Author: "Gialluisi A" / Topic: male - Searchworks@Jio Institute Digital Library Search Results

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31 results on '"Gialluisi A"'

1. Identification of sixteen novel candidate genes for late onset Parkinson’s disease

Author: Gialluisi, Alessandro, Reccia, Mafalda Giovanna, Modugno, Nicola, Nutile, Teresa, Lombardi, Alessia, Di Giovannantonio, Luca Giovanni, Pietracupa, Sara, Ruggiero, Daniela, Scala, Simona, Gambardella, Stefano, Iacoviello, Licia, Gianfrancesco, Fernando, Acampora, Dario, D’Esposito, Maurizio, Simeone, Antonio, Ciullo, Marina, and Esposito, Teresa
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Prevention, Brain Disorders, Aging, Neurodegenerative, Parkinson's Disease, Clinical Research, Neurosciences, Aetiology, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, 2.1 Biological and endogenous factors, Neurological, Adult, Age of Onset, Aged, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Parkinson Disease, Pedigree, Exome Sequencing, International Parkinson’s Disease Genomics Consortium, Late onset Parkinson’s disease, Novel candidate genes for Parkinson’s disease, Rare variant burden analysis, Whole exome sequencing, Clinical Sciences, Neurology & Neurosurgery, Biochemistry and cell biology
Abstract: BackgroundParkinson's disease (PD) is a neurodegenerative movement disorder affecting 1-5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis of PD.MethodsThe study includes a discovery stage based on the analysis of whole exome data from 26 dominant late onset PD families, a validation analysis performed on 1542 independent PD patients and 706 controls from different cohorts and the assessment of polygenic variants load in the Italian cohort (394 unrelated patients and 203 controls).ResultsFamily-based approach identified 28 disrupting variants in 26 candidate genes for PD including PARK2, PINK1, DJ-1(PARK7), LRRK2, HTRA2, FBXO7, EIF4G1, DNAJC6, DNAJC13, SNCAIP, AIMP2, CHMP1A, GIPC1, HMOX2, HSPA8, IMMT, KIF21B, KIF24, MAN2C1, RHOT2, SLC25A39, SPTBN1, TMEM175, TOMM22, TVP23A and ZSCAN21. Sixteen of them have not been associated to PD before, were expressed in mesencephalon and were involved in pathways potentially deregulated in PD. Mutation analysis in independent cohorts disclosed a significant excess of highly deleterious variants in cases (p = 0.0001), supporting their role in PD. Moreover, we demonstrated that the co-inheritance of multiple rare variants (≥ 2) in the 26 genes may predict PD occurrence in about 20% of patients, both familial and sporadic cases, with high specificity (> 93%; p = 4.4 × 10- 5). Moreover, our data highlight the fact that the genetic landmarks of late onset PD does not systematically differ between sporadic and familial forms, especially in the case of small nuclear families and underline the importance of rare variants in the genetics of sporadic PD. Furthermore, patients carrying multiple rare variants showed higher risk of manifesting dyskinesia induced by levodopa treatment.ConclusionsBesides confirming the extreme genetic heterogeneity of PD, these data provide novel insights into the genetic of the disease and may be relevant for its prediction, diagnosis and treatment.
Published: 2021

2. Global, regional, and national burden of stroke and its risk factors, 1990–2019 : a systematic analysis for the Global Burden of Disease Study 2019

Author: Mosiur Rahman, Rehab Salah, Mario F P Peres, Licia Iacoviello, Benjamin A Stark, Mahalaqua Nazli Khatib, Amir Radfar, Kamarul Imran Musa, Yannick Béjot, Deanna Anderlini, Carlos Cantú-Brito, Feng Sha, V. E. Nwatah, Pradip Gyanwali, Boris Bikbov, Bartosz Miazgowski, Sindhura Lakshmi Koulmane Laxminarayana, Ali Bijani, Imteyaz A Khan, Yaser Mokhayeri, Bogdan Oancea, Tarang Parekh, Martin Dichgans, Linh Gia Vu, Naohiro Yonemoto, Ahmad Ghashghaee, Marcos Roberto Tovani-Palone, Gebiyaw Wudie Tsegaye, Mona Pathak, Maciej Banach, Marissa B Reitsma, Derrick A Bennett, Treska S Hassan, Allen Seylani, Gdiom Gebreheat Abady, Islam Y. Elgendy, Hassan Mehmood Lak, Ismael R. Campos-Nonato, Sorin Hostiuc, Sheikh Mohammed Shariful Islam, Alessandra C. Goulart, Silvia Schiavolin, Simona Sacco, Atif Amin Baig, Azeem Majeed, Sahar Eftekharzadeh, Badr Hasan Sobaih, Archith Boloor, Aimé Bonny, Graeme J. Hankey, Jiregna Darega Gela, Mohamed I Hegazy, Pedram Keshavarz, Segun Emmanuel Ibitoye, Maseer Khan, Hatem Abdelaziz Mohamed Wafa, Hualiang Lin, Enayet Karim Chowdhury, Simon I. Hay, Vanessa De la Cruz-Góngora, Xuefeng Liu, Arokiasamy Perianayagam, Maryam Zamanian, Sezer Kisa, Preetam Bhalchandra Mahajan, Junmei Miao Jonasson, Alberto Raggi, Shubha Jayaram, Tahira Ashraf, Ejaz Ahmad Khan, Matthias Endres, Masoumeh Sadeghi, Dominique Vervoort, Hanadi Al Hamad, Mowafa Househ, Elena V. Gnedovskaya, Johan Ärnlöv, Andrea Sylvia Winkler, Yousef Khader, Mikhail Sergeevich Zastrozhin, Yuming Guo, Yunquan Zhang, Sami Almustanyir, Lalit Dandona, Amir Masoud Rahmani, Chythra R Rao, Giancarlo Lucchetti, Irena Ilic, Suzanne Barker-Collo, Priya Rathi, Emerito Jose A. Faraon, Mohamad-Hani Temsah, Reza Ghanei Gheshlagh, Gyu Ri Kim, Carlos A Castañeda-Orjuela, Alaa Makki, Yun Jin Kim, Vida Abedi, Shanshan Li, Kewal Krishan, David Flood, Abdollah Mohammadian-Hafshejani, Michele Romoli, Gregory A. Roth, Jagdish Khubchandani, Isabela M. Benseñor, Rupak Desai, Mohammed Shannawaz, Aziz Sheikh, Claudiu Herteliu, Xiaoyue Xu, Santi Martini, Kenji Shibuya, Jasvinder A. Singh, Ravi Prakash Jha, Kairat Davletov, Mahya Beheshti, Rahmatollah Moradzadeh, Ismaeel Yunusa, Maria Inês Schmidt, Koustuv Dalal, Sohail Ahmad, Patrick D. M. C. Katoto, Oladimeji Adebayo, Nima Hafezi-Nejad, Ranil Jayawardena, Giampiero Mazzaglia, Mitra Abbasifard, Usman Iqbal, Hamid Yimam Hassen, Alireza Rafiei, Catherine O. Johnson, Mark Thomaz Ugliara Barone, Simona Giampaoli, Gaetano Isola, Ricardo Lutzky Saute, Mandira Lamichhane Dhimal, Vishnu Renjith, Farshad Farzadfar, Irina Filip, Daniel Diaz, André Karch, Samer Hamidi, Diego Augusto Santos Silva, David Colozza, Gbenga A. Kayode, Dinh-Toi Chu, Truong-Minh Pham, Arielle Wilder Bell, Aziz Rezapour, David Laith Rawaf, Anasthasia Zastrozhina, Yves Miel H Zuniga, Ivo Iavicoli, Adrian Pana, Salman Rawaf, Pankaj Bhardwaj, Omid Dadras, Anayat Ullah, Gina Agarwal, Shafiu Mohammed, Bing-Fang Hwang, Eyayou Girma Tadesse, Charles D.A. Wolfe, Sanjay Basu, Michael Brauer, Tanuj Kanchan, Ahmad Azam Malik, Brigid Unim, Min Seo Kim, Kia Vosoughi, Tomasz Miazgowski, Warren D. Lo, Vivek Podder, Dana Bryazka, Chuanhua Yu, Hassan Magdy Abd El Razek, Rufus Akinyemi, Zhi-Jiang Zhang, Ettore Beghi, Xiaochen Dai, Meghnath Dhimal, Mehrnoosh Samaei, Sathish Kumar Jayapal, Bay Vo, Amanual Getnet Mersha, Rajaa Al-Raddadi, Savita Lasrado, Jalal Arabloo, Pablo M. Lavados, Samaneh Akbarpour, Khezar Hayat, Ritesh G. Menezes, Vahid Alipour, Sowmya J. Rao, Mariam Molokhia, Trang Huyen Nguyen, Aletta E. Schutte, Zahra Kamiab, Lidia Morawska, Mohammad Ali Moni, Bo Norrving, Tommi Vasankari, Bruno Ramos Nascimento, Ai Koyanagi, Tissa Wijeratne, Rizwan Kalani, Chenwen Zhong, Bright Opoku Ahinkorah, Sepideh Ahmadi, Bruce Bartholow Duncan, Andrzej Rynkiewicz, Pradyumna Agasthi, Saeed Shahabi, Adnan Kisa, Fares Alahdab, Vafa Rahimi-Movaghar, Adnan Ansar, Matilde Leonardi, Ali Koolivand, Jefferson Antonio Buendia Rodriguez, Leonardo Roever, Daniel Asfaw Erku, Alok Atreya, Jean Jacques Noubiap, Dhaval Kolte, Shajedur Rahman Shawon, Michael Ekholuenetale, Navid Manafi, Narayanaswamy Venketasubramanian, Syed Amir Gilani, Mohamed M. Gad, Christopher J L Murray, Louis Jacob, Robert Ancuceanu, Simona Costanzo, Erkin M. Mirrakhimov, Seyed Hossein Yahyazadeh Jabbari, Nazanin Rajai, Muhammed Elhadi, Abdelrahman Ibrahim Abushouk, Alireza Zandifar, Walter Muruet, Jagadish Rao Padubidri, Promit Ananyo Chakraborty, Hans Orru, Mikk Jürisson, Rajeev Gupta, Kurnia Dwi Artanti, Till Bärnighausen, Mark Woodward, Masao Iwagami, Brijesh Sathian, Bingyu Li, Vijay Krishnamoorthy, Ahamarshan Jayaraman Nagarajan, Sherief Ghozy, Amanda G. Thrift, Michael A. Piradov, Florian Fischer, Mayowa O. Owolabi, Lorenzo G. Mantovani, Aman Yesuf Endries, Sara Sheikhbahaei, Stefan Lorkowski, Muhammed Shahriar Zaman, Ali Yadollahpour, Abdiwahab Hashi, Sreenivas Narasimha Swamy, Krittika Bhattacharyya, Hiroshi Yatsuya, Mika Kivimäki, Olayinka Stephen Ilesanmi, Irmina Maria Michalek, Ruxandra Irina Negoi, Alberico L. Catapano, Gholamreza Bazmandegan, Ahmed Al Montasir, Fakher Rahim, Amirhossein Sahebkar, Syed Mohamed Aljunid, Giang Thu Vu, G Anil Kumar, Juan Jesus Carrero, Hiroyasu Iso, Abdallah M. Samy, Stefan Stortecky, Reza Malekzadeh, Ashwin Kamath, Nevine El Nahas, Ayesha Humayun, Miguel A Barboza, Sheng-Chia Chung, Carlo La Vecchia, Oluwakemi Ololade Odukoya, Rita Krishnamurthi, Masood Ali Shaikh, Milena Ilic, Lalit Yadav, Nahlah Elkudssiah Ismail, Abdel Douiri, Yousef Mohammad, Jason H Y Wu, Sahar Saeedi Moghaddam, Ramesh Holla, Sadaf G. Sepanlou, Itamar S. Santos, Jost B. Jonas, Dian Kusuma, Atte Meretoja, Yasir Waheed, Ben Lacey, Zahra Aryan, Mulugeta Molla Birhanu, Moien Ab Khan, K. M. Saif-Ur-Rahman, Ramin Zand, Anna Aleksandrovna Skryabina, Sung In Jang, Rakhi Dandona, Emanuele D'Amico, Priyanga Ranasinghe, Jaykaran Charan, Bhaskaran Unnikrishnan, Davide Sattin, Akram Pourshams, Markus P. Schlaich, Arief Hargono, Samaneh Asgari, Ovidiu Baltatu, Ippazio Cosimo Antonazzo, Sandhya Neupane Kandel, Nizal Sarrafzadegan, Jakub Morze, Man Mohan Mehndiratta, Manjari Tripathi, Panniyammakal Jeemon, Rohollah Kalhor, Yogeshwar Kalkonde, Soraya Siabani, Sojib Bin Zaman, Seyed Sina Naghibi Irvani, Shilpa Gaidhane, Sahel Valadan Tahbaz, Yihienew Mequanint Bezabih, Samath D Dharmaratne, Ingan Ukur Tarigan, Vivek Gupta, Klara Dokova, Alireza Vakilian, Vardhmaan Jain, Akshaya Srikanth Bhagavathula, Sarah Wulf Hanson, Umar Farooque, Mohammad Ali Mansournia, Vera Marisa Costa, Alessandro Gialluisi, Valery L. Feigin, Himal Kandel, Suzanne Polinder, Nermin Ghith, Deepak Dhamnetiya, Michael H. Criqui, Asif Hanif, Ahmed Abualhasan, Veer Bala Gupta, Mahaveer Golechha, Bach Xuan Tran, Jason A. Anderson, Catherine Bisignano, Kazumasa Yamagishi, Zahid A Butt, Budi Aji, Baye Dagnew, Rasmus Havmoeller, Victor Volovici, Jitendra Singh, Paramjit Gill, Saverio Stranges, Eun Cheol Park, Andrew T Olagunju, Milena Santric-Milicevic, Woldesellassie M. Bezabhe, Sheikh M. Alif, Junjie Huang, Foad Abd-Allah, Yvonne Teuschl, Rajkumar Doshi, Nelson Alvis-Guzman, Marcel Ausloos, Mohsen Naghavi, Yusra Ahmed Salih, Mohsen Abbasi-Kangevari, Maarten J. Postma, Ghozali Ghozali, Yanzhong Wang, Ali H. Mokdad, Valentin Yurievich Skryabin, Nitin Joseph, Andre M. N. Renzaho, Muhammad Aziz Rahman, Mohammad Athar, Rustam Al-Shahi Salman, Albertino Damasceno, Fatemeh Pashazadeh Kan, Marcello Tonelli, Florentino Luciano Caetano dos Santos, Sonali G. Choudhari, Abdullah Hamid Feroze, Walter D. Johnson, Ro-Ting Lin, Francesca Giulia Magnani, Hermann Brenner, Shaimaa I. El-Jaafary, Tea Lallukka, Niveen M E Abu-Rmeileh, Jacek Jerzy Jozwiak, GBD 2019 Stroke Collaborators, Feigin, V. L., Stark, B. A., Johnson, C. O., Roth, G. A., Bisignano, C., Abady, G. G., Abbasifard, M., Abbasi-Kangevari, M., Abd-Allah, F., Abedi, V., Abualhasan, A., Abu-Rmeileh, N. M. E., Abushouk, A. I., Adebayo, O. M., Agarwal, G., Agasthi, P., Ahinkorah, B. O., Ahmad, S., Ahmadi, S., Salih, Y. A., Aji, B., Akbarpour, S., Akinyemi, R. O., Al Hamad, H., Alahdab, F., Alif, S. M., Alipour, V., Aljunid, S. M., Almustanyir, S., Al-Raddadi, R. M., Salman, R. A. -S., Alvis-Guzman, N., Ancuceanu, R., Anderlini, D., Anderson, J. A., Ansar, A., Antonazzo, I. C., Arabloo, J., Arnlov, J., Artanti, K. D., Aryan, Z., Asgari, S., Ashraf, T., Athar, M., Atreya, A., Ausloos, M., Baig, A. A., Baltatu, O. C., Banach, M., Barboza, M. A., Barker-Collo, S. L., Barnighausen, T. W., Barone, M. T. U., Basu, S., Bazmandegan, G., Beghi, E., Beheshti, M., Bejot, Y., Bell, A. W., Bennett, D. A., Bensenor, I. M., Bezabhe, W. M., Bezabih, Y. M., Bhagavathula, A. S., Bhardwaj, P., Bhattacharyya, K., Bijani, A., Bikbov, B., Birhanu, M. M., Boloor, A., Bonny, A., Brauer, M., Brenner, H., Bryazka, D., Butt, Z. A., Dos Santos, F. L. C., Campos-Nonato, I. R., Cantu-Brito, C., Carrero, J. J., Castaneda-Orjuela, C. A., Catapano, A. L., Chakraborty, P. A., Charan, J., Choudhari, S. G., Chowdhury, E. K., Chu, D. -T., Chung, S. -C., Colozza, D., Costa, V. M., Costanzo, S., Criqui, M. H., Dadras, O., Dagnew, B., Dai, X., Dalal, K., Damasceno, A. A. M., D'Amico, E., Dandona, L., Dandona, R., Gela, J. D., Davletov, K., De La Cruz-Gongora, V., Desai, R., Dhamnetiya, D., Dharmaratne, S. D., Dhimal, M. L., Dhimal, M., Diaz, D., Dichgans, M., Dokova, K., Doshi, R., Douiri, A., Duncan, B. B., Eftekharzadeh, S., Ekholuenetale, M., El Nahas, N., Elgendy, I. Y., Elhadi, M., El-Jaafary, S. I., Endres, M., Endries, A. Y., Erku, D. A., Faraon, E. J. A., Farooque, U., Farzadfar, F., Feroze, A. H., Filip, I., Fischer, F., Flood, D., Gad, M. M., Gaidhane, S., Gheshlagh, R. G., Ghashghaee, A., Ghith, N., Ghozali, G., Ghozy, S., Gialluisi, A., Giampaoli, S., Gilani, S. A., Gill, P. S., Gnedovskaya, E. V., Golechha, M., Goulart, A. C., Guo, Y., Gupta, R., Gupta, V. B., Gupta, V. K., Gyanwali, P., Hafezi-Nejad, N., Hamidi, S., Hanif, A., Hankey, G. J., Hargono, A., Hashi, A., Hassan, T. S., Hassen, H. Y., Havmoeller, R. J., Hay, S. I., Hayat, K., Hegazy, M. I., Herteliu, C., Holla, R., Hostiuc, S., Househ, M., Huang, J., Humayun, A., Hwang, B. -F., Iacoviello, L., Iavicoli, I., Ibitoye, S. E., Ilesanmi, O. S., Ilic, I. M., Ilic, M. D., Iqbal, U., Irvani, S. S. N., Islam, S. M. S., Ismail, N. E., Iso, H., Isola, G., Iwagami, M., Jacob, L., Jain, V., Jang, S. -I., Jayapal, S. K., Jayaram, S., Jayawardena, R., Jeemon, P., Jha, R. P., Johnson, W. D., Jonas, J. B., Joseph, N., Jozwiak, J. J., Jurisson, M., Kalani, R., Kalhor, R., Kalkonde, Y., Kamath, A., Kamiab, Z., Kanchan, T., Kandel, H., Karch, A., Katoto, P. D. M. C., Kayode, G. A., Keshavarz, P., Khader, Y. S., Khan, E. A., Khan, I. A., Khan, M., Khan, M. A. B., Khatib, M. N., Khubchandani, J., Kim, G. R., Kim, M. S., Kim, Y. J., Kisa, A., Kisa, S., Kivimaki, M., Kolte, D., Koolivand, A., Laxminarayana, S. L. K., Koyanagi, A., Krishan, K., Krishnamoorthy, V., Krishnamurthi, R. V., Kumar, G. A., Kusuma, D., Vecchia, C. L., Lacey, B., Lak, H. M., Lallukka, T., Lasrado, S., Lavados, P. M., Leonardi, M., Li, B., Li, S., Lin, H., Lin, R. -T., Liu, X., Lo, W. D., Lorkowski, S., Lucchetti, G., Saute, R. L., Abd El Razek, H. M., Magnani, F. G., Mahajan, P. B., Majeed, A., Makki, A., Malekzadeh, R., Malik, A. A., Manafi, N., Mansournia, M. A., Mantovani, L. G., Martini, S., Mazzaglia, G., Mehndiratta, M. M., Menezes, R. G., Meretoja, A., Mersha, A. G., Jonasson, J. M., Miazgowski, B., Miazgowski, T., Michalek, I. M., Mirrakhimov, E. M., Mohammad, Y., Mohammadian-Hafshejani, A., Mohammed, S., Mokdad, A. H., Mokhayeri, Y., Molokhia, M., Moni, M. A., Al Montasir, A., Moradzadeh, R., Morawska, L., Morze, J., Muruet, W., Musa, K. I., Nagarajan, A. J., Naghavi, M., Swamy, S. N., Nascimento, B. R., Negoi, R. I., Kandel, S. N., Nguyen, T. H., Norrving, B., Noubiap, J. J., Nwatah, V. E., Oancea, B., Odukoya, O. O., Olagunju, A. T., Orru, H., Owolabi, M. O., Padubidri, J. R., Pana, A., Parekh, T., Park, E. -C., Kan, F. P., Pathak, M., Peres, M. F. P., Perianayagam, A., Pham, T. -M., Piradov, M. A., Podder, V., Polinder, S., Postma, M. J., Pourshams, A., Radfar, A., Rafiei, A., Raggi, A., Rahim, F., Rahimi-Movaghar, V., Rahman, M., Rahman, M. A., Rahmani, A. M., Rajai, N., Ranasinghe, P., Rao, C. R., Rao, S. J., Rathi, P., Rawaf, D. L., Rawaf, S., Reitsma, M. B., Renjith, V., Renzaho, A. M. N., Rezapour, A., Rodriguez, J. A. B., Roever, L., Romoli, M., Rynkiewicz, A., Sacco, S., Sadeghi, M., Moghaddam, S. S., Sahebkar, A., Saif-Ur-Rahman, K. M., Salah, R., Samaei, M., Samy, A. M., Santos, I. S., Santric-Milicevic, M. M., Sarrafzadegan, N., Sathian, B., Sattin, D., Schiavolin, S., Schlaich, M. P., Schmidt, M. I., Schutte, A. E., Sepanlou, S. G., Seylani, A., Sha, F., Shahabi, S., Shaikh, M. A., Shannawaz, M., Shawon, Md. S. R., Sheikh, A., Sheikhbahaei, S., Shibuya, K., Siabani, S., Silva, D. A. S., Singh, J. A., Singh, J. K., Skryabin, V. Y., Skryabina, A. A., Sobaih, B. H., Stortecky, S., Stranges, S., Tadesse, E. G., Tarigan, I. U., Temsah, M. -H., Teuschl, Y., Thrift, A. G., Tonelli, M., Tovani-Palone, M. R., Tran, B. X., Tripathi, M., Tsegaye, G. W., Ullah, A., Unim, B., Unnikrishnan, B., Vakilian, A., Tahbaz, S. V., Vasankari, T. J., Venketasubramanian, N., Vervoort, D., Vo, B., Volovici, V., Vosoughi, K., Vu, G. T., Vu, L. G., Wafa, H. A., Waheed, Y., Wang, Y., Wijeratne, T., Winkler, A. S., Wolfe, C. D. A., Woodward, M., Wu, J. H., Hanson, S. W., Xu, X., Yadav, L., Yadollahpour, A., Jabbari, S. H. Y., Yamagishi, K., Yatsuya, H., Yonemoto, N., Yu, C., Yunusa, I., Zaman, M. S., Zaman, S. B., Zamanian, M., Zand, R., Zandifar, A., Zastrozhin, M. S., Zastrozhina, A., Zhang, Y., Zhang, Z. -J., Zhong, C., Zuniga, Y. M. H., Murray, C. J. L., Public Health, Neurosurgery, Department of Public Health, University of Helsinki, Faculty of Medicine, Helsinki Inequality Initiative (INEQ), HUS Neurocenter, Neurologian yksikkö, Helsinki University Hospital Area, Feigin, V, Stark, B, Johnson, C, Roth, G, Bisignano, C, Abady, G, Abbasifard, M, Abbasi-Kangevari, M, Abd-Allah, F, Abedi, V, Abualhasan, A, Abu-Rmeileh, N, Abushouk, A, Adebayo, O, Agarwal, G, Agasthi, P, Ahinkorah, B, Ahmad, S, Ahmadi, S, Salih, Y, Aji, B, Akbarpour, S, Akinyemi, R, Al Hamad, H, Alahdab, F, Alif, S, Alipour, V, Aljunid, S, Almustanyir, S, Al-Raddadi, R, Salman, R, Alvis-Guzman, N, Ancuceanu, R, Anderlini, D, Anderson, J, Ansar, A, Antonazzo, I, Arabloo, J, Arnlov, J, Artanti, K, Aryan, Z, Asgari, S, Ashraf, T, Athar, M, Atreya, A, Ausloos, M, Baig, A, Baltatu, O, Banach, M, Barboza, M, Barker-Collo, S, Barnighausen, T, Barone, M, Basu, S, Bazmandegan, G, Beghi, E, Beheshti, M, Bejot, Y, Bell, A, Bennett, D, Bensenor, I, Bezabhe, W, Bezabih, Y, Bhagavathula, A, Bhardwaj, P, Bhattacharyya, K, Bijani, A, Bikbov, B, Birhanu, M, Boloor, A, Bonny, A, Brauer, M, Brenner, H, Bryazka, D, Butt, Z, Dos Santos, F, Campos-Nonato, I, Cantu-Brito, C, Carrero, J, Castaneda-Orjuela, C, Catapano, A, Chakraborty, P, Charan, J, Choudhari, S, Chowdhury, E, Chu, D, Chung, S, Colozza, D, Costa, V, Costanzo, S, Criqui, M, Dadras, O, Dagnew, B, Dai, X, Dalal, K, Damasceno, A, D'Amico, E, Dandona, L, Dandona, R, Gela, J, Davletov, K, De La Cruz-Gongora, V, Desai, R, Dhamnetiya, D, Dharmaratne, S, Dhimal, M, Diaz, D, Dichgans, M, Dokova, K, Doshi, R, Douiri, A, Duncan, B, Eftekharzadeh, S, Ekholuenetale, M, El Nahas, N, Elgendy, I, Elhadi, M, El-Jaafary, S, Endres, M, Endries, A, Erku, D, Faraon, E, Farooque, U, Farzadfar, F, Feroze, A, Filip, I, Fischer, F, Flood, D, Gad, M, Gaidhane, S, Gheshlagh, R, Ghashghaee, A, Ghith, N, Ghozali, G, Ghozy, S, Gialluisi, A, Giampaoli, S, Gilani, S, Gill, P, Gnedovskaya, E, Golechha, M, Goulart, A, Guo, Y, Gupta, R, Gupta, V, Gyanwali, P, Hafezi-Nejad, N, Hamidi, S, Hanif, A, Hankey, G, Hargono, A, Hashi, A, Hassan, T, Hassen, H, Havmoeller, R, Hay, S, Hayat, K, Hegazy, M, Herteliu, C, Holla, R, Hostiuc, S, Househ, M, Huang, J, Humayun, A, Hwang, B, Iacoviello, L, Iavicoli, I, Ibitoye, S, Ilesanmi, O, Ilic, I, Ilic, M, Iqbal, U, Irvani, S, Islam, S, Ismail, N, Iso, H, Isola, G, Iwagami, M, Jacob, L, Jain, V, Jang, S, Jayapal, S, Jayaram, S, Jayawardena, R, Jeemon, P, Jha, R, Johnson, W, Jonas, J, Joseph, N, Jozwiak, J, Jurisson, M, Kalani, R, Kalhor, R, Kalkonde, Y, Kamath, A, Kamiab, Z, Kanchan, T, Kandel, H, Karch, A, Katoto, P, Kayode, G, Keshavarz, P, Khader, Y, Khan, E, Khan, I, Khan, M, Khatib, M, Khubchandani, J, Kim, G, Kim, M, Kim, Y, Kisa, A, Kisa, S, Kivimaki, M, Kolte, D, Koolivand, A, Laxminarayana, S, Koyanagi, A, Krishan, K, Krishnamoorthy, V, Krishnamurthi, R, Kumar, G, Kusuma, D, Vecchia, C, Lacey, B, Lak, H, Lallukka, T, Lasrado, S, Lavados, P, Leonardi, M, Li, B, Li, S, Lin, H, Lin, R, Liu, X, Lo, W, Lorkowski, S, Lucchetti, G, Saute, R, Abd El Razek, H, Magnani, F, Mahajan, P, Majeed, A, Makki, A, Malekzadeh, R, Malik, A, Manafi, N, Mansournia, M, Mantovani, L, Martini, S, Mazzaglia, G, Mehndiratta, M, Menezes, R, Meretoja, A, Mersha, A, Jonasson, J, Miazgowski, B, Miazgowski, T, Michalek, I, Mirrakhimov, E, Mohammad, Y, Mohammadian-Hafshejani, A, Mohammed, S, Mokdad, A, Mokhayeri, Y, Molokhia, M, Moni, M, Al Montasir, A, Moradzadeh, R, Morawska, L, Morze, J, Muruet, W, Musa, K, Nagarajan, A, Naghavi, M, Swamy, S, Nascimento, B, Negoi, R, Kandel, S, Nguyen, T, Norrving, B, Noubiap, J, Nwatah, V, Oancea, B, Odukoya, O, Olagunju, A, Orru, H, Owolabi, M, Padubidri, J, Pana, A, Parekh, T, Park, E, Kan, F, Pathak, M, Peres, M, Perianayagam, A, Pham, T, Piradov, M, Podder, V, Polinder, S, Postma, M, Pourshams, A, Radfar, A, Rafiei, A, Raggi, A, Rahim, F, Rahimi-Movaghar, V, Rahman, M, Rahmani, A, Rajai, N, Ranasinghe, P, Rao, C, Rao, S, Rathi, P, Rawaf, D, Rawaf, S, Reitsma, M, Renjith, V, Renzaho, A, Rezapour, A, Rodriguez, J, Roever, L, Romoli, M, Rynkiewicz, A, Sacco, S, Sadeghi, M, Moghaddam, S, Sahebkar, A, Saif-Ur-Rahman, K, Salah, R, Samaei, M, Samy, A, Santos, I, Santric-Milicevic, M, Sarrafzadegan, N, Sathian, B, Sattin, D, Schiavolin, S, Schlaich, M, Schmidt, M, Schutte, A, Sepanlou, S, Seylani, A, Sha, F, Shahabi, S, Shaikh, M, Shannawaz, M, Shawon, M, Sheikh, A, Sheikhbahaei, S, Shibuya, K, Siabani, S, Silva, D, Singh, J, Skryabin, V, Skryabina, A, Sobaih, B, Stortecky, S, Stranges, S, Tadesse, E, Tarigan, I, Temsah, M, Teuschl, Y, Thrift, A, Tonelli, M, Tovani-Palone, M, Tran, B, Tripathi, M, Tsegaye, G, Ullah, A, Unim, B, Unnikrishnan, B, Vakilian, A, Tahbaz, S, Vasankari, T, Venketasubramanian, N, Vervoort, D, Vo, B, Volovici, V, Vosoughi, K, Vu, G, Vu, L, Wafa, H, Waheed, Y, Wang, Y, Wijeratne, T, Winkler, A, Wolfe, C, Woodward, M, Wu, J, Hanson, S, Xu, X, Yadav, L, Yadollahpour, A, Jabbari, S, Yamagishi, K, Yatsuya, H, Yonemoto, N, Yu, C, Yunusa, I, Zaman, M, Zaman, S, Zamanian, M, Zand, R, Zandifar, A, Zastrozhin, M, Zastrozhina, A, Zhang, Y, Zhang, Z, Zhong, C, Zuniga, Y, Murray, C, Value, Affordability and Sustainability (VALUE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Microbes in Health and Disease (MHD)
Subjects: Male, Aging, 030204 cardiovascular system & hematology, Stroke data, GUIDELINES, 3124 Neurology and psychiatry, Body Mass Index, Global Burden of Disease, 0302 clinical medicine, RA0421, Risk Factors, Epidemiology, Strokes, YOUNG-ADULTS, Prevalence, 80 and over, Aetiology, 610 Medicine & health, Stroke, POPULATION, 1103 Clinical Sciences, 1109 Neurosciences, Cause of death, Aged, 80 and over, education.field_of_study, Mortality rate, Incidence (epidemiology), Incidence, 1. No poverty, Articles, Hälsovetenskaper, Middle Aged, Stroke types, ddc, 3. Good health, ISCHEMIC-STROKE, Income, Female, Quality-Adjusted Life Years, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, GBD, Population, Clinical Sciences, Clinical Neurology, 03 medical and health sciences, Clinical Research, MIDDLE-INCOME COUNTRIES, Health Sciences, medicine, Humans, Risk factor, education, GBD 2019 Stroke Collaborators, Cerebral Hemorrhage, Aged, Ischemic Stroke, Global burden, Science & Technology, Neurology & Neurosurgery, HYPERTENSION, business.industry, MORTALITY, Prevention, 3112 Neurosciences, Neurosciences, 1103 Clinical Sciences, SERVICES, Subarachnoid Hemorrhage, medicine.disease, PREVENTION, Brain Disorders, Good Health and Well Being, Attributable risk, Human medicine, Neurology (clinical), Neurosciences & Neurology, business, 1109 Neurosciences, 030217 neurology & neurosurgery, Demography, 2.4 Surveillance and distribution, RC
Abstract: Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding Bill & Melinda Gates Foundation.
Published: 2021

