de moelle osseuse, Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universitätsklinikum Frankfurt, Infectious Diseases, San Martino Hospital, Università degli studi di Genova = University of Genoa (UniGe), Department of Maternal and Pediatric Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Maternal-Infantile Department, Unit of Paediatrics and Oncohematology, University Hospital of Parma, Department of Infectious Diseases, IRCCS S. Matteo, Department of Paediatrics, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Dipartimento di Ingegneria [Benevento], Università degli Studi del Sannio, University of Twente, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Infectious Diseases and Perinatal Screening, Center for Infectious Disease Control, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Synthèse, Structure et Propriétés de Matériaux Fonctionnels (STEP), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Stichting HIV Monitoring, Universidade Federal do Ceará = Federal University of Ceará (UFC), Departamento de Química Orgánica, Universidade de Vigo, Polytechnical University of Valencia, Fac Biol, Dept Genet, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Service des maladies infectieuses, Hôpitaux Universitaires de Genève (HUG), University of Basel (Unibas), Dysfonctions métaboliques et diabètes: Mécanismes et approches thérapeutiques, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), University Heart Centre Freiburg - Bad Krozingen, Prapokklao Hospital [Chanthaburi, Thailand], Nakornping Hospital [Chiang Mai, Thailand], Samutsakhon Hospital [Samutsakhon, Thailand], Kalasin Hospital [Kalasin, Thailand], Sanpatong Hospital [Chiang Mai, Thailand], Chiang Mai University (CMU), Microbiology Department, St. Jame's Hospital, University of Edinburgh, Infectious Diseases and Microbiology Unit, Great Ormond Street Hospital for Children [London] (GOSH)-Institute of Child Health, European Synchrotron Radiation Facility (ESRF), Centre for Ecology and Hydrology [Bangor] (CEH), Natural Environment Research Council (NERC), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), University of London [London], London South Bank University (LSBU), Dipartimento di Pediatria, Azienda Ospedaliera di Padova, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group in EuroCoord, Florence University, Harvard University [Cambridge]-Chiang Mai University (CMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), University of Genoa (UNIGE), Catholic University of Rome, University of Twente [Netherlands], Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), University of the Basque Country [Bizkaia] (UPV/EHU), Université Nice Sophia Antipolis (... - 2019) (UNS), Pediatrics, Virology, Chappell, Elizabeth, Riordan, Andrew, Jourdain, Gonzague, Soriano-Arandes, Antoni, Ene, Luminita, J Scherpbier, Henriette, Warszawski, Josiane, J Collins, Intira, Smit, Colette, Marques, Laura, Klein, Nigel, Guillén, Sara, Judd, Ali, Thorne, Claire, Goodall, Ruth, Königs, Christoph, Spoulou, Vana, Prata, Filipa, Goetghebuer, Tessa, Chiappini, Elena, Galli, Luisa, Naver, Lar, Giaquinto, Carlo, M Gibb, Diana, Marczynska, Magdalena, Okhonskaia, Liubov, Klimkait, Thoma, Lallemant, Marc, Ngo-Giang-Huong, Nicole, Kiseleva, Galyna, Malyuta, Ruslan, Volokha, Alla, Hainaut, Marc, Delforge, Marc, Le Chenadec, Jerome, Ramos, Elisa, Dialla, Olivia, Wack, Thierry, Laurent, Corine, Ait Si Selmi, Lamya, Leymarie, Isabelle, Ait Benali, Fazia, Brossard, Maud, Boufassa, Leila, Floch-Tudal, Corinne, Firtion, Ghislaine, Hau, Isabelle, Chace, Anne, Bolot, Pascal, Blanche, Stéphane, Levine, Martine, Kremlin Bicëtre, Le, Fourcade, Corinne, Heller-Roussin, Brigitte, Runel-Belliard, Camille, Tricoire, Joëlle, Chirouze, Catherine, Reliquet, Véronique, Brouard, Jacque, Kebaili, Kamila, Fialaire, Pascale, Lalande, Muriel, Schultze-Strasser, Stephan, Baumann, U, Niehues, T, Neubert, J, Kobbe, R, Berlin, Charite, Feiterna-Sperling, C, Königs, C, Buchholz, B, Notheis, G, de Martino, Maurizio, Angelo Tovo, Pier, Patrizia, Osimani, Larovere, Domenico, Ruggeri, Maurizio, Faldella, Giacomo, Baldi, Francesco, Badolato, Raffaele, Montagnani, Carlotta, Venturini, Elisabetta, Lisi, Catiuscia, Di Biagio, Antonio, Taramasso, Lucia, Giacomet, Vania, Erba, Paola, Esposito, Susanna, Lipreri, Rita, Salvini, Filippo, Tagliabue, Claudia, Cellini, Monica, Bruzzese, Eugenia, LO VECCHIO, Andrea, Paediatric Infectious Diseases / Rheumatology / Immunology, Amsterdam institute for Infection and Immunity, AII - Infectious diseases, Amsterdam Reproduction & Development (AR&D), APH - Aging & Later Life, Infectious diseases, and Global Health
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0301 basic medicine ,medicine.medical_treatment ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,HIV Infections ,Rate ratio ,Cohort Studies ,0302 clinical medicine ,Pregnancy ,Antiretroviral Therapy, Highly Active ,Prevalence ,030212 general & internal medicine ,Child ,poor immune response ,ddc:618 ,Immunosuppression ,Viral Load ,Hepatitis B ,Thailand ,3. Good health ,Europe ,Thailand/epidemiology ,Infectious Diseases ,Cohort ,Coinfection ,Female ,Cohort study ,Adult ,Microbiology (medical) ,viral suppression ,medicine.medical_specialty ,Adolescent ,Anti-HIV Agents ,antiretroviral therapy ,030106 microbiology ,Europe/epidemiology ,03 medical and health sciences ,children ,Acquired immunodeficiency syndrome (AIDS) ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Humans ,HIV ,Aged ,Settore MED/38 - Pediatria Generale e Specialistica ,business.industry ,Immunity ,medicine.disease ,HIV Infections/drug therapy/epidemiology ,CD4 Lymphocyte Count ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Anti-HIV Agents/therapeutic use ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children Results Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P < .001). Conclusions One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders.
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- 2020
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7. Selective Changes in the Immune Profile of Tumor-Draining Lymph Nodes After Different Neoadjuvant Chemoradiation Regimens for Locally Advanced Cervical Cancer
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Fattorossi, Andrea [Gynecologic Oncology Unit, Catholic University of Rome, Rome (Italy)]
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- 2010
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8. Post cholecystectomy bile duct injury: early, intermediate or late repair with hepaticojejunostomy – an E-AHPBA multi-center study
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Rystedt, J.M.L., Kleeff, J., Salvia, R., Besselink, M.G., Prasad, R., Lesurtel, M., Sturesson, C., Abu Hilal, M., Aljaiuossi, A., Antonucci, A., Ardito, F., Ausania, F., Bernon, M., Berrevoet, F., Bjornsson, B., Bonsing, B.A., Boonstra, E.A., Bracke, B., Brusadin, R., Burda, L., Caraballo, M., Casellas-Robert, M., Coker, A., Davide, J., Gelder, A. de, Rose, A.M. de, Djokic, M., Dudek, K., Ekmekcigil, E., Filauro, M., Fulop, A., Gallagher, T.K., Gastaca, M., Gefen, R., Giuliante, F., Habibeh, H., Halle-Smith, J., Haraldsdottir, K.H., Hartman, V., Hauer, A., Hemmingsson, O., Hoskovec, D., Isaksson, B., Jonas, E., K.A., Klug, R., Krige, J., Lignier, D., Lindemann, J., Lopez-Lopez, V., Lucidi, V., Mabrut, J.Y., Mansson, C., Mieog, S., Mirza, D.F., Oldhafer, K.J., Omoshoro-Jones, J.A.O., Ortega-Torrecilla, N., Otto, W., Panaro, F., Pando, E., Paterna-Lopez, S., Pekmezci, S., Pesce, A., Porte, R.J., Poves, I., Calvo, M.P., Primavesi, F., Puleo, S., Recordare, A., Rizell, M., Roberts, K., Robles-Campos, R., Sanchiz-Cardenas, E., Sandstrom, P., Saribeyoglu, K., Schauer, M., Schreuder, M., Siriwardena, A.K., Smith, M.D., Silva, D.S., Sparrelid, E., Stattner, S., Stavrou, G.A., Straka, M., Stromberg, C., Sutcliffe, R.P., Szijarto, A., Taflin, H., Trotovsek, B., Gulik, T. van, Wallach, N., Zieniewicz, K., European-African HepatoPancreato, Skane University Hospital [Lund], Fachbereich Physik [Halle-Saale], Martin-Luther-Universität Halle Wittenberg (MLU), Azienda Ospedaliera Universitaria Integrata of Verona, University of Amsterdam [Amsterdam] (UvA), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Karolinska University Hospital [Stockholm], University of Southampton, Policlinico di Monza, Partenaires INRAE, Universita 'La Sapienza' Roma (Istituto CNR), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Catholic University, Rome, Italy, Complexo Hospitalario Universitario de Vigo, Ghent University Hospital, Linköping University (LIU), Universiteit Leiden [Leiden], University Medical Center Groningen [Groningen] (UMCG), Universiteit Antwerpen [Antwerpen], Universidad de Murcia, J. G. Mendel Cancer Center Novy Jicin, Universidad de Salamanca, Hospital Dr Josep Trueta de Girona, Izmir University, TURKEY, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto, University of Ljubljana, University of Warsaw (UW), İZMİR EGE University Medical Faculty Hospital, Univeristà di Genova, Semmelweis University of Medicine [Budapest], University of Dublin, Universidad de Deusto [Bilbao] (DEUSTO), Universidad de Deusto (DEUSTO), Hospital Universitario Cruces = Cruces University Hospital, Hadassah Hebrew University Hospital, The Hebrew University of Jerusalem (HUJ), Catholic University of Rome, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Queens Elizabeth Hospital [Birmingham], University of Iceland [Reykjavik], Community Hospital of horn, Umeå University, University Hospital Motol [Prague], Uppsala Universitet [Uppsala], University of Cape Town, Hadassah Hebrew University Medical Center [Jerusalem], Community Hospital Horn, CHU Amiens-Picardie, Vrije Universiteit Brussel (VUB), Université de Lyon, Asklepios Klinik Barmbek, University of Johannesburg (UJ), Vall d'Hebron University Hospital [Barcelona], Facultad de Medicina [Zaragoza], University of Zaragoza - Universidad de Zaragoza [Zaragoza], Cerrahpasa Medical Faculty, University of Catania [Italy], IMIM-Hospital del Mar, Generalitat de Catalunya, Innsbruck Medical University [Austria] (IMU), Unité Expérimentale Recherches Intégrées - Gotheron (UERI), Institut National de la Recherche Agronomique (INRA), University of Pristina-Kosovo, Peja/Pec Hospital, Sahlgrenska Academy at University of Gothenburg [Göteborg], Universidad de Málaga [Málaga] = University of Málaga [Málaga], University Hospital Düsseldorf, Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Manchester Royal Infirmary, University of Manchester [Manchester], Chris Hani Baragwanath Hospital, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), European-African HepatoPancreato, Ege Üniversitesi, Groningen Institute for Organ Transplantation (GIOT), Surgery, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, CCA - Cancer Treatment and Quality of Life, and AGEM - Endocrinology, metabolism and nutrition
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INTRAOPERATIVE CHOLANGIOGRAPHY ,Male ,IMPACT ,Settore MED/18 - CHIRURGIA GENERALE ,medicine.medical_treatment ,Jejunostomy ,Hepatic Duct, Common ,Comorbidity ,030230 surgery ,0302 clinical medicine ,Cholangiography ,Older patients ,Hepatic Duct ,Clinical endpoint ,LAPAROSCOPIC CHOLECYSTECTOMY ,COMPLICATIONS ,OUTCOMES ,medicine.diagnostic_test ,Bile duct ,Gastroenterology ,Hepaticojejunostomy ,Middle Aged ,Common ,3. Good health ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Adult ,medicine.medical_specialty ,Bile duct injuries (BDI) ,CLASSIFICATION ,Time-to-Treatment ,Biliary injury ,03 medical and health sciences ,Sex Factors ,HEPATIC-ARTERY INJURY ,medicine ,MANAGEMENT ,Humans ,Cholecystectomy ,Aged ,Retrospective Studies ,Hepatology ,business.industry ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,BILIARY INJURY ,Surgery ,Multi center study ,Concomitant ,RISK-FACTORS ,Human medicine ,Bile Ducts ,business - Abstract
13th World Biennial Congress of the International-Hepato-Pancreato-Biliary-Association (IHPBA) -- SEP 04-07, 2018 -- Geneva, SWITZERLAND, Ardito, Francesco/0000-0003-1596-2862; PESCE, ANTONIO MD/0000-0002-7560-551X; Gallagher, Tom/0000-0002-5765-2574; Bernon, Marc/0000-0002-7967-8548; Stattner, Stefan/0000-0002-5226-7597; GIULIANTE, FELICE/0000-0003-2087-2589; Omoshoro-Jones, Jones A. O./0000-0002-1071-298X; de Rose, Agostino Maria/0000-0003-3310-8088; Abu Hilal, Mohammed/0000-0002-3162-4639; Kleeff, Jorg/0000-0003-3432-6669; Prieto, Mikel/0000-0001-6662-4252; Stromberg, Cecilia/0000-0003-0843-7920, WOS: 000500283700006, PubMed: 31151812, Background: Treatment of bile duct injuries (BDI) during cholecystectomy depends on the severity of injury and the timing of diagnosis. Standard of care for severe BDIs is hepaticojejunostomy. the aim of this retrospective multi-center study was to assess the optimal timing for repair of BDI with hepaticojejunostomy. Methods: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients with hepaticojejunostomy after BDI from January 2000 to June 2016. Patients were stratified according to the timing of biliary reconstruction with hepaticojejunostomy: early (day 0-7), intermediate (1-6 weeks) and late (6 weeks-6 months). Primary endpoint was re-intervention >90 days after the hepaticojejunostomy and secondary endpoints were severe 90-day complications and liver-related mortality. Results: in total 913 patients from 48 centers were included in the analysis. in 401 patients (44%) the bile duct injury was diagnosed intraoperatively, and 126 patients (14%) suffered from concomitant vascular injury. in multivariable analysis the timing of hepaticojejunostomy had no impact on postoperative complications, the need for re-intervention after 90 days nor liver-related mortality. the rate of re-intervention more than 90 days after the hepaticojejunostomy was significantly increased in male patients but decreased in older patients. Severe co-morbidity increased the risk for liver-related mortality (HR 3.439; CI 1.37-8.65; p = 0.009). Conclusion: After BDI occurring during cholecystectomy, the timing of biliary reconstruction with hepaticojejunostomy did not have any impact on severe postoperative complications, the need for re-intervention or liver-related mortality. Individualised treatment after iatrogenic bile duct injury is still advisable., Int Hepato Pancreato Biliary Assoc
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- 2019
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9. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice
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Max Nieuwdorp, Colleen R. Kelly, Gianluca Ianiro, Luca Masucci, Dina Kao, E.M. Terveer, Patrizia Kump, Maria J G T Vehreschild, Ailsa Hart, Antonio Gasbarrini, Franco Scaldaferri, Antonio López-Sanromán, Benjamin H. Mullish, Reetta Satokari, Juozas Kupcinskas, Zain Kassam, Josbert J. Keller, Stacy A. Kahn, Lorenza Putignani, Giovanni Cammarota, Perttu Arkkila, Jessica R. Allegretti, Herbert Tilg, Loris Riccardo Lopetuso, Ed J. Kuijper, Monika Fischer, Samuel P Costello, Harry Sokol, Cristina Pintus, Experimental Vascular Medicine, Vascular Medicine, ACS - Diabetes & metabolism, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Internal Medicine and Gastroenterology, Day Hospital of Gastroenterology and Intestinal Microbiota Transplantation, Fondazione Policlinico A Gemelli IRCCS, Catholic University of Medicine-Catholic University of Medicine, Warren Alpert Medical School of Brown University, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London-Imperial College London, Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School [Boston] (HMS)-Harvard Medical School [Boston] (HMS), Microbiome Informatics, Massachusetts Institute of Technology (MIT), OpenBiome, Parasitology Unit and Human Microbiome Unit, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Department of Medicine, Indiana State University, Department of Gastroenterologyand Hepatology, Haaglanden Medical Center, National Donor Feces Bank, Department of Gastroenterology, The Queen Elizabeth Hospital, University of South Australia [Adelaide]-University of South Australia [Adelaide], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), French Group of Fecal Microbiota Transplantation, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Karl-Franzens-Universität [Graz, Autriche]-Karl-Franzens-Universität [Graz, Autriche], Human Microbiome Research Program, University of Helsinki-University of Helsinki, Hepatology and Nutrition, Boston Children's Hospital-Boston Children's Hospital, University of Alberta-University of Alberta, Department of Clinic of Gastroenterology, University of Helsinki, Department of Medical Microbiology, LeidenUniversity Medical Centre, Department I of Internal Medicine, German Centre for Infection Research, University Hospital of Cologne [Cologne]-University Hospital of Cologne [Cologne], Tissues and Cells Area, Italian National Transplant Center, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Microbiology, VU University Medical Center [Amsterdam], Gastroenterology and Hepatology Department, Hospital Universitario Ramon y Cajal, Partenaires INRAE-Partenaires INRAE, Institute for Digestive Research, Medical Academy, Lithuanian University of health Sciences-Lithuanian University of health Sciences-Medical Academy, Lithuanian University of health Sciences-Lithuanian University of health Sciences, St Mark's Hospital, Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Innsbruck Medical University [Austria] (IMU), Catholic University of Rome, Line D-1, Service de Gastroenterologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, University of Graz-University of Graz, Reetta Maria Satokari / Principal Investigator, HUMI - Human Microbiome Research, HUS Abdominal Center, University Management, Gastroenterologian yksikkö, Clinicum, and Internal medicine
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0301 basic medicine ,Delphi method ,Donor Feces ,Frozen ,0302 clinical medicine ,stool bank ,Medicine ,Gastroenterology ,Consensus conference ,fecal microbiota transplantation ,Metaanalysis ,3. Good health ,Clinical Practice ,Editorial ,030211 gastroenterology & hepatology ,Medical emergency ,Recurrent ,guideline ,Consensus ,Efficacy ,Settore MED/12 - GASTROENTEROLOGIA ,Faecal microbiota transplantation ,Donor Selection ,Specimen Handling ,03 medical and health sciences ,microbiota ,Humans ,Organ donation ,Active Ulcerative-colitis ,Gastroenterology & Hepatology ,business.industry ,1103 Clinical Sciences ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Guideline ,Clostridium difficile ,medicine.disease ,Gastrointestinal Microbiome ,030104 developmental biology ,Workflow ,3121 General medicine, internal medicine and other clinical medicine ,Intestinal Microbiota ,Insulin Sensitivity ,Organ Donation ,clostridioides difficile ,Clostridium Infections ,Fecal Microbiota Transplantation ,1114 Paediatrics and Reproductive Medicine ,business ,Clostridium-difficile Infection ,Clostridioides - Abstract
Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.
