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3. Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation.

Author

Soo, Y., Zietz, A., Yiu, B., Mok, V.C.T., Polymeris, A.A., Seiffge, D., Ambler, G., Wilson, D., Leung, T.W.H., Tsang, S.F., Chu, W., Abrigo, J., Cheng, C., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H., Collet, R., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Demirelli, D.S., Bornstein, N.M., Assayag, E.B., Hallevi, H., Molad, J., Nishihara, M., Tanaka, J., Coutts, S.B., Kappelle, L.J., Al-Shahi Salman, R., Jager, Rolf, Lip, G.Y.H., Goeldlin, M.B., Panos, L.D., Mas, J.L., Legrand, Laurence, Karayiannis, C., Phan, T., Bellut, M., Chappell, F., Makin, S., Hayden, D., Williams, D., Dam-Nolen, D.H.K. Van, Nederkoorn, P.J., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Mendyk, A.M., Köhler, S., Oostenburgge, R. van, Zhou, Ying, Xu, Chao, Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Hendrikse, Jeroen, Wardlaw, J., Kelly, P., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Smith, E.E., Hara, H., Yakushiji, Y., Orken, D.N., Fazekas, F., Thijs, V., Heo, J.H., Veltkamp, R., Ay, H., Imaizumi, T., Lau, K.K., Jouvent, E., Toyoda, K., Yoshimura, S., Bae, H.J., Martí-Fàbregas, J., Prats-Sánchez, L., Lyrer, P., Best, J. de, Werring, D., Engelter, S.T., Peters, Nils, Soo, Y., Zietz, A., Yiu, B., Mok, V.C.T., Polymeris, A.A., Seiffge, D., Ambler, G., Wilson, D., Leung, T.W.H., Tsang, S.F., Chu, W., Abrigo, J., Cheng, C., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H., Collet, R., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Demirelli, D.S., Bornstein, N.M., Assayag, E.B., Hallevi, H., Molad, J., Nishihara, M., Tanaka, J., Coutts, S.B., Kappelle, L.J., Al-Shahi Salman, R., Jager, Rolf, Lip, G.Y.H., Goeldlin, M.B., Panos, L.D., Mas, J.L., Legrand, Laurence, Karayiannis, C., Phan, T., Bellut, M., Chappell, F., Makin, S., Hayden, D., Williams, D., Dam-Nolen, D.H.K. Van, Nederkoorn, P.J., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Mendyk, A.M., Köhler, S., Oostenburgge, R. van, Zhou, Ying, Xu, Chao, Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Hendrikse, Jeroen, Wardlaw, J., Kelly, P., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Smith, E.E., Hara, H., Yakushiji, Y., Orken, D.N., Fazekas, F., Thijs, V., Heo, J.H., Veltkamp, R., Ay, H., Imaizumi, T., Lau, K.K., Jouvent, E., Toyoda, K., Yoshimura, S., Bae, H.J., Martí-Fàbregas, J., Prats-Sánchez, L., Lyrer, P., Best, J. de, Werring, D., Engelter, S.T., and Peters, Nils

Abstract

01 juli 2023, Contains fulltext : 294348.pdf (Publisher’s version ) (Open Access), OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet). METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76-4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04-1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. ANN NEUROL 2023;94:61-74.

Published
2023

4. Can CHA2DS2-VASc and HAS–BLED Foresee the Presence of Cerebral Microbleeds, Lacunar and Non-Lacunar Infarcts in Elderly Patients With Atrial Fibrillation? Data From Strat–AF Study

Author

Bianconi E., Del Freo G., Salvadori E., Barbato C., Formelli B., Pescini F., Pracucci G., Sarti C., Cesari F., Chiti S., Diciotti S., Gori A. M., Marzi C., Fainardi E., Giusti B., Marcucci R., Bertaccini B., Poggesi A., Bianconi E., Del Freo G., Salvadori E., Barbato C., Formelli B., Pescini F., Pracucci G., Sarti C., Cesari F., Chiti S., Diciotti S., Gori A.M., Marzi C., Fainardi E., Giusti B., Marcucci R., Bertaccini B., and Poggesi A.

Subjects
brain MRI, Neurology, cerebral small vessel disease, HAS-BLED scale, CHA, VASc scale, atrial fibrillation, Neurology (clinical), anticoagulation, DS, intracerebral hemorrhage, stroke
Abstract

Anticoagulants reduce embolic risk in atrial fibrillation (AF), despite increasing hemorrhagic risk. In this context, validity of congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke, vascular disease, age 65–74 years and sex category (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly (HAS–BLED) scales, used to respectively evaluate thrombotic and hemorrhagic risks, is incomplete. In patients with AF, brain MRI has led to the increased detection of “asymptomatic” brain changes, particularly those related to small vessel disease, which also represent the pathologic substrate of intracranial hemorrhage, and silent brain infarcts, which are considered risk factors for ischemic stroke. Routine brain MRI in asymptomatic patients with AF is not yet recommended. Our aim was to test predictive ability of risk stratification scales on the presence of cerebral microbleeds, lacunar, and non-lacunar infarcts in 170 elderly patients with AF on oral anticoagulants. Ad hoc developed R algorithms were used to evaluate CHA2DS2-VASc and HAS–BLED sensitivity and specificity on the prediction of cerebrovascular lesions: (1) Maintaining original items' weights; (2) augmenting weights' range; (3) adding cognitive, motor, and depressive scores. Accuracy was poor for each outcome considering both scales either in phase 1 or phase 2. Accuracy was never improved by the addition of cognitive scores. The addition of motor and depressive scores to CHA2DS2-VASc improved accuracy for non-lacunar infarcts (sensitivity = 0.70, specificity = 0.85), and sensitivity for lacunar–infarcts (sensitivity = 0.74, specificity = 0.61). Our results are a very first step toward the attempt to identify those elderly patients with AF who would benefit most from brain MRI in risk stratification.

Published
2022
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6. Alcohol-induced oxidative stress in head and neck cancer. Updates on the role of genetic, epigenetics, oral microbiota, antioxidants, and alkylating agents

Author

Ferraguti G, Terracina S, Petrella C, Greco A, Minni A, Lucarelli M, Agostinelli E, Ralli M, de Vincentiis M, Raponi G, Polimeni A, Ceccanti M, Caronti B, Di Certo MG, Barbato C, Mattia A, and Fiore M (corresponding author).

Subjects
head and neck, tumor, alcohol, cancer, oxidative stress, ethanol
Abstract

Head and neck cancer (HNC) concerns more than 890,000 patients worldwide annually and is associated with the advanced stage at presentation and heavy outcomes. Alcohol drinking, together with tobacco smoking, and human papillomavirus infection are the main recognized risk factors. The tumorigenesis of HNC represents an intricate sequential process that implicates a gradual acquisition of genetic and epigenetics alterations targeting crucial pathways regulating cell growth, motility, and stromal interactions. Tumor microenvironment and growth factors also play a major role in HNC. Alcohol toxicity is caused both directly by ethanol and indirectly by its metabolic products, with the involvement of the oral microbiota and oxidative stress; alcohol might enhance the exposure of epithelial cells to carcinogens, causing epigenetic modifications, DNA damage, and inaccurate DNA repair with the formation of DNA adducts. Long-term markers of alcohol consumption, especially those detected in the hair, may provide crucial information on the real alcohol drinking of HNC patients. Strategies for prevention could include food supplements as polyphenols, and alkylating drugs as therapy that play a key role in HNC management. Indeed, polyphenols throughout their antioxidant and anti-inflammatory actions may counteract or limit the toxic effect of alcohol whereas alkylating agents inhibiting cancer cells' growth could reduce the carcinogenic damage induced by alcohol. Despite the established association between alcohol and HNC, a concerning pattern of alcohol consumption in survivors of HNC has been shown. It is of primary importance to increase the awareness of cancer risks associated with alcohol consumption, both in oncologic patients and the general population, to provide advice for reducing HNC prevalence and complications.

