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1. Spotlight on sirukumab for the treatment of rheumatoid arthritis: the evidence to date

Author

Lazzerini PE, Capecchi PL, Guidelli GM, Selvi E, Acampa M, and Laghi-Pasini F

Subjects
sirukumab, rheumatoid arthritis, interleukin-6, Therapeutics. Pharmacology, RM1-950
Abstract

Pietro Enea Lazzerini,1 Pier Leopoldo Capecchi,1 Giacomo Maria Guidelli,1 Enrico Selvi,1 Maurizio Acampa,2 Franco Laghi-Pasini1 1Department of Medical Sciences, Surgery and Neurosciences, University of Siena, 2Stroke Unit, University Hospital of Siena, Siena, Italy Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease primarily affecting synovial joints and is characterized by persistent high-grade systemic inflammation. Proinflammatory cytokines, particularly interleukin-6 (IL-6), are of crucial importance in the pathogenesis of the disease, driving both joint inflammation and extra-articular comorbidities. Tocilizumab, a humanized IL-6 receptor-inhibiting monoclonal antibody, has been the first, and, to date, the only, IL-6 inhibitor approved for the treatment of RA. Many studies have demonstrated the potency and effectiveness of tocilizumab in controlling disease activity and radiological progression of RA. These successful results have encouraged the development of novel IL-6 inhibitors, among which a promising agent is sirukumab (SRK), a human anti-IL-6 monoclonal antibody currently under evaluation in Phase II/III studies in patients with RA, systemic lupus erythematosus, giant-cell arteritis, and major depressive disorder. The evidence to date indicates SRK as an effective and well-tolerated new therapeutic tool for patients with active RA, with some preliminary data suggesting a specific beneficial impact on relevant systemic complications associated with the disease, such as depression and cardiovascular disease. Conversely, although pathophysiological considerations make plausible the hypothesis that IL-6 blockade with SRK may also be beneficial in the treatment of many diseases other than RA (either autoimmune or not), available clinical data in patients with systemic lupus erythematosus do not seem to support this view, also giving rise to potentially relevant concerns about drug safety. If large Phase III clinical trials currently in progress in patients with RA confirm the efficacy and tolerability of SRK, then in the long term, this drug could, in the near future, occupy a place in the treatment of the disease, potentially also opening the doors to a more extended use of SRK in a wide range of disorders in which IL-6 plays a key pathogenic role. Keywords: sirukumab, rheumatoid arthritis, interleukin-6, tocilizumab, systemic lupus erythematosus, cardiovascular disease, interleukin-6

Published
2016

2. Effect of the Factor XIa Inhibitor Asundexian According to Baseline Infarct Pattern and on MRI Covert Infarct Outcomes

