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1. Immunochip analysis identifies novel susceptibility loci in the human leukocyte antigen region for acquired thrombotic thrombocytopenic purpura

Author

Mancini, I., Ricaño‐Ponce, I., Pappalardo, E., Cairo, A., Gorski, M.M., Casoli, G., Ferrari, B., Alberti, M., Mikovic, D., Noris, M., Wijmenga, C., Peyvandi, F., Rinaldi, E., Melpignano, A., Campus, S., Podda, R.A., Caria, C., Caddori, A., Di Francesco, E., Giuffrida, G., Agostini, V., Roncarati, U., Mannarella, C., Fragasso, A., Podda, G.M., Bertinato, E., Cerbone, A.M., Tufano, A., Loffredo, G., Poggi, V., Pizzuti, M., Re, G., Ronchi, M., Codeluppi, K., Facchini, L., De Fanti, A., Amarri, S., Trisolini, S.M., Capria, S., Aprile, L., Defina, M., and Cerù, S.

Published
2016
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2. Management of intracranial hypertension following traumatic brain injury: a best clinical practice adoption proposal for intracranial pressure monitoring and decompressive craniectomy. Joint statements by the Traumatic Brain Injury Section of the Italian Society of Neurosurgery (SINch) and the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI)

Author

Iaccarino C., Lippa L., Munari M., Castioni C. A., Robba C., Caricato A., Pompucci A., Signoretti S., Zona G., Rasulo F. A., Aimar E., Amato S., Angileri F. F., Anile C., Assietti R., Baratto V., Barbanera A., Basile L., Battaglia R., Bellocchi S., Bertuccio A., Blanco S., Bolognini A., Boniferro B., Bordi L., Bortolotti C., Brandini V., Broger M., Brollo M., Caffarella D. D., Caggiano C., Cantisani P. L., Capone C., Cappelletto B., Capuano C., Carangelo B., Caruselli G., Chessa M. A., Chiara M., Chibbaro S., Cioffi V., Ciprianocecchi P., Colistra D., Conti C., Contratti F., Costella G. B., Cuoci A., D'Avella D., D'Ercole M., Deangelis M., Defalco R., de Luca G., de Marinis P., Del Vecchio C., Delfinis C., Denaro L., Deodato F., Desogus N., Disomma A., Domenicucci M., Dones F., Fina M., Fiori L., Fricia M., Gaetani P., Gazzeri R., Gentile M., Germano A., Ghadirpour R., Gianfreda C. D., Gigante N., Gigli R., Giorgetti J., Giusa M., Gravina U. G., Grippi L., Guida F., Guizzardi G., Iannuzzo G., Kropp M., Lattanzi L., Lucantoni D., Maffei L., Magliulo M., Marconi F., Marruzzo D., Martellotta N., Marton E., Maugeri R., Mauro G., Meli F., Menniti A., Merciadri P., Milanese L., Nardacci B., Nasi D., Orvieto P., Pacca P., Pansini G., Panzarasa G., Passanisi M., Pavesi G., Pizzoni C., Pulera F., Rapana A., Ricci A., Rispoli R., Rotondo M., Russo N., Santilli S., Scarano E., Schwarz A., Servadei F., Simonetti G., Stefini R., Talamonti G., Turrisi A., Valente V. M., Villa A., Vindigni M., Visocchi M., Vitali M., Wierzbicki V., Zambon G., Zanotti B., Zenga F., Alampi D., Alessandri F., Aloj F., Amigoni A., Aspide R., Bertuetti R., Betti V., Bilotta F., Bonato V., Bosco E., Brita M., Buscema G., Cafiero T., Cappuccio D., Caradonna M., Caria C. G., Casartelliliviero M., Ciritella P., Cirrincione S., Citerio G., Colelli S., Coletta F., Concordia L., Congedo E., Covotta M., Crimella F., Dall'Acqua G., De Cassai A., Defulviis S., Deperi E., Deana C., Delgaudio A., Denittis N., Dicolandrea S., Divezza F., Ferri F., Flocco R., Fontana C., Forastierimolinari A., Frangiosa A., Fumagalli P., Fuselli E., Garbarino M. M., Gelormini D., Geraci C., Geraldini F., Giacomucci A., Giampaoli V., Giorgetti D., Gritti P., Gualdani S., Iacovazzo C., Iermano C., Latronico N., Lugari S., Lusenti F., Maglione C., Magnoni S., Maiarota F., Malla M., Marchesi M., Martino C., Matteotti I., Mazzeo A. T., Morello G., Nardiello I., Paticchio F., Pegoli M., Perotti V., Piazzolla M., Picciafuochi F., Rachedi N., Radolovich D. K., Recchia A., Riccardi S., Romagnoli S., Sala S., Scafuro M. A., Sgarlata P., Soragni A., Stefani F., Stival E., Stofella G., Terranova F., Tinturini R., Togni T., Toto R., Trapani D., Tringali E., Tullo L., Valente A., Valeo T., Varelli G., Villani R., Zamacavicchi F., Zanello M., Zarrillo N., Zugni N., Iaccarino, C, Lippa, L, Munari, M, Castioni, C, Robba, C, Caricato, A, Pompucci, A, Signoretti, S, Zona, G, Rasulo, F, Aimar, E, Amato, S, Angileri, F, Anile, C, Assietti, R, Baratto, V, Barbanera, A, Basile, L, Battaglia, R, Bellocchi, S, Bertuccio, A, Blanco, S, Bolognini, A, Boniferro, B, Bordi, L, Bortolotti, C, Brandini, V, Broger, M, Brollo, M, Caffarella, D, Caggiano, C, Cantisani, P, Capone, C, Cappelletto, B, Capuano, C, Carangelo, B, Caruselli, G, Chessa, M, Chiara, M, Chibbaro, S, Cioffi, V, Ciprianocecchi, P, Colistra, D, Conti, C, Contratti, F, Costella, G, Cuoci, A, D'Avella, D, D'Ercole, M, Deangelis, M, Defalco, R, de Luca, G, de Marinis, P, Del Vecchio, C, Delfinis, C, Denaro, L, Deodato, F, Desogus, N, Disomma, A, Domenicucci, M, Dones, F, Fina, M, Fiori, L, Fricia, M, Gaetani, P, Gazzeri, R, Gentile, M, Germano, A, Ghadirpour, R, Gianfreda, C, Gigante, N, Gigli, R, Giorgetti, J, Giusa, M, Gravina, U, Grippi, L, Guida, F, Guizzardi, G, Iannuzzo, G, Kropp, M, Lattanzi, L, Lucantoni, D, Maffei, L, Magliulo, M, Marconi, F, Marruzzo, D, Martellotta, N, Marton, E, Maugeri, R, Mauro, G, Meli, F, Menniti, A, Merciadri, P, Milanese, L, Nardacci, B, Nasi, D, Orvieto, P, Pacca, P, Pansini, G, Panzarasa, G, Passanisi, M, Pavesi, G, Pizzoni, C, Pulera, F, Rapana, A, Ricci, A, Rispoli, R, Rotondo, M, Russo, N, Santilli, S, Scarano, E, Schwarz, A, Servadei, F, Simonetti, G, Stefini, R, Talamonti, G, Turrisi, A, Valente, V, Villa, A, Vindigni, M, Visocchi, M, Vitali, M, Wierzbicki, V, Zambon, G, Zanotti, B, Zenga, F, Alampi, D, Alessandri, F, Aloj, F, Amigoni, A, Aspide, R, Bertuetti, R, Betti, V, Bilotta, F, Bonato, V, Bosco, E, Brita, M, Buscema, G, Cafiero, T, Cappuccio, D, Caradonna, M, Caria, C, Casartelliliviero, M, Ciritella, P, Cirrincione, S, Citerio, G, Colelli, S, Coletta, F, Concordia, L, Congedo, E, Covotta, M, Crimella, F, Dall'Acqua, G, De Cassai, A, Defulviis, S, Deperi, E, Deana, C, Delgaudio, A, Denittis, N, Dicolandrea, S, Divezza, F, Ferri, F, Flocco, R, Fontana, C, Forastierimolinari, A, Frangiosa, A, Fumagalli, P, Fuselli, E, Garbarino, M, Gelormini, D, Geraci, C, Geraldini, F, Giacomucci, A, Giampaoli, V, Giorgetti, D, Gritti, P, Gualdani, S, Iacovazzo, C, Iermano, C, Latronico, N, Lugari, S, Lusenti, F, Maglione, C, Magnoni, S, Maiarota, F, Malla, M, Marchesi, M, Martino, C, Matteotti, I, Mazzeo, A, Morello, G, Nardiello, I, Paticchio, F, Pegoli, M, Perotti, V, Piazzolla, M, Picciafuochi, F, Rachedi, N, Radolovich, D, Recchia, A, Riccardi, S, Romagnoli, S, Sala, S, Scafuro, M, Sgarlata, P, Soragni, A, Stefani, F, Stival, E, Stofella, G, Terranova, F, Tinturini, R, Togni, T, Toto, R, Trapani, D, Tringali, E, Tullo, L, Valente, A, Valeo, T, Varelli, G, Villani, R, Zamacavicchi, F, Zanello, M, Zarrillo, N, Zugni, N, Iaccarino, C., Lippa, L., Munari, M., Castioni, C. A., Robba, C., Caricato, A., Pompucci, A., Signoretti, S., Zona, G., Rasulo, F. A., Aimar, E., Amato, S., Angileri, F. F., Anile, C., Assietti, R., Baratto, V., Barbanera, A., Basile, L., Battaglia, R., Bellocchi, S., Bertuccio, A., Blanco, S., Bolognini, A., Boniferro, B., Bordi, L., Bortolotti, C., Brandini, V., Broger, M., Brollo, M., Caffarella, D. D., Caggiano, C., Cantisani, P. L., Capone, C., Cappelletto, B., Capuano, C., Carangelo, B., Caruselli, G., Chessa, M. A., Chiara, M., Chibbaro, S., Cioffi, V., Ciprianocecchi, P., Colistra, D., Conti, C., Contratti, F., Costella, G. B., Cuoci, A., D'Avella, D., D'Ercole, M., Deangelis, M., Defalco, R., de Luca, G., de Marinis, P., Del Vecchio, C., Delfinis, C., Denaro, L., Deodato, F., Desogus, N., Disomma, A., Domenicucci, M., Dones, F., Fina, M., Fiori, L., Fricia, M., Gaetani, P., Gazzeri, R., Gentile, M., Germano, A., Ghadirpour, R., Gianfreda, C. D., Gigante, N., Gigli, R., Giorgetti, J., Giusa, M., Gravina, U. G., Grippi, L., Guida, F., Guizzardi, G., Iannuzzo, G., Kropp, M., Lattanzi, L., Lucantoni, D., Maffei, L., Magliulo, M., Marconi, F., Marruzzo, D., Martellotta, N., Marton, E., Maugeri, R., Mauro, G., Meli, F., Menniti, A., Merciadri, P., Milanese, L., Nardacci, B., Nasi, D., Orvieto, P., Pacca, P., Pansini, G., Panzarasa, G., Passanisi, M., Pavesi, G., Pizzoni, C., Pulera, F., Rapana, A., Ricci, A., Rispoli, R., Rotondo, M., Russo, N., Santilli, S., Scarano, E., Schwarz, A., Servadei, F., Simonetti, G., Stefini, R., Talamonti, G., Turrisi, A., Valente, V. M., Villa, A., Vindigni, M., Visocchi, M., Vitali, M., Wierzbicki, V., Zambon, G., Zanotti, B., Zenga, F., Alampi, D., Alessandri, F., Aloj, F., Amigoni, A., Aspide, R., Bertuetti, R., Betti, V., Bilotta, F., Bonato, V., Bosco, E., Brita, M., Buscema, G., Cafiero, T., Cappuccio, D., Caradonna, M., Caria, C. G., Casartelliliviero, M., Ciritella, P., Cirrincione, S., Citerio, G., Colelli, S., Coletta, F., Concordia, L., Congedo, E., Covotta, M., Crimella, F., Dall'Acqua, G., De Cassai, A., Defulviis, S., Deperi, E., Deana, C., Delgaudio, A., Denittis, N., Dicolandrea, S., Divezza, F., Ferri, F., Flocco, R., Fontana, C., Forastierimolinari, A., Frangiosa, A., Fumagalli, P., Fuselli, E., Garbarino, M. M., Gelormini, D., Geraci, C., Geraldini, F., Giacomucci, A., Giampaoli, V., Giorgetti, D., Gritti, P., Gualdani, S., Iacovazzo, C., Iermano, C., Latronico, N., Lugari, S., Lusenti, F., Maglione, C., Magnoni, S., Maiarota, F., Malla, M., Marchesi, M., Martino, C., Matteotti, I., Mazzeo, A. T., Morello, G., Nardiello, I., Paticchio, F., Pegoli, M., Perotti, V., Piazzolla, M., Picciafuochi, F., Rachedi, N., Radolovich, D. K., Recchia, A., Riccardi, S., Romagnoli, S., Sala, S., Scafuro, M. A., Sgarlata, P., Soragni, A., Stefani, F., Stival, E., Stofella, G., Terranova, F., Tinturini, R., Togni, T., Toto, R., Trapani, D., Tringali, E., Tullo, L., Valente, A., Valeo, T., Varelli, G., Villani, R., Zamacavicchi, F., Zanello, M., Zarrillo, N., and Zugni, N.

