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2. TRPM8 on mucosal sensory nerves regulates colitogenic responses by innate immune cells via CGRP

Author

de Jong, PR, Takahashi, N, Peiris, M, Bertin, S, Lee, J, Gareau, MG, Paniagua, A, Harris, AR, Herdman, DS, Corr, M, Blackshaw, LA, and Raz, E

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Immunology, Digestive Diseases, Autoimmune Disease, Inflammatory Bowel Disease, 1.1 Normal biological development and functioning, Aetiology, Underpinning research, 2.1 Biological and endogenous factors, Inflammatory and immune system, Animals, Calcitonin Gene-Related Peptide, Colitis, Colon, Dendritic Cells, Dextran Sulfate, Epithelial Cells, Female, Gene Expression Regulation, Humans, Immunity, Innate, Immunity, Mucosal, Intestinal Mucosa, Male, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Receptors, Neurokinin-1, Sensory Receptor Cells, Signal Transduction, TRPM Cation Channels, Biological Sciences, Medical and Health Sciences
Abstract

TRPM8 is the molecular sensor for cold; however, the physiological role of TRPM8+ neurons at mucosal surfaces is unclear. Here we evaluated the distribution and peptidergic properties of TRPM8+ fibers in naive and inflamed colons, as well as their role in mucosal inflammation. We found that Trpm8(-/-) mice were hypersusceptible to dextran sodium sulfate (DSS)-induced colitis, and that Trpm8(-/-) CD11c+ DCs (dendritic cells) showed hyperinflammatory responses to toll-like receptor (TLR) stimulation. This was phenocopied in calcitonin gene-related peptide (CGRP) receptor-deficient mice, but not in substance P receptor-deficient mice, suggesting a functional link between TRPM8 and CGRP. The DSS phenotype of CGRP receptor-deficient mice could be adoptively transferred to wild-type (WT) mice, suggesting that CGRP suppresses the colitogenic activity of bone marrow-derived cells. TRPM8+ mucosal fibers expressed CGRP in human and mouse colon. Furthermore, neuronal CGRP contents were increased in colons from naive and DSS-treated Trpm8(-/-) mice, suggesting deficient CGRP release in the absence of TRPM8 triggering. Finally, treatment of Trpm8(-/-) mice with CGRP reversed their hyperinflammatory phenotype. These results suggest that TRPM8 signaling in mucosal sensory neurons is indispensable for the regulation of innate inflammatory responses via the neuropeptide CGRP.

Published
2015

3. O-041 Primary results of the pRESET for occlusive stroke treatment (PROST) randomized clinical trial

Author

Hanel, R, primary, Klisch, J, additional, Möhlenbruch, M, additional, Vollherbst, D, additional, Ulfert, C, additional, Bozorgchami, H, additional, Samaniego, EA, additional, Liebeskind, DS, additional, Lobsien, D, additional, Pielenz, D, additional, Sauvageau, E, additional, Aghaebrahim, A, additional, Clark, WM, additional, Priest, R, additional, Ortega-Gutierrez, S, additional, Lopes, D, additional, Billingsley, J, additional, Haussen, DC, additional, Al-Bayati, AR, additional, Siddiqui, AH, additional, Chen, M, additional, Schramm, P, additional, Narayanan, S, additional, Roth, C, additional, Boeckh-Behrens, T, additional, Hassan, AE, additional, Fifi, JT, additional, Budzik, R, additional, Tarpley, JW, additional, Starke, R, additional, Raz, E, additional, and Nogueira, R, additional

Published
2023
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5. Linking human Dead end 1 (DND1) variants to male infertility employing zebrafish embryos.

Author

Westerich, K.J., Reinecke, S., Emich, J., Wyrwoll, M.J., Stallmeyer, B., Meyer, Matthias, Oud, M.S., Fietz, D., Pilatz, A., Kliesch, S., Reichman-Fried, M., Tarbashevich, K., Limon, T., Stehling, M., Friedrich, C., Tüttelmann, F., Raz, E., Westerich, K.J., Reinecke, S., Emich, J., Wyrwoll, M.J., Stallmeyer, B., Meyer, Matthias, Oud, M.S., Fietz, D., Pilatz, A., Kliesch, S., Reichman-Fried, M., Tarbashevich, K., Limon, T., Stehling, M., Friedrich, C., Tüttelmann, F., and Raz, E.

Abstract

Item does not contain fulltext, STUDY QUESTION: Is the vertebrate protein Dead end (DND1) a causative factor for human infertility and can novel in vivo assays in zebrafish help in evaluating this? SUMMARY ANSWER: Combining patient genetic data with functional in vivo assays in zebrafish reveals a possible role for DND1 in human male fertility. WHAT IS KNOWN ALREADY: About 7% of the male population is affected by infertility but linking specific gene variants to the disease is challenging. The function of the DND1 protein was shown to be critical for germ cell development in several model organisms but a reliable and cost-effective method for evaluating the activity of the protein in the context of human male infertility is still missing. STUDY DESIGN, SIZE, DURATION: Exome data from 1305 men included in the Male Reproductive Genomics cohort were examined in this study. A total of 1114 of the patients showed severely impaired spermatogenesis but were otherwise healthy. Eighty-five men with intact spermatogenesis were included in the study as controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: We screened the human exome data for rare, stop-gain, frameshift, splice site, as well as missense variants in DND1. The results were validated by Sanger sequencing. Immunohistochemical techniques and, when possible, segregation analyses were performed for patients with identified DND1 variants. The amino acid exchange in the human variant was mimicked at the corresponding site of the zebrafish protein. Using different aspects of germline development in live zebrafish embryos as biological assays, we examined the activity level of these DND1 protein variants. MAIN RESULTS AND THE ROLE OF CHANCE: In human exome sequencing data, we identified four heterozygous variants in DND1 (three missense and one frameshift variant) in five unrelated patients. The function of all of the variants was examined in the zebrafish and one of those was studied in more depth in this model. We demonstrate the use of zebrafish assays

Published
2023

8. O05 Flow diversion for recurrent aneurysms after stent-assisted coiling: multicenter experience

Author

Salem, M, primary, Fargen, K, additional, Lanzino, G, additional, Tanweer, O, additional, Spiotta, A, additional, Shapiro, M, additional, Tjoumakaris, SI, additional, Kim, L, additional, Levitt, MR, additional, Kan, P, additional, Hassan, A, additional, Ducruet, A, additional, Wolfe, SC, additional, Albuquerque, F, additional, Colby, G, additional, Ogilvy, C, additional, Thomas, A, additional, Levy, E, additional, Nelson, PK, additional, Siddiqui, A, additional, Riina, H, additional, Raz, E, additional, Starke, R, additional, Jabbour, P, additional, Jankowitz, B, additional, and Burkhardt, J-K, additional