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- 2019
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10. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
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John Hardy, Nick C. Fox, Lena Lilius, Christine Van Broeckhoven, Mindy J. Katz, Carlos Cruchaga, Joshua W. Miller, Carol Brayne, Letizia Concari, Christopher Shaw, Minerva M. Carrasquillo, Richard Mayeux, Anne Boland, Charles DeCarli, Helena C. Chui, Laura B. Cantwell, Yoland Aladro Benito, Chuang Kuo Wu, Elaine R. Peskind, Andrew McDavid, M. Ilyas Kamboh, Amanda Smith, Pascual Sánchez-Juan, Jean-François Deleuze, Jayanadra J. Himali, Thomas H. Mosley, Thomas J. Montine, Chuanhai Cao, Andreas J. Forstner, Thomas G. Beach, Robert Barber, Miquel Aguilar, Liming Qu, Jerome I. Rotter, Matthew J. Huentelman, Christiane Reitz, Christopher J. O'Donnell, Steven G. Younkin, Bradley T. Hyman, Bruce L. Miller, Rachelle S. Doody, Eric B. Larson, Ronald L. Hamilton, Todd E. Golde, Steven E. Arnold, Melissa E. Garcia, Rachel Raybould, Lena Kilander, Mark A. Sager, Kevin Morgan, Kathryn L. Lunetta, William Perry, Joseph D. Buxbaum, Craig S. Atwood, Thomas D. Bird, Michael Conlon O'Donovan, Robert Olaso, Juan Fortea, Susanne Moebus, Lisa L. Barnes, Rachel Marshall, Huntington Potter, Mercè Boada, Shahzad Ahmad, Paolo Caffarra, Daniel C. Marson, Jonathan L. Haines, Perrie M. Adams, John M Olichney, Lars Lannfelt, Stefanie Heilmann-Heimbach, Markus M. Nöthen, Shubhabrata Mukherjee, John Malamon, Xue Wang, Christopher S. Carlson, Karen Ritchie, Roger N. Rosenberg, Paul K. Crane, Alexa S. Beiser, Céline Bellenguez, Robert C. Green, Maria Urbano, Petra Proitsi, John Powell, Elisa Majounie, Ammar Al-Chalabi, Hakon Hakonarson, Yogen Patel, Martin Scherer, Julie Williams, Richard B. Lipton, Vincent Dermecourt, Adam L. Boxer, Gerard D. Schellenberg, David G. Clark, Anita L. DeStefano, Joel H. Kramer, Victoria Alvarez, Nandini Badarinarayan, Oscar L. Lopez, Chris Corcoran, Ubaldo Bonuccelli, Donald R. Royall, James Bowen, Monica Diez Fairen, Tricia A. Thornton-Wells, Nilufer Ertekin-Taner, Florence Pasquier, Martin Ingelsson, Yi Zhao, John R. Gilbert, Valentina Escott-Price, Amanda B. Kuzma, Fabienne Garzia, Reinhard Heun, Otto Valladares, Andrew J. Saykin, Sara Ortega-Cubero, Liana G. Apostolova, Henry L. Paulson, John K Kauwe, Imelda Barber, Carolina Ceballos Diaz, Douglas Galasko, M. Arfan Ikram, Lluís Tárraga, Carlo Caltagirone, Joan S. Reisch, Wolfgang Maier, Bruno Vellas, Rebecca Sims, Angela Hodges, Matthew P. Frosch, Isabel Henández, Annakaisa Haapasalo, Thor Aspelund, Håkan Thonberg, Aimee Pierce, Roger L. Albin, Wayne W. Poon, Rebecca Sussams, Amy Braddel, Ranjan Duara, Albert V. Smith, Kirk C. Wilhelmsen, Gianfranco Spalletta, Simon Lovestone, Peter Passmore, Ana Frank-García, Cynthia M. Carlsson, Jade Chapman, Nathan D. Price, Philip L. De Jager, John M. Ringman, Seung Hoan Choi, Nicola Denning, Michael John Owen, Clinton T. Baldwin, Amalia C. Bruni, Denis A. Evans, Rudolph E. Tanzi, Dominique Campion, Laura Fratiglioni, Alberto Lleó, Per Hoffmann, Carole Dufouil, Charlotte Forsell, Alun Meggy, Charlene Thomas, Robert S. Stern, James B. Leverenz, Tatiana Foroud, William W. Seeley, James J. Lah, Brian A. Lawlor, Kenneth B. Fallon, Matthias Riemenschneider, Ryan M. Huebinger, Regina M. Carney, Clinton B. Wright, Didier Hannequin, Deborah Blacker, Anne Kinhult-Ståhlbom, Ekaterina Rogaeva, Andrew P. Lieberman, Bernardino Ghetti, Linda J. Van Eldik, Bernadette McGuinness, Thomas Fairchild, Margaret A. Pericak-Vance, Ashok Raj, Reinhold Schmidt, Ronald C. Petersen, Harald Hampel, María J. Bullido, Steven L. Carroll, Maria Candida Deniz Naranjo, Kathleen A. Welsh-Bohmer, Myriam Fornage, Joseph F. Quinn, Caroline Graff, Claudia L. Satizabal, Patrice L. Whitehead, David Wallon, Christopher Medway, Lindsay A. Farrer, Vilmundur Gudnason, Peter St George-Hyslop, Pau Pastor, Frank Jessen, Erin L. Abner, Johanna Jakobsdottir, Hieab H.H. Adams, Roberta Cecchetti, Walter A. Kukull, Thomas S. Wingo, Michelle K. Lupton, Valur Emilsson, Susan M. McCurry, Simon Mead, Hilkka Soininen, Sandra Weintraub, Amy Gerrish, Lindy E. Harrell, Lina Keller, Jean-Charles Lambert, Denise Harold, Stephen Todd, Wei Gu, Maura Gallo, Najaf Amin, Lenore J. Launer, Eleonora Sacchinelli, Mikko Hiltunen, Cécile Dulary, Eliecer Coto, Xueqiu Jian, Nathalie Fievet, Patrizia Mecocci, Sarah Taylor, Eric Boerwinkle, Maria Serpente, Ronald G. Munger, Ina Giegling, Carlo Masullo, Aoibhinn Lynch, Eliezer Masliah, Anne M. Koivisto, Chang En Yu, Qiong Yang, Benedetta Nacmias, Wayne C. McCormick, Kristelle Brown, Alessio Squassina, Deborah C. Mash, Brian W. Kunkle, Makrina Daniilidou, Alison Goate, David Carrell, Kara L. Hamilton-Nelson, Sandra Barral, Vincent Chouraki, Kristel Sleegers, Frank J. Wolters, Joseph E. Parisi, Iwona Kłoszewska, Ronald C. Kim, Sonia Moreno-Grau, Marina Arcaro, Carmen Muñoz Fernadez, Vernon S. Pankratz, Duane Beekly, Sabrina Pichler, Gislain Septier, Delphine Bacq, Amanda J. Myers, Adam C. Naj, Frank Martiniuk, Sudha Seshadri, Badri N. Vardarajan, Joshua A. Sonnen, M.-Marsel Mesulam, Howard J. Rosen, James T. Becker, Chiara Fenoglio, Ge Li, Alberto Pilotto, Mary Sano, Olivier Hanon, Honghuang Lin, Jean Paul G. Vonsattel, W. T. Longstreth, Daniela Galimberti, David C. Rubinsztein, RoseMarie Brundin, Vilmantas Giedraitis, Christine M. Hulette, Peter Holmans, Martin Dichgans, Maria Vronskaya, Céline Derbois, Michelangelo Mancuso, Constantine G. Lyketsos, Christophe Tzourio, Jacques Epelbaum, Raffaele Maletta, Mariet Allen, Hong-Dong Li, James R. Burke, Rik Vandenberghe, David G. Mann, Bruce M. Psaty, Lawrence S. Honig, Beth A. Dombroski, Erik D. Roberson, Cornelia M. van Duijn, Benjamin Grenier-Boley, Seppo Helisalmi, Jean-François Dartigues, Russell H. Swerdlow, Paola Bossù, Ashley R. Winslow, Elio Scarpini, Lesley Jones, Sebastien Engelborghs, John Q. Trojanowski, Jeffrey Kaye, Jenny Lord, Chiara Cupidi, Janet A. Johnston, Dan Rujescu, Feroze Golamaully, Anne Braae, Rafael Blesa, L. Adrienne Cupples, Dennis W. Dickson, Gail P. Jarvik, David W. Fardo, David H. Cribbs, Michael Gill, Jose Bras, Allan I. Levey, Jennifer Williamson, Rhodri Thomas, John C. Morris, Lei Yu, Debby W. Tsuang, Annette M. Hartmann, John H. Growdon, John Collinge, Claudine Berr, Fernando Rivadeneira, Oliver Peters, Albert Hofman, Frank M. LaFerla, Vivianna M. Van Deerlin, James Uphill, David A. Bennett, Onofre Combarros, Gudny Eiriksdottir, Jeremy D. Burgess, Melanie L. Dunstan, Elizabeth Crocco, Keeley J. Brookes, Robert R. Graham, Lon S. Schneider, Eden R. Martin, Matt Hill, Neill R. Graff-Radford, Joseph T. Hughes, Vincenzo Solfrizzi, Taniesha Morgan, Antonio Ciaramella, Bruno Dubois, Juan C. Troncoso, Paolo Bosco, Jordi Clarimón, Daniel H. Geschwind, Virginia Boccardi, Barry Reisberg, Timothy W. Behrens, Annette L. Fitzpatrick, Salvatore Spina, Alexis Brice, Eileen H. Bigio, Marla Gearing, Jeffrey M. Burns, Carol A. Miller, Marilyn S. Albert, Sven J. van der Lee, Sandro Sorbi, C. Dirk Keene, Daniel Levy, Antonio Daniele, Eric M. Reiman, Paramita Chakrabarty, Oscar Sotolongo-Grau, Helena Schmidt, Francesco Panza, Murray A. Raskind, Rita Guerreiro, Gyungah Jun, Anna Karydas, Markus Leber, Harry V. Vinters, Cory C. Funk, Charles C. White, Jill R. Murrell, Sid E. O'Bryant, Nigel J. Cairns, Josée Dupuis, Ann C. McKee, Julie A. Schneider, Megan L. Grove, Malcolm B. Dick, Bradley F. Boeve, Jennifer A. Brody, Sanjay Asthana, Agustín Ruiz, Stefan Herms, Yuning Chen, David Craig, Neil W. Kowall, Maria Donata Orfei, JoAnn T. Tschanz, Florentino Sanchez Garcia, Manuel Mayhaus, Alfredo Ramirez, James Turton, André G. Uitterlinden, Davide Seripa, Lee-Way Jin, Kelley Faber, Maria C. Norton, Shuo Li, Steven H. Ferris, Steffi G. Riedel-Heller, Joshua C. Bis, Li-San Wang, Johannes Kornhuber, Peter Paul De Deyn, Martin R. Farlow, Randall L. Woltjer, Gary W. Beecham, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Icelandic Heart Association [Kopavogur, Iceland] (IHA), John P. Hussman Institute for Human Genomics [Miami, FL, USA], University of Miami [Coral Gables], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Medicine, University of Washington [Seattle], Dr. John T. Macdonald Foundation [Miami, FL, USA] (Department of Human Genetics), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], Department of Molecular Genetics, Institut Català de Neurociències Aplicades [Barcelona, Spain], Well Advanced Solutions, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], The University of Texas Health Science Center at Houston (UTHealth), Columbia University [New York], University of Eastern Finland, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), John P. Hussman Institute for Human Genomics, Neurobiologie de la Croissance et de la Senescence, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Emmy Noether Project (SFB 833), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Boston University [Boston] (BU), Department of Genomics, Institute for Systems Biology [Seattle, WA, USA], Universitätsklinikum Bonn (UKB), Centre of Excellence for Robotic Vision [Canberra], Australian Research Council [Canberra] (ARC), Neuroscience and Mental Health Research Institute [Cardiff, UK] (School of Medicine), Boston University School of Medicine (BUSM), Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, University of Pennsylvania [Philadelphia], Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Department of Epidemiology and Biostatistics, ERASMUS, Hospital Universitario Doctor Negrín [Las Palmas de Gran Canaria, Spain], Department of Neurodegenerative Diseases, University of Mississippi Medical Center (UMMC), Pathology and Laboratory Medicine [Philadelphia, PA, USA] (Penn Neurodegeneration Genomics Center), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioinformatics, GlaxoSmithKline, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], University of Nottingham, UK (UON), University of Texas Health Science Center, Department of Neurobiology, Caring Sciences and Society (NVS), University of Bari Aldo Moro (UNIBA), Ageing Group, Centre for Public Health, Queen's University [Belfast] (QUB), Mayo Clinic [Jacksonville], Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Università degli Studi di Perugia (UNIPG), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), CHU Rouen, Normandie Université (NU), Universidad Autonoma de Madrid (UAM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Florida [Gainesville] (UF), University of Parma = Università degli studi di Parma [Parme, Italie], Center for Cognitive Disorders AUSL [Parma, Italy], School of Public Health [Boston], Uppsala University, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Xi'an Jiaotong University (Xjtu), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Institute of Gerontology and Geriatrics, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Geriatric Medicine and Metabolic Diseases, Departments of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf [Hamburg, Germany], University of Texas Southwestern Medical Center [Dallas], University of Cologne, Laboratoire d'Etudes et de Recherche en Informatique d'Angers (LERIA), Université d'Angers (UA), Johns Hopkins University (JHU), Universität Leipzig [Leipzig], University of Iceland [Reykjavik], Metacohorts Consortium, Harvard School of Public Health, Catholic University of Rome, Medical University Graz, Baylor College of Medicine (BCM), Baylor University, University of North Texas Health Science Center [Fort Worth], Santa Lucia Foundation (IRCCS), Nextel S.A. [Bilbao], Massachusetts General Hospital [Boston], Department of Pathology and Laboratory Medicine and Indiana Alzheimer disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Joint Institute for the Study of the Atmosphere and Ocean (JISAO), Beijing University of Technology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Saul B. Korey Department of Neurology, Albert Einstein College of Medicine [New York]-Yeshiva University, Utah State University (USU), Fundació per la Recerca Biomèdica i Social Mútua Terrassa [Barcelona, Spain], Hospital Universitario Mutua de Terrassa, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Medical University of Łódź (MUL), University of Leicester, MRC Prion Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Fondazione Istituto di Ricerca e Cura Carattere Scientifico [Rome], Università degli Studi di Roma Tor Vergata [Roma], Saarland University Hospital, Universitat Autònoma de Barcelona (UAB), Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Universidade do Porto, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Experimental and Clinical Pharmacology, St. James Hospital and Trinity College [Dublin, Ireland], School of Medicine [Dublin], Trinity College Dublin, University of Sheffield [Sheffield], Lancaster University, University of Michigan [Ann Arbor], University of Michigan System, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, University of Wisconsin-Madison, Rush Alzheimer Disease Center [Chicago, IL, États-Unis], Rush University Medical Center [Chicago], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), School of Engineering [Cardiff], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Northwestern University Feinberg School of Medicine, Mayo Clinic [Rochester], Swedish Medical Center [Seattle, WA, USA], University of California [San Francisco] (UCSF), University of California, Duke University [Durham], University of Kansas Medical Center [Lawrence], Laboratory of Molecular Neuropsychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Washington University in Saint Louis (WUSTL), University of South Florida [Tampa] (USF), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Medical University of South Carolina [Charleston] (MUSC), University of Southern California (USC), Los Alamos National Laboratory (LANL), Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), University of California [Irvine] (UCI), Mount Sinai Medical Center, Indiana State University, University of Alabama at Birmingham [ Birmingham] (UAB), University of Kentucky, New York University [New York] (NYU), NYU System (NYU), Department of Medical and Molecular Genetics, Department of Epidemiology and biostatistics, VU University Medical Center [Amsterdam], Emory University [Atlanta, GA], Department of Neurology, University of California-University of California-David Geffen School of Medicine [Los Angeles], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Department of Medical Genetics, HMNC Brain Health, Alzheimer Disease Research Laboratory, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Laboratoire d'Informatique, Systèmes, Traitement de l'Information et de la Connaissance (LISTIC), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Psychiatry, School of Medicine-Johns Hopkins University and Johns Hopkins Bayview Medical Center, Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Department of neurosciences, University of California [San Diego] (UC San Diego), Department of Physics and Astronomy [Fort Worth], Texas