Citations
13 citation(s) found for "Zheng, Xi‐Long".
Epidemiologic Study of Transfusion-Related Alpha-Gal Syndrome
Kaufman, Richard M., Hoen, Anne G., Khan, Jenna, Knudson, C. Michael, Romero, Andres E. Mindiola, Mo, Allison , Takanashi, Minoko , Collaborative, UPTICK Study Group; for the Biomedical Excellence for Safer Transfusion (BEST), Cardigan, Rebecca, Stanworth, Simon J., Commins, Scott P. , Scherer, Emily A., Davenport, Robertson D., Afraz, Sajjad, Andrews, Jennifer , Casey, John, Sullivan, Jensyn Cone , Cousins, Clara C. , Giorgi, Valeria De , Delaney, Meghan, DelBaugh, Regina M. , Gilstad, Colleen W. , Gofton, Alexander , Hill, Kate, Hogan, Keenan , Humbrecht, Catherine , Ikeda, Kazuhiko, Javanbakht, Ayda, Juskewitch, Justin E, Wojtowicz, Monique M. Menzies, Miller, Maureen J., Mills, Georgia, Nelson, Anna C. , Pauly, Marie C., Poisson, Jessica , Raval, Jay S., Samy, Nikitha, Sato, Tomohiko, Takeda, Yoshinori , Thibodeaux, Suzanne R. , Nunen, Sheryl van, Virk, Mrigender S., West-Mitchell, Kamille, Yamanouchi, Jun, Yoshihara, Satoshi, Zheng, X. Long, Ziman, Alyssa, Cone Sullivan, Jensyn , Kaufman, Richard Max , Hoen, Anne Gatewood , Knudson, Charles Michael , Metcalf, Ryan A. , Schäfer, Richard , Dunbar, Nancy M. , Cardigan, Rebecca A. , Stanworth, Simon J., Scherer, Emily A. , Cervinski, Mark A , Arai, Yasuyuki , Brugnara, Carlo , Allen, Elizabeth S. , Aurich, Konstanze , Casey, John , Cohn, Claudia S. , Crowe, Elizabeth P , Delaney, Meghan , Hendrickson, Jeanne E. , Hill, Kate, Ikeda, Kazuhiko , Jacquot, Cyril , Javanbakht, Ayda , Juskewitch, Justin E. , Lu, Wen , Wojtowicz, Monique Menzies , Miller, Maureen J. , Nelson, Anna , Pagano, Monica B. , Pauly, Marie-Christin , Saifee, Nabiha H , Sato, Tomohiko, Takeda, Yoshinori, Tiberghien, Pierre , Nunen, Sheryl van, Virk, Mrigender , Wood, Erica M , Yoshihara, Satoshi , Zheng, X. Long, Ziman, Alyssa
JAMA Internal Medicine | August 24, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
10.1001/jamainternmed.2026.3983
| PMID 42636004
Importance Recent case reports suggest that B antigen–containing blood products may be associated with anaphylactic transfusion reactions in recipients with preformed immunoglobulin E to galactose- α -1,3-galactose (alpha-gal). Objective To test the association of local alpha-gal syndrome (AGS) prevalence and allergic transfusion reaction (ATR) in patients with blood type O. Design, Setting, and Participants In this international, multicenter, retrospective cohort study at academic medical centers, sites were assigned to AGS high- or low-prevalence clusters based on the known geographic distribution of AGS. Data were collected on platelet or plasma transfusions and ATRs during 2020 to 2024. Consecutive patients receiving platelet or plasma transfusions were included. Exposures Patients with blood type O who received B or AB units and patients with blood type O who received O units (reference group) in AGS high- and low-prevalence clusters were compared. Main Outcomes and Measures Before data collection, the hypothesis was that if transfusion-related alpha-gal syndrome (TRAGS) is a true clinical entity, excess ATRs to group B or AB units would be detected in AGS high-prevalence regions exclusively. The main measure was the overall risk ratio (RR) for ATRs to B or AB plasma or platelets in AGS high- vs low-prevalence clusters. Results In total, 558 823 platelet and plasma transfusions at 40 sites in 5 countries were analyzed, of which ATRs occurred in 1744 transfusions (0.3%). In the US AGS high-prevalence cluster (9 sites), significantly more ATRs of any severity occurred among patients with blood type O who received B or AB units vs patients with blood type O who received O units (overall RR, 3.93; 95% CI, 2.96-5.21; P < .001). In contrast, in the primary analysis of the AGS low-prevalence cluster (15 sites), excess ATRs to B or AB units were not detected. In subgroup analyses among patients with blood type O receiving B units, the RR for moderate to severe ATRs was 9.14 (95% CI, 5.39-15.52; P < .001) in the AGS high-prevalence cluster vs 2.15 (95% CI, 1.34-3.47; P = .002) in the AGS low-prevalence cluster. Outside the US, a signal consistent with TRAGS was not detected. Conclusions and Relevance This cohort study provides provocative epidemiologic evidence that TRAGS may be a unique manifestation of AGS and a previously unrecognized risk associated with transfusion. In AGS high-prevalence regions, blood collectors and hospital transfusion services should consider approaches to preventing severe ATRs from B or AB plasma or platelet units.
Relapse-free survival is progressively shortened in a subset of Black patients with immune-mediated TTP treated in the rituximab era
Fatola, Ayotola , Evans, Michael D. , Brown, Jenna , Davis, Elizabeth E. , Johnson, Andrew D. , Antun, Ana G., Farland, Andrew M., Metjian, Ara , Park, Yara A. , Ridder, Gustaaf de, Gibson, Briana, Eubanks, Susan, Akwaa, Frank, Clover, Todd, Sadler, J. Evan, Upreti, Harsh Vardhan , Kocher, Nicole K. , Gangaraju, Radhika , Masias, Camila , Mazepa, Marshall , Metjian, Ara , Kasthuri, Raj S , Baumann Kreuziger, Lisa , Sridharan, Meera , McCrae, Keith R , Lim, Ming Y , Zheng, X Long , Raval, Jay S , Cataland, Spero R , Mazepa, Marshall A , Evans, Michael D , Davis, Elizabeth, Woods, Ryan, Kasthuri, Raj S. , Liles, Darla , Kreuziger, Lisa Baumann , Sridharan, Meera , Go, Ronald S. , McCrae, Keith R. , Zheng, X. Long , Raval, Jay S. , Cataland, Spero R. , Chaturvedi, Shruti
Blood Advances | December 3, 2024 | Volume: 9 | Issue: 2 | Pages: 417-424
10.1182/bloodadvances.2024013313
| PMID 39626301
Abstract Immune thrombotic thrombocytopenic purpura (iTTP) is a chronically relapsing disorder caused by autoantibody-mediated deficiency of ADAMTS13. Rituximab is frequently administered to prevent relapses, but whether the durability of rituximab effect is maintained with subsequent treatment courses has not been studied. Using the United States Thrombotic Microangiopathy Consortium (USTMA) retrospective iTTP registry, we evaluated clinical relapse-free survival (RFS) with subsequent courses of rituximab treatment in multiply relapsing patients. Separately, we evaluated overall RFS (composite of time to clinical relapse, ADAMTS13 relapse, or preemptive rituximab) in a prospective iTTP cohort from the Johns Hopkins University and the University of Minnesota. In the USTMA registry, median clinical RFS was shorter after the second or subsequent rituximab-treated episode than the first (2.1 vs 6.0 years; P = .04). White patients’ clinical relapse risk after the second and subsequent rituximab courses was not significantly different compared with the first (hazard ratio [HR], 1.86; 95% confidence interval [CI], 0.22-15.80; P = .57), whereas for Black patients, clinical relapse risk was significantly higher after the second or subsequent courses (HR, 2.82; 95% CI, 1.52-5.24; P = .001). In the prospective cohort, overall RFS progressively shortened after each episode of rituximab treatment with the first episode having the longest RFS (2.8 years; interquartile range, 2.0-6.0) and this loss of response durability was most pronounced in Black patients. The durability of rituximab’s effect declines with subsequent treatments, which is more pronounced in Black patients, who may benefit from closer monitoring and alternative immunomodulatory approaches such as maintenance rituximab and consideration of other agents.