Published
2022
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10. O-072 Characteristics of a COVID-19 cohort with large vessel occlusion: a multicenter international study

Author

Jabbour, P, primary, Dmytriw, A, additional, Sweid, A, additional, Piotin, M, additional, Bekelis, K, additional, Sourour, N, additional, Raz, E, additional, Linfante, I, additional, Kole, M, additional, Nimjee, S, additional, Lopes, D, additional, Hassan, A, additional, Kan, P, additional, Ghorbani, M, additional, Levitt, M, additional, Pandey, A, additional, Starke, R, additional, El Naamani, K, additional, Abbas, R, additional, Mansour, O, additional, Walker, M, additional, Heran, M, additional, Kuhn, A, additional, Menon, B, additional, Sivakumar, S, additional, Mowla, A, additional, Zha, A, additional, Cooke, D, additional, Siddiqui, A, additional, Gupta, G, additional, Tiu, C, additional, Portela, P, additional, De la Ossa, N, additional, Orra, X, additional, De Lera, M, additional, Ribo, M, additional, Piano, M, additional, De Sousa, K, additional, Al Mufti, F, additional, Hashim, Z, additional, Renieri, L, additional, Nguyen, T, additional, Feineigle, P, additional, Patel, A, additional, Grossberg, J, additional, Saad, H, additional, Gooch, M, additional, Tjoumakaris, S, additional, Herial, N, additional, and Rosenwasser, R, additional

Published
2022
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12. Immunostimulatory-Sequence DNA is an Effective Mucosal Adjuvant

Author

Horner, A. A., Raz, E., Compans, R. W., editor, Cooper, M., editor, Hogle, J. M., editor, Ito, Y., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, and Wagner, Hermann, editor

Published
2000
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15. Thrombectomy for Primary Distal Posterior Cerebral Artery Occlusion Stroke: The TOPMOST Study

Author

Meyer, L. Stracke, C.P. Jungi, N. Wallocha, M. Broocks, G. Sporns, P.B. Maegerlein, C. Dorn, F. Zimmermann, H. Naziri, W. Abdullayev, N. Kabbasch, C. Behme, D. Jamous, A. Maus, V. Fischer, S. Möhlenbruch, M. Weyland, C.S. Langner, S. Meila, D. Miszczuk, M. Siebert, E. Lowens, S. Krause, L.U. Yeo, L.L.L. Tan, B.Y.-Q. Anil, G. Gory, B. Galván, J. Arteaga, M.S. Navia, P. Raz, E. Shapiro, M. Arnberg, F. Zeleňák, K. Martinez-Galdamez, M. Fischer, U. Kastrup, A. Roth, C. Papanagiotou, P. Kemmling, A. Gralla, J. Psychogios, M.-N. Andersson, T. Chapot, R. Fiehler, J. Kaesmacher, J. Hanning, U.

Abstract

Importance: Clinical evidence of the potential treatment benefit of mechanical thrombectomy for posterior circulation distal, medium vessel occlusion (DMVO) is sparse. Objective: To investigate the frequency as well as the clinical and safety outcomes of mechanical thrombectomy for isolated posterior circulation DMVO stroke and to compare them with the outcomes of standard medical treatment with or without intravenous thrombolysis (IVT) in daily clinical practice. Design, Setting, and Participants: This multicenter case-control study analyzed patients who were treated for primary distal occlusion of the posterior cerebral artery (PCA) of the P2 or P3 segment. These patients received mechanical thrombectomy or standard medical treatment (with or without IVT) at 1 of 23 comprehensive stroke centers in Europe, the United States, and Asia between January 1, 2010, and June 30, 2020. All patients who met the inclusion criteria were matched using 1:1 propensity score matching. Interventions: Mechanical thrombectomy or standard medical treatment with or without IVT. Main Outcomes and Measures: Clinical end point was the improvement of National Institutes of Health Stroke Scale (NIHSS) scores at discharge from baseline. Safety end point was the occurrence of symptomatic intracranial hemorrhage and hemorrhagic complications were classified based on the Second European-Australasian Acute Stroke Study (ECASSII). Functional outcome was evaluated with the modified Rankin Scale (mRS) score at 90-day follow-up. Results: Of 243 patients from all participating centers who met the inclusion criteria, 184 patients were matched. Among these patients, the median (interquartile range [IQR]) age was 74 (62-81) years and 95 (51.6%) were female individuals. Posterior circulation DMVOs were located in the P2 segment of the PCA in 149 patients (81.0%) and in the P3 segment in 35 patients (19.0%). At discharge, the mean NIHSS score decrease was -2.4 points (95% CI, -3.2 to -1.6) in the standard medical treatment cohort and -3.9 points (95% CI, -5.4 to -2.5) in the mechanical thrombectomy cohort, with a mean difference of -1.5 points (95% CI, 3.2 to -0.8; P =.06). Significant treatment effects of mechanical thrombectomy were observed in the subgroup of patients who had higher NIHSS scores on admission of 10 points or higher (mean difference, -5.6; 95% CI, -10.9 to -0.2; P =.04) and in the subgroup of patients without IVT (mean difference, -3.0; 95% CI, -5.0 to -0.9; P =.005). Symptomatic intracranial hemorrhage occurred in 4 of 92 patients (4.3%) in each treatment cohort. Conclusions and Relevance: This study suggested that, although rarely performed at comprehensive stroke centers, mechanical thrombectomy for posterior circulation DMVO is a safe, and technically feasible treatment option for occlusions of the P2 or P3 segment of the PCA compared with standard medical treatment with or without IVT.. © 2021 American Medical Association. All rights reserved.