Author

Smith, Eric E., Shoamanesh, Ashkan, Xu, Lizhen, Heenan, Laura, Saad, Feryal, Colorado, Pablo, Chen, Chih-Hao, Lemmens, Robin, De Marchis, Gian Marco, Caso, Valeria, Masjuan, Jaime, Hirano, Teruyuki, Milanov, Ivan, Campbell, Bruce C.V., Mas, Jean-Louis, Connolly, Stuart J., Mundl, Hardi, Hart, Robert G., Bailey, P., Campbell, B.C.V., Kleinig, T., Cordato, D., Choi, P., Garcia-Esperon, C., Chew, A., Cloud, G., Stanislaus, V., Krause, M., Priglinger, M., Grimley, R., Ghia, D., Sahathevan, R., Brown, H., Kwan, C., Devlin, M., Greisenegger, S., Bonelli-Nauer, S., Rath, J., Langer, A., Marko, M., Ferrari, J., Bernegger, A., Baumgartinger, M., Vigl, M., Krebs, S., Lang, W., Knoflach, M., Dejakum, B., Kiechl, S., Töll, T., Domig, L., Mutzenbach, J.S., Ganser, B., Hecker, C., Rösler, C., Bubel, N., Pikija, S., Zellner, T., Leitner, U., Berger, O., Surböck, B., Beirer, S., Staykov, D., Schrammel, D., Halilovic, A., Frattner, M., Barmherzigen, D., Lampl, C., Höfer, C., Nagl, S., Bocksrucker, C., Lemmens, R., Demeestere, J., Desfontaines, P., Ciobanu, C., De Pauw, A., Terwecoren, A., Hasenbroekx, M.C., Clement, F., De Klippel, N., Soors, P., Hermans, S., De Raedt, S., Vandervorst, F., Seynaeve, L., Fockaert, N., Smet, S., Rutgers, M., Del Gaudio, N., Paindeville, P., Staikov, I., Simeonova, A., Stoyanova, I., Cholakova, M., Mihnev, N., Petrova, T., Koralova, A., Dimov, D., Kuzev, Y., Danovska, M., Marinova, D., Marinova-Trifonova, D., Ovcharova, E., Mladenovski, I., Yanakieva, M., Stoev, P., Dimitrova, M., Todorova-Georgieva, S., Haralanov, L., Milkov, B., Solakov, D., Petkova, N., Ignatova-Valkova, V., Karabinov, V., Marinova, V., Miteva, Y., Andonova, V., Kasabova, D., Kostadinova, E., Shopova-Vrabcheva, Y., Gatev, D., Semova, D., Halil, E., Kaprelyan, A., Ivanov, B., Panov, G., Grudkova, M., Syuleyman, N., Kalpachki, R., Alexiev, F., Ivanova, I., Kancheva, K., Sakelarova, T., Maslarov, D., Drenska, D., Georgiev, V., Petrova, K., Petrova, N., Ivanova, I., Milanov, I., Semerdjieva, N., Zhelyazkov, P., Spasova-Markova, S., Dong, X., Wang, D., Wang, S., Huang, W., Zhao, H., Wang, C., Jie, L., Xinyang, Y., Ping, Z., Dong, Q., Wang, Y., Fuling, Y., Yue, W., Liu, R., Yang, Y., Stetkarova, I., Mikulenka, P., Vasko, P., Peisker, T., Bar, M., Roubec, M., Mikulik, R., Cabukova, M., Vinklarek, J., Kovar, M., Pansky, M., Mencl, P., Skoda, O., Carek, M., Pernicka, M., Skodova, M., Geier, P., Cepkova, J., Drlik, J., Prax, T., Herzig, R., Krajickova, D., Vitkova, E., Haluskova, S., Vaclavik, D., Martinkova, J., Blejcharova, K., Tkacova, M., Pavlik, O., Nevšímalová, M., Rosol, J., Nevsimalova, M., Hruby, R., Iversen, H., Andersen, A.V., Rahimi, D., Christensen, H., Grundtvig, J., Hjort, N., Andersen, G., Sandal, B., Stilund, M., Modrau, B., Strade, A., Porobic, M., Andersen, S.D., Kruuse, C., Ölmestig, J., Kolmos, M., Parvez, A., Christensen, T., Stokholm, J., Jensen, H.B., Putaala, J., Strbian, D., Sibolt, G., Tiainen, M., Martinez-Majander, N., Curtze, S., Raty, S., Kraemer, Y., Roine, R., Aivo, J., Ruuskanen, J., Ylikotila, P., Roine, S., Hallikainen, M., Jakala, P., Kurl, S., Julkunen, V., Sibon, I., Olindo, S., Richard, S., Larrue, V., Gollion, C., Catala, H., Henon, H., Lucie, D.S., Nelly, D., Mas, J.L., Calvet, D., Malbranque, A., Mazé, B., Barbieux-Ghitu, C., Pitie Salpetriere, G.H., Rosso, C., Samson, Y., Vannier, S., Moulin, T., Bonnet, L., Reiner, P., Buffon, F., Denier, C., Amri, K., Legris, N., Chassin, O., Selli, N., Mariana, S., Berrouschot, J., Stoll, A., Klunk, D., Keilitz, J., Neustadt, M., Zerrenner, S., Veltkamp, R., Hajjar, K., Heeger, A., Winezki, E., Apel, L., Pompsch, M., Mueller, P., Rappard, P., Auer, R., Ringleb, P.A., Berberich, A., Heyse, M., Mundiyanapurath, S., Reiff, T., Poli, S., Gomez-Exposito, A., Mengel, A., Tünnerhoff, J., Adeyemi, K., Poli, K., Kusch, V., Pelz, J., Michalski, D., Wartenberg, K., Althaus, K., Tavares, F., Mueller, S., Soda, H., Rascher, A., Hiermann, E., Weinhardt, R., Weissenborn, K., Leotescu, A., Grosse, G., Worthmann, H., Ernst, J., Gabriel, M., Schuppner, R., Schäfer, J.H., Charisse, D., Gruber, K., Kurka, N., Reitz, S.C., Pfeilschifter, W., Lee, J.I., Gliem, M., Moll, M., Steiner, T., Segura, L., Szegedi, N., Barandi, D., Uhrinakova, L., Czencz, M., Pasztor, M., Gyuker, N., Bartha, N.E., May, Z., Simony, Z., Szasz, G., Kakuk, I., Pető, N., Panczel, G.F., Olah, A., Racz, O., Balla, T., Horvath, B., Tuba, K., Czinderi, V., Klivenyi, P., Annus, A., Hertelendy, P., Szapary, L., Bosnyak, E., Kalmar, P., Karadi, Z., Cziba, L., Olah, L., Berki, A., Hudak, L., Kozák, M., Babel, S., Nemeth, L., Molnár, B., Simon, Z., Roveri, L., Cerri, F., Giacalone, G., Zini, A., Mauro, G., Asioli, G.M., Forlivesi, S., Arnone, G., Caso, V., Fiaccadori, A., Maria Fontana Francesca, E., Allegra, G., Mosconi, M.G., Longoni, M., Terlizzi, R., Paolucci, M., Tassi, R., Franci, B., Lucani, B., Domenichelli, C., Paoletti, D., Acampa, M., Zedde, M.L., Pezzella, F.R., Mangiardi, M., Galizia, P., Anticoli, S., Scalise, S., Lattanzi, S., Norata, D., Cannuccia, M., Cavallini, A., Federica, F., Denaro, M.F., Tosi, P., Sonoda, K., Kawajiri, M., Kusano, Y., Haraguchi, K., Kawano, H., Terasaki, T., Kaneko, C., Murase, S., Kumagai, M., Murai, N., Miyazaki, Y., Mori, T., Hatano, T., Kawanishi, M., Ochiai, J., Ishihara, S., Uehara, T., Yasaka, M., Nakagawa, H., Makino, M., Yonehara, T., Fukushima, Y., Hirotsune, N., Sakai, N., Yamasaki, M., Coutinho, J., Wouters, A., den Hertog, H., Zwartbol, R., Beumer, D., Kerklaan, J., Hilkens, P., Schreuder, T., Propper, D., Slowik, A., Wlodarczyk, E., Wrona, P., Pulyk, R., Lasek-Bal, A., Kosarz-Lanczek, K., Puz, P., Bilik, M., Magielska, A., Zamiela – Żółciak, A., Ochocinska, L., Bahdasaryan, S., Stępień, A., Dębiec, A., Joanna, K., Pawel, M., Jacek, S., Daniel, P., Marta, S., Rejdak, K., Wojczal, J., Luchowski, P., Fryze, W., Wisniewska, A., Krzyzanowska, M., Skowron, P., Wolosz, A., Galan, A., Grzymala, K., Krajewska, M., Nowak, R., Kłos, M., Cruz, V., Castro, P., Ferro, J., Canhão, P., Gouveia, R., Inácio, N., Rodrigues, M., Rachão, A., Ionel, C., Pereira, L., Viana-Baptista, M., Machado, C., Fernandes, C., Sargento, J., Inácio, N., Timchenko, L., Mironova, J., Zhadan, O., Torgashova, A., Bazhenova, O., Barashenkova, M., Kireeva, M., Romadina, N., Stepanova, I., Lenskaya, L., Lukinykh, L., Vorontsova, T., Agafina, A., Fedorova, A., Yashina, A., Alasheev, A., Smolkin, A., Prazdnichkova, E., Lutskovich, O., Gonysheva, Y., Mordvintseva, E., Nechaev, A., Martynova, E., Fedoraeva, N., Vishnyakova, T., Popov, D., Merzliakova, A., Margarita, K., Rechkalova, L., Ilyina, A., Kurenkova, N., Barbarash, O., Bazdyrev, E., Zvereva, T., Hromova, A., Morkvenas, A., Postnikova, E., Kovalenko, G., Taran, I., Pavlov, L., Ott, M., Chernitsova, N., Vodopyanova, N., Drozdova, E., Korebo, E., Lobanova, M., Lazareva, N., Snegova, N., Nikolaeva, O., Kolesnikov, Y., Kosheleva, Y., Krastev, G., Tomasova, K., Danis, M., Mako, M., Jankovicova, Z., Stevkova, Z., Kovacik, M., Kubikova, T., Jarosova, A., Serdahely, V., Cilingova, I., Pribulova, I., Sedlak, J., Slebodova, K., Paldaufova, M., Risnovsky, R., Berndtova, B., Urbanova, I., Junas, R., Karapetian, S., Gurcik, L., Vantrobova, A., Verbovsky, F., Vanacka, K., Ferenc, M., Galik, P., Bucakova, S., Ferencova, M., Kubalova, P., Boksanska, Z., Zacharova, E., Mahundi, E., Judita, H., Bachnak, M., Turcani, P., Kvasnicova Kamenska, A., Jurik, M., Vestenicka, V., Kycina, M., Sagatova, E., Dvorak, M., Hlubekova, A., Kucera, C., Gernath, L., Ferenc, M., Frimmelova, P., Slebodnikova, J., Aksteinerova, N., Horny, V., Gregova, Z., Segura, T., Romero, C., Ayo, O., Masjuan Vallejo, J., Cruz, A., . De felipe, A, Matute, M.C., Garcia, S., Tembl Ferrairo, J., Vielba, I., Morales Caba, L., Molina, C., Garcia-Tornel García-Camba, Á., Requena Ruiz, M., Noelia, R., Rodriguez-Yañez, M., Rodriguez Castro, E., Lopez, I., Santamaria, M., Arias, S., Purroy García, F., Vázquez Justes, D., Mauri Capdevila, G., Vicente Pascual, M., Martí Fabregas, J., Camps Renom, P., Rodríguez Campello, A., Giralt, E., Krupinski, J., Molina, J., Trillo Senin, C. Ramos Martin, S., De La Fuente Sanz, E., Moniche, F., Manuel, M.R., Pardo, B., Martínez, I., Hernández Pérez, M., Arenillas Lara, J.F., De Lera, M., Egido, J.A., Gomez Escalonilla, C., Guillan, M., Martinez, J., Lindgren, A., Andsberg, G., Wictor, L., Leonidou, M., Stenman, M., Dalberg, N., Laska, A.C., Grünfeldt, A., Lundström, A., Nadzjafov, E., Rooth, E., Dalenbring, I., Sandén, P., Johansson, E., Thomas, G., De Marchis, G.M., Zietz, A.V., Rudin, S., Dittrich, T.D., Lilian, K., Kägi, G., Vehoff, J., Arnold, M., Scutelnic, A., Clénin, L., Beyeler, M., Madlaine, M., Maamari, B., Siepen, B., Vynckier, J., Tarnutzer, A., Bertschi, D., Luciani, M., Cereda, C., Maulucci, F., Bianco, G., Shairin, S., Pihan, H.A., Salmen, S., Quinn, T., McAlpine, C., Wright, F., Kalladka, D., Taylor, E., Sohaa, J., Brown, Z., Dawson, J., Cameron, A., Muir, S., Dima, S., Khan, U., Zhang, L., Warburton, E., Chatterjee, K., Nallasivan, A., Curran, D., Haider, S., Ghani, U., Kenton, A., Dallol, B., Mirza, M., Menezes, B., Davies, R., Robinson, T.G., Manning, L., Sztriha, L., Phinney, T., Sethi, P., Altafullah, I., Sharaf, A., Ostrander, M., Renati, S., Burgin, W.S., Olds, K., Delio, P., Malek, A., Dissin, J., Khatri, P., Flaherty, M., Demel, S., and Dofitas, S.