3. Association of nutritional glycaemic indices with global DNA methylation patterns: results from the Moli-sani cohort

Author: Fabrizia, Noro, Federica, Santonastaso, Annalisa, Marotta, Marialaura, Bonaccio, Sabatino, Orlandi, Alfonsina, Tirozzi, Simona, Costanzo, Amalia, De Curtis, Francesco, Gianfagna, Augusto, Di Castelnuovo, Furio, Brighenti, Chiara, Cerletti, Maria Benedetta, Donati, Giovanni, de Gaetano, Licia, Iacoviello, Alessandro, Gialluisi, Benedetta, Izzi, and Americo, Bonanni
Subjects: Male, Glycaemic index, Hydroxymethylation, Metabolic disorders, DNA Methylation, Glycaemic load, Methylation, Diet, Glycemic Index, Genetics, Linear Models, Humans, Female, Molecular Biology, Genetics (clinical), Developmental Biology
Abstract: Background High dietary glycaemic index (GI) and load (GL) have been associated with increased risk of various cardiometabolic conditions. Among the molecular potential mechanisms underlying this relationship, DNA methylation has been studied, but a direct link between high GI and/or GL of diet and global DNA methylation levels has not been proved yet. We analyzed the associations between GI and GL and global DNA methylation patterns within an Italian population. Results Genomic DNA methylation (5mC) and hydroxymethylation (5hmC) levels were measured in 1080 buffy coat samples from participants of the Moli-sani study (mean(SD) = 54.9(11.5) years; 52% women) via ELISA. A 188-item Food Frequency Questionnaire was used to assess food intake and dietary GI and GL for each participant were calculated. Multiple linear regressions were used to investigate the associations between dietary GI and GL and global 5mC and 5hmC levels, as well as the proportion of effect explained by metabolic and inflammatory markers. We found negative associations of GI with both 5mC (β (SE) = − 0.073 (0.027), p = 0.007) and 5hmC (− 0.084 (0.030), p = 0.006), and of GL with 5mC (− 0.14 (0.060), p = 0.014). Circulating biomarkers did not explain the above-mentioned associations. Gender interaction analyses revealed a significant association of the gender-x-GL interaction with 5mC levels, with men showing an inverse association three times as negative as in women (interaction β (SE) = − 0.16 (0.06), p = 0.005). Conclusions Our findings suggest that global DNA methylation and hydroxymethylation patterns represent a biomarker of carbohydrate intake. Based on the differential association of GL with 5mC between men and women, further gender-based separate approaches are warranted.
Published: 2022

4. Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering

Author: Anna Sabena, Gabriele Giuliano, Raffaele Bruno, Francesco Cacciatore, Carlo Torti, Silvia Marongiu, Gloria Maccagni, Claudia Marotta, Giovanni Larizza, Francesco Petri, Massimo Mapelli, Giulio Maresca, Giulia Righetti, Alessandra Vergori, Ilaria Rossi, Damiano D'Ardes, Nicola Schiano Moriello, Ivan Gentile, Enrica Tamburrini, Luca Aiello, Piergiuseppe Agostoni, Antonio Cascio, Jovana Milic, Carlo Andrea Pivato, Agostino Virdis, Stefano Maitan, Francesco Cannata, Simona Costanzo, Carlo Signorelli, Franco Mastroianni, Federica Magni, Crizia Colombo, Giulio G. Stefanini, Lucia Caiano, Francesca Crosta, Lorenzo Marra, Giuseppe Patti, Katleen de Gaetano Donati, Valerio Langella, Annalisa Crisetti, Filippo Aucella, Antonella Cingolani, Francesco Salinaro, Augusto Di Castelnuovo, Giacomo Castiglione, Alessandro Gialluisi, Anna Odone, Cristina Mussini, Samir Al Moghazi, Lorenzo Blandi, Maria Musso, Marialaura Bonaccio, Raffaele De Caterina, Marco Olivieri, Roberto Cauda, Emanuela Pasi, Arturo Ciccullo, Stefano Perlini, Claudia Colomba, Antonella Palimodde, Gianpiero D'Offizi, Marco G. Mennuni, Walter Ageno, Raffaele Pesavento, Rosa Manuele, Roberta Mussinelli, Vincenzo Sangiovanni, Paolo Bonfanti, Andrea Antinori, Francesco Gianfagna, Andrea Rognoni, Laura Scorzolini, Riccardo Maragna, Rossella Marcucci, Filippo Minutolo, Armando Leone, Giustino Parruti, Licia Iacoviello, Lorenzo Menicanti, Sandro Mancarella, Rosa Arboretti, Greta Barbieri, Carlo Gaudiosi, Marco Rossato, Claudia Ravaglia, Andrea Vianello, Marianna Rossi, Emauele Graziani, Martina Barchitta, Giovanni Guaraldi, Enrico Maria Trecarichi, Gian Battista Danzi, Francesco Cipollone, Carlo Sanrocco, Marco Vinceti, Francesca Santilli, Marianna Meschiari, Gabriella Guarnieri, Antonella Agodi, Roberto Vettor, Raffaella Sgariglia, Ilaria My, Francesco Di Gennaro, Alessandro Mengozzi, Giuseppe Di Tano, Laura Carrozzi, Michele Spinicci, Venerino Poletti, Paola Simeone, Nausicaa Berselli, Francesco Maria Fusco, Di Castelnuovo A., Gialluisi A., Antinori A., Berselli N., Blandi L., Bonaccio M., Bruno R., Cauda R., Costanzo S., Guaraldi G., Menicanti L., Mennuni M., My I., Parruti G., Patti G., Perlini S., Santilli F., Signorelli C., Stefanini G., Vergori A., Ageno W., Agodi A., Agostoni P., Aiello L., Moghazi S.A., Arboretti R., Aucella F., Barbieri G., Barchitta M., Bonfanti P., Cacciatore F., Caiano L., Cannata F., Carrozzi L., Cascio A., Castiglione G., Cicullo A., Cingolani A., Cipollone F., Colomba C., Colombo C., Crisetti A., Crosta F., Danzi G.B., D'Ardes D., de Gaetano Donati K., Di Gennaro F., Di Tano G., D'Offizi G., Fusco F.M., Gaudiosi C., Gentile I., Gianfagna F., Giuliano G., Graziani E., Guarnieri G., Langella V., Larizza G., Leone A., Maccagni G., Magni F., Maitan S., Mancarella S., Manuele R., Mapelli M., Maragna R., Marcucci R., Maresca G., Marongiu S., Marotta C., Marra L., Mastroianni F., Mengozzi A., Meschiari M., Milic J., Minutolo F., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Palimodde A., Pasi E., Pesavento R., Petri F., Pivato C.A., Poletti V., Ravaglia C., Righetti G., Rognoni A., Rossato M., Rossi I., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Moriello N.S., Scorzolini L., Sgariglia R., Simeone P.G., Spinicci M., Tamburrini E., Torti C., Trecarichi E.M., Vettor R., Vianello A., Vinceti M., Virdis A., de Caterina R., Iacoviello L., Di Castelnuovo, A, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Bruno, R, Cauda, R, Costanzo, S, Guaraldi, G, Menicanti, L, Mennuni, M, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Castiglione, G, Cicullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gaudiosi, C, Gentile, I, Gianfagna1, F, Giuliano, G, Graziani, E, Guarnieri, G, Langella, V, Larizza, G, Leone, A, Maccagni, G, Magni, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Meschiari, M, Milic, J, Minutolo, F, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pivato, C, Poletti, V, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Schiano Moriello, N, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Tamburrini, E, Torti, C, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virdis, A, De Caterina, R, Iacoviello, L, Di Castelnuovo, A., Gialluisi, A., Antinori, A., Berselli, N., Blandi, L., Bonaccio, M., Bruno, R., Cauda, R., Costanzo, S., Guaraldi, G., Menicanti, L., Mennuni, M., My, I., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G., Vergori, A., Ageno, W., Agodi, A., Agostoni, P., Aiello, L., Moghazi, S. A., Arboretti, R., Aucella, F., Barbieri, G., Barchitta, M., Bonfanti, P., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Castiglione, G., Cicullo, A., Cingolani, A., Cipollone, F., Colomba, C., Colombo, C., Crisetti, A., Crosta, F., Danzi, G. B., D’Ardes, D., de Gaetano Donati, K., Di Gennaro, F., Di Tano, G., D’Offizi, G., Fusco, F. M., Gaudiosi, C., Gentile, I., Gianfagna, F., Giuliano, G., Graziani, E., Guarnieri, G., Langella, V., Larizza, G., Leone, A., Maccagni, G., Magni, F., Maitan, S., Mancarella, S., Manuele, R., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marongiu, S., Marotta, C., Marra, L., Mastroianni, F., Mengozzi, A., Meschiari, M., Milic, J., Minutolo, F., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Palimodde, A., Pasi, E., Pesavento, R., Petri, F., Pivato, C. A., Poletti, V., Ravaglia, C., Righetti, G., Rognoni, A., Rossato, M., Rossi, I., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Moriello, N. S., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinicci, M., Tamburrini, E., Torti, C., Trecarichi, E. M., Vettor, R., Vianello, A., Vinceti, M., Virdis, A., de Caterina, R., and Iacoviello, L.
Subjects: Male, Medicine (General), Antimalarial, 030204 cardiovascular system & hematology, Severity of Illness Index, Hospital Mortality, 0302 clinical medicine, Retrospective Studie, 80 and over, Cluster Analysis, 030212 general & internal medicine, Aged, Aged, 80 and over, Antimalarials, COVID-19, Female, Humans, Hydroxychloroquine, Italy, Middle Aged, Retrospective Studies, SARS-CoV-2, Treatment Outcome, Biotechnology, medicine.drug, Research Article, medicine.medical_specialty, Article Subject, Biomedical Engineering, Renal function, Health Informatics, 03 medical and health sciences, R5-920, Internal medicine, Diabetes mellitus, Severity of illness, medicine, Medical technology, R855-855.5, Cluster Analysi, business.industry, Cancer, Retrospective cohort study, medicine.disease, Obesity, COVID-19 Drug Treatment, Surgery, Observational study, business
Abstract: The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction ( p < 0.001 ). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.
Published: 2021
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5. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Author: Zhou, B, Carrillo-Larco, Rm, Danaei, G, Riley, Lm, Paciorek, Cj, Stevens, Ga, Gregg, Ew, Bennett, Je, Solomon, B, Singleton, Rk, Sophiea, Mk, Iurilli, Mlc, Lhoste, Vpf, Cowan, Mj, Savin, S, Woodward, M, Balanova, Y, Cifkova, R, Damasceno, A, Elliott, P, Farzadfar, F, He, J, Ikeda, N, Kengne, Ap, Khang, Yh, Kim, Hc, Laxmaiah, A, Lin, Hh, Maira, Pm, Miranda, Jj, Neuhauser, H, Sundstrom, J, Varghese, C, Widyahening, Is, Zdrojewski, T, Ezzati, M, Abarca-Gomez, L, Abdeen, Za, Rahim, Hfa, Abu-Rmeileh, Nm, Acosta-Cazares, B, Adams, Rj, Aekplakorn, W, Afsana, K, Afzal, S, Agdeppa, Ia, Aghazadeh-Attari, J, Aguilar-Salinas, Ca, Agyemang, C, Ahmad, Na, Ahmadi, A, Ahmadi, N, Ahmadizar, F, Ahmed, Sh, Ahrens, W, Ajlouni, K, Al-Raddadi, R, Alarouj, M, Albuhairan, F, Aldhukair, S, Ali, Mm, Alkandari, A, Alkerwi, A, Allin, K, Aly, E, Amarapurkar, Dn, Amougou, N, Amouyel, P, Andersen, Lb, Anderssen, Sa, Anjana, Rm, Ansari-Moghaddam, A, Ansong, D, Aounallah-Skhiri, H, Araujo, J, Ariansen, I, 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Kazakbaeva, Ulrich Keil, Lital Keinan Boker, Sirkka Keinänen-Kiukaanniemi, Roya Kelishadi, Han Cg Kemper, Maryam Keramati, Alina Kerimkulova, Mathilde Kersting, Timothy Key, Yousef Saleh Khader, Davood Khalili, Kay-Tee Khaw, Bahareh Kheiri, Motahareh Kheradmand, Alireza Khosravi, Ursula Kiechl-Kohlendorfer, Stefan Kiechl, Japhet Killewo, Dong Wook Kim, Jeongseon Kim, Heidi Klakk, Magdalena Klimek, Jurate Klumbiene, Michael Knoflach, Elin Kolle, Patrick Kolsteren, Jukka P Kontto, Raija Korpelainen, Paul Korrovits, Jelena Kos, Seppo Koskinen, Katsuyasu Kouda, Sudhir Kowlessur, Slawomir Koziel, Jana Kratenova, Vilma Kriaucioniene, Peter Lund Kristensen, Steiner Krokstad, Daan Kromhout, Herculina S Kruger, Ruzena Kubinova, Renata Kuciene, Urho M Kujala, Zbigniew Kulaga, R Krishna Kumar, Pawel Kurjata, Yadlapalli S Kusuma, Vladimir Kutsenko, Kari Kuulasmaa, Catherine Kyobutungi, Tiina Laatikainen, Carl Lachat, Youcef Laid, Tai Hing Lam, Orlando Landrove, Vera Lanska, Georg Lappas, Bagher Larijani, Tint Swe Latt, Gwenaëlle Le Coroller, Khanh Le Nguyen Bao, Tuyen D Le, Jeannette Lee, Jeonghee Lee, Nils Lehmann, Terho Lehtimäki, Daniel Lemogoum, Naomi S Levitt, Yanping Li, Christa L Lilly, Wei-Yen Lim, M Fernanda Lima-Costa, Xu Lin, Yi-Ting Lin, Lars Lind, Vijaya Lingam, Allan Linneberg, Lauren Lissner, Mieczyslaw Litwin, Wei-Cheng Lo, Helle-Mai Loit, Esther Lopez-Garcia, Tania Lopez, Paulo A Lotufo, José Eugenio Lozano, Iva Lukačević Lovrenčić, Janice L Lukrafka, Dalia Luksiene, Annamari Lundqvist, Robert Lundqvist, Nuno Lunet, Michala Lustigová, Edyta Luszczki, Guansheng Ma, Jun Ma, George Ll Machado-Coelho, Aristides M Machado-Rodrigues, Enguerran Macia, Luisa M Macieira, Ahmed A Madar, Stefania Maggi, Dianna J Magliano, Emmanuella Magriplis, Gowri Mahasampath, Bernard Maire, Marjeta Majer, Marcia Makdisse, Fatemeh Malekzadeh, Reza Malekzadeh, Rahul Malhotra, Kodavanti Mallikharjuna Rao, Sofia K Malyutina, Lynell V Maniego, Yannis Manios, Jim I Mann, Fariborz 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M., Hantunen, Sari, Hao, Jie, Hardman, Carla Meneses, Kumar, Rachakulla Hari, Hashemi-Shahri, Seyed Mohammad, Hata, Jun, Haugsgjerd, Teresa, Hayes, Alison J., He, Yuna, Heier, Margit, Hendriks, Marleen Elisabeth, Henrique, Rafael dos Santos, Henriques, Ana, Cadena, Leticia Hernandez, Herrala, Sauli, Heshmat, Ramin, Hill, Allan G., Ho, Sai Yin, Ho, Suzanne C., Hobbs, Michael, Holdsworth, Michelle, Homayounfar, Reza, Dinc, Gonul Horasan, Horimoto, Andrea R. V. R., Hormiga, Claudia M., Horta, Bernardo L., Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Htike, Maung Maung Than, Hu, Yonghua, Huerta, Jose Maria, Huhtaniemi, Ilpo Tapani, Huiart, Laetitia, Huisman, Martijn, Husseini, Abdullatif S., Huybrechts, Inge, Hwalla, Nahla, Iacoviello, Licia, Iannone, Anna G., Ibrahim, Mohsen M., Wong, Norazizah Ibrahim, Ikram, M. Arfan, Iotova, Violeta, Irazola, Vilma E., Ishida, Takafumi, Isiguzo, Godsent C., Islam, Muhammad, Islam, Sheikh Mohammed Shariful, Iwasaki, Masanori, Jackson, Rod T., Jacobs, Jeremy M., Jaddou, Hashem Y., Jafar, Tazeen, James, Kenneth, Jamrozik, Konrad, Janszky, Imre, Janus, Edward, Jarvelin, Marjo-Riitta, Jasienska, Grazyna, Jelakovic, Ana, Jelakovic, Bojan, Jennings, Garry, Jha, Anjani Kumar, Jiang, Chao Qiang, Jimenez, Ramon O., Joeckel, Karl-Heinz, Joffres, Michel, Johansson, Mattias, Jokelainen, Jari J., Jonas, Jost B., Jorgensen, Torben, Joshi, Pradeep, Joukar, Farahnaz, Jozwiak, Jacek, Juolevi, Anne, Jurak, Gregor, Juresa, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kajantie, Eero O., Kalmatayeva, Zhanna, Kalpourtzi, Natasa, Kalter-Leibovici, Ofra, Kampmann, Freja B., Kannan, Srinivasan, Karaglani, Eva, Karhus, Line L., Karki, Khem B., Katibeh, Marzieh, Katz, Joanne, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli M., Keil, Ulrich, Boker, Lital Keinan, Keinanen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kemper, Han C. G., Keramati, Maryam, Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khaw, Kay-Tee, Kheiri, Bahareh, Kheradmand, Motahareh, Khosravi, Alireza, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Dong Wook, Kim, Jeongseon, Klakk, Heidi, Klimek, Magdalena, Klumbiene, Jurate, Knoflach, Michael, Kolle, Elin, Kolsteren, Patrick, Kontto, Jukka P., Korpelainen, Raija, Korrovits, Paul, Kos, Jelena, Koskinen, Seppo, Kouda, Katsuyasu, Kowlessur, Sudhir, Koziel, Slawomir, Kratenova, Jana, Kriaucioniene, Vilma, Kristensen, Peter Lund, Krokstad, Steiner, Kromhout, Daan, Kruger, Herculina S., Kubinova, Ruzena, Kuciene, Renata, Kujala, Urho M., Kulaga, Zbigniew, Kumar, R. Krishna, Kurjata, Pawel, Kusuma, Yadlapalli S., Kutsenko, Vladimir, Kuulasmaa, Kari, Kyobutungi, Catherine, Laatikainen, Tiina, Lachat, Carl, Laid, Youcef, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Latt, Tint Swe, Le Coroller, Gwenaelle, Khanh Le Nguyen Bao, Le, Tuyen D., Lee, Jeannette, Lee, Jeonghee, Lehmann, Nils, Lehtimaki, Terho, Lemogoum, Daniel, Levitt, Naomi S., Li, Yanping, Lilly, Christa L., Lim, Wei-Yen, Lima-Costa, M. Fernanda, Lin, Xu, Lin, Yi-Ting, Lind, Lars, Lingam, Vijaya, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Lo, Wei-Cheng, Loit, Helle-Mai, Lopez-Garcia, Esther, Lopez, Tania, Lotufo, Paulo A., Lozano, Jose Eugenio, Lovrencic, Iva Lukacevic, Lukrafka, Janice L., Luksiene, Dalia, Lundqvist, Annamari, Lundqvist, Robert, Lunet, Nuno, Lustigova, Michala, Luszczki, Edyta, Ma, Guansheng, Ma, Jun, Machado-Coelho, George L. L., Machado-Rodrigues, Aristides M., Macia, Enguerran, Macieira, Luisa M., Madar, Ahmed A., Maggi, Stefania, Magliano, Dianna J., Magriplis, Emmanuella, Mahasampath, Gowri, Maire, Bernard, Majer, Marjeta, Makdisse, Marcia, Malekzadeh, Fatemeh, Malekzadeh, Reza, Malhotra, Rahul, Mallikharjuna, Kodavanti, Malyutina, Sofia K., Maniego, Lynell V., Manios, Yannis, Mann, Jim I., Mansour-Ghanaei, Fariborz, Manzato, Enzo, Marcil, Anie, Margozzini, Paula, Marild, Staffan B., Glavic, Mihalea Marinovic, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martorell, Reynaldo, Mascarenhas, Luis P., Matasin, Marija, Mathiesen, Ellisiv B., Mathur, Prashant, Matijasevich, Alicia, Matlosz, Piotr, Matsha, Tandi E., Mavrogianni, Christina, Mbanya, Jean Claude N., Mc Donald Posso, Anselmo J., McFarlane, Shelly R., McGarvey, Stephen T., McLachlan, Stela, McLean, Rachael M., McLean, Scott B., McNulty, Breige A., Benchekor, Sounnia Mediene, Medzioniene, Jurate, Mehdipour, Parinaz, Mehlig, Kirsten, Mehrparvar, Amir Houshang, Meirhaeghe, Aline, Meisinger, Christa, Mendoza Montano, Carlos, Menezes, Ana Maria B., Menon, Geetha R., Mereke, Alibek, Meshram, Indrapal I., Metspalu, Andres, Meyer, Haakon E., Mi, Jie, Michels, Nathalie, Mikkel, Kairit, Milkowska, Karolina, Miller, Jody C., Minderico, Claudia S., Mini, G. K., Mirjalili, Mohammad Reza, Mirrakhimov, Erkin, Misigoj-Durakovic, Marjeta, Modesti, Pietro A., Moghaddam, Sahar Saeedi, Mohajer, Bahram, Mohamed, Mostafa K., Mohamed, Shukri F., Mohammad, Kazem, Mohammadi, Mohammad Reza, Mohammadi, Zahra, Mohammadifard, Noushin, Mohammadpourhodki, Reza, Mohan, Viswanathan, Mohanna, Salim, Yusoff, Muhammad Fadhli Mohd, Mohebbi, Iraj, Mohebi, Farnam, Moitry, Marie, Mollehave, Line T., Molnar, Denes, Momenan, Amirabbas, Mondo, Charles K., Monterrubio-Flores, Eric, Monyeki, Kotsedi Daniel K., Moon, Jin Soo, Moosazadeh, Mahmood, Moreira, Leila B., Morejon, Alain, Moreno, Luis A., Morgan, Karen, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mostafavi, Seyed-Ali, Mota, Jorge, Motlagh, Mohammad Esmaeel, Motta, Jorge, Andre Moura-dos-Santos, Marcos, Mridha, Malay K., Msyamboza, Kelias P., Mu, Thet Thet, Muhihi, Alfa J., Muiesan, Maria L., Muller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Musa, Kamarul Imran, Milanovic, Sanja Music, Musil, Vera, Mustafa, Norlaila, Nabipour, Iraj, Naderimagham, Shohreh, Nagel, Gabriele, Naidu, Balkish M., Najafi, Farid, Nakamura, Harunobu, Namesna, Jana, Nang, Ei Ei K., Nangia, Vinay B., Narake, Sameer, Ndiaye, Ndeye Coumba, Neal, William A., Nejatizadeh, Azim, Nenko, Ilona, Neovius, Martin, Neuhauser, Hannelore K., Nguyen, Chung T., Nguyen, Nguyen D., Nguyen, Quang V., Quang Ngoc Nguyen, Nieto-Martinez, Ramfis E., Niiranen, Teemu J., Nikitin, Yury P., Ninomiya, Toshiharu, Nishtar, Sania, Njelekela, Marina A., Noale, Marianna, Noboa, Oscar A., Noorbala, Ahmad Ali, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Borge G., Noto, Davide, Nowak-Szczepanska, Natalia, Al Nsour, Mohannad, Nunes, Baltazar, O'Neill, Terence W., O'Reilly, Dermot, Ochimana, Caleb, Oda, Eiji, Odili, Augustine N., Oh, Kyungwon, Ohara, Kumiko, Ohtsuka, Ryutaro, Olie, Valerie, Olinto, Maria Teresa A., Oliveira, Isabel O., Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M., Ordunez, Pedro, Ornelas, Rui, Ortiz, Pedro J., Osmond, Clive, Ostojic, Sergej M., Ostovar, Afshin, Otero, Johanna A., Overvad, Kim, Owusu-Dabo, Ellis, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, de Paiva, Karina Mary, Pajak, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Paoli, Mariela, Papandreou, Dimitrios, Park, Soon-Woo, Park, Suyeon, Parnell, Winsome R., Parsaeian, Mahboubeh, Pasquet, Patrick, Patel, Nikhil D., Pavlyshyn, Halyna, Pecin, Ivan, Pednekar, Mangesh S., Pedro, Joao M., Peer, Nasheeta, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C., Peres, Karen G. D. A., Peres, Marco A., Peters, Annette, Petkeviciene, Janina, Peykari, Niloofar, Son Thai Pham, Pichardo, Rafael N., Pigeot, Iris, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Pizarro, Andreia N., Plans-Rubio, Pedro, Polasek, Ozren, Porta, Miquel, Poudyal, Anil, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J., Price, Jacqueline F., Providencia, Rui, Puhakka, Soile E., Puiu, Maria, Punab, Margus, Qasrawi, Radwan F., Qorbani, Mostafa, Queiroz, Daniel, Tran Quoc Bao, Radic, Ivana, Radisauskas, Ricardas, Rahimikazerooni, Salar, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina M., Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Rangel Reina, Daniel A., Rarra, Vayia, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M., Regecova, Valeria, Revilla, Luis, Rezaianzadeh, Abbas, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, de Wit, Tobias F. Rinke, Ritti-Dias, Raphael M., Robitaille, Cynthia, Rodriguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, Maria, Rodriguez-Villamizar, Laura A., Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Romaguera, Dora, Romeo, Elisabetta L., Rosengren, Annika, Roy, Joel G. R., Rubinstein, Adolfo, Ruidavets, Jean-Bernard, Sandra Ruiz-Betancourt, Blanca, Ruiz-Castell, Maria, Rusakova, Iuliia A., Russo, Paola, Rutkowski, Marcin, Sabanayagam, Charumathi, Sabbaghi, Hamideh, Sachdev, Harshpal S., Sadjadi, Alireza, Safarpour, Ali Reza, Safi, Sare, Safiri, Saeid, Saidi, Olfa, Saki, Nader, Salanave, Benoit, Salazar Martinez, Eduardo, Salmeron, Diego, Salomaa, Veikko, Salonen, Jukka T., Salvetti, Massimo, Sanchez-Abanto, Jose, Sans, Susana, Santos, Diana A., Santos, Ina S., Santos, Lelita C., Santos, Maria Paula, Santos, Rute, Saramies, Jouko L., Sardinha, Luis B., Sarganas, Giselle, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savvas, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D., Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O., Schnohr, Peter, Schoettker, Ben, Schramm, Sara, Schultsz, Constance, Schutte, Aletta E., Sebert, Sylvain, Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O., Sepanlou, Sadaf G., Servais, Jennifer, Shalnova, Svetlana A., Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K., Shaw, Jonathan E., Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M., de Moura Silva, Caroline Ramos, Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A., Sjostrom, Michael, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobngwi, Eugene, Soderberg, Stefan, Soemantri, Agustinus, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sorensen, Thorkild I. A., Sorgjerd, Elin P., Soric, Maroje, Jerome, Charles Sossa, Soumare, Aicha, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Staessen, Jan A., Starc, Gregor, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D., Stergiou, George S., Stessman, Jochanan, Stieber, Jutta, Stoeckl, Doris, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Suka, Machi, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G., Syddall, Holly E., Sylva, Rene Charles, Szklo, Moyses, Tai, E. Shyong, Tammesoo, Mari-Liis, Tamosiunas, Abdonas, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B., Taylor, Anne, Taylor, Julie, Tebar, William R., Tell, Grethe S., Tello, Tania, Tham, Yih Chung, Thankappan, K. R., Theobald, Holger, Theodoridis, Xenophon, Thinggaard, Mikael, Thomas, Nihal, Thorand, Barbara, Thuesen, Betina H., Timmermans, Erik J., Tjandrarini, Dwi H., Tjonneland, Anne, Toft, Ulla, Tolonen, Hanna K., Tolstrup, Janne S., Topbas, Murat, Topor-Madry, Roman, Jose Tormo, Maria, Tornaritis, Michael J., Torrent, Maties, Torres-Collado, Laura, Touloumi, Giota, Traissac, Pierre, Triantafyllou, Areti, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Trinh, Oanh T. H., Trivedi, Atul, Tshepo, Lechaba, Tsugane, Shoichiro, Tuliakova, Azaliia M., Tulloch-Reid, Marshall K., Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L., Twig, Gilad, Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ulmer, Hanno, Uusitalo, Hannu M. T., Valdivia, Gonzalo, Valvi, Damaskini, van Dam, Rob M., van den Born, Bert-Jan, Van der Heyden, Johan, van der Schouw, Yvonne T., Van Herck, Koen, Hoang Van Minh, Van Schoor, Natasja M., van Valkengoed, Irene G. M., van Zutphen, Elisabeth M., Vanuzzo, Diego, Varbo, Anette, Vasan, Senthil K., Vega, Tomas, Veidebaum, Toomas, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Verschuren, W. M. Monique, Verstraeten, Roosmarijn, Victora, Cesar G., Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesus, Virtanen, Jyrki K., Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Ari, Wade, Alisha N., Walton, Janette, Wambiya, Elvis O. A., Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, Wanderley Junior, Rildo de Souza, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S. Goya, Wareham, Nicholas, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H., Widhalm, Kurt, Wiecek, Andrzej, Wilks, Rainford J., Willeit, Johann, Willeit, Peter, Williams, Emmanuel A., Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A., Wong, Andrew, Wong, Tien Yin, Woo, Jean, Wu, Frederick C., Wu, Shouling, Wyszynska, Justyna, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K., Yoosefi, Moein, Yoshihara, Akihiro, You, San-Lin, Younger-Coleman, Novie O., Yusoff, Ahmad Faudzi, Zainuddin, Ahmad A., Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antonis, Elisa Zapata, Maria, Zaw, Ko Ko, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhao, Dong, Zhao, Ming-Hui, Zhen, Shiqi, Zheng, Yingfeng, Zholdin, Bekbolat, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Zoghlami, Nada, Zuniga Cisneros, Julio., School of Medicine, ACS - Diabetes & metabolism, APH - Global Health, Pulmonology, Medical Informatics, Adult Psychiatry, Global Health, APH - Quality of Care, APH - Methodology, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Anesthesiology, Graduate School, and ACS - Heart failure & arrhythmias
Subjects: Male, Latin Americans, Nutrition and Disease, Epidemiology, [SDV]Life Sciences [q-bio], Medizin, BLOOD-PRESSURE, 030204 cardiovascular system & hematology, Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants, Hypertension, Prevalence, Control, Tretament, GUIDELINES, Global Health, Worldwide trends, 0302 clinical medicine, Hypertension prevalence, Voeding en Ziekte, Medicine and Health Sciences, kohonnut verenpaine, Medicine, 030212 general & internal medicine, Prevention and Control, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, education.field_of_study, food and beverages, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Noncommunicable diseases, Period prevalence, Middle Aged, kansainvälinen vertailu, 3142 Public health care science, environmental and occupational health, 3. Good health, MIDDLE-INCOME, Pooled analysis, SYSTEMATIC ANALYSIS, INCOME COUNTRIES, ADULTS, PREVENTION, MANAGEMENT, ADHERENCE, DIAGNOSIS, Western europe, [SDE]Environmental Sciences, Hypertension/diagnosis, NCD Risk Factor Collaboration (NCD-RisC), Female, B990 Subjects Allied to Medicine not elsewhere classified, Life Sciences & Biomedicine, Adult, health-care, esiintyvyys, Central asia, Population, Nursing, 3121 Internal medicine, 03 medical and health sciences, Medicine, General & Internal, Drug Therapy, General & Internal Medicine, Life Science, Humans, ddc:610, education, Antihypertensive Agents, VLAG, Aged, Science & Technology, Antihypertensive Agents/therapeutic use, business.industry, Omvårdnad, fungi, General and internal medicine, Estados de Saúde e de Doença, Taking medication, Treatment, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Blood pressure, Faculdade de Ciências Sociais, 3121 General medicine, internal medicine and other clinical medicine, lääkehoito, 1182 Biochemistry, cell and molecular biology, business, Demography
Abstract: Background: hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods: we used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings: the number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings., British Heart Foundation Centre of Research Excellence Grant; World Health Organization (WHO); Abdul Latif Jameel Institute for Disease and Emergency Analytics Fellowship
Published: 2021