Christian University (TCU), Department of Computer Science [University of California, Davis], Indiana University System, Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), Department of Laboratory Medicine and Pathology, Mayo Clinic, Institute for Memory Impairments and Neurological Disorders [Irvine], University of Colorado Anschutz [Aurora], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Keck School of Medicine [Los Angeles], Indiana University [South Bend], Massachusetts General Hospital, Novartis Institutes for Biomedical Research [Cambridge, MA, USA], Departments of Pathology and Laboratory Medicine (Neuropathology) and Neurology, UCLA Medical Center-David Geffen School of Medicine [Los Angeles], University of California-University of California-University of California [Los Angeles] (UCLA), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Institut de Génomique d'Evry (IG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Antwerp (UA), Institute Born-Bunge, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University of Kuopio, Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Laboratoire d'Analyse Génomique, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Inserm-U1167, Dpt Gériatrie [CHU Broca], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Epidemiology, University of Washington, School of Medicine [Los Angeles], Albert Einstein College of Medicine [New York], IdiPAZ - Instituto de Investigación La Paz [Madrid, Spain], Instituto de Física Teórica UAM/CSIC (IFT), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Department of Internal Medicine, University of Central Asturias [Oviedo, Spain], Human Genome Sequencing Center, Baylor College of Medicine, Baylor University-Baylor University, Department of Epidemiology, Erasmus Medical Centre, Translational Genomics Research Institute [Phoenix, AZ, USA], University of Arizona, Banner Alzheimer's Institute [Phoenix, AZ, États-Unis], University of Texas Health Science Center at San Antonio [San Antonio], Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department. of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Centre for Research in Neurodegenerative Diseases, VA Puget Sound Health Care System/GRECC [Seattle, WA, USA], University of Pisa - Università di Pisa, Pfizer Worldwide Research and Development [Cambridge, MA, USA], Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt), Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Saarland University [Saarbrücken], University of Bonn, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Cambridge Institute for Medical Research (CIMR), Department of Molecular Neurosciences, Institute of Neurology, UCL, Institute of Psychiatry, Institute of psychiatry, University of British Columbia (UBC), the Clinical Neuroscience Research Group, University of Manchester [Manchester]-Greater Manchester Neurosciences Centre, Aristotle University of Thessaloniki, Memory and Dementia Centre, 3rd Department of Neurology, G. Pa, University of Barcelona, University of Southampton, Department of Psychiatry [Oxford] (POWIC), University of Oxford [Oxford]-The Warneford Hospital, School of Psychology [Cardiff University], Department of Medical Sciences, UCL, Institute of Neurology [London], Washington University School of Medicine, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), School of Medecine, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], School of Life Sciences, Department of Neuroscience, Mayo Clinic Jacksonville, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Clínica Universidad de Navarra [Pamplona], Neurodegenerative Brain Diseases Group, VIB, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Brigham Young University (BYU), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, The Gertrude H Sergivesky Center, Columbia University College of Physicians and Surgeons, Genetic Epidemiology Unit, Section of Clinical and Molecular Neurogenetics, Universität zu Lübeck [Lübeck], University of Pennsylvania - Department of Pathology & Laboratory Medecine, Framingham Heart Study [Framingham, MA, USA], ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), European Project: 29845,LSH-ACC-MENTOR, University of Pennsylvania-University of Pennsylvania, Universität Bonn = University of Bonn-Institute of Human Genetics [Bonn, Germany], Universität Leipzig-Universität Leipzig, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli Studi di Perugia = University of Perugia (UNIPG), Universidad Autónoma de Madrid (UAM), Università degli studi di Parma = University of Parma (UNIPR), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Universität Leipzig, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Yeshiva University- Albert Einstein College of Medicine [New York], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Università degli Studi di Milano = University of Milan (UNIMI), Saarland University Hospital (UKS), Università degli Studi di Firenze = University of Florence (UniFI), Universidade do Porto = University of Porto, University of California (UC)-University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Kansas Medical Center [Kansas City, KS, USA], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of Kentucky (UK), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Department of Computer Science [Univ California Davis] (CS - UC Davis), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), University of Texas Health Science Center at San Antonio [San Antonio, Tx, USA], Universität Bonn = University of Bonn, University of Oxford-The Warneford Hospital, Medical Research Council-Cardiff University, Universität zu Lübeck = University of Lübeck [Lübeck], Epidemiology, Neurology, Gastroenterology & Hepatology, Internal Medicine, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen, IRCCS 'Casa Sollievo della Sofferenza', Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (Ciberned), University of Florida [Gainesville], University of Parma, Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, Yeshiva University- Albert Einstein College of Medicine, Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), Autonomous University of Barcelona (UAB), Università degli Studi di Firenze [Firenze], Universidade do Porto [Porto], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Washington University in St Louis, University of South Florida (USF), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, McGill University, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique, Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Albert Einstein College of Medicine, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Università Cattolica del S. Cuore - Catholic University of the Sacred Hearth, University of Florence (UNIFI), CIBER de Enfermedades Neurodegenerativas (CIBERNED), Universität zu Lübeck [Lübeck] - University of Lübeck [Lübeck], [ANR-10-IAIHU-06],« Investissements d'avenir » ,Agence nationale de la recherche (ANR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Department of Psychiatry, van der Lee, Sven J [0000-0003-1606-8643], Naj, Adam C [0000-0002-9621-2942], Badarinarayan, Nandini [0000-0002-6944-748X], Chouraki, Vincent [0000-0002-4698-1794], Graham, Robert R [0000-0001-7151-4277], Hoffmann, Per [0000-0002-6573-983X], Smith, Albert V [0000-0003-1942-5845], Satizabal, Claudia L [0000-0002-1115-4430], Brody, Jennifer A [0000-0001-8509-148X], Wolters, Frank J [0000-0003-2226-4050], Lupton, Michelle K [0000-0002-7274-7299], Lin, Honghuang [0000-0003-3043-3942], Adams, Hieab H [0000-0003-3687-2508], Giedraitis, Vilmantas [0000-0003-3423-2021], Pasquier, Florence [0000-0001-9880-9788], Chen, Yuning [0000-0002-7358-7055], Bossù, Paola [0000-0002-1432-0078], Ghetti, Bernardino [0000-0002-1842-8019], Yang, Qiong [0000-0002-3658-1375], Aspelund, Thor [0000-0002-7998-5433], Bullido, María J [0000-0002-6477-1117], Rivadeneira, Fernando [0000-0001-9435-9441], Rubinsztein, David C [0000-0001-5002-5263], Al-Chalabi, Ammar [0000-0002-4924-7712], Tsolaki, Magda [0000-0002-2072-8010], De Jager, Philip L [0000-0002-8057-2505], Dickson, Dennis W [0000-0001-7189-7917], Van Broeckhoven, Christine [0000-0003-0183-7665], Ikram, M Arfan [0000-0003-0372-8585], Amouyel, Philippe [0000-0001-9088-234X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Berr, Claudine, Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID, and Mentoring of LifeSciHealth-Multipliers in the Accession Candidate Countries - LSH-ACC-MENTOR - 29845 - OLD
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0301 basic medicine ,Linkage disequilibrium ,[SDV]Life Sciences [q-bio] ,Medizin ,Sequence Homology ,Genome-wide association study ,genetics [Alzheimer Disease] ,metabolism [Microglia] ,Linkage Disequilibrium ,0302 clinical medicine ,genetics [Protein Interaction Maps] ,genetics [Membrane Glycoproteins] ,Gene Frequency ,Immunologic ,genetics [Adaptor Proteins, Signal Transducing] ,Receptors ,genetics [Exome] ,Odds Ratio ,Innate ,genetics [Receptors, Immunologic] ,Exome ,Protein Interaction Maps ,genetics [Genetic Predisposition to Disease] ,Receptors, Immunologic ,ABI3 protein, human ,Genetics ,Adaptor Proteins, Signal Transducing ,Alzheimer Disease ,Amino Acid Sequence ,Case-Control Studies ,Gene Expression Profiling ,Genetic Predisposition to Disease ,Genotype ,Humans ,Immunity, Innate ,Membrane Glycoproteins ,Microglia ,Phospholipase C gamma ,Sequence Homology, Amino Acid ,Polymorphism, Single Nucleotide ,Adaptor Proteins ,Single Nucleotide ,3. Good health ,[SDV] Life Sciences [q-bio] ,Amino Acid ,Settore MED/26 - NEUROLOGIA ,genetics [Phospholipase C gamma] ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Alzheimer's disease ,Common disease-common variant ,Biology ,Article ,03 medical and health sciences ,ddc:570 ,medicine ,Journal Article ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Polymorphism ,Allele frequency ,TREM2 protein, human ,TREM2 ,Case-control study ,Signal Transducing ,Immunity ,medicine.disease ,R1 ,Minor allele frequency ,genetics [Immunity, Innate] ,030104 developmental biology ,Human medicine ,030217 neurology & neurosurgery - Abstract
International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
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- 2017
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11. Liver Transplantation for Alcoholic Liver Disease
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Georges Philippe Pageaux, Andrea DiMartini, Ivo Graziadei, Patrizia Burra, Michael R. Lucey, Ramon Bataller, John G. OʼGrady, Philippe Mathurin, Giovanni Addolorato, Marina Berenguer, Institute of Internal Medicine, Catholic University of Rome, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
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medicine.medical_specialty ,Alcoholic liver disease ,Alcohol Drinking ,medicine.medical_treatment ,education ,Disease ,[SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery ,Comorbidity ,030230 surgery ,Liver transplantation ,Chronic liver disease ,Hepatitis ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,medicine ,Humans ,Intensive care medicine ,Liver Diseases, Alcoholic ,Immunosuppression Therapy ,Transplantation ,liver transplantation ,business.industry ,Alcohol Abstinence ,Settore MED/09 - MEDICINA INTERNA ,Guideline ,medicine.disease ,3. Good health ,Treatment Outcome ,Practice Guidelines as Topic ,Quality of Life ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,030211 gastroenterology & hepatology ,business - Abstract
International audience; Alcohol-related liver disease is the second most frequent indication for liver transplantation (LT), yet as many as 90% to 95% of patients with alcohol-related end-stage liver disease are never formally evaluated for LT. Furthermore, despite its significance as a cause of chronic liver disease and indication for LT, it has received little attention in recent years for several reasons, including the good posttransplant short-term results, and the lack of specific "drugs" used for this disease. A writing group, endorsed by the International Liver Transplant Society, was convened to write guidelines on Liver Transplantation for Alcoholic Liver Disease to summarize current knowledge and provide answers to controversial and delicate ethical as well as clinical problems. We report here a short version of the guidelines (long version available at www.ilts.org) with the final recommendations graded for level of evidence. The writing group membership is expected to remain active for 5 years, reviewing the guideline annually, and updating the online version when appropriate.
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- 2016
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12. Long-term safety and tolerability of apremilast in patients with psoriasis: Pooled safety analysis for ≥156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2)
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Rongdean Chen, Pascal Joly, Robert M. Day, Jeffrey J. Crowley, Diamant Thaçi, Ketty Peris, K. Shah, Kim A. Papp, Joana Carla Soares Gonçalves, Jennifer Clay Cather, Carlos Ferrándiz, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Catholic University of Rome, Université de Sherbrooke (UdeS), and Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt)
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Male ,Time Factors ,[SDV]Life Sciences [q-bio] ,Suicide, Attempted ,law.invention ,030207 dermatology & venereal diseases ,0302 clinical medicine ,Randomized controlled trial ,law ,Neoplasms ,Respiratory Tract Infections ,ComputingMilieux_MISCELLANEOUS ,education.field_of_study ,Depression ,Incidence ,Anti-Inflammatory Agents, Non-Steroidal ,Headache ,Nausea ,Middle Aged ,Thalidomide ,3. Good health ,Clinical trial ,Tolerability ,Cardiovascular Diseases ,Psoriatic arthritis ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Safety ,Settore MED/35 - MALATTIE CUTANEE E VENEREE ,medicine.drug ,Adult ,Diarrhea ,medicine.medical_specialty ,Population ,Dermatology ,03 medical and health sciences ,Internal medicine ,Psoriasis ,medicine ,Humans ,Apremilast ,Phosphodiesterase 4 inhibitor ,education ,Adverse effect ,ESTEEM ,030203 arthritis & rheumatology ,2708 ,business.industry ,Tension-Type Headache ,medicine.disease ,Nasopharyngitis ,Physical therapy ,business - Abstract
BACKGROUND: Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis. OBJECTIVE: Assess long-term safety of oral apremilast in psoriasis patients. METHODS: Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2. RESULTS: The 0 to ≥156-week apremilast-exposure period included 1184 patients treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156-week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52-week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported. Limitations: This study had a high dropout rate (21% of patients ongoing [156 weeks); most were $1 56 weeks, no new AEs (affecting $5 % of the population) were reported. LIMITATIONS: This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns. CONCLUSIONS: Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.