Published
2024
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3. Global impact of the COVID-19 pandemic on subarachnoid haemorrhage hospitalisations, aneurysm treatment and in-hospital mortality: 1-year follow-up

Author

Nguyen, Tn, Qureshi, Mm, Klein, P, Yamagami, H, Mikulik, R, Etminan, N, Abdalkader, M, Mansour, Oy, Czlonkowska, A, Lo, H, Sathya, A, Demeestere, J, Tsivgoulis, G, Sakai, N, Sedova, P, Kristoffersen, Es, Mohammaden, M, Lereis, Vp, Scollo, Sd, Ma, A, Rahman, A, Bonnet, T, Cortier, J, De Raedt, S, Lemmens, R, Ligot, N, Hidalgo, Rct, Cuervo, Dlm, Neves, Ld, Rezende, Mts, Santiago, Ib, Sirakov, A, Sirakov, S, Cora, Ea, Kelly, Me, Lavoie, P, Peeling, L, Pikula, A, Rivera, R, Chen, Hs, Chen, Ym, Fang, Hl, Bedekovic, Mr, Budincevic, H, Strossmayer, Jj, Hrabanovska, E, Jurak, L, Cabal, M, Kadlckova, J, Karpowicz, I, Palouskova, H, Reiser, M, Klecka, L, Kovar, M, Neumann, J, Rekova, P, Sramek, M, Vitkova, E, Skorna, M, Zakova, L, Sobh, K, Alpay, K, Rautio, R, Strbian, D, Gentric, Jc, Magro, E, Naggara, O, Reiner, P, Abdulazim, A, Bohmann, Fo, Boskamp, S, Gerber, Jc, Kaiser, Dpo, Kestner, Ri, Mbroh, J, Neyazi, M, Rosenkranz, M, Sani, Af, Poli, S, Thomalla, G, Karapanayiotides, T, Kargiotis, O, Koutroulou, I, Palaiodimou, L, Guerra, Jdb, Huded, V, Nagendra, S, Prajapati, C, Krishna, A, Ghoreishi, A, Ilkhchi, Rb, Jalili, J, Sabetay, Si, Abu Raya, T, Acampa, M, Longoni, M, Bigliani, Cr, Castellan, L, Ornello, R, Renieri, L, Romoli, M, Sacco, S, Sangalli, D, Vigano, M, Zini, A, Tokimura, H, Sonoda, K, Todo, K, Fukuda, H, Fujita, K, Sakaguchi, M, Uno, M, Kan, I, Kosuke, M, Kono, R, Kimura, N, Yamamoto, N, Yamamoto, R, Doijiri, R, Shindo, S, Ohara, N, Imamura, H, Ogawa, T, Uwatoko, T, Kanamaru, T, Fujinaka, T, Takenobu, Y, Toyoda, K, Matsumaru, Y, Yazawa, Y, Sugiura, Y, Baek, Jh, Sunmonu, Ta, Kwon, Ys, Lee, Yh, Seo, Kd, Sohn, Si, Chan, Yc, Zaidi, Waw, Barrientos-Prieto, J, Gongora-Rivera, F, Martinez-Marino, M, Calderon-Vallejo, A, Groppa, S, Pavel, L, Coutinho, Jm, Dippel, D, Rinkel, L, Van Dam-Nolen, Dhk, Nwazor, Eo, Al Hashimi, Am, Ahmad, S, Rashid, U, Rodriguez-Kadota, L, Vences, Ma, Yalung, Pm, Jsh, Dy, Brola, W, Dorobek, M, Karlinski, Ma, Labuz-Roszak, Bm, Lasek-Bal, A, Sienkiewicz-Jarosz, H, Staszewski, J, Sobolewski, P, Zielinska-Turek, J, Araujo, Ap, Fonseca, L, Debiec, A, Silva, Ml, Castro, P, Rocha, M, Falup-Pecurariu, Rc, Venketasubramanian, N, Mako, Gkm, Ayo-Martin, O, Wiacek, M, Blasco, J, Cruz-Culebras, A, Hernandez-Fernandez, F, Fernandez, Cr, Lopez, Je, Rodriguez, A, Bolognese, M, Karwacki, Gm, Keller, E, Machi, P, Bernava, G, Boonyakarnkul, S, Churojana, A, Hammami, N, Bajrami, A, Senadim, S, Hussain, Si, John, S, Dow, G, Krishnan, K, Lenthall, R, Wong, K, Zhang, Lq, Altschul, D, Asif, Ks, Aziz-Sultan, Ma, Bach, I, Below, K, Biller, J, Cervantes-Arslanian, Am, Chaudhry, Sa, Chebl, A, Chen, M, Colasurdo, M, Czap, A, Dasenbrock, H, Bahiru, Z, de Havenon, Ah, Dharmadhikari, S, Dmytriw, Aa, Eskey, Cj, Etherton, M, Ezepue, C, Fink, L, Gasimova, U, Goyal, N, Grimmett, Kb, Hakemi, M, Hester, T, Inoa, V, Kan, Pt, Kasper, Em, Khandelwal, P, Khatri, R, Khoury, Nn, Kim, Bs, Kolikonda, M, Kuhn, Al, Linares, G, Linfante, I, Loochtan, Ai, Lukovits, Tg, Male, Ss, Khawaja, Am, Maali, L, Galecio-Castillo, Em, Min, Jy, Mohamed, Ga, Nalleballe, K, Ortega-Gutierrez, S, Radaideh, Y, Ramakrishnan, P, Masoud, He, Reddy, Ab, Ruland, S, Omran, Ss, Sheth, Sa, Puri, As, Rahangdale, Rh, Siegler, Je, Starosciak, Ak, Tarlov, Ne, Taylor, Ra, Tsai, J, Wang, Mj, Wong, Kh, Zaidat, Oo, Hv, Le, Phan, Ht, Ton, Md, Tran, Ad, Sirakova, K, Pham, Tn, Mohlenbruch, Ma, Nagel, S, Raymond, J, Nogueira, Rg, Neurology, ACS - Atherosclerosis & ischemic syndromes, and ANS - Neurovascular Disorders

Subjects
Psychiatry and Mental health, SDG 3 - Good Health and Well-being, COVID-19, SUBARACHNOID HAEMORRHAGE, CEREBROVASCULAR DISEASE, Surgery, Neurology (clinical)
Abstract

BackgroundPrior studies indicated a decrease in the incidences of aneurysmal subarachnoid haemorrhage (aSAH) during the early stages of the COVID-19 pandemic. We evaluated differences in the incidence, severity of aSAH presentation, and ruptured aneurysm treatment modality during the first year of the COVID-19 pandemic compared with the preceding year.MethodsWe conducted a cross-sectional study including 49 countries and 187 centres. We recorded volumes for COVID-19 hospitalisations, aSAH hospitalisations, Hunt-Hess grade, coiling, clipping and aSAH in-hospital mortality. Diagnoses were identified by International Classification of Diseases, 10th Revision, codes or stroke databases from January 2019 to May 2021.ResultsOver the study period, there were 16 247 aSAH admissions, 344 491 COVID-19 admissions, 8300 ruptured aneurysm coiling and 4240 ruptured aneurysm clipping procedures. Declines were observed in aSAH admissions (−6.4% (95% CI −7.0% to −5.8%), p=0.0001) during the first year of the pandemic compared with the prior year, most pronounced in high-volume SAH and high-volume COVID-19 hospitals. There was a trend towards a decline in mild and moderate presentations of subarachnoid haemorrhage (SAH) (mild: −5% (95% CI −5.9% to –4.3%), p=0.06; moderate: −8.3% (95% CI −10.2% to –6.7%), p=0.06) but no difference in higher SAH severity. The ruptured aneurysm clipping rate remained unchanged (30.7% vs 31.2%, p=0.58), whereas ruptured aneurysm coiling increased (53.97% vs 56.5%, p=0.009). There was no difference in aSAH in-hospital mortality rate (19.1% vs 20.1%, p=0.12).ConclusionDuring the first year of the pandemic, there was a decrease in aSAH admissions volume, driven by a decrease in mild to moderate presentation of aSAH. There was an increase in the ruptured aneurysm coiling rate but neither change in the ruptured aneurysm clipping rate nor change in aSAH in-hospital mortality.Trial registration numberNCT04934020.