Published
2021

16. Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

Author

Nguyen, T.N. Haussen, D.C. Qureshi, M.M. Yamagami, H. Fujinaka, T. Mansour, O.Y. Abdalkader, M. Frankel, M. Qiu, Z. Taylor, A. Lylyk, P. Eker, O.F. Mechtouff, L. Piotin, M. Lima, F.O. Mont'Alverne, F. Izzath, W. Sakai, N. Mohammaden, M. Al-Bayati, A.R. Renieri, L. Mangiafico, S. Ozretic, D. Chalumeau, V. Ahmad, S. Rashid, U. Hussain, S.I. John, S. Griffin, E. Thornton, J. Fiorot, J.A. Rivera, R. Hammami, N. Cervantes-Arslanian, A.M. Dasenbrock, H.H. Vu, H.L. Nguyen, V.Q. Hetts, S. Bourcier, R. Guile, R. Walker, M. Sharma, M. Frei, D. Jabbour, P. Herial, N. Al-Mufti, F. Ozdemir, A.O. Aykac, O. Gandhi, D. Chugh, C. Matouk, C. Lavoie, P. Edgell, R. Beer-Furlan, A. Chen, M. Killer-Oberpfalzer, M. Pereira, V.M. Nicholson, P. Huded, V. Ohara, N. Watanabe, D. Shin, D.H. Magalhaes, P.S.C. Kikano, R. Ortega-Gutierrez, S. Farooqui, M. Abou-Hamden, A. Amano, T. Yamamoto, R. Weeks, A. Cora, E.A. Sivan-Hoffmann, R. Crosa, R. Möhlenbruch, M. Nagel, S. Al-Jehani, H. Sheth, S.A. Rivera, V.S.L. Siegler, J.E. Sani, A.F. Puri, A.S. Kuhn, A.L. Bernava, G. Machi, P. Abud, D.G. Pontes-Neto, O.M. Wakhloo, A.K. Voetsch, B. Raz, E. Yaghi, S. Mehta, B.P. Kimura, N. Murakami, M. Lee, J.S. Hong, J.M. Fahed, R. Walker, G. Hagashi, E. Cordina, S.M. Roh, H.G. Wong, K. Arenillas, J.F. Martinez-Galdamez, M. Blasco, J. Vasquez, A.R. Fonseca, L. Silva, M.L. Wu, T.Y. John, S. Brehm, A. Psychogios, M. Mack, W.J. Tenser, M. Todaka, T. Fujimura, M. Novakovic, R. Deguchi, J. Sugiura, Y. Tokimura, H. Khatri, R. Kelly, M. Peeling, L. Murayama, Y. Winters, H.S. Wong, J. Teleb, M. Payne, J. Fukuda, H. Miyake, K. Shimbo, J. Sugimura, Y. Uno, M. Takenobu, Y. Matsumaru, Y. Yamada, S. Kono, R. Kanamaru, T. Morimoto, M. Iida, J. Saini, V. Yavagal, D. Bushnaq, S. Huang, W. Linfante, I. Kirmani, J. Liebeskind, D.S. Szeder, V. Shah, R. Devlin, T.G. Birnbaum, L. Luo, J. Churojana, A. Masoud, H.E. Lopez, C.Y. Steinfort, B. Ma, A. Hassan, A.E. Al Hashmi, A. McDermott, M. Mokin, M. Chebl, A. Kargiotis, O. Tsivgoulis, G. Morris, J.G. Eskey, C.J. Thon, J. Rebello, L. Altschul, D. Cornett, O. Singh, V. Pandian, J. Kulkarni, A. Lavados, P.M. Olavarria, V.V. Todo, K. Yamamoto, Y. Silva, G.S. Geyik, S. Johann, J. Multani, S. Kaliaev, A. Sonoda, K. Hashimoto, H. Alhazzani, A. Chung, D.Y. Mayer, S.A. Fifi, J.T. Hill, M.D. Zhang, H. Yuan, Z. Shang, X. Castonguay, A.C. Gupta, R. Jovin, T.G. Raymond, J. Zaidat, O.O. Nogueira, R.G.

Subjects
cardiovascular diseases, nervous system diseases
Abstract

Background During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. Methods We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. Findings There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p

Published
2021

17. Global impact of COVID-19 on stroke care

Author

Nogueira, R.G. Abdalkader, M. Qureshi, M.M. Frankel, M.R. Mansour, O.Y. Yamagami, H. Qiu, Z. Farhoudi, M. Siegler, J.E. Yaghi, S. Raz, E. Sakai, N. Ohara, N. Piotin, M. Mechtouff, L. Eker, O. Chalumeau, V. Kleinig, T.J. Pop, R. Liu, J. Winters, H.S. Shang, X. Vasquez, A.R. Blasco, J. Arenillas, J.F. Martinez-Galdamez, M. Brehm, A. Psychogios, M.-N. Lylyk, P. Haussen, D.C. Al-Bayati, A.R. Mohammaden, M.H. Fonseca, L. Luís Silva, M. Montalverne, F. Renieri, L. Mangiafico, S. Fischer, U. Gralla, J. Frei, D. Chugh, C. Mehta, B.P. Nagel, S. Mohlenbruch, M. Ortega-Gutierrez, S. Farooqui, M. Hassan, A.E. Taylor, A. Lapergue, B. Consoli, A. Campbell, B.C.V. Sharma, M. Walker, M. Van Horn, N. Fiehler, J. Nguyen, H.T. Nguyen, Q.T. Watanabe, D. Zhang, H. Le, H.V. Nguyen, V.Q. Shah, R. Devlin, T. Khandelwal, P. Linfante, I. Izzath, W. Lavados, P.M. Olavarría, V.V. Sampaio Silva, G. de Carvalho Sousa, A.V. Kirmani, J. Bendszus, M. Amano, T. Yamamoto, R. Doijiri, R. Tokuda, N. Yamada, T. Terasaki, T. Yazawa, Y. Morris, J.G. Griffin, E. Thornton, J. Lavoie, P. Matouk, C. Hill, M.D. Demchuk, A.M. Killer-Oberpfalzer, M. Nahab, F. Altschul, D. Ramos-Pachón, A. Pérez de la Ossa, N. Kikano, R. Boisseau, W. Walker, G. Cordina, S.M. Puri, A. Luisa Kuhn, A. Gandhi, D. Ramakrishnan, P. Novakovic-White, R. Chebl, A. Kargiotis, O. Czap, A. Zha, A. Masoud, H.E. Lopez, C. Ozretic, D. Al-Mufti, F. Zie, W. Duan, Z. Yuan, Z. Huang, W. Hao, Y. Luo, J. Kalousek, V. Bourcier, R. Guile, R. Hetts, S. Al-Jehani, H.M. AlHazzani, A. Sadeghi-Hokmabadi, E. Teleb, M. Payne, J. Lee, J.S. Hong, J.M. Sohn, S.-I. Hwang, Y.-H. Shin, D.H. Roh, H.G. Edgell, R. Khatri, R. Smith, A. Malik, A. Liebeskind, D. Herial, N. Jabbour, P. Magalhaes, P. Ozdemir, A.O. Aykac, O. Uwatoko, T. Dembo, T. Shimizu, H. Sugiura, Y. Miyashita, F. Fukuda, H. Miyake, K. Shimbo, J. Sugimura, Y. Beer-Furlan, A. Joshi, K. Catanese, L. Abud, D.G. Neto, O.G. Mehrpour, M. Al Hashmi, A. Saqqur, M. Mostafa, A. Fifi, J.T. Hussain, S. John, S. Gupta, R. Sivan-Hoffmann, R. Reznik, A. Sani, A.F. Geyik, S. Akıl, E. Churojana, A. Ghoreishi, A. Saadatnia, M. Sharifipour, E. Ma, A. Faulder, K. Wu, T. Leung, L. Malek, A. Voetsch, B. Wakhloo, A. Rivera, R. Barrientos Iman, D.M. Pikula, A. Lioutas, V.-A. Thomalla, G. Birnbaum, L. Machi, P. Bernava, G. McDermott, M. Kleindorfer, D. Wong, K. Patterson, M.S. Fiorot, J.A., Jr. Huded, V. Mack, W. Tenser, M. Eskey, C. Multani, S. Kelly, M. Janardhan, V. Cornett, O. Singh, V. Murayama, Y. Mokin, M. Yang, P. Zhang, X. Yin, C. Han, H. Peng, Y. Chen, W. Crosa, R. Frudit, M.E. Pandian, J.D. Kulkarni, A. Yagita, Y. Takenobu, Y. Matsumaru, Y. Yamada, S. Kono, R. Kanamaru, T. Yamazaki, H. Sakaguchi, M. Todo, K. Yamamoto, N. Sonoda, K. Yoshida, T. Hashimoto, H. Nakahara, I. Cora, E. Volders, D. Ducroux, C. Shoamanesh, A. Ospel, J. Kaliaev, A. Ahmed, S. Rashid, U. Rebello, L.C. Pereira, V.M. Fahed, R. Chen, M. Sheth, S.A. Palaiodimou, L. Tsivgoulis, G. Chandra, R. Koyfman, F. Leung, T. Khosravani, H. Dharmadhikari, S. Frisullo, G. Calabresi, P. Tsiskaridze, A. Lobjanidze, N. Grigoryan, M. Czlonkowska, A. de Sousa, D.A. Demeestere, J. Liang, C. Sangha, N. Lutsep, H.L. Ayo-Martín, Ó. Cruz-Culebras, A. Tran, A.D. Young, C.Y. Cordonnier, C. Caparros, F. De Lecinana, M.A. Fuentes, B. Yavagal, D. Jovin, T. Spelle, L. Moret, J. Khatri, P. Zaidat, O. Raymond, J. Martins, S. Nguyen, T.