A descriptive analysis of fatal outcomes in immune thrombotic thrombocytopenic purpura in the USTMA TTP Registry
Chaturvedi, Shruti , Antun, Ana G., Farland, Andrew M., Metjian, Ara , Park, Yara A. , Ridder, Gustaaf de, Gibson, Briana, Akwaa, Frank, Clover, Todd, Upreti, Harsh Vardhan , Gangaraju, Radhika , Kocher, Nicole K. , Masias, Camila , Johnson, Andrew D. , Davis, Elizabeth E. , Evans, Michael D. , Mazepa, Marshall , Abou-Ismail, Mouhamed Yazan , Chaturvedi, Shruti , Metjian, Ara , Kasthuri, Raj S , Baumann Kreuziger, Lisa , Sridharan, Meera , McCrae, Keith R , Gangaraju, Radhika , Zheng, X Long , Raval, Jay S , Cataland, Spero R , Evans, Michael D , Mazepa, Marshall A , Lim, Ming Y , Zhang, Chong , Presson, Angela P. , Woods, Ryan, Kasthuri, Raj S. , Liles, Darla , Kreuziger, Lisa Baumann , Sridharan, Meera , Go, Ronald S. , McCrae, Keith R. , Zheng, X. Long , Raval, Jay S. , Cataland, Spero R. , Davis, Elizabeth
Blood Advances | December 15, 2023 | Volume: 8 | Issue: 3 | Pages: 620-623
An international multi-institution real-world study of the optimal surveillance frequency for stage II/III gastric cancer: the more, the better?
Lü, Jun, Lin, Jia, Xu, Binbin , Xue, Zhen , Zheng, Hua‐Long , Lin, Guosheng, Huang, Jiao-bao, Shen, Li-li, Zheng, Chao‐Hui , Li, Ping , Cao, Long‐Long, Ma, Yu‐Bin , Truty, Mark J. , Huang, Chang-Ming, Wu, Dong , Lin, Jia, Huang, Jiao-bao, Shen, Li-li, Xie, Jian‐Wei , Wang, Jia-Bin , Lin, Jian‐Xian , Chen, Qi‐Yue , Huang, Chang-Ming
International Journal of Surgery | October 6, 2023 | Volume: 109 | Issue: 12 | Pages: 4101-4112
10.1097/js9.0000000000000731
| PMID 37800589
Background: Due to lacking evidence on surveillance for gastric cancer (GC), this study aimed to determine the optimal postsurgical surveillance strategy for pathological stage (pStage) II/III GC patients and compare its cost-effectiveness with traditional surveillance strategies. Methods: Prospectively collected data from stage II/III GC patients (n=1661) who underwent upfront surgery at a large-volume tertiary cancer center in China (FJMUUH cohort) between January 2010 and October 2015. For external validation, two independent cohorts were included, which were composed of 380 stage II/III GC patients at an tertiary cancer center in U.S.A (Mayo cohort) between July 1991 and July 2012 and 270 stage II/III GC patients at another tertiary cancer center in China (QUAH cohort) between May 2010 and October 2014. Random forest models were used to predict dynamic recurrence hazards and to construct individual surveillance strategies for stage II/III GC. Cost-effectiveness was assessed by the Markov model. Results: The median follow-up period of the FJMUUH, the Mayo, and QUAH cohorts were 55, 158, and 70 months, respectively. In the FJMUUH cohort, the 5-year recurrence risk was higher in pStage III compared with pStage II GC patients (P<0.001). Our novel individual surveillance strategy achieved optimal cost-effectiveness for pStage II GC patients (ICER =$490/QALY). The most intensive NCCN surveillance guideline was more cost-effective (ICER =$983/QALY) for pStage III GC patients. The external validations confirmed our results. Conclusion: For patients with pStage II GC, individualized risk-based surveillance outperformed the JGCTG and NCCN surveillance guidelines. However, the NCCN surveillance guideline may be more suitable for patients with pStage III GC. Even though our results are limited by the retrospective study design, the authors believe that our findings should be considered when recommending postoperative surveillance for stage II/III GC with upfront surgery in the absence of a randomized clinical trial.
A Novel ypTLM Staging System Based on LODDS for Gastric Cancer After Neoadjuvant Therapy: Multicenter and Large‐Sample Retrospective Study
Que, Si‐Jin, Zhong, Qing , Truty, Mark J. , Yan, Su , Ma, Yu‐Bin , Ding, Fanghui , Zheng, Chao‐Hui , Li, Ping , Wang, Jia‐Bin , Lü, Jun, Cao, Long‐Long, Lin, Ju‐Li , Zheng, Hua‐Long , Huang, Chang‐Ming , Chen, Qi‐Yue , Lin, Jian‐Xian , Lin, Mi , Tu, Ru‐Hong
World Journal of Surgery | April 17, 2023 | Volume: 47 | Issue: 7 | Pages: 1762-1771
10.1007/s00268-023-06994-7
| PMID 37069317
AbstractBackgroundThe accuracy of the eighth AJCC ypTNM staging system on the prognosis of gastric cancer (GC) patients after neoadjuvant therapy (NAT) is controversial. This study aimed to develop and validate a novel staging system using the log odds of positive lymph nodes scheme (LODDS).MethodsA retrospective analysis of 606 GC patients who underwent radical gastrectomy after neoadjuvant therapy was conducted as the development cohort. (Fujian Medical University Affiliated Union Hospital (n = 183), Qinghai University Affiliated Hospital (n = 169), Mayo Clinic (n = 236), Lanzhou University First Hospital (n = 18)). The validation cohort came from the SEER database (n = 1701). A novel ypTLoddsS (ypTLM) staging system was established using the 3‐year overall survival. The predictive performance of two systems was compared. ResultsTwo‐step multivariate Cox regression analysis in both cohorts showed that ypTLM was an independent predictor of overall survival of GC patients after neoadjuvant therapy (HR: 1.57, 95% CI: 1.30–1.88, p < 0.001). In the development cohort, ypTLM had better discrimination ability than ypTNM (C‐index: 0.663 vs 0.633, p < 0.001), better prediction homogeneity (LR: 97.7 vs. 70.9), and better prediction accuracy (BIC: 3067.01 vs 3093.82; NRI: 0.36). In the validation cohort, ypTLM had a better prognostic predictive ability (C‐index: 0.614 vs 0.588, p < 0.001; LR: 11,909.05 vs. 11,975.75; BIC: 13,263.71 vs 13,328.24; NRI: 0.22). The time‐dependent ROC curve shows that the predictive performance of ypTLM is better than ypTNM, and the analysis of the decision curve shows that ypTLM achieved better net benefits. ConclusionA LODDS‐based ypTLM staging system based on multicenter data was established and validated. The predictive performance was superior to the eighth AJCC ypTNM staging system.
Race, rituximab, and relapse in TTP
Antun, Ana G., Farland, Andrew M., Metjian, Ara , Park, Yara A. , Ridder, Gustaaf de, Gibson, Briana, Kasthuri, Raj S. , Akwaa, Frank, Clover, Todd, Upreti, Harsh Vardhan , Liu, Angela , Gangaraju, Radhika , Zheng, X. Long , Masias, Camila , Johnson, Andrew D. , Davis, Elizabeth E. , Evans, Michael D. , Mazepa, Marshall , Metjian, Ara , Kasthuri, Raj S , Baumann Kreuziger, Lisa , Sridharan, Meera , McCrae, Keith R , Lim, Ming Y , Zheng, X Long , Raval, Jay S , Evans, Michael D , Mazepa, Marshall A , Chaturvedi, Shruti , Woods, Ryan, Liles, Darla , Kreuziger, Lisa Baumann , Sadler, J. Evan , Sridharan, Meera , Go, Ronald S. , McCrae, Keith R. , Raval, Jay S. , Cataland, Spero R. , Davis, Elizabeth