Published
2022

4. Oral anticoagulants in the oldest old with recent stroke and atrial fibrillation

Author

Polymeris, A. A., Macha, K., Paciaroni, M., Wilson, D., Koga, M., Cappellari, M., Schaedelin, S., Zietz, A., Peters, N., Seiffge, D. J., Haupenthal, D., Gassmann, L., De Marchis, G. M., Wang, R., Gensicke, H., Stoll, S., Thilemann, S., Avramiotis, N. S., Bonetti, B., Tsivgoulis, G., Ambler, G., Alberti, A., Yoshimura, S., Brown, M. M., Shiozawa, M., Lip, G. Y. H., Venti, M., Acciarresi, M., Tanaka, K., Mosconi, M. G., Takagi, M., Jager, R. H., Muir, K., Inoue, M., Schwab, S., Bonati, L. H., Lyrer, P. A., Toyoda, K., Caso, V., Werring, D. J., Kallmunzer, B., Engelter, S. T., Traenka, C., Hert, L., Wagner, B., Schaub, F., Meya, L., Fladt, J., Dittrich, T., Fisch, U., Volbers, B., Siedler, G., Bovi, P., Tomelleri, G., Micheletti, N., Zivelonghi, C., Emiliani, A., Parry-Jones, A., Patterson, C., Price, C., Elmarimi, A., Parry, A., Nallasivam, A., Nor, A. M., Esis, B., Bruce, D., Bhaskaran, B., Roffe, C., Cullen, C., Holmes, C., Cohen, D., Hargroves, D., Mangion, D., Chadha, D., Vahidassr, D., Manawadu, D., Giallombardo, E., Warburton, E., Flossman, E., Gunathilagan, G., Proschel, H., Emsley, H., Anwar, I., Burger, I., Okwera, J., Putterill, J., O'Connell, J., Bamford, J., Corrigan, J., Scott, J., Birns, J., Kee, K., Saastamoinen, K., Pasco, K., Dani, K., Sekaran, L., Choy, L., Iveson, L., Mamun, M., Sajid, M., Cooper, M., Burn, M., Smith, M., Power, M., Davis, M., Smyth, N., Veltkamp, R., Sharma, P., Guyler, P., O'Mahony, P., Wilkinson, P., Datta, P., Aghoram, P., Marsh, R., Luder, R., Meenakishundaram, S., Subramonian, S., Leach, S., Ispoglou, S., Andole, S., England, T., Manoj, A., Harrington, F., Rehman, H., Sword, J., Staals, J., Mahawish, K., Harkness, K., Shaw, L., Mccormich, M., Sprigg, N., Mansoor, S., Krishnamurthy, V., Giustozzi, M., Agnelli, G., Becattini, C., D'Amore, C., Cimini, L. A., Bandini, F., Liantinioti, C., Chondrogianni, M., Yaghi, S., Furie, K. L., Tadi, P., Zedde, M., Abdul-Rahim, A. H., Lees, K. R., Carletti, M., Rigatelli, A., Putaala, J., Tomppo, L., Tatlisumak, T., Marcheselli, S., Pezzini, A., Poli, L., Padovani, A., Vannucchi, V., Masotti, L., Sohn, S. -I., Lorenzini, G., Tassi, R., Guideri, F., Acampa, M., Martini, G., Ntaios, G., Athanasakis, G., Makaritsis, K., Karagkiozi, E., Vadikolias, K., Mumoli, N., Galati, F., Sacco, S., Tiseo, C., Corea, F., Ageno, W., Bellesini, M., Colombo, G., Silvestrelli, G., Ciccone, A., Lanari, A., Scoditti, U., Denti, L., Mancuso, M., Maccarrone, M., Ulivi, L., Orlandi, G., Giannini, N., Tassinari, T., De Lodovici, M. L., Rueckert, C., Baldi, A., Toni, D., Letteri, F., Pieroni, A., Giuntini, M., Lotti, E. M., Flomin, Y., Kargiotis, O., Karapanayiotides, T., Monaco, S., Baronello, M. M., Csiba, L., Szabo, L., Chiti, A., Giorli, E., Del Sette, M., Imberti, D., Zabzuni, D., Doronin, B., Volodina, V., Michel, P., Vanacker, P., Barlinn, K., Pallesen, L. -P., Barlinn, J., Deleu, D., Melikyan, G., Ibrahim, F., Akhtar, N., Gourbali, V., Todo, K., Kimura, K., Shibazaki, K., Yagita, Y., Furui, E., Itabashi, R., Terasaki, T., Shiokawa, Y., Hirano, T., Suzuki, R., Kamiyama, K., Nakagawara, J., Takizawa, S., Homma, K., Okuda, S., Okada, Y., Maeda, K., Kameda, T., Kario, K., Nagakane, Y., Hasegawa, Y., Akiyama, H., Shibuya, S., Mochizuki, H., Ito, Y., Nakashima, T., Matsuoka, H., Takamatsu, K., Nishiyama, K., Endo, K., Miyagi, T., Osaki, M., Kobayashi, J., Okata, T., Tanaka, E., Sakamoto, Y., Tokunaga, K., Takizawa, H., Takasugi, J., Matsubara, S., Higashida, K., Matsuki, T., Kinoshita, N., Ide, T., Yoshimoto, T., Ando, D., Fujita, K., Kumamoto, M., Kamimura, T., Kikuno, M., Mizoguchi, T., and Sato, T.

Subjects
Male, medicine.medical_specialty, Vitamin K, medicine.drug_class, 610 Medicine & health, Aged, 80 and over, Atrial Fibrillation, Factor Xa Inhibitors, Female, Humans, Stroke, Continuous variable, Internal medicine, 80 and over, medicine, Aged, Proportional hazards model, business.industry, Anticoagulant, Confounding, Atrial fibrillation, Patient data, medicine.disease, Oldest old, Neurology, Neurology (clinical), 610 Medizin und Gesundheit, business
Abstract

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (≥85y = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR = 0.79, 95%-CI [0.66, 0.95]) in simple (p interaction = 0.129), adjusted (p interaction = 0.094) or weighted (p interaction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). Interpretation: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2021.