Published
2022
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7. Early routine biomarkers of SARS-CoV-2 morbidity and mortality. Outcomes from an emergency section

Author

Ceci FM, Fiore M (corresponding author), Gavaruzzi, F, Angeloni A, Lucarelli M, Scagnolari C, Bonci E, Gabanella F, Di Certo MG, Barbato C, Petrella C, Greco A, De Vincentiis M, Ralli M, Passananti C, Poscia R, Minni A, Ceccanti M, Tarani L, and Ferraguti G.

Subjects
Medicine (General), COVID-19, SARS-CoV-2, emergency section, intensive care unit, mortality, morbidity, biomarker, early predictor, Clinical Biochemistry, covid, Article, early, R5-920
Abstract

Background. COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, a virus belonging to the Coronaviridae family. This disease has spread rapidly around the world and soon became an international public health emergency leading to an unpredicted pressure on the hospital emergency units. Early routine blood biomarkers could be key predicting factors of COVID-19 morbidity and mortality as suggested for C-reactive protein (CRP), IL-6, prothrombin and D-dimer. This study aims to identify other early routine blood biomarkers for COVID-19 severity prediction disclosed directly into the emergency section. Methods. Our research was conducted on 156 COVID-19 patients hospitalized at the Sapienza University Hospital “Policlinico Umberto I” of Rome, Italy, between March 2020 and April 2020 during the paroxysm’s initial phase of the pandemic. In this retrospective study, patients were divided into three groups according to their outcome: (1) emergency group (patients who entered the emergency room and were discharged shortly after because they did not show severe symptoms); (2) intensive care unit (ICU) group (patients who attended the ICU after admission to the emergency unit); (3) the deceased group (patients with a fatal outcome who attended the emergency and, afterward, the ICU units). Routine laboratory tests from medical records were collected when patients were admitted to the emergency unit. We focused on Aspartate transaminase (AST), Alanine transaminase (ALT), Lactate dehydrogenase (LDH), Creatine kinase (CK), Myoglobin (MGB), Ferritin, CRP, and D-dimer. Results. As expected, ANOVA data show an age morbidity increase in both ICU and deceased groups compared with the emergency group. A main effect of morbidity was revealed by ANOVA for all the analyzed parameters with an elevation between the emergency group and the deceased group. Furthermore, a significant increase in LDH, Ferritin, CRP, and D-dimer was also observed between the ICU group and the emergency group and between the deceased group and ICU group. Receiver operating characteristic (ROC) analyses confirmed and extended these findings. Conclusions. This study suggests that the contemporaneous presence of high levels of LDH, Ferritin, and as expected, CRP, and D-dimer could be considered as potential predictors of COVID-19 severity and death.

Published
2022
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10. 13P High neutrophils-to-lymphocyte ratio (NLR) predicts poor survival of high-PD-L1-expressing metastatic non-small cell lung carcinoma patients undergoing first-line immunotherapy with pembrolizumab

Author

Romano, F.J., primary, Barbato, C., additional, Arundine, D., additional, Ambrosio, F., additional, Ronga, R., additional, Failla, G., additional, Moccia, L., additional, Corcione, N., additional, Guggino, G., additional, Raucci, A., additional, Romano, L., additional, Campione, S., additional, De Dominicis, G., additional, Santoriello, C., additional, Tinto, A., additional, Russo, C., additional, De Michele, F., additional, Russo, A., additional, Starace, A., additional, and Riccardi, F., additional

Published
2021
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11. Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Best, J.G., Ambler, G., Wilson, D., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Li, L, Lovelock, C., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H.K.F., Prats-Sanchez, L., Martínez-Domeño, A., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Tanriverdi, Z., Bornstein, N.M., Assayag, E. Ben, Hallevi, H., Molad, J., Nishihara, M., Tanaka, J., Coutts, S.B., Polymeris, A., Wagner, B., Seiffge, D.J., Lyrer, P., Algra, A., Kappelle, L.J., Al-Shahi Salman, R., Jäger, H.R., Lip, G.Y.H., Fischer, U., El-Koussy, M., Mas, J.L., Legrand, Laurence, Karayiannis, C., Phan, T., Gunkel, S., Christ, N., Abrigo, J., Leung, T., Chu, W., Chappell, F., Makin, S., Hayden, D., Williams, D.J., Mess, W.H., Nederkoorn, P.J., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Maaijwee, N., Guevarra, A.C., Yatawara, C., Mendyk, A.M., Delmaire, C., Köhler, S., Oostenbrugge, R van, Zhou, Y, Xu, Chao, Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Hendrikse, Jeroen, Kelly, P.J., Wardlaw, J., Soo, Y., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Engelter, S.T., Peters, Nils, Smith, E.E., Hara, H., Yakushiji, Y., Orken, D.N., Best, J.G., Ambler, G., Wilson, D., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Li, L, Lovelock, C., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H.K.F., Prats-Sanchez, L., Martínez-Domeño, A., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Tanriverdi, Z., Bornstein, N.M., Assayag, E. Ben, Hallevi, H., Molad, J., Nishihara, M., Tanaka, J., Coutts, S.B., Polymeris, A., Wagner, B., Seiffge, D.J., Lyrer, P., Algra, A., Kappelle, L.J., Al-Shahi Salman, R., Jäger, H.R., Lip, G.Y.H., Fischer, U., El-Koussy, M., Mas, J.L., Legrand, Laurence, Karayiannis, C., Phan, T., Gunkel, S., Christ, N., Abrigo, J., Leung, T., Chu, W., Chappell, F., Makin, S., Hayden, D., Williams, D.J., Mess, W.H., Nederkoorn, P.J., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Maaijwee, N., Guevarra, A.C., Yatawara, C., Mendyk, A.M., Delmaire, C., Köhler, S., Oostenbrugge, R van, Zhou, Y, Xu, Chao, Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Hendrikse, Jeroen, Kelly, P.J., Wardlaw, J., Soo, Y., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Engelter, S.T., Peters, Nils, Smith, E.E., Hara, H., Yakushiji, Y., and Orken, D.N.

Abstract

Item does not contain fulltext, BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with

Published
2021

12. Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Author

Best J.G., Ambler G., Wilson D., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Ben Assayag E., Hallevi H., Molad J., Nishihara M., Tanaka J., Coutts S.B., Polymeris A., Wagner B., Seiffge D.J., Lyrer P., Algra A., Kappelle L.J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Fischer U., El-Koussy M., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Mess W.H., Nederkoorn P.J., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra A.C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., Hendrikse J., Kelly P.J., Wardlaw J., Soo Y., Fluri F., Srikanth V., Calvet D., Jung S., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Hara H., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., Gratz P., Mattle H., Panos L., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Douven E., Delgado-Mederos R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Van Dam-Nolen D., Kooi M.E., Van der Lugt A., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Best J.G., Ambler G., Wilson D., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Ben Assayag E., Hallevi H., Molad J., Nishihara M., Tanaka J., Coutts S.B., Polymeris A., Wagner B., Seiffge D.J., Lyrer P., Algra A., Kappelle L.J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Fischer U., El-Koussy M., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Mess W.H., Nederkoorn P.J., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra A.C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., Hendrikse J., Kelly P.J., Wardlaw J., Soo Y., Fluri F., Srikanth V., Calvet D., Jung S., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Hara H., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., Gratz P., Mattle H., Panos L., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Douven E., Delgado-Mederos R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Van Dam-Nolen D., Kooi M.E., Van der Lugt A., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., and Mitchell J.