Subjects
medicine.medical_specialty, Decompressive Craniectomy, Consensus development conference, Decompressive craniectomy, Guideline, Traumatic brain injuries, Critical Care, Intracranial Pressure, medicine.medical_treatment, MEDLINE, Neurosurgery, Traumatic brain injurie, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Intensive care, Settore MED/41 - ANESTESIOLOGIA, Brain Injuries, Traumatic, medicine, Humans, Anesthesia, Intensive care medicine, Randomized Controlled Trials as Topic, business.industry, Neurointensive care, Evidence-based medicine, Italy, 030220 oncology & carcinogenesis, Intracranial pressure monitoring, Surgery, Neurology (clinical), Analgesia, Intracranial Hypertension, business, 030217 neurology & neurosurgery, Human
Abstract

No robust evidence is provided by literature regarding the management of intracranial hypertension following severe traumatic brain injury (TBI). This is mostly due to the lack of prospective randomized controlled trials (RCTs), the presence of studies containing extreme heterogeneously collected populations and controversial considerations about chosen outcome. A scientific society should provide guidelines for care management and scientific support for those areas for which evidence-based medicine has not been identified. However, RCTs in severe TBI have failed to establish intervention effectiveness, arising the need to make greater use of tools such as Consensus Conferences between experts, which have the advantage of providing recommendations based on experience, on the analysis of updated literature data and on the direct comparison of different logistic realities. The Italian scientific societies should provide guidelines following the national laws ruling the best medical practice. However, many limitations do not allow the collection of data supporting high levels of evidence for intracranial pressure (ICP) monitoring and decompressive craniectomy (DC) in patients with severe TBI. This intersociety document proposes best practice guidelines for this subsetting of patients to be adopted on a national Italian level, along with joint statements from "TBI Section" of the Italian Society of Neurosurgery (SINch) endorsed by the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). Presented here is a recap of recommendations on management of ICP and DC supported a high level of available evidence and rate of agreement expressed by the assemblies during the more recent consensus conferences, where members of both groups have had a role of active participants and supporters. The listed recommendations have been sent to a panel of experts consisting of the 107 members of the "TBI Section" of the SINch and the 111 members of the Neuroanesthesia and Neurocritical Care Study Group of the SIAARTI. The aim of the survey was to test a preliminary evaluation of the grade of predictable future adherence of the recommendations following this intersociety proposal. The following recommendations are suggested as representing best clinical practice, nevertheless, adoption of local multidisciplinary protocols regarding thresholds of ICP values, drug therapies, hemostasis management and perioperative care of decompressed patients is strongly recommended to improve treatment efficiency, to increase the quality of data collection and to provide more powerful evidence with future studies. Thus, for this future perspective a rapid overview of the role of the multimodal neuromonitoring in the optimal severe TBI management is also provided in this document. It is reasonable to assume that the recommendations reported in this paper will in future be updated by new observations arising from future trials. They are not binding, and this document should be offered as a guidance for clinical practice through an intersociety agreement, taking in consideration the low level of evidence.

Published
2021

3. Management of intracranial hypertension following traumatic brain injury: A best clinical practice adoption proposal for intracranial pressure monitoring and decompressive craniectomy: Joint statements by the Traumatic Brain Injury Section of the Italian Society of Neurosurgery (SINch) and the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI)