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- 2017
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13. Epigenetic Silencing of DKK3 in Medulloblastoma
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Sara Stigliani, Gian Paolo Tonini, Marcel Kool, Massimo Romani, André Oberthuer, Francesca Valdora, Claudio Brigati, Barbara Banelli, Marc Remke, Giuseppe Cinalli, Massimo Zollo, Simona Coco, Tiziana Servidei, Alfa H.C. Bai, Stefano Moretti, Thomas Hielscher, Stefan M. Pfister, Valdora, F, Banelli, B, Stigliani, S, Pfister, Sm, Moretti, S, Kool, M, Remke, M, Bai, Ah, Brigati, C, Hielscher, T, Romani, M, Servidei, T, Zollo, Massimo, Cinalli, G, Oberthuer, A, Tonini, Gp, Coco, S., National Cancer Research Institute, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Laboratoire d'analyse et modélisation de systèmes pour l'aide à la décision (LAMSADE), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), The University of Hong Kong (HKU), Division of Pediatric Oncology, Catholic University of Rome, Ceinge, centro di Ingegneria Genetica e Biotecnologie Avanzate, Children's Hospital of Cologne, and Universita degli Studi di Padova
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Male ,DKK family ,lcsh:Chemistry ,0302 clinical medicine ,Databases, Genetic ,medulloblastoma ,Wnt antagonists ,DKK3 downregulation ,histone deacetylase ,TSA ,RNA, Neoplasm ,Child ,lcsh:QH301-705.5 ,Spectroscopy ,Regulation of gene expression ,Genetics ,0303 health sciences ,Wnt signaling pathway ,General Medicine ,Methylation ,Middle Aged ,Computer Science Applications ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Child, Preschool ,Intercellular Signaling Peptides and Proteins ,Female ,Chemokines ,medicine.drug ,Adult ,Adolescent ,Biology ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Cell Line, Tumor ,microRNA ,medicine ,Gene silencing ,Humans ,[INFO]Computer Science [cs] ,Epigenetics ,Gene Silencing ,RNA, Messenger ,Physical and Theoretical Chemistry ,Molecular Biology ,030304 developmental biology ,Adaptor Proteins, Signal Transducing ,Aged ,Gene Expression Profiling ,Organic Chemistry ,Infant ,Chromatin Assembly and Disassembly ,Trichostatin A ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cancer research ,Histone deacetylase - Abstract
Cet article est en libre accès.; International audience; Medulloblastoma (MB) is a malignant pediatric brain tumor arising in the cerebellum consisting of four distinct subgroups: WNT, SHH, Group 3 and Group 4, which exhibit different molecular phenotypes. We studied the expression of Dickkopf (DKK) 1–4 family genes, inhibitors of the Wnt signaling cascade, in MB by screening 355 expression profiles derived from four independent datasets. Upregulation of DKK1, DKK2 and DKK4 mRNA was observed in the WNT subgroup, whereas DKK3 was downregulated in 80% MBs across subgroups with respect to the normal cerebellum (p < 0.001). Since copy number aberrations targeting the DKK3 locus (11p15.3) are rare events, we hypothesized that epigenetic factors could play a role in DKK3 regulation. Accordingly, we studied 77 miRNAs predicting to repress DKK3; however, no significant inverse correlation between miRNA/mRNA expression was observed. Moreover, the low methylation levels in the DKK3 promoters (median: 3%, 5% and 5% for promoter 1, 2 and 3, respectively) excluded the downregulation of gene expression by methylation. On the other hand, the treatment of MB cells with Trichostatin A (TSA), a potent inhibitor of histone deacetylases (HDAC), was able to restore both DKK3 mRNA and protein. In conclusion, DKK3 downregulation across all MB subgroups may be due to epigenetic mechanisms, in particular, through chromatin condensation.
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- 2013
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14. The MRC1/CD68 Ratio Is Positively Associated with Adipose Tissue Lipogenesis and with Muscle Mitochondrial Gene Expression in Humans
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Geltrude Mingrone, Francisco J. Ortega, Belén Peral, José María Moreno-Navarrete, María Gómez-Serrano, José Manuel Fernández-Real, Francisco J. Tinahones, Wifredo Ricart, Eva García-Santos, [Moreno-Navarrete,JM, Ortega,F, Ricart,W, Fernández-Real,JM] Service of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain. [Gómez-Serrano,M, García-Santos,E, Peral,B] Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (IIB), Consejo Superior de Investigaciones Científicas (CSIC) and Universidad Autónoma de Madrid (UAM), Madrid, Spain. [Tinahones,F] Department of Endocrinology and Nutrition, Hospital Universitario Virgen de la Victoria de Málaga, CIBEROBN Fisiopatologia Obesidad y Nutricion (CB06/03/018), Instituto de Salud Carlos III, Málaga, Spain. [Mingrone,G] Institute of Internal Medicine, Catholic University of Rome, Rome, Italy., and This work was supported by grant SAF-2009-10461 and grant PI11-00214 from the Ministerio de Economía y Competitividad, Spain.
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Male ,Anatomy and Physiology ,Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Mitochondria::Mitochondria, Muscle [Medical Subject Headings] ,Obesidad ,Gene Expression ,lcsh:Medicine ,Adipose tissue ,ComputingMilieux_LEGALASPECTSOFCOMPUTING ,Mitochondrion ,Biochemistry ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Endocrinology ,Molecular Cell Biology ,Adipocytes ,Tejido Adiposo ,Receptors, Immunologic ,lcsh:Science ,Musculoskeletal System ,Regulation of gene expression ,Membrane Glycoproteins ,Multidisciplinary ,Middle Aged ,Anatomy::Tissues::Connective Tissue::Adipose Tissue [Medical Subject Headings] ,Humanos ,Genes, Mitochondrial ,medicine.anatomical_structure ,Adipose Tissue ,Adipogenesis ,Anatomy::Cells::Connective Tissue Cells::Adipocytes [Medical Subject Headings] ,Marcadores Biológicos ,Lipogenesis ,Muscle ,Medicine ,Female ,Adiponectin ,Cellular Types ,Mannose Receptor ,Research Article ,Adult ,Muscle tissue ,medicine.medical_specialty ,Expresión Génica ,Immune Cells ,Adipose tissue macrophages ,Subcutaneous Fat ,Antigens, Differentiation, Myelomonocytic ,Receptors, Cell Surface ,Biology ,Mitocondrias Musculares ,Molecular Genetics ,Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Lipogenesis [Medical Subject Headings] ,Antigens, CD ,Internal medicine ,Weight Loss ,Adipocitos ,Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings] ,medicine ,Humans ,Lectins, C-Type ,Lipogénesis ,Obesity ,Nutrition ,lcsh:R ,Computational Biology ,Lipid Metabolism ,Mitochondria, Muscle ,Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings] ,Mannose-Binding Lectins ,Metabolism ,Gene Expression Regulation ,lcsh:Q ,Transcriptome ,Physiological Processes ,Energy Metabolism - Abstract
This is an open-access article distributed under the terms of the Creative Commons Attribution License., [Background]: Alternative macrophages (M2) express the cluster differentiation (CD) 206 (MCR1) at high levels. Decreased M2 in adipose tissue is known to be associated with obesity and inflammation-related metabolic disturbances. Here we aimed to investigate MCR1 relative to CD68 (total macrophages) gene expression in association with adipogenic and mitochondrial genes, which were measured in human visceral [VWAT, n = 147] and subcutaneous adipose tissue [SWAT, n = 76] and in rectus abdominis muscle (n = 23). The effects of surgery-induced weight loss were also longitudinally evaluated (n = ).[Results]: MCR1 and CD68 gene expression levels were similar in VWAT and SWAT. A higher proportion of CD206 relative to total CD68 was present in subjects with less body fat and lower fasting glucose concentrations. The ratio MCR1/CD68was positively associated with IRS1gene expression and with the expression of lipogenic genes such as ACACA, FASN and THRSP, even after adjusting for BMI. The ratio MCR1/CD68 in SWAT increased significantly after the surgery-induced weight loss (+44.7%; p = 0.005) in parallel to the expression of adipogenic genes. In addition, SWAT MCR1/CD68ratio was significantly associated with muscle mitochondrial gene expression (PPARGC1A, TFAM and MT-CO3). AT CD206 was confirmed by immunohistochemistry to be specific of macrophages, especially abundant in crown-like structures. [Conclusion]: A decreased ratio MCR1/CD68 is linked to adipose tissue and muscle mitochondrial dysfunction at least at the level of expression of adipogenic and mitochondrial genes. © 2013 moreno-navarrete et al., This work was supported by grant SAF-2009-10461 and grant PI11-00214 from the Ministerio de Economía y Competitividad, Spain.
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- 2013
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15. Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype.
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Sarli C, van der Laan L, Reilly J, Trajkova S, Carli D, Brusco A, Levy MA, Relator R, Kerkhof J, McConkey H, Tedder ML, Skinner C, Alders M, Henneman P, Hennekam RCM, Ciaccio C, D'Arrigo S, Vitobello A, Faivre L, Weber S, Vincent-Devulder A, Perrin L, Bourgois A, Yamamoto T, Metcalfe K, Zollino M, Kini U, Oliveira D, Sousa SB, Williams D, Cappuccio G, Sadikovic B, and Brunetti-Pierri N
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- Humans, Male, Female, Child, Homeodomain Proteins genetics, Child, Preschool, Nerve Tissue Proteins genetics, DNA Methylation, Mutation, Adolescent, Nuclear Proteins genetics, Developmental Disabilities genetics, Developmental Disabilities pathology, Facies, Heart Diseases, Foot Deformities, Congenital, Hypotrichosis, Autism Spectrum Disorder, Neurodevelopmental Disorders, Intellectual Disability genetics, Intellectual Disability pathology, Blepharophimosis genetics, Blepharophimosis pathology, Phenotype, Transcription Factors genetics
- Abstract
Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides-Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in SMARCA2, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM-associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of ADNP present with the neurodevelopmental disorder known as Helsmoortel-Van Der Aa Syndrome (HVDAS). Distinct DNA methylation profiles referred to as episignatures have been reported in HVDAS and BAF complex disorders. Due to molecular interactions between ADNP and BAF complex, and an overlapping craniofacial phenotype with narrowing of the palpebral fissures in a subset of patients with HVDAS and BIS, we hypothesized the possibility of a common phenotype-specific episignature. A distinct episignature was shared by 15 individuals with BIS-causing SMARCA2 pathogenic variants and 12 individuals with class II HVDAS caused by truncating pathogenic ADNP variants. This represents first evidence of a sensitive phenotype-specific episignature biomarker shared across distinct genetic conditions that also exhibit unique gene-specific episignatures., (© 2024 The Author(s). American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.)
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- 2024
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16. Lumbo-sacral pedicular aplasia diagnosis and treatment: a systematic literature review and case report.
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Galieri G, Mazzucchi E, Pignotti F, Rinaldi P, De Santis V, La Rocca G, and Sabatino G
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- Humans, Spinal Fusion methods, Sacrum abnormalities, Sacrum diagnostic imaging, Male, Adult, Lumbosacral Region abnormalities, Spondylolisthesis diagnosis, Spondylolisthesis surgery, Spondylolisthesis diagnostic imaging, Female, Low Back Pain etiology, Low Back Pain diagnosis, Lumbar Vertebrae abnormalities, Lumbar Vertebrae surgery, Lumbar Vertebrae diagnostic imaging
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Aplasia of the lumbar pedicle is a rare condition, frequently associated with low back pain. Its recognition is fundamental in the definition of the correct treatment. We performed a literature review in order to clarify how to best diagnose and treat this rare anatomical condition. A comprehensive literature search for studies published through October 2020 was performed, using the following algorithm: "aplasia" OR "aplastic" OR "hypoplasia" OR "hypoplastic" OR "absent" OR absence" AND "pedicle" AND "lumbar" OR "sacral" OR "lumbosacral". References from reviewed papers were further evaluated for the inclusion of other relevant studies. Eighteen studies were included in the systematic review for a total of 24 adult patients. Another case of left L5 pedicle aplasia treated at our hospital has been described and included in the present review. This anatomical condition may be suspected in plain x-Ray, but CT scan 3D reconstructions may help to confirm the diagnosis in equivocal cases. Low-back pain and radiculopathy are the main signs and symptoms. The treatment was described in 14 cases. Eight patients underwent surgical intervention. In cases with spondylolisthesis, fusion surgery was performed with different techniques, obtaining an excellent clinical outcome. Pedicular aplasia is a rare condition that must be recognized in patients with a low back. When it is associated with spondylolisthesis, fusion surgery should be the preferred option.
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- 2024
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17. Italian Expert Opinion on Chronic Hand Eczema: from Guidelines to Clinical Practice.