Abstract

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March–31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, −19.7 to −18.7), 11.5% (95%CI, −12.6 to −10.6), and 12.7% (95%CI, −13.6 to −11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (−20.5%) had greater declines in mechanical thrombectomy volumes than mid- (−10.1%) and low-volume (−8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes. © 2021 World Stroke Organization.

Published
2021

18. Global Impact of COVID-19 on Stroke Care and IV Thrombolysis

Author

Nogueira, R.G. Qureshi, M.M. Abdalkader, M. Martins, S.O. Yamagami, H. Qiu, Z. Mansour, O.Y. Sathya, A. Czlonkowska, A. Tsivgoulis, G. Aguiar de Sousa, D. Demeestere, J. Mikulik, R. Vanacker, P. Siegler, J.E. Kõrv, J. Biller, J. Liang, C.W. Sangha, N.S. Zha, A.M. Czap, A.L. Holmstedt, C.A. Turan, T.N. Ntaios, G. Malhotra, K. Tayal, A. Loochtan, A. Ranta, A. Mistry, E.A. Alexandrov, A.W. Huang, D.Y. Yaghi, S. Raz, E. Sheth, S.A. Mohammaden, M.H. Frankel, M. Bila Lamou, E.G. Aref, H.M. Elbassiouny, A. Hassan, F. Menecie, T. Mustafa, W. Shokri, H.M. Roushdy, T. Sarfo, F.S. Alabi, T.O. Arabambi, B. Nwazor, E.O. Sunmonu, T.A. Wahab, K. Yaria, J. Mohammed, H.H. Adebayo, P.B. Riahi, A.D. Sassi, S.B. Gwaunza, L. Ngwende, G.W. Sahakyan, D. Rahman, A. Ai, Z. Bai, F. Duan, Z. Hao, Y. Huang, W. Li, G. Li, W. Liu, G. Luo, J. Shang, X. Sui, Y. Tian, L. Wen, H. Wu, B. Yan, Y. Yuan, Z. Zhang, H. Zhang, J. Zhao, W. Zi, W. Leung, T.W. Chugh, C. Huded, V. Menon, B. Pandian, J.D. Sylaja, P.N. Usman, F.S. Farhoudi, M. Hokmabadi, E.S. Horev, A. Reznik, A. Sivan Hoffmann, R. Ohara, N. Sakai, N. Watanabe, D. Yamamoto, R. Doijiri, R. Tokuda, N. Yamada, T. Terasaki, T. Yazawa, Y. Uwatoko, T. Dembo, T. Shimizu, H. Sugiura, Y. Miyashita, F. Fukuda, H. Miyake, K. Shimbo, J. Sugimura, Y. Yagita, Y. Takenobu, Y. Matsumaru, Y. Yamada, S. Kono, R. Kanamaru, T. Yamazaki, H. Sakaguchi, M. Todo, K. Yamamoto, N. Sonoda, K. Yoshida, T. Hashimoto, H. Nakahara, I. Kondybayeva, A. Faizullina, K. Kamenova, S. Zhanuzakov, M. Baek, J.-H. Hwang, Y. Lee, J.S. Lee, S.B. Moon, J. Park, H. Seo, J.H. Seo, K.-D. Sohn, S.I. Young, C.J. Ahdab, R. Wan Zaidi, W.A. Aziz, Z.A. Basri, H.B. Chung, L.W. Ibrahim, A.B. Ibrahim, K.A. Looi, I. Tan, W.Y. Yahya, N.W. Groppa, S. Leahu, P. Al Hashmi, A.M. Imam, Y.Z. Akhtar, N. Pineda-Franks, M.C. Co, C.O. Kandyba, D. Alhazzani, A. Al-Jehani, H. Tham, C.H. Mamauag, M.J. Venketasubramanian, N. Chen, C.-H. Tang, S.-C. Churojana, A. Akil, E. Aykaç, Ö. Ozdemir, A.O. Giray, S. Hussain, S.I. John, S. Le Vu, H. Tran, A.D. Nguyen, H.H. Nhu Pham, T. Nguyen, T.H. Nguyen, T.Q. Gattringer, T. Enzinger, C. Killer-Oberpfalzer, M. Bellante, F. De Blauwe, S. Vanhooren, G. De Raedt, S. Dusart, A. Lemmens, R. Ligot, N. Pierre Rutgers, M. Yperzeele, L. Alexiev, F. Sakelarova, T. Bedeković, M.R. Budincevic, H. Cindric, I. Hucika, Z. Ozretic, D. Saric, M.S. Pfeifer, F. Karpowic, I. Cernik, D. Sramek, M. Skoda, M. Hlavacova, H. Klecka, L. Koutny, M. Vaclavik, D. Skoda, O. Fiksa, J. Hanelova, K. Nevsimalova, M. Rezek, R. Prochazka, P. Krejstova, G. Neumann, J. Vachova, M. Brzezanski, H. Hlinovsky, D. Tenora, D. Jura, R. Jurák, L. Novak, J. Novak, A. Topinka, Z. Fibrich, P. Sobolova, H. Volny, O. Krarup Christensen, H. Drenck, N. Klingenberg Iversen, H. Simonsen, C.Z. Truelsen, T.C. Wienecke, T. Vibo, R. Gross-Paju, K. Toomsoo, T. Antsov, K. Caparros, F. Cordonnier, C. Dan, M. Faucheux, J.-M. Mechtouff, L. Eker, O. Lesaine, E. Ondze, B. Peres, R. Pico, F. Piotin, M. Pop, R. Rouanet, F. Gubeladze, T. Khinikadze, M. Lobjanidze, N. Tsiskaridze, A. Nagel, S. Ringleb, P.A. Rosenkranz, M. Schmidt, H. Sedghi, A. Siepmann, T. Szabo, K. Thomalla, G. Palaiodimou, L. Sagris, D. Kargiotis, O. Klivenyi, P. Szapary, L. Tarkanyi, G. Adami, A. Bandini, F. Calabresi, P. Frisullo, G. Renieri, L. Sangalli, D. Pirson, A. Uyttenboogaart, M. van den Wijngaard, I. Kristoffersen, E.S. Brola, W. Fudala, M. Horoch-Lyszczarek, E. Karlinski, M. Kazmierski, R. Kram, P. Rogoziewicz, M. Kaczorowski, R. Luchowski, P. Sienkiewicz-Jarosz, H. Sobolewski, P. Fryze, W. Wisniewska, A. Wiszniewska, M. Ferreira, P. Ferreira, P. Fonseca, L. Marto, J.P. Pinho E Melo, T. Nunes, A.P. Rodrigues, M. Tedim Cruz, V. Falup-Pecurariu, C. Krastev, G. Mako, M. de Leciñana, M.A. Arenillas, J.F. Ayo-Martin, O. Cruz Culebras, A. Tejedor, E.D. Montaner, J. Pérez-Sánchez, S. Tola Arribas, M.A. Rodriguez Vasquez, A. Mayza, M. Bernava, G. Brehm, A. Machi, P. Fischer, U. Gralla, J. Michel, P.L. Psychogios, M.-N. Strambo, D. Banerjee, S. Krishnan, K. Kwan, J. Butt, A. Catanese, L. Demchuk, A.M. Field, T. Haynes, J. Hill, M.D. Khosravani, H. Mackey, A. Pikula, A. Saposnik, G. Scott, C.A. Shoamanesh, A. Shuaib, A. Yip, S. Barboza, M.A. Barrientos, J.D. Portillo Rivera, L.I. Gongora-Rivera, F. Novarro-Escudero, N. Blanco, A. Abraham, M. Alsbrook, D. Altschul, D. Alvarado-Ortiz, A.J. Bach, I. Badruddin, A. Barazangi, N. Brereton, C. Castonguay, A. Chaturvedi, S. Chaudry, S.A. Choe, H. Choi, J.H. Dharmadhikari, S. Desai, K. Devlin, T.G. Doss, V.T. Edgell, R. Etherton, M. Farooqui, M. Frei, D. Gandhi, D. Grigoryan, M. Gupta, R. Hassan, A.E. Helenius, J. Kaliaev, A. Kaushal, R. Khandelwal, P. Khawaja, A.M. Khoury, N.N. Kim, B.S. Kleindorfer, D.O. Koyfman, F. Lee, V.H. Leung, L.Y. Linares, G. Linfante, I. Lutsep, H.L. Macdougall, L. Male, S. Malik, A.M. Masoud, H. McDermott, M. Mehta, B.P. Min, J. Mittal, M. Morris, J.G. Multani, S.S. Nahab, F. Nalleballe, K. Nguyen, C.B. Novakovic-White, R. Ortega-Gutierrez, S. Rahangdale, R.H. Ramakrishnan, P. Romero, J.R. Rost, N. Rothstein, A. Ruland, S. Shah, R. Sharma, M. Silver, B. Simmons, M. Singh, A. Starosciak, A.K. Strasser, S.L. Szeder, V. Teleb, M. Tsai, J.P. Voetsch, B. Balaguera, O. Pujol Lereis, V.A. Luraschi, A. Almeida, M.S. Cardoso, F.B. Conforto, A. De Deus Silva, L. Varrone Giacomini, L. Oliveira Lima, F. Longo, A.L. Magalhães, P.S.C. Martins, R.T. Mont'alverne, F. Mora Cuervo, D.L. Costa Rebello, L. Valler, L. Zetola, V.F. Lavados, P.M. Navia, V. Olavarría, V.V. Almeida Toro, J.M. Amaya, P.F.R. Bayona, H. Corredor, A. Rivera Ordonez, C.E. Mantilla Barbosa, D.K. Lara, O. Patiño, M.R. Diaz Escobar, L.F. Dejesus Melgarejo Fariña, D.E. Cardozo Villamayor, A. Zelaya Zarza, A.J. Barrientos Iman, D.M. Rodriguez Kadota, L. Campbell, B. Hankey, G.J. Hair, C. Kleinig, T. Ma, A. Tomazini Martins, R. Sahathevan, R. Thijs, V. Salazar, D. Yuan-Hao Wu, T. Haussen, D.C. Liebeskind, D. Yavagal, D.R. Jovin, T.G. Zaidat, O.O. Nguyen, T.N. SVIN COVID-19 Global Stroke Registry SVIN COVID-19 Global Stroke Registry

Abstract

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months. © 2021 American Academy of Neurology.