6. Egg consumption and risk of all-cause and cause-specific mortality in an Italian adult population

Author: Ruggiero, E, Di Castelnuovo, A, Costanzo, S, Persichillo, M, De Curtis, A, Cerletti, C, Donati, Mb, de Gaetano, G, Iacoviello, L, Bonaccio, M, Moli-sani Study Investigators: Licia Iacoviello, Giovanni de Gaetano, Maria Benedetta Donati, Marialaura, Bonaccio, Americo, Bonanni, Chiara, Cerletti, Simona, Costanzo, Amalia De Curtis, Augusto Di Castelnuovo, Francesco, Gianfagna, Mariarosaria, Persichillo, Teresa Di Prospero, Jos, Vermylen, Ignacio De Paula Carrasco, Antonio, Spagnuolo, Deodato, Assanelli, Vincenzo, Centritto, Marco, Olivieri, Teresa, Panzera, Marialaura Bonaccio Simona Costanzo Simona Esposito, Gialluisi, A, Emilia, Ruggiero, Sara, Magnacca, Benedetta, Izzi, Annalisa, Marotta, Fabrizia, Noro, Roberta, Parisi, Alfonsina, Tirozzi, Francesca, Bracone, Francesca De Lucia, Cristiana, Mignogna, and Livia, Rago
Subjects: Adult, Male, Mediterranean diet, Eggs, Medicine (miscellaneous), Physiology, Blood lipids, Disease, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Cause of Death, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Mortality risk, Cause of death, Nutrition and Dietetics, business.industry, Hazard ratio, Original Contribution, Dietary cholesterol, Diet, Italy, Cardiovascular Diseases, Cohort, Female, business, Cohort study
Abstract: Purpose Dietary guidelines recommend to limit egg consumption to 4 servings per week but the relation between egg intake and health outcomes is still controversial. To evaluate the association of egg consumption and mortality risk in Italian adults and to investigate nutritional factors and serum lipids as potentially explaining such associations. Methods Longitudinal analysis on 20,562 men and women aged ≥ 35y, free from cardiovascular disease (CVD) and cancer belonging to the Moli-sani Study cohort (enrolled 2005–2010) followed up for a median of 8.2 years. Results In multivariable-adjusted analysis as compared to low intake (> 0 ≤ 1 egg/week), eating > 4 eggs/week led to an increased risk of all-cause (Hazard ratio [HR] = 1.50; 95%CI 1.13–1.99), CVD (HR = 1.75; 1.07–2.87) and cancer mortality (HR = 1.52; 0.99–2.33). Similarly, an intake of 2–4 eggs/week was associated with higher all-cause (HR = 1.22; 1.01–1.46) and CVD mortality risk (HR = 1.43; 1.03–1.97). An increase of 1 egg per week was associated with higher mortality risk among high-risk individuals, such as those with hypertension and hyperlipidaemia. Dietary cholesterol explained about 43.0% and 39.3% (p values e.g., total cholesterol) accounted for a small proportion of egg-mortality relation. Conclusions Among Italian adults, high egg consumption leads to an increased risk of all-cause and CVD mortality, with the risk being evident even at the recommended intake of 2–4 eggs per week. A substantial part of this association was likely due to the egg contribution to dietary cholesterol. Our findings suggest limiting the consumption of eggs in the diet and these results should be considered in the development of dietary guidelines and updates.
Published: 2021

7. Combined influence of depression severity and low-grade inflammation on incident hospitalization and mortality risk in Italian adults

Author: Chiara Cerletti, Augusto Di Castelnuovo, Simona Costanzo, Alessandro Gialluisi, Licia Iacoviello, Francesca Bracone, Amalia De Curtis, Marialaura Bonaccio, Giovanni de Gaetano, Moli-sani Study Investigators, Sara Magnacca, and Maria Benedetta Donati
Subjects: Adult, Male, Mediation (statistics), medicine.medical_specialty, lifestyles, Systemic inflammation, Low grade inflammation, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, cardiovascular disease, Internal medicine, Diabetes mellitus, Humans, cancer, Medicine, hospitalizations, Stroke, Depression (differential diagnoses), diabetes, business.industry, medicine.disease, mortality, stroke, 030227 psychiatry, Hospitalization, Patient Health Questionnaire, Psychiatry and Mental health, Clinical Psychology, Italy, depression, inflammation, Cohort, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Background Depression and low-grade systemic inflammation are associated risk factors for hospitalizations and mortality, although the nature of this relationship is under-investigated. Methods We performed multivariable Cox regressions of first hospitalization/mortality for all and specific causes vs depression severity, in an Italian population cohort (N=13,176; age≥35 years; 49.4% men), incrementally adjusting for sociodemographic, health and lifestyle factors. We tested potential mediation, additive and interactive effects of INFLA-score, a composite circulating inflammation index, and potential concurrent mediations of main lifestyles and chronic conditions. Results Over 4,856 hospitalizations (median follow-up 7.28 years), we observed an increased incident risk of events by 24% (CI=17-32%) and 59% (30-90%) for moderate and severe depression, which also showed a 125% (33-281%) increased risk of all-cause mortality (over 471 deaths, 8.24 years). These remained stable after adjustment for lifestyles, health conditions and INFLA-score, which explained 2.1%, 7.6%, 16.3% and 8%, 14.9% and 12% of depression influence on hospitalizations and mortality risk, respectively. These proportions remained substantially stable after reciprocal adjustments. INFLA-score showed significant additive (but not interactive) effects on both hospitalizations and mortality risk. Limitations Depression severity was defined using a sub-version of Patient Health Questionnaire 9, which was validated here. Directionality links among exposures could not be established since they were collected simultaneously. Conclusions These findings suggest a combined influence of depression and low-grade inflammation on health, which is partly intertwined and dependent on lifestyles and chronic conditions. This suggests the existence of pathways other than inflammation through which depression may play its detrimental effect.
Published: 2021

8. Clinical Network for Big Data and Personalized Health: Study Protocol and Preliminary Results

Author: Simona, Esposito, Sabatino, Orlandi, Sara, Magnacca, Amalia, De Curtis, Alessandro, Gialluisi, Licia, Iacoviello, and On Behalf Of The Neuromed Clinical Network Big Data And Personalised Health Investigators
Subjects: Adult, Big Data, Male, electronical health records, Informed Consent, Medical Records Systems, Computerized, Health, Toxicology and Mutagenesis, personalized medicine, prevention, Aged, Chronic Disease, Female, Hospitals, Humans, Middle Aged, Public Health, Environmental and Occupational Health, Computerized, Medical Records Systems
Abstract: The use of secondary hospital-based clinical data and electronical health records (EHR) represent a cost-efficient alternative to investigate chronic conditions. We present the Clinical Network Big Data and Personalised Health project, which collects EHRs for patients accessing hospitals in Central-Southern Italy, through an integrated digital platform to create a digital hub for the collection, management and analysis of personal, clinical and environmental information for patients, associated with a biobank to perform multi-omic analyses. A total of 12,864 participants (61.7% women, mean age 52.6 ± 17.6 years) signed a written informed consent to allow access to their EHRs. The majority of hospital access was in obstetrics and gynaecology (36.3%), while the main reason for hospitalization was represented by diseases of the circulatory system (21.2%). Participants had a secondary education (63.5%), were mostly retired (25.45%), reported low levels of physical activity (59.6%), had low adherence to the Mediterranean diet and were smokers (30.2%). A large percentage (35.8%) were overweight and the prevalence of hypertension, diabetes and hyperlipidemia was 36.4%, 11.1% and 19.6%, respectively. Blood samples were retrieved for 8686 patients (67.5%). This project is aimed at creating a digital hub for the collection, management and analysis of personal, clinical, diagnostic and environmental information for patients, and is associated with a biobank to perform multi-omic analyses.
Published: 2022

9. Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study

Author: Augusto Di Castelnuovo, Marialaura Bonaccio, Simona Costanzo, Alessandro Gialluisi, Andrea Antinori, Nausicaa Berselli, Lorenzo Blandi, Raffaele Bruno, Roberto Cauda, Giovanni Guaraldi, Ilaria My, Lorenzo Menicanti, Giustino Parruti, Giuseppe Patti, Stefano Perlini, Francesca Santilli, Carlo Signorelli, Giulio G. Stefanini, Alessandra Vergori, Amina Abdeddaim, Walter Ageno, Antonella Agodi, Piergiuseppe Agostoni, Luca Aiello, Samir Al Moghazi, Filippo Aucella, Greta Barbieri, Alessandro Bartoloni, Carolina Bologna, Paolo Bonfanti, Serena Brancati, Francesco Cacciatore, Lucia Caiano, Francesco Cannata, Laura Carrozzi, Antonio Cascio, Antonella Cingolani, Francesco Cipollone, Claudia Colomba, Annalisa Crisetti, Francesca Crosta, Gian B. Danzi, Damiano D'Ardes, Katleen de Gaetano Donati, Francesco Di Gennaro, Gisella Di Palma, Giuseppe Di Tano, Massimo Fantoni, Tommaso Filippini, Paola Fioretto, Francesco M. Fusco, Ivan Gentile, Leonardo Grisafi, Gabriella Guarnieri, Francesco Landi, Giovanni Larizza, Armando Leone, Gloria Maccagni, Sandro Maccarella, Massimo Mapelli, Riccardo Maragna, Rossella Marcucci, Giulio Maresca, Claudia Marotta, Lorenzo Marra, Franco Mastroianni, Alessandro Mengozzi, Francesco Menichetti, Jovana Milic, Rita Murri, Arturo Montineri, Roberta Mussinelli, Cristina Mussini, Maria Musso, Anna Odone, Marco Olivieri, Emanuela Pasi, Francesco Petri, Biagio Pinchera, Carlo A. Pivato, Roberto Pizzi, Venerino Poletti, Francesca Raffaelli, Claudia Ravaglia, Giulia Righetti, Andrea Rognoni, Marco Rossato, Marianna Rossi, Anna Sabena, Francesco Salinaro, Vincenzo Sangiovanni, Carlo Sanrocco, Antonio Scarafino, Laura Scorzolini, Raffaella Sgariglia, Paola G. Simeone, Enrico Spinoni, Carlo Torti, Enrico M. Trecarichi, Francesca Vezzani, Giovanni Veronesi, Roberto Vettor, Andrea Vianello, Marco Vinceti, Raffaele De Caterina, Licia Iacoviello, Di Castelnuovo, A., Bonaccio, M., Costanzo, S., Gialluisi, A., Antinori, A., Berselli, N., Blandi, L., Bruno, R., Cauda, R., Guaraldi, G., My, I., Menicanti, L., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., Vergori, A., Abdeddaim, A., Ageno, W., Agodi, A., Agostoni, P., Aiello, L., Al Moghazi, S., Aucella, F., Barbieri, G., Bartoloni, A., Bologna, C., Bonfanti, P., Brancati, S., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Cingolani, A., Cipollone, F., Colomba, C., Crisetti, A., Crosta, F., Danzi, G. B., D'Ardes, D., de Gaetano Donati, K., Di Gennaro, F., Di Palma, G., Di Tano, G., Fantoni, M., Filippini, T., Fioretto, P., Fusco, F. M., Gentile, I., Grisafi, L., Guarnieri, G., Landi, F., Larizza, G., Leone, A., Maccagni, G., Maccarella, S., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marotta, C., Marra, L., Mastroianni, F., Mengozzi, A., Menichetti, F., Milic, J., Murri, R., Montineri, A., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Pasi, E., Petri, F., Pinchera, B., Pivato, C. A., Pizzi, R., Poletti, V., Raffaelli, F., Ravaglia, C., Righetti, G., Rognoni, A., Rossato, M., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scarafino, A., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinoni, E., Torti, C., Trecarichi, E. M., Vezzani, F., Veronesi, G., Vettor, R., Vianello, A., Vinceti, M., De Caterina, R., Iacoviello, L., Di Castelnuovo, Augusto, Bonaccio, Marialaura, Costanzo, Simona, Gialluisi, Alessandro, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bruno, Raffaele, Cauda, Roberto, Guaraldi, Giovanni, My, Ilaria, Menicanti, Lorenzo, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G, Vergori, Alessandra, Abdeddaim, Amina, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bologna, Carolina, Bonfanti, Paolo, Brancati, Serena, Cacciatore, Francesco, Caiano, Lucia, Cannata, Francesco, Carrozzi, Laura, Cascio, Antonio, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian B, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Palma, Gisella, Di Tano, Giuseppe, Fantoni, Massimo, Filippini, Tommaso, Fioretto, Paola, Fusco, Francesco M, Gentile, Ivan, Grisafi, Leonardo, Guarnieri, Gabriella, Landi, Francesco, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Maccarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mengozzi, Alessandro, Menichetti, Francesco, Milic, Jovana, Murri, Rita, Montineri, Arturo, Mussinelli, Roberta, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Pasi, Emanuela, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A, Pizzi, Roberto, Poletti, Venerino, Raffaelli, Francesca, Ravaglia, Claudia, Righetti, Giulia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scarafino, Antonio, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola G, Spinoni, Enrico, Torti, Carlo, Trecarichi, Enrico M, Vezzani, Francesca, Veronesi, Giovanni, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A, Bonaccio, M, Costanzo, S, Gialluisi, A, Antinori, A, Berselli, N, Blandi, L, Bruno, R, Cauda, R, Guaraldi, G, My, I, Menicanti, L, Parruti, A, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abdeddaim, A, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Aucella, F, Barbieri, G, Bartoloni, A, Bologna, C, Bonfanti, P, Brancati, S, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Cingolani, A, Cipollone, F, Colomba, C, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Palma, G, Di Tano, G, Fantoni, M, Filippini, T, Fioretto, P, Fusco, F, Gentile, I, Grisafi, L, Guarnieri, G, Landi, F, Larizza, G, Leone, A, Maccagni, G, Maccarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marotta, C, Marra, L, Mastroianni, F, Mengozzi, A, Menichetti, F, Milic, J, Miurri, R, Montineri, A, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Petri, F, Pinchera, B, Pivato, C, Pizzi, R, Poletti, V, Raffaelli, F, Ravaglia, C, Righetti, G, Rognoni, A, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scarafino, A, Scorzolini, L, Sgariglia, R, Simeone, P, Spinoni, E, Torti, C, Trecarichi, E, Vezzani, F, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, De Caterina, R, and Iacoviello, L
Subjects: Male, Epidemiology, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030204 cardiovascular system & hematology, computer.software_genre, Machine Learning, 0302 clinical medicine, Retrospective Studie, Risk Factors, Cardiovascular Disease, 80 and over, Medicine, Age Factor, Viral, Hospital Mortality, Betacoronavirus Hospital Mortality, Young adult, Aged, 80 and over, Nutrition and Dietetics, COVID-19, In-hospital mortality, Risk factors, Mortality rate, Hazard ratio, Age Factors, Middle Aged, C-Reactive Protein, Cardiovascular Diseases, Female, Survival Analysi, Cardiology and Cardiovascular Medicine, Coronavirus Infections, Human, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Adolescent, Pneumonia, Viral, 030209 endocrinology & metabolism, Settore MED/17 - MALATTIE INFETTIVE, Machine learning, Aged, Humans, Pandemics, Retrospective Studies, SARS-CoV-2, Survival Analysis, Young Adult, Betacoronavirus, Article, 03 medical and health sciences, Risk factor, Survival analysis, Pandemic, Betacoronaviru, business.industry, Coronavirus Infection, Risk Factor, Retrospective cohort study, Pneumonia, Confidence interval, Artificial intelligence, business, computer
Abstract: Background and aims There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels, Highlights • Impaired renal function, elevated C-reactive protein and advanced age were major indicators of death in COVID-19 patients. • These associations were substantially homogenous across all sub-groups analysed. • No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. • Death rates were higher in the Northern as opposed to Central-Southern Italian regions.
Published: 2020

10. Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

Author: Venerino Poletti, Damiano D'Ardes, Paola Simeone, Cristina Mussini, Giustino Parruti, Sandro Maccarella, Licia Iacoviello, Giulio G. Stefanini, Roberta Mussinelli, Vincenzo Sangiovanni, Paolo Bonfanti, Roberto Vettor, Andrea Vianello, Arturo Montineri, Roberto Cauda, Elvira Grandone, Maria Mazzitelli, Claudia Ravaglia, Marialaura Bonaccio, Giulio Maresca, Francesco Di Gennaro, Alessandro Mengozzi, Anna Sabena, Gian Battista Danzi, Giuseppe Di Tano, Emanuela Pasi, Ilaria Rossi, Lucia Caiano, Laura Carrozzi, Francesco Landi, Francesca Crosta, Tommaso Filippini, Francesco Menichetti, Piergiuseppe Agostoni, Andrea Madaro, Antonio Cascio, Carlo Signorelli, Michele Spinicci, Carlo Sanrocco, Enrico Guido Spinoni, Maria Musso, Alessandra Vergori, Lorenzo Marra, Giuseppe Patti, Laura Vocciante, Marco Olivieri, Francesca Santilli, Stefano Perlini, Claudia Colomba, Francesco Salinaro, Marianna Meschiari, Gabriella Guarnieri, Giampiero D'Offizi, Riccardo Maragna, Paola Del Giacomo, Giancarlo Gini, Katleen de Gaetano Donati, Andrea Antinori, Filippo Aucella, Raffaele De Caterina, Lorenzo Menicanti, Gloria Maccagni, Amedeo Venezia, Chiara Dal Pra, Carlo Andrea Pivato, Walter Ageno, Antonella Agodi, Francesco Cannata, Francesco Petri, Luca Aiello, Biagio Pinchera, Marinella Astuto, Raffaella Sgariglia, Giovanni Guaraldi, Marco Vinceti, Laura Scorzolini, Samir Al Moghazi, Armando Leone, Giovanni Veronesi, Arturo Ciccullo, Leonardo Grisafi, Francesco Cipollone, Massimo Mapelli, Greta Barbieri, Silvia Lamonica, Raffaele Bruno, Filippo Minutolo, Antonella Cingolani, Alessandro Gialluisi, Marco Rossato, Andrea Rognoni, Marianna Rossi, Claudia Marotta, Franco Mastroianni, Ilaria My, Enrico Maria Trecarichi, Anna Odone, Alessandro Bartoloni, Simona Costanzo, Francesco Cacciatore, Ivan Gentile, Massimo Rinaldi, Nausicaa Berselli, Francesco Maria Fusco, Augusto Di Castelnuovo, Lorenzo Blandi, Castelnuovo A.D., Costanzo S., Antinori A., Berselli N., Blandi L., Bruno R., Cauda R., Guaraldi G., Menicanti L., My I., Parruti G., Patti G., Perlini S., Santilli F., Signorelli C., Spinoni E., Stefanini G.G., Vergori A., Ageno W., Agodi A., Aiello L., Agostoni P., Moghazi S.A., Astuto M., Aucella F., Barbieri G., Bartoloni A., Bonaccio M., Bonfanti P., Cacciatore F., Caiano L., Cannata F., Carrozzi L., Cascio A., Ciccullo A., Cingolani A., Cipollone F., Colomba C., Crosta F., Pra C.D., Danzi G.B., D'Ardes D., Donati K.D.G., Giacomo P.D., Gennaro F.D., Di Tano G., D'Offizi G., Filippini T., Fusco F.M., Gentile I., Gialluisi A., Gini G., Grandone E., Grisafi L., Guarnieri G., Lamonica S., Landi F., Leone A., Maccagni G., Maccarella S., Madaro A., Mapelli M., Maragna R., Marra L., Maresca G., Marotta C., Mastroianni F., Mazzitelli M., Mengozzi A., Menichetti F., Meschiari M., Minutolo F., Montineri A., Mussinelli R., Mussini C., Musso M., Odone A., Olivieri M., Pasi E., Petri F., Pinchera B., Pivato C.A., Poletti V., Ravaglia C., Rinaldi M., Rognoni A., Rossato M., Rossi I., Rossi M., Sabena A., Salinaro F., Sangiovanni V., Sanrocco C., Scorzolini L., Sgariglia R., Simeone P.G., Spinicci M., Trecarichi E.M., Venezia A., Veronesi G., Vettor R., Vianello A., Vinceti M., Vocciante L., De Caterina R., Iacoviello L., Castelnuovo, A. D., Costanzo, S., Antinori, A., Berselli, N., Blandi, L., Bruno, R., Cauda, R., Guaraldi, G., Menicanti, L., My, I., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Spinoni, E., Stefanini, G. G., Vergori, A., Ageno, W., Agodi, A., Aiello, L., Agostoni, P., Moghazi, S. A., Astuto, M., Aucella, F., Barbieri, G., Bartoloni, A., Bonaccio, M., Bonfanti, P., Cacciatore, F., Caiano, L., Cannata, F., Carrozzi, L., Cascio, A., Ciccullo, A., Cingolani, A., Cipollone, F., Colomba, C., Crosta, F., Pra, C. D., Danzi, G. B., D'Ardes, D., Donati, K. D. G., Giacomo, P. D., Gennaro, F. D., Di Tano, G., D'Offizi, G., Filippini, T., Fusco, F. M., Gentile, I., Gialluisi, A., Gini, G., Grandone, E., Grisafi, L., Guarnieri, G., Lamonica, S., Landi, F., Leone, A., Maccagni, G., Maccarella, S., Madaro, A., Mapelli, M., Maragna, R., Marra, L., Maresca, G., Marotta, C., Mastroianni, F., Mazzitelli, M., Mengozzi, A., Menichetti, F., Meschiari, M., Minutolo, F., Montineri, A., Mussinelli, R., Mussini, C., Musso, M., Odone, A., Olivieri, M., Pasi, E., Petri, F., Pinchera, B., Pivato, C. A., Poletti, V., Ravaglia, C., Rinaldi, M., Rognoni, A., Rossato, M., Rossi, I., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scorzolini, L., Sgariglia, R., Simeone, P. G., Spinicci, M., Trecarichi, E. M., Venezia, A., Veronesi, G., Vettor, R., Vianello, A., Vinceti, M., Vocciante, L., De Caterina, R., Iacoviello, L., Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bruno, R, Cauda, R, Guaraldi, G, Menicanti, L, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Spinoni, E, Stefanini, G, Vergori, A, Ageno, W, Agodi, A, Aiello, L, Agostoni, P, Moghazi, S, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonaccio, M, Bonfanti, P, Cacciatore, F, Caiano, L, Cannata, F, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Crosta, F, Pra, C, Danzi, G, D'Ardes, D, Donati, K, Giacomo, P, Gennaro, F, Tano, G, D'Offizi, G, Filippini, T, Fusco, F, Gentile, I, Gialluisi, A, Gini, G, Grandone, E, Grisafi, L, Guarnieri, G, Lamonica, S, Landi, F, Leone, A, Maccagni, G, Maccarella, S, Madaro, A, Mapelli, M, Maragna, R, Marra, L, Maresca, G, Marotta, C, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Minutolo, F, Montineri, A, Mussinelli, R, Mussini, C, Musso, M, Odone, A, Olivieri, M, Pasi, E, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rinaldi, M, Rognoni, A, Rossato, M, Rossi, I, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Spinicci, M, Trecarichi, E, Venezia, A, Veronesi, G, Vettor, R, Vianello, A, Vinceti, M, Vocciante, L, De Caterina, R, and Iacoviello, L
Subjects: Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, Lower risk, law.invention, COVID-19, Disease severity, Hydroxychloroquine, Inflammation, Mortality, Aged, Aged, 80 and over, Female, Hospital Mortality, Humans, Italy, Middle Aged, Retrospective Studies, Treatment Outcome, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Retrospective Studie, law, Internal medicine, 80 and over, Internal Medicine, medicine, 030212 general & internal medicine, Risk factor, business.industry, Mortality rate, Retrospective cohort study, COVID-19 Drug Treatment, Propensity score matching, Commentary, Observational study, business, Human, medicine.drug
Abstract: Background Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.
Published: 2020

11. RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

Author: Francesca Santilli, Marianna Meschiari, Gabriella Guarnieri, Francesco Petri, Anna Sabena, Gloria Maccagni, Giovanni Larizza, Massimo Mapelli, Maria Mazzitelli, Gian Battista Danzi, Katleen de Gaetano Donati, Annalisa Crisetti, Jovana Milic, Raffaele Pesavento, Biagio Pinchera, Riccardo Maragna, Carlo Andrea Pivato, Lorenzo Menicanti, Francesco Maria Fusco, Luca Aiello, Sandro Mancarella, Carlo Sanrocco, Alessandra Vergori, Greta Barbieri, Filippo Aucella, Silvia Marongiu, Giulio Maresca, Marianna Rossi, Andrea Antinori, Venerino Poletti, Francesco Cacciatore, Giacomo Castiglione, Enrico Maria Trecarichi, Lucia Caiano, Francesca Crosta, Roberto Vettor, Francesco Menichetti, Maria Musso, Francesco Salinaro, Marco Olivieri, Stefano Perlini, Claudia Colomba, Crizia Colombo, Ottavia Cozzi, Stefano Maitan, Marialaura Bonaccio, Ilaria My, Alexandra Virano, Paola Simeone, Marco Vinceti, Antonella Cingolani, Gianpiero D'Offizi, Damiano D'Ardes, Claudia Marotta, M. B. Lucia, Carlo Signorelli, Lorenzo Marra, Giuseppe Patti, Raffaele De Caterina, Armando Leone, Veronica Lio, Beatrice Molena, Giustino Parruti, Giulio G. Stefanini, Licia Iacoviello, Laura Vocciante, Franco Mastroianni, Raffaella Sgariglia, Cristina Mussini, Francesco Cipollone, Marco Rossato, Lorenzo Blandi, Emanuela Pasi, Samir Al Moghazi, Andrea Vianello, Filippo Minutolo, Ivan Gentile, Giovanni Guaraldi, Rosa Manuele, Pasquale Abete, Arturo Ciccullo, Antonella Palimodde, Giancarlo Scoppettuolo, Walter Ageno, Marco G. Mennuni, Roberta Mussinelli, Vincenzo Sangiovanni, Roberto Cauda, Laura Scorzolini, Paolo Bonfanti, Alessandro Gialluisi, Stefania Cianfrone, Piergiuseppe Agostoni, Antonio Cascio, Simona Costanzo, Augusto Di Castelnuovo, Nausicaa Berselli, Rosa Arboretti, Emauele Graziani, Martina Barchitta, Anna Odone, Francesco Di Gennaro, Alessandro Mengozzi, Alessandro Bartoloni, Giuseppe Di Tano, Laura Carrozzi, Ferruccio Madaro, Rossella Marcucci, Claudia Ravaglia, Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Gialluisi, Alessandro, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Mussinelli, Roberta, My, Ilaria, Parruti, Giustino, Patti, Giuseppe, Perlini, Stefano, Santilli, Francesca, Signorelli, Carlo, Stefanini, Giulio G., Vergori, Alessandra, Abete, Pasquale, Ageno, Walter, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Aucella, Filippo, Barbieri, Greta, Barchitta, Martina, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Castiglione, Giacomo, Cianfrone, Stefania, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Cozzi, Ottavia, Crisetti, Annalisa, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fusco, Francesco Maria, Gentile, Ivan, Graziani, Emauele, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Lio, Veronica, Lucia, Mothanje Barbara, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Manuele, Rosa, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Mussini, Cristina, Musso, Maria, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Pivato, Carlo A., Poletti, Venerino, Ravaglia, Claudia, Rossato, Marco, Rossi, Marianna, Sabena, Anna, Salinaro, Francesco, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scoppettuolo, Giancarlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Trecarichi, Enrico Maria, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo, A., Costanzo, S., Antinori, A., Berselli, N., Bl, I, L., Bonaccio, M., Cauda, R., Gialluisi, A., Guaraldi, G., Menicanti, L., Mennuni, M., Mussinelli, R., My, I., Parruti, G., Patti, G., Perlini, S., Santilli, F., Signorelli, C., Stefanini, G. G., Vergori, A., Abete, P., Ageno, W., Agostoni, P., Aiello, L., Al Moghazi, S., Arboretti, R., Aucella, F., Barbieri, G., Barchitta, M., Bartoloni, A., Bonfanti, P., Cacciatore, F., Caiano, L., Carrozzi, L., Cascio, A., Castiglione, G., Cianfrone, S., Ciccullo, A., Cingolani, A., Cipollone, F., Colomba, C., Colombo, C., Cozzi, O., Crisetti, A., Crosta, F., Danzi, G. B., D'Ardes, D., de Gaetano Donati, K., Di Gennaro, F., Di Tano, G., D'Offizi, G., Fusco, F. M., Gentile, I., Graziani, E., Guarnieri, G., Larizza, G., Leone, A., Lio, V., Lucia, M. B., Maccagni, G., Madaro, F., Maitan, S., Mancarella, S., Manuele, R., Mapelli, M., Maragna, R., Marcucci, R., Maresca, G., Marongiu, S., Marotta, C., Marra, L., Mastroianni, F., Mazzitelli, M., Mengozzi, A., Menichetti, F., Meschiari, M., Milic, J., Minutolo, F., Molena, B., Mussini, C., Musso, M., Odone, A., Olivieri, M., Palimodde, A., Pasi, E., Pesavento, R., Petri, F., Pinchera, B., Pivato, C. A., Poletti, V., Ravaglia, C., Rossato, M., Rossi, M., Sabena, A., Salinaro, F., Sangiovanni, V., Sanrocco, C., Scoppettuolo, G., Scorzolini, L., Sgariglia, R., Simeone, P. G., Trecarichi, E. M., Vettor, R., Vianello, A., Vinceti, M., Virano, A., Vocciante, L., De Caterina, R., Iacoviello, L., Blandi, L., Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Gialluisi, A, Guaraldi, G, Menicanti, L, Mennuni, M, Mussinelli, R, My, I, Parruti, G, Patti, G, Perlini, S, Santilli, F, Signorelli, C, Stefanini, G, Vergori, A, Abete, P, Ageno, W, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Aucella, F, Barbieri, G, Barchitta, M, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Castiglione, G, Cianfrone, S, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Cozzi, O, Crisetti, A, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fusco, F, Gentile, I, Graziani, E, Guarnieri, G, Larizza, G, Leone, A, Lio, V, Lucia, M, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Manuele, R, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Mussini, C, Musso, M, Odone, A, Olivieri, M, Palimodde, A, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Pivato, C, Poletti, V, Ravaglia, C, Rossato, M, Rossi, M, Sabena, A, Salinaro, F, Sangiovanni, V, Sanrocco, C, Scoppettuolo, G, Scorzolini, L, Sgariglia, R, Simeone, P, Trecarichi, E, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, Iacoviello, L, and De Caterina, R
Subjects: 0301 basic medicine, Male, Physiology, Middle Aged, Renin-Angiotensin System, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, ACE-I, ARB, COVID-19, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, mortality, sartans, Severity of Illness Index, Renin-Angiotensin System, 0302 clinical medicine, Risk Factors, 80 and over, Medicine, Hospital Mortality, Sartan, Aged, 80 and over, Incidence (epidemiology), Incidence, Hazard ratio, Angiotensin Receptor Antagonist, Middle Aged, Hospitalization, Antihypertensive Agent, Italy, Meta-analysis, Hypertension, Sartans, Molecular Medicine, Female, Risk assessment, Human, medicine.medical_specialty, Angiotensin converting enzyme inhibitors, Angiotensin receptor blockers, Mortality, Coronavirus disease 2019 (COVID-19), Risk Assessment, Article, COVID−19, 03 medical and health sciences, Angiotensin Receptor Antagonists, Meta-Analysis as Topic, Internal medicine, Severity of illness, Humans, Angiotensin receptor blocker, Antihypertensive Agents, Aged, Pharmacology, business.industry, Risk Factor, Angiotensin-Converting Enzyme Inhibitor, Confidence interval, 030104 developmental biology, COVID-19, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, mortality, sartans, Observational study, Angiotensin converting enzyme inhibitor, business
Abstract: Objective The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418 ) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting–enzyme inhibitors (ACE I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method. Results Out of 4069 COVID−19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID−19 treatments: 0.96, 95% confidence interval 0.77–1.20 and HR = 0.89, 0.67–1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N = 2057) patients (HR = 1.00, 0.78–1.26 and HR = 0.88, 0.65–1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID−19 adult patients, 9700 with hypertension) confirmed the absence of association. Conclusions In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID−19 patients.
Published: 2020

12. Retrospective Recall of Psychological Distress Experienced During the First COVID-19 Lockdown in Italy: Results From the ALT RISCOVID-19 Survey

Author: Francesca Bracone, Alessandro Gialluisi, Simona Costanzo, Augusto Di Castelnuovo, Mariarosaria Persichillo, Marco Olivieri, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, and Marialaura Bonaccio
Subjects: Adult, Male, Health (social science), SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, Middle Aged, anxiety, depression, lockdown, post-traumatic stress disorder, psychological distress, stress, Anxiety, Communicable Disease Control, Cross-Sectional Studies, Depression, Female, Humans, Italy, Retrospective Studies, Stress, Psychological, Surveys and Questionnaires, Psychological Distress, Psychological, Public aspects of medicine, RA1-1270
Abstract: Objectives: To estimate psychological distress experienced during the Italian lockdown (March-May 2020) by assessing, in the transition period of the pandemic (June-September 2020), participants’ recalling of their psychological state.Methods: Cross-sectional analysis on 1,880 adults (mean age 48.9 ± 14.5 years) from the web-based ALT RISCOVID-19 survey. Participants were asked to retrospectively recall their psychological state during lockdown concerning symptoms of depression (Patients’ Health Questionnaire), anxiety (General Anxiety Disorder), stress (Perceived Stress Scale) and post-traumatic stress (Screening Questionnaire for Disaster Mental Health).Results: Experienced symptoms of depression, anxiety and post-traumatic stress was recalled by 15.8, 15.3 and 13.1% of respondents, respectively. These psychometric scales tended to decrease during the 4-month period of assessment (p < 0.05), while perceived stress levels did not (p = 0.13). Men and older individuals reported lower symptoms of depression (β = −0.42 and β = −0.42; p < 0.0001, respectively), anxiety (β = −0.41 and β = −0.45; p < 0.0001, respectively), stress (β = −0.36 and β = 0.50; p < 0.0001, respectively) and post-traumatic stress (β = −0.42; p < 0.0001, men vs women).Conclusion: Recalled psychological distress experienced during COVID-19 lockdown tended to decrease during the transition period of the pandemic, except for stress. Women and younger people were at higher risk to recall psychological distress.
Published: 2022

13. Use of multidimensional item response theory methods for dementia prevalence prediction: an example using the Health and Retirement Survey and the Aging, Demographics, and Memory Study