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Stingeni L, Fargnoli MC, Guarneri F, Balato A, Corazza M, Fortina AB, Pinton PC, Costanzo A, Ferrucci SM, Naldi L, Pellacani G, Peris K, Prignano F, and Girolomoni G
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Introduction: Chronic hand eczema (CHE) is an inflammatory skin condition characterized by different pathomechanisms, clinical presentations, and prognoses. Treatment is often challenging because of limited approved drugs, and severe CHE is associated with reduced quality of life (QoL) and poor overall health measures in terms of psychological, functional, and occupational challenges. This study aims to describe the real-life management practices of Italian dermatologists who frequently treat patients with CHE, compare these practices with existing guidelines, and propose practical clinical recommendations for the management of these patients., Methods: An 11-question survey was administered to 14 participating dermatologists to gather their insights on the diagnosis, treatment, and management of CHE. Moreover, a comprehensive literature search was conducted over the previous 10 years as a starting point for discussion among experts., Results: CHE was the reason for 6.9% of dermatological consultations by the 14 experts. Median time to CHE diagnosis was 12 (range: 2-24) months. Fissuring and itching (85.7% for both) were the most frequently reported signs and symptoms of CHE. The survey highlighted the need for long-term treatment that is effective and well tolerated, with experts emphasizing the importance of improving disease awareness among physicians and patients. Practical clinical approaches were proposed, emphasizing the significance of a thorough medical history and identification of symptoms in the management of CHE. Experts advocated for specifically developed CHE treatment approaches, concentrating on alleviating symptoms and signs, minimizing adverse events/safety issues, enhancing the QoL of patients, and long-term disease control. Findings from this survey were further discussed and compared to recommendations of the available guidelines for the management of CHE., Conclusions: Managing CHE requires a comprehensive approach that considers both objective clinical factors and subjective patient expectations. Experts emphasized the need for effective and well-tolerated long-term therapies, improved disease awareness, and communication among physicians and patients., Competing Interests: Declarations. Conflict of Interest: The authors disclose the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Luca Stingeni has acted as Principal Investigator, speaker, and board member for AbbVie, Almirall, Amgen, Bristol Meyer Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis and Sanofi. Maria Concetta Fargnoli has served on advisory boards, received honoraria for lectures and/or research grants from Amgen, Almirall, AbbVie, Boehringer-Ingelheim, BMS, Galderma, Kyowa Kyrin, Incyte, Leo Pharma, Pierre Fabre, UCB, Lilly, Pfizer, Janssen, MSD, Novartis, Sanofi, Regeneron and Sun Pharma. Fabrizio Guarneri has served as advisory board member for Leo Pharma. Anna Balato has served as advisory board member, consultant and/or has received fees, speakers’ honoraria or has participated in clinical trials for AbbVie, Almirall, Amgen, Boehringer-Ingelheim, BMS, LeoPharma, Eli Lilly, Incyte, Janssen, Novartis, Sanofi and UCB. Monica Corazza has acted as Principal Investigator, speaker, and board member for AbbVie, Almirall, Amgen, Janssen, Leo Pharma, Novartis and Sanofi. Anna Belloni Fortina has participated in advisory boards, acted as consultant and/or received fees from AbbVie, Amgen, Almirall, Sanofi Genzyme, Leo Pharma, Eli Lilly, Pfizer, Unifarco and Novartis. Piergiacomo Calzavara-Pinton served as advisory board member and consultant and has received fees and speakers’ honoraria or has participated in clinical trials for AbbVie, Almirall, Leo Pharma, Cantabria, Galderma, Incyte, Janssen, Novartis, Biogen, Sanofi Genzyme, La Roche Posay, Naos, Boehringer-Ingelheim and Sun Pharma. Antonio Castanzo has served as advisory board member and consultant and has received fees and speakers’ honoraria or has participated in clinical trials for AbbVie, Almirall, Amgen Leo Pharma, Lilly, Galderma, Incyte, Janssen, Novartis, Sanofi Genzyme, Boehringer-Ingelheim and UCB. Silvia Mariel Ferrucci has acted as Principal Investigator in clinical trials, Speaker and Member of Advisory board for: AbbVie, Amgen, Almirall, Bayer, Sanofi Genzyme, Leo Pharma, Eli Lilly, Pfizer, Unifarco and Novartis. Luigi Naldi has been consultant and speaker for AbbVie, Almirall, Boheringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Novartis and Sanofi. Giovanni Pellacani has served as advisory board member, consultant and investigator for: AbbVie, Allergan, Almirall, Amgen, Beiersdorf, Boheringer, Canfield, Difa-Cooper Ifc, Eli Lilly, Galderma, Janssen-Cilag, Krymi, Kyowa-Kirin, Leo Pharma, L’oreal, Mavig, Menarini, Pfizer, Pierre-Fabre, Sanofi, UCB and Viatris. Ketty Peris received grants from: AbbVie, Almirall, Lilly, Novartis and Sanofi; Advisory Board or consulting fees from: AbbVie, Almirall, Biogen, Galderma, Leo Pharma, Lilly, MSD, Pierre Fabre, Sun Pharma, Janssen and Sanofi. Francesca Prignano has served as advisory board member and consultant and has received fees and speaker's honoraria or has participated in clinical trials for AbbVie, Almirall, Leo Pharma, Lilly, Janssen, Novartis, Biogen, Sanofi Genzyme, UCB and Boehringer-Ingelheim. Giampiero Girolomoni has received personal fees from AbbVie, Almirall, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Leo Pharma, Merck Serono, Novartis, Pfizer, Pierre Fabre, Samsung Bioepis and Sanofi. Ethical Approval: This article is based on data derived from a survey conducted among dermatologists and previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors., (© 2024. The Author(s).)
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- 2024
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18. How to preserve the native or reconstructed esophagus after perforations or postoperative leaks: A multidisciplinary 15-year experience.
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Nachira D, Calabrese G, Senatore A, Pontecorvi V, Kuzmych K, Belletatti C, Boskoski I, Meacci E, Biondi A, Raveglia F, Bove V, Congedo MT, Vita ML, Santoro G, Petracca Ciavarella L, Lococo F, Punzo G, Trivisonno A, Petrella F, Barbaro F, Spada C, D'Ugo D, Cioffi U, and Margaritora S
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Background: Esophageal perforation or postoperative leak after esophageal surgery remain a life-threatening condition. The optimal management strategy is still unclear., Aim: To determine clinical outcomes and complications of our 15-year experience in the multidisciplinary management of esophageal perforations and anastomotic leaks., Methods: A retrospective single-center observational study was performed on 60 patients admitted at our department for esophageal perforations or treated for an anastomotic leak developed after esophageal surgery from January 2008 to December 2023. Clinical outcomes were analyzed, and complications were evaluated to investigate the efficacy and safety of our multidisciplinary management based on the preservation of the native or reconstructed esophagus, when feasible., Results: Among the whole series of 60 patients, an urgent surgery was required in 8 cases due to a septic state. Fifty-six patients were managed by endoscopic or hybrid treatments, obtaining the resolution of the esophageal leak/perforation without removal of the native or reconstructed esophagus. The mean time to resolution was 54.95 ± 52.64 days, with a median of 35.5 days. No severe complications were recorded. Ten patients out of 56 (17.9%) developed pneumonia that was treated by specific antibiotic therapy, and in 6 cases (10.7%) an atrial fibrillation was recorded. Seven patients (12.5%) developed a stricture within 12 months, requiring one or two endoscopic pneumatic dilations to solve the problem. Mortality was 1.7%., Conclusion: A proper multidisciplinary approach with the choice of the most appropriate treatment can be the key for success in managing esophageal leaks or perforations and preserving the esophagus., Competing Interests: Conflict-of-interest statement: Boskoski I is consultant for Apollo Endosurgery, Boston Scientific, Cook Medical, Nitinotes, Erbe Elektromedizin, Pentax Medical, Fractyl Health, and Lecturer for Microteach. All the other authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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19. Rational design, synthesis, and biophysical characterization of a peptidic MDM2-MDM4 interaction inhibitor.
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Ballarotto M, Bianconi E, Valentini S, Temperini A, Moretti F, and Macchiarulo A
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- Humans, Protein Binding, Cell Cycle Proteins antagonists & inhibitors, Cell Cycle Proteins metabolism, Proto-Oncogene Proteins antagonists & inhibitors, Proto-Oncogene Proteins metabolism, Nuclear Proteins antagonists & inhibitors, Nuclear Proteins metabolism, Nuclear Proteins chemistry, Proto-Oncogene Proteins c-mdm2 metabolism, Proto-Oncogene Proteins c-mdm2 antagonists & inhibitors, Proto-Oncogene Proteins c-mdm2 chemistry, Drug Design, Peptides chemistry, Peptides pharmacology, Peptides chemical synthesis
- Abstract
In recent years, the restoration of p53 physiological functions has become an attractive therapeutic approach to develop novel and efficacious cancer therapies. Among other mechanisms, the oncosuppressor protein p53 is functionally regulated by MDM2 through its E3 ligase function. MDM2 promotes p53 ubiquitination and degradation following homodimerization or heterodimerization with MDM4. Recently, we discovered Pep3 (1, Pellegrino et al., 2015), a novel peptidic inhibitor of MDM2 dimerization able to restore p53 oncosuppressive functions both in vitro and in vivo. In this work, we were able to identify the key interactions between peptide 1 and MDM2 RING domain and to design peptide 2, a truncated version of 1 that is still able to bind MDM2. Integrating both computational and biophysical techniques, we show that peptide 2 maintains the conserved peptide 1-MDM2 interactions and is still able to bind to full-length MDM2., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Antonio Macchiarulo reports financial support was provided by Consorzio Interuniversitario Nazionale Metodologie e Processi Innovativi di Sintesi (C.I.N.M.P.I.S). Fabiola Moretti reports financial support was provided by the Italian Association for Cancer Research Grant (AIRC IG 21814). Andrea Temperini reports financial support was provided by Consorzio Interuniversitario Nazionale Metodologie e Processi Innovativi di Sintesi (C.I.N.M.P.I.S). Antonio Macchiarulo has patent #IT102023000015816 pending to CNR, Via del Fosso di Fiorano 64, 00143 Roma. Fabiola Moretti has patent #IT102023000015816 pending to CNR, Via del Fosso di Fiorano 64, 00143 Roma. Andrea Temperini has patent #IT102023000015816 pending to CNR, Via del Fosso di Fiorano 64, 00143 Roma. Marco Ballarotto has patent #IT102023000015816 pending to CNR, Via del Fosso di Fiorano 64, 00143 Roma. Sonia Valentini has patent #IT102023000015816 pending to CNR, Via del Fosso di Fiorano 64, 00143 Roma. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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20. The Three Pillars of Glioblastoma: A Systematic Review and Novel Analysis of Multi-Omics and Clinical Data.
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De Luca C, Virtuoso A, Papa M, Cirillo G, La Rocca G, Corvino S, Barbarisi M, and Altieri R
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- Humans, Multiomics, Glioblastoma pathology, Brain Neoplasms pathology, Brain Neoplasms genetics
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Glioblastoma is the most fatal and common malignant brain tumor, excluding metastasis and with a median survival of approximately one year. While solid tumors benefit from newly approved drugs, immunotherapy, and prevention, none of these scenarios are opening for glioblastoma. The key to unlocking the peculiar features of glioblastoma is observing its molecular and anatomical features tightly entangled with the host's central nervous system (CNS). In June 2024, we searched the PUBMED electronic database. Data collection and analysis were conducted independently by two reviewers. Results: A total of 215 articles were identified, and 192 were excluded based on inclusion and exclusion criteria. The remaining 23 were used for collecting divergent molecular pathways and anatomical features of glioblastoma. The analysis of the selected papers revealed a multifaced tumor with extreme variability and cellular reprogramming that are observable within the same patient. All the variability of glioblastoma could be clustered into three pillars to dissect the physiology of the tumor: 1. necrotic core; 2. vascular proliferation; 3. CNS infiltration. These three pillars support glioblastoma survival, with a pivotal role of the neurovascular unit, as supported by the most recent paper published by experts in the field.
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- 2024
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21. The Low-Income and Middle-Income Countries' Perspective on Global Neurosurgery Collaborations.
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Marchesini N, Kamalo P, Foroglou N, Garozzo D, Gonzalez-Lopez P, Ivanov M, Lafuente J, Olldashi F, Paternò V, Petr O, Rotim K, Rzaev J, Timothy J, Tisell M, Visocchi M, Negida A, Uche E, Rasulic L, and Demetriades AK
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Background and Objectives: Access to neurosurgical care is limited in low-income and middle-income countries (LMICs) and in marginalized communities in high-income countries (HICs). International partnerships represent one possible means of addressing this issue. Insights from surgeons in HICs have been explored, but data from LMICs' counterparts are scarce. We aimed to study the perspectives of neurosurgeons and trainees from LMICs regarding global neurosurgery (GN) collaborations and interests, motivators, and challenges in participating., Methods: An online survey was conducted targeting neurosurgeons and trainees from LMICs. The survey explored demographics, previous experiences, ongoing activities, interests, and barriers related to GN activities. Data were collected between July 2022 and December 2022 and analyzed., Results: Responses involved 436 individuals. The most represented region (25%) was sub-Saharan Africa, and most respondents were male (87.8%) aged 35-49 years. Interest in GN was high, with 91% after its developments. Most respondents (96.1%) expressed interest in training, professional, or research experience in HICs, but only 18.1% could cover the expenses. A majority (73.2%) strongly agreed to return to their home country for work after HIC training. Ongoing HIC-LMIC partnerships were reported by 27.8% of respondents. Clinical exposure emerged as the most relevant motivating factor (87%), while financial concerns, lack of opportunities, and lack of program support were identified as important barriers. Funding and dedicated time were highlighted as the most crucial facilitators., Conclusion: Understanding the perspectives of neurosurgeons and trainees from LMICs is essential to expanding HICs-LMICs collaborations and improving access to neurosurgical care worldwide. Financial support and targeted interventions are needed to address barriers and promote equitable partnerships in GN., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)
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- 2024
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22. Correction: Standards for conducting and reporting consensus and recommendation documents: European Society of Cardiovascular Radiology policy from the Guidelines Committee.
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Lupi A, Suchá D, Cundari G, Fink N, Alkadhi H, Budde RPJ, Caobelli F, De Cecco CN, Galea N, Hrabak-Paar M, Loewe C, Luetkens JA, Muscogiuri G, Natale L, Nikolaou K, Pirnat M, Saba L, Salgado R, Williams MC, Wintersperger BJ, Vliegenthart R, Francone M, and Pepe A
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- 2024
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23. Clinically Relevant Extracardiac Findings at Cardiac Imaging: Insights from the European MR/CT Registry.
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Moser LJ, Gutberlet M, Vliegenthart R, Francone M, Budde RPJ, Salgado R, Hrabak Paar M, Pirnat M, Loewe C, Nikolaou K, Williams MC, Muscogiuri G, Natale L, Gohmann RF, Lücke C, Eberhard M, and Alkadhi H
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- Humans, Male, Middle Aged, Aged, Europe epidemiology, Retrospective Studies, Female, Adult, Incidental Findings, Tomography, X-Ray Computed, Prevalence, Cardiac Imaging Techniques, Registries, Magnetic Resonance Imaging
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Purpose To determine the prevalence of clinically relevant extracardiac findings at cardiac CT and MRI examinations from a multicenter, multinational MR/CT registry and the relationship of prevalence with examination indications and patient characteristics. Materials and Methods This was a retrospective analysis of data from the European Society of Cardiovascular Radiology MR/CT Registry. Data from 208 506 cardiac CT examinations (median patient age, 66 years [IQR, 55-77]; 121 617 [58.33%] male patients) and 228 462 cardiac MRI examinations (median patient age, 57 years [IQR, 42-69]; 145 792 [63.81%] male patients) entered into the registry between January 2011 and November 2023 were analyzed. Clinically relevant extracardiac findings were defined as findings requiring follow-up examinations or influencing clinical management. The association of examination indication and patient characteristics, including age, with prevalence of extracardiac findings was evaluated using incidence rate ratios (IRRs) derived from multivariable Poisson regression models. Results The prevalence of clinically relevant extracardiac findings was 3.28% (6832 of 208 506) at cardiac CT and 1.50% (3421 of 228 462) at cardiac MRI examinations. Extracardiac findings were more common at CT examinations performed for transcatheter aortic valve replacement (IRR, 2.07; P < .001) and structural heart disease (IRR, 1.44; P < .001) compared with CT performed for coronary artery disease (IRR, 1; reference). Extracardiac findings were more common at MRI examinations performed for myocarditis (IRR, 1.36; P < .001) and structural heart disease (IRR, 1.16; P < .001) than for coronary artery disease. Older patient age was also significantly associated with higher prevalence of extracardiac findings, with an IRR for both CT and MRI examinations of 1.02 ( P < .001). Conclusion Data from the multicenter, multinational MR/CT registry indicate that clinically relevant extracardiac findings are present at cardiovascular CT and MRI examinations, and the prevalence of these findings is associated with examination indication and patient age. Keywords: Cardiac Imaging Techniques, Incidental Findings, MRI, CT Angiography, CT, Heart Disease Supplemental material is available for this article. © RSNA, 2024.
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- 2024
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24. The Molecular Mechanisms of Portal Vein Thrombosis in Hepatocellular Carcinoma.
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Galasso L, Cerrito L, Termite F, Mignini I, Esposto G, Borriello R, Ainora ME, Gasbarrini A, and Zocco MA
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Hepatocellular carcinoma (HCC) represents the sixth most diagnosed cancer worldwide and is the second leading cause of cancer-related death in the world. The association of HCC and portal vein thrombosis (PVT) represents an advanced stage of the tumor. PVT has a prevalence of about 25-50% in HCC, determining poor prognosis and a remarkable reduction in therapeutic perspectives in these patients, leading to severe complications such as ascites, metastasis, an increase in portal hypertension and potentially fatal gastrointestinal bleeding. The aim of this review is to evaluate the molecular mechanisms that are at the basis of PVT development, trying to evaluate possible strategies in the early detection of patients at high risk of PVT.
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- 2024
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25. Low-dose ondansetron: A candidate prospective precision medicine to treat alcohol use disorder endophenotypes.