Blood | July 7, 2022 | Volume: 140 | Issue: 12 | Pages: 1335-1344
10.1182/blood.2022016640
| PMID 35797471
Abstract Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, Daniel J., Abdel‐Aziz, Amal Kamal , Abdellatif, Mahmoud , Abdoli, Asghar , Abel, Steffen , Abeliovich, Hagai , Abildgaard, Marie H. , Abudu, Yakubu Princely , Acevedo‐Arozena, Abraham , Adamopoulos, Iannis E. , Adeli, Khosrow , Adolph, Timon E. , Adornetto, Annagrazia , Aflaki, Elma, Agam, Galila , Aggarwal, Bharat B. , Agnello, Maria, Agostinis, Patrizia , Agrewala, Javed N. , Agrotis, Alexander , Aguilar, Patricia V., Ahmad, S. Tariq, Ahumada-Castro, Ulises , Aits, Sonja , Aizawa, Shu, Akkoç, Yunus , Akoumianaki, Tonia, Akpinar, Hafize Aysin , Al‐Abd, Ahmed M. , Al-Akra, Lina, Gharaibeh, Abeer , Alaoui‐Jamali, Moulay A. , Alberti, Simon , Alessandri, Cristiano , Alonso, Alicia , Altan‐Bonnet, Nihal , Álvarez, Élida, Alves, Sara , Costa, Cristine Alvès da , Alzaharna, Mazen M. , Amadio, Marialaura , Amantini, Consuelo , Amaral, Cristina , Ambrosio, Susanna , Amer, Amal O. , Ammanathan, Veena , An, Zhenyi, Andrabi, Shaida A. , Andres, Allen M. , Ann, David K. , Anozie, Uche C. , Ansari, Mohammad Y. , Antas, Pedro , Antebi, Adam , Antón, Zuriñe , Anwar, Tahira , Apétoh, Lionel , Araki, Toshiyuki , Araki, Yasuhiro , Araya, Jun , Arévalo, María‐Ángeles , Argüelles, Sandro , Arias, Esperanza , Arikkath, Jyothi , Ariosa, Aileen, Aroca, Ángeles , Arroyo, Daniela S., Arsov, Ivica, Artero, Rubén , Asaro, Dalia Maria Lucia, Ashur‐Fabian, Osnat , Atanasov, Atanas G. , Au, Alicia K. , Auberger, Patrick , Auner, Holger W. , Aurelian, Laure , Avagliano, Laura , Ávalos, Yenniffer , Aveleira, Célia A. , Aydın, Yücel , Ayyadevara, Srinivas , Azzopardi, Maria , Baba, Misuzu, Backer, Jonathan , Bae, Soo Han , Baehrecke, Eric H. , Bagetta, Giacinto , Bagniewska‐Zadworna, Agnieszka , Bai, Hua , Bai, Xiyuan , Bairagi, Nandadulal , Baksi, Shounak , Balbi, Teresa , Ballester, María , Balazadeh, Salma , Balzan, Rena , Bandopadhyay, Rina , Banerjee, Sulagna , Bánréti, Ágnes , Baracca, Alessandra , Barbati, Cristiana , Bargiela, Ariadna , Barilà, Daniela , Barlow, Peter G. , Barmada, Sami J. , Barreiro, Esther , Bártek, Jiří , Bartel, Bonnie , Bartolomé, Alberto , Barve, Gaurav , Bassham, Diane C. , Baulieu, E.E. , Baumgarner, Bradley L. , Bayry, Jagadeesh , Beale, Rupert , Beau, Isabelle , Beaumatin, Florian , Bechara, Luiz Roberto Grassmann , Beck, George R. , Beers, Michael F. , Begun, Jakob , Behrends, Christian , Bejarano, Eloy , Bel, Shai , Belaïd, Amine , Belgareh‐Touzé, Naïma, Bellarosa, Cristina , Belleudi, Francesca , Belló-Pérez, Melissa , Beltran, Jackeline Soares de Oliveira , Beltran, Sebastián, Benbrook, Doris M. , Bendorius, Mykolas , Benítez, Bruno A. , Benito‐Cuesta, Irene , Bensalem, Julien , Berchtold, Martin W. , Berezowska, Sabina , Bergamaschi, Daniele , Berliocchi, Laura , Berlioz‐Torrent, Clarisse , Bernard, Amélie , Besirli, Cagri G. , Besteiro, Sébastien , Betin, Virginie M.S., Beyaert, Rudi , Bezbradica, Jelena S. , Bhaskar, Kiran , Bhatia‐Kiššová, Ingrid, Bhattacharya, Sujoy , Bhuiyan, Md. Shenuarin , Bi, Xiaolin , Biden, Trevor J. , Bijian, Krikor , Billes, Viktor , Binart, Nadine , Bincoletto, Cláudia , Blanco, Gonzalo , Blas‐García, Ana , Błasiak, Janusz , Blomgran, Robert , Blum, Janice S. , Boada-Romero, Emilio, Boban, Mirta , Boeuf, Philippe , Boland, Barry , Bomont, Pascale , Bonaldo, Paolo , Bonam, Srinivasa Reddy , Bonfili, Laura , Bootman, Martin D. , Bordi, Matteo , Borner, Christoph , Bornhäuser, Beat , Bose, Santanu , Botas, Juan , Boulanger, Chantal M. , Bourgeois, Benjamin , Bourke, Nollaig M. , Bousquet, Guilhem , Boya, Patricia , Bozhkov, Peter V. , Bozi, Luiz H. M. , Bozkurt, Tolga O. , Pedro, José Manuel Bravo‐San , Brest, Patrick , Bringer, Marie-Agnès , Briones‐Herrera, Alfredo , Broaddus, V. Courtney, Brodersen, Peter , Brodsky, Jeffrey L. , Bronson, Paola G. , Bronstein, Jeff M. , Brown, Rhoderick E. , Brum, Patrı́cia C. , Bruno, Daniele , Bryson‐Richardson, Robert J. , Bucci, Cecilia , Buchrieser, Carmen , Bueno, Marta , Buchan, J. Ross , Buckingham, Erin M., Budak, Hikmet , Budini, Mauricio , Bultynck, Geert , Burada, Florin , Burgoyne, Joseph R. , Burón, María I. , Bustos, Victor , Büttner, Sabrina , Byrd, Aaron , Cabas, Isabel , Cabrera, Sandra , Cadwell, Ken , Cai, Jingjing , Cai, Lu , Cai, Qian , Calbet, José A. L. , Caldwell, Guy A. , Call, Jarrod A. , Calvani, Riccardo , Calvo, Ana Cristina , Calvo‐Rubio, Miguel , Câmara, Niels Olsen Saraiva , Camonis, Jacques , Camougrand, Nadine , Campanella, Michelangelo , Campbell, Edward M. , Campos, Juliane C. , Camuzard, Olivier , Cancino, Jorge , Caniggia, Isabella , Canonico, Barbara , Cantı́, Carles , Cao, Bin , Caramés, B. , Cardenal‐Muñoz, Elena , Cárdenas, César , Cárdenas, Luis , Cardoso, Sandra M. , Carew, Jennifer S. , Carle, Georges F. , Carleton, Gillian , Carloni, Silvia , Carneiro, Letícia A. M. , Carosi, Julian M. , Carra, Serena , Carrier, Alice , Carter, A. Brent, Carvalho, Andreia Neves , Casanova, Magali , Casas, Josefina , Cassioli, Chiara , Castillo, Karen , Castillo‐Lluva, Sonia , Castoldi, Francesca , Castori, Marco , Castro, Ariel F. , Castro‐Hernández, Javier , Cavadas, Cláudia , Cavaliere, Federica, Cavallini, Gabriella , Cavinato, Maria , Rica, Paula Cebollada , Cechowska‐Pasko, Marzanna , Cerqueira, João , Cerutti, Janete M. , Çetintaş, Vildan Bozok , Cetrullo, Silvia , Chagin, Andrei S. , Chai, Chee‐Yin , Chakrabarti, Gopal , Chakraborty, Tapas , Chakraborty, Trinad , Chami, Mounia , Chamilos, Georgios , Chan, David W. , Chan, Edmond Y. W., Chan, Ho Yin Edwin , Chan, Helen H., Chan, Hung , Chan, Matthew T.V. , Chan, Yau Sang , Chang, Hao‐Chun , Chang, Kai , Chao, Jie , Charlet‐Berguerand, Nicolas , Chatterjee, Samrat , Chaube, Shail K. , Chaudhary, Anu , Chauhan, Santosh , Chaum, Edward , Checler, Frédéric , Cheetham, Michael E. , Chen, Chang‐Shi , Chen, Jian‐Fu , Chen, Liam L., Chen, Mingliang , Chen, Mu‐Kuan , Chen, Ning , Chen, Wei , Chen, Xinming , Chen, Xiongwen , Chen, Yan , Chen, Ye‐Guang , Chen, Yingyu , Chen, Yongqiang , Chen, Zhefan Stephen , Chen, Zhihua , Cheng, Xiu‐Tang , Cheng, Yiyun , Cheng, Zhiyong , Cheong, Jit Kong , Cherry, Sara , Cheung, Chi F., Cheung, Chun Hei Antonio , Cheung, King‐Ho , Chevet, Éric , Chi, Richard J., Chiaradonna, Ferdinando , Chiariello, M , Chica, Nathalia , Chiocca, Susanna , Chiong, Mario , Chiou, Shih‐Hwa , Chiramel, Abhilash I., Chiurchiù, Valerio , Cho, Dong-Hyung, Choe, Seong‐Kyu , Choi, Augustine M.K. , Choi, Mary