Author

Iaccarino, C, Lippa, L, Munari, M, Castioni, C, Robba, C, Caricato, A, Pompucci, A, Signoretti, S, Zona, G, Rasulo, F, Aimar, E, Amato, S, Angileri, F, Anile, C, Assietti, R, Baratto, V, Barbanera, A, Basile, L, Battaglia, R, Bellocchi, S, Bertuccio, A, Blanco, S, Bolognini, A, Boniferro, B, Bordi, L, Bortolotti, C, Brandini, V, Broger, M, Brollo, M, Caffarella, D, Caggiano, C, Cantisani, P, Capone, C, Cappelletto, B, Capuano, C, Carangelo, B, Caruselli, G, Chessa, M, Chiara, M, Chibbaro, S, Cioffi, V, Ciprianocecchi, P, Colistra, D, Conti, C, Contratti, F, Costella, G, Cuoci, A, D'Avella, D, D'Ercole, M, Deangelis, M, Defalco, R, de Luca, G, de Marinis, P, Del Vecchio, C, Delfinis, C, Denaro, L, Deodato, F, Desogus, N, Disomma, A, Domenicucci, M, Dones, F, Fina, M, Fiori, L, Fricia, M, Gaetani, P, Gazzeri, R, Gentile, M, Germano, A, Ghadirpour, R, Gianfreda, C, Gigante, N, Gigli, R, Giorgetti, J, Giusa, M, Gravina, U, Grippi, L, Guida, F, Guizzardi, G, Iannuzzo, G, Kropp, M, Lattanzi, L, Lucantoni, D, Maffei, L, Magliulo, M, Marconi, F, Marruzzo, D, Martellotta, N, Marton, E, Maugeri, R, Mauro, G, Meli, F, Menniti, A, Merciadri, P, Milanese, L, Nardacci, B, Nasi, D, Orvieto, P, Pacca, P, Pansini, G, Panzarasa, G, Passanisi, M, Pavesi, G, Pizzoni, C, Pulera, F, Rapana, A, Ricci, A, Rispoli, R, Rotondo, M, Russo, N, Santilli, S, Scarano, E, Schwarz, A, Servadei, F, Simonetti, G, Stefini, R, Talamonti, G, Turrisi, A, Valente, V, Villa, A, Vindigni, M, Visocchi, M, Vitali, M, Wierzbicki, V, Zambon, G, Zanotti, B, Zenga, F, Alampi, D, Alessandri, F, Aloj, F, Amigoni, A, Aspide, R, Bertuetti, R, Betti, V, Bilotta, F, Bonato, V, Bosco, E, Brita, M, Buscema, G, Cafiero, T, Cappuccio, D, Caradonna, M, Caria, C, Casartelliliviero, M, Ciritella, P, Cirrincione, S, Citerio, G, Colelli, S, Coletta, F, Concordia, L, Congedo, E, Covotta, M, Crimella, F, Dall'Acqua, G, De Cassai, A, Defulviis, S, Deperi, E, Deana, C, Delgaudio, A, Denittis, N, Dicolandrea, S, Divezza, F, Ferri, F, Flocco, R, Fontana, C, Forastierimolinari, A, Frangiosa, A, Fumagalli, P, Fuselli, E, Garbarino, M, Gelormini, D, Geraci, C, Geraldini, F, Giacomucci, A, Giampaoli, V, Giorgetti, D, Gritti, P, Gualdani, S, Iacovazzo, C, Iermano, C, Latronico, N, Lugari, S, Lusenti, F, Maglione, C, Magnoni, S, Maiarota, F, Malla, M, Marchesi, M, Martino, C, Matteotti, I, Mazzeo, A, Morello, G, Nardiello, I, Paticchio, F, Pegoli, M, Perotti, V, Piazzolla, M, Picciafuochi, F, Rachedi, N, Radolovich, D, Recchia, A, Riccardi, S, Romagnoli, S, Sala, S, Scafuro, M, Sgarlata, P, Soragni, A, Stefani, F, Stival, E, Stofella, G, Terranova, F, Tinturini, R, Togni, T, Toto, R, Trapani, D, Tringali, E, Tullo, L, Valente, A, Valeo, T, Varelli, G, Villani, R, Zamacavicchi, F, Zanello, M, Zarrillo, N, Zugni, N, Iaccarino C., Lippa L., Munari M., Castioni C. A., Robba C., Caricato A., Pompucci A., Signoretti S., Zona G., Rasulo F. A., Aimar E., Amato S., Angileri F. F., Anile C., Assietti R., Baratto V., Barbanera A., Basile L., Battaglia R., Bellocchi S., Bertuccio A., Blanco S., Bolognini A., Boniferro B., Bordi L., Bortolotti C., Brandini V., Broger M., Brollo M., Caffarella D. D., Caggiano C., Cantisani P. L., Capone C., Cappelletto B., Capuano C., Carangelo B., Caruselli G., Chessa M. A., Chiara M., Chibbaro S., Cioffi V., Ciprianocecchi P., Colistra D., Conti C., Contratti F., Costella G. B., Cuoci A., D'Avella D., D'Ercole M., Deangelis M., Defalco R., de Luca G., de Marinis P., Del Vecchio C., Delfinis C., Denaro L., Deodato F., Desogus N., Disomma A., Domenicucci M., Dones F., Fina M., Fiori L., Fricia M., Gaetani P., Gazzeri R., Gentile M., Germano A., Ghadirpour R., Gianfreda C. D., Gigante N., Gigli R., Giorgetti J., Giusa M., Gravina U. G., Grippi L., Guida F., Guizzardi G., Iannuzzo G., Kropp M., Lattanzi L., Lucantoni D., Maffei L., Magliulo M., Marconi F., Marruzzo D., Martellotta N., Marton E., Maugeri R., Mauro G., Meli F., Menniti A., Merciadri P., Milanese L., Nardacci B., Nasi D., Orvieto P., Pacca P., Pansini G., Panzarasa G., Passanisi M., Pavesi G., Pizzoni C., Pulera F., Rapana A., Ricci A., Rispoli R., Rotondo M., Russo N., Santilli S., Scarano E., Schwarz A., Servadei F., Simonetti G., Stefini R., Talamonti G., Turrisi A., Valente V. M., Villa A., Vindigni M., Visocchi M., Vitali M., Wierzbicki V., Zambon G., Zanotti B., Zenga F., Alampi D., Alessandri F., Aloj F., Amigoni A., Aspide R., Bertuetti R., Betti V., Bilotta F., Bonato V., Bosco E., Brita M., Buscema G., Cafiero T., Cappuccio D., Caradonna M., Caria C. G., Casartelliliviero M., Ciritella P., Cirrincione S., Citerio G., Colelli S., Coletta F., Concordia L., Congedo E., Covotta M., Crimella F., Dall'Acqua G., De Cassai A., Defulviis S., Deperi E., Deana C., Delgaudio A., Denittis N., Dicolandrea S., Divezza F., Ferri F., Flocco R., Fontana C., Forastierimolinari A., Frangiosa A., Fumagalli P., Fuselli E., Garbarino M. M., Gelormini D., Geraci C., Geraldini F., Giacomucci A., Giampaoli V., Giorgetti D., Gritti P., Gualdani S., Iacovazzo C., Iermano C., Latronico N., Lugari S., Lusenti F., Maglione C., Magnoni S., Maiarota F., Malla M., Marchesi M., Martino C., Matteotti I., Mazzeo A. T., Morello G., Nardiello I., Paticchio F., Pegoli M., Perotti V., Piazzolla M., Picciafuochi F., Rachedi N., Radolovich D. K., Recchia A., Riccardi S., Romagnoli S., Sala S., Scafuro M. A., Sgarlata P., Soragni A., Stefani F., Stival E., Stofella G., Terranova F., Tinturini R., Togni T., Toto R., Trapani D., Tringali E., Tullo L., Valente A., Valeo T., Varelli G., Villani R., Zamacavicchi F., Zanello M., Zarrillo N., Zugni N., Iaccarino, C, Lippa, L, Munari, M, Castioni, C, Robba, C, Caricato, A, Pompucci, A, Signoretti, S, Zona, G, Rasulo, F, Aimar, E, Amato, S, Angileri, F, Anile, C, Assietti, R, Baratto, V, Barbanera, A, Basile, L, Battaglia, R, Bellocchi, S, Bertuccio, A, Blanco, S, Bolognini, A, Boniferro, B, Bordi, L, Bortolotti, C, Brandini, V, Broger, M, Brollo, M, Caffarella, D, Caggiano, C, Cantisani, P, Capone, C, Cappelletto, B, Capuano, C, Carangelo, B, Caruselli, G, Chessa, M, Chiara, M, Chibbaro, S, Cioffi, V, Ciprianocecchi, P, Colistra, D, Conti, C, Contratti, F, Costella, G, Cuoci, A, D'Avella, D, D'Ercole, M, Deangelis, M, Defalco, R, de Luca, G, de Marinis, P, Del Vecchio, C, Delfinis, C, Denaro, L, Deodato, F, Desogus, N, Disomma, A, Domenicucci, M, Dones, F, Fina, M, Fiori, L, Fricia, M, Gaetani, P, Gazzeri, R, Gentile, M, Germano, A, Ghadirpour, R, Gianfreda, C, Gigante, N, Gigli, R, Giorgetti, J, Giusa, M, Gravina, U, Grippi, L, Guida, F, Guizzardi, G, Iannuzzo, G, Kropp, M, Lattanzi, L, Lucantoni, D, Maffei, L, Magliulo, M, Marconi, F, Marruzzo, D, Martellotta, N, Marton, E, Maugeri, R, Mauro, G, Meli, F, Menniti, A, Merciadri, P, Milanese, L, Nardacci, B, Nasi, D, Orvieto, P, Pacca, P, Pansini, G, Panzarasa, G, Passanisi, M, Pavesi, G, Pizzoni, C, Pulera, F, Rapana, A, Ricci, A, Rispoli, R, Rotondo, M, Russo, N, Santilli, S, Scarano, E, Schwarz, A, Servadei, F, Simonetti, G, Stefini, R, Talamonti, G, Turrisi, A, Valente, V, Villa, A, Vindigni, M, Visocchi, M, Vitali, M, Wierzbicki, V, Zambon, G, Zanotti, B, Zenga, F, Alampi, D, Alessandri, F, Aloj, F, Amigoni, A, Aspide, R, Bertuetti, R, Betti, V, Bilotta, F, Bonato, V, Bosco, E, Brita, M, Buscema, G, Cafiero, T, Cappuccio, D, Caradonna, M, Caria, C, Casartelliliviero, M, Ciritella, P, Cirrincione, S, Citerio, G, Colelli, S, Coletta, F, Concordia, L, Congedo, E, Covotta, M, Crimella, F, Dall'Acqua, G, De Cassai, A, Defulviis, S, Deperi, E, Deana, C, Delgaudio, A, Denittis, N, Dicolandrea, S, Divezza, F, Ferri, F, Flocco, R, Fontana, C, Forastierimolinari, A, Frangiosa, A, Fumagalli, P, Fuselli, E, Garbarino, M, Gelormini, D, Geraci, C, Geraldini, F, Giacomucci, A, Giampaoli, V, Giorgetti, D, Gritti, P, Gualdani, S, Iacovazzo, C, Iermano, C, Latronico, N, Lugari, S, Lusenti, F, Maglione, C, Magnoni, S, Maiarota, F, Malla, M, Marchesi, M, Martino, C, Matteotti, I, Mazzeo, A, Morello, G, Nardiello, I, Paticchio, F, Pegoli, M, Perotti, V, Piazzolla, M, Picciafuochi, F, Rachedi, N, Radolovich, D, Recchia, A, Riccardi, S, Romagnoli, S, Sala, S, Scafuro, M, Sgarlata, P, Soragni, A, Stefani, F, Stival, E, Stofella, G, Terranova, F, Tinturini, R, Togni, T, Toto, R, Trapani, D, Tringali, E, Tullo, L, Valente, A, Valeo, T, Varelli, G, Villani, R, Zamacavicchi, F, Zanello, M, Zarrillo, N, Zugni, N, Iaccarino C., Lippa L., Munari M., Castioni C. A., Robba C., Caricato A., Pompucci A., Signoretti S., Zona G., Rasulo F. A., Aimar E., Amato S., Angileri F. F., Anile C., Assietti R., Baratto V., Barbanera A., Basile L., Battaglia R., Bellocchi S., Bertuccio A., Blanco S., Bolognini A., Boniferro B., Bordi L., Bortolotti C., Brandini V., Broger M., Brollo M., Caffarella D. D., Caggiano C., Cantisani P. L., Capone C., Cappelletto B., Capuano C., Carangelo B., Caruselli G., Chessa M. A., Chiara M., Chibbaro S., Cioffi V., Ciprianocecchi P., Colistra D., Conti C., Contratti F., Costella G. B., Cuoci A., D'Avella D., D'Ercole M., Deangelis M., Defalco R., de Luca G., de Marinis P., Del Vecchio C., Delfinis C., Denaro L., Deodato F., Desogus N., Disomma A., Domenicucci M., Dones F., Fina M., Fiori L., Fricia M., Gaetani P., Gazzeri R., Gentile M., Germano A., Ghadirpour R., Gianfreda C. D., Gigante N., Gigli R., Giorgetti J., Giusa M., Gravina U. G., Grippi L., Guida F., Guizzardi G., Iannuzzo G., Kropp M., Lattanzi L., Lucantoni D., Maffei L., Magliulo M., Marconi F., Marruzzo D., Martellotta N., Marton E., Maugeri R., Mauro G., Meli F., Menniti A., Merciadri P., Milanese L., Nardacci B., Nasi D., Orvieto P., Pacca P., Pansini G., Panzarasa G., Passanisi M., Pavesi G., Pizzoni C., Pulera F., Rapana A., Ricci A., Rispoli R., Rotondo M., Russo N., Santilli S., Scarano E., Schwarz A., Servadei F., Simonetti G., Stefini R., Talamonti G., Turrisi A., Valente V. M., Villa A., Vindigni M., Visocchi M., Vitali M., Wierzbicki V., Zambon G., Zanotti B., Zenga F., Alampi D., Alessandri F., Aloj F., Amigoni A., Aspide R., Bertuetti R., Betti V., Bilotta F., Bonato V., Bosco E., Brita M., Buscema G., Cafiero T., Cappuccio D., Caradonna M., Caria C. G., Casartelliliviero M., Ciritella P., Cirrincione S., Citerio G., Colelli S., Coletta F., Concordia L., Congedo E., Covotta M., Crimella F., Dall'Acqua G., De Cassai A., Defulviis S., Deperi E., Deana C., Delgaudio A., Denittis N., Dicolandrea S., Divezza F., Ferri F., Flocco R., Fontana C., Forastierimolinari A., Frangiosa A., Fumagalli P., Fuselli E., Garbarino M. M., Gelormini D., Geraci C., Geraldini F., Giacomucci A., Giampaoli V., Giorgetti D., Gritti P., Gualdani S., Iacovazzo C., Iermano C., Latronico N., Lugari S., Lusenti F., Maglione C., Magnoni S., Maiarota F., Malla M., Marchesi M., Martino C., Matteotti I., Mazzeo A. T., Morello G., Nardiello I., Paticchio F., Pegoli M., Perotti V., Piazzolla M., Picciafuochi F., Rachedi N., Radolovich D. K., Recchia A., Riccardi S., Romagnoli S., Sala S., Scafuro M. A., Sgarlata P., Soragni A., Stefani F., Stival E., Stofella G., Terranova F., Tinturini R., Togni T., Toto R., Trapani D., Tringali E., Tullo L., Valente A., Valeo T., Varelli G., Villani R., Zamacavicchi F., Zanello M., Zarrillo N., and Zugni N.