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Johnson B, Alho H, Addolorato G, Lesch OM, Chick J, Liu L, and Schuyler V
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- Humans, Male, Female, Adult, Middle Aged, Double-Blind Method, Treatment Outcome, Serotonin Plasma Membrane Transport Proteins genetics, Prospective Studies, Ondansetron therapeutic use, Alcoholism drug therapy, Endophenotypes, Precision Medicine methods
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Background: Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise in reducing alcohol consumption among affected individuals while minimizing adverse effects., Methods: This was a phase III, 6-month, 25-site, randomized, placebo-controlled clinical trial using AD04 to treat DSM-V-categorized AUD individuals who were pre-stratified into the endophenotypes of heavy or very heavy drinking individuals and possessed a pre-defined profile of genetic variants related to the serotonin transporter and serotonin-3AB receptor. Participants (N = 303) presented moderate to severe AUD, >80 % were men, mostly in their fifties, and >95 % were of European descent. Low-dose AD04 (approx. 033 mg twice daily) or a matching placebo was administered twice daily for 6 months. Brief Behavioral Compliance Enhancement Treatment (BBCET [53]) was administered every two weeks to enhance medication compliance and clinic attendance., Results: There was a significant reduction in the monthly percentage of heavy drinking days, PHDD (-46·7 % (2·7 %), 95 %CI: -52·1 % to -41·2 % vs. -38·1 % (2·9 %), 95 %CI: -43·8 % to -32·5 %, respectively; LS mean difference=-8·5 %; p = 0.03) among AD04-treated vs. placebo-receiving heavy drinking individuals at month 6. Heavy drinking individuals were also less likely to be diagnosed with AUD [Month 1: -32·0 % (2·8 %), 95 %CI: -37·5 % to -26·5 % vs. -23·2 % (2·9 %), 95 %CI: -28·9 to -17·5 %; LS mean difference= -8·8 %; p = 0·026)], and improved on the WHO quality of life BREF scale with a significant effect for at least a 1-level downward shift (OR = 3.4; 95 % CI: 1·03-11·45, p = 0·044). Importantly, heavy drinking individuals, as distinct from very heavy drinking individuals, were the bio-psychosocial endophenotype more predictive of therapeutic response to AD04. AD04 had an exceptional safety and tolerability profile, like the placebo's., Conclusions: In this Phase 3 clinical trial, AD04 was shown to be a promising treatment for currently drinking heavy drinking individuals with AUD who also possess a specific genotypic profile in the serotonin transporter and serotonin-3AB receptor complex. Using AD04 to reduce the harm of AUD in heavy drinking individuals who are currently drinking, without the necessity of abstinence or detoxification from alcohol use, is an important advance in the field of precision medicine. AD04's adverse events profile, which was like placebo, should enhance accessibility and acceptance of modern medical treatment for AUD by lowering the incorrect but commonly perceived stigma of personal failure., Competing Interests: Declaration of competing interest All authors are paid consultants of Adial Pharmaceuticals Inc. Vinzant Schuyler and Bankole Johnson are officers of Adial Pharmaceuticals Inc., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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26. Competence of radiologists in cardiac CT and MR imaging in Europe: insights from the ESCR Registry.
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Catapano F, Moser LJ, Francone M, Catalano C, Vliegenthart R, Budde RPJ, Salgado R, Hrabak Paar M, Pirnat M, Loewe C, Nikolaou K, Williams MC, Muscogiuri G, Natale L, Lehmkuhl L, Sieren MM, Gutberlet M, and Alkadhi H
- Subjects
- Humans, Europe, Heart Diseases diagnostic imaging, Male, Registries, Magnetic Resonance Imaging methods, Tomography, X-Ray Computed methods, Radiologists statistics & numerical data, Clinical Competence
- Abstract
Rationale: To provide an overview of the current status of cardiac multimodality imaging practices in Europe and radiologist involvement using data from the European Society of Cardiovascular Radiology (ESCR) MRCT-registry., Materials and Methods: Numbers on cardiac CT and MRI examinations were extracted from the MRCT-registry of the ESCR, entered between January 2011 and October 2023 (n = 432,265). Data collection included the total/annual numbers of examinations, indications, complications, and reporting habits., Results: Thirty-two countries contributed to the MRCT-registry, including 29 European countries. Between 2011 and 2022, there was a 4.5-fold increase in annually submitted CT examinations, from 3368 to 15,267, and a 3.8-fold increase in MRI examinations, from 3445 to 13,183. The main indications for cardiac CT were suspected coronary artery disease (CAD) (59%) and transcatheter aortic valve replacement planning (21%). The number of patients with intermediate pretest probability who underwent CT for suspected CAD showed an increase from 61% in 2012 to 82% in 2022. The main MRI indications were suspected myocarditis (26%), CAD (21%), and suspected cardiomyopathy (19%). Adverse event rates were very low for CT (0.3%) and MRI (0.7%) examinations. Reporting of CT and MRI examinations was performed mainly by radiologists (respectively 76% and 71%) and, to a lesser degree, in consensus with non-radiologists (19% and 27%, respectively). The remaining examinations (4.9% CT and 1.7% MRI) were reported by non-radiological specialties or in separate readings of radiologists and non-radiologists., Conclusions: Real-life data on cardiac imaging in Europe using the largest available MRCT-registry demonstrate a considerable increase in examinations over the past years, the vast majority of which are read by radiologists. These findings indicate that radiologists contribute to meeting the increasing demands of competent and effective care in cardiac imaging to a relevant extent., Clinical Relevance Statement: The number of cardiac CT and MRI examinations has risen over the past years, and radiologists read the vast majority of these studies as recorded in the MRCT-registry., Key Points: • The number of cardiac imaging examinations is constantly increasing. • Radiologists play a central role in providing cardiac CT and MR imaging services to a large volume of patients. • Cardiac CT and MR imaging examinations performed and read by radiologists show a good safety profile., (© 2024. The Author(s).)
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- 2024
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27. Fluorescence guidance in skull base surgery: Applications and limitations - A systematic review.
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Suero Molina E, Bruneau M, Reuter G, Shahein M, Cavallo LM, Daniel RT, Kasper EM, Froelich S, Jouanneau E, Manet R, Messerer M, Mazzatenta D, Meling TR, Roche PH, Schroeder HW, Tatagiba M, Visocchi M, Prevedello DM, Stummer W, and Cornelius JF
- Abstract
Introduction: Intraoperative fluorescence guidance is a well-established surgical adjunct in high-grade glioma surgery. In contrast, the clinical use of such dyes and technology has been scarcely reported in skull base surgery., Research Question: We aimed to systematically review the clinical applications of different fluorophores in both open and endonasal skull base surgery., Material and Methods: We performed a systematic review and discussed the current literature on fluorescence guidance in skull base surgery., Results: After a comprehensive literature search, 77 articles on skull base fluorescence guidance were evaluated. A qualitative analysis of the articles is presented, discussing clinical indications and current controversies. The use of intrathecal fluorescein was the most frequently reported in the literature. Beyond that, 5-ALA and ICG were two other fluorescent dyes most extensively discussed, with some experimental fluorophore applications in skull base surgery., Discussion and Conclusion: Intraoperative fluorescence imaging can serve as an adjunct technology in skull base surgery. The scope of initial indications of these fluorophores has expanded beyond malignant glioma resection alone. We discuss current use and controversies and present an extensive overview of additional indications for fluorescence imaging in skull base pathologies. Further quantitative studies will be needed in the future, focusing on tissue selectivity and time-dependency of the different fluorophores currently commercially available, as well as the development of new compounds to expand applications and facilitate skull base surgeries., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eric Suero Molina reports a relationship with Carl Zeiss Meditec AG that includes: funding grants. Walter Stummer has received speaker and consultant fees from Medac, Carl Zeiss Meditec AG, Leica Microsystems, Photonamic, and NXDC and funding grants from Carl Zeiss Meditec AG. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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28. Enhancing Oral 5-ASA Effectiveness in Mild-to-Moderate Ulcerative Colitis through an H. erinaceus -Based Nutraceutical Add-on Multi-Compound: The "HERICIUM-UC" Two-Arm Multicentre Retrospective Study.
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Tursi A, D'Avino A, Brandimarte G, Mocci G, Pellegrino R, Savarino EV, Gravina AG, and The Hericium-Uc Study Group
- Abstract
Mild-to-moderate ulcerative colitis (UC) management is centred on 5-aminosalicylic acid (5-ASA) derivatives. Whether supplementing 5-ASA with nutraceuticals can provide real advantages in UC-relevant outcomes is unclear. This retrospective multicentre study compared clinical remission, response rates, and faecal calprotectin levels in a two-arm design, including patients treated with 5-ASA alone and those with additional H. erinaceus -based multi-compound supplementation. In the 5-ASA alone group, clinical response rates were 41% at three months (T
1 ) and 60.2% at six months (T2 ), while corresponding clinical remission rates were 16.9% and 36.1%. In the nutraceutical supplementation group, clinical response rates were 49.6% (T1 ) and 70.4% (T2 ), with clinical remission rates of 30.4% (T1 ) and 50.9% (T2 ). No significant differences in clinical response rates between the groups at T1 ( p = 0.231) and T2 ( p = 0.143) emerged. Clinical remission rates differed significantly at both time points ( p = 0.029 and p = 0.042, respectively). Faecal calprotectin levels decreased significantly in both groups during the retrospective follow-up ( p < 0.05), and this was more pronounced in nutraceutical supplementation patients at both T1 ( p = 0.005) and T2 ( p = 0.01). No adverse events were reported. This multi-component nutraceutical supplementation offers real-world potential in controlling disease activity in patients with mild-to-moderate UC.- Published
- 2024
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29. Anaphylaxis after SonoVue: A Case Report and a Literature Review.
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Longhino D, Buonomo A, Zocco MA, Ainora ME, Esposto G, Mignini I, Cerrito L, Ponziani FR, Gasbarrini A, Nucera E, and Aruanno A
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SonoVue (Bracco, Milan, Italy) is a drug used in ultrasonography for the purpose of increasing the echogenicity of blood or fluids by improving the signal-to-noise ratio. Background/Objectives/Methods : We described a case of anaphylaxis due to SonoVue and performed a literature review. Results and Conclusions : We reported a case of anaphylaxis secondary to the administration of SonoVue and described all the 13 literature cases. Given its widespread use and the potentially dangerous nature of the reactions it can cause, it is advisable to know how to promptly recognize fatal reactions.
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- 2024
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30. Standards for conducting and reporting consensus and recommendation documents: European Society of Cardiovascular Radiology policy from the Guidelines Committee.
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Lupi A, Suchá D, Cundari G, Fink N, Alkadhi H, Budde RPJ, Caobelli F, De Cecco CN, Galea N, Hrabak-Paar M, Loewe C, Luetkens J, Muscogiuri G, Natale L, Nikolaou K, Pirnat M, Saba L, Salgado R, Williams MC, Wintersperger BJ, Vliegenthart R, Francone M, and Pepe A
- Abstract
Cardiovascular imaging is exponentially increasing in the diagnosis, risk stratification, and therapeutic management of patients with cardiovascular disease. The European Society of Cardiovascular Radiology (ESCR) is a non-profit scientific medical society dedicated to promoting and coordinating activities in cardiovascular imaging. The purpose of this paper, written by ESCR committees and Executive board members and approved by the ESCR Executive Board and Guidelines committee, is to codify a standardized approach to creating ESCR scientific documents. Indeed, consensus development methods must be adopted to ensure transparent decision-making that optimizes national and global health and reaches a certain scientific credibility. ESCR consensus documents developed based on a rigorous methodology will improve their scientific impact on the management of patients with cardiac involvement. CRITICAL RELEVANCE STATEMENT: This document aims to codify the methodology for producing consensus documents of the ESCR. These ESCR indications will broaden the scientific quality and credibility of further publications and, consequently, the impact on the diagnostic management of patients with cardiac involvement. KEY POINTS: Cardiovascular imaging is exponentially increasing for diagnosis, risk stratification, and therapeutic management. The ESCR is committed to promoting cardiovascular imaging. A rigorous methodology for ESCR consensus documents will improve their scientific impact., (© 2024. The Author(s).)
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- 2024
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31. Parapneumonic empyema in children: a scoping review of the literature.
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Buonsenso D, Cusenza F, Passadore L, Bonanno F, Calanca C, Mariani F, Di Martino C, Rasmi S, and Esposito S
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- Adolescent, Child, Child, Preschool, Humans, Infant, Anti-Bacterial Agents therapeutic use, Community-Acquired Infections therapy, Drainage, Empyema, Pleural therapy, Empyema, Pleural microbiology
- Abstract
Community-acquired pneumonia can lead to a serious complication called empyema, which refers to pus within the pleural space. While it poses a significant threat to morbidity, particularly in children, it is fortunately not associated with high mortality rates. However, determining the best course of management for children, including decisions regarding antibiotic selection, administration methods, and treatment duration, remains a topic of ongoing debate. This scoping review aims to map the existing literature on empyema in children, including types of studies, microbiology, therapies (both antimicrobial and surgical) and patient outcomes. We systematically searched PubMed and SCOPUS using the terms "pediatric" (encompassing children aged 0 to 18 years) and "pleural empyema" to identify all relevant studies published since 2000. This search adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA ScR) checklist.A total of 127 studies was included. Overall, 15 attempted to compare medical treatments (alone or in combination with pleural drainage or fibrinolysis) with more invasive surgical approaches, and six studies compared diverse surgical interventions. However, the diversity of study designs makes it difficult to derive firm conclusions on the optimal approach to pediatric empyema. The heterogeneity in inclusion criteria, pharmacological/surgical approaches and settings limit the ability to draw definitive conclusions. Overall, 78 out of 10,896 children (0.7%) included in the review died, with mortality being higher in Asia and Africa. Our scoping review highlights important gaps regarding several aspects of empyema in children, including specific serotypes of the most common bacteria involved in the etiology, the optimal pharmacological and surgical approach, and the potential benefits of newer antibiotics with optimal lung penetration. New trials, designed on a multi-country level a higher number of patients and more rigorous inclusion criteria and designs, should be urgently funded., (© 2024. The Author(s).)
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- 2024
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32. Crohn's Disease: Radiological Answers to Clinical Questions and Review of the Literature.
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Minordi LM, D'Angelo FB, Privitera G, Papa A, Larosa L, Laterza L, Scaldaferri F, Barbaro B, Carbone L, and Pugliese D
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Background: Crohn's disease (CD) is a chronic, progressive inflammatory condition, involving primarily the bowel, characterized by a typical remitting-relapsing pattern. Despite endoscopy representing the reference standard for the diagnosis and assessment of disease activity, radiological imaging has a key role, providing information about mural and extra-visceral involvement. Methods: Computed Tomography and Magnetic Resonance Imaging are the most frequently used radiological techniques in clinical practice for both the diagnosis and staging of CD involving the small bowel in non-urgent settings. The contribution of imaging in the management of CD is reported on by answering the following practical questions: (1) What is the best technique for the assessment of small bowel CD? (2) Is imaging a good option to assess colonic disease? (3) Which disease pattern is present: inflammatory, fibrotic or fistulizing? (4) Is it possible to identify the presence of strictures and to discriminate inflammatory from fibrotic ones? (5) How does imaging help in defining disease extension and localization? (6) Can imaging assess disease activity? (7) Is it possible to evaluate post-operative recurrence? Results: Imaging is suitable for assessing disease activity, extension and characterizing disease patterns. CT and MRI can both answer the abovementioned questions, but MRI has a greater sensitivity and specificity for assessing disease activity and does not use ionizing radiation. Conclusions: Radiologists are essential healthcare professionals to be involved in multidisciplinary teams for the management of CD patients to obtain the necessary answers for clinically relevant questions.
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- 2024
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33. Quantitative assessment of self-management in patients with non-alcoholic fatty liver disease: An unmet clinical need.