E. , Choudhury, Kamalika Roy , Chow, Norman , Chua, Jason P. , Chua, John Jia En , Chung, Hyewon , Chung, Kin Pan , Chung, So‐Hyang , Chung, Yuen-Li, Ciechomska, Iwona A. , Cinque, Laura , Çırak, Sebahattin , Clarke, Robert , Clementi, Emilio , Coccia, Eliana M. , Codogno, Patrice , Colasanti, Tania , Colasuonno, Fiorella , Colbert, Robert A. , Colell, Anna , Coll, Núria S. , Collins, Mark O. , Colombo, Marı́a I. , Colón‐Ramos, Daniel A. , Cominetti, Márcia R. , Consiglio, Antonella , Conte, A. , Contu, Viorica Raluca , Cookson, Mark , Coombs, Kevin M. , Costa, Maria do Carmo , Costantino, Sarah , Costelli, Paola , Criollo, Alfredo , Crippa, V. , Cristofani, Riccardo , Csizmadia, Tamás , Cui, Bing , Cui, Yixian , Culetto, Emmanuel , Cumino, Andrea C. , Cybulsky, Andrey V. , Czaja, Mark J. , Czuczwar, Stanisław J. , D’Adamo, Stefania , D’Amelio, Marcello , D’Orazi, Gabriella , Silva, James Almada da , Dafsari, Hormos Salimi , Daglia, Maria , Dai, Xiaoxia , Dai, Yun , Dai, Yuyuan , Col, Jessica Dal , Dalhaimer, Paul , Valle, Luisa Dalla , Dallenga, Tobias , Dalmasso, Guillaume , Dando, Ilaria , Das, Hiranmoy , Dasari, Santosh K. , Dash, Srikanta, Dauphinee, Adrian N. , Davies, Jeffrey S. , Dávila, Valeria A. , Davis, Roger J. , Naidu, Sharadha Dayalan , Bosscher, Karolien De , Leonibus, Chiara De , Barbosa, Mayara Garcia de Mattos , Meyer, Guido R.Y. De , Palma, Clara De , Virgilio, Claudio De , Zio, Daniela De , Decuypere, Jean-Paul , Deehan, Mark , Deflorian, Gianluca , Dehay, Benjamin , Delaney, Joe R. , Delorme‐Axford, Elizabeth , Demers, Nicholas D. , Deng, Hongbin , Dengjel, Jörn , Dent, Paul, DePamphilis, Melvin L., Descoteaux, Albert , Devis, Laura , Devkota, Sushil , Devuyst, Olivier , Dewson, Grant , Dharmasivam, Mahendiran , Domenico, Fabio Di , Fazio, Pietro Di , Fonzo, Alessio Di , Guardo, Giovanni Di , Guglielmo, Gianni M. Di , Leo, Luca Di , Malta, Chiara Di , Nardo, Alessia Di, Rienzo, Martina Di , Diao, Jiajie , Diaz-Araya, Guillermo, Díaz‐Laviada, Inés , Dickinson, Jared M. , Diederich, Marc , Dieudé, Mélanie , Ding, Shiping , Ding, Wen-Xing, Dinić, Jelena , Dinić, Miroslav , Dinkova‐Kostova, Albena T. , Distler, Jörg H. W. , Đokić, Jelena , Emre, Serap , Dong, Xiaonan , Dong, Zhiwu , Dorn, Gerald W. , Dou, Juan, Dowaidar, Moataz , Drucker, Liat , Du, Ailian , Du, Guangwei , Du, Hai‐Ning , Toit, André du , Duan, Shao-Bin , Duan, Xiaoqiong , Duarte, Sónia , Dupont, Nicolas , Durán, Raúl V. , Dyshlovoy, Sergey A. , Ebrahimi‐Fakhari, Darius , Eckhart, Leopold , Edelstein, Charles L. , Efferth, Thomas , Eid, Nabil , Eisenberg, Tobias , Eissa, N. Tony, Ejarque, Miriam , Andaloussi, Abdeljabar El, El‐Hage, Nazira , Eleuteri, Anna Maria , El‐Shafey, Eman S. , Elgendy, Mohamed , Elizalde, María Mercedes , Elsässer, Hans‐Peter , Elsherbiny, Eslam S. , Emre, N. C. Tolga , Eng, Christina H. , Engedal, Nikolai , Engelsen, Agnete S. T. , Enserink, Jorrit M. , Escalante, Ricardo , Esclatine, Audrey , Eskelinen, Eeva‐Liisa , Espert, Lucile , Eusebio, Makandjou-Ola , Facchiano, Antonio , Facchiano, Francesco , Fadeel, Bengt , Fader, Claudio M., Faesen, Alex C. , Fairlie, W. 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H. , Ma, Ning-Fang, Ma, Quanhong , Ma, Xinliang , Ma, Yueyun , Ma, Zhenyi , MacDougald, Ormond A. , MacIntosh, Gustavo C. , Macleod, Kay F. , Maday, Sandra , Madeo, Frank , Madesh, Muniswamy , Madl, Tobias , Madrigal‐Matute, Julio , Maeda, Akiko, Maejima, Yasuhiro , Magariños, Marta , Mahavadi, Poornima , Maiani, Emiliano , Maiese, Kenneth , Maiti, Panchanan , Maiuri, Maria Chiara , Major, Michael Ben, Makareeva, Elena , Malik, Fayaz , Mallilankaraman, Karthik , Maloyan, Alina , Mammadova, Najiba, Man, Gene Chi Wai , Manai, Federico , Mancias, Joseph D. , Mandelkow, Eva‐Maria , Manfredi, Angelo A. , Manshian, Bella B. , Manzano, Raquel , Marchese, Chiara , Marchetti, Sandrine , Marcucci, F, Mardente, Stefania , Mareninova, Olga A. , Mari, Muriel , Marinelli, Sara , Mariño, Guillermo , Mariotto, Sofia , Martin, Alexandre , Martin, Katie R. , Martin, Sara L. , Martín‐Segura, Adrián , Martin-Burriel, Inmaculada, Martín-Rincón, Marcos , Martín‐Sanz, Paloma , Martinez, Aitor , Martı́nez, Ana , Martinez-Lopez, Nuria, Martínez‐Vicente, Marta , Martins, Daniel Oliveira , Martins, Joilson O. , Martins, Waleska K. , Martins-Marques, Tania, Marzetti, Emanuele , Masaldan, Shashank , Masclaux-Daubresse, Celine, Mashek, Douglas G. , Massa, Valentina , Massieu, Lourdes , Masyuk, Anatoliy I. , Masyuk, Tetyana V., Matheu, Ander , Matoba, Satoaki , Matsuzaki, Sachiko , Mattar, Pamela , Mattè, Alessandro , Mauriz, José L., Mauthe, Mario , Maycotte, Paola , Mayer, Johanna , Mazzoni, Cristina , Mazzulli, Joseph R. , McCarty, Nami , McGill, Mitchell R. , McKenna, Sharon L. , McLoughlin, Fionn , McNiven, Mark A., McWilliams, Thomas G. , Medeiros, Tania , Medina, Diego L., Megeney, Lynn A. , Megyeri, Klára , Mehrpour, Maryam , Mehta, Jawahar L. , Meijer, Alfred J., Mejlvang, Jakob , Meléndez, Alicia , Melk, Annette, Memişoğlu, Gönen , Mendes, A.F. , Meng, Delong , Meng, Fei, Mercier, A., Mergny, Jean‐Louis , Merkley, Seth D. , Meske, Volker, Mestre, Ana Cecilia, Metur, Shree Padma, Meyer, C., Meyer, Hemmo , Mi, Wenyi , Mialet‐Perez, Jeanne , Miao, Jun‐Ying, Micale, Lucia , Miki, Yasuo, Milan, Enrico , Milczarek, Małgorzata , Miller, Samuel I. , Millward, Steven W. , Mirzaei, Hamed, Mirzaei, Hamid Reza , Mirzaei, Mehdi , Mishra, Amit , Mishra, Nandita , Mishra, Paras Kumar, Misirkić, Maja , Misasi, Roberta, Misra, Amit , Misso, Gabriella , Mitchell, Claire H. , Mitou, Géraldine, Miura, Tetsuji , Miyazaki, Makoto, Miyazaki, Mitsunori , Miyazaki, Taiga , Miyazawa, Keisuke, Mizushima, Noboru , Mogensen, Trine H. , Mohammadinejad, Reza , Mohamud, Yasir , Mohanty, Abhishek , Möhlmann, Torsten , Moley, Kelle H. , Möller, Andreas, Mollereau, Bertrand , Mollinedo, Faustino, Montagna, Costanza , Monteiro, Mervyn J. , Montella, Andrea , Montes, L. Ruth , Montico, Barbara , Mony, Vinod K., Compagnoni, Giacomo Monzio , Moore, Michael N. , Moosavi, Mohammad Amin , Morales‐Álamo, David , Moratalla, Rosario , Moreira, Paula I. , Morelli, Elena , Moreno-Blas, Daniel , Morgan, Alwena H. , Morin, Fabrice , Morishita, Hideaki , Moriyama, Mariko , Moriyasu, Yuji, Morleo, Manuela , Morselli, Eugenia , Moruno-Manchon, Jose F. , Moscat, Jorge , Motori, Elisa , Moura, Andréa Felinto , Mrakovcic, Maria, Muciño-Hernández, Gabriel, Mukherjee, Anupam , Mukhopadhyay, Subhadip , Levy, Jean M. Mulcahy , Mulero, Victoriano, Muller, Sylviane, Münch, Christian , Muñoz-Cánoves, Pura, Muñoz‐Galdeano, Teresa , Murakawa, Tomokazu , Murphy, Brona M. , Murthy, Aditya, Myöhänen, Timo