Author: Nichols E, Abd-Allah F, Abdoli A, Abualhasan A, Abu-Gharbieh E, Afshin A, Akinyemi R, Alanezi F, Alipour V, Almasi-Hashiani A, Arabloo J, Ashraf-Ganjouei A, Ayano G, Ayuso-Mateos J, Baig A, Banach M, Barboza M, Barker-Collo S, Baune B, Bhagavathula A, Bhattacharyya K, Bijani A, Biswas A, Boloor A, Brayne C, Brenner H, Burkart K, Nagaraja S, Carvalho F, Castro-de-Araujo L, Catala-Lopez F, Cerin E, Cherbuin N, Chu D, Dai X, De Sa A, Djalalinia S, Douiri A, Edvardsson D, El-Jaafary S, Eskandarieh S, Faro A, Farzadfar F, Feigin V, Fereshtehnejad S, Fernandes E, Ferrara P, Filip I, Fischer F, Gaidhane S, Galluzzo L, Gebremeskel G, Ghashghaee A, Gialluisi A, Gnedovskaya E, Golechha M, Gupta R, Hachinski V, Haider M, Haile T, Hamiduzzaman M, Hankey G, Hay S, Heidari G, Heidari-Soureshjani R, Ho H, Househ M, Hwang B, Iacoviello L, Ilesanmi O, Ilic I, Ilic M, Irvani S, Iwagami M, Iyamu I, Jha R, Kalani R, Karch A, Kasa A, Khader Y, Khan E, Khatib M, Kim Y, Kisa S, Kisa A, Kivimaki M, Koyanagi A, Kumar M, Landires I, Lasrado S, Li B, Lim S, Liu X, Kunjathur S, Majeed A, Malik P, Mehndiratta M, Menezes R, Mohammad Y, Mohammed S, Mokdad A, Moni M, Nagel G, Naveed M, Nayak V, Nguyen C, Nguyen H, Nunez-Samudio V, Olagunju A, Ostroff S, Otstavnov N, Owolabi M, Kan F, Patel U, Phillips M, Piradov M, Pond C, Pottoo F, Prada S, Radfar A, Rahim F, Rana J, Rashedi V, Rawaf S, Rawaf D, Reinig N, Renzaho A, Rezaei N, Rezapour A, Romoli M, Roshandel G, Sachdev P, Sahebkar A, Sahraian M, Samaei M, Saylan M, Sha F, Shaikh M, Shibuya K, Shigematsu M, Shin J, Shiri R, Silva D, Singh J, Singhal D, Skryabin V, Skryabina A, Soheili A, Sotoudeh H, Spurlock E, Szoeke C, Tabares-Seisdedos R, Taddele B, Tovani-Palone M, Tsegaye G, Vacante M, Venketasubramanian N, Vidale S, Vlassov V, Vu G, Wang Y, Weiss J, Weldemariam A, Westerman R, Wimo A, Winkler A, Wu C, Yadollahpour A, Yesiltepe M, Yonemoto N, Yu C, Zastrozhin M, Zastrozhina A, Zhang Z, Murray C, Vos T, Apollo - University of Cambridge Repository, Nichols, E, Abd-Allah, F, Abdoli, A, Abualhasan, A, Abu-Gharbieh, E, Afshin, A, Akinyemi, R, Alanezi, F, Alipour, V, Almasi-Hashiani, A, Arabloo, J, Ashraf-Ganjouei, A, Ayano, G, Ayuso-Mateos, J, Baig, A, Banach, M, Barboza, M, Barker-Collo, S, Baune, B, Bhagavathula, A, Bhattacharyya, K, Bijani, A, Biswas, A, Boloor, A, Brayne, C, Brenner, H, Burkart, K, Burugina Nagaraja, S, Carvalho, F, Castro-de-Araujo, L, Catala-Lopez, F, Cerin, E, Cherbuin, N, Chu, D, Dai, X, de Sa-Junior, A, Djalalinia, S, Douiri, A, Edvardsson, D, El-Jaafary, S, Eskandarieh, S, Faro, A, Farzadfar, F, Feigin, V, Fereshtehnejad, S, Fernandes, E, Ferrara, P, Filip, I, Fischer, F, Gaidhane, S, Galluzzo, L, Gebremeskel, G, Ghashghaee, A, Gialluisi, A, Gnedovskaya, E, Golechha, M, Gupta, R, Hachinski, V, Haider, M, Haile, T, Hamiduzzaman, M, Hankey, G, Hay, S, Heidari, G, Heidari-Soureshjani, R, Ho, H, Househ, M, Hwang, B, Iacoviello, L, Ilesanmi, O, Ilic, I, Ilic, M, Irvani, S, Iwagami, M, Iyamu, I, Jha, R, Kalani, R, Karch, A, Kasa, A, Khader, Y, Khan, E, Khatib, M, Kim, Y, Kisa, S, Kisa, A, Kivimaki, M, Koyanagi, A, Kumar, M, Landires, I, Lasrado, S, Li, B, Lim, S, Liu, X, Madhava Kunjathur, S, Majeed, A, Malik, P, Mehndiratta, M, Menezes, R, Mohammad, Y, Mohammed, S, Mokdad, A, Moni, M, Nagel, G, Naveed, M, Nayak, V, Nguyen, C, Nguyen, H, Nunez-Samudio, V, Olagunju, A, Ostroff, S, Otstavnov, N, Owolabi, M, Pashazadeh Kan, F, Patel, U, Phillips, M, Piradov, M, Pond, C, Pottoo, F, Prada, S, Radfar, A, Rahim, F, Rana, J, Rashedi, V, Rawaf, S, Rawaf, D, Reinig, N, Renzaho, A, Rezaei, N, Rezapour, A, Romoli, M, Roshandel, G, Sachdev, P, Sahebkar, A, Sahraian, M, Samaei, M, Saylan, M, Sha, F, Shaikh, M, Shibuya, K, Shigematsu, M, Shin, J, Shiri, R, Silva, D, Singh, J, Singhal, D, Skryabin, V, Skryabina, A, Soheili, A, Sotoudeh, H, Spurlock, E, Szoeke, C, Tabares-Seisdedos, R, Taddele, B, Tovani-Palone, M, Tsegaye, G, Vacante, M, Venketasubramanian, N, Vidale, S, Vlassov, V, Vu, G, Wang, Y, Weiss, J, Weldemariam, A, Westerman, R, Wimo, A, Winkler, A, Wu, C, Yadollahpour, A, Yesiltepe, M, Yonemoto, N, Yu, C, Zastrozhin, M, Zastrozhina, A, Zhang, Z, Murray, C, and Vos, T
Subjects: Gerontology, Male, Computer applications to medicine. Medical informatics, Population Dynamics, R858-859.7, Global health, Health Informatics, Sample (statistics), MINI-MENTAL-STATE, Logistic regression, DISEASE, Validity, Item response theory, GBD 2019 Dementia Collaborators, medicine, Prevalence, Dementia, Humans, Neuropsychological assessment, Longitudinal Studies, Aged, 80 and over, Retirement, Science & Technology, medicine.diagnostic_test, Health Policy, 1103 Clinical Sciences, Cognition, NEUROPSYCHOLOGICAL ASSESSMENT, medicine.disease, Computer Science Applications, Cognitive test, Algorithm, 0806 Information Systems, Female, Psychology, Life Sciences & Biomedicine, Medical Informatics, Algorithms, Research Article
Abstract: BackgroundData sparsity is a major limitation to estimating national and global dementia burden. Surveys with full diagnostic evaluations of dementia prevalence are prohibitively resource-intensive in many settings. However, validation samples from nationally representative surveys allow for the development of algorithms for the prediction of dementia prevalence nationally.MethodsUsing cognitive testing data and data on functional limitations from Wave A (2001–2003) of the ADAMS study (n = 744) and the 2000 wave of the HRS study (n = 6358) we estimated a two-dimensional item response theory model to calculate cognition and function scores for all individuals over 70. Based on diagnostic information from the formal clinical adjudication in ADAMS, we fit a logistic regression model for the classification of dementia status using cognition and function scores and applied this algorithm to the full HRS sample to calculate dementia prevalence by age and sex.ResultsOur algorithm had a cross-validated predictive accuracy of 88% (86–90), and an area under the curve of 0.97 (0.97–0.98) in ADAMS. Prevalence was higher in females than males and increased over age, with a prevalence of 4% (3–4) in individuals 70–79, 11% (9–12) in individuals 80–89 years old, and 28% (22–35) in those 90 and older.ConclusionsOur model had similar or better accuracy as compared to previously reviewed algorithms for the prediction of dementia prevalence in HRS, while utilizing more flexible methods. These methods could be more easily generalized and utilized to estimate dementia prevalence in other national surveys.
Published: 2021

14. Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families

Author: Federica Scotto di Carlo, Paolo De Blasiis, Simone Sampaolo, Giorgia Bruno, Teresa Esposito, Mariarosa A. B. Melone, Nicole Piera Palomba, Alessandro Gialluisi, Filomena Napolitano, Stefano Navarro, Chiara Terracciano, Elisabetta Signoriello, Giuseppina Franzese, Napolitano, Filomena, Bruno, Giorgia, Terracciano, Chiara, Franzese, Giuseppina, Piera Palomba, Nicole, Scotto di Carlo, Federica, Signoriello, Elisabetta, DE BLASIIS, Paolo, Navarro, Stefano, Gialluisi, Alessandro, Melone, Mariarosa Anna Beatrice, Sampaolo, Simone, and Esposito, Teresa
Subjects: Male, modifiers factor, Osteoporosis, modifiers factors, Disease, Compound heterozygosity, whole exome sequencing, lcsh:Chemistry, Keywords: late-onset form of Pompe disease, lcsh:QH301-705.5, Spectroscopy, Exome sequencing, genetic modifier, Glycogen Storage Disease Type II, General Medicine, Enzyme replacement therapy, Middle Aged, Phenotype, Respiratory Muscles, Computer Science Applications, Pedigree, Italy, Female, Adult, skeletal muscle biopsies, autophagy gene, autophagy genes, Catalysis, vitamin D deficiency, Article, Inorganic Chemistry, late-onset form of Pompe disease, genetic modifiers, medicine, Autophagy, Humans, Enzyme Replacement Therapy, Family, Physical and Theoretical Chemistry, Muscle, Skeletal, Molecular Biology, skeletal muscle biopsie, Aged, business.industry, Siblings, Organic Chemistry, Genetic Variation, alpha-Glucosidases, medicine.disease, lcsh:Biology (General), lcsh:QD1-999, Immunology, Mutation, business
Abstract: Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of GAA mutations. The result is an unpredictable genotype–phenotype correlation. The purpose of this study was to identify the genetic factors responsible for the progression, severity and drug response in LOPD. We report here on a detailed clinical, morphological and genetic study, including a whole exome sequencing (WES) analysis of 11 adult LOPD siblings belonging to two Italian families carrying compound heterozygous GAA mutations. We disclosed a heterogeneous pattern of myopathic impairment, associated, among others, with cardiac defects, intracranial vessels abnormality, osteoporosis, vitamin D deficiency, obesity and adverse response to enzyme replacement therapy (ERT). We identified deleterious variants in the genes involved in autophagy, immunity and bone metabolism, which contributed to the severity of the clinical symptoms observed in the LOPD patients. This study emphasizes the multisystem nature of LOPD and highlights the polygenic nature of the complex phenotype disclosed in these patients.
Published: 2021

15. Mediterranean diet and other dietary patterns in association with biological aging in the Moli-sani Study cohort

Author: Simona Esposito, Alessandro Gialluisi, Simona Costanzo, Augusto Di Castelnuovo, Emilia Ruggiero, Amalia De Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, Marialaura Bonaccio, Americo Bonanni, Francesco Gianfagna, Teresa Di Prospero, Jos Vermylen, Ignacio De Paula Carrasco, Antonio Spagnuolo, Deodato Assanelli, Vincenzo Centritto, Marco Olivieri, Teresa Panzera, Sara Magnacca, Benedetta Izzi, Annalisa Marotta, Fabrizia Noro, Roberta Parisi, Alfonsina Tirozzi, Francesca Bracone, Francesca De Lucia, Cristiana Mignogna, Livia Rago, null Direzione Generale per la Salute - Regione Molise, null Azienda Sanitaria Regionale del Molise, null Molise Dati Spa, null Offices of vital statistics of the Molise region, null Ospedale A. Cardarelli – Campobasso, null Ospedale F. Veneziale – Isernia, null Ospedale San Timoteo - Termoli (CB), null Ospedale Ss. Rosario - Venafro (IS), null Ospedale Vietri – Larino (CB), null Ospedale San Francesco Caracciolo - Agnone (IS), null Casa di Cura Villa Maria - Campobasso, null Ospedale Gemelli Molise - Campobasso, and null IRCCS Neuromed - Pozzilli (IS)
Subjects: Adult, Male, Aging, Nutrition and Dietetics, Nordic diet, Polyphenols, Mediterranean, Critical Care and Intensive Care Medicine, Diet, Mediterranean, Diet, Dash diet, Cohort Studies, Biological aging, Cross-Sectional Studies, Palaeolithic diet, Mediterranean diet, Humans, Female
Abstract: Biological age (BA) is the hypothetical underlying age of an organism and has been proposed as a more powerful predictor of health than chronological age (CA). The difference between BA and CA (Δage) reflects the rate of biological aging, with lower values indicating slowed-down aging. We sought to compare the relationship of four a priori-defined dietary patterns, including a traditional Mediterranean diet (MD) and three non-Mediterranean diets, with biological aging (Δage) among Italian adults. We also examined distinctive nutritional traits of these diets as potential mediators of such associations.Cross-sectional analysis on a sub-cohort of 4510 subjects (aged ≥35 y; 52.0% women) from the Moli-sani Study (enrolment, 2005-2010). Food intake was recorded by a 188-item semi-quantitative food-frequency questionnaire. A Mediterranean diet score (MDS) was used as exposure and compared with non-Mediterranean dietary patterns, i.e. DASH (Dietary Approaches to Stop Hypertension), Palaeolithic and the Nordic diets. A Deep Neural Network based on 36 blood biomarkers was used to compute BA and the resulting Δage (BA-CA), which was tested as outcome in multivariable linear regressions adjusted for clinical factors, lifestyles and sociodemographic factors.In a multivariable-adjusted model, 1 standard deviation increase in the MDS was inversely associated with Δage (β = -0.23; 95%CI -0.40, -0.07), and similar findings were observed with the DASH diet (β = -0.17; 95%CI -0.33, -0.01). High dietary polyphenol content explained 29.8% (p = 0.04) and 65.8% (p = 0.02) of these associations, respectively, while other nutritional factors analysed (e.g. dietary fibre) were unlikely to be on the pathway. No significant associations were found with either the Palaeolithic or the Nordic diets.Increasing adherence to either the traditional MD or the DASH diet was associated with delayed biological aging, possibly through their high polyphenol content.
Published: 2021

16. Platelet Distribution Width Is Associated with P-Selectin Dependent Platelet Function: Results from the Moli-Family Cohort Study

Author: Izzi, Benedetta, Gialluisi, Alessandro, Gianfagna, Francesco, Orlandi, Sabatino, Curtis, Amalia De, Magnacca, Sara, Costanzo, Simona, Castelnuovo, Augusto Di, Donati, Maria Benedetta, Gaetano, Giovanni de, Hoylaerts, Marc F., Cerletti, Chiara, Iacoviello, Licia, and Investigators, on behalf of the Moli-family Study Investigators on behalf of the Moli-family Study
Subjects: Adult, Blood Platelets, Male, medicine.medical_specialty, P-selectin, QH301-705.5, 030204 cardiovascular system & hematology, Article, Cohort Studies, 03 medical and health sciences, thrombo-inflammation, 0302 clinical medicine, Von Willebrand factor, Internal medicine, von Willebrand Factor, Leukocytes, Medicine, Humans, VWF, platelet distribution width, Platelet, Family, Platelet activation, Coagulation, Mean platelet volume, Platelet distribution width, Thrombo-inflammation, Blood Coagulation, Female, Inflammation, P-Selectin, Platelet Activation, Sex Characteristics, Biology (General), coagulation, 030304 developmental biology, Whole blood, 0303 health sciences, mean platelet volume, biology, business.industry, Platelet Distribution Width, General Medicine, 3. Good health, Endocrinology, biology.protein, business
Abstract: Defined as an index of platelet size heterogeneity, the platelet distribution width (PDW) is still a poorly characterized marker of platelet function in (sub)clinical disease. We presently validated PDW as a marker of P-selectin dependent platelet activation in the Moli-family cohort. Platelet-bound P-selectin and platelet/leukocyte mixed aggregates were measured by flow cytometry in freshly collected venous blood, both before and after in vitro platelet activation, and coagulation time was assessed in unstimulated and LPS- or TNFα-stimulated whole blood. Closure Times (CT) were measured in a Platelet Function Analyzer (PFA)-100. Multivariable linear mixed effect regression models (with age, sex and platelet count as fixed and family structure as random effect) revealed PDW to be negatively associated with platelet P-selectin, platelet/leukocyte aggregates and von Willebrand factor (VWF), and positively with PFA-100 CT, and LPS- and TNF-α-stimulated coagulation times. With the exception of VWF, all relationships were sex-independent. In contrast, no association was found between mean platelet volume (MPV) and these variables. PDW seems a simple, useful marker of ex vivo and in vitro P-selectin dependent platelet activation. Investigations of larger cohorts will define the usefulness of PDW as a risk predictor of thrombo-inflammatory conditions where activated platelets play a contributing role. ispartof: CELLS vol:10 issue:10 ispartof: location:Switzerland status: published
Published: 2021

17. Exome-wide association study of levodopa-induced dyskinesia in Parkinson's disease

Author: Irene Pichler, Francisco S. Domingues, Nicola Modugno, Alessandra Nicoletti, Alessandro Gialluisi, Mario Zappia, Grazia Annesi, Andrew A. Hicks, Peter P. Pramstaller, Teresa Esposito, Cristian Pattaro, Roberto Melotti, Christine Schwienbacher, Marina Ciullo, Hagen Blankenburg, Eva König, and Anne Picard
Subjects: Male, Candidate gene, Dyskinesia, Drug-Induced, Parkinson's disease, Molecular biology, Diseases, Disease, Pathogenesis, Bioinformatics, Whole Exome Sequencing, Levodopa, Gene Frequency, Odds Ratio, Medicine, Exome, RISK, Multidisciplinary, Molecular medicine, Parkinson Disease, Middle Aged, Neurology, Female, Disease Susceptibility, Symptom Assessment, medicine.drug, Science, Article, Medical research, Exome Sequencing, Genetics, Humans, Gene, Alleles, Genetic association, Aged, Levodopa-induced dyskinesia, Dyskinesia, business.industry, Health care, medicine.disease, Computational biology and bioinformatics, Risk factors, Drug-Induced, business, Biomarkers, Neuroscience
Abstract: Levodopa is the standard long-term dopamine replacement therapy to treat Parkinson’s disease (PD) symptoms. With time, levodopa may induce debilitating dyskinesias (LID), the treatment of which represents a large clinically unmet need. However, time-to-LID onset varies between patients, reflecting a possible genetic component. We performed an hypothesis-free whole-exome sequencing (WES)-based screening of time-to-LID onset and attempted replication of previously published candidate gene studies. A WES association analysis was carried out in 134 PD patients in a meta-analytical framework. Replication was attempted in an independent study of 97 PD patients. Variants from previously reported candidate genes (OPRM1, COMT, BDNF) were also specifically examined. We significantly replicated, for the first time, an association of variant rs1799971 in the OPRM1 gene with time-to-LID onset. Furthermore, we identified two novel potentially functional variants, in the MAD2L2 (rs2233019) and MAP7 (rs35350783) genes, which were significantly associated at the discovery stage. In the replication study, the two variants showed direction-consistent effects but did not achieve the replication significance threshold. Our study provides the first WES results for time-to-LID onset, where we replicate association at OPRM1, and suggest new variants in MAD2L2 and MAP7 genes that are significant in discovery, but require larger datasets for replication. The results are being made publicly available to allow for independent external validation.
Published: 2021

18. Dietary Polyphenol Intake Is Associated with Biological Aging, a Novel Predictor of Cardiovascular Disease: Cross-Sectional Findings from the Moli-Sani Study