Published
2021

19. Global impact of COVID-19 on stroke care

Author

Nogueira, RG, Abdalkader, M, Qureshi, MM, Frankel, MR, Mansour, OY, Yamagami, H, Qiu, Z, Farhoudi, M, Siegler, JE, Yaghi, S, Raz, E, Sakai, N, Ohara, N, Piotin, M, Mechtouff, L, Eker, O, Chalumeau, V, Kleinig, TJ, Pop, R, Liu, J, Winters, HS, Shang, X, Rodriguez Vasquez, A, Blasco, J, Arenillas, JF, Martinez-Galdamez, M, Brehm, A, Psychogios, M-N, Lylyk, P, Haussen, DC, Al-Bayati, AR, Mohammaden, MH, Fonseca, L, Luis Silva, M, Montalverne, F, Renieri, L, Mangiafico, S, Fischer, U, Gralla, J, Frei, D, Chugh, C, Mehta, BP, Nagel, S, Mohlenbruch, M, Ortega-Gutierrez, S, Farooqui, M, Hassan, AE, Taylor, A, Lapergue, B, Consoli, A, Campbell, BCV, Sharma, M, Walker, M, Van Horn, N, Fiehler, J, Huy, TN, Nguyen, QT, Watanabe, D, Zhang, H, Le, HV, Nguyen, VQ, Shah, R, Devlin, T, Khandelwal, P, Linfante, I, Izzath, W, Lavados, PM, Olavarria, VV, Silva, GS, de Carvalho Sousa, AV, Kirmani, J, Bendszus, M, Amano, T, Yamamoto, R, Doijiri, R, Tokuda, N, Yamada, T, Terasaki, T, Yazawa, Y, Morris, JG, Griffin, E, Thornton, J, Lavoie, P, Matouk, C, Hill, MD, Demchuk, AM, Killer-Oberpfalzer, M, Nahab, F, Altschul, D, Ramos-Pachon, A, Perez de la Ossa, N, Kikano, R, Boisseau, W, Walker, G, Cordina, SM, Puri, A, Kuhn, AL, Gandhi, D, Ramakrishnan, P, Novakovic-White, R, Chebl, A, Kargiotis, O, Czap, A, Zha, A, Masoud, HE, Lopez, C, Ozretic, D, Al-Mufti, F, Zie, W, Duan, Z, Yuan, Z, Huang, W, Hao, Y, Luo, J, Kalousek, V, Bourcier, R, Guile, R, Hetts, S, Al-Jehani, HM, AlHazzani, A, Sadeghi-Hokmabadi, E, Teleb, M, Payne, J, Lee, JS, Hong, JM, Sohn, S-I, Hwang, Y-H, Shin, DH, Roh, HG, Edgell, R, Khatri, R, Smith, A, Malik, A, Liebeskind, D, Herial, N, Jabbour, P, Magalhaes, P, Ozdemir, AO, Aykac, O, Uwatoko, T, Dembo, T, Shimizu, H, Sugiura, Y, Miyashita, F, Fukuda, H, Miyake, K, Shimbo, J, Sugimura, Y, Beer-Furlan, A, Joshi, K, Catanese, L, Abud, DG, Pontes Neto, O, Mehrpour, M, Al Hashmi, A, Saqqur, M, Mostafa, A, Fifi, JT, Hussain, S, John, S, Gupta, R, Sivan-Hoffmann, R, Reznik, A, Sani, AF, Geyik, S, Akil, ECR, Churojana, A, Ghoreishi, A, Saadatnia, M, Sharifipour, E, Ma, A, Faulder, K, Wu, T, Leung, L, Malek, A, Voetsch, B, Wakhloo, A, Rivera, R, Barrientos Iman, DM, Pikula, A, Lioutas, V-A, Thomalla, G, Birnbaum, L, Machi, P, Bernava, G, McDermott, M, Kleindorfer, D, Wong, K, Patterson, MS, Fiorot, JA, Huded, V, Mack, W, Tenser, M, Eskey, C, Multani, S, Kelly, M, Janardhan, V, Cornett, O, Singh, V, Murayama, Y, Mokin, M, Yang, P, Zhang, X, Yin, C, Han, H, Peng, Y, Chen, W, Crosa, R, Frudit, ME, Pandian, JD, Kulkarni, A, Yagita, Y, Takenobu, Y, Matsumaru, Y, Yamada, S, Kono, R, Kanamaru, T, Yamazaki, H, Sakaguchi, M, Todo, K, Yamamoto, N, Sonoda, K, Yoshida, T, Hashimoto, H, Nakahara, I, Cora, E, Volders, D, Ducroux, C, Shoamanesh, A, Ospel, J, Kaliaev, A, Ahmed, S, Rashid, U, Rebello, LC, Pereira, VM, Fahed, R, Chen, M, Sheth, SA, Palaiodimou, L, Tsivgoulis, G, Chandra, R, Koyfman, F, Leung, T, Khosravani, H, Dharmadhikari, S, Frisullo, G, Calabresi, P, Tsiskaridze, A, Lobjanidze, N, Grigoryan, M, Czlonkowska, A, de Sousa, DA, Demeestere, J, Liang, C, Sangha, N, Lutsep, HL, Ayo-Martin, O, Cruz-Culebras, A, Tran, AD, Young, CY, Cordonnier, C, Caparros, F, Alonso De