T. , Mysorekar, Indira U. , Mytych, Jennifer , Nabavi, Seyed Mohammad , Nagy, Péter , Nahimana, Aimable , Nakagawa, Ichiro, Nakamura, Ken , Nandi, Shyam Sundar , Nanjundan, Meera, Nanni, Monica , Napolitano, Gennaro , Narita, Masashi, Nassif, Melissa , Nathan, Ilana , Natsumeda, Manabu , Naudé, Ryno J., Naumann, Christin , Naveiras, Olaia , Navid, Fatemeh , Nawrocki, Steffan T., Nazarko, Taras Y. , Nazio, Francesca , Negoita, Florentina , Neill, Thomas , Neisch, Amanda L. , Netea, Mihai G. , Neubert, Patrick , Neumann, Dietbert , Neutzner, Albert , Newton, Phillip T. , Ney, Paul A., Ng, Charlene Cheuk Wing, Ng, T.B., Nguyen, Hang Thi Thu , Nguyen, Long T. , Ni, Hong-Min, Cheallaigh, Clíona Ní , Ni, Zhenhong , Nicolao, M. Celeste, Nicoli, Francesco , Nieto‐Díaz, Manuel , Niranjan, Rituraj , Nishimune, Hiroshi , Niso-Santano, Mireia, Nixon, Ralph A. , Nobili, Annalisa , Noda, Takeshi , Nogueira-Recalde, Uxía , Nombela, Iván , Novak, Ivana, Novoa, Beatriz , Nukina, Nobuyuki , Nussbaum-Krammer, Carmen, Nylandsted, Jesper , O’Donovan, Tracey R. , O’Leary, Seónadh M. , O’Rourke, Eyleen J. , O’Sullivan, Mary P. , O’Sullivan, Timothy E., Oddo, Salvatore , Oehme, Ina, Ogawa, Michinaga , Ogier‐Denis, Éric , Ögmundsdóttir, Margrét H. , Öğretmen, Besim , Oh, Goo Taeg , Oh, Seon‐Hee , Oh, Young J. , Ohama, Takashi, Ohashi, Yohei , Ohmuraya, Masaki, Oikonomou, Vasileios , Ojha, Rani , Okazawa, Hitoshi , Oku, M., Oliván, Sara , Oliveira, Jorge M.A. , Ollmann, Michael, Olzmann, James A. , Omari, Shakib , Önal, Gizem, Ondrej, Martin , Ong, Sang‐Bing , Onnis, Anna , Orellana, Juan , Orellana‐Muñoz, Sara , Ortega-Villaizán, María del Mar , Ortiz‐González, Xilma R. , Osiewacz, Heinz D. , Osman, Abdel‐Hamid K. , Otsu, Kinya, Ott, Christiane , Ou, Jing-hsiung James, Outeiro, Tiago F., Öztürk, Melek , Pagès, Gilles, Pahari, Susanta , Pajares, Marta, Pal, Rituraj, Paladino, Simona , Palmieri, Michela , Palmisano, Giuseppe , Pan, Qingjun , Pan, Xin , Panasyuk, Ganna , Pandey, Rahul , Pandey, Udai B., Pandya, Vrajesh , Paneni, Francesco , Pang, Shirley Yin-Yu, Papademetrio, Daniela L. , Papinski, Daniel, Papp, Diana , Park, Hwan Tae , Park, Ji-Man, Park, Jong‐In , Park, Junsoo, Park, Sang-Youel, Pasquier, Adrien , Pasquier, Benoit , Passos, João F. , Pastore, Nunzia , Patschan, Daniel , Pattingre, Sophie , Pedraza‐Alva, Gustavo , Pedraza-Chaverri, Jose, Pedrozo, Zully , Pei, Gang , Pei, Jianming , Peled-Zehavi, Hadas, Pellegrini, Joaquín Miguel , Pelletier, Joffrey , Peñalva, Miguel A., Peng, Di , Peng, Ying , Pennuto, Maria , Pentimalli, Francesca , Pereira, Cláudia MF, Pereira, Gustavo J.S. , Pereira, Lílian Cristina , Almeida, Luís Pereira de , Perera, Nirma D. , Pérez-Lara, Ángel, Pérez‐Oliva, Ana B. , Perl, András , Pestell, Richard G. , Petrache, I., Petrovski, Goran , Pfirrmann, Thorsten , Pfister, Astrid S., Pi, Huifeng , Pickrell, Alicia M. , Picot, Sandy, Pierantoni, Giovanna Maria , Pierre, Philippe , Pierrefite‐Carle, Valérie , Pierzynowska, Karolina , Pietruczuk, Mirosława , Pimentel-Muiños, Felipe X., Pinar, Mario , Pinheiro, Roberta Olmo , Pinkas‐Kramarski, Ronit , Pircs, Karolina , Piya, Sujan , Pizzo, Paola , Platta, Harald W. , Plomann, Markus , Pocock, Roger , Pöggeler, Stefanie , Pohl, Christian, Poirot, Marc , Poletti, Angelo , Ponpuak, Marisa , Popelka, Hana , Popova, Bilyana , Porta, Helena, Alcón, Soledad Porte , Portilla-Fernández, Eliana , Potts, Malia B. , Powers, Ted, Prahlad, Veena , Prajsnar, Tomasz K. , Praticò, Domenico , Prencipe, Rosaria, Priault, Muriel , Proikas‐Cezanne, Tassula , Puertollano, Rosa , Puglielli, Luigi, Pulinilkunnil, Thomas , Puri, Deepika , Puri, Rajat, Puyal, Julien , Qi, Yongmei , Quadrilatero, Joe , Quarleri, Jorge, Raben, Nina, Rabinowich, Hannah, Ragona, Debora, Rahmati, Marveh , Raia, Valeria, Raimundo, Nuno , Rajasekaran, Namakkal-Soorappan, Rao, Sriganesh Ramachandra , Rami, Abdelhaq, Ramírez‐Pardo, Ignacio , Ramsden, D. , Randow, Felix , Ranieri, Danilo , Rao, Hai , Rao, Rekha , Rathore, Sumit , Ratnayaka, J. Arjuna , Ratovitski, Edward A., Ravanan, Palaniyandi, Ravegnini, Gloria , Ray, Swapan K. , Rebecca, Vito, Reggiori, Fulvio , Reigada, David , Reiling, Jan H., Rein, Theo , Reipert, Siegfried , Rekha, Rokeya Sultana , Ren, Hongmei, Ren, Jun , Ren, Weichao , Renault, Tristan, Renga, Giorgia , Reue, Karen, Rewitz, Kim , Ramos, Bruna Ribeiro de Andrade , Riazuddin, S. Amer, Ribeiro‐Rodrigues, Teresa , Riccio, Victoria , Richardson, Des R. , Risbud, Makarand V. , Risueño, Ruth M. , Ritis, Konstantinos, Rizza, Salvatore , Rizzuto, Rosario , Roberts, Scott J. , Roberts, Luke D., Robinson, Katherine J. , Rocchi, Stéphane , Rodrigues, Tiago , Silva, Vagner Ramon Rodrigues , Rodriguez-Barrueco, Ruth, Rodríguez‐Henche, Nieves , Rogers, Robert S. , Rogov, Vladimir V., Rojo, Ana I. , Romanello, Vanina, Romani, Luigina , Romano, Alessandra , Romano, Patricia Silvia , Romeo-Guitart, David, Romero, Luís C. , Romero, Montserrat , Roney, Joseph C. , Rongo, Christopher , Rosenfeldt, Mathias T. , Rosenstiel, Philip , Rosenwald, Anne , Roth, Steven, Rouschop, Kasper M.A. , Roussel, Benoit D. , Roux, Sophie , Rovere–Querini, Patrizia, Roy, Ajit , Rozières, Aurore , Ruano, Diego , Rubtsova, Maria P. , Ruckdeschel, Klaus, Ruckenstuhl, Christoph , Rudolf, Emil, Rudolf, Rüdiger, Ruggieri, Alessandra , Ruparelia, Avnika A. , Rusmini, P. , Russell, Ryan R., Russo, Gian Luigi , Russo, Maria , Russo, Rossella , Ryabaya, O. O. , Sabater-Arcis, María , Sacher, M, Sachse, Carsten , Sadhu, Abhishek , Säftig, Paul , Sahebkar, Amirhossein, Şahin, Mustafa , Şahin, Özgür , Saito, Nayuta , Saito, Tsunenori , Sakai, Yasuyoshi , Sakamaki, Jun-Ichi , Saksela, Kalle , Salazar, Gloria , Salazar-Degracia, Anna, Salekdeh, Ghasem Hosseini , Saluja, Ashok K. , Sampaio‐Marques, Belém , Sánchez, Marı́a C. , Sánchez-Alcázar, José A., Sanchez‐Vera, Victoria , Sancho‐Shimizu, Vanessa , Santambrogio, Laura , Santana, Magda M., Santoni, G, Sanz, Alberto , Saran, Shweta , Sardiello, Marco, Sargeant, Timothy J. , Sarin, Apurva , Sarkar, Chinmoy, Sarkar, Sovan , Sarrias, Maria-Rosa, Sarkar, Surajit , Sarmah, Dipanka Tanu, Sarparanta, J. , Sathyanarayan, Aishwarya , Ranganayaki, S. , Scaglione, K. Matthew , Scatozza, Francesca , Schafer, Zachary T. , Schaible, Ulrich E., Schapira, Anthony H.V. , Scharl, Michael , Schein, Catherine H. , Schiaffino, Maria Vittoria , Schiappacassi, Mónica , Schindl, Rainer , Schlattner, Uwe , Schmidt, Oliver, Schmitt, Roland , Schmidt, Stephen D., Schmitz, Ingo , Schmukler, Eran, Schneider, Anja , Schneider, Bianca E. , Schober, Romana , Schoijet, Alejandra C. , Schramm, M., Schröder, Bernd , Schuh, Kai , Schüller, Christoph , Schulze, Ryan