Abstract

Background: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. Method(s): We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. Finding(s): The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0.73 (95% CI 0.69-0.77) with a calibration slope of 0.94 (0.81-1.06) for the intracranial haemorrhage model and 0.63 (0.62-0.65) w

Published
2021

13. Effects of capacitive and resistive electric transfer therapy in patients with painful shoulder impingement syndrome: a comparative study

Author

Barbato C, Letizia Pezzi, Raoul Saggini, Teresa Paolucci, Rosa Grazia Bellomo, M A Centra, and Annamaria Porreca

Subjects
Special Issue: Rehabilitation, Adult, Male, 030506 rehabilitation, medicine.medical_specialty, Medicine (General), shoulder pain, medicine.medical_treatment, Capacitive sensing, case-control study, Impingement syndrome, Electric Stimulation Therapy, Biochemistry, rehabilitation, 03 medical and health sciences, thermotherapy, 0302 clinical medicine, Quality of life (healthcare), R5-920, Diathermy, medicine, Humans, In patient, Aged, Retrospective Studies, Resistive touchscreen, capacitive and resistive electric transfer therapy, Rehabilitation, business.industry, Biochemistry (medical), Cell Biology, General Medicine, Middle Aged, medicine.disease, Treatment Outcome, Shoulder Impingement Syndrome, Case-Control Studies, Physical therapy, Quality of Life, Female, Painful shoulder, 0305 other medical science, business, 030217 neurology & neurosurgery
Abstract

ObjectiveCapacitive and resistive electric transfer therapy (CARE) reduces pain and improves quality of life for many orthopaedic degenerative and inflammatory disorders. The research aim was to determine the effects of CARE on painful shoulder. The outcomes were pain reduction and recovery of shoulder function.MethodsA retrospective, observational case-control study was conducted. Participants were 46 patients (22 in the CARE group and 24 in the SHAM group). Clinical data, pain (visual analogic scale, VAS) and functional scale scores (Disabilities of the Arm, Shoulder and Hand scale, and Constant–Murley Scale) were measured at baseline T0 (before treatment), T1 (after treatment) and follow-up T2 (2 months after the end of the treatment).ResultsVAS scores in the CARE group improved from 7.23 ± 1.11 at baseline to 2.68 ± 0.99 at follow-up. The SHAM group did not experience any improvement. Similarly, functional scale scores improved in the CARE group compared with the SHAM group.ConclusionConsidering the small number of sessions needed, low cost and long-term benefits, CARE could be a useful therapeutic option for the conservative management of shoulder pain to restore pain-free and powerful movement to the shoulder joint.

Published
2020

15. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Wilson, D., Ambler, G., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Li, L, Lovelock, C., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H.K.F., Prats-Sanchez, L., Martinez-Domeno, A., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Schrooten, M., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Tanriverdi, Z., Bornstein, N.M., Assayag, E.B., Hallevi, H., Tanaka, J., Hara, H., Coutts, S.B., Hert, L., Polymeris, A., Seiffge, D.J., Lyrer, P., Algra, A., Kappelle, J., Al-Shahi Salman, R., Jager, H.R., Lip, G.Y.H., Mattle, H.P., Panos, L.D., Mas, J.L., Legrand, L., Karayiannis, C., Phan, T., Gunkel, S., Christ, N., Abrigo, J., Leung, T., Chu, W., Chappell, F., Makin, S., Hayden, D., Williams, D.J., Kooi, M.E., Dam-Nolen, D.H.K., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Maaijwee, N., Guevarra, C., Yatawara, C., Mendyk, A.M., Delmaire, C., Kohler, S., Oostenbrugge, R van, Zhou, Y, Xu, C., Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Lugt, A. van der, Kelly, P.J., Wardlaw, J.M., Soo, Y., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Engelter, S.T., Peters, N, Smith, E.E., Yakushiji, Y., Orken, D.N., Fazekas, F., Marti-Fabregas, J., Werring, D.J., Wilson, D., Ambler, G., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Li, L, Lovelock, C., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H.K.F., Prats-Sanchez, L., Martinez-Domeno, A., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Schrooten, M., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Tanriverdi, Z., Bornstein, N.M., Assayag, E.B., Hallevi, H., Tanaka, J., Hara, H., Coutts, S.B., Hert, L., Polymeris, A., Seiffge, D.J., Lyrer, P., Algra, A., Kappelle, J., Al-Shahi Salman, R., Jager, H.R., Lip, G.Y.H., Mattle, H.P., Panos, L.D., Mas, J.L., Legrand, L., Karayiannis, C., Phan, T., Gunkel, S., Christ, N., Abrigo, J., Leung, T., Chu, W., Chappell, F., Makin, S., Hayden, D., Williams, D.J., Kooi, M.E., Dam-Nolen, D.H.K., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Maaijwee, N., Guevarra, C., Yatawara, C., Mendyk, A.M., Delmaire, C., Kohler, S., Oostenbrugge, R van, Zhou, Y, Xu, C., Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Lugt, A. van der, Kelly, P.J., Wardlaw, J.M., Soo, Y., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Engelter, S.T., Peters, N, Smith, E.E., Yakushiji, Y., Orken, D.N., Fazekas, F., Marti-Fabregas, J., and Werring, D.J.

Abstract

Contains fulltext : 208975.pdf (publisher's version ) (Open Access), BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of intr

Published
2019

16. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Author

Jung S., van Dam-Nolen D.H.K., Douven E., Delgado-Mederos, R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Nishihara M., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Hendrikse J., Nederkoorn P., Mess W., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Wilson D., Ambler G., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Schrooten M., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Assayag E.B., Hallevi H., Tanaka J., Hara H., Coutts S.B., Hert L., Polymeris A., Seiffge D.J., Lyrer P., Algra A., Kappelle J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Mattle H.P., Panos L.D., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Kooi M.E., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., van der Lugt A., Kelly P.J., Wardlaw J.M., Soo Y., Fluri F., Srikanth V., Calvet D., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., El-Koussy M., Gratz P., Molad J., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Jung S., van Dam-Nolen D.H.K., Douven E., Delgado-Mederos, R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Nishihara M., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Hendrikse J., Nederkoorn P., Mess W., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Wilson D., Ambler G., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Schrooten M., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Assayag E.B., Hallevi H., Tanaka J., Hara H., Coutts S.B., Hert L., Polymeris A., Seiffge D.J., Lyrer P., Algra A., Kappelle J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Mattle H.P., Panos L.D., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Kooi M.E., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., van der Lugt A., Kelly P.J., Wardlaw J.M., Soo Y., Fluri F., Srikanth V., Calvet D., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., El-Koussy M., Gratz P., Molad J., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., and Schembri M.

Abstract

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Method(s): We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Finding(s): Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of