Author: Simona Esposito, Alessandro Gialluisi, Simona Costanzo, Augusto Di Castelnuovo, Emilia Ruggiero, Amalia De Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, Marialaura Bonaccio, and on behalf of the Investigators for the Moli-Sani Study
Subjects: Adult, Male, 0301 basic medicine, Aging, Antioxidant, Mediterranean diet, Cross-sectional study, medicine.medical_treatment, dietary polyphenols, Trolox equivalent antioxidant capacity, Diet, Mediterranean, Diet Surveys, Risk Assessment, Antioxidants, Article, Dietary Polyphenol, Cohort Studies, Eating, 03 medical and health sciences, 0302 clinical medicine, cardiovascular disease, Humans, Medicine, TX341-641, Food science, bone health, Chronobiology Phenomena, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Nutrition. Foods and food supply, Polyphenols, food and beverages, Diet, Cross-Sectional Studies, Italy, Cardiovascular Diseases, Heart Disease Risk Factors, Polyphenol, biological aging, Cohort, Linear Models, Female, Neural Networks, Computer, business, Biomarkers, 030217 neurology & neurosurgery, Food Science, Cohort study
Abstract: Biological aging, or the discrepancy between biological and chronological age of a subject (Δage), has been associated with a polyphenol-rich Mediterranean diet and represents a new, robust indicator of cardiovascular disease risk. We aimed to disentangle the relationship of dietary polyphenols and total antioxidant capacity with Δage in a cohort of Italians. A cross-sectional analysis was performed on a sub-cohort of 4592 subjects (aged ≥ 35 y, 51.8% women) from the Moli-sani Study (2005–2010). Food intake was recorded by a 188-item food-frequency questionnaire. The polyphenol antioxidant content (PAC)-score was constructed to assess the total dietary content of polyphenols. Total antioxidant capacity was measured in foods by these assays: trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric reducing-antioxidant power (FRAP). A deep neural network, based on 36 circulating biomarkers, was used to compute biological age and the resulting Δage, which was tested as outcome in multivariable-adjusted linear regressions. Δage was inversely associated with the PAC-score (β = −0.31, 95%CI −0.39, −0.24) but not with total antioxidant capacity of the diet. A diet rich in polyphenols, by positively contributing to deceleration of the biological aging process, may exert beneficial effects on the long-term risk of cardiovascular disease and possibly of bone health.
Published: 2021

19. Lacosamide as first add-on or conversion monotherapy: A retrospective real-life study

Author: Alessandro Gialluisi, Giancarlo Di Gennaro, Sara Casciato, Liliana G. Grammaldo, Pier Paolo Quarato, Addolorata Mascia, and Alfredo D'Aniello
Subjects: Adult, Male, medicine.medical_specialty, Lacosamide, Behavioral Neuroscience, Epilepsy, Pharmacokinetics, Internal medicine, medicine, Humans, Adverse effect, Retrospective Studies, business.industry, equipment and supplies, medicine.disease, Regimen, Treatment Outcome, Neurology, Tolerability, Pharmacodynamics, Adjunctive treatment, Anticonvulsants, Neurology (clinical), Epilepsies, Partial, business, medicine.drug
Abstract: Purpose Lacosamide (LCM), the R-enantiomer of 2-acetamido-N-benzyl-3-methoxypropionamide, is a newer approved antiseizure medication characterized by a novel pharmacodynamic and favorable pharmacokinetic profile that was approved as adjunctive treatment for adults with focal onset and focal to bilateral tonic-clonic seizures in 2008, and recently also for monotherapy. The aim of this study was to evaluate the effectiveness and tolerability of LCM as first add-on or conversion monotherapy in adult subjects with focal epilepsy. Methods We retrospectively included all adult patients who received LCM as first add-on regimen or as substitution monotherapy at least 12 months before starting the chart review, with a historical baseline of 6 months prior to day of the first administration of LCM. The choice of treatment was made independently by the epilepstologists, according to routine clinical practice. Clinical data were obtained at 3, 6, and 12 months after subjects started LCM and then analyzed to assess retention rate, seizure freedom, and adverse events (AE). Results A total of 101 patients (58 men) with a mean age of 44 years and a median epilepsy duration of 6.6 years (range 1–53) were included in the study. At 12 months 72 patients retained LCM, 54 (75%) of them were seizure free, 44 (81.5%) in monotherapy and 10 (18.5%) in add-on LCM treatment. Among all subjects, 31 (57.4%) were free from seizure under LCM monotherapy throughout the entire observation period. Thirty one out of 72 (43%) PwE who retained LCM at 12 months, were free from seizures throughout the entire observation period. The maintenance median dosage of LCM was 200 mg/day. Ten (10%) subjects reported mild to moderate AE, most commonly drowsiness and dizziness. No serious AE were documented. Conclusions This real-life study confirms that LCM is an effective and well tolerated treatment option as first add-on or conversion monotherapy for focal seizures.
Published: 2021

20. Exploring domains, clinical implications and environmental associations of a deep learning marker of biological ageing

Author: Alessandro Gialluisi, Simona Costanzo, Enrico Capobianco, Augusto Di Castelnuovo, Mariarosaria Persichillo, Maria Benedetta Donati, Licia Iacoviello, Giovanni de Gaetano, Sara Magnacca, Amalia De Curtis, Chiara Cerletti, and Marialaura Bonaccio
Subjects: Estimation, Adult, Male, medicine.medical_specialty, Aging, business.industry, Biological age, Public health, Deep learning, Biology, medicine.disease, Diet, Mediterranean, Obesity, Deep Learning, Ageing, medicine, Educational Status, Humans, Female, Liver function, Artificial intelligence, business, Socioeconomic status, Biomarkers, Demography
Abstract: Deep Neural Networks (DNN) have been recently developed for the estimation of Biological Age (BA), the hypothetical underlying age of an organism, which can differ from its chronological age (CA). Although promising, these population-specific algorithms warrant further characterization and validation, since their biological, clinical and environmental correlates remain largely unexplored.Here, an accurate DNN was trained to compute BA based on 36 circulating biomarkers in an Italian population (N=23,858; age≥35 years; 51.7% women). This estimate was heavily influenced by markers of metabolic, heart, kidney and liver function. The resulting Δage (BA-CA) significantly predicted mortality and hospitalization risk for all and specific causes. Slowed biological aging (Δage0) was associated with smoking and obesity. Together, lifestyles and socioeconomic variables explained □48% of the total variance in Δage, potentially suggesting the existence of a genetic basis.These findings validate blood-based biological aging as a marker of public health in adult Italians and provide a robust body of knowledge on its biological architecture, clinical implications and potential environmental influences.
Published: 2020

21. Association of a traditional Mediterranean diet and non-Mediterranean dietary scores with all-cause and cause-specific mortality: prospective findings from the Moli-sani Study

Author: Bonaccio, M., Di Castelnuovo, A., Costanzo, S., De Curtis, A., Persichillo, M., Cerletti, C., Donati, M. B., de Gaetano, G., Iacoviello, L., Bonanni, A., Decurtis, A., Dicastelnuovo, A., Diprospero, T., Vermylen, J., DePaula Carrasco, I., Giampaoli, S., Spagnuolo, A., Assanelli, D., Centritto, V., Olivieri, M., Gialluisi, A., Gianfagna, F., Ruggiero, E., Magnacca, S., Izzi, B., Marotta, A., Noro, F., Delucia, F., Bracone, F., Dudiez, S., Rago, L., and Panzera, T.
Subjects: 0301 basic medicine, Adult, Male, Mediterranean diet, DASH diet, Population, Medicine (miscellaneous), 030209 endocrinology & metabolism, Lower risk, Diet, Mediterranean, 03 medical and health sciences, 0302 clinical medicine, Palaeolithic diet, Risk Factors, Cause of Death, CVD risk factors, Inflammation, Mortality, Nordic diet, Dash, Risk of mortality, Medicine, Humans, Prospective Studies, education, education.field_of_study, 030109 nutrition & dietetics, Nutrition and Dietetics, Proportional hazards model, business.industry, Hazard ratio, Italy, Cardiovascular Diseases, Female, business, Demography
Abstract: To evaluate in an Italian general population, the association with mortality of a traditional Mediterranean diet (MD) and non-Mediterranean dietary (non-MD) patterns, and their combined effect, and to test some biomarkers of cardiovascular (CVD) risk as potential mediators of such associations. Longitudinal analysis on 22,849 men and women aged ≥ 35 years, recruited in the Moli-sani Study (2005–2010), followed up for 8.2 years (median). The MD was assessed by the Mediterranean diet score (MDS). The Dietary Approaches to Stop Hypertension (DASH), the Palaeolithic diet, and the Nordic diet were chosen as reportedly healthy non-MD patterns. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated by multivariable Cox regression. Participants reaching higher MDS or DASH diet score experienced lower risk of both all-cause (HR 0.77; 95% CI 0.66–0.90 and 0.81; 0.69–0.96, respectively, highest vs lowest quartile) and CVD (0.77; 0.59–1.00 and 0.81; 0.69–0.96, respectively) death risk; risk reduction associated with the Palaeolithic diet was limited to total and other cause death, whereas the Nordic diet did not alter risk of mortality. Increasing adherence to MD was associated with higher survival in each stratum of non-MD diets. Biomarkers of glucose metabolism accounted for 7% and 21.6% of the association between either MDS or DASH diet, respectively, with total mortality risk. Both the traditional MD and DASH diet may reduce risk of all-cause mortality among Italians, as well as risk of dying from cardiovascular causes. The Palaeolithic diet did not appear to reduce cardiovascular risk, while the Nordic eating pattern was unlikely to be associated with any substantial health advantage.
Published: 2020

22. A genetic epidemiology study of congenital adrenal hyperplasia in Italy

Author: Gialluisi, A, Menabò, S, Baldazzi, L, Casula, L, Meloni, A, Farci, M. C, Mariotti, S, Balestrino, L, ORTOLANO, RITA, Murru, S, Carcassi, C, Loche, S, Balsamo, A, ROMEO, GIOVANNI, Gialluisi, A, Menabò, S, Baldazzi, L, Casula, L, Meloni, A, Farci, M. C, Mariotti, S, Balestrino, L, Ortolano, R, Murru, S, Carcassi, C, Loche, S, Balsamo, A, and Romeo, G.
Subjects: Male, endocrine system diseases, Adolescent, Genotype, CYP21A2 mutations, 21-hydroxylase deficiency, Sardinia, autosomal recessive disorders, congenital adrenal hyperplasia, newborn screening, pathogenic allele frequency, prevalence, urologic and male genital diseases, Neonatal Screening, Gene Frequency, Humans, Point Mutation, Child, Molecular Epidemiology, autosomal recessive disorder, Adrenal Hyperplasia, Congenital, Infant, Newborn, Infant, CYP21A2 mutation, Italy, Child, Preschool, Female, Steroid 21-Hydroxylase
Abstract: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD-CAH) is an autosomal recessive disorder affecting steroidogenesis, due to mutations in CYP21A2 (6p21.3). 21OHD-CAH neonatal screening is based on 17-hydroxyprogesterone (17OHP) serum levels, showing high type I error rate and low sensitivity to mild CAH forms. Here, we used an epidemiological approach, which estimates the allelic frequency (q) of an autosomal recessive disorder using the proportion of homozygous patients, the mutational spectrum and the inbreeding coefficient in a sample of affected individuals. We applied this approach to 2 independent Italian cohorts of patients with both clinical and molecular diagnosis of 21OHD-CAH from mainland Italy (N = 240) and Sardinia (N = 53). We inferred q estimates of 2.87% and 1.83%, corresponding to a prevalence of 1/1214 and 1/2986, respectively. CYP21A2 mutational spectra were quite discrepant between the 2 cohorts, with V281L representing 74% of all the mutations detected in Sardinia vs 37% in mainland Italy. These findings provide an updated fine-grained picture of 21OHD-CAH genetic epidemiology in Italy and suggest the need for a screening approach suitable to the detection of the largest number of clinically significant forms of CAH.
Published: 2018

23. Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia

Author: Jacqueline Hulslander, Thomas Bourgeron, Dénes Tóth, Till F. M. Andlauer, John F. Stein, Alessandro Gialluisi, Clyde Francks, Ferenc Honbolygó, Erik G. Willcutt, Darina Czamara, Juha Kere, Markus M. Nöthen, Kerstin U. Ludwig, Anniek Vaessen, John C. DeFries, Thomas S. Scerri, Gerd Schulte-Körne, Nazanin Mirza-Schreiber, Shelley D. Smith, Guillaume Huguet, Per Hoffmann, Anthony P. Monaco, Paavo H.T. Leppänen, Kristina Moll, Andrew P. Morris, Joel B. Talcott, Daniel Brandeis, Johannes Schumacher, Silvia Paracchini, Milene Bonte, Valéria Csépe, Simon E. Fisher, William M. Brandler, Bruce F. Pennington, Arndt Wilcke, Urs Maurer, Karin Landerl, Fabien Fauchereau, Richard K. Olson, Beate St Pourcain, Franck Ramus, Myriam Peyrard-Janvid, Jessica Becker, Bertram Müller-Myhsok, Heikki Lyytinen, STEMM - Stem Cells and Metabolism Research Program, Juha Kere / Principal Investigator, Research Programs Unit, University of Helsinki, Rheinische Friedrich-Wilhelms-Universität Bonn, Université de Montréal [Montréal], Universität Heidelberg [Heidelberg], Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS), Institute of Human Genetics, Department of Genomics, Life and Brain Center, University of Bonn, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Munich, Publica, University of St Andrews. School of Medicine, University of St Andrews. Cellular Medicine Division, University of St Andrews. Biomedical Sciences Research Complex, University of St Andrews. Centre for Biophotonics, RS: FPN CN 7, Language, Université de Montréal (UdeM), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Leipzig-Universität Leipzig, Radboud University [Nijmegen], University of Oxford, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Universität Bonn = University of Bonn, École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris)
Subjects: 0301 basic medicine, Male, Candidate gene, Multifactorial Inheritance, Imaging genetics, QH301 Biology, LANGUAGE, Genome-wide association study, 3124 Neurology and psychiatry, CANDIDATE GENES, Dyslexia, Cohort Studies, READING-DISABILITY, MOLECULAR-GENETICS, 0302 clinical medicine, Cognition, AUTOMATIZED NAMING RAN, Child, SUSCEPTIBILITY LOCUS, Rapid automatized naming, R2C, SHORT-TERM-MEMORY, ~DC~, IMAGING-GENETICS, RJ Pediatrics, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Psychiatry and Mental health, Dyslexia/genetics, Anxiety, Female, medicine.symptom, BDC, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry, Clinical psychology, Neuroinformatics, Adult, Reading disability, Adolescent, Genotype, RJ, Polymorphism, Single Nucleotide, Article, lcsh:RC321-571, ENVIRONMENTAL-INFLUENCES, 03 medical and health sciences, Cellular and Molecular Neuroscience, QH301, Young Adult, medicine, dysleksia, Humans, Genetic Predisposition to Disease, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, geenit, business.industry, DAS, medicine.disease, Comorbidity, predictors, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, RC0321, DEVELOPMENTAL DYSLEXIA, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562–3468). We observed a genome-wide significant effect (p, Translational Psychiatry, 9 (1), ISSN:2158-3188
Published: 2019

24. Lifestyle and biological factors influence the relationship between mental health and low-grade inflammation

Author: M.B. Donati, G. de Gaetano, Alessandro Gialluisi, Chiara Cerletti, A. Di Castelnuovo, Simona Costanzo, M Sarchiapone, Marialaura Bonaccio, A. De Curtis, and Licia Iacoviello
Subjects: Adult, Male, Platelets, Immunology, Biological factors, Depression, Immunity, Inflammation, Lifestyle, Mental health, Psychological resilience, Wellbeing, Adult population, Disease, Low grade inflammation, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Diabetes mellitus, Medicine, Humans, Blood markers, Association (psychology), Life Style, Depression (differential diagnoses), Endocrine and Autonomic Systems, business.industry, Cancer, Baseline model, medicine.disease, 030227 psychiatry, Lifestyle factors, Italy, Cohort, medicine.symptom, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Mental health modulates the risk of common chronic conditions like cardiovascular disease, cancer and diabetes. Although inflammation is thought to partly explain this link, its relation with mental health is still unclear and largely unexplored.We investigated three scales assessing psychological resilience (CD-RISC), depression symptoms (PHQ8) and mental wellbeing (SF36-MCS) in an Italian adult population cohort (Nmax=16,952). We performed stepwise generalized linear models to test the association between each scale and INFLA-score, a composite blood-based inflammation index. At each step, a class of potential mediators was included in the model, namely health conditions, lifestyle factors, or both (full model). Full model analysis was also conducted on single blood markers involved in the inflammatory process.In the baseline model, we observed significant associations of PHQ8 (standardized β=0.024, p=8.9×10−3) and SF36-MCS (β = −0.021, p=7×10−3) with INFLA-score. These associations survived adjustment for health conditions but not for lifestyle factors, which explained 81% and 17% of the association with PHQ8 and SF36-MCS, respectively. Significant associations (p−3) after mediator adjustment were observed for single low-grade inflammation markers, including platelet distribution width (with PHQ8 and CD-RISC), granulocyte-and neutrophil-to-lymphocyte ratios, monocyte and lymphocyte fractions (with SF36-MCS).These findings suggest that the relationship between mental health and low-grade inflammation is largely influenced by lifestyle. However, the associations with specific biomarkers related to inflammation are partly independent and might be explained by biological factors. Interestingly, these associations are in line with recent blood transcriptomic analyses of depressed subjects, reporting up- and down-regulation of genes related to innate and adaptive immunity, respectively.
Published: 2019

25. ZBTB12 DNA methylation is associated with coagulation- and inflammation-related blood cell parameters: findings from the Moli-family cohort

Author: Noro, F., Gianfagna, F., Gialluisi, A., De Curtis, A., Di Castelnuovo, A., Napoleone, E., Cerletti, C., Donati, M. B., de Gaetano, G., Hoylaerts, M. F., Iacoviello, L., Izzi, B., Vohnout, B., Arca, M., Lorenzet, R., di Castelnuovo, A., Costanzo, S., di Giuseppe, R., Cutrone, A., Magnacca, S., Crescente, M., Pampuch, A., Tamburrelli, C., Zurlo, F., and Nanni, L.
Subjects: Male, 0301 basic medicine, Myocardial Infarction, Cohort Studies, Pathogenesis, Blood cell, Leukocyte Count, 0302 clinical medicine, PLATELET, Genetics (clinical), Genetics & Heredity, DNA methylation, Granulocyte counts, White blood cell counts, Whole blood coagulation time, Zinc fingers, Cardiovascular risk, Principal Component Analysis, DNA methylation, TRANSCRIPTIONAL REGULATION, Methylation, Middle Aged, Blood Coagulation Factors, DNA-Binding Proteins, MEDITERRANEAN DIET, Haematopoiesis, Granulocyte counts, Zinc fingers, medicine.anatomical_structure, Oncology, CpG site, MONOCYTES, 030220 oncology & carcinogenesis, Female, Life Sciences & Biomedicine, Adult, Biology, Granulocyte, REGION, Young Adult, 03 medical and health sciences, ADHERENCE, White blood cell, Cardiovascular risk, White blood cell counts, Whole blood coagulation time, Genetics, medicine, Humans, Blood Coagulation, Molecular Biology, Science & Technology, Tumor Necrosis Factor-alpha, Research, 030104 developmental biology, TISSUE FACTOR, Immunology, CpG Islands, Granulocytes, Transcription Factors, Developmental Biology
Abstract: Background Zinc finger and BTB domain-containing protein 12 (ZBTB12) is a predicted transcription factor with potential role in hematopoietic development. Recent evidence linked low methylation level of ZBTB12 exon1 to myocardial infarction (MI) risk. However, the role of ZBTB12 in the pathogenesis of MI and cardiovascular disease in general is not yet clarified. We investigated the relation between ZBTB12 methylation and several blood parameters related to cardio-cerebrovascular risk in an Italian family-based cohort. Results ZBTB12 methylation was analyzed on white blood cells from the Moli-family cohort using the Sequenom EpiTYPER MassARRAY (Agena). A total of 13 CpG Sequenom units were analyzed in the small CpG island located in the only translated ZBTB12 exon. Principal component analysis (PCA) was performed to identify groups of CpG units with similar methylation estimates. Linear mixed effect regressions showed a positive association between methylation of ZBTB12 Factor 2 (including CpG units 8, 9–10, 16, 21) and TNF-ɑ stimulated procoagulant activity, a measure of procoagulant and inflammatory potential of blood cells. In addition, we also found a negative association between methylation of ZBTB12 Factor 1 (mainly characterized by CpG units 1, 3–4, 5, 11, and 26) and white blood cell and granulocyte counts. An in silico prediction analysis identified granulopoiesis- and hematopoiesis-specific transcription factors to potentially bind DNA sequences encompassing CpG1, CpG3–4, and CpG11. Conclusions ZBTB12 hypomethylation is linked to shorter TNF-ɑ stimulated whole blood coagulation time and increased WBC and granulocyte counts, further elucidating the possible link between ZBTB12 methylation and cardiovascular disease risk. Electronic supplementary material The online version of this article (10.1186/s13148-019-0665-6) contains supplementary material, which is available to authorized users.
Published: 2019