J. , Schürmanns, Lea , Schwamborn, Jens C. , Schwarten, Melanie , Scott, Melanie J. , Scotto, Kathleen W., Scrima, Andrea , Scrivo, Aurora , Sebastián, David , Sebti, Salwa , Sedej, Simon , Segev, Nava , Seglen, Per O., Selleck, Scott B. , Selsby, Joshua, Sendtner, Michael , Şentürk, Şerif , Seranova, Elena, Sergi, Consolato M., Serra-Moreno, Ruth , Sesaki, Hiromi , Settembre, Carmine, Setty, Subba Rao Gangi , Sgarbi, Gianluca , Sha, Ou , Shacka, John J., Shah, Javeed A. , Shang, Dantong, Shao, Feng, Sharbati, Soroush , Sharkey, Lisa M. , Sharma, Dipali , Sharma, Gaurav, Sharma, Kulbhushan , Sharma, Pawan , Sharma, Surendra, Shen, Han‐Ming , Shen, Hongtao , Shen, Jiangang , Shen, Ming , Shen, Weili , Shen, Zheni, Sheng, Rui , Sheng, Zu-Hang, Shi, Jianjian , Shi, Ying–Hong , Shiba‐Fukushima, Kahori, Shieh, Jeng‐Jer , Shimada, Yohta , Shimizu, Shigeomi, Shimozawa, Makoto , Shintani, Takahiro , Shoemaker, Christopher J. , Shojaei, Shahla, Shoji, Ikuo , Shravage, Bhupendra V. , Shridhar, Viji, Shu, Chih‐Wen , Shu, Hong-Bing, Shui, Ke, Shukla, Arvind Kumar , Shutt, Timothy E. , Sica, Valentina , Siddiqui, Aleem , Sierra-Torre, Virginia, Signorelli, Santiago , Silva, Bruno Jorge de Andrade , Silva, Johnatas D. , Silva-Pavez, Eduardo , Silvente‐Poirot, Sandrine , Simmonds, Rachel E. , Singh, Anurag K. , Singh, Rajat Kumar , Singh, Shivendra V. , Singh, Shrawan Kumar , Singh, Sudha , Singh, Sunaina , Singh, Surinder Pal , Sinha, Debasish, Sinha, Rohit A. , Sinha, Sangita, Sirko, Agnieszka , Sivridis, Efthimios L., Skendros, Panagiotis , Sohn, Eun Jung , Sok, Sophia P. 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David , Sze, Stephen Cho Wing , Szewczyk, Nathaniel J. , Tabęcka-Łonczynska, Anna, Tabolacci, Claudio , Taegtmeyer, Heinrich, Tagaya, Mitsuo , Tai, Haoran , Tait, Stephen W. G., Takahashi, Yoshinori , Tam, Chit , Tam, Shing Yau , Tampellini, Davide , Tamura, Atsushi , Tan, Eng-King, Tan, Ya‐Qin , Tanaka, Masaki , Tang, Daolin , Tang, Jingfeng , Tang, Tie-Shan , Tao, Zhipeng , Taouis, Mohammed , Tavernarakis, Nektarios, Taylor, Allen, Teixeira, Natércia , Tekirdağ, Kumsal Ayşe, Tencomnao, Tewin , Tenreiro, Sandra , Tharaux, Pierre‐Louis , Thedieck, Kathrin , Thekkinghat, Arvind A. , Thinwa, Josephine , Thirumalaikumar, Venkatesh P. , Thomes, Paul G. , Thorburn, Andrew , Thum, Thomas, Thumm, Michael , Tian, Ling, Tichý, Aleš , Timmerman, Vincent , Titorenko, Vladimir I. , Toivonen, Janne M. , Tomaipitinca, Luana , Tomar, Dhanendra , Tomás‐Zapico, Cristina , Tomić, Sergej , Tong, Chao, Tong, Xin , Torgersen, Maria L., Torii, Satoru , Torres-López, Liliana , Torriglia, Alicia , Towers, Christina G. , Towns, Roberto, Tran, Quynh‐Giao , Travassos, Leonardo H. , Tremel, Shirley , Trougakos, Ioannis P., Tsao, Betty P. , Tse, Tak Fu, Tsvetkov, Andrey S. , Tumbarello, David A. , Tyler, Jessica K., Tyutereva, Elena V. , Uchiyama, Yasuo , Ugun‐Klusek, Aslihan , Uhlig, Holm H. , Ułamek-Kozioł, Marzena, Ulasov, Ilya V. , Umekawa, Midori, Ungermann, Christian , Urbe, Sylvie, Uribe-Carretero, Elisabet , Uversky, Vladimir N. , Vaccaro, María I. , Vahsen, Björn F. , Vakifahmetoglu-Norberg, Helin, Valdor, Rut , Valente, Maria João , Valko, Ayelén , Vallée, Richard, Valverde, Ángela M. , Berghe, Greet Van den, Veen, Stijn van der , Kaer, Luc Van , Loosdregt, Jorg van , Wijk, Sjoerd J. L. van , Vandenberghe, Wim , Vanhorebeek, Ilse , Vannier-Santos, Marcos A., Vannini, Nicola , Vanrell, M. Cristina, Vantaggiato, Chiara , Varela‐Nieto, Isabel , Varga, Máté , Vasconcelos, M. Helena , Vats, Somya , Vega-Rubín-de-Celis, Silvia , Velasco, Guillermo , Velázquez, Ariadna P., Vellai, Tibor , Vellenga, Edo , Verdier, Mireille , Verginis, Panayotis , Vergne, Isabelle , Verkade, Paul , Verma, Manish , Verstreken, Patrik , Vervliet, Tim , Vervoorts, Jörg , Víctor, Víctor M., Vidoni, Chiara , Vieira, Otília V. , Vierstra, Richard D., Viganò, Sonia , Vihinen, Helena , Vijayan, Vinoy, Vila, Miquel , Villalba, José M., Villalobo, Antonio , Villarejo‐Zori, Beatriz , Vincent, Olivier , Vindis, Cécile , Viret, Christophe , Vocadlo, David J. , Voitsekhovskaja, Olga V. , Volonté, Cinzia , Volta, Mattia , Vomero, Marta , Haefen, Clarissa von, Vooijs, Marc , Voos, Wolfgang , Vučićević, Ljubica , Waguri, Satoshi , Waite, Kenrick A., Wakatsuki, Shuji , Walker, David W., Walker, Mark J. , Walter, Jochen, Wandosell, Francisco , Wang, Bo , Wang, Chao-Yung, Wang, Chen , Wang, Chenran, Wang, Chenwei , Wang, Cun-Yu, Wang, Fengming, Wang, Han, Wang, Hexiang , Wang, Hong‐Gang , Wang, Jianrong, Wang, Jigang , Wang, Jun-Dong , Wang, Kui , Wang, Lianrong, Wang, Liming , Wang, Maggie Haitian, Wang, Meiqing , Wang, Nanbu , Wang, Pengwei , Wang, Ping , Wang, Ping, Wang, Q., Wang, Qiong , Wang, Wentao , Wang, Xinnan, Wang, Xuejun , Wang, Yan, Wang, Yanchang , Wang, Yanzhuang , Wang, Yihua , Wang, Yu , Wang, Yuqi , Wang, Zhe, Wang, Zhenyu , Wang, Zhouguang , Watanabe, Eizo, Watchon, Maxinne , Wawrzyńska, Anna , Weaver, Timothy E., Węgrzyn, Grzegorz, Wehman, Ann M. , Wei, Huafeng , Wei, Taotao , Wei, Yongjie, Weiergräber, Oliver H. , Weihl, Conrad C., Weindl, Günther , Weiskirchen, Ralf , Wen, Runxia H. , Werner, Antonia, Weykopf, Beatrice , Whitton, J. 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N. , Bei, Roberto , Behl, Christian , Bello‐Morales, Raquel , Beltrán, Sebastián , Bergami, Matteo , Bergmann, Andreas , Berthoux, Lionel , Bhattacharya, Resham , Bhattacharyya, Shalmoli , Bhutia, Sujit Kumar , Bi, Lanrong , Birgisdottir, Åsa Birna , Bjørkøy, Geir , Blomgren, Klas , Boada-Romero, Emilio , Boesze‐Battaglia, Kathleen , Bonifacino, Juan S. , Boone, Brian A. , Borthakur, Gautam , Bosch, Jürgen , Bose, Santanu , Botana, Luis Miguel , Boulton, Michael E. , Bourdenx, Mathieu , Brackney, Doug E. , Brandts, Christian , Braun, Ralf J. , Braus, Gerhard H. , Bravo, Roberto , Brody, Steven L. , Brown, Carolyn Nicole , Brumell, John Hunter , Brunetti‐Pierri, Nicola , Buitrago‐Molina, Laura Elisa , Buraschi, Simone , Buch, Shilpa J. , Butturini, Elena , Cairó, Montserrat , Caldwell, Kim A. , Campbell‐Valois, François‐Xavier , Campello, Silvia , Campesi, Ilaria , Almeida, Danilo Cândido de , Canesi, Laura , Caraglia, Michele , Carchman, Evie H. , Carmona‐Gutiérrez, Didac , Carnevali, Oliana , Carrier, Lucie , Carroll, Bernadette , Carter, A. Brent , Casas, Caty , Castillo, Eliseo F. , Castro‐Caldas, Margarida , Castro‐Obregón, Susana , Catz, Sergio , Cayuela, María Luisa , Cecarini, Valentina , Cecconi, Francesco , Cenci, Simone , Ceperuelo‐Mallafré, Victòria , Cervia, Davide , Chae, Han–Jung , Chakrabarti, Oishee , Chan, Edmond Y. 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G.