Published
2022

5. Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation

Author

Polymeris, A.A. Macha, K. Paciaroni, M. Wilson, D. Koga, M. Cappellari, M. Schaedelin, S. Zietz, A. Peters, N. Seiffge, D.J. Haupenthal, D. Gassmann, L. De Marchis, G.M. Wang, R. Gensicke, H. Stoll, S. Thilemann, S. Avramiotis, N.S. Bonetti, B. Tsivgoulis, G. Ambler, G. Alberti, A. Yoshimura, S. Brown, M.M. Shiozawa, M. Lip, G.Y.H. Venti, M. Acciarresi, M. Tanaka, K. Mosconi, M.G. Takagi, M. Jäger, R.H. Muir, K. Inoue, M. Schwab, S. Bonati, L.H. Lyrer, P.A. Toyoda, K. Caso, V. Werring, D.J. Kallmünzer, B. Engelter, S.T. Engelter, S.T. Lyrer, P.A. Bonati, L.H. Seiffge, D.J. Traenka, C. Polymeris, A.A. Zietz, A. Peters, N. De Marchis, G.M. Thilemann, S. Avramiotis, N.S. Gensicke, H. Hert, L. Wagner, B. Schaub, F. Meya, L. Fladt, J. Dittrich, T. Fisch, U. Macha, K. Haupenthal, D. Gassmann, L. Wang, R. Stoll, S. Schwab, S. Volbers, B. Siedler, G. Kallmünzer, B. Cappellari, M. Bonetti, B. Bovi, P. Tomelleri, G. Micheletti, N. Zivelonghi, C. Emiliani, A. Parry-Jones, A. Patterson, C. Price, C. Elmarimi, A. Parry, A. Nallasivam, A. Nor, A.M. Esis, B. Bruce, D. Bhaskaran, B. Roffe, C. Cullen, C. Holmes, C. Cohen, D. Hargroves, D. Mangion, D. Chadha, D. Vahidassr, D. Manawadu, D. Giallombardo, E. Warburton, E. Flossman, E. Gunathilagan, G. Proschel, H. Emsley, H. Anwar, I. Burger, I. Okwera, J. Putterill, J. O’Connell, J. Bamford, J. Corrigan, J. Scott, J. Birns, J. Kee, K. Saastamoinen, K. Pasco, K. Dani, K. Sekaran, L. Choy, L. Iveson, L. Mamun, M. Sajid, M. Cooper, M. Burn, M. Smith, M. Power, M. Davis, M. Smyth, N. Veltkamp, R. Sharma, P. Guyler, P. O’Mahony, P. Wilkinson, P. Datta, P. Aghoram, P. Marsh, R. Luder, R. Meenakishundaram, S. Subramonian, S. Leach, S. Ispoglou, S. Andole, S. England, T. Manoj, A. Harrington, F. Rehman, H. Sword, J. Staals, J. Mahawish, K. Harkness, K. Shaw, L. McCormich, M. Sprigg, N. Mansoor, S. Krishnamurthy, V. Giustozzi, M. Acciarresi, M. Agnelli, G. Becattini, C. Alberti, A. D’Amore, C. Cimini, L.A. Bandini, F. Tsivgoulis, G. Liantinioti, C. Chondrogianni, M. Yaghi, S. Furie, K.L. Tadi, P. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Vannucchi, V. Masotti, L. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Athanasakis, G. Makaritsis, K. Karagkiozi, E. Vadikolias, K. Mumoli, N. Galati, F. Sacco, S. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Tassinari, T. De Lodovici, M.L. Rueckert, C. Baldi, A. Toni, D. Letteri, F. Pieroni, A. Giuntini, M. Lotti, E.M. Flomin, Y. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Barlinn, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Todo, K. Kimura, K. Shibazaki, K. Yagita, Y. Furui, E. Itabashi, R. Terasaki, T. Shiokawa, Y. Hirano, T. Suzuki, R. Kamiyama, K. Nakagawara, J. Takizawa, S. Homma, K. Okuda, S. Okada, Y. Maeda, K. Kameda, T. Kario, K. Nagakane, Y. Hasegawa, Y. Akiyama, H. Shibuya, S. Mochizuki, H. Ito, Y. Nakashima, T. Matsuoka, H. Takamatsu, K. Nishiyama, K. Tanaka, K. Endo, K. Miyagi, T. Osaki, M. Kobayashi, J. Okata, T. Tanaka, E. Sakamoto, Y. Tokunaga, K. Takizawa, H. Takasugi, J. Matsubara, S. Higashida, K. Matsuki, T. Kinoshita, N. Shiozawa, M. Ide, T. Yoshimoto, T. Ando, D. Fujita, K. Kumamoto, M. Kamimura, T. Kikuno, M. Mizoguchi, T. Sato, T. NOACISP-LONGTERM, Erlangen Registry, CROMIS-2, RAF, RAF-DOAC, SAMURAI-NVAF Verona Registry Collaborators

Abstract

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (

Published
2022

6. Risk Factors for Intracerebral Hemorrhage in Patients with Atrial Fibrillation on Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention

Author

Paciaroni, M. Agnelli, G. Giustozzi, M. Caso, V. Toso, E. Angelini, F. Canavero, I. Micieli, G. Antonenko, K. Rocco, A. Diomedi, M. Katsanos, A.H. Shoamanesh, A. Giannopoulos, S. Ageno, W. Pegoraro, S. Putaala, J. Strbian, D. Sallinen, H. Mac Grory, B.C. Furie, K.L. Stretz, C. Reznik, M.E. Alberti, A. Venti, M. Mosconi, M.G. Vedovati, M.C. Franco, L. Zepponi, G. Romoli, M. Zini, A. Brancaleoni, L. Riva, L. Silvestrelli, G. Ciccone, A. Zedde, M.L. Giorli, E. Kosmidou, M. Ntais, E. Palaiodimou, L. Halvatsiotis, P. Tassinari, T. Saia, V. Ornello, R. Sacco, S. Bandini, F. Mancuso, M. Orlandi, G. Ferrari, E. Pezzini, A. Poli, L. Cappellari, M. Forlivesi, S. Rigatelli, A. Yaghi, S. Scher, E. Frontera, J.A. Masotti, L. Grifoni, E. Caliandro, P. Zauli, A. Reale, G. Marcheselli, S. Gasparro, A. Terruso, V. Arnao, V. Aridon, P. Abdul-Rahim, A.H. Dawson, J. Saggese, C.E. Palmerini, F. Doronin, B. Volodina, V. Toni, D. Risitano, A. Schirinzi, E. Del Sette, M. Lochner, P. Monaco, S. Mannino, M. Tassi, R. Guideri, F. Acampa, M. Martini, G. Lotti, E.M. Padroni, M. Pantoni, L. Rosa, S. Bertora, P. Ntaios, G. Sagris, D. Baldi, A. D'Amore, C. Mumoli, N. Porta, C. Denti, L. Chiti, A. Corea, F. Acciarresi, M. Flomin, Y. Popovic, N. Tsivgoulis, G.

Subjects
cardiovascular diseases
Abstract

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA2DS2-VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA2DS2-VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA2DS2-VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468-0.525) and 0.530 (95% CI, 0.500-0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA2DS2-VASc scores. © 2021 Lippincott Williams and Wilkins. All rights reserved.

Published
2021

7. Safety of Anticoagulation in Patients Treated with Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation

Author

Giustozzi, M. Acciarresi, M. Agnelli, G. Caso, V. Bandini, F. Tsivgoulis, G. Yaghi, S. Furie, K.L. Tadi, P. Becattini, C. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. D'Amore, C. Giulia Mosconi, M. Anna Cimini, L. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Athanasakis, G. Makaritsis, K. Karagkiozi, E. Vadikolias, K. Liantinioti, C. Theodorou, A. Halvatsiotis, P. Mumoli, N. Galati, F. Sacco, S. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. Ferrari, E. Ulivi, L. Orlandi, G. Giannini, N. Tassinari, T. Luisa De Lodovici, M. Rueckert, C. Baldi, A. Toni, D. Letteri, F. Giuntini, M. Maria Lotti, E. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Maimone Baronello, M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Barlinn, J. Deleu, D. Gourbali, V. Paciaroni, M. Masotti, L.

Abstract

Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either Vitamin K antagonists or nonVitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant. © 2020 The Authors.

Published
2020

8. Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes

Author

Paciaroni, M. Agnelli, G. Giustozzi, M. Tsivgoulis, G. Yaghi, S. Grory, B.M. Furie, K.L. Tadi, P. Zedde, M. Abdul-Rahim, A.H. Dawson, J. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Mosconi, M.G. Bogini, V. Cappellari, M. Rigatelli, A. Bonetti, B. Putaala, J. Tomppo, L. Tatlisumak, T. Bandini, F. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Grifoni, E. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Athanasakis, G. Makaritsis, K. Karagkiozi, E. Vadikolias, K. Liantinioti, C. Palaiodimou, L. Mumoli, N. Porta, C. Galati, F. Sacco, S. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Silvestrelli, G. Ciccone, A. Scoditti, U. Denti, L. Mancuso, M. Caselli, M.C. Maccarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Tassinari, T. Lodovici, M.L.D. Rueckert, C. Baldi, A. Toni, D. Gentile, L. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Mannino, M. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Sette, M.D. Schirinzi, E. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Eskandari, A. Vanacker, P. Barlinn, K. Barlinn, J. Deleu, D. Gourbali, V. Caso, V.

Abstract

Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80). Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT. © European Stroke Organisation 2020.

Published
2020

10. Cardiac disease and Rett syndrome

Author

Acampa, M. and Guideri, F.