Abstract

No robust evidence is provided by literature regarding the management of intracranial hypertension following severe traumatic brain injury (TBI). This is mostly due to the lack of prospective randomized controlled trials (RCTs), the presence of studies containing extreme heterogeneously collected populations and controversial considerations about chosen outcome. A scientific society should provide guidelines for care management and scientific support for those areas for which evidence-based medicine has not been identified. However, RCTs in severe TBI have failed to establish intervention effectiveness, arising the need to make greater use of tools such as Consensus Conferences between experts, which have the advantage of providing recommendations based on experience, on the analysis of updated literature data and on the direct comparison of different logistic realities. The Italian scientific societies should provide guidelines following the national laws ruling the best medical practice. However, many limitations do not allow the collection of data supporting high levels of evidence for intracranial pressure (ICP) monitoring and decompressive craniectomy (DC) in patients with severe TBI. This intersociety document proposes best practice guidelines for this subsetting of patients to be adopted on a national Italian level, along with joint statements from “TBI Section” of the Italian Society of Neurosurgery (SINch) endorsed by the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). Presented here is a recap of recommendations on management of ICP and DC supported a high level of available evidence and rate of agreement expressed by the assemblies during the more recent consensus conferences, where members of both groups have had a role of active participants and supporters. The listed recommendations have been sent to a panel of experts consisting of the 107 members of the “T

Published
2021

4. Management of intracranial hypertension following traumatic brain injury: A best clinical practice adoption proposal for intracranial pressure monitoring and decompressive craniectomy: Joint statements by the Traumatic Brain Injury Section of the Italian Society of Neurosurgery (SINch) and the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI)

Author

Iaccarino, C., Lippa, L., Munari, M., Castioni, C. A., Robba, C., Caricato, Anselmo, Pompucci, Angelo, Signoretti, S., Zona, G., Rasulo, F. A., Aimar, E., Amato, S., Angileri, F. F., Anile, Carmelo, Assietti, R., Baratto, V., Barbanera, A., Basile, L., Battaglia, R., Bellocchi, S., Bertuccio, A., Blanco, S., Bolognini, A., Boniferro, B., Bordi, L., Bortolotti, C., Brandini, V., Broger, Maximilian, Brollo, M., Caffarella, D. D., Caggiano, Cinzia, Cantisani, P. L., Capone, C., Cappelletto, B., Capuano, C., Carangelo, B., Caruselli, G., Chessa, M. A., Chiara, M., Chibbaro, S., Cioffi, V., Ciprianocecchi, P., Colistra, D., Conti, C., Contratti, F., Costella, G. B., Cuoci, A., D'Avella, D., D'Ercole, Manuela, Deangelis, M., Defalco, R., de Luca, G., de Marinis, P., Del Vecchio, C., Delfinis, C., Denaro, Luca, Deodato, F., Desogus, N., Disomma, A., Domenicucci, M., Dones, F., Fina, M., Fiori, L., Fricia, M., Gaetani, P., Gazzeri, R., Gentile, M., Germano, A., Ghadirpour, R., Gianfreda, C. D., Gigante, N., Gigli, R., Giorgetti, J., Giusa, M., Gravina, U. G., Grippi, L., Guida, F., Guizzardi, G., Iannuzzo, G., Kropp, M., Lattanzi, L., Lucantoni, D., Maffei, L., Magliulo, M., Marconi, F., Marruzzo, D., Martellotta, N., Marton, E., Maugeri, R., Mauro, G., Meli, F., Menniti, A., Merciadri, P., Milanese, L., Nardacci, B., Nasi, D., Orvieto, P., Pacca, P., Pansini, G., Panzarasa, G., Passanisi, M., Pavesi, G., Pizzoni, C., Pulera, F., Rapana, A., Ricci, A., Rispoli, R., Rotondo, M., Russo, N., Santilli, S., Scarano, E., Schwarz, A., Servadei, Franco, Simonetti, G., Stefini, R., Talamonti, G., Turrisi, A., Valente, V. M., Villa, A., Vindigni, M., Visocchi, Massimiliano, Vitali, M., Wierzbicki, V., Zambon, G., Zanotti, B., Zenga, F., Alampi, D., Alessandri, F., Aloj, F., Amigoni, A., Aspide, R., Bertuetti, R., Betti, V., Bilotta, F., Bonato, V., Bosco, E., Brita, M., Buscema, G., Cafiero, T., Cappuccio, D., Caradonna, M., Caria, C. G., Casartelliliviero, M., Ciritella, P., Cirrincione, S., Citerio, G., Colelli, S., Coletta, F., Concordia, L., Congedo, E., Covotta, M., Crimella, F., Dall'Acqua, G., De Cassai, A., Defulviis, S., Deperi, E., Deana, C., Delgaudio, A., Denittis, N., Dicolandrea, S., Divezza, F., Ferri, F., Flocco, R., Fontana, C., Forastierimolinari, A., Frangiosa, A., Fumagalli, P., Fuselli, E., Garbarino, M. M., Gelormini, D., Geraci, C., Geraldini, F., Giacomucci, A., Giampaoli, V., Giorgetti, D., Gritti, P., Gualdani, S., Iacovazzo, C., Iermano, C., Latronico, N., Lugari, S., Lusenti, F., Maglione, C., Magnoni, S., Maiarota, F., Malla, M., Marchesi, M., Martino, C., Matteotti, I., Mazzeo, A. T., Morello, G., Nardiello, I., Paticchio, F., Pegoli, M., Perotti, Valerio, Piazzolla, M., Picciafuochi, F., Rachedi, N., Radolovich, D. K., Recchia, A., Riccardi, S., Romagnoli, S., Sala, S., Scafuro, M. A., Sgarlata, P., Soragni, A., Stefani, F., Stival, Eleonora, Stofella, G., Terranova, F., Tinturini, R., Togni, T., Toto, R., Trapani, D., Tringali, E., Tullo, L., Valente, A., Valeo, T., Varelli, G., Villani, R., Zamacavicchi, F., Zanello, M., Zarrillo, N., Zugni, N., Caricato A. (ORCID:0000-0001-5929-120X), Pompucci A. (ORCID:0000-0002-5427-9719), Anile C. (ORCID:0000-0002-0481-9713), Broger M., Caggiano C., D'Ercole M., Denaro L., Servadei F., Visocchi M. (ORCID:0000-0003-1087-0491), Perotti V. (ORCID:0000-0001-9461-2101), Stival E., Iaccarino, C., Lippa, L., Munari, M., Castioni, C. A., Robba, C., Caricato, Anselmo, Pompucci, Angelo, Signoretti, S., Zona, G., Rasulo, F. A., Aimar, E., Amato, S., Angileri, F. F., Anile, Carmelo, Assietti, R., Baratto, V., Barbanera, A., Basile, L., Battaglia, R., Bellocchi, S., Bertuccio, A., Blanco, S., Bolognini, A., Boniferro, B., Bordi, L., Bortolotti, C., Brandini, V., Broger, Maximilian, Brollo, M., Caffarella, D. D., Caggiano, Cinzia, Cantisani, P. L., Capone, C., Cappelletto, B., Capuano, C., Carangelo, B., Caruselli, G., Chessa, M. A., Chiara, M., Chibbaro, S., Cioffi, V., Ciprianocecchi, P., Colistra, D., Conti, C., Contratti, F., Costella, G. B., Cuoci, A., D'Avella, D., D'Ercole, Manuela, Deangelis, M., Defalco, R., de Luca, G., de Marinis, P., Del Vecchio, C., Delfinis, C., Denaro, Luca, Deodato, F., Desogus, N., Disomma, A., Domenicucci, M., Dones, F., Fina, M., Fiori, L., Fricia, M., Gaetani, P., Gazzeri, R., Gentile, M., Germano, A., Ghadirpour, R., Gianfreda, C. D., Gigante, N., Gigli, R., Giorgetti, J., Giusa, M., Gravina, U. G., Grippi, L., Guida, F., Guizzardi, G., Iannuzzo, G., Kropp, M., Lattanzi, L., Lucantoni, D., Maffei, L., Magliulo, M., Marconi, F., Marruzzo, D., Martellotta, N., Marton, E., Maugeri, R., Mauro, G., Meli, F., Menniti, A., Merciadri, P., Milanese, L., Nardacci, B., Nasi, D., Orvieto, P., Pacca, P., Pansini, G., Panzarasa, G., Passanisi, M., Pavesi, G., Pizzoni, C., Pulera, F., Rapana, A., Ricci, A., Rispoli, R., Rotondo, M., Russo, N., Santilli, S., Scarano, E., Schwarz, A., Servadei, Franco, Simonetti, G., Stefini, R., Talamonti, G., Turrisi, A., Valente, V. M., Villa, A., Vindigni, M., Visocchi, Massimiliano, Vitali, M., Wierzbicki, V., Zambon, G., Zanotti, B., Zenga, F., Alampi, D., Alessandri, F., Aloj, F., Amigoni, A., Aspide, R., Bertuetti, R., Betti, V., Bilotta, F., Bonato, V., Bosco, E., Brita, M., Buscema, G., Cafiero, T., Cappuccio, D., Caradonna, M., Caria, C. G., Casartelliliviero, M., Ciritella, P., Cirrincione, S., Citerio, G., Colelli, S., Coletta, F., Concordia, L., Congedo, E., Covotta, M., Crimella, F., Dall'Acqua, G., De Cassai, A., Defulviis, S., Deperi, E., Deana, C., Delgaudio, A., Denittis, N., Dicolandrea, S., Divezza, F., Ferri, F., Flocco, R., Fontana, C., Forastierimolinari, A., Frangiosa, A., Fumagalli, P., Fuselli, E., Garbarino, M. M., Gelormini, D., Geraci, C., Geraldini, F., Giacomucci, A., Giampaoli, V., Giorgetti, D., Gritti, P., Gualdani, S., Iacovazzo, C., Iermano, C., Latronico, N., Lugari, S., Lusenti, F., Maglione, C., Magnoni, S., Maiarota, F., Malla, M., Marchesi, M., Martino, C., Matteotti, I., Mazzeo, A. T., Morello, G., Nardiello, I., Paticchio, F., Pegoli, M., Perotti, Valerio, Piazzolla, M., Picciafuochi, F., Rachedi, N., Radolovich, D. K., Recchia, A., Riccardi, S., Romagnoli, S., Sala, S., Scafuro, M. A., Sgarlata, P., Soragni, A., Stefani, F., Stival, Eleonora, Stofella, G., Terranova, F., Tinturini, R., Togni, T., Toto, R., Trapani, D., Tringali, E., Tullo, L., Valente, A., Valeo, T., Varelli, G., Villani, R., Zamacavicchi, F., Zanello, M., Zarrillo, N., Zugni, N., Caricato A. (ORCID:0000-0001-5929-120X), Pompucci A. (ORCID:0000-0002-5427-9719), Anile C. (ORCID:0000-0002-0481-9713), Broger M., Caggiano C., D'Ercole M., Denaro L., Servadei F., Visocchi M. (ORCID:0000-0003-1087-0491), Perotti V. (ORCID:0000-0001-9461-2101), and Stival E.