Autophagy | March 24, 2021 | Volume: 17 | Issue: 1 | Pages: 1-382
Clinical and Outcomes Findings for Thrombotic Thrombocytopenic Purpura among 467 Persons with Severely Versus Not Severely Deficient ADAMTS-13 Levels.
Bennett, Charles L. , Luu, Thanh Ha, Zakarija, Anaadriana, Kwaan, Hau C. , Bandarenko, Nicholas, McKoy, June M. , Buffie, Charlie G., Raife, Thomas J. , Fujimura, Yoshihiro , Rock, Gail A., Pandey, Dilip K. , Cursio, John , Winters, Jeffrey L. , Ortel, Thomas L. , Sarode, Ravi , Zheng, X. Long , Matsumoto, Masanori , Rock, Gail A.
Blood | April 18, 2020 | Volume: 110 | Issue: 11 | Pages: 2088-2088
10.1182/blood.v110.11.2088.2088
Abstract Background: Thrombotic thrombocytopenic purpura (TTP) is a rare disorder that presents with microangiopathic hemolytic anemia and thrombocytopenia, fevers, renal insufficiency and neurologic features. We reviewed clinical, laboratory, and outcome data for TTP cases with severely deficient versus non-severely deficient ADAMTS13 activity levels. Methods: Mean and median data were from the Surveillance, Epidemiology and Risk Factors for TTP (SERF-TTP) study group for idiopathic TTP cases, the Canadian Apheresis Group (CAG), and five published series (Zheng 2004, Raife 2004, Vesely 2003 (Oklahoma TTP-HUS Registry), Matsumoto 2004 (Japan Referral Center), Bennett 2007). Results: Compared to TTP cases with near-normal ADAMTS13 activity levels (n= 282), TTP cases with severe ADAMTS13-deficiency (n=185) were more likely to have severe thrombocytopenia, normal renal function and neutralizing ADAMTS13 antibodies. Severe ADAMTS13 deficient TTP cases have better overall survival after therapeutic plasma exchange (TPE) but are more likely to relapse. TTP patients with severe ADAMTS13 deficiency were primarily categorized as idiopathic or ticlopidine-associated, while TTP patients with non-severely deficient ADAMTS13 activity levels were frequently categorized as idiopathic, secondary to drugs (clopidogrel, quinine), stem cell transplantation, or cancer. Conclusions: Severe ADAMTS13 deficiency is most commonly idiopathic, has better survival following TPE, and a 35–40% spontaneous relapse rate. By contrast, non-ADAMTS13 deficient TTP cases are usually associated with an underlying disorder or external insults. Amongst this cohort, four series have 47–62% survival rates and three series, which contain mostly idiopathic cases, have 83–90% survival rates following TPE. From this, we propose that TTP may occur by three possible mechanism; ADAMTS13-deficient (antibody-mediated), an immunologic mediated pathway independent of ADAMTS13 (i.e. quinine) that is responsive to TPE, and endothelial injury related TTP that is unresponsive to TPE. Platelet count mean (x10^9/L) Creatinine mean (mg/dl) ADAMTS13 neutralizing antibodies (%) Survival % Relapse % * <15% ADAMTS13 activity cutoff Severe ADAMTS13 Deficiency (<10–15%) SERF-TTP (n=30) 19 1.3 83 97 41 Zheng (n=16) 19 1.6 44 81 38 Bennett (n=26) 15 85 Oklahoma (n=18) 12 1.8 94 81 38 Raife (n=50) * 13 1.2 92 35 Japan (n=34) 35 91 Canada (n=11) 16 2.4 82 Not Severely Deficient ADAMTS13 Activity (> 15%) SERF-TTP (n=22) 57 3.9 35 90 0 Raife (n=57) * 44 2.7 83 9 Canada (n=17) 57 4.1 88 Zheng (n=13) 40 3.0 0 54 Bennett (n=13) 62 Japan (n=66) 9 62 Oklahoma (n=94 ) 23 47 3
Differential Effect of Rituximab on Relapse-Free Survival in De Novo and Relapsed Immune Thrombotic Thrombocytopenic Purpura in African-American and Caucasian Populations
Marshall, Mazepa A., Evans, Michael , Johnson, Andrew D. , Antun, Ana G., Farland, Andrew M., Metjian, Ara , Bagby, Kristin, Park, Yara, Ridder, Gustaaf de, Gibson, Briana, Eubanks, Susan, Akwaa, Frank, Upreti, Harsh Vardhan , Kohli, Rahil, Kocher, Nicole K. , Gangaraju, Radhika , Evans, Michael, Davis, Elizabeth A. , Woods, Ryan R, Raval, Jay S. , Kasthuri, Raj S. , Liles, Darla , Kreuziger, Lisa Baumann , Sadler, J. Evan , Sridharan, Meera , Go, Ronald S. , McCrae, Keith R. , Chaturvedi, Shruti , Lim, Ming Y , Zheng, X. Long , Cataland, Spero R.