Subjects
Rett syndrome -- Development and progression, Heart diseases -- Development and progression
Published
2006

13. Anticoagulation after Stroke in Patients with Atrial Fibrillation: To Bridge or Not with Low-Molecular-Weight Heparin?

Author

Altavilla, R. Caso, V. Bandini, F. Agnelli, G. Tsivgoulis, G. Yaghi, S. Furie, K.L. Tadi, P. Becattini, C. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D'Amore, C. Giulia Mosconi, M. Anna Cimini, L. Fusaro, J. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Athanasakis, G. Makaritsis, K. Karagkiozi, E. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. MacCarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Barlinn, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Paciaroni, M.

Abstract

Background and Purpose-Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods-We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results-Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P

Published
2019

14. Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke

Author

Paciaroni, M. Angelini, F. Agnelli, G. Tsivgoulis, G. Furie, K.L. Tadi, P. Becattini, C. Falocci, N. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. Altavilla, R. D’Amore, C. Mosconi, M.G. Cimini, L.A. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Bandini, F. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Karagkiozi, E. Athanasakis, G. Makaritsis, K. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Silvestrelli, G. Ciccone, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. Lodovici, M.L.D. Bono, G. Rueckert, C. Baldi, A. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Sette, M.D. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel Pd-Mer, P. Vanacker, P. Barlinn, K. Pallesen, L.P. Kepplinger, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Yaghi, S. Caso, V.

Subjects
cardiovascular system, macromolecular substances, cardiovascular diseases
Abstract

Background: The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. Purpose: In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. Methods: In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. Results: A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24–2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74–2.04)). Conclusions: After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence. © European Stroke Organisation 2018.

Published
2019

15. Causes and Risk Factors of Cerebral Ischemic Events in Patients with Atrial Fibrillation Treated with Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention: The RENo Study

Author

Paciaroni, M. Agnelli, G. Caso, V. Silvestrelli, G. Seiffge, D.J. Engelter, S. De Marchis, G.M. Polymeris, A. Zedde, M.L. Yaghi, S. Michel, P. Eskandari, A. Antonenko, K. Sohn, S.-I. Cappellari, M. Tassinari, T. Tassi, R. Masotti, L. Katsanos, A.H. Giannopoulos, S. Acciarresi, M. Alberti, A. Venti, M. Mosconi, M.G. Vedovati, M.C. Pierini, P. Giustozzi, M. Lotti, E.M. Ntaios, G. Kargiotis, O. Monaco, S. Lochner, P. Bandini, F. Liantinioti, C. Palaiodimou, L. Abdul-Rahim, A.H. Lees, K. Mancuso, M. Pantoni, L. Rosa, S. Bertora, P. Galliazzo, S. Ageno, W. Toso, E. Angelini, F. Chiti, A. Orlandi, G. Denti, L. Flomin, Y. Marcheselli, S. Mumoli, N. Rimoldi, A. Verrengia, E. Schirinzi, E. Del Sette, M. Papamichalis, P. Komnos, A. Popovic, N. Zarkov, M. Rocco, A. Diomedi, M. Giorli, E. Ciccone, A. Grory, B.C.M. Furie, K.L. Bonetti, B. Saia, V. Guideri, F. Acampa, M. Martini, G. Grifoni, E. Padroni, M. Karagkiozi, E. Perlepe, K. Makaritsis, K. Mannino, M. MacCarrone, M. Ulivi, L. Giannini, N. Ferrari, E. Pezzini, A. Doronin, B. Volodina, V. Baldi, A. D'Amore, C. Deleu, D. Corea, F. Putaala, J. Santalucia, P. Nardi, K. Risitano, A. Toni, D. Tsivgoulis, G.

Abstract

Background and Purpose-Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non-Vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods-Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results-Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95-5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63-9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83-3.16), and CHA2DS2-VASc score (OR, 1.72 for each point increase; 95% CI, 1.58-1.88) were associated with ischemic events. Among the CHA2DS2-VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33-0.61). Conclusions-In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA2DS2-VASc score were associated with increased risk of cerebrovascular events. © 2019 American Heart Association, Inc.

Published
2019

18. Hemorrhagic transformation in patients with acute ischemic stroke and atrial fibrillation: Time to initiation of oral anticoagulant therapy and outcomes

Author

Paciaroni, M. Bandini, F. Agnelli, G. Tsivgoulis, G. Yaghi, S. Furie, K.L. Tadi, P. Becattini, C. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D’Amore, C. Mosconi, M.G. Cimini, L.A. Altavilla, R. Volpi, G. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Athanasakis, G. Makaritsis, K. Karagkiozi, E. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Barlinn, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Caso, V.

Abstract

Background—In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results—HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions—In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability. © 2018 The Authors.

Published
2018

20. Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients with Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study

Author

Paciaroni, M. Agnelli, G. Caso, V. Tsivgoulis, G. Furie, K.L. Tadi, P. Becattini, C. Falocci, N. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D'Amore, C. Mosconi, M.G. Cimini, L.A. Procopio, A. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Bandini, F. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Masotti, L. Vannucchi, V. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Karagkiozi, E. Athanasakis, G. Makaritsis, K. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Mumoli, N. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Silvestrelli, G. Ciccone, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Orlandi, G. Giannini, N. Gialdini, G. Tassinari, T. De Lodovici, M.L. Bono, G. Rueckert, C. Baldi, A. D'Anna, S. Toni, D. Letteri, F. Giuntini, M. Lotti, E.M. Flomin, Y. Pieroni, A. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Kepplinger, J. Bodechtel, U. Gerber, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Yaghi, S.

Abstract

Background and Purposes - This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods - The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. Results - The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. Conclusions - In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc.

Published
2017

21. Early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with Non-Vitamin-K oral anticoagulants (RAF-NOACs) Study

Author

Paciaroni, M. Agnelli, G. Falocci, N. Tsivgoulis, G. Vadikolias, K. Liantinioti, C. Chondrogianni, M. Bovi, P. Carletti, M. Cappellari, M. Zedde, M. Ntaios, G. Karagkiozi, E. Athanasakis, G. Makaritsis, K. Silvestrelli, G. Lanari, A. Ciccone, A. Putaala, J. Tomppo, L. Tatlisumak, T. Abdul-Rahim, A.H. Lees, K.R. Alberti, A. Venti, M. Acciarresi, M. D'Amore, C. Becattini, C. Mosconi, M.G. Cimini, L.A. Soloperto, R. Masotti, L. Vannucchi, V. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Sohn, S.-I. Marcheselli, S. Mumoli, N. De Lodovici, M.L. Bono, G. Furie, K.L. Tadi, P. Yaghi, S. Toni, D. Letteri, F. Tassinari, T. Kargiotis, O. Lotti, E.M. Flomin, Y. Mancuso, M. Maccarrone, M. Giannini, N. Bandini, F. Pezzini, A. Poli, L. Padovani, A. Scoditti, U. Denti, L. Consoli, D. Galati, F. Sacco, S. Carolei, A. Tiseo, C. Gourbali, V. Orlandi, G. Giuntini, M. Chiti, A. Giorli, E. Gialdini, G. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Monaco, S. Baronello, M.M. Karapanayiotides, T. Caso, V.

Abstract

Background--The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within90 days)and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and Results--Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA2DS2-VASc score > 4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated > 14 days after acute stroke. Conclusions--In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days. © 2017 The Authors.