Abstract

No robust evidence is provided by literature regarding the management of intracranial hypertension following severe traumatic brain injury (TBI). This is mostly due to the lack of prospective randomized controlled trials (RCTs), the presence of studies containing extreme heterogeneously collected populations and controversial considerations about chosen outcome. A scientific society should provide guidelines for care management and scientific support for those areas for which evidence-based medicine has not been identified. However, RCTs in severe TBI have failed to establish intervention effectiveness, arising the need to make greater use of tools such as Consensus Conferences between experts, which have the advantage of providing recommendations based on experience, on the analysis of updated literature data and on the direct comparison of different logistic realities. The Italian scientific societies should provide guidelines following the national laws ruling the best medical practice. However, many limitations do not allow the collection of data supporting high levels of evidence for intracranial pressure (ICP) monitoring and decompressive craniectomy (DC) in patients with severe TBI. This intersociety document proposes best practice guidelines for this subsetting of patients to be adopted on a national Italian level, along with joint statements from “TBI Section” of the Italian Society of Neurosurgery (SINch) endorsed by the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). Presented here is a recap of recommendations on management of ICP and DC supported a high level of available evidence and rate of agreement expressed by the assemblies during the more recent consensus conferences, where members of both groups have had a role of active participants and supporters. The listed recommendations have been sent to a panel of experts consisting of the 107 members of the “T

Published
2021

5. The features of acquired thrombotic thrombocytopenic purpura occurring at advanced age

Author

Agosti, P, Mancini, I, Artoni, A, Ferrari, B, Pontiggia, S, Trisolini, Sm, Facchini, L, Peyvandi, F, Capria, S, Codeluppi, K, Rinaldi, E, Pastore, D, Campus, S, Podda, Ra, Caria, C, Caddori, A, Nicolosi, D, Giuffrida, G, Agostini, V, Roncarati, U, Mannarella, C, Fragasso, A, Podda, Gm, Birocchi, S, Cerbone, Am, Tufano, A, Loffredo, G, Menna, G, Pizzuti, M, Ronchi, M, De Fanti, A, Amarri, S, Defina, M, Bocchia, M, Ceru, S, Gattillo, S, Agosti, P., Mancini I., Artoni A., Ferrari B., Pontiggia S., Trisolini S. M., Facchini L., Peyvandi F., and Tufano, A.

Subjects
medicine.medical_specialty, Thrombotic microangiopathy, ADAMTS13 Protein, Hemorrhage, Disease, 030204 cardiovascular system & hematology, Kidney, Adamts13 activity, 03 medical and health sciences, 0302 clinical medicine, Elderly, Older patients, Internal medicine, medicine, Humans, Registries, Acute thrombotic thrombocytopenic purpura management, ADAMTS13, Rare disease, Aged, Acquired Thrombotic Thrombocytopenic Purpura, Purpura, Thrombotic Thrombocytopenic, business.industry, Hematology, Microangiopathic hemolytic anemia, medicine.disease, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Female, business
Abstract

Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare life-threatening thrombotic microangiopathy (TMA) affecting more frequently women of 30–50 years of age. There is scarce information on the clinical features of aTTP occurring in the elderly. Our goal was to evaluate the impact of an elderly-onset disease on the expression, severity and management of aTTP. Materials and methods: We performed a cross-sectional study of patients enrolled in the Milan TTP Registry (www.ttpdatabase.org) after a first acute episode of aTTP from January 2002 to March 2018. The aTTP diagnosis was suspected on the basis of the presence of thrombocytopenia and microangiopathic hemolytic anemia with no alternative causes, and was confirmed centrally by a severe plasma deficiency of ADAMTS13 activity (

Published
2020

7. Síntese do estudo da recarga de águas subterrâneas do concelho de Almada

Author

Caria, C., Oliveira, M. M., and Silva, M.

Subjects
Almada, Balanço hídrico, Recarga, Águas subterrâneas, Balseq_mod
Abstract

O estudo presente refere-se à estimativa da recarga natural de águas subterrâneas na área abrangida pelo concelho de Almada. A recarga foi estimada através do modelo BALSEQ_MOD de balanço hídrico sequencial diário ao nível do solo. O balanço baseou-se no período de referência entre 1981-10-01 e 2011-09-30 com base nas séries de precipitação do Monte da Caparica e de evapotranspiração determinada com base nos registos da estação de Lisboa Geofísico. Os parâmetros necessários à corrida do modelo foram determinados com base nos mapas de solos e de ocupação do solo. Os resultados obtidos permitiram estimar a recarga média no concelho de Almada em 77 mm/ano, o que corresponde a cerca de 11% da precipitação ocorrida na área do concelho. FCT, GRUNDFOS, AQUAGRIACE, GRANDEWATER; Nemus 7 4p URL do 9º Seminário sobre Águas Subterrâneas: http://www.aprh.pt/9sas/ DHA/NAS 2013 7 a 8 de Março

Published
2013

8. Efficient Regiocontrolled Synthesis and Antimicrobial Activity of Pyrazoles

Author

Caria C. Costa, Mara Elisa Fortes Braibante, Luciana de Carvalho Tavares, Robert A. Burrow, Simone F. Rohte, Hugo T. S. Braibante, Ademir F. Morel, and Caroline Z. Stüker

Subjects
chemistry.chemical_compound, Montmorillonite, Chemistry, Organic Chemistry, Organic chemistry, Structure–activity relationship, General Medicine, Antimicrobial, Combinatorial chemistry, Catalysis, Hydrazine derivatives
Abstract

A series of 1,5-diphenyl-1 H-pyrazol-3-amines, 3-ethoxy-5-phenyl-1 H-pyrazole, 5-ethoxy-1,3-diphenyl-1 H-pyr-azole and 3-ethoxy-1,5-diphenyl-1 H-pyrazole were efficiently prepared from the regiocontrolled cyclization of α-oxoketene O, N-acetals and/or β-oxo thioxoesters with hydrazine derivatives using montmorillonite K-10 as solid support with ultrasound. The antimicrobial activity of the heterocyclic compounds was evaluated by direct bioautography test.