Blood | February 14, 2020 | Volume: 134 | Issue: Supplement_1 | Pages: 90-90
Introduction The United States Thrombotic Microangiopathy (USTMA) Consortium consists of high-volume US referral centers that are committed to collaborative research in TMAs. The USTMA Immune Thrombotic Thrombocytopenic Purpura (iTTP) registry has compiled retrospective data on demographics, treatments and outcomes in patients with iTTP to create the world's largest database of patients with this rare disease. While there is consensus on the use of therapeutic plasma exchange (TPE) for treatment of iTTP, there are no large randomized trials on which to base use of rituximab. The drug is frequently used for refractory or relapsed iTTP, but is currently being used more frequently for de novo (first episode) iTTP. We queried the USTMA iTTP registry to determine whether relapse free survival (RFS) is superior when rituximab is added to TPE and corticosteroids for treatment of iTTP. We hypothesized that the addition of rituximab would improve RFS at 5 years in both de novo and relapsing iTTP. Methods Following IRB approval at each institution, investigators independently reviewed individual patient records to confirm diagnostic criteria and entered demographic, treatment and outcomes data into the REDCap database housed at the University of North Carolina. The diagnosis of iTTP was defined as ADAMTS13 < 10% or ADAMTS13 < 20% with an inhibitor or antibody detected at any point or a clinical diagnosis of iTTP based on presenting characteristics, response to treatment and/or relapsing phenotype before ADAMTS13 testing became available (N=173). Relapse was defined as a recurrence of iTTP after at least 30 days of remission (recurrence within 30 days was considered an exacerbation, or continuation of the prior episode). To explore the effect of rituximab added to TPE and corticosteroids, we first assessed the treatment effect in de novo iTTP patients and then separately in relapse. We constructed Kaplan-Meier curves to compare RFS for patients treated with rituximab plus corticosteroids versus corticosteroids alone in both groups, and compared RFS at specific time points using the Klein method. To better understand whether other patient variables had an effect on RFS in both de novo episodes and relapses, ordinary (time-to-event) and mixed-effects (recurrent time-to-event) Cox proportional hazards models were used to examine the relationships of treatment, race/ethnicity, sex, age, treatment year, and presenting signs/symptoms with the outcome. Analyses were conducted using R version 3.5.2 (R Foundation for Statistical Computing, Vienna, Austria). Results As of July, 2019, the USTMA database contains 775 unique study patients with a confirmed diagnosis of iTTP with 1397 unique iTTP episodes. The treatment of patients' de novo iTTP episode was available for analysis in 375 patients, 188 of whom were treated with corticosteroids alone, 131 with corticosteroids plus rituximab, and 56 with other therapies. RFS was significantly higher in patients treated with corticosteroids and rituximab compared to those treated with corticosteroids alone at 1 year (0.93 vs. 0.78, p=0.0002) and 3 years (0.82 vs. 0.66, p=0.004) but not 5 years (0.60 vs. 0.56, p=0.39). In addition, the risk of relapse decreased with later treatment year for de novo iTTP (hazard ratio (HR) 0.95, 95% CI 0.92-0.99, p=0.03), consistent with rituximab use increasing over time, and was increased in African Americans compared with Caucasians (HR 1.83, 1.10-3.06, p=0.02). We then explored the treatment effect in all iTTP relapses (743 relapses in 426 patients). Here, a significant (p=0.0007) interaction between treatment and race was found. Among African Americans, we found no difference in RFS when rituximab was added (HR 1.15, 0.81-1.62, p=0.43). However, among Caucasians, RFS was significantly improved when rituximab was added (HR 0.15, 0.06-0.35, p<0.0001). Conclusions For de novo iTTP, adding rituximab to corticosteroids for immunosuppression likely delays but does not prevent relapse. Unlike in de novo disease, in patients with relapsed iTTP, we found a novel and significant interaction between race and treatment: while Caucasians had significantly improved RFS with the addition of rituximab, there was no effect on RFS in African Americans. Further investigation is warranted to determine the mechanisms of this difference in the response to rituximab in relapsed iTTP to improve outcomes in African Americans. Figure Disclosures Marshall: Sanofi: Membership on an entity's Board of Directors or advisory committees. Farland:Sanofi: Membership on an entity's Board of Directors or advisory committees. Metjian:Sanofi: Membership on an entity's Board of Directors or advisory committees. Raval:Bayer, Inc: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Liles:Imara: Other: PI on Clinical trial- Sickle cell ; Shire: Other: PI on clinical trial Sickle cell ; Novartis: Other: PI on clinical trial Sickle cell . Baumann Kreuziger:CSL Behring: Consultancy; Vaccine Injury Compensation Program: Consultancy. McCrae:Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceutical: Membership on an entity's Board of Directors or advisory committees. Chaturvedi:Shire/Takeda: Research Funding; Sanofi: Consultancy; Alexion: Consultancy. Zheng:Clotsolution: Other: Co-Founder; Shire/Takeda: Research Funding; Ablynx/Sanofi: Consultancy, Speakers Bureau; Alexion: Speakers Bureau. Cataland:Ablynx/Sanofi: Consultancy, Research Funding; Alexion: Consultancy, Research Funding. Off Label Disclosure: rituximab for immunosuppression in TTP.
African American Race Is Associated with Decreased Relapse-Free Survival in Immune Thrombotic Thrombocytopenic Purpura
Johnson, Andrew D. , Antun, Ana G., Farland, Andrew M., Metjian, Ara , Bagby, Kristin, Park, Yara, Ridder, Gustaaf de, Gibson, Briana, Eubanks, Susan, Akwaa, Frank, Kohli, Rahil, Upreti, Harsh Vardhan , Kocher, Nicole K. , Gangaraju, Radhika , Liu, Angela , Mazepa, Marshall , Davis, Elizabeth A. , Woods, Ryan R, Raval, Jay S. , Kasthuri, Raj S. , Liles, Darla , Kreuziger, Lisa Baumann , Sadler, J. Evan , Sridharan, Meera , Go, Ronald S. , McCrae, Keith R. , Lim, Ming Y , Zheng, X. Long , Cataland, Spero R. , Chaturvedi, Shruti
Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 1066-1066
Background: Immune thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal hematologic disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and ischemic organ impairment. The incidence of iTTP is higher among African-Americans (AA), however, differences in presentation and outcomes have not been fully investigated. In a multi-center cohort of patients with iTTP from the United States Thrombotic Microangiopathy (USTMA) Consortium, we tested the hypothesis that AA race is an independent predictor of poor outcomes including iTTP related mortality and relapse. Methods: We queried data from the USTMA iTTP registry, which currently includes data from 785 individual patients from 15 institutions across the United States. Data from at least one iTTP episode are available for 734 patients. The cohort is 35.1% (N = 272) White, 58.7% (N = 455) African American, 0.4% (N=3) Asian, 1.8% (N=14) Hispanic, and 4.0 % (N=31) other/unknown race. We restricted our analyses to AA and White participants because of small numbers in the other groups. We compared presenting features and treatments using the chi-squared test and t-test for categorical and continuous variables, respectively. A relapse was defined as a recurrent iTTP episode occurring at least 30 days after last therapeutic plasma exchange. To evaluate relapse-free survival, we included only patients enrolled in the registry at their first TTP episode (144 White and 246 AA) since patients presenting with a relapse as their index episode are already confirmed to have relapsing iTTP. Kaplan Meier analysis was used to compare relapse-free survival in White and AA patients, and a Cox regression model was developed to evaluate the independent effect of race on relapse, adjusting for potential confounders including age, sex, and the use of rituximab. Results: Demographics and presenting features of 390 individuals (144 White and 246 AA) presenting with a first episode of iTTP are shown in Table 1. Presenting symptoms including fever, confusion, seizure, memory deficits, stupor, headache, stroke, chest pain, abdominal pain, fatigue, and dark urine were similar between Whites and AA except for petechiae, which were more frequently documented in Whites (28.8% vs 17.7%, p=0.011). Presenting laboratory studies were also comparable though AA had a higher rate of elevated serum troponin (50.6% vs 32.5%, p=0.003), lower hemoglobin level (8.27 ± 0.13 vs 8.81 ± 0.19, p=0.0176) and platelet count (20.3 ± 1.2 vs 26.2 ± 3.2, p=0.0432). In addition to therapeutic plasma exchange and corticosteroids, rituximab was administered to 23.7% of White patients and 22.7% of AA during their first iTTP episode (P=0.815). Median time to platelet count recovery (days of daily plasma exchange until normal platelet count for two consecutive days) was shorter in AA compared with White patients [5 (IQR 4, 10) vs. 8 (IQR 5, 14), log rank P = 0.004]. AA race remained a significant predictor of the shorter time to platelet count recovery [HR 1.44 (95% CI 1.12, 1.85), P=0.004] after adjusting for rituximab therapy [HR 0.60 (95% CI 0.0.46, 0.80), P<0.001], female sex [HR 0.95 (95% CI 0.73, 1.22), P=0.669], age [HR 0.99 (95% CI 0.99, 1.01), P=0.682], platelet count [HR 1.00 (95% CI 0.99, 1.04), P=0.820] and LDH at presentation [HR 1.00 (95% CI 1.00, 1.00), P=0.525]. Death during the first episode occurred in 8.9% of White patients and 5.5% of AA patients (P=0.206). Relapse-free survival after the first episode of iTTP was lower in AA than White patients (Figure 1). AA race was associated with the reduced relapse free survival [HR 1.79 (95% CI 1.08, 2.98), P=0.024] in a Cox regression model adjusted for age [HR 1.00 (95% CI 0.98, 1.01), P=0.683], sex [HR 0.96 (95% CI 0.60, 1.54), P=0.867], and rituximab therapy [HR 0.93 (95% CI 0.55, 1.59), P=0.806]. Conclusion: African Americans with iTTP have a higher relapse rate and shorter relapse free survival after the first episode of the disease compared with Caucasian patients, which is independent of age, sex and rituximab therapy. Contrary to our hypothesis, acute outcomes of iTTP (time to platelet count recovery and mortality) were not worse in AA patients. The factors contributing to the higher relapse rate in AA with iTTP need to be further investigated. Our findings suggest that AA patients may also benefit from closer follow up. Disclosures Farland: Sanofi: Membership on an entity's Board of Directors or advisory committees. Metjian:Sanofi: Membership on an entity's Board of Directors or advisory committees. Raval:Bayer, Inc: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Liles:Shire: Other: PI on clinical trial Sickle cell ; Imara: Other: PI on Clinical trial- Sickle cell ; Novartis: Other: PI on clinical trial Sickle cell . Baumann Kreuziger:CSL Behring: Consultancy; Vaccine Injury Compensation Program: Consultancy. McCrae:Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Zheng:Alexion: Speakers Bureau; Ablynx/Sanofi: Consultancy, Speakers Bureau; Clotsolution: Other: Co-Founder; Shire/Takeda: Research Funding. Cataland:Alexion: Consultancy, Research Funding; Ablynx/Sanofi: Consultancy, Research Funding. Chaturvedi:Shire/Takeda: Research Funding; Sanofi: Consultancy; Alexion: Consultancy.