Published
2019

17. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Wilson, D. (Duncan), Ambler, G. (Gareth), Lee, K.-J. (Keon-Joo), Lim, J.-S. (Jae-Sung), Shiozawa, M. (Masayuki), Koga, M. (Masatoshi), Li, L. (Linxin), Lovelock, C. (Caroline), Chabriat, H. (Hugues), Hennerici, M.G. (Michael), Wong, Y.K. (Yuen Kwun), Mak, H.K.F. (Henry Ka Fung), Prats-Sánchez, L. (Luis), Martínez-Domeño, A. (Alejandro), Inamura, S. (Shigeru), Yoshifuji, K. (Kazuhisa), Arsava, E.M. (Ethem Murat), Horstmann, S. (Solveig), Purrucker, J. (Jan), Lam, B.Y.K. (Bonnie Yin Ka), Wong, A. (Adrian), Kim, Y.D. (Young Dae), Song, T.-J. (Tae-Jin), Schrooten, M. (Maarten), Lemmens, R. (Robin), Eppinger, S. (Sebastian), Gattringer, T. (Thomas), Uysal, E. (Ender), Tanriverdi, Z. (Zeynep), Bornstein, S.R. (Stefan), Assayag, E.B. (Einor Ben), Hallevi, H. (Hen), Tanaka, J. (Jun), Hara, H. (Hideo), Coutts, S.B. (Shelagh B), Hert, L. (Lisa), Polymeris, A. (Alexandros), Seiffge, D.J. (David J), Lyrer, P.A. (Philippe), Algra, A. (Ale), Kappelle, L.J. (Jaap), Al-Shahi Salman, R. (Rustam), Jäger, H.R. (Rolf), Lip, G.Y.H. (Gregory Y H), Mattle, H., Panos, L.D. (Leonidas D), Mas, J.L. (J.), Legrand, L. (Laurence), Karayiannis, C. (Christopher), Phan, T.G. (Thanh), Gunkel, S. (Sarah), Christ, N. (Nicolas), Abrigo, J. (Jill), Leung, T. (Thomas), Chu, W. (Winnie), Chappell, F. (Francesca), Makin, S. (Stephen), Hayden, D. (Derek), Williams, D.J. (David J), Kooi, M.E. (M. Eline), van Dam-Nolen, D.H.K. (Dianne H K), Barbato, C. (Carmen), Browning, S. (Simone), Wiegertjes, K. (Kim), Tuladhar, A.M. (Anil M.), Maaijwee, N. (Noortje), Guevarra, C. (Christine), Yatawara, C. (Chathuri), Mendyk, A.-M. (Anne-Marie), Delmaire, C. (Christine), Köhler, S. (Sebastian), Oostenbrugge, R.J. (Robert) van, Zhou, Y. (Ying), Xu, C. (Chao), Hilal, S. (Saima), Gyanwali, B. (Bibek), Chen, C. (Christopher), Lou, M. (Min), Staals, J. (Julie), Bordet, R. (Régis), Kandiah, N. (Nagaendran), Leeuw, H.F. (Frank) de, Simister, R. (Robert), Lugt, A. (Aad) van der, Kelly, P.J. (Peter J), Wardlaw, J.M. (J.), Soo, Y. (Yannie), Fluri, F. (Felix), Srikanth, V. (Velandai), Calvet, D. (David), Jung, S. (Simon), Kwa, V.I.H., Engelter, S.T. (Stefan), Peters, N. (Nils), Smith, E.E. (Eric), Yakushiji, Y. (Yusuke), Orken, D.N. (Dilek Necioglu), Fazekas, F. (Franz), Thijs, V. (Vincent), Heo, J.H. (Ji Hoe), Mok, V. (Vincent), Veltkamp, R. (Roland), Ay, H. (Hakan), Imaizumi, T. (Toshio), Gomez-Anson, B. (Beatriz), Lau, K.K. (Kui Kai), Jouvent, E. (Eric), Rothwell, P.M. (Peter), Toyoda, K. (Kazunori), Bae, H.-J. (Hee-Joon), Marti-Fabregas, J. (Joan), Werring, D.J. (David), Harkness, K. (Kirsty), Shaw, L. (Louise), Sword, J. (Jane), Mohd Nor, A. (Azlisham), Sharma, P. (Pankaj), Kelly, D. (Deborah), Harrington, F. (Frances), Randall, M. (Marc), Smith, M. (Matthew), Mahawish, K. (Karim), Elmarim, A. (Abduelbaset), Esisi, B. (Bernard), Cullen, C. (Claire), Nallasivam, A. (Arumug), Price, C. (Christopher), Barry, A. (Adrian), Roffe, C. (Christine), Coyle, J. (John), Hassan, A. (Ahamad), Birns, J. (Jonathan), Cohen, D. (David), Sekaran, L. (Lakshmanan), Parry-Jones, A. (Adrian), Parry, A. (Anthea), Hargroves, D. (David), Proschel, H. (Harald), Datta, P. (Prabel), Darawil, K. (Khaled), Manoj, A. (Aravindakshan), Burn, M. (Mathew), Patterson, C. (Chris), Giallombardo, E. (Elio), Smyth, N. (Nigel), Mansoor, S. (Syed), Anwar, I. (Ijaz), Marsh, R. (Rachel), Ispoglou, S. (Sissi), Chadha, D. (Dinesh), Prabhakaran, M. (Mathuri), Meenakishundaram, S. (Sanjeevikumar), O'Connell, J. (Janice), Scott, J. (Jon), Krishnamurthy, V. (Vinodh), Aghoram, P. (Prasanna), McCormick, M. (Michael), Sprigg, N. (Nikola), O'Mahony, P. (Paul), Cooper, M. (Martin), Choy, L. (Lillian), Wilkinson, P. (Peter), Leach, S. (Simon), Caine, S. (Sarah), Burger, I. (Ilse), Gunathilagan, G. (Gunaratam), Guyler, P. (Paul), Emsley, H. (Hedley), Davis, M. (Michelle), Manawadu, D. (Dulka), Pasco, K. (Kath), Mamun, M. (Maam), Luder, R. (Robert), Sajid, M. (Mahmud), Okwera, J. (James), Warburton, E. (Elizabeth), Saastamoinen, K. (Kari), England, T. (Timothy), Putterill, J. (Janet), Flossman, E. (Enrico), Power, M. (Michael), Dani, K. (Krishna), Mangion, D. (David), Suman, A. (Appu), Corrigan, J. (John), Lawrence, E. (Enas), Vahidassr, D. (Djamil), Shakeshaft, C. (Clare), Brown, M. (Martin), Charidimou, A. (Andreas), Cohen, H. (Hannah), Banerjee, G. (Gargi), Houlden, H. (Henry), White, M. (Mark), Yousry, T. (Tarek), Flossmann, E. (Enrico), Muir, K. (Keith), El-Koussy, M. (Marwan), Gratz, P. (Pascal), Molad, J. (Jeremy), Korczyn, A.D. (A.), Kliper, E. (Efrat), Maeder, P. (Philippe), Gass, A. (Achim), Pachai, C. (Chahin), Bracoub, L. (Luc), Douste-Blazy, M.-Y. (Marie-Yvonne), Fratacci, M.D. (Marie Dominique), Vicaut, E. (Eric), Sato, S. (Shoichiro), Miwa, K. (Kaori), Fujita, K. (Kyohei), Ide, T. (Toshihiro), Ma, H. (Henry), Ly, J. (John), Singhal, S. (Shahoo), Chandra, R. (Ronil), Slater, L.-A. (Lee-Anne), Soufan, C. (Cathy), Moran, C. (Christopher), Traenka, C. (Christopher), Thilemann, S. (Sebastian), Fladt, J. (Joachim), Gensicke, H. (Henrik), Bonati, L. (Leo), Kim, B.J. (Beom Joon), Han, M.-K. (Moon-Ku), Kang, J. (Jihoon), Ko, E. (Eunbin), Yang, M.H. (Mi Hwa), Jang, M.S. (Myung Suk), Murphy, S. (Sean), Carty, F. (Fiona), Akijian, L. (Layan), Thornton, J. (John), Schembri, M. (Mark), Douven, E. (Elles), Delgado-Mederos;, R. (Raquel), Marín, R. (Rebeca), Camps-Renom, P. (Pol), Guisado-Alonso, D. (Daniel), Nuñez, F. (Fidel), Medrano-Martorell, S. (Santiago), Merino, E. (Elisa), Iida, K. (Kotaro), Ikeda, S. (Syuhei), Nishihara, M. (Masashi), Irie, H. (Hiroyuki), Demirelli, D.S. (Derya Selcuk), Medanta, J.M. (Jayesh Modi), Zerna, C. (Charlotte), Hernández, M.V. (Maria Valdés), Armitage, P. (Paul), Heye, A. (Anna), Muñoz Maniega, S. (Susana), Sakka, E. (Eleni), Thrippleton, M. (Michael), Dennis, M.S. (M.), Beigneux, Y. (Ysoline), Silva, M. (Mauro), Venketasubramanian, N. (Narayanaswamy), Ho, S.L. (Shu Leung), Cheung, R.T.F. (Raymond Tak Fai), Chan, K.H. (Koon Ho), Teo, K.C. (Kay Cheong), Hui, E. (Edward), Kwan, J.S.K. (Joseph Shiu Kwong), Chang, R. (Richard), Tse, M.Y. (Man Yu), Hoi, C.P. (Chu Peng), Chan, C.Y. (Chung Yan), Chan, O.L. (Oi Ling), Cheung, R.H.K. (Ryan Hoi Kit), Wong, E.K.M. (Edmund Ka Ming), Leung, K.T. (Kam Tat), Tsang, S.F. (Suk Fung), Ip, H.L. (Hing Lung), Ma, S.H. (Sze Ho), Ma, K. (Karen), Fong, W.C. (Wing Chi), Li, S.H. (Siu Hung), Li, R. (Richard), Ng, P.W. (Ping Wing), Wong, K.K. (Kwok Kui), Liu, W. (Wenyan), Wong, L. (Lawrence), Ramos, L. (Lino), Schryver, E.L.L.M. (Els) de, Jöbsis, J. (Joost), van der Sande, J. (Jaap), Brouwers, P.J. (Paul), Roos, Y.B.W.E.M. (Yvo), Stam, J. (Jan), Bakker, S.L.M. (Stef), Verbiest, H. (Henk), Schoonewille, W. (Wouter), Linn, C. (Cisca), Hertzberger, L., Gemert, M. (Maarten) van, Berntsen, P. (Paul), Hendrikse, J. (Jeroen), Nederkoorn, P.J. (Paul), Mess, W.H. (Werner), Koudstaal, P.J. (Peter), Leff, A. (Alexander), Ward, N. (Nicholas), Nachev, P. (Parashkev), Perry, R. (Richard), Ozkan, H. (Hatice), Mitchell, J. (John), Wilson, D. (Duncan), Ambler, G. (Gareth), Lee, K.