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Borriello R, Esposto G, Mignini I, Gasbarrini A, and Zocco MA
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- Humans, Disease Progression, Healthy Lifestyle, Life Style, Non-alcoholic Fatty Liver Disease therapy, Non-alcoholic Fatty Liver Disease psychology, Non-alcoholic Fatty Liver Disease diagnosis, Patient Compliance statistics & numerical data, Self-Management methods, Exercise
- Abstract
In this editorial we comment on the article titled "Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease" by Zeng et al published in a recent issue of the World Journal of Gastroenterology . Non-alcoholic fatty liver disease (NAFLD) represents one of the current challenges in hepatology and public health, due to its continuous growing prevalence and the rising incidence of NAFLD-related fibrosis, non-alcoholic steatohepatitis and cirrhosis. The only effective therapeutic strategy for this disease is represented by encouraging patients to improve their lifestyle through the modification of dietary intake and increased physical exercise, but the effective application of such modifications is often limited by various factors such as lack of information, psychological barriers or poor social support. While poor adherence to a healthy lifestyle can be decisive in determining the clinical outcome, in daily practice there is a lack of quantitative instruments aimed at identifying patients with the lowest adherence to lifestyle changes and higher risk of disease progression in the course of follow-up. In this article, Zeng et al propose a quantitative scale to assess the grade of adherence of patients with NAFLD to healthy lifestyle intervention, called the Exercise and Diet Adherence Scale (EDAS). This scale, consisting of 33 items divided into 6 dimensions which relates to six subjective aspects in the self-management of NAFLD, has shown a good correlation with the identification of the sub-cohort of patients with the highest reduction in caloric intake, increase in physical exercise, probability of a reduction in liver stiffness measurement and alanine aminotransferase levels. The correlation among clinical outcomes and specific dimensions of this scale also highlights the pivotal role of a good and confidential doctor-patient relationship and of an effective communication. There is an urgent need for practical and effective instruments to assess the grade of self-management of NAFLD patients, together with the development of multidisciplinary teams with the aim of applying structured behavioral interventions., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to disclose regarding this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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34. Quantum Medicine and Irritable Bowel Syndrome-Associated Chronic Low-Back Pain: A Pilot Observational Study on the Clinical and Bio-Psycho-Social Effects of Bioresonance Therapy.
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Barassi G, Pirozzi GA, Di Iorio A, Pellegrino R, Galasso P, Heimes D, Praitano B, Gallenga PE, Prosperi L, Moccia A, and Panunzio M
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- Humans, Male, Female, Pilot Projects, Middle Aged, Adult, Leukocyte L1 Antigen Complex analysis, Chronic Pain therapy, Chronic Pain psychology, Treatment Outcome, Irritable Bowel Syndrome psychology, Irritable Bowel Syndrome therapy, Irritable Bowel Syndrome complications, Irritable Bowel Syndrome physiopathology, Low Back Pain therapy, Low Back Pain psychology, Quality of Life
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Background and Objectives : Irritable bowel syndrome (IBS) is an invasive and potentially disabling syndrome characterized by a multitude of symptoms capable of reducing the quality of life of patients. Among the most disabling symptoms of IBS is certainly physical pain, which manifests itself mainly at the abdominal level but can also appear in other areas of the body, particularly in the form of chronic low-back pain (CLBP). Among the non-invasive methods of treating organ-specific pathologies and organ-related musculoskeletal problems, the use of Bioresonance Therapy (BT)-based on the administration of self-modulating Extremely Low-Frequency Electromagnetic Fields, capable of determining a rebalance of bio-electrical and metabolic activity in the presence of various functional alterations-is currently gaining acceptance. Therefore, we decided to monitor results obtained from patients suffering from IBS and CLBP subjected to a cycle of treatments with BT. Materials and Methods : We monitored 20 patients (12 women and 8 men, average age of 51 years) suffering from CLBP and other visceral symptoms related to IBS. Patients were monitored through the use of the Bristol Stool Form Scale (BSFS), the Fecal Calprotectin test and the Short-Form Health Survey 36 (SF-36), collected before (T0) and after (T1) the execution of the cycle of treatments. They undertook a treatment protocol consisting of eight sessions of BT carried out over about a month. Results : At the end of the treatments with BT, it was possible to observe a general and significant improvement in all the parameters observed, as well as a close inversely proportional correlation between the Calprotectin values detected and the quality of life experienced by the patients in relation to their perceived IBS symptoms. Conclusions : Overall, our pilot study would seem to suggest a potential beneficial effect of BT in modulating organic and musculoskeletal symptoms derived from IBS.
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- 2024
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35. Role of Device-Assisted Enteroscopy in Crohn's Disease.
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Catassi G, Marmo C, Gasbarrini A, and Riccioni ME
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Crohn's Disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, posing diagnostic and management challenges due to its potential involvement of any segment from the mouth to the anus. Device-assisted enteroscopy (DAE) has emerged as a significant advancement in the management of CD, particularly for its ability to access the small intestine-a region difficult to evaluate with conventional endoscopic methods. This review discusses the pivotal role of DAE in the nuanced management of CD, emphasizing its enhanced diagnostic precision and therapeutic efficacy. DAE techniques, including double-balloon enteroscopy (DBE), single-balloon enteroscopy (SBE), and the now-withdrawn spiral enteroscopy, enable comprehensive mucosal assessment, targeted biopsies, and therapeutic interventions like stricture dilation, bleeding control, and foreign body removal. Despite its benefits, DAE carries risks such as perforation, bleeding, and pancreatitis, which require careful procedural planning and a skilled execution. The review highlights DAE's impact on reducing surgical interventions and improving patient outcomes through minimally invasive approaches, thereby enhancing the quality of life for patients with CD. Continuous improvement and research are essential in order to maximize DAE's utility and safety in clinical practice.
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- 2024
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36. Inflammatory Response in the Pathogenesis and Treatment of Hepatocellular Carcinoma: A Double-Edged Weapon.
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Galasso L, Cerrito L, Maccauro V, Termite F, Mignini I, Esposto G, Borriello R, Ainora ME, Gasbarrini A, and Zocco MA
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- Humans, Animals, Immunotherapy methods, Carcinoma, Hepatocellular therapy, Carcinoma, Hepatocellular etiology, Carcinoma, Hepatocellular immunology, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular virology, Liver Neoplasms therapy, Liver Neoplasms pathology, Liver Neoplasms etiology, Liver Neoplasms immunology, Liver Neoplasms virology, Inflammation pathology
- Abstract
Hepatocellular carcinoma (HCC) is the most frequent among primary liver tumors (90%) and one of the main causes of cancer-related death. It develops usually in a chronically inflamed environment, ranging from compensatory parenchymal regeneration to fibrosis and cirrhosis: carcinogenesis can potentially happen in each of these stages. Inflammation determined by chronic viral infection (hepatitis B, hepatitis C, and hepatitis delta viruses) represents an important risk factor for HCC etiology through both viral direct damage and immune-related mechanisms. The deregulation of the physiological liver immunological network determined by viral infection can lead to carcinogenesis. The recent introduction of immunotherapy as the gold-standard first-line treatment for HCC highlights the role of the immune system and inflammation as a double-edged weapon in both HCC carcinogenesis and treatment. In this review we highlight how the inflammation is the key for the hepatocarcinogenesis in viral, alcohol and metabolic liver diseases.
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- 2024
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37. Dynamic contrast enhanced ultrasound in differential diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis.
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Esposto G, Santini P, Termite F, Galasso L, Mignini I, Ainora ME, Gasbarrini A, and Zocco MA
- Abstract
Background: Non-invasive differential diagnosis between hepatocellular carcinoma (HCC) and other liver cancer ( i.e. cholangiocarcinoma or metastasis) is highly challenging and definitive diagnosis still relies on histological exam. The patterns of enhancement and wash-out of liver nodules can be used to stratify the risk of malignancy only in cirrhotic patients and HCC frequently shows atypical features. Dynamic contrast-enhanced ultrasound (DCEUS) with standardized software could help to overcome these obstacles, providing functional and quantitative parameters and potentially improving accuracy in the evaluation of tumor perfusion., Aim: To explore clinical evidence regarding the application of DCEUS in the differential diagnosis of liver nodules., Methods: A comprehensive literature search of clinical studies was performed to identify the parameters of DCEUS that could relate to histological diagnosis. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned., Results: Rise time was significantly higher in HCC patients with a standardized mean difference (SMD) of 0.83 (95%CI: 0.48-1.18). Similarly, other statistically significant parameters were mean transit time local with a SMD of 0.73 (95%CI: 0.20-1.27), peak enhancement with a SMD of 0.37 (95%CI: 0.03-0.70), area wash-in area under the curve with a SMD of 0.47 (95%CI: 0.13-0.81), wash-out area under the curve with a SMD of 0.55 (95%CI: 0.21-0.89) and wash-in and wash-out area under the curve with SMD of 0.51 (95%CI: 0.17-0.85). SMD resulted not significant in fall time and wash-in rate, but the latter presented a trend towards greater values in HCC compared to intrahepatic cholangiocarcinoma., Conclusion: DCEUS could improve non-invasive diagnosis of HCC, leading to less liver biopsy and early treatment. This quantitative analysis needs to be applied on larger cohorts to confirm these preliminary results., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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38. Identification of the DNA methylation signature of Mowat-Wilson syndrome.
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Caraffi SG, van der Laan L, Rooney K, Trajkova S, Zuntini R, Relator R, Haghshenas S, Levy MA, Baldo C, Mandrile G, Lauzon C, Cordelli DM, Ivanovski I, Fetta A, Sukarova E, Brusco A, Pavinato L, Pullano V, Zollino M, McConkey H, Tartaglia M, Ferrero GB, Sadikovic B, and Garavelli L
- Subjects
- Humans, Female, Male, Child, Child, Preschool, Adolescent, CpG Islands, DNA Methylation, Intellectual Disability genetics, Intellectual Disability diagnosis, Intellectual Disability pathology, Zinc Finger E-box Binding Homeobox 2 genetics, Zinc Finger E-box Binding Homeobox 2 metabolism, Microcephaly genetics, Microcephaly diagnosis, Microcephaly pathology, Hirschsprung Disease genetics, Hirschsprung Disease diagnosis, Hirschsprung Disease pathology, Homeodomain Proteins genetics, Repressor Proteins genetics, Facies
- Abstract
Mowat-Wilson syndrome (MOWS) is a rare congenital disease caused by haploinsufficiency of ZEB2, encoding a transcription factor required for neurodevelopment. MOWS is characterized by intellectual disability, epilepsy, typical facial phenotype and other anomalies, such as short stature, Hirschsprung disease, brain and heart defects. Despite some recognizable features, MOWS rarity and phenotypic variability may complicate its diagnosis, particularly in the neonatal period. In order to define a novel diagnostic biomarker for MOWS, we determined the genome-wide DNA methylation profile of DNA samples from 29 individuals with confirmed clinical and molecular diagnosis. Through multidimensional scaling and hierarchical clustering analysis, we identified and validated a DNA methylation signature involving 296 differentially methylated probes as part of the broader MOWS DNA methylation profile. The prevalence of hypomethylated CpG sites agrees with the main role of ZEB2 as a transcriptional repressor, while differential methylation within the ZEB2 locus supports the previously proposed autoregulation ability. Correlation studies compared the MOWS cohort with 56 previously described DNA methylation profiles of other neurodevelopmental disorders, further validating the specificity of this biomarker. In conclusion, MOWS DNA methylation signature is highly sensitive and reproducible, providing a useful tool to facilitate diagnosis., (© 2024. The Author(s).)
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- 2024
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39. Navigating the Intersection: Sarcopenia and Sarcopenic Obesity in Inflammatory Bowel Disease.
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Calvez V, Becherucci G, Covello C, Piccirilli G, Mignini I, Esposto G, Laterza L, Ainora ME, Scaldaferri F, Gasbarrini A, and Zocco MA
- Abstract
Inflammatory bowel diseases (IBDs) are intricate systemic conditions that can extend beyond the gastrointestinal tract through both direct and indirect mechanisms. Sarcopenia, characterized by a reduction in muscle mass and strength, often emerges as a consequence of the clinical course of IBDs. Indeed, sarcopenia exhibits a high prevalence in Crohn's disease (52%) and ulcerative colitis (37%). While computed tomography and magnetic resonance imaging remain gold-standard methods for assessing muscle mass, ultrasound is gaining traction as a reliable, cost-effective, and widely available diagnostic method. Muscle strength serves as a key indicator of muscle function, with grip strength test emerging nowadays as the most reliable assessment method. In IBDs, sarcopenia may arise from factors such as inflammation, malnutrition, and gut dysbiosis, leading to the formulation of the 'gut-muscle axis' hypothesis. This condition determines an increased need for surgery with poorer post-surgical outcomes and a reduced response to biological treatments. Sarcopenia and its consequences lead to reduced quality of life (QoL), in addition to the already impaired QoL. Of emerging concern is sarcopenic obesity in IBDs, a challenging condition whose pathogenesis and management are still poorly understood. Resistance exercise and nutritional interventions, particularly those aimed at augmenting protein intake, have demonstrated efficacy in addressing sarcopenia in IBDs. Furthermore, anti-TNF biological therapies showed interesting outcomes in managing this condition. This review seeks to furnish a comprehensive overview of sarcopenia in IBDs, elucidating diagnostic methodologies, pathophysiological mechanisms, and clinical implications and management. Attention will also be paid to sarcopenic obesity, exploring the pathophysiology and possible treatment modalities of this condition.
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- 2024
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40. Gut-Brain Axis: Focus on Sex Differences in Neuroinflammation.
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Caldarelli M, Rio P, Marrone A, Ocarino F, Chiantore M, Candelli M, Gasbarrini A, Gambassi G, and Cianci R
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- Humans, Animals, Dysbiosis, Gonadal Steroid Hormones metabolism, Brain metabolism, Female, Male, Inflammation metabolism, Brain-Gut Axis physiology, Gastrointestinal Microbiome, Neuroinflammatory Diseases metabolism, Sex Characteristics
- Abstract
In recent years, there has been a growing interest in the concept of the "gut-brain axis". In addition to well-studied diseases associated with an imbalance in gut microbiota, such as cancer, chronic inflammation, and cardiovascular diseases, research is now exploring the potential role of gut microbial dysbiosis in the onset and development of brain-related diseases. When the function of the intestinal barrier is altered by dysbiosis, the aberrant immune system response interacts with the nervous system, leading to a state of "neuroinflammation". The gut microbiota-brain axis is mediated by inflammatory and immunological mechanisms, neurotransmitters, and neuroendocrine pathways. This narrative review aims to illustrate the molecular basis of neuroinflammation and elaborate on the concept of the gut-brain axis by virtue of analyzing the various metabolites produced by the gut microbiome and how they might impact the nervous system. Additionally, the current review will highlight how sex influences these molecular mechanisms. In fact, sex hormones impact the brain-gut microbiota axis at different levels, such as the central nervous system, the enteric nervous one, and enteroendocrine cells. A deeper understanding of the gut-brain axis in human health and disease is crucial to guide diagnoses, treatments, and preventive interventions.
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- 2024
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41. Hepatocellular Carcinoma and the Multifaceted Relationship with Its Microenvironment: Attacking the Hepatocellular Carcinoma Defensive Fortress.
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Galasso L, Cerrito L, Maccauro V, Termite F, Ainora ME, Gasbarrini A, and Zocco MA
- Abstract
Hepatocellular carcinoma is a malignant tumor that originates from hepatocytes in an inflammatory substrate due to different degrees of liver fibrosis up to cirrhosis. In recent years, there has been growing interest in the role played by the complex interrelationship between hepatocellular carcinoma and its microenvironment, capable of influencing tumourigenesis, neoplastic growth, and its progression or even inhibition. The microenvironment is made up of an intricate network of mesenchymal cells, immune system cells, extracellular matrix, and growth factors, as well as proinflammatory cytokines and translocated bacterial products coming from the intestinal microenvironment via the enterohepatic circulation. The aim of this paper is to review the role of the HCC microenvironment and describe the possible implications in the choice of the most appropriate therapeutic scheme in the prediction of tumor response or resistance to currently applied treatments and in the possible development of future therapeutic perspectives, in order to circumvent resistance and break down the tumor's defensive fort.
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- 2024
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42. Sex-specific behavioural, metabolic, and immunohistochemical changes after repeated administration of the synthetic cannabinoid AKB48 in mice.