Published
2007
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11. Inhibition of translational initiation in Saccharomyces cerevisiae by secondary structure: the roles of the stability and position of stem-loops in the mRNA leader

Author

Joop van den Heuvel, John E.G. McCarthy, and Caria C. Oliveira

Subjects
Chloramphenicol O-Acetyltransferase, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Molecular Sequence Data, Microbiology, Eukaryotic translation, Start codon, Genes, Reporter, Gene Expression Regulation, Fungal, Luciferase, RNA, Messenger, Luciferases, Peptide Chain Initiation, Translational, Promoter Regions, Genetic, Molecular Biology, Gene, Genetics, Reporter gene, biology, Base Sequence, Translation (biology), biology.organism_classification, Cell biology, Restriction site, Enzyme Induction, Nucleic Acid Conformation, Plasmids
Abstract

Summary A new modular gene-expression system for use in studies of translational control in Saccharomyces cerevisiae was constructed. A GAL::PGK fusion promoter (GPF) directed the inducible synthesis of mRNAs initiated at a single major site. A series of leader sequences were tested in combination with each of two reporter genes (encoding chloramphenicol acetyl transferase (cat) and luciferase (luc)). Stem-loop structures of three different sizes and predicted stabilities were inserted into each of two different unique restriction sites in the leader. After correction for relative mRNA abundance, a stem-loop of predicted stability equivalent to approximately −18kcal mol−1 inhibited translation by up to 89%. The degree of inhibition exerted by the other stem-loops correlated positively with their predicted stabilities. Combinations of two stem-l oops at different sites yielded an inhibitory effect greater than that of either individual stem-loop alone. Similar inhibitory effects were observed with both reporter genes. However, inhibition of translation, particularly of the cat gene, was more effective when the stem-loop was positioned close to the start codon rather than at the 5′ end of the leader. The observed results reflect an important form of post-transcriptional control that is expected to act on a large number of genes in yeast.

Published
1993

14. The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians

Author

Clara Mannarella, Erminia Rinaldi, Katia Codeluppi, Anna Maria Cerbone, Sergio Amarri, Daniela Nicolosi, Michele Pizzuti, Luca Facchini, Alessandro De Fanti, Michela Ronchi, Emanuela Pappalardo, Barbara Ferrari, Monica Bocchia, Gaetano Giuffrida, Vanessa Agostini, Cinzia Caria, Silvia Maria Trisolini, Salvatore Gattillo, Elisa Giacomini, Gian Marco Podda, Aldo Caddori, Saveria Capria, Antonella Tufano, Silvia Cerù, Marzia Defina, Alberto Fragasso, Roberta Gualtierotti, Andrea Artoni, Simona Campus, Flora Peyvandi, Silvia Pontiggia, Umberto Roncarati, Ilaria Mancini, Giuseppe Menna, Domenico Pastore, Frits R. Rosendaal, Simone Birocchi, Mancini, I., Giacomini, E., Pontiggia, S., Artoni, A., Ferrari, B., Pappalardo, E., Gualtierotti, R., Trisolini, S. M., Capria, S., Facchini, L., Codeluppi, K., Rinaldi, E., Pastore, D., Campus, S., Caria, C., Caddori, A., Nicolosi, D., Giuffrida, G., Agostini, V., Roncarati, U., Mannarella, C., Fragasso, A., Podda, G. M., Birocchi, S., Cerbone, A. M., Tufano, A., Menna, G., Pizzuti, M., Ronchi, M., De Fanti, A., Amarri, S., Defina, M., Bocchia, M., Ceru, S., Gattillo, S., Rosendaal, F. R., and Peyvandi, F.

Subjects
medicine.medical_specialty, Thrombotic microangiopathy, ADAMTS13, HLA, autoimmune disease, genotyping, relapse, risk factor, thrombotic thrombocytopenic purpura, Thrombotic thrombocytopenic purpura, lcsh:Medicine, Human leukocyte antigen, 030204 cardiovascular system & hematology, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Risk factor, business.industry, lcsh:R, Absolute risk reduction, General Medicine, Odds ratio, medicine.disease, business, 030215 immunology, Cohort study
Abstract

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) deficiency, recurring in 30&ndash, 50% of patients. The common human leukocyte antigen (HLA) variant rs6903608 was found to be associated with prevalent iTTP, but whether this variant is associated with disease relapse is unknown. To estimate the impact of rs6903608 on iTTP onset and relapse, we performed a case-control and cohort study in 161 Italian patients with a first iTTP episode between 2002 and 2018, and in 456 Italian controls. Variation in rs6903608 was strongly associated with iTTP onset (homozygotes odds ratio (OR) 4.68 (95% confidence interval (CI) 2.67 to 8.23), heterozygotes OR 1.64 (95%CI 0.95 to 2.83)), which occurred over three years earlier for each extra risk allele (&beta, &minus, 3.34, 95%CI &minus, 6.69 to 0.02). Of 153 survivors (median follow-up 4.9 years (95%CI 3.7 to 6.1)), 44 (29%) relapsed. The risk allele homozygotes had a 46% (95%CI 36 to 57%) absolute risk of relapse by year 6, which was significantly higher than both heterozygotes (22% (95%CI 16 to 29%)) and reference allele homozygotes (30% (95%CI 23 to 39%)). In conclusion, HLA variant rs6903608 is a risk factor for both iTTP onset and relapse. This newly identified biomarker may help with recognizing patients at high risk of relapse, who would benefit from close monitoring or intensified immunosuppressive therapy.

Published
2020

15. Immunochip analysis identifies novel susceptibility loci in the human leukocyte antigen region for acquired thrombotic thrombocytopenic purpura

Author

I. Mancini, I. Ricaño‐Ponce, E. Pappalardo, A. Cairo, M.M. Gorski, G. Casoli, B. Ferrari, M. Alberti, D. Mikovic, M. Noris, C. Wijmenga, F. Peyvandi, E. Rinaldi, A. Melpignano, S. Campus, R.A. Podda, C. Caria, A. Caddori, E. Di Francesco, G. Giuffrida, V. Agostini, U. Roncarati, C. Mannarella, A. Fragasso, G.M. Podda, E. Bertinato, A.M. Cerbone, A. Tufano, G. Loffredo, V. Poggi, M. Pizzuti, G. Re, M. Ronchi, K. Codeluppi, L. Facchini, A. De Fanti, S. Amarri, S.M. Trisolini, S. Capria, L. Aprile, M. Defina, S. Cerù, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Mancini, I., Ricano-Ponce, I., Pappalardo, E., Cairo, A., Gorski, M. M., Casoli, G., Ferrari, B., Alberti, M., Mikovic, D., Noris, M., Wijmenga, C., Peyvandi, F., Rinaldi, E., Melpignano, A., Campus, S., Podda, R. A., Caria, C., Caddori, A., Di Francesco, E., Giuffrida, G., Agostini, V., Roncarati, U., Mannarella, C., Fragasso, A., Podda, G. M., Bertinato, E., Cerbone, A. M., Tufano, A., Loffredo, G., Poggi, V., Pizzuti, M., Re, G., Ronchi, M., Codeluppi, K., Facchini, L., De Fanti, A., Amarri, S., Trisolini, S. M., Capria, S., Aprile, L., Defina, M., and Ceru, S.

Subjects
0301 basic medicine, Male, genetic association studies, Genome-wide association study, Autoimmunity, 030204 cardiovascular system & hematology, DISEASE, 0302 clinical medicine, Risk Factors, HLA-DQ beta-Chains, thrombotic thrombocytopenic purpura, POPULATION, GENE-EXPRESSION, education.field_of_study, CLASSICAL HLA ALLELES, Principal Component Analysis, FACTOR-CLEAVING PROTEASE, genetic association studie, Chromosome Mapping, Hematology, Middle Aged, ADAMTS13, Europe, risk factor, Italy, Female, SNPs, Adult, Thrombotic microangiopathy, Genotype, Population, Thrombotic thrombocytopenic purpura, SNP, Single-nucleotide polymorphism, Human leukocyte antigen, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, human leukocyte antigen, medicine, HODGKINS LYMPHOMA, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, Alleles, Autoantibodies, Acquired Thrombotic Thrombocytopenic Purpura, Purpura, Thrombotic Thrombocytopenic, medicine.disease, RISK LOCI, 030104 developmental biology, Case-Control Studies, Immunology, HEMOLYTIC-UREMIC SYNDROME
Abstract

Essentials Genetic predisposition to acquired thrombotic thrombocytopenic purpura (aTTP) is mainly unknown. Genetic risk factors for aTTP were studied by Immunochip analysis and replication study. Human leukocyte antigen (HLA) variant rs6903608 conferred a 2.5-fold higher risk of developing aTTP. rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in aTTP. Click to hear Dr Cataland's presentation on acquired thrombotic thrombocytopenic purpura. Summary: Background Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy associated with the development of autoantibodies against the von Willebrand factor-cleaving protease ADAMTS-13. Similarly to what has been found for other autoimmune disorders, there is evidence of a genetic contribution, including the association of the human leukocyte antigen (HLA) class II complex with disease risk. Objective To identify novel genetic risk factors in acquired TTP. Patients/Methods We undertook a case–control genetic association study in 190 European-origin TTP patients and 1255 Italian healthy controls by using the Illumina Immunochip. Replication analysis in 88 Italian cases and 456 controls was performed with single-nucleotide polymorphism (SNP) TaqMan assays. Results and conclusion We identified one common variant (rs6903608) located within the HLA class II locus that was independently associated with acquired TTP at genome-wide significance and conferred a 2.6-fold increased risk of developing a TTP episode (95% confidence interval [CI] 2.02–3.27, P = 1.64 × 10−14). We also found five non-HLA variants mapping to chromosomes 2, 6, 8 and X that were suggestively associated with the disease: rs9490550, rs115265285, rs5927472, rs7823314, and rs1334768 (nominal P-values ranging from 1.59 × 10−5 to 7.60 × 10-5). Replication analysis confirmed the association of HLA variant rs6903608 with acquired TTP (pooled P = 3.95 × 10-19). Imputation of classic HLA genes followed by stepwise conditional analysis revealed that the combination of rs6903608 and HLA-DQB1*05:03 may explain most of the HLA association signal in acquired TTP. Our results refined the association of the HLA class II locus with acquired TTP, confirming its importance in the etiology of this autoimmune disease.

Published
2016

16. The international Hip Outcome Tool 12 questionnaire (iHOT-12): an Italian language cross-cultural adaptation and validation.