-J. (Keon-Joo), Lim, J.-S. (Jae-Sung), Shiozawa, M. (Masayuki), Koga, M. (Masatoshi), Li, L. (Linxin), Lovelock, C. (Caroline), Chabriat, H. (Hugues), Hennerici, M.G. (Michael), Wong, Y.K. (Yuen Kwun), Mak, H.K.F. (Henry Ka Fung), Prats-Sánchez, L. (Luis), Martínez-Domeño, A. (Alejandro), Inamura, S. (Shigeru), Yoshifuji, K. (Kazuhisa), Arsava, E.M. (Ethem Murat), Horstmann, S. (Solveig), Purrucker, J. (Jan), Lam, B.Y.K. (Bonnie Yin Ka), Wong, A. (Adrian), Kim, Y.D. (Young Dae), Song, T.-J. (Tae-Jin), Schrooten, M. (Maarten), Lemmens, R. (Robin), Eppinger, S. (Sebastian), Gattringer, T. (Thomas), Uysal, E. (Ender), Tanriverdi, Z. (Zeynep), Bornstein, S.R. (Stefan), Assayag, E.B. (Einor Ben), Hallevi, H. (Hen), Tanaka, J. (Jun), Hara, H. (Hideo), Coutts, S.B. (Shelagh B), Hert, L. (Lisa), Polymeris, A. (Alexandros), Seiffge, D.J. (David J), Lyrer, P.A. (Philippe), Algra, A. (Ale), Kappelle, L.J. (Jaap), Al-Shahi Salman, R. (Rustam), Jäger, H.R. (Rolf), Lip, G.Y.H. (Gregory Y H), Mattle, H., Panos, L.D. (Leonidas D), Mas, J.L. (J.), Legrand, L. (Laurence), Karayiannis, C. (Christopher), Phan, T.G. (Thanh), Gunkel, S. (Sarah), Christ, N. (Nicolas), Abrigo, J. (Jill), Leung, T. (Thomas), Chu, W. (Winnie), Chappell, F. (Francesca), Makin, S. (Stephen), Hayden, D. (Derek), Williams, D.J. (David J), Kooi, M.E. (M. Eline), van Dam-Nolen, D.H.K. (Dianne H K), Barbato, C. (Carmen), Browning, S. (Simone), Wiegertjes, K. (Kim), Tuladhar, A.M. (Anil M.), Maaijwee, N. (Noortje), Guevarra, C. (Christine), Yatawara, C. (Chathuri), Mendyk, A.-M. (Anne-Marie), Delmaire, C. (Christine), Köhler, S. (Sebastian), Oostenbrugge, R.J. (Robert) van, Zhou, Y. (Ying), Xu, C. (Chao), Hilal, S. (Saima), Gyanwali, B. (Bibek), Chen, C. (Christopher), Lou, M. (Min), Staals, J. (Julie), Bordet, R. (Régis), Kandiah, N. (Nagaendran), Leeuw, H.F. (Frank) de, Simister, R. (Robert), Lugt, A. (Aad) van der, Kelly, P.J. (Peter J), Wardlaw, J.M. (J.), Soo, Y. (Yannie), Fluri, F. (Felix), Srikanth, V. (Velandai), Calvet, D. (David), Jung, S. (Simon), Kwa, V.I.H., Engelter, S.T. (Stefan), Peters, N. (Nils), Smith, E.E. (Eric), Yakushiji, Y. (Yusuke), Orken, D.N. (Dilek Necioglu), Fazekas, F. (Franz), Thijs, V. (Vincent), Heo, J.H. (Ji Hoe), Mok, V. (Vincent), Veltkamp, R. (Roland), Ay, H. (Hakan), Imaizumi, T. (Toshio), Gomez-Anson, B. (Beatriz), Lau, K.K. (Kui Kai), Jouvent, E. (Eric), Rothwell, P.M. (Peter), Toyoda, K. (Kazunori), Bae, H.-J. (Hee-Joon), Marti-Fabregas, J. (Joan), Werring, D.J. (David), Harkness, K. (Kirsty), Shaw, L. (Louise), Sword, J. (Jane), Mohd Nor, A. (Azlisham), Sharma, P. (Pankaj), Kelly, D. (Deborah), Harrington, F. (Frances), Randall, M. (Marc), Smith, M. (Matthew), Mahawish, K. (Karim), Elmarim, A. (Abduelbaset), Esisi, B. (Bernard), Cullen, C. (Claire), Nallasivam, A. (Arumug), Price, C. (Christopher), Barry, A. (Adrian), Roffe, C. (Christine), Coyle, J. (John), Hassan, A. (Ahamad), Birns, J. (Jonathan), Cohen, D. (David), Sekaran, L. (Lakshmanan), Parry-Jones, A. (Adrian), Parry, A. (Anthea), Hargroves, D. (David), Proschel, H. (Harald), Datta, P. (Prabel), Darawil, K. (Khaled), Manoj, A. (Aravindakshan), Burn, M. (Mathew), Patterson, C. (Chris), Giallombardo, E. (Elio), Smyth, N. (Nigel), Mansoor, S. (Syed), Anwar, I. (Ijaz), Marsh, R. (Rachel), Ispoglou, S. (Sissi), Chadha, D. (Dinesh), Prabhakaran, M. (Mathuri), Meenakishundaram, S. (Sanjeevikumar), O'Connell, J. (Janice), Scott, J. (Jon), Krishnamurthy, V. (Vinodh), Aghoram, P. (Prasanna), McCormick, M. (Michael), Sprigg, N. (Nikola), O'Mahony, P. (Paul), Cooper, M. (Martin), Choy, L. (Lillian), Wilkinson, P. (Peter), Leach, S. (Simon), Caine, S. (Sarah), Burger, I. (Ilse), Gunathilagan, G. (Gunaratam), Guyler, P. (Paul), Emsley, H. (Hedley), Davis, M. (Michelle), Manawadu, D. (Dulka), Pasco, K. (Kath), Mamun, M. (Maam), Luder, R. (Robert), Sajid, M. (Mahmud), Okwera, J. (James), Warburton, E. (Elizabeth), Saastamoinen, K. (Kari), England, T. (Timothy), Putterill, J. (Janet), Flossman, E. (Enrico), Power, M. (Michael), Dani, K. (Krishna), Mangion, D. (David), Suman, A. (Appu), Corrigan, J. (John), Lawrence, E. (Enas), Vahidassr, D. (Djamil), Shakeshaft, C. (Clare), Brown, M. (Martin), Charidimou, A. (Andreas), Cohen, H. (Hannah), Banerjee, G. (Gargi), Houlden, H. (Henry), White, M. (Mark), Yousry, T. (Tarek), Flossmann, E. (Enrico), Muir, K. (Keith), El-Koussy, M. (Marwan), Gratz, P. (Pascal), Molad, J. (Jeremy), Korczyn, A.D. (A.), Kliper, E. (Efrat), Maeder, P. (Philippe), Gass, A. (Achim), Pachai, C. (Chahin), Bracoub, L. (Luc), Douste-Blazy, M.-Y. (Marie-Yvonne), Fratacci, M.D. (Marie Dominique), Vicaut, E. (Eric), Sato, S. (Shoichiro), Miwa, K. (Kaori), Fujita, K. (Kyohei), Ide, T. (Toshihiro), Ma, H. (Henry), Ly, J. (John), Singhal, S. (Shahoo), Chandra, R. (Ronil), Slater, L.-A. (Lee-Anne), Soufan, C. (Cathy), Moran, C. (Christopher), Traenka, C. (Christopher), Thilemann, S. (Sebastian), Fladt, J. (Joachim), Gensicke, H. (Henrik), Bonati, L. (Leo), Kim, B.J. (Beom Joon), Han, M.-K. (Moon-Ku), Kang, J. (Jihoon), Ko, E. (Eunbin), Yang, M.H. (Mi Hwa), Jang, M.S. (Myung Suk), Murphy, S. (Sean), Carty, F. (Fiona), Akijian, L. (Layan), Thornton, J. (John), Schembri, M. (Mark), Douven, E. (Elles), Delgado-Mederos;, R. (Raquel), Marín, R. (Rebeca), Camps-Renom, P. (Pol), Guisado-Alonso, D. (Daniel), Nuñez, F. (Fidel), Medrano-Martorell, S. (Santiago), Merino, E. (Elisa), Iida, K. (Kotaro), Ikeda, S. (Syuhei), Nishihara, M. (Masashi), Irie, H. (Hiroyuki), Demirelli, D.S. (Derya Selcuk), Medanta, J.M. (Jayesh Modi), Zerna, C. (Charlotte), Hernández, M.V. (Maria Valdés), Armitage, P. (Paul), Heye, A. (Anna), Muñoz Maniega, S. (Susana), Sakka, E. (Eleni), Thrippleton, M. (Michael), Dennis, M.S. (M.), Beigneux, Y. (Ysoline), Silva, M. (Mauro), Venketasubramanian, N. (Narayanaswamy), Ho, S.L. (Shu Leung), Cheung, R.T.F. (Raymond Tak Fai), Chan, K.H. (Koon Ho), Teo, K.C. (Kay Cheong), Hui, E. (Edward), Kwan, J.S.K. (Joseph Shiu Kwong), Chang, R. (Richard), Tse, M.Y. (Man Yu), Hoi, C.P. (Chu Peng), Chan, C.Y. (Chung Yan), Chan, O.L. (Oi Ling), Cheung, R.H.K. (Ryan Hoi Kit), Wong, E.K.M. (Edmund Ka Ming), Leung, K.T. (Kam Tat), Tsang, S.F. (Suk Fung), Ip, H.L. (Hing Lung), Ma, S.H. (Sze Ho), Ma, K. (Karen), Fong, W.C. (Wing Chi), Li, S.H. (Siu Hung), Li, R. (Richard), Ng, P.W. (Ping Wing), Wong, K.K. (Kwok Kui), Liu, W. (Wenyan), Wong, L. (Lawrence), Ramos, L. (Lino), Schryver, E.L.L.M. (Els) de, Jöbsis, J. (Joost), van der Sande, J. (Jaap), Brouwers, P.J. (Paul), Roos, Y.B.W.E.M. (Yvo), Stam, J. (Jan), Bakker, S.L.M. (Stef), Verbiest, H. (Henk), Schoonewille, W. (Wouter), Linn, C. (Cisca), Hertzberger, L., Gemert, M. (Maarten) van, Berntsen, P. (Paul), Hendrikse, J. (Jeroen), Nederkoorn, P.J. (Paul), Mess, W.H. (Werner), Koudstaal, P.J. (Peter), Leff, A. (Alexander), Ward, N. (Nicholas), Nachev, P. (Parashkev), Perry, R. (Richard), Ozkan, H. (Hatice), and Mitchell, J. (John)