Lecinana, M, Fuentes, B, Yavagal, D, Jovin, T, Spelle, L, Moret, J, Khatri, P, Zaidat, O, Raymond, J, Martins, S, Thanh, N, Nogueira, RG, Abdalkader, M, Qureshi, MM, Frankel, MR, Mansour, OY, Yamagami, H, Qiu, Z, Farhoudi, M, Siegler, JE, Yaghi, S, Raz, E, Sakai, N, Ohara, N, Piotin, M, Mechtouff, L, Eker, O, Chalumeau, V, Kleinig, TJ, Pop, R, Liu, J, Winters, HS, Shang, X, Rodriguez Vasquez, A, Blasco, J, Arenillas, JF, Martinez-Galdamez, M, Brehm, A, Psychogios, M-N, Lylyk, P, Haussen, DC, Al-Bayati, AR, Mohammaden, MH, Fonseca, L, Luis Silva, M, Montalverne, F, Renieri, L, Mangiafico, S, Fischer, U, Gralla, J, Frei, D, Chugh, C, Mehta, BP, Nagel, S, Mohlenbruch, M, Ortega-Gutierrez, S, Farooqui, M, Hassan, AE, Taylor, A, Lapergue, B, Consoli, A, Campbell, BCV, Sharma, M, Walker, M, Van Horn, N, Fiehler, J, Huy, TN, Nguyen, QT, Watanabe, D, Zhang, H, Le, HV, Nguyen, VQ, Shah, R, Devlin, T, Khandelwal, P, Linfante, I, Izzath, W, Lavados, PM, Olavarria, VV, Silva, GS, de Carvalho Sousa, AV, Kirmani, J, Bendszus, M, Amano, T, Yamamoto, R, Doijiri, R, Tokuda, N, Yamada, T, Terasaki, T, Yazawa, Y, Morris, JG, Griffin, E, Thornton, J, Lavoie, P, Matouk, C, Hill, MD, Demchuk, AM, Killer-Oberpfalzer, M, Nahab, F, Altschul, D, Ramos-Pachon, A, Perez de la Ossa, N, Kikano, R, Boisseau, W, Walker, G, Cordina, SM, Puri, A, Kuhn, AL, Gandhi, D, Ramakrishnan, P, Novakovic-White, R, Chebl, A, Kargiotis, O, Czap, A, Zha, A, Masoud, HE, Lopez, C, Ozretic, D, Al-Mufti, F, Zie, W, Duan, Z, Yuan, Z, Huang, W, Hao, Y, Luo, J, Kalousek, V, Bourcier, R, Guile, R, Hetts, S, Al-Jehani, HM, AlHazzani, A, Sadeghi-Hokmabadi, E, Teleb, M, Payne, J, Lee, JS, Hong, JM, Sohn, S-I, Hwang, Y-H, Shin, DH, Roh, HG, Edgell, R, Khatri, R, Smith, A, Malik, A, Liebeskind, D, Herial, N, Jabbour, P, Magalhaes, P, Ozdemir, AO, Aykac, O, Uwatoko, T, Dembo, T, Shimizu, H, Sugiura, Y, Miyashita, F, Fukuda, H, Miyake, K, Shimbo, J, Sugimura, Y, Beer-Furlan, A, Joshi, K, Catanese, L, Abud, DG, Pontes Neto, O, Mehrpour, M, Al Hashmi, A, Saqqur, M, Mostafa, A, Fifi, JT, Hussain, S, John, S, Gupta, R, Sivan-Hoffmann, R, Reznik, A, Sani, AF, Geyik, S, Akil, ECR, Churojana, A, Ghoreishi, A, Saadatnia, M, Sharifipour, E, Ma, A, Faulder, K, Wu, T, Leung, L, Malek, A, Voetsch, B, Wakhloo, A, Rivera, R, Barrientos Iman, DM, Pikula, A, Lioutas, V-A, Thomalla, G, Birnbaum, L, Machi, P, Bernava, G, McDermott, M, Kleindorfer, D, Wong, K, Patterson, MS, Fiorot, JA, Huded, V, Mack, W, Tenser, M, Eskey, C, Multani, S, Kelly, M, Janardhan, V, Cornett, O, Singh, V, Murayama, Y, Mokin, M, Yang, P, Zhang, X, Yin, C, Han, H, Peng, Y, Chen, W, Crosa, R, Frudit, ME, Pandian, JD, Kulkarni, A, Yagita, Y, Takenobu, Y, Matsumaru, Y, Yamada, S, Kono, R, Kanamaru, T, Yamazaki, H, Sakaguchi, M, Todo, K, Yamamoto, N, Sonoda, K, Yoshida, T, Hashimoto, H, Nakahara, I, Cora, E, Volders, D, Ducroux, C, Shoamanesh, A, Ospel, J, Kaliaev, A, Ahmed, S, Rashid, U, Rebello, LC, Pereira, VM, Fahed, R, Chen, M, Sheth, SA, Palaiodimou, L, Tsivgoulis, G, Chandra, R, Koyfman, F, Leung, T, Khosravani, H, Dharmadhikari, S, Frisullo, G, Calabresi, P, Tsiskaridze, A, Lobjanidze, N, Grigoryan, M, Czlonkowska, A, de Sousa, DA, Demeestere, J, Liang, C, Sangha, N, Lutsep, HL, Ayo-Martin, O, Cruz-Culebras, A, Tran, AD, Young, CY, Cordonnier, C, Caparros, F, Alonso De Lecinana, M, Fuentes, B, Yavagal, D, Jovin, T, Spelle, L, Moret, J, Khatri, P, Zaidat, O, Raymond, J, Martins, S, and Thanh, N

