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1. RECOVER-NEURO: study protocol for a multi-center, multi-arm, phase 2, randomized, active comparator trial evaluating three interventions for cognitive dysfunction in post-acute sequelae of SARS-CoV-2 infection (PASC)

Author

Knopman, David S., Laskowitz, Daniel T., Koltai, Deborah C., Charvet, Leigh E., Becker, Jacqueline H., Federman, Alex D., Wisnivesky, Juan, Mahncke, Henry, Van Vleet, Thomas M., Bateman, Lucinda, Kim, Dong-Yun, O’Steen, Ashley, James, Melissa, Silverstein, Adam, Lokhnygina, Yuliya, Rich, Jennifer, Feger, Bryan J., and Zimmerman, Kanecia O.

Published
2024
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4. Association of Early Dexmedetomidine Utilization With Clinical and Functional Outcomes Following Moderate-Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study*

Author

Liu, Sunny Yang, Kelly-Hedrick, Margot, Temkin, Nancy, Barber, Jason, Komisarow, Jordan, Hatfield, Jordan, Ohnuma, Tetsu, Manley, Geoffrey, Treggiari, Miriam M., Colton, Katharine, Vavilala, Monica S., Grandhi, Ramesh, Laskowitz, Daniel T., Mathew, Joseph P., Hernandez, Adrian, James, Michael L., Raghunathan, Karthik, Goldstein, Ben, Markowitz, Amy, Krishnamoorthy, Vijay, Badjatia, Neeraj, Ferguson, Adam R., Foreman, Brandon, Madden, Christopher, McCrea, Michael, Merchant, Randall, Ngwenya, Laura B., Okonkwo, David, Schnyer, David, Yue, John K., and Zafonte, Ross

Published
2024
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5. Incidence and Clinical Impact of Myocardial Injury Following Traumatic Brain Injury: A Pilot TRACK-TBI Study.

Author

Krishnamoorthy, Vijay, Manley, Geoffrey T, Jain, Sonia, Sun, Shelly, Foreman, Brandon, Komisarow, Jordan, Laskowitz, Daniel T, Mathew, Joseph P, Hernandez, Adrian, James, Michael L, Vavilala, Monica S, Markowitz, Amy J, Korley, Frederick K, and TRACK-TBI Investigators

Subjects
TRACK-TBI Investigators, Humans, Glasgow Coma Scale, Incidence, Cohort Studies, Prospective Studies, Pilot Projects, Adult, Male, Brain Injuries, Traumatic, Traumatic Head and Spine Injury, Brain Disorders, Neurosciences, Traumatic Brain Injury (TBI), Physical Injury - Accidents and Adverse Effects, Clinical Research, Prevention, Rehabilitation, Injuries and accidents, myocardial injury, trauma, traumatic brain injury, high sensitivity troponin, outcome, Clinical Sciences, Psychology, Anesthesiology
Abstract

BackgroundTraumatic brain injury (TBI) is a major global health problem. Little research has addressed extracranial organ dysfunction following TBI, particularly myocardial injury. Using a sensitive marker of myocardial injury-high sensitivity troponin (hsTn)-we examined the incidence of early myocardial injury following TBI and explored its association with neurological outcomes following moderate-severe TBI.MethodsWe conducted a pilot cohort study of 133 adult (age above 17 y) subjects enrolled in the TRACK-TBI 18-center prospective cohort study. Descriptive statistics were used to examine the incidence of myocardial injury (defined as hsTn >99th percentile for a standardized reference population) across TBI severities, and to explore the association of myocardial injury with a 6-month extended Glasgow Outcome Score among patients with moderate-severe TBI.ResultsThe mean (SD) age of the participants was 44 (17) years, and 87 (65%) were male. Twenty-six patients (20%) developed myocardial injury following TBI; myocardial injury was present in 15% of mild TBI patients and 29% of moderate-severe TBI patients (P=0.13). Median (interquartile range) hsTn values were 3.8 ng/L (2.1, 9.0), 5.8 ng/L (4.5, 34.6), and 10.2 ng/L (3.0, 34.0) in mild, moderate, and severe TBI participants, respectively (P=0.04). Overall, 11% of participants with moderate-severe TBI and myocardial injury experienced a good outcome (6-mo extended Glasgow Outcome Score≥5) at 6 months, compared with 65% in the group that did not experience myocardial injury (P=0.01).ConclusionsMyocardial injury is common following TBI, with a likely dose-response relationship with TBI severity. Early myocardial injury was associated with poor 6-month clinical outcomes following moderate-severe TBI.