Published
2017

24. Homocysteine and P wave dispersion in patients with heart transplantation

Author

Acampa, M, Lazzerini, PIETRO ENEA, Guideri, Francesca, Rechichi, S, Capecchi, PIER LEOPOLDO, Maccherini, M, and LAGHI PASINI, Franco

Subjects
Male, Hyperhomocysteinemia, Arrhythmias, Cardiac, Heart, Middle Aged, Survival Rate, Electrocardiography, Treatment Outcome, Case-Control Studies, Heart Transplantation, Humans, Female, Prospective Studies, Homocysteine, Follow-Up Studies
Abstract

Hyperhomocysteinemia (HHcy), a putative independent risk factor for the development of atherotrombosis in the general population, represents a very common finding in orthotopic heart transplantation (OHT) patients. Starting from previous studies suggesting a pro-arrhythmogenic activity of homocysteine (Hcy), we evaluated the possible correlation among Hcy plasma levels and P wave dispersion (PWD), corrected QT interval (QTc), and QTc dispersion (QTcD) as parameters of electric instability of the myocardium in patients undergone OHT whose hearts are therefore completely denervated, thus unresponsive to autonomic influences.Homocysteine plasma levels, PWD, QTc, QTcD, and QTc dynamics were measured in 32 patients, who underwent OHT, and in 20 control subjects. In OHT patients, PWD (39.5 ± 11 vs. 34 ± 6 ms, p = 0.04) and QTc interval (438 ± 20 vs. 410 ± 10 ms, p0.001) were significantly higher in comparison with control subjects. Moreover, OHT subjects with HHcy had higher PWD values than those with normal Hcy plasma levels (44.1 ± 10.7 vs. 33.9 ± 8.8 ms, p = 0.007), but no difference was found between this latter OHT group and controls. Accordingly, in OHT patients, plasma Hcy level correlated significantly with PWD (Spearman r = 0.70; p0.0001), whereas no correlation was found with QTc, QTcD, and QTc circadian dynamics.HHcy seems associated with an alteration in the electrical atrial conduction, possibly contributing, at least in part, to the increased risk of cardiac arrhythmias in the denervated hearts of OHT patients.

Published
2009

26. Genetic influence in antithrombotic actions of atorvastatin in hypercholesterolaemia

Author

Puccetti L, Bruni F, Al, Pasqui, Pastorelli M, Ciani F, Alberto Palazzuoli, Acampa M, and Auteri A

Subjects
Adult, Male, Polymorphism, Genetic, Adolescent, Anticholesteremic Agents, Hypercholesterolemia, Coronary Artery Disease, Middle Aged, Scavenger Receptors, Class E, Lipoproteins, LDL, Fibrinolytic Agents, Heptanoic Acids, Atorvastatin, Humans, Female, Pyrroles, Nitric Oxide Synthase, Aged
Abstract

Recent data indicate that statins could offer coronary artery disease (CAD) benefit even by mechanisms beyond lipid lowering. Genetic influence has been shown for some antithrombotic actions of statins via oxidized-low-density lipoprotein cholesterol (ox-LDL) receptors and nitric oxide synthase (NOS) activity modulation. The present study was designed to evaluate the influence of ox-LDL lectin-like receptor-1 (LOX-1) and NOS polymorphisms in the incidence of cardiovascular events in pure hypercholesterolaemic subjects during statin treatment.A prospective 4-year study involving 1039 event-free subjects (643 males, 396 females) treated with atorvastatin (10-40 mg day(-1)) to reach the appropriate Adult Treatment Panel-III LDL target of 3.36 mmol L(-1). Enrolled subjects were evaluated every 6 months or at a clinical event. LOX-1 3'UTR/T-C and NOS G894T polymorphisms were detected by allelic discrimination assays (polymerase chain reaction), lipid profile by enzymatic-colorimetric method, ox-LDL by enzyme linked immunosorbent assay, platelet activation by P-selectin (P-sel) expression (FACScan), NOS activity (by intracellular citrullin recovery) and homocysteine (high performance liquid chromatography), C-reactive protein (CRP) by sensitive nephelometric technique.LOX-1 3'UTR/T showed the strongest association with events in the whole cohort with respect to each other variable including LDL reduction and NOS G894T (OR 4.90, 95% CI 3.19-6.98, P0.00001). Smoking influenced events in LDL-targeted subjects (P0.0001). Ox-LDL and P-sel were better indicators than LDL or other variables according to 3'UTR/C genotype regardless of the magnitude of LDL reduction (OR 4.21, 95% CI 2.29-6.70 P0.0001).LOX-1 polymorphisms could influence statin effectiveness in CAD prevention by induction of sensitivity to antithrombotic mechanisms such as antiplatelet activity.

Published
2008

27. Delineation of the phenotype associated with 7q36.1q36.2 deletion: long QT syndrome, renal hypoplasia and mental retardation

Author

Caselli, R., Mencarelli, M. A., Papa, F. T., Ariani, Francesca, Longo, I., Meloni, I., Vonella, G., Acampa, M., Auteri, A., Vicari, S., Orsi, A., Hayek, G., Renieri, A., Mari, Francesca, and Papa, FILOMENA TIZIANA

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Long QT syndrome, Kidney, QT interval, Holoprosencephaly, Pregnancy, Hypotelorism, Intellectual Disability, Genetics, medicine, Humans, Multiplex ligation-dependent probe amplification, Child, Maternal-Fetal Exchange, Genetics (clinical), DNA Primers, Chromosome 7 (human), Base Sequence, business.industry, Syndrome, medicine.disease, Subtelomere, Renal hypoplasia, Long QT Syndrome, Phenotype, Phenytoin, Anticonvulsants, Female, Chromosome Deletion, business, Chromosomes, Human, Pair 7
Abstract

Terminal deletions of the long arm of chromosome 7 are well known and are frequently associated with hypotelorism or holoprosencephaly due to the involvement of the SHH gene located in 7q36.3. These deletions are easily detectable with routine subtelomeric MLPA analysis. Deletions affecting a more proximal part of 7q36, namely bands 7q36.1q36.2 are less common, and may be missed by subtelomeric MLPA analysis. We report a 9-year-old girl with a 5.27 Mb deletion in 7q36.1q36.2, and compare her to literature patients proposing a phenotype characterized by mental retardation, unusual facial features, renal hypoplasia and long QT syndrome due to loss of the KCNH2 gene. These characteristics are sufficiently distinct that the syndrome may be diagnosed on clinical grounds.

Published
2008

30. Microvascular abnormalities in Rett syndrome

Author

Bianciardi, G., primary, Acampa, M., additional, Lamberti, I., additional, Sartini, S., additional, Servi, M., additional, Biagi, F., additional, Bocchi, V., additional, Hayek, J., additional, and Pastorelli, M., additional

Published
2013
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32. Bosentan Treatment for Raynaud's Phenomenon and Skin Fibrosis in Patients with Systemic Sclerosis and Pulmonary Arterial Hypertension: An Open-Label, Observational, Retrospective Study

Author

Giordano, N., primary, Puccetti, L., additional, Papakostas, P., additional, Di Pietra, N., additional, Bruni, F., additional, Pasqui, A.L., additional, Acampa, M., additional, Bocchi, V., additional, Donati, V., additional, Voglino, M., additional, Fioravanti, A., additional, Montella, A., additional, Auteri, A., additional, Nuti, R., additional, and Pastorelli, M., additional

Published
2010
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43. Acute effects of glibenclamide on reactive hyperaemia in the lower limbs in humans.

Author

Capecchi, P.L., Guideri, F., Colafati, M., Acampa, M., Cuomo, A., Lazzerini, P.E., and Pasini, F. Laghi

Subjects
GLIBENCLAMIDE, ADENOSINE triphosphate, POTASSIUM channels, HYPEREMIA, LEG
Abstract

Three episodes of 1 min ischemia in the lower limbs in humans reduced the metabolic debt repayment (expressed as AUC of reactive hyperaemia) following more prolonged ischemia (666.6±86.6 vs 500.0±33.5 ml/100 ml). The administration of the ATP-dependent K [ABSTRACT FROM AUTHOR]

Published
2002

44. Effects of alprostadil on blood rheology and nucleoside metabolism in patients affected with lower limb chronic ischaemia.

Author

Acciavatti, A., Laghi Pasini, F., Capecchi, P.L., Messa, G.L., Lazzerini, P.E., De Giorgi, L., Acampa, M., and Di Perri, T.