Abstract

BACKGROUND: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. AIMS: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). METHODS: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. RESULTS: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. CONCLUSION: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.

Published
2021

22. Reply

Author

Shapiro, M., primary, Srivatanakul, K., additional, Raz, E., additional, Litao, M., additional, Nossek, E., additional, and Nelson, P.K., additional

Published
2021
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23. Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses

Author

Lee J, Zhang J, Chung YJ, Kim JH, Kook CM, González-Navajas JM, Herdman DS, Nürnberg B, Insel PA, Corr M, Mo JH, Tao A, Yasuda K, Rifkin IR, Broide DH, Sciammas R, Webster NJ, and Raz E

Subjects
immunology, Th2, PRR, IRF4, inflammation, cAMP, Th17, dendritic cells, mouse
Abstract

Cyclic AMP (cAMP) is involved in many biological processes but little is known regarding its role in shaping immunity. Here we show that cAMP-PKA-CREB signaling (a pattern recognition receptor [PRR]-independent mechanism) regulates conventional type-2 Dendritic Cells (cDC2s) in mice and reprograms their Th17-inducing properties via repression of IRF4 and KLF4, transcription factors essential for cDC2-mediated Th2 induction. In mice, genetic loss of IRF4 phenocopies the effects of cAMP on Th17 induction and restoration of IRF4 prevents the cAMP effect. Moreover, curdlan, a PRR-dependent microbial product, activates CREB and represses IRF4 and KLF4, resulting in a pro-Th17 phenotype of cDC2s. These in vitro and in vivo results define a novel signaling pathway by which cDC2s display plasticity and provide a new molecular basis for the classification of novel cDC2 and cDC17 subsets. The findings also reveal that repressing IRF4 and KLF4 pathway can be harnessed for immuno-regulation.

Published
2020

24. E-085 Multicenter retrospective study of the sofia for aspiration in acute ischemic stroke (mrs sofia)

Author

Brinjikji, W, primary, DeLeacy, R, additional, Meila, D, additional, Mokin, M, additional, Samaniego, E, additional, Cora, A, additional, Shapiro, M, additional, Agarwal, S, additional, Bageac, D, additional, Roa, J, additional, Ren, Z, additional, Li, W, additional, Rinaldo, L, additional, Cloft, H, additional, Volders, D, additional, Huynh, T, additional, and Raz, E, additional

Published
2020
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26. Cerebral Venous Thrombosis Associated with COVID-19

Author

Cavalcanti, D.D., primary, Raz, E., additional, Shapiro, M., additional, Dehkharghani, S., additional, Yaghi, S., additional, Lillemoe, K., additional, Nossek, E., additional, Torres, J., additional, Jain, R., additional, Riina, H.A., additional, Radmanesh, A., additional, and Nelson, P.K., additional

Published
2020
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32. DNA vaccines

Author

Spiegelberg, H. L. and Raz, E.

Published
1999

33. Chemokine-guided cell migration and motility in zebrafish development

Author

Bussmann, J., Raz, E., Bussmann J., Raz E., and Bussmann J., Raz E.

Subjects
Male, Chemokine, Neutrophils, Cell, Reviews, Context (language use), Models, Biological, General Biochemistry, Genetics and Molecular Biology, Chemokine receptor, Cell Movement, medicine, Animals, Receptor, Molecular Biology, Zebrafish, General Immunology and Microbiology, biology, General Neuroscience, Cell migration, biology.organism_classification, Cell biology, medicine.anatomical_structure, biology.protein, Cytokines, Female, Chemokines, Developmental biology
Abstract

Chemokines are vertebrate-specific, structurally related proteins that function primarily in controlling cell movements by activating specific 7-transmembrane receptors. Chemokines play critical roles in a large number of biological processes and are also involved in a range of pathological conditions. For these reasons, chemokines are at the focus of studies in developmental biology and of clinically oriented research aimed at controlling cancer, inflammation, and immunological diseases. The small size of the zebrafish embryos, their rapid external development, and optical properties as well as the large number of eggs and the fast expansion in genetic tools available make this model an extremely useful one for studying the function of chemokines and chemokine receptors in an in vivo setting. Here, we review the findings relevant to the role that chemokines play in the context of directed single-cell migration, primarily in neutrophils and germ cells, and compare it to the collective cell migration of the zebrafish lateral line. We present the current knowledge concerning the formation of the chemokine gradient, its interpretation within the cell, and the molecular mechanisms underlying the cellular response to chemokine signals during directed migration.