Author

Randelli F, Fioruzzi A, Clemente A, Radaelli A, Menon A, Di Via D, Caria C, Mazzoleni MG, Buono C, Di Benedetto P, Paciotti M, Papalia R, Fiorentino G, Collarile M, Panasci M, Carulli C, Rosolani M, Rocca FD, Cerulli S, Potestio D, Conati M, Costantini A, Bisciotti GN, Aprato A, Perticarini L, Santori N, Loppini M, Solarino G, Vicenti G, Pavone V, Di Martino A, and Rivera F

Subjects
Adult, Aged, Female, Humans, Male, Middle Aged, Cross-Cultural Comparison, Italy, Language, Patient Reported Outcome Measures, Reproducibility of Results, Surveys and Questionnaires, Translations, Hip Joint surgery, Psychometrics, Quality of Life
Abstract

Background: Patient-reported outcome (PRO) measures are essential for evaluating disease-related quality of life. The International Hip Outcome Tool 12 (iHOT12) assesses various aspects of hip-related symptoms, function, sports participation, and social limitations. This study aimed to adapt and validate an Italian version of the iHOT12 according to COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines., Materials and Methods: A multicenter observational cohort study was conducted to translate and validate the iHOT-12 into Italian (iHOT-12-ita) and assess its psychometric properties. Following international guidelines, we translated and culturally adapted the iHOT-12-ita. Patients with hip pain included in the study completed the iHOT-12-ita and mHHS-ita questionnaires at three timepoints: initial consultation (T0), 10-20 days later (T1), and at least 2 months after treatment (T2): hip injection, hip arthroscopy or total hip replacement. The evaluation of the iHOT-12-ita psychometric properties was conducted following the COSMIN checklist, assessing its reliability, responsiveness, interpretability, and acceptability., Results: Between May 2019 to September 2022, 104 patients were included, from two tertiary hip surgery referral center clinics, they completed both questionnaires and were available for data analysis. The psychometric evaluations revealed robust test-retest reliability on 27 patients at T1, with a Lin coefficient of 0.709 [95% confidence interval (CI) 0.553-0.888] and a high Pearson correlation coefficient of 0.745. At T2 after treatment, there was significant responsiveness (p < 0.001, n = 72), with excellent correlation observed between the iHOT-12-Ita and mHHS-Ita questionnaires (pwcorr = 0.7971). All predefined hypotheses were confirmed., Conclusions: The Italian iHOT-12-ita proved reliable, valid, and responsive in assessing hip disease-related quality of life. Its implementation in routine clinical practice and research can enhance patient care and research quality in hip preservation surgery for the Italian orthopedic community., Level of Evidence: II., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Not applicable., (© 2024. The Author(s).)

Published
2024
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17. Femoral cartilage thickness measured on MRI varies among individuals: Time to deepen one of the principles of kinematic alignment in total knee arthroplasty. A systematic review.

Author

Giurazza G, Caria C, Campi S, Franceschetti E, Papalia GF, Basciani S, Zampoli A, Gregori P, Papalia R, and Marinozzi A

Abstract

Purpose: Kinematically aligned total knee arthroplasty (KA TKA), as a pure resurfacing procedure, is based on matching implant thickness with bone cut and kerf thickness, plus cartilage wear. However, the assumption of a consistent 2 mm femoral cartilage thickness remains unproven. This study aimed to systematically review the available literature concerning magnetic resonance imaging (MRI) assessment of femoral cartilage thickness in non-arthritic patients. Our hypothesis was that cartilage thickness values would vary significantly among individuals, thereby challenging the established KA paradigm of 'one-cartilage-fits-all'., Methods: Systematic literature searches (Pubmed, Scopus and Cochrane Library) followed PRISMA guidelines. English-language studies assessing distal and posterior femoral cartilage thickness using MRI in non-arthritic adults were included. Studies lacking numerical cartilage thickness data, involving post-operative MRI, considering total femoro-tibial cartilage thickness, or failing to specify the compartment of the knee being studied were excluded., Results: Overall, 27 studies comprising 8170 MRIs were analysed. Weighted mean femoral cartilage thicknesses were: 2.05 ± 0.62 mm (mean range 1.06-2.6) for the distal medial condyle, 1.95 ± 0.4 mm (mean range 1.15-2.5) for the distal lateral condyle, 2.44 ± 0.5 mm (mean range 1.37-2.6) for the posterior medial condyle and 2.27 ± 0.38 mm (mean range 1.48-2.5) for the posterior lateral condyle., Discussion: Femoral cartilage thickness varies significantly across patients. In KA TKA, relying on a fixed thickness of 2 mm may jeopardize the accurate restoration of individual anatomy, leading to errors in implant coronal and rotational alignment. An intraoperative assessment of cartilage thickness may be advisable to express the KA philosophy at its full potential., Level of Evidence: Level IV., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Published
2024
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18. Modular Enantioselective Total Syntheses of the erythro -7,9-Dihydroxy- and 9-Hydroxy-7-Keto-8,4'-Oxyneolignans.

Author

Benda MC, Evans C, Yuan S, McClish IM, Berkey WJ, Areheart HE, Arnold ES, Tang ML, and France S

Abstract

A modular, enantioselective approach to access the bioactive 7,9-dihydroxy- and 9-hydroxy-7-keto-8,4'-oxyneolignans is disclosed, which employs stereoselective Mitsunobu reactions of enantiopure 2-aryl-1,3-dioxan-5-ols and functionalized phenols. The enantiopure dioxanols are prepared through Sharpless asymmetric dihydroxylation of protected coniferyl or sinapyl alcohols and subsequent benzylidene acetal formation. Through a mix-and-match coupling approach, six of the eight possible erythro -7,9-dihydroxy-8,4'-oxyneolignan enantiomeric natural products (bearing a C-1' hydroxypropyl chain) were generated following sequential deprotection. Subsequent benzylic oxidation afforded the 7-keto-derivatives, resulting in enantioselective syntheses of each enantiomer of the natural products asprenol B and icariol A 1 .

Published
2024
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19. Effects of feeding bergamot pulp and olive leaves on performance and meat quality in Apulo-Calabrese pigs.

Author

Scerra M, Foti F, Caparra P, Cilione C, Bognanno M, Paolo F, Paolo C, Natalello A, Musati M, and Chies L

Abstract

To determine the effects of dietary inclusion of bergamot pulp and olive leaves on pork quality, thirty-six barrows (Apulo-Calabrese; 112.5 ± 7.40 kg initial bodyweight) were randomly assigned to four experimental treatments and fed for 100 days a control diet (control group) or a diet similar to the control diet in which part of the cereals were replaced with 20 % (DM on the diet fed) of ensiled bergamot pulp (dry matter on the diet fed, EBP group) or olive leaves (OLL group) or a 1:1 mixture of both by-products (BPOL group). In the present study, the dietary administration of by-products did not influence the accumulation of IMF ( P  > 0.05) in meat. As for individual fatty acids, no differences were observed among groups. However, the dietary supplementation of bergamot pulp tended to increase ( P  = 0.073) the level of α-linolenic acid in meat. In raw and cooked meat TBARS values were higher ( P  < 0.001) in the Control group than in EBP, OLL and BPOL groups. The integration of 20 % of bergamot pulp and/or olive leaves by-products increased the levels of tocopherol and phenolic compounds in the diets, positively influencing the shelf life of meat. No effect of diet was observed on animal performance. The results of present study indicated mainly that partial replacement of cereals with 20 % DM on the diet fed of ensiled bergamot pulp and olive leaves, either alone or in combination, in the pig's diet led to greater oxidative stability of the meat., Competing Interests: The authors 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 Author(s).)

Published
2024
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20. Zr-Catalyzed Synthesis of Tetrasubstituted 1,3-Diacylpyrroles from N -Acyl α-Aminoaldehydes and 1,3-Dicarbonyls.

Author

Evans C, Berkey WJ, Jones CW, and France S

Subjects
Catalysis, Aldehydes chemistry, Amino Acids
Abstract

A Zr-catalyzed synthesis of tetrasubstituted 1,3-diacylpyrroles is reported that employs the direct use of N -acyl α-aminoaldehydes with 1,3-dicarbonyl compounds. The products were formed in up to 88% yield and shown to be hydrolytically and configurationally stable under the reaction conditions (THF/1,4-dioxane and H 2 O). The N -acyl α-aminoaldehydes were readily prepared from the corresponding α-amino acids. The reaction tolerates a wide array of substrate types including alkyl-, aryl-, heteroaryl-, and heteroatom-containing groups on the aminoaldehyde side chain. A variety of 1,3-dicarbonyls proved amenable to the reaction along with an aldehyde derived from a l,l-dipeptide, an aldehyde generated in situ , and an N -acylated glucosamine.

Published
2023
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21. Medium- and Long-Term Re-Treatment of Root Canals Filled with a Calcium Silicate-Based Sealer: An Experimental Ex Vivo Study.

Author

Bardini G, Cotti E, Congiu T, Caria C, Aru D, and Mercadè M

Abstract

This study investigated the possibility of re-treating a calcium silicate-based sealer (CSBS), compared to an epoxy-resin sealer (RBS), using rotary instrumentation at different times from obturation (1 month/1 year). Thirty-six human mandibular premolars, extracted as a result of orthodontic or periodontal problems, were instrumented and randomly divided into three groups of 12: BR and BR*, which were filled with CSBS and re-treated after one month and one year of storage, respectively, and AH, which was filled with RBS and re-treated after one month. The same re-treatment protocol was used for all teeth, and the times required for the procedure was recorded. The re-treated specimens were longitudinally sectioned and examined at the stereomicroscope (SM) at 20× magnification. Image J Software was used to process the microphotographs. The percentage of residual filling materials in the root canal and the apical third, the ability to reach working length WL and patency, and the time taken to complete the re-treatment were recorded and analyzed by ANOVA and post hoc Bonferroni test ( p = 0.05). Scanning electron microscopy (SEM) and coupled energy-dispersive spectroscopy (EDS) were applied to representative samples to evaluate canal cleanliness and chemical elements. Patency and WL were re-established in all of the teeth. Residual filling materials were retained in all specimens of the three groups. The mean percentage of residual materials was significantly different between BR and BR* ( p -value = 0.048), with BR* showing the highest values. The mean time to complete re-treatment was significantly lower for AH, followed by BR ( p = 0.0001) and BR* ( p = 0.0078). Conclusions: After both medium and long storage periods, the CSBS can be concluded to have been successfully removed from canals with simple anatomy.