Published
2022

6. Association of Early Dexmedetomidine Utilization With Clinical Outcomes After Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study

Author

Liu, Sunny Yang, Kelly-Hedrick, Margot, Komisarow, Jordan, Hatfield, Jordan, Ohnuma, Tetsu, Treggiari, Miriam M., Colton, Katharine, Arulraja, Evangeline, Vavilala, Monica S., Laskowitz, Daniel T., Mathew, Joseph P., Hernandez, Adrian, James, Michael L., Raghunathan, Karthik, and Krishnamoorthy, Vijay

Published
2024
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7. Association of Vasopressor Choice with Clinical and Functional Outcomes Following Moderate to Severe Traumatic Brain Injury: A TRACK-TBI Study

Author

Toro, Camilo, Temkin, Nancy, Barber, Jason, Manley, Geoffrey, Jain, Sonia, Ohnuma, Tetsu, Komisarow, Jordan, Foreman, Brandon, Korley, Frederick K, Vavilala, Monica S, Laskowitz, Daniel T, Mathew, Joseph P, Hernandez, Adrian, Sampson, John, James, Michael L, Goldstein, Benjamin A, Markowitz, Amy J, and Krishnamoorthy, Vijay

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rehabilitation, Traumatic Brain Injury (TBI), Clinical Research, Physical Injury - Accidents and Adverse Effects, Patient Safety, Neurosciences, Brain Disorders, Traumatic Head and Spine Injury, Injuries and accidents, Adult, Brain Injuries, Traumatic, Glasgow Coma Scale, Humans, Male, Prospective Studies, Retrospective Studies, Vasoconstrictor Agents, Traumatic brain injury, Shock, Vasopressors, TRACK-TBI Investigators, Neurology & Neurosurgery, Clinical sciences, Nursing
Abstract

BackgroundEarly hypotension following moderate to severe traumatic brain injury (TBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors to support blood pressure following TBI; however, guidelines do not specify vasopressor type, resulting in variation in clinical practice. Minimal data are available to guide clinicians on optimal early vasopressor choice to support blood pressure following TBI. Therefore, we conducted a multicenter study to examine initial vasopressor choice for the support of blood pressure following TBI and its association with clinical and functional outcomes after injury.MethodsWe conducted a retrospective cohort study of patients enrolled in the transforming research and clinical knowledge in traumatic brain injury (TRACK-TBI) study, an 18-center prospective cohort study of patients with TBI evaluated in participating level I trauma centers. We examined adults with moderate to severe TBI (defined as Glasgow Coma Scale score

Published
2022

8. Association of Early Multiple Organ Dysfunction With Clinical and Functional Outcomes Over the Year Following Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study

Author

Krishnamoorthy, Vijay, Temkin, Nancy, Barber, Jason, Foreman, Brandon, Komisarow, Jordan, Korley, Fred K, Laskowitz, Daniel T, Mathew, Joseph P, Hernandez, Adrian, Sampson, John, James, Michael L, Bartz, Raquel, Raghunathan, Karthik, Goldstein, Benjamin A, Markowitz, Amy J, and Vavilala, Monica S

Subjects
Rehabilitation, Neurosciences, Traumatic Head and Spine Injury, Physical Injury - Accidents and Adverse Effects, Brain Disorders, Clinical Research, Traumatic Brain Injury (TBI), Injuries and accidents, Adult, Brain Injuries, Traumatic, Cohort Studies, Female, Functional Status, Glasgow Coma Scale, Glasgow Outcome Scale, Humans, Male, Multiple Organ Failure, Organ Dysfunction Scores, Proportional Hazards Models, Prospective Studies, Retrospective Studies, multiple organ dysfunction, outcomes, shock, trauma, traumatic brain injury, Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) Investigators, Clinical Sciences, Nursing, Public Health and Health Services, Emergency & Critical Care Medicine
Abstract