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Corli G, Roda E, Tirri M, Bilel S, De Luca F, Strano-Rossi S, Gaudio RM, De-Giorgio F, Fattore L, Locatelli CA, and Marti M
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- Mice, Male, Female, Animals, Cannabinoid Receptor Agonists pharmacology, Receptors, Cannabinoid, Down-Regulation, Receptor, Cannabinoid, CB1, Cannabinoids pharmacology, Cannabis
- Abstract
Background and Purpose: AKB48 is a synthetic cannabinoid illegally sold for its psychoactive cannabis-like effects that have been associated with acute intoxication and whose effects are poorly known., Experimental Approach: Using a behavioural, neurochemical, and immunohistochemical approach, we investigated the pharmaco-toxicological effects, pharmacokinetics, and neuroplasticity at cannabinoid CB
1 receptors in the cerebellum and cortex induced by repeated AKB48 administration in male and female mice., Key Results: The effects of AKB48 varied significantly depending on sex and treatment duration. The first injection impaired sensorimotor responses and reduced body temperature, analgesia, and breath rate to a greater extent in females than in males; the second injection induced stronger effects in males while the third injection of AKB48 induced weaker responses in both sexes, suggesting emergence of tolerance. The CB1 receptor antagonist NESS-0327 prevented the effects induced by repeated AKB48, confirming a CB1 receptor-mediated action. Blood AKB48 levels were higher in females than in males and repeated administration caused a progressive rise of AKB48 levels in both sexes, suggesting an inhibitory effect on cytochrome activity. Finally, immunohistochemical analysis revealed higher expression of CB1 receptors in the cerebellum and cortex of females, and a rapid CB1 receptor down-regulation in cerebellar and cortical areas following repeated AKB48 injections, with neuroadaptation occurring generally more rapidly in females than in males., Conclusion and Implications: We have shown for the first time that AKB48 effects significantly vary with prolonged use and that sex affects the pharmacodynamic/pharmacokinetic responses to repeated administration, suggesting a sex-tailored approach in managing AKB48-induced intoxication., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)- Published
- 2024
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43. Surgical Outcomes and Complications of Custom-Made Prostheses in Upper Limb Oncological Reconstruction: A Systematic Review.
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Fulchignoni C, Pietramala S, Lopez I, Mazzella GG, Comisi C, Perisano C, Rocchi L, and Greco T
- Abstract
Bone tumors of the upper limb are a common cause of bone pain and pathological fractures in both old and young populations. Surgical reconstruction and limb salvage have become valid options for these patients despite this kind of surgery being challenging due to the need for wide bone resection and the involvement of surrounding soft tissues. Computer-assisted technology helps the surgeon in pre-operative planning and in designing customized implants. The aim of this study was to investigate the surgical outcomes and complications of custom-made prostheses in oncologic reconstruction of the upper limb and if they are reliable options for patients suffering from aggressive tumors. An electronic search on PubMed, Google Scholar, and Web of Knowledge was conducted to identify all available articles on the use of custom-made prostheses in oncological resections of the upper limb. Twenty-one studies were included in the review, comprising a total of 145 patients with a mean age of 33.68 years. The bone involved was the humerus in 93 patients, and the radius was involved in 36 patients. There were only six cases involving proximal ulna, three cases involving the scapula, and seven cases involving the elbow as well as soft tissues around it. The most frequent primary tumor was the giant cell tumor, with 36 cases, followed by osteosarcoma with 25 cases, Ewing Sarcoma with 17 cases, and Chondrosarcoma with 7 total cases. Forty patients were affected by bone metastases (such as renal cell cancer, breast cancer, melanoma, and rectal cancer) or hematologic diseases involving bone (lymphoma, myeloma, or non-Hodgkin disease). Custom-made prostheses are a viable option for patients who suffer from malignant tumors in their upper limbs. They are a reliable aid for surgeons in cases of extensive resections.
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- 2024
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44. Hemorrhage Volume Drives Early Brain Injury and Outcome in Poor-Grade Aneurysmal SAH.
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Panni P, Simionato F, Cao R, Pedicelli A, Marchese E, Caricato A, Alexandre A, Feletti A, Testa M, Zanatta P, Gitti N, Piva S, Mardighian D, Semeraro V, Nardin G, Lozupone E, Paiano G, Picetti E, Montanaro V, Petranca M, Bortolotti C, Scibilia A, Cirillo L, Aspide R, Lanterna AL, Ambrosi A, Mortini P, Azzolini ML, Calvi MR, and Falini A
- Subjects
- Humans, Treatment Outcome, Retrospective Studies, Prospective Studies, Cerebral Hemorrhage, Brain Edema diagnostic imaging, Brain Edema etiology, Subarachnoid Hemorrhage diagnostic imaging, Subarachnoid Hemorrhage surgery, Brain Injuries
- Abstract
Background and Purpose: Early brain injury is a major determinant of clinical outcome in poor-grade (World Federation of Neurosurgical Societies [WFNS] IV-V) aneurysmal SAH and is radiologically defined by global cerebral edema. Little is known, though, about the effect of global intracranial hemorrhage volume on early brain injury development and clinical outcome., Materials and Methods: Data from the multicentric prospective Poor-Grade Aneurysmal Subarachnoid Hemorrhage (POGASH) Registry of consecutive patients with poor-grade aneurysmal SAH admitted from January 1, 2015, to August 31, 2022, was retrospectively evaluated. Poor grade was defined according to the worst-pretreatment WFNS grade. Global intracranial hemorrhage volume as well as the volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH were calculated by means of analytic software in a semiautomated setting. Outcomes included severe global cerebral edema (defined by Subarachnoid Hemorrhage Early Brain Edema Score grades 3-4), in-hospital mortality (mRS 6), and functional independence (mRS 0-2) at follow-up., Results: Among 400 patients (median global intracranial hemorrhage volume of 91 mL; interquartile range, 59-128), severe global cerebral edema was detected in 218/400 (54.5%) patients. One hundred twenty-three (30.8%) patients died during the acute phase of hospitalization. One hundred fifty-five (38.8%) patients achieved mRS 0-2 at a median of 13 (interquartile range, 3-26) months of follow-up. Multivariable analyses showed global intracranial hemorrhage volume as independently associated with severe global cerebral edema (adjusted OR, 1.009; 95% CI, 1.004-1.014; P < .001), mortality (adjusted OR, 1.006; 95% CI, 1.001-1.01; P = .018) and worse clinical outcome (adjusted OR, 0.992; 95% CI, 0.98-0.996; P < .010). The effect of global intracranial hemorrhage volume on clinical-radiologic outcomes changed significantly according to different age groups (younger than 50, 50-70, older than 70 year of age). Volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH affected the 3 predefined outcomes differently. Intracerebral hemorrhage volume independently predicted global cerebral edema and long-term outcome, intraventricular hemorrhage volume predicted mortality and long-term outcome, and SAH volume predicted long-term clinical outcome., Conclusions: Global intracranial hemorrhage volume plays a pivotal role in global cerebral edema development and emerged as an independent predictor of both mortality and long-term clinical outcome. Aging emerged as a reducing predictor in the relationship between global intracranial hemorrhage volume and global cerebral edema., (© 2024 by American Journal of Neuroradiology.)
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- 2024
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45. Nasal intermittent positive pressure ventilation during less invasive surfactant administration in preterm infants: An open-label randomized controlled study.
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Dani C, Napolitano M, Barone C, Manna A, Nigro G, Scarpelli G, Bonanno E, Gatto S, Cavigioli F, Forcellini C, Petoello E, Beghini R, Ciarcià M, Fusco M, Mosca F, Lavizzari A, Gitto E, Barbuscia L, Betta P, Mattia C, Corvaglia L, Vedovato S, Vento G, Maffei G, Falsaperla R, Lago P, Boni L, and Lista G
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- Infant, Newborn, Humans, Infant, Premature, Intermittent Positive-Pressure Ventilation, Surface-Active Agents, Respiration, Artificial, Continuous Positive Airway Pressure adverse effects, Pulmonary Surfactants therapeutic use, Infant, Premature, Diseases etiology, Respiratory Distress Syndrome, Newborn drug therapy
- Abstract
Introduction: Approximately half of very preterm infants with respiratory distress syndrome (RDS) fail treatment with nasal continuous positive airway pressure (NCPAP) and need mechanical ventilation (MV)., Objectives: Our aim with this study was to evaluate if nasal intermittent positive pressure ventilation (NIPPV) during less invasive surfactant treatment (LISA) can improve respiratory outcome compared with NCPAP., Materials and Methods: We carried out an open-label randomized controlled trial at tertiary neonatal intensive care units in which infants with RDS born at 25
+0 -31+6 weeks of gestation between December 1, 2020 and October 31, 2022 were supported with NCPAP before and after surfactant administration and received NIPPV or NCPAP during LISA. The primary endpoint was the need for a second dose of surfactant or MV in the first 72 h of life. Other endpoints were need and duration of invasive and noninvasive respiratory supports, changes in SpO2 /FiO2 ratio after LISA, and adverse effect rate., Results: We enrolled 101 infants in the NIPPV group and 99 in the NCPAP group. The unadjusted odds ratio for the composite primary outcome was 0.873 (95% confidence interval: 0.456-1.671; p = .681). We found that the SpO2 /FiO2 ratio was transiently higher in the LISA plus NIPPV than in the LISA plus NCPAP group, while adverse effects of LISA had similar occurrence in the two arms., Conclusions: The application of NIPPV or NCPAP during LISA in very preterm infants supported with NCPAP before and after surfactant administration had similar effects on the short-term respiratory outcome and are both safe. Our study does not support the use of NIPPV during LISA., (© 2024 Wiley Periodicals LLC.)- Published
- 2024
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46. Spindle-cell myoepithelioma, a rare neoplasm with various clinical presentations that can affect fingers.
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Fulchignoni C, Pietramala S, and Rocchi L
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- Humans, Fingers surgery, Fingers pathology, Myoepithelioma pathology, Myoepithelioma surgery, Soft Tissue Neoplasms pathology, Soft Tissue Neoplasms surgery
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- 2024
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47. ESR Essentials: ten steps to cardiac MR-practice recommendations by ESCR.
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Emrich T, Wintersperger BJ, Greco FD, Suchá D, Natale L, Paar MH, and Francone M
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- Humans, Magnetic Resonance Imaging methods, Heart, Cardiovascular Diseases diagnostic imaging
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Cardiovascular MR imaging has become an indispensable noninvasive tool in diagnosing and monitoring a broad range of cardiovascular diseases. Key to its clinical success and efficiency are appropriate clinical indication triage, technical expertise, patient safety, standardized preparation and execution, quality assurance, efficient post-processing, structured reporting, and communication and clinical integration of findings. Technological advancements are driving faster, more accessible, and cost-effective approaches. This ESR Essentials article presents a ten-step guide for implementing a cardiovascular MR program, covering indication assessments, optimized imaging, post-processing, and detailed reporting. Future goals include streamlined protocols, improved tissue characterization, and automation for greater standardization and efficiency., Clinical Relevance Statement: The growing clinical role of cardiovascular MR in risk assessment, diagnosis, and treatment planning highlights the necessity for radiologists to achieve expertise in this modality, advancing precision medicine and healthcare efficiency., Key Points: • Cardiovascular MR is essential in diagnosing and monitoring many acute and chronic cardiovascular pathologies. • Features such as technical expertise, quality assurance, patient safety, and optimized tailored imaging protocols, among others, are essential for a successful cardiovascular MR program. • Ongoing technological advances will push rapid multi-parametric cardiovascular MR, thus improving accessibility, patient comfort, and cost-effectiveness., Key Points: • Cardiovascular MR is essential in diagnosing and monitoring a wide array of cardiovascular pathologies (Level of Evidence: High). • A successful cardiovascular MR program depends on standardization (Level of Evidence: Low). • Future developments will increase the efficiency and accessibility of cardiovascular MR (Level of Evidence: Low)., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)
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- 2024
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48. Immune Cells, Gut Microbiota, and Vaccines: A Gender Perspective.
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Rio P, Caldarelli M, Chiantore M, Ocarino F, Candelli M, Gasbarrini A, Gambassi G, and Cianci R
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- Female, Humans, Male, Vaccination, Gastrointestinal Microbiome, Vaccines
- Abstract
The development of preventive and therapeutic vaccines has played a crucial role in preventing infections and treating chronic and non-communicable diseases, respectively. For a long time, the influence of sex differences on modifying health and disease has not been addressed in clinical and preclinical studies. The interaction of genetic, epigenetic, and hormonal factors plays a role in the sex-related differences in the epidemiology of diseases, clinical manifestations, and the response to treatment. Moreover, sex is one of the leading factors influencing the gut microbiota composition, which could further explain the different predisposition to diseases in men and women. In the same way, differences between sexes occur also in the immune response to vaccines. This narrative review aims to highlight these differences, focusing on the immune response to vaccines. Comparative data about immune responses, vaccine effectiveness, and side effects are reviewed. Hence, the intricate interplay between sex, immunity, and the gut microbiota will be discussed for its potential role in the response to vaccination. Embracing a sex-oriented perspective in research may improve the efficacy of the immune response and allow the design of tailored vaccine schedules.
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- 2024
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49. Procalcitonin and Presepsin as Markers of Infectious Respiratory Diseases in Children: A Scoping Review of the Literature.
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Sodero G, Gentili C, Mariani F, Pulcinelli V, Valentini P, and Buonsenso D
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Introduction: Procalcitonin and presepsin have been suggested to be able to discriminate bacterial and viral infections, also in children. This scoping review aims to better explore the available evidence around the potential role of these biomarkers in the subgroup of children with respiratory infectious diseases., Methods: We performed a systematic scoping review of studies published until March 2023 in the following bibliographic databases: PubMed, EMBASE, Cochrane and SCOPUS., Results: In children with bacterial infection, procalcitonin values ranged from 0.5 ng/mL to 8.31 ng/dL, while in those hospitalized in an intensive care unit ranged from 0.6 ng/dL to 452.8 ng/dL with PCR from 2 ng/dL to 51.7 ng/dL. In children with viral infections, procalcitonin value values ranged from 0.2 ng/dL to 0.84 ng/dL, while in those hospitalized in an intensive care unit ranged from 0.61 ng/dL to 46.6 ng/dL. No studies on presepsin in children with respiratory infections were retrieved., Conclusions: Although the available literature is highly heterogeneous, evidence does not suggest a role of procalcitonin in accurately differentiating bacterial and viral infections in children with respiratory infections. In future, new approaches based on multiple markers may better help determine which febrile children require antibiotics.
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- 2024
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50. Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication: A systematic review and meta-analysis.
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Esposto G, Santini P, Galasso L, Mignini I, Ainora ME, Gasbarrini A, and Zocco MA
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- Humans, Treatment Outcome, Elasticity Imaging Techniques methods, Liver Neoplasms diagnostic imaging, Liver Neoplasms virology, Liver Neoplasms pathology, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular virology, Carcinoma, Hepatocellular pathology, Antiviral Agents therapeutic use, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic complications, Hepatitis C, Chronic diagnostic imaging, Sustained Virologic Response, Predictive Value of Tests, Hepacivirus drug effects, Liver diagnostic imaging, Liver pathology, Liver Cirrhosis diagnostic imaging, Liver Cirrhosis virology
- Abstract
Background: Direct-acting antiviral agents (DAAs) are highly effective treatment for chronic hepatitis C (CHC) with a significant rate of sustained virologic response (SVR). The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression. The assessment of fibrosis degree can be performed with transient elastography, magnetic resonance elastography or shear-wave elastography (SWE). Liver elastography could function as a predictor for hepatocellular carcinoma (HCC) in CHC patients treated with DAAs., Aim: To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus (HCV)., Methods: A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned., Results: At baseline and after 12 wk of follow-up, a trend was shown towards greater liver stiffness (LS) in those who go on to develop HCC compared to those who do not [baseline LS standardized mean difference (SMD): 1.15, 95% confidence interval (95%CI): 020-2.50; LS SMD after 12 wk: 0.83, 95%CI: 0.33-1.98]. The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data. There was a statistically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not (0.64; 95%CI: 0.04-1.24)., Conclusion: SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs. Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2024
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