Published
2022
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22. Effects of long-term consumption of sucralose associated with high-fat diet in male mice.

Author

Santos PS, Ruy CC, Rabelo Paiva Caria C, and Gambero A

Subjects
Animals, Appetite drug effects, Body Composition drug effects, Endotoxemia metabolism, Fatty Liver metabolism, Gastrointestinal Microbiome drug effects, Humans, Intestines metabolism, Liver metabolism, Male, Mice, Muscle, Skeletal metabolism, Sucrose pharmacology, Blood Glucose metabolism, Diet, High-Fat adverse effects, Energy Metabolism drug effects, Sucrose analogs & derivatives, Sweetening Agents pharmacology, Weight Gain drug effects
Abstract

Sucralose is a widely consumed non-nutritive sweetener (NNS). Studies have shown that some NNS can favor weight gain by altering the intestinal microbiota, satiety hormone production, or aspects related to glucose homeostasis. In this study, we investigated the effects of ad libitum sucralose consumption in mice fed with normal or high-fat diet (HFD) for an extended period (16 weeks). Weight gain, final body composition, energy expenditure, intestinal and pancreatic hormone production, and endotoxemia during a voracity test, as well as liver and skeletal muscles were evaluated after 16 weeks. We observed that sucralose supplementation reduced weight gain in HFD-fed mice but did not change weight gain in mice fed with normal diet. The evaluation of HFD mice showed that sucralose supplementation resulted in improvements in glycemic homeostasis, hepatic steatosis, and increased energy expenditure. Our results suggest that sucralose consumption promotes different outcomes in relation to weight gain when combined with different diets, which may explain the controversial data in previous studies, and can be considered in future clinical research aimed at clarifying the impact of NNS consumption on human health.

Published
2021
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23. The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians.

Author

Mancini I, Giacomini E, Pontiggia S, Artoni A, Ferrari B, Pappalardo E, Gualtierotti R, Trisolini SM, Capria S, Facchini L, Codeluppi K, Rinaldi E, Pastore D, Campus S, Caria C, Caddori A, Nicolosi D, Giuffrida G, Agostini V, Roncarati U, Mannarella C, Fragasso A, Podda GM, Birocchi S, Cerbone AM, Tufano A, Menna G, Pizzuti M, Ronchi M, De Fanti A, Amarri S, Defina M, Bocchia M, Cerù S, Gattillo S, Rosendaal FR, and Peyvandi F

Abstract

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) deficiency, recurring in 30-50% of patients. The common human leukocyte antigen (HLA) variant rs6903608 was found to be associated with prevalent iTTP, but whether this variant is associated with disease relapse is unknown. To estimate the impact of rs6903608 on iTTP onset and relapse, we performed a case-control and cohort study in 161 Italian patients with a first iTTP episode between 2002 and 2018, and in 456 Italian controls. Variation in rs6903608 was strongly associated with iTTP onset (homozygotes odds ratio (OR) 4.68 (95% confidence interval (CI) 2.67 to 8.23); heterozygotes OR 1.64 (95%CI 0.95 to 2.83)), which occurred over three years earlier for each extra risk allele (β -3.34, 95%CI -6.69 to 0.02). Of 153 survivors (median follow-up 4.9 years (95%CI 3.7 to 6.1)), 44 (29%) relapsed. The risk allele homozygotes had a 46% (95%CI 36 to 57%) absolute risk of relapse by year 6, which was significantly higher than both heterozygotes (22% (95%CI 16 to 29%)) and reference allele homozygotes (30% (95%CI 23 to 39%)). In conclusion, HLA variant rs6903608 is a risk factor for both iTTP onset and relapse. This newly identified biomarker may help with recognizing patients at high risk of relapse, who would benefit from close monitoring or intensified immunosuppressive therapy.

Published
2020
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24. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus.

Author

Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, and Khatami H

Subjects
Adolescent, Adult, Aged, Dipeptidyl Peptidase 4, Humans, Middle Aged, Placebos, Sitagliptin Phosphate, Adenosine Deaminase Inhibitors, Diabetes Mellitus, Type 2 drug therapy, Dipeptidyl-Peptidase IV Inhibitors, Glycoproteins antagonists & inhibitors, Hypoglycemic Agents therapeutic use, Pyrazines therapeutic use, Triazoles therapeutic use
Abstract

Aims/hypothesis: The aim of this study was to assess the efficacy and safety of sitagliptin (MK-0431) as monotherapy in patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA(1c) > or =7% and < or =10%) on exercise and diet., Methods: A total of 521 patients aged 27-76 years with a mean baseline HbA(1c) of 8.1% were randomised in a 1:2:2 ratio to treatment with placebo, sitagliptin 100 mg once daily, or sitagliptin 200 mg once daily, for 18 weeks. The efficacy analysis was based on an all-patients-treated population using an analysis of covariance, excluding data obtained after glycaemic rescue., Results: After 18 weeks, HbA(1c) was significantly reduced with sitagliptin 100 mg and 200 mg compared with placebo (placebo-subtracted HbA(1c) reduction: -0.60% and -0.48%, respectively). Sitagliptin also significantly decreased fasting plasma glucose relative to placebo. Patients with higher baseline HbA(1c) (> or =9%) experienced greater placebo-subtracted HbA(1c) reductions with sitagliptin (-1.20% for 100 mg and -1.04% for 200 mg) than those with HbA(1c) <8% (-0.44% and -0.33%, respectively) or > or =8% to 8.9% (-0.61% and -0.39%, respectively). Homeostasis model assessment beta cell function index and fasting proinsulin:insulin ratio, markers of insulin secretion and beta cell function, were significantly improved with sitagliptin. The incidence of hypoglycaemia and gastrointestinal adverse experiences was not significantly different between sitagliptin and placebo. Sitagliptin had a neutral effect on body weight., Conclusions/interpretation: Sitagliptin significantly improved glycaemic control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet.

Published
2006
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25. Myocardial stunning reduces the effects of nitric oxide on coronary capillary perfusion in the rabbit.

Author

Caria C, Katz E, Scholz PM, Lazar MJ, and Weiss HR

Subjects
Alkaline Phosphatase metabolism, Analysis of Variance, Animals, Capillaries drug effects, Endothelium, Vascular drug effects, Endothelium, Vascular physiology, Enzyme Inhibitors pharmacology, Epithelium blood supply, Epithelium physiology, Fluorescein-5-isothiocyanate, Fluorescent Dyes, In Vitro Techniques, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide Synthase antagonists & inhibitors, Nitric Oxide Synthase Type III, Rabbits, Bronchodilator Agents pharmacology, Coronary Circulation drug effects, Myocardial Stunning physiopathology, Nitric Oxide pharmacology
Abstract

This investigation tested the hypothesis that the effects of nitric oxide synthase on myocardial capillary perfusion were reduced during myocardial stunning. Anaesthetized open-chest rabbits were assigned to either a control group or a group treated with a nitric oxide synthase inhibitor. To induce myocardial stunning, a coronary artery was occluded (for 15 min) and then reperfused (for 15 min) twice. During reperfusion, rabbits were given either saline or N(G)-nitro-L-arginine methyl ester (L-NAME, 30 mg kg(-1)) followed by i.v. injection of 150 mg kg(-1) fluorescein isothiocyanate (FITC)-labelled dextran (molecular weight, 150,000) for 14 s. Fluorescence microscopy was used to identify the perfused vessels and an alkaline phosphatase stain was used to locate the total microvasculature. The 'closest-individual' method was used to estimate the geometric distribution of capillaries. No significant differences were observed in the total volume fraction (mm(3) of capillaries per mm(3) of tissue) between the control and stunned regions in either the saline- (0.045 +/- 0.008 and 0.042 +/- 0.009, respectively) or the L-NAME-treated hearts (0.060 +/- 0.010 and 0.049 +/- 0.005, respectively). There were no significant differences in the percentage volume fraction of perfused capillaries between the control and the stunned regions (49 +/- 4 % and 54 +/- 4 %, respectively) in saline-treated hearts. In hearts treated with L-NAME, the percentage of perfused capillaries was significantly reduced. The reduction was significantly greater in the control region (approximately 27 %) than the stunned region (approximately 17 %). Closest-individual analysis of the perfused capillary distribution in both groups demonstrated a similar unchanged distribution. Thus, nitric oxide synthase is an important regulator of basal coronary capillary perfusion, and its effects are significantly reduced by myocardial stunning.

Published
2002
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26. Behavioral response to m-CPP.

Author

Hollander E, De Caria C, Stein D, Simeon D, Cohen L, Hwang M, and Islam M

Subjects
Cerebrovascular Circulation drug effects, Humans, Serotonin metabolism, Metergoline pharmacology, Obsessive-Compulsive Disorder metabolism, Serotonin Receptor Agonists pharmacology
Published
1994
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27. Studies on the effects of antidepressant drugs on the antinociceptive action of morphine and on plasma morphine in rat and man.

Author

Ventafridda V, Blanchi M, Ripamonti C, Sacerdote P, De Conno F, Zecca E, and Panerai AE

Subjects
Amitriptyline pharmacology, Animals, Clomipramine pharmacology, Drug Synergism, Humans, Nortriptyline pharmacology, Rats, Rats, Inbred Strains, Analgesia, Antidepressive Agents, Tricyclic pharmacology, Morphine blood, Trazodone pharmacology
Abstract

In the rat we studied the effect of 3 tricyclic antidepressants: chlorimipramine, amitriptyline and nortriptyline, and the atypical antidepressant trazodone on pain thresholds when administered alone or together with morphine. Moreover, we evaluated the effect of the antidepressants on free morphine plasma concentrations both in the rat and in man. We observed that chlorimipramine and amitriptyline, two tricyclic antidepressants active on the serotoninergic system, induce analgesia and potentiate morphine analgesia in a dose-related fashion. The noradrenergic tricyclic nortriptyline and trazodone did not elicit analgesia and inconsistently affected morphine analgesia. In the rat, all drugs tested increased plasma concentrations of morphine with the exception of amitriptyline. In man, only chlorimipramine and amitriptyline increased the plasma concentration of the free opiate.

Published
1990
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