26. Chili Pepper Consumption and Mortality in Italian Adults

Author: Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Emilia Ruggiero, Amalia De Curtis, Mariarosaria Persichillo, Claudio Tabolacci, Francesco Facchiano, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, Americo Bonanni, Francesco Gianfagna, Teresa Di Prospero, Jos Vermylen, Ignacio De Paula Carrasco, Simona Giampaoli, Antonio Spagnuolo, Deodato Assanelli, Vincenzo Centritto, Marco Olivieri, Alessandro Gialluisi, Francesco Gianfagna°, Sara Magnacca, Benedetta Izzi, Annalisa Marotta, Fabrizia Noro, Francesca De Lucia, Francesca Bracone, Salvatore Dudiez, Livia Rago, and Teresa Panzera
Subjects: Adult, Male, cerebrovascular mortality, medicine.medical_specialty, Mediterranean diet, Chili pepper, Population, Disease, 030204 cardiovascular system & hematology, Diet, Mediterranean, 03 medical and health sciences, 0302 clinical medicine, cardiovascular mortality, Epidemiology, medicine, Humans, risk factors, 030212 general & internal medicine, Prospective Studies, Mortality, education, total mortality, Aged, education.field_of_study, business.industry, Hazard ratio, food and beverages, Middle Aged, Confidence interval, Italy, Cardiovascular Diseases, inflammation, Cohort, Female, chili pepper, Cardiology and Cardiovascular Medicine, business, Capsicum, Demography
Abstract: Background Chili pepper is a usual part of a traditional Mediterranean diet. Yet epidemiological data on the association between chili pepper intake and mortality risk are scarce, with a lack of studies from Mediterranean populations. Objectives This study sought to examine the association between chili pepper consumption and risk of death in a large sample of the adult Italian general population, and to account for biological mediators of the association. Methods Longitudinal analysis was performed on 22,811 men and women enrolled in the Moli-sani Study cohort (2005 to 2010). Chili pepper intake was estimated by the EPIC (European Prospective Investigation Into Cancer) Food Frequency Questionnaire and categorized as none/rare consumption, up to 2 times/week, >2 to ≤4 times/week, and >4 times/week. Results Over a median follow-up of 8.2 years, a total of 1,236 deaths were ascertained. Multivariable hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality among participants in the regular (>4 times/week) relative to none/rare intake were 0.77 (95% confidence interval [CI]: 0.66 to 0.90) and 0.66 (95% CI: 0.50 to 0.86), respectively. Regular intake was also inversely associated with ischemic heart disease (HR: 0.56; 95% CI: 0.35 to 0.87) and cerebrovascular (HR: 0.39; 95% CI: 0.20 to 0.75) death risks. The association of chili pepper consumption with total mortality appeared to be stronger in hypertension-free individuals (p for interaction = 0.021). Among known biomarkers of CVD, only serum vitamin D marginally accounted for such associations. Conclusions In a large adult Mediterranean population, regular consumption of chili pepper is associated with a lower risk of total and CVD death independent of CVD risk factors or adherence to a Mediterranean diet. Known biomarkers of CVD risk only marginally mediate the association of chili pepper intake with mortality.
Published: 2019

27. Multivariate genome-wide association study of rapid automatised naming and rapid alternating stimulus in Hispanic American and African-American youth

Author: Richard Boada, Andrew K. Adams, Maryanne Wolf, Jan C. Frijters, Jeffrey R. Gruen, John C. DeFries, Simon E. Fisher, Clyde Francks, Bruce F. Pennington, Dongnhu T. Truong, Shelley D. Smith, Joan Bosson-Heenan, E. Mark Mahone, Dina E. Hill, Richard K. Olson, Maureen W. Lovett, Steven Paniagua, Alessandro Gialluisi, and Erik G. Willcutt
Subjects: Neuroinformatics, 0301 basic medicine, Male, Reading disability, Genome-wide association study, Locus (genetics), Neuroimaging, Biology, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Epigenesis, Genetic, Language in Interaction, Structural variation, Dyslexia, genome-wide, 03 medical and health sciences, 0302 clinical medicine, Quantitative Trait, Heritable, Meta-Analysis as Topic, Genetics, Humans, Genetic Predisposition to Disease, Genetics (clinical), Alleles, Genetic Association Studies, Genetic association, epigenetics, Genome, Human, Complex Traits, Computational Biology, Genomics, Hispanic or Latino, psychiatry, Black or African American, 030104 developmental biology, Ran, Trait, Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: BackgroundRapid automatised naming (RAN) and rapid alternating stimulus (RAS) are reliable predictors of reading disability. The underlying biology of reading disability is poorly understood. However, the high correlation among RAN, RAS and reading could be attributable to shared genetic factors that contribute to common biological mechanisms.ObjectiveTo identify shared genetic factors that contribute to RAN and RAS performance using a multivariate approach.MethodsWe conducted a multivariate genome-wide association analysis of RAN Objects, RAN Letters and RAS Letters/Numbers in a sample of 1331 Hispanic American and African–American youth. Follow-up neuroimaging genetic analysis of cortical regions associated with reading ability in an independent sample and epigenetic examination of extant data predicting tissue-specific functionality in the brain were also conducted.ResultsGenome-wide significant effects were observed at rs1555839 (p=4.03×10−8) and replicated in an independent sample of 318 children of European ancestry. Epigenetic analysis and chromatin state models of the implicated 70 kb region of 10q23.31 support active transcription of the gene RNLS in the brain, which encodes a catecholamine metabolising protein. Chromatin contact maps of adult hippocampal tissue indicate a potential enhancer–promoter interaction regulating RNLS expression. Neuroimaging genetic analysis in an independent, multiethnic sample (n=690) showed that rs1555839 is associated with structural variation in the right inferior parietal lobule.ConclusionThis study provides support for a novel trait locus at chromosome 10q23.31 and proposes a potential gene–brain–behaviour relationship for targeted future functional analysis to understand underlying biological mechanisms for reading disability.
Published: 2019

28. Mediterranean diet and mortality in the elderly: a prospective cohort study and a meta-analysis

Author: Marialaura Bonaccio, Simona Costanzo, Alessandro Gialluisi, Licia Iacoviello, Chiara Cerletti, Mariarosaria Persichillo, Augusto Di Castelnuovo, Giovanni de Gaetano, and Maria Benedetta Donati
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Mediterranean diet, Population, Medicine (miscellaneous), Lower risk, Diet, Mediterranean, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Elderly, Risk Factors, Internal medicine, Cause of Death, medicine, Moli-sani Study, Humans, 030212 general & internal medicine, Prospective Studies, Mortality, education, Prospective cohort study, Aged, Proportional Hazards Models, Aged, 80 and over, education.field_of_study, 030109 nutrition & dietetics, Nutrition and Dietetics, Meta-analyses, Proportional hazards model, business.industry, Hazard ratio, Cardiovascular Diseases, Meta-analysis, Cohort, Female, business
Abstract: The Mediterranean diet (MD) has been associated with prolonged survival in the general population, but no meta-analysis has apparently investigated the potential health benefits in relation to mortality in the elderly. We performed a longitudinal analysis on 5200 individuals aged ≥65 years identified within the general population recruited in the Moli-sani study cohort (2005–2010). Adherence to the MD was appraised by the a priori Mediterranean diet score (MDS; range 0–9). Survival estimates were derived using Cox regression and competing risk models. For the meta-analysis, PubMed and Scopus databases were searched from inception until April 2018 to identify prospective studies on the MD and death risk in the elderly. Over a median follow-up of 8·1 years, a total of 900 deaths were ascertained in the elderly sub-sample of the Moli-sani cohort. A one-point increase in the MDS was associated with lower risk of all-cause, coronary artery disease/cerebrovascular and non-cardiovascular/non-cancer mortality (multi-variable hazard ratio (HR)=0·94; 95 % CI 0·90, 0·98; HR=0·91; 95 % CI 0·83, 0·99 and HR=0·89; 95 % CI 0·81, 0·96, respectively). In a meta-analysis of seven prospective studies, including our results, for a total of 11 738 participants and 3874 deaths, one-point increment in MDS was associated with 5 % (4–7 %) lower risk of all-cause death. An inverse linear dose–response relationship was found from a meta-analysis including three studies. In conclusion, a prospective cohort study and a meta-analysis showed that closer adherence to the MD was associated with prolonged survival in elderly individuals, suggesting the appropriateness for older persons to adopt/preserve the MD to maximise their prospects for survival.
Published: 2018

29. Neuroimaging genetic analyses of novel candidate genes associated with reading and language

Author: Tulio Guadalupe, Simon E. Fisher, Clyde Francks, and Alessandro Gialluisi
Subjects: Male, Neuroinformatics, 0301 basic medicine, Linguistics and Language, Candidate gene, Imaging genetics, Cognitive Neuroscience, Middle temporal gyrus, Planum temporale, Inferior frontal gyrus, Experimental and Cognitive Psychology, Grey matter, Polymorphism, Single Nucleotide, Language and Linguistics, Cortical thickness, 03 medical and health sciences, Speech and Hearing, Superior temporal gyrus, 0302 clinical medicine, RBFOX2, Cortical thickness, Language, Reading, Brain, Imaging genetics, medicine, Chromosomes, Human, Humans, FLNC, Gray Matter, RBFOX2, Language, Brain Mapping, Brain, Neoplasm Proteins, Repressor Proteins, Alternative Splicing, 030104 developmental biology, medicine.anatomical_structure, Reading, Female, RNA Splicing Factors, Psychology, Neuroscience, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Neuroimaging measures provide useful endophenotypes for tracing genetic effects on reading and language. A recent Genome-Wide Association Scan Meta-Analysis (GWASMA) of reading and language skills (N = 1862) identified strongest associations with the genes CCDC136/FLNC and RBFOX2. Here, we follow up the top findings from this GWASMA, through neuroimaging genetics in an independent sample of 1275 healthy adults. To minimize multiple-testing, we used a multivariate approach, focusing on cortical regions consistently implicated in prior literature on developmental dyslexia and language impairment. Specifically, we investigated grey matter surface area and thickness of five regions selected a priori: middle temporal gyrus (MTG); pars opercularis and pars triangularis in the inferior frontal gyrus (IFG-PO and IFG-PT); postcentral parietal gyrus (PPG) and superior temporal gyrus (STG). First, we analysed the top associated polymorphisms from the reading/language GWASMA: rs59197085 (CCDC136/FLNC) and rs5995177 (RBFOX2). There was significant multivariate association of rs5995177 with cortical thickness, driven by effects on left PPG, right MTG, right IFG (both PO and PT), and STG bilaterally. The minor allele, previously associated with reduced reading-language performance, showed negative effects on grey matter thickness. Next, we performed exploratory gene-wide analysis of CCDC136/FLNC and RBFOX2; no other associations surpassed significance thresholds. RBFOX2 encodes an important neuronal regulator of alternative splicing. Thus, the prior reported association of rs5995177 with reading/language performance could potentially be mediated by reduced thickness in associated cortical regions. In future, this hypothesis could be tested using sufficiently large samples containing both neuroimaging data and quantitative reading/language scores from the same individuals.
Published: 2017

30. Next-gen sequencing identifies non-coding variation disrupting miRNA-binding sites in neurological disorders

Author: Xiaowei Sylvia Chen, Sonja C. Vernes, Paolo Devanna, Simon E. Fisher, Clyde Francks, Shelley D. Smith, Alessandro Gialluisi, Joses Ho, Dianne F. Newbury, Dario Gajewski, and University of St Andrews. School of Biology
Subjects: 0301 basic medicine, Male, Schizophrenia/genetics, Bipolar Disorder, QH301 Biology, Disease, microRNAs/genetics, High-throughput nucleotide sequencing/methods, Cohort Studies, Genetic variation/genetics, DNA, intergenic/genetics, Nervous system diseases/genetics, Child, 3' Untranslated Regions, Regulation of gene expression, Binding sites/genetics, Mental Disorders, High-Throughput Nucleotide Sequencing, Genomics, 3. Good health, Psychiatry and Mental health, 3' Untranslated Regions/genetics, Schizophrenia, Cohort studies, DNA, Intergenic, Female, Original Article, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry, Sequence Analysis, Neuroinformatics, Adult, Mental disorders/genetics, MiRNA binding, Computational biology, QH426 Genetics, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, QH301, SDG 3 - Good Health and Well-being, Autistic disorder/genetics, medicine, Humans, Genetic Predisposition to Disease, Language Development Disorders, Bipolar disorder/genetics, Language development disorders/genetics, Autistic Disorder, Molecular Biology, Gene, QH426, Sequence analysis/methods, Binding Sites, Genetic predisposition to Disease, Neurodevelopmental disorders/genetics, Genetic Variation, DAS, medicine.disease, Gene expression regulation/genetics, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, Neurodevelopmental Disorders, Behavioral medicine, RC0321, Autism, Nervous System Diseases, Neuroscience
Abstract: Funding: This work was funded by a Marie Curie Career Integration Grant and by a Max Planck Research Group Grant both awarded to SCV. The work of the Newbury lab is funded by the Medical Research Council (G1000569/1 and MR/J003719/1). XSC, AG, CF and SEF were supported by the Max Planck Society. The UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol provided core support for ALSPAC. The work of the Wellcome Trust Centre in Oxford is supported by the Wellcome Trust (090532/Z/09/Z). JH was supported by a scholarship from the Agency for Science, Technology, and Research, Singapore. The work of SDS is supported by the grant HD027802 from NIH. Understanding the genetic factors underlying neurodevelopmental and neuropsychiatric disorders is a major challenge given their prevalence and potential severity for quality of life. While large-scale genomic screens have made major advances in this area, for many disorders the genetic underpinnings are complex and poorly understood. To date the field has focused predominantly on protein coding variation, but given the importance of tightly controlled gene expression for normal brain development and disorder, variation that affects non-coding regulatory regions of the genome is likely to play an important role in these phenotypes. Herein we show the importance of 3 prime untranslated region (3'UTR) non-coding regulatory variants across neurodevelopmental and neuropsychiatric disorders. We devised a pipeline for identifying and functionally validating putatively pathogenic variants from next generation sequencing (NGS) data. We applied this pipeline to a cohort of children with severe specific language impairment (SLI) and identified a functional, SLI-associated variant affecting gene regulation in cells and post-mortem human brain. This variant and the affected gene (ARHGEF39) represent new putative risk factors for SLI. Furthermore, we identified 3'UTR regulatory variants across autism, schizophrenia and bipolar disorder NGS cohorts demonstrating their impact on neurodevelopmental and neuropsychiatric disorders. Our findings show the importance of investigating non-coding regulatory variants when determining risk factors contributing to neurodevelopmental and neuropsychiatric disorders. In the future, integration of such regulatory variation with protein coding changes will be essential for uncovering the genetic causes of complex neurological disorders and the fundamental mechanisms underlying health and disease. Publisher PDF
Published: 2016

31. Genome-wide screening for DNA variants associated with reading and language traits

Author: Gialluisi, Alessandro, Newbury, Dianne F, Wilcutt, Erik G, Olson, Richard K, DeFries, John C, Brandler, William M, Pennington, Bruce F, Smith, Shelley D, Scerri, Thomas S, Simpson, Nuala H, The SLI Consortium, Luciano, Michelle, Evans, David M, Bates, Timothy C, Stein, John F, Talcott, Joel B, Monaco, Anthony P, Paracchini, Silvia, Francks, Clyde, Fisher, Simon E, University of St Andrews. School of Medicine, and University of St Andrews. Biomedical Sciences Research Complex
Subjects: Neuroinformatics, Male, CLDRC, BF Psychology, Adolescent, SLIC, Developmental dyslexia, Pleiotropic variants, BF, QH426 Genetics, Polymorphism, Single Nucleotide, Dyslexia, reading, GWAS, Humans, Child, QH426, Language, language, Language Tests, Genome, Human, reading disability, RNA-Binding Proteins, Genetic Pleiotropy, Original Articles, pleiotropic variants, developmental dyslexia, Neoplasm Proteins, meta-analysis, Repressor Proteins, Meta-analysis, specific language impairment, Reading, Specific language impairment, Case-Control Studies, Female, Reading disability, RNA Splicing Factors, BDC, Genome-Wide Association Study
Abstract: This research was funded by: Max Planck Society, the University of St Andrews - Grant Number: 018696, US National Institutes of Health - Grant Number: P50 HD027802, Wellcome Trust - Grant Number: 090532/Z/09/Z, and Medical Research Council Hub Grant Grant Number: G0900747 91070 Reading and language abilities are heritable traits that are likely to share some genetic influences with each other. To identify pleiotropic genetic variants affecting these traits, we first performed a genome‐wide association scan (GWAS) meta‐analysis using three richly characterized datasets comprising individuals with histories of reading or language problems, and their siblings. GWAS was performed in a total of 1862 participants using the first principal component computed from several quantitative measures of reading‐ and language‐related abilities, both before and after adjustment for performance IQ. We identified novel suggestive associations at the SNPs rs59197085 and rs5995177 (uncorrected P ≈ 10–7 for each SNP), located respectively at the CCDC136/FLNC and RBFOX2 genes. Each of these SNPs then showed evidence for effects across multiple reading and language traits in univariate association testing against the individual traits. FLNC encodes a structural protein involved in cytoskeleton remodelling, while RBFOX2 is an important regulator of alternative splicing in neurons. The CCDC136/FLNC locus showed association with a comparable reading/language measure in an independent sample of 6434 participants from the general population, although involving distinct alleles of the associated SNP. Our datasets will form an important part of on‐going international efforts to identify genes contributing to reading and language skills. Publisher PDF
Published: 2014

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31 results on '"Gialluisi A"'

1. Identification of sixteen novel candidate genes for late onset Parkinson’s disease

2. Global, regional, and national burden of stroke and its risk factors, 1990–2019 : a systematic analysis for the Global Burden of Disease Study 2019

3. Association of nutritional glycaemic indices with global DNA methylation patterns: results from the Moli-sani cohort

4. Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering

5. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

6. Egg consumption and risk of all-cause and cause-specific mortality in an Italian adult population

7. Combined influence of depression severity and low-grade inflammation on incident hospitalization and mortality risk in Italian adults

8. Clinical Network for Big Data and Personalized Health: Study Protocol and Preliminary Results

9. Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study

10. Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

11. RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

12. Retrospective Recall of Psychological Distress Experienced During the First COVID-19 Lockdown in Italy: Results From the ALT RISCOVID-19 Survey

13. Use of multidimensional item response theory methods for dementia prevalence prediction: an example using the Health and Retirement Survey and the Aging, Demographics, and Memory Study

14. Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families

15. Mediterranean diet and other dietary patterns in association with biological aging in the Moli-sani Study cohort

16. Platelet Distribution Width Is Associated with P-Selectin Dependent Platelet Function: Results from the Moli-Family Cohort Study

17. Exome-wide association study of levodopa-induced dyskinesia in Parkinson's disease

18. Dietary Polyphenol Intake Is Associated with Biological Aging, a Novel Predictor of Cardiovascular Disease: Cross-Sectional Findings from the Moli-Sani Study

19. Lacosamide as first add-on or conversion monotherapy: A retrospective real-life study

20. Exploring domains, clinical implications and environmental associations of a deep learning marker of biological ageing

21. Association of a traditional Mediterranean diet and non-Mediterranean dietary scores with all-cause and cause-specific mortality: prospective findings from the Moli-sani Study

22. A genetic epidemiology study of congenital adrenal hyperplasia in Italy

23. Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia

24. Lifestyle and biological factors influence the relationship between mental health and low-grade inflammation

25. ZBTB12 DNA methylation is associated with coagulation- and inflammation-related blood cell parameters: findings from the Moli-family cohort

26. Chili Pepper Consumption and Mortality in Italian Adults

27. Multivariate genome-wide association study of rapid automatised naming and rapid alternating stimulus in Hispanic American and African-American youth

28. Mediterranean diet and mortality in the elderly: a prospective cohort study and a meta-analysis

29. Neuroimaging genetic analyses of novel candidate genes associated with reading and language

30. Next-gen sequencing identifies non-coding variation disrupting miRNA-binding sites in neurological disorders

31. Genome-wide screening for DNA variants associated with reading and language traits

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31 results on '"Gialluisi A"'

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