Abstract

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or

Published
2019
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18. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Wilson, D, Ambler, G, Lee, K-J, Lim, J-S, Shiozawa, M, Koga, M, Li, L, Lovelock, C, Chabriat, H, Hennerici, M, Wong, YK, Mak, HKF, Prats-Sanchez, L, Martinez-Domeno, A, Inamura, S, Yoshifuji, K, Arsava, EM, Horstmann, S, Purrucker, J, Lam, BYK, Wong, A, Kim, YD, Song, T-J, Schrooten, M, Lemmens, R, Eppinger, S, Gattringer, T, Uysal, E, Tanriverdi, Z, Bornstein, NM, Ben Assayag, E, Hallevi, H, Tanaka, J, Hara, H, Coutts, SB, Hert, L, Polymeris, A, Seiffge, DJ, Lyrer, P, Algra, A, Kappelle, J, Salman, RA-S, Jager, HR, Lip, GYH, Mattle, HP, Panos, LD, Mas, J-L, Legrand, L, Karayiannis, C, Phan, T, Gunkel, S, Christ, N, Abrigo, J, Leung, T, Chu, W, Chappell, F, Makin, S, Hayden, D, Williams, DJ, Kooi, ME, van Dam-Nolen, DHK, Barbato, C, Browning, S, Wiegertjes, K, Tuladhar, AM, Maaijwee, N, Guevarra, C, Yatawara, C, Mendyk, A-M, Delmaire, C, Kohler, S, van Oostenbrugge, R, Zhou, Y, Xu, C, Hilal, S, Gyanwali, B, Chen, C, Lou, M, Staals, J, Bordet, R, Kandiah, N, de Leeuw, F-E, Simister, R, van der Lugt, A, Kelly, PJ, Wardlaw, JM, Soo, Y, Fluri, F, Srikanth, V, Calvet, D, Jung, S, Kwa, VIH, Engelter, ST, Peters, N, Smith, EE, Yakushiji, Y, Orken, DN, Fazekas, F, Thijs, V, Heo, JH, Mok, V, Veltkamp, R, Ay, H, Imaizumi, T, Gomez-Anson, B, Lau, KK, Jouvent, E, Rothwell, PM, Toyoda, K, Bae, H-J, Marti-Fabregas, J, Werring, DJ, Wilson, D, Ambler, G, Lee, K-J, Lim, J-S, Shiozawa, M, Koga, M, Li, L, Lovelock, C, Chabriat, H, Hennerici, M, Wong, YK, Mak, HKF, Prats-Sanchez, L, Martinez-Domeno, A, Inamura, S, Yoshifuji, K, Arsava, EM, Horstmann, S, Purrucker, J, Lam, BYK, Wong, A, Kim, YD, Song, T-J, Schrooten, M, Lemmens, R, Eppinger, S, Gattringer, T, Uysal, E, Tanriverdi, Z, Bornstein, NM, Ben Assayag, E, Hallevi, H, Tanaka, J, Hara, H, Coutts, SB, Hert, L, Polymeris, A, Seiffge, DJ, Lyrer, P, Algra, A, Kappelle, J, Salman, RA-S, Jager, HR, Lip, GYH, Mattle, HP, Panos, LD, Mas, J-L, Legrand, L, Karayiannis, C, Phan, T, Gunkel, S, Christ, N, Abrigo, J, Leung, T, Chu, W, Chappell, F, Makin, S, Hayden, D, Williams, DJ, Kooi, ME, van Dam-Nolen, DHK, Barbato, C, Browning, S, Wiegertjes, K, Tuladhar, AM, Maaijwee, N, Guevarra, C, Yatawara, C, Mendyk, A-M, Delmaire, C, Kohler, S, van Oostenbrugge, R, Zhou, Y, Xu, C, Hilal, S, Gyanwali, B, Chen, C, Lou, M, Staals, J, Bordet, R, Kandiah, N, de Leeuw, F-E, Simister, R, van der Lugt, A, Kelly, PJ, Wardlaw, JM, Soo, Y, Fluri, F, Srikanth, V, Calvet, D, Jung, S, Kwa, VIH, Engelter, ST, Peters, N, Smith, EE, Yakushiji, Y, Orken, DN, Fazekas, F, Thijs, V, Heo, JH, Mok, V, Veltkamp, R, Ay, H, Imaizumi, T, Gomez-Anson, B, Lau, KK, Jouvent, E, Rothwell, PM, Toyoda, K, Bae, H-J, Marti-Fabregas, J, and Werring, DJ

Abstract

BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intr

Published
2019

19. Staying tuned for post-COVID-19 syndrome: looking for new research to sniff out.

Author

BARBATO, C., DI CERTO, M. G., GABANELLA, F., PETRELLA, C., FIORE, M., PASSANANTI, C., COLIZZA, A., CAVALCANTI, L., RALLI, M., GRECO, A., DE VINCENTIIS, M., and MINNI, A.