Subjects
PROSTAGLANDIN E1, ISCHEMIA, BLOOD, NUCLEOSIDES, THERAPEUTICS
Abstract

The acute (0.57 µg/kg i.v. in 2 hours) and long-term (0.57 µg/kg i.v. in 2 hours for 5 days over 4 weeks) effects of the PGE1 analogue alprostadil were studied in patients affected with intermittent claudication. Whole Blood Viscosity (WBV), Whole Blood Filterability (WBF), haematocrit (Htc) and fibrinogen plasma concentration, were studied together with P50, 2,3-diphosphoglycerate, and adenosine plasma levels. Moreover, in the long-term study, painfree (PFWD) and maximal walking distance (MWD) were measured. Single alprostadil infusion induced an improvement in WBV, WBF, and oxygen transport, and an increase in adenosine plasma levels. Long-term alprostadil administration produced a decrease in WBV only, without significant changes in WBF, Htc, fibrinogen, P50, 2,3-diphosphoglycerate, also inducing a significant prolongation of PFWD and MWD. The possibility is suggested that pulse rises in adenosine plasma levels play a role in the effects of chronic alprostadil administration, maybe in a way similar to that observed in the phenomenon of ischaemic preconditioning. [ABSTRACT FROM AUTHOR]

Published
2001

45. Cranial osteolytic metastases as the only recurrence of gastric carcinoma.

Author

PASTORELLI, M., PUCCETTI, L., DI PIETRA, N., BRUNI, F., ACAMPA, M., COSTA, A., BEERMANN, U., BOCCHI, V ., DONATI, V ., AUTERI, A., and CERASE, A.

Abstract

The purpose of this case report is to increase the knowledge about bone metastatic pattern in gastric cancer. A 59-year-old man presented with headache three years after a total gastrectomy for signet-ring cell carcinoma. Head computed tomography and magnetic resonance imaging showed multiple osteolytic lesions of the cranial vault and base, consistent with metastatic or haematological disease. Bone scintigraphy confirmed areas of accumulation only in the skull. An extensive search didn't show any other tumor. Bone biopsy revealed metastatic signet-ring cell carcinoma. In gastric cancer, bone metastases are generally associated with metastases in lymph nodes, liver, and lung, and have a higher frequency in the thoracolumbar spine. However, cranial bone metastases presenting with headache may be the only manifestation of gastric cancer recurrence. [ABSTRACT FROM AUTHOR]

Published
2011

46. Nerve Growth Factor Plasma Levels and Ventricular Repolarization in Rett Syndrome.

Author

Guided, F., Acampa, M., Catamandrei, G., Aloe, L., Zappella, M., and Hayek, Y.

Subjects
*RETT syndrome, *NERVE growth factor, *LONG QT syndrome, *SUDDEN death in children, *NEUROPLASTICITY, *PEDIATRIC cardiology
Abstract

Rett syndrome is a severe neurological developmental disorder. In this syndrome, the high incidence of sudden death is correlated with an alteration of ventricular repolarization. The purpose of this study was to evaluate plasmatic levels of nerve growth factor (NGF) in Rett patients with prolonged corrected QT (QTc) interval in comparison with those of Rett patients with normal QTc. We observed 23 female Rett patients (9.9 ± 4.7 years). NGF plasma levels and QTc interval were measured in all patients. Student t-test was performed for statistical analysis. NGF plasma levels were significantly lower in Rett patients with QTc interval prolongation (QTc > 0.44 sec) in comparison with Rett patients with a normal QTc interval (4.5 ± 4.5 vs 11 ± 8.3 pg/ml, p = 0.02). The alteration of NGF levels, observed in Rett patients with a long QTc interval, may explain the presence of an altered ventricular repolarization associated with a higher risk of cardiac arrhythmias. [ABSTRACT FROM AUTHOR]

Published
2004
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48. INTRACEREBRAL HEMORRHAGE FROM UNDETERMINED CAUSE AMONG 817 YOUNG-ADULT STROKE PATIENTS ENROLLED IN THE FABRY STROKE ITALIAN REGISTRY

Author

Accavone, D., Romani, I., Pracucci, G., Biagini, S., Sarti, C., Nucera, A., Zedde, M. L., Cianci, V., Aguglia, U., Cosenza, D., Toni, D., Sbardella, E., Pennigi, G., Bella, R., Francesco Fisicaro, Palumbo, P., Direnzo, V., Diomedi, M., Orsucci, D., Vista, M., Tassi, R., Acampa, M., Bonetti, B., Forlivesi, S., Volpi, G., Nannucci, S., Del Bene, A., Cavallini, A., Cuzzoni, M. G., Ricci, S., Barcellona, C., Rasura, M., Di Lisi, F., Chiti, A., Teatini, F., Buechner, S., Seppi, D., Consoli, D., Galati, F., Passarella, B., Pinto, V., Inzitari, D., and Nencini, P.

49. [Neuroimaging and definition of transient ischemic attack]

Author

Cerase A, Lazzeretti L, Im, Vallone, Ferretti F, Bracco S, Galluzzi P, Gennari P, Monti L, Menci E, Bellini M, Arrigucci U, Cioni S, Romano D, Sanna A, Zandonella A, Acampa M, Rossana Tassi, Martini G, and Venturi C

Subjects
Adult, Aged, 80 and over, Male, Time Factors, Neuroimaging, Middle Aged, Statistics, Nonparametric, Fibrin Fibrinogen Degradation Products, Diffusion Magnetic Resonance Imaging, Ischemic Attack, Transient, Risk Factors, Acute Disease, Humans, Female, Tomography, X-Ray Computed, Biomarkers, Aged, Retrospective Studies
Abstract

Transient ischemic attack (TIA) has to be considered an "alarm bell" of a more or less severe organic or systemic vasculopathy. Positive findings at neuroimaging means tissue damage. The purpose of this retrospective study was to assess the role of neuroimaging in the management of patients presenting with TIA, and to consider the relative implications.In a consecutive series of 82 patients (53 males, 29 females, mean age: 65.9±13.1 years) admitted for TIA, it was possible to review the history and the clinical data of 66 patients, including ABCD2 score, laboratory including plasmatic D-dimer, and neuroimaging data including computed tomography (CT) and magnetic resonance imaging including diffusion-weighted with apparent diffusion coefficient measure (DWI-ADC) obtained at diagnosis and by a week later (16 by CT, and 50 by DWI-ADC). Thirty-three patients underwent DWI-ADC within 24 hours from symptoms onset. Statistical analysis has been performed by non-parametric tests (χ2 and Mann-Whitney), and logistic regression by a commercially available software.CT and/or DWI-ADC showed signs of acute ischemic lesions in 23/66 (35%) patients. 12 out of the 35 patients with a 24-hour DWI-ADC follow-up were positive. Statistical analysis showed that positive neuroimaging was significantly associated only with familial history of cardiovascular diseases (P0.012) and previous TIA/stroke (P0.046).In this patients series, at least 35% of patients with TIA had a positive neuroimaging, especially DWI-ADC. Positive neuroimaging seems an independent factor. Patients with TIA need an early assessment by neuroimaging including DWI-ADC, in order to obtain a correct classification and prognosis.

50. WHICH ARE NON EMBOLIC CRYPTOGENIC ISCHEMIC STROKES? CONSIDERATIONS FROM THE FABRY ITALIAN YOUNG ADULT STROKE REGISTRY

Author

Biagini, S., Romani, I., Nencini, P., Pracucci, G., Accavone, D., Nucera, A., Zedde, M., Cianci, V., Aguglia, U., Gallo, G., Musolino, R. F., Casella, C., Cosenza, D., Sbardella, E., Pennisi, G., Bella, R., Toni, D., Francesco Fisicaro, Palumbo, P., Valenti, R., Barbarini, L., Direnzo, V., Linoli, G., Calchetti, B., Diomedi, M., D Agostino, F., Ragno, M., Di Marzio, F., Orsucci, D., Vista, M., Tassi, R., Acampa, M., Bonetti, B., Forlivesi, S., Volpi, G., Nannucci, S., Del Bene, A., Cavallini, A., Cuzzoni, M. G., Ricci, S., Barcellona, C., Delodovici, M. L., Rasura, M., Di Lisi, F., Chiti, A., Teatini, F., Buechner, S., Seppi, D., Consoli, D., Galati, F., Passarella, B., Pinto, V., Inzitari, D., and Sarti, C.

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