Published
2015

42. Is There an Association between Cerebral Microbleeds and Leukoaraiosis?

Author

Saba L, Raz E, Bassareo PP, di Martino M, de Cecco CN, Mercuro G, Suri JS, Piga M., GRASSI, Roberto, Saba, L, Raz, E, Bassareo, Pp, di Martino, M, de Cecco, Cn, Mercuro, G, Grassi, Roberto, Suri, J, and Piga, M.

Subjects
Cerebral microbleed, leukoaraiosis
Abstract

Cerebral microbleeds (CMBs) are small dot-like lesions appearing as hyposignals on gradient echo (GRE) T2* magnetic resonance (MR) sequences, whereas the leukoaraiosis (LA) indicates the presence of patchy areas of hypersignal on fluid-attenuated inversion recovery (FLAIR) MR sequences in the periventricular white matter. The purpose of this work was to evaluate the association between LA and CMBs. MATERIAL AND METHODS: Eighty-five consecutive (men 55; median age 64 years) patients were retrospectively analyzed using a 1.5 T system; CMBs were studied using a T2*-weighted GRE sequence and classified as absent (grade 1), mild (grade 2; total number of microbleeds, 1-2), moderate (grade 3; total number of microbleeds, 3-10), and severe (grade 4; total number of microbleeds, >10). LA was assessed with FLAIR MR sequences and was graded based on the European Task Force on Age-Related White Matter Changes as follows: 1 (no lesions), 2 (focal lesions > 5 mm), 3 (early confluent lesions), and 4 (diffuse involvement of an entire brain region). RESULTS: We considered 170 cerebral hemispheres. The prevalence of CMBs was 24.7% (42 of 170), whereas the prevalence of LA was 27.1% (46 of 170). A statistically significant correlation was observed between LA and CMBs (correlation rho = .495, P value = .001). Multiple logistic regression analysis showed an association between CMBs and cerebrovascular symptoms (P = .0023). CONCLUSION: Results of this study suggest an association between CMBs and LA. Moreover, we found that LA is associated with the presence of cerebrovascular symptom

Published
2014

44. MR and CT of brain's cava

Author

Saba L, Anzidei M, Raz E, Suri J, Piga M, Catalano C., GRASSI, Roberto, Saba, L, Anzidei, M, Raz, E, Suri, J, Piga, M, Grassi, Roberto, and Catalano, C.

Abstract

The Cavum Septi Pellucidi (CSP), Cavum Vergae (CV) and Cavum Veli Interpositi, are anatomical variants located in the midline of the brain. It is important to identify these conditions to distinguish them from other entities that may require treatment. In this paper, our purpose is to describe MR and CT findings of CSP, CV and Cavum Veli Interpositi, explaining the differential diagnosis.

Published
2013

45. Attraction, Active Migration, and Clustering of Zebrafish Primordial Germ Cells

Author

Weidinger, G., Koprunner, M., Wolke, U., Thisse, C., Thisse, B., and Raz, E.

Subjects
Germ cells -- Physiological aspects, Zebra fish -- Genetic aspects, Developmental genetics -- Research, Biological sciences
Abstract

Migration of primordial germ cells (PGCs) from their site of specification toward the developing gonad occurs in distinct steps, which are controlled by interaction with somatic tissues. Here we show that zebrafish PGCs actively migrate toward the lateral mesoderm of the anterior trunk to form bilateral clusters and we provide evidence that this region constitutes a signaling center that acts in long range to attract PGCs. We found that the Wilm's tumor suppressor gene 1 (wt-1), a transcription factor required for kidney and gonad formation in mammals, is expressed in this tissue. Using time-lapse observation of live embryos expressing GFP in the PGCs, we show that PGCs actively migrate toward the wt-1-expressing region from medial and posterior positions. In mutants that have severe trunk mesodermal defects, the presence of the wt-1-expressing tissue is correlated with the formation of PGC clusters. In live mutant embryos PGC cluster formation occurs by active migration of ectopic anterior PGCs toward the wt-1-expressing area. Hence, PGCs migrate toward this region from medial, posterior, and anterior positions, strongly suggesting that they are attracted by the wt-1-expressing tissue. The cells expressing wt-1 are fated to give rise to the nephron primordium, while the PGCs migrate toward more posterior regions during late somito-genesis. Thus, we provide evidence that the cells fated to form the zebra fish nephron serve as a signaling center that attracts PGC to regulate an intermediate step of their migration.

Published
2001

49. TRPM8 on mucosal sensory nerves regulates colitogenic responses by innate immune cells via CGRP.

Author

de Jong, P, de Jong, P, Takahashi, N, Peiris, M, Bertin, S, Lee, J, Gareau, Melanie, Paniagua, A, Harris, A, Herdman, D, Corr, M, Blackshaw, L, Raz, E, de Jong, P, de Jong, P, Takahashi, N, Peiris, M, Bertin, S, Lee, J, Gareau, Melanie, Paniagua, A, Harris, A, Herdman, D, Corr, M, Blackshaw, L, and Raz, E

Abstract

TRPM8 is the molecular sensor for cold; however, the physiological role of TRPM8+ neurons at mucosal surfaces is unclear. Here we evaluated the distribution and peptidergic properties of TRPM8+ fibers in naive and inflamed colons, as well as their role in mucosal inflammation. We found that Trpm8(-/-) mice were hypersusceptible to dextran sodium sulfate (DSS)-induced colitis, and that Trpm8(-/-) CD11c+ DCs (dendritic cells) showed hyperinflammatory responses to toll-like receptor (TLR) stimulation. This was phenocopied in calcitonin gene-related peptide (CGRP) receptor-deficient mice, but not in substance P receptor-deficient mice, suggesting a functional link between TRPM8 and CGRP. The DSS phenotype of CGRP receptor-deficient mice could be adoptively transferred to wild-type (WT) mice, suggesting that CGRP suppresses the colitogenic activity of bone marrow-derived cells. TRPM8+ mucosal fibers expressed CGRP in human and mouse colon. Furthermore, neuronal CGRP contents were increased in colons from naive and DSS-treated Trpm8(-/-) mice, suggesting deficient CGRP release in the absence of TRPM8 triggering. Finally, treatment of Trpm8(-/-) mice with CGRP reversed their hyperinflammatory phenotype. These results suggest that TRPM8 signaling in mucosal sensory neurons is indispensable for the regulation of innate inflammatory responses via the neuropeptide CGRP.

Published
2015

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