Abstract

Post-COVID-19 syndrome was defined as a persistent and protracted illness, which follows acute COVID-19 infection. This condition continues for more than 12 weeks and cannot be attributed to other clinical situations. Researchers and clinicians are allied in unraveling the molecular pathogenetic mechanisms and the clinical development of this unexpected SARS-CoV-2 infectious evolution. Anosmia, dysgeusia, fatigue, dyspnea, and 'brain fog' are common symptoms observed in the Post-COVID-19 syndrome, depicting a multiorgan involvement associated with injuries involving mainly cardiovascular, pulmonary, musculoskeletal, and neuropsychiatric systems. This commentary analyzes the state of the art of Post-COVID-19 interdisciplinary studies, confirming that we are facing a truly intricate biomedicine story. [ABSTRACT FROM AUTHOR]

Published
2021

21. S43ZeOxaNMulti trial: a randomized, double-blinded, placebo-controlled trial of oral zeolite 'Multizeo Med' (based on PMA-zeolite – a double activated zeolite clinoptilolite called also Panalite) to prevent chemotherapy-induced side effects, in particular peripheral neuropathy

Author

Vitale, M. G., Barbato, C., HABETSWALLNER, Francesco, De Martino, B. M., Sirico, F., Crispo, A., Cartenì, G., Vitale, M. G., Barbato, C., Habetswallner, Francesco, De Martino, B. M., Sirico, F., Crispo, A., and Cartenì, G.

Published
2016

25. MicroRNA Landscape in Alzheimer's Disease

Author

Cogoni C, Ruberti F, and Barbato C

Subjects
MicroRNAs, gene silencing, microRNA, Alzheimer Disease, Alzheimer, Brain, Humans, microRNA, Alzheimer, gene silencing
Abstract

Individual microRNAs and/or microRNA signatures were associated with AD. We report here the recent advances brought to the identification of microRNA changes in Alzheimer's disease (AD) brain and their biological function in the molecular pathways associated with the disease. This field represents a fertile route to understand the pathogenic mechanisms underlying Alzheimer's disease. In addition we review recent studies aimed to discover promising biomarkers for AD diagnosis by microRNA expression profiles of biofluids from AD patients.

Published
2015
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26. MicroRNA expression profiling and ALzheimer's disease

Author

D'ONOFRIO M, ARISI I, BRANDI R, DI MAMBRO A, FELSANI A, BARBATO C, COGONI C, CAPSONI, SIMONA, CATTANEO, ANTONINO, D'Onofrio, M, Arisi, I, Brandi, R, DI MAMBRO, A, Felsani, A, Barbato, C, Cogoni, C, Capsoni, Simona, and Cattaneo, Antonino

Published
2009

28. Use of anti-tumor necrosis factor alpha therapy in patients with concurrent rheumatoid arthritis and hepatitis B or hepatitis C: a retrospective analysis of 32 patients

Author

Ballanti, E, Conigliaro, P, Chimenti, Ms, Kroegler, B, DI MUZIO, G, Guarino, Md, Triggianese, P, Gigliucci, G, Novelli, L, Barbato, C, and Perricone, R

Subjects
rheumatoid arthritis, Male, Comorbidity, Antibodies, Monoclonal, Humanized, Antibodies, Receptors, Tumor Necrosis Factor, Etanercept, Arthritis, Rheumatoid, Rheumatoid, Monoclonal, Receptors, Humans, Aspartate Aminotransferases, Humanized, Aged, Retrospective Studies, Tumor Necrosis Factor-alpha, Arthritis, Adalimumab, Alanine Transaminase, anti-TNF, Middle Aged, Hepatitis B, hepatitis B, hepatitis C, Antirheumatic Agents, Female, Hepatitis C, Immunoglobulin G, Italy, Settore MED/16 - Reumatologia, Tumor Necrosis Factor
Abstract

The safety of tumor necrosis factor-alpha (TNF-α) inhibitors in the setting of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is controversial. The use of anti-TNF-α in rheumatoid arthritis (RA) is associated with an increased risk of hepatitis re-activation. This paper reports experience of using etanercept and adalimumab in 32 patients with RA and previous HBV or HCV infection. No cases of HBV or HCV reactivation were seen. In just over a fifth of patients, increased transaminases levels were seen, which were associated with concomitant use of disease-modifying antirheumatic drugs, isoniazid prophylaxis, or alcohol abuse. In our experience, anti-TNF-α therapy appears to be safe in RA patients with previous HBV or HCV infection, but monitoring remains necessary in these patients.

Published
2014

29. Selective inhibition of miR-92 in hippocampal neurons alters contextual fear memory

Author

Vetere, G., Barbato, C., Pezzola, S., Frisone, P., Aceti, M., Ciotti, M. T., Cogoni, Carlo, Ammassari Teule, M., and Ruberti, F.

Subjects
Neurons, Symporters, MEF2 Transcription Factors, Dendritic Spines, Conditioning, Classical, RNA-Binding Proteins, Fear, Hippocampus, Mice, Inbred C57BL, MicroRNAs, Memory, Animals, Rats, Wistar, Cells, Cultured
Abstract

Post-transcriptional gene regulation mediated by microRNAs (miRNAs) is implicated in memory formation; however, the function of miR-92 in this regulation is uncharacterized. The present study shows that training mice in contextual fear conditioning produces a transient increase in miR-92 levels in the hippocampus and decreases several miR-92 gene targets, including: (i) the neuronal Cl(-) extruding K(+) Cl(-) co-transporter 2 (KCC2) protein; (ii) the cytoplasmic polyadenylation protein (CPEB3), an RNA-binding protein regulator of protein synthesis in neurons; and (iii) the transcription factor myocyte enhancer factor 2D (MEF2D), one of the MEF2 genes which negatively regulates memory-induced structural plasticity. Selective inhibition of endogenous miR-92 in CA1 hippocampal neurons, by a sponge lentiviral vector expressing multiple sequences imperfectly complementary to mature miR-92 under the control of the neuronal specific synapsin promoter, leads to up-regulation of KCC2, CPEB3 and MEF2D, impairs contextual fear conditioning, and prevents a memory-induced increase in the spine density. Taken together, the results indicate that neuronal-expressed miR-92 is an endogenous fine regulator of contextual fear memory in mice.

Published
2014

30. ZeOxaNMulti trial: a randomized, double-blinded, placebo-controlled trial of oral zeolite “Multizeo Med” (based on PMA-zeolite – a double activated zeolite clinoptilolite called also Panalite) to prevent chemotherapy-induced side effects, in particular peripheral neuropathy

Author

Vitale, M.G., primary, Barbato, C., additional, Habetswallner, F., additional, De Martino, B.M., additional, Sirico, F., additional, Crispo, A., additional, and Cartenì, G., additional

Published
2016
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31. Serological Screening of Celiac Disease: Choosing the best tests under two years

Author

Martellossi, S, Baldas, V, Barbato, C, Bonamico, M, Fontana, M, Gasperrini, G, Lambertini, A, Lionetti, P, Romano, C, Troncone, R., ACCOMANDO, Salvatore, Accomando, S, Barbato, M, Bonamico, M, Fontana, G, Gasperrini, M, Lambertini, R, Lionetti, P, Romano, C, Troncone, R, Baldas, V, Martellossi, S, Barbato, C, Fontana, M, Gasperrini, G, and Lambertini, A

Subjects
Aga, Celiachia, Settore MED/38 - Pediatria Generale E Specialistica, Aga, Serology
Published
2005

35. Neurotrasmettitori

Author

Barbato, C and Canu, N

Subjects
Settore BIO/09
Published
2010

37. Che-1 enhances cyclin-dependent kinase 5 expression and interacts with the active kinase-complex

Author

Buontempo S, Barbato C, Bruno T, Corbi N, Ciotti MT, Floridi A, Fanciulli M, and Passananti C.

