Browsing by Author "Park, John J"
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Item Open Access Immunomodulatory lipid mediator profiling of cerebrospinal fluid following surgery in older adults.(Scientific reports, 2021-02-04) Terrando, Niccolò; Park, John J; Devinney, Michael; Chan, Cliburn; Cooter, Mary; Avasarala, Pallavi; Mathew, Joseph P; Quinones, Quintin J; Maddipati, Krishna Rao; Berger, Miles; MADCO-PC Study TeamArachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) derived lipids play key roles in initiating and resolving inflammation. Neuro-inflammation is thought to play a causal role in perioperative neurocognitive disorders, yet the role of these lipids in the human central nervous system in such disorders is unclear. Here we used liquid chromatography-mass spectrometry to quantify AA, DHA, and EPA derived lipid levels in non-centrifuged cerebrospinal fluid (CSF), centrifuged CSF pellets, and centrifuged CSF supernatants of older adults obtained before, 24 h and 6 weeks after surgery. GAGE analysis was used to determine AA, DHA and EPA metabolite pathway changes over time. Lipid mediators derived from AA, DHA and EPA were detected in all sample types. Postoperative lipid mediator changes were not significant in non-centrifuged CSF (p > 0.05 for all three pathways). The AA metabolite pathway showed significant changes in centrifuged CSF pellets and supernatants from before to 24 h after surgery (p = 0.0000247, p = 0.0155 respectively), from before to 6 weeks after surgery (p = 0.0000497, p = 0.0155, respectively), and from 24 h to 6 weeks after surgery (p = 0.0000499, p = 0.00363, respectively). These findings indicate that AA, DHA, and EPA derived lipids are detectable in human CSF, and the AA metabolite pathway shows postoperative changes in centrifuged CSF pellets and supernatants.Item Open Access Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.(The New England journal of medicine, 2021-08-04) REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators; Goligher, Ewan C; Bradbury, Charlotte A; McVerry, Bryan J; Lawler, Patrick R; Berger, Jeffrey S; Gong, Michelle N; Carrier, Marc; Reynolds, Harmony R; Kumar, Anand; Turgeon, Alexis F; Kornblith, Lucy Z; Kahn, Susan R; Marshall, John C; Kim, Keri S; Houston, Brett L; Derde, Lennie PG; Cushman, Mary; Tritschler, Tobias; Angus, Derek C; Godoy, Lucas C; McQuilten, Zoe; Kirwan, Bridget-Anne; Farkouh, Michael E; Brooks, Maria M; Lewis, Roger J; Berry, Lindsay R; Lorenzi, Elizabeth; Gordon, Anthony C; Ahuja, Tania; Al-Beidh, Farah; Annane, Djillali; Arabi, Yaseen M; Aryal, Diptesh; Baumann Kreuziger, Lisa; Beane, Abi; Bhimani, Zahra; Bihari, Shailesh; Billett, Henny H; Bond, Lindsay; Bonten, Marc; Brunkhorst, Frank; Buxton, Meredith; Buzgau, Adrian; Castellucci, Lana A; Chekuri, Sweta; Chen, Jen-Ting; Cheng, Allen C; Chkhikvadze, Tamta; Coiffard, Benjamin; Contreras, Aira; Costantini, Todd W; de Brouwer, Sophie; Detry, Michelle A; Duggal, Abhijit; Džavík, Vladimír; Effron, Mark B; Eng, Heather F; Escobedo, Jorge; Estcourt, Lise J; Everett, Brendan M; Fergusson, Dean A; Fitzgerald, Mark; Fowler, Robert A; Froess, Joshua D; Fu, Zhuxuan; Galanaud, Jean P; Galen, Benjamin T; Gandotra, Sheetal; Girard, Timothy D; Goodman, Andrew L; Goossens, Herman; Green, Cameron; Greenstein, Yonatan Y; Gross, Peter L; Haniffa, Rashan; Hegde, Sheila M; Hendrickson, Carolyn M; Higgins, Alisa M; Hindenburg, Alexander A; Hope, Aluko A; Horowitz, James M; Horvat, Christopher M; Huang, David T; Hudock, Kristin; Hunt, Beverley J; Husain, Mansoor; Hyzy, Robert C; Jacobson, Jeffrey R; Jayakumar, Devachandran; Keller, Norma M; Khan, Akram; Kim, Yuri; Kindzelski, Andrei; King, Andrew J; Knudson, M Margaret; Kornblith, Aaron E; Kutcher, Matthew E; Laffan, Michael A; Lamontagne, Francois; Le Gal, Grégoire; Leeper, Christine M; Leifer, Eric S; Lim, George; Gallego Lima, Felipe; Linstrum, Kelsey; Litton, Edward; Lopez-Sendon, Jose; Lother, Sylvain A; Marten, Nicole; Saud Marinez, Andréa; Martinez, Mary; Mateos Garcia, Eduardo; Mavromichalis, Stavroula; McAuley, Daniel F; McDonald, Emily G; McGlothlin, Anna; McGuinness, Shay P; Middeldorp, Saskia; Montgomery, Stephanie K; Mouncey, Paul R; Murthy, Srinivas; Nair, Girish B; Nair, Rahul; Nichol, Alistair D; Nicolau, Jose C; Nunez-Garcia, Brenda; Park, John J; Park, Pauline K; Parke, Rachael L; Parker, Jane C; Parnia, Sam; Paul, Jonathan D; Pompilio, Mauricio; Quigley, John G; Rosenson, Robert S; Rost, Natalia S; Rowan, Kathryn; Santos, Fernanda O; Santos, Marlene; Santos, Mayler O; Satterwhite, Lewis; Saunders, Christina T; Schreiber, Jake; Schutgens, Roger EG; Seymour, Christopher W; Siegal, Deborah M; Silva, Delcio G; Singhal, Aneesh B; Slutsky, Arthur S; Solvason, Dayna; Stanworth, Simon J; Turner, Anne M; van Bentum-Puijk, Wilma; van de Veerdonk, Frank L; van Diepen, Sean; Vazquez-Grande, Gloria; Wahid, Lana; Wareham, Vanessa; Widmer, R Jay; Wilson, Jennifer G; Yuriditsky, Eugene; Zhong, Yongqi; Berry, Scott M; McArthur, Colin J; Neal, Matthew D; Hochman, Judith S; Webb, Steven A; Zarychanski, RyanBackground
Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.Methods
In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.Results
The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.Conclusions
In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).