Subjects
nervous system
Abstract

Che-1 is a nuclear protein involved in the regulation of gene transcription and cell proliferation. It has also been shown to localize to the cytoplasm of postmitotic neuronal cells, where it is able to interact with the microtubule-associated protein tau. Cyclin-dependent kinase 5 (Cdk5) is a postmitotic proline-directed serine/threonine kinase that hyperphosphorylates tau under pathological conditions. We observed that Che-1 overexpression induces Cdk5 expression both at the mRNA and protein levels. Furthermore, we show that Che-1 directly interacts with Cdk5 protein in vivo. Cdk5/Che-1 complex formation does not compete with Cdk5/p35 interaction, thus Che-1 is able to bind the active kinase complex. Finally, we demonstrated that Che-1 is itself a Cdk5 substrate.

Published
2008

40. THU0281 Use of Anti-Tumor Necrosis Factor Alpha Therapy in Patients with Inflammatory Arthritis and Concurrent History of Hepatitis B or Hepatitis C Infection: A Retrospective Analysis of 44 Patients

Author

Ballanti, E., primary, Conigliaro, P., additional, Chimenti, M.S., additional, Barbato, C., additional, Kroegler, B., additional, Di Muzio, G., additional, Guarino, M.D., additional, Triggianese, P., additional, Gigliucci, G., additional, Novelli, L., additional, Duca, I., additional, and Perricone, R., additional

Published
2014
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41. Rb binding protein Che-1 interacts with Tau in cerebellar granule neurons: Modulation during neuronal apoptosis

Author

Barbato C., Corbi N., Canu N., Fanciulli M., Serafino A., Ciotti M.T., Libri V., Bruno T., Amadoro G., De Angelis R., Calissano P., and Passananti C.

Subjects
cerebellum, Wistar, morphogenesis, protein assembly, binding protein, Apoptosis, tau Proteins, protein binding, protein localization, immunoprecipitation, Retinoblastoma Protein, Settore BIO/09, tau protein, Cercopithecus aethiops, cell lysate, Dogs, CheA kinase, Chlorocebus aethiops, Animals, Humans, human, nerve fiber, protein interaction, Rats, Wistar, protein expression, Neurons, human cell, article, cell line, protein function, Rats, priority journal, protein analysis, Checkpoint Kinase 1, Mutation, cytoplasm, protein transport, cell cycle, apoptosis, cell structure, microtubule, nerve cell, Cerebellum, Protein Binding, Protein Kinases
Abstract

Che-1 is a recently identified human Rb binding protein that inhibits the Rb growth-suppressing function and regulates cell proliferation. Che-1 contacts the Rb and competes with HDAC1 for Rb-binding site, removing HDAC1 from the Rb/E2F cell cycle-regulated promoters. We have investigated the expression of Che-1 in neuronal cells and we showed that Che-1 directly interacts with Tau. Tau is a microtubule-associated protein involved in the assembly and stabilization of neuronal microtubules network that plays a crucial role modulating neuronal morphogenesis, axonal shape, and transport. In rat cerebellar granule neurons (CGNs) Che-1 partially colocalizes with Tau in the cytoplasm. Che-1 binds the amino-terminal region of Tau protein, which is not involved in microtubule interactions. Tau and Che-1 endogenous proteins coimmunoprecipitate from CGNs cellular lysates. In addition, Che-1/Tau interaction was demonstrated both in overexpressing COS-7 cells and CGNs by FRET analysis. Finally, we observed that Tau/Che-1 interaction is modulated during neuronal apoptosis.

Published
2003

42. A tachykinin-like factor increases glutamate toxicity in rat cerebellar granule cells

Author

Severini C. 1, Ciotti M.T. 2, Mercanti D. 3, Barbato C. 4, and Calissano P. 5

Subjects
nervous system, Neurokinin B, Neurokinin A, Excitotoxicity, Glutamate toxicity, Cerebellar Granule Cells
Abstract

Tachykinins (TKs), which include substance P, neurokinin A and neurokinin B, constitute a group of neuropeptides widely expressed in the CNS where they play several functions connected with neural modulation often in synergy with glutamate excitatory transmission. The aim of this study was to assess whether TKs modulate glutamate response of in vitro cultured cerebellar granule neurons and whether GSA (glutamate-sensitizing activity), a peptide released by these neurons, belongs to the TKs family. Treatment with substance P and other neurokinin 1 receptor (NK1) agonists does not affect the response of cerebellar granule neurons to glutamate toxicity. On the contrary, agonists neurokinin 2 receptor (NK2) and neurokinin 3 receptor (NK3) agonists increase, in a dose and time dependent fashion, the response of the same neurons to glutamate. MEN 10,627, a selective NK2 receptor antagonist, and (Trp(7),betaAla(8)) NKA (4-10), a selective NK3 receptor antagonist inhibit not only the sensitizing action to glutamate of their respective agonists. These antagonists almost equally reduce the glutamate-sensitizing activity of GSA. Such activity is also abolished in the presence of a polyclonal antibody directed against neurokinin B (NKB). These findings indicate that TKs increase glutamate sensitivity in cerebellar granule neurons and that the GSA previously detected in conditioned media of the same cultured neurons belongs to the TK family although its primary structure as compared to known TKs remains to be established.

Published
2003

43. Rb binding protein Che-1 interacts with Tau cerebellar granule neurons. Modulation during neuronal apoptosis

Author

Barbato C, Corbi N, Canu N, Fanciulli M, Serafino A, Ciotti M, Libri V, Bruno T, Amadoro G, De Angelis R, Calissano P, and Passananti C.

Abstract

Che-1 is a recently identified human Rb binding protein that inhibits the Rb growth-suppressing function and regulates cell proliferation. Che-1 contacts the Rb and competes with HDAC1 for Rb-binding site, removing HDAC1 from the Rb/E2F cell cycle-regulated promoters. We have investigated the expression of Che-1 in neuronal cells and we showed that Che-1 directly interacts with Tau. Tau is a microtubule-associated protein involved in the assembly and stabilization of neuronal microtubules network that plays a crucial role modulating neuronal morphogenesis, axonal shape, and transport. In rat cerebellar granule neurons (CGNs) Che-1 partially colocalizes with Tau in the cytoplasm. Che-1 binds the amino-terminal region of Tau protein, which is not involved in microtubule interactions. Tau and Che-1 endogenous proteins coimmunoprecipitate from CGNs cellular lysates. In addition, Che-1/Tau interaction was demonstrated both in overexpressing COS-7 cells and CGNs by FRET analysis. Finally, we observed that Tau/Che-1 interaction is modulated during neuronal apoptosis.

Published
2002

50. Neuroendocrine Tumors Diagnosed at the “Antonio Cardarelli” Hospital (Naples, Campania, Italy) between 2006–2009: A Single-Institution Analysis

Author

Riccardi, F., primary, Nappi, O., additional, Balzano, A., additional, De Palma, M., additional, Buonerba, C., additional, Rizzo, M., additional, Barbato, C., additional, De Dominicis, G., additional, Buonocore, U., additional, De Sena, G., additional, Lastoria, S., additional, Molino, C., additional, Monaco, G., additional, Rabitti, P.G., additional, Romano, L., additional, Scavuzzo, F., additional, Suozzo, R., additional, Uomo, G., additional, Volpe, R., additional, Di Lorenzo, G., additional, and Cartenì, G., additional

Published
2011
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