ObjectivesTraumatic brain injury is a leading cause of death and disability in the United States. While the impact of early multiple organ dysfunction syndrome has been studied in many critical care paradigms, the clinical impact of early multiple organ dysfunction syndrome in traumatic brain injury is poorly understood. We examined the incidence and impact of early multiple organ dysfunction syndrome on clinical, functional, and disability outcomes over the year following traumatic brain injury.DesignRetrospective cohort study.SettingPatients enrolled in the Transforming Clinical Research and Knowledge in Traumatic Brain Injury study, an 18-center prospective cohort study of traumatic brain injury patients evaluated in participating level 1 trauma centers.SubjectsAdult (age > 17 yr) patients with moderate-severe traumatic brain injury (Glasgow Coma Scale < 13). We excluded patients with major extracranial injury (Abbreviated Injury Scale score ≥ 3).InterventionsDevelopment of early multiple organ dysfunction syndrome, defined as a maximum modified Sequential Organ Failure Assessment score greater than 7 during the initial 72 hours following admission.Measurements and main resultsThe main outcomes were: hospital mortality, length of stay, 6-month functional and disability domains (Glasgow Outcome Scale-Extended and Disability Rating Scale), and 1-year mortality. Secondary outcomes included: ICU length of stay, 3-month Glasgow Outcome Scale-Extended, 3-month Disability Rating Scale, 1-year Glasgow Outcome Scale-Extended, and 1-year Disability Rating Scale. We examined 373 subjects with moderate-severe traumatic brain injury. The mean (sd) Glasgow Coma Scale in the emergency department was 5.8 (3.2), with 280 subjects (75%) classified as severe traumatic brain injury (Glasgow Coma Scale 3-8). Among subjects with moderate-severe traumatic brain injury, 252 (68%) developed early multiple organ dysfunction syndrome. Subjects that developed early multiple organ dysfunction syndrome had a 75% decreased odds of a favorable outcome (Glasgow Outcome Scale-Extended 5-8) at 6 months (adjusted odds ratio, 0.25; 95% CI, 0.12-0.51) and increased disability (higher Disability Rating Scale score) at 6 months (adjusted mean difference, 2.04; 95% CI, 0.92-3.17). Subjects that developed early multiple organ dysfunction syndrome experienced an increased hospital length of stay (adjusted mean difference, 11.4 d; 95% CI, 7.1-15.8), with a nonsignificantly decreased survival to hospital discharge (odds ratio, 0.47; 95% CI, 0.18-1.2).ConclusionsEarly multiple organ dysfunction following moderate-severe traumatic brain injury is common and independently impacts multiple domains (mortality, function, and disability) over the year following injury. Further research is necessary to understand underlying mechanisms, improve early recognition, and optimize management strategies.

Published
2021

9. Association of Early Dexmedetomidine Utilization With Clinical and Functional Outcomes Following Moderate-Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study

Author

Liu, Sunny Yang, Kelly-Hedrick, Margot, Temkin, Nancy, Barber, Jason, Komisarow, Jordan, Hatfield, Jordan, Ohnuma, Tetsu, Manley, Geoffrey, Treggiari, Miriam M., Colton, Katharine, Vavilala, Monica S., Grandhi, Ramesh, Laskowitz, Daniel T., Mathew, Joseph P., Hernandez, Adrian, James, Michael L., Raghunathan, Karthik, Goldstein, Ben, Markowitz, Amy, Krishnamoorthy, Vijay, Badjatia, Neeraj, Ferguson, Adam R., Foreman, Brandon, Madden, Christopher, McCrea, Michael, Merchant, Randall, Ngwenya, Laura B., Okonkwo, David, Schnyer, David, Yue, John K., and Zafonte, Ross

Published
2023
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12. International Comparison of Patient Characteristics and Quality of Care for Ischemic Stroke: Analysis of the China National Stroke Registry and the American Heart Association Get With The Guidelines––Stroke Program

Author

Wangqin, Runqi, Laskowitz, Daniel T, Wang, Yongjun, Li, Zixiao, Wang, Yilong, Liu, Liping, Liang, Li, Matsouaka, Roland A, Saver, Jeffrey L, Fonarow, Gregg C, Bhatt, Deepak L, Smith, Eric E, Schwamm, Lee H, Bettger, Janet Prvu, Hernandez, Adrian F, Peterson, Eric D, and Xian, Ying

Subjects
Clinical Research, Stroke, Brain Disorders, Neurosciences, Hematology, Rehabilitation, Prevention, Age Distribution, Aged, Brain Ischemia, China, Female, Guideline Adherence, Humans, Male, Middle Aged, Practice Guidelines as Topic, Quality Improvement, Quality of Health Care, United States, international comparison, patient characteristics, performance measures, quality of care, stroke, Cardiorespiratory Medicine and Haematology
Abstract

Background Adherence to evidence-based guidelines is an important quality indicator; yet, there is lack of assessment of adherence to performance measures in acute ischemic stroke for most world regions. Methods and Results We analyzed 19 604 patients with acute ischemic stroke in the China National Stroke Registry and 194 876 patients in the Get With The Guidelines--Stroke registry in the United States from June 2012 to January 2013. Compared with their US counterparts, Chinese patients were younger, had a lower prevalence of comorbidities, and had similar median, lower mean, and less variability in National Institutes of Health Stroke Scale (median 4 [25th percentile-75th percentile, 2-7], mean 5.4±5.6 versus median 4 [1-10], mean 6.8±7.7). Chinese patients were more likely to experience delays from last known well to hospital arrival (median 1318 [330-3209] versus 644 [142-2055] minutes), less likely to receive thrombolytic therapy (2.5% versus 8.1%), and more likely to experience treatment delays (door-to-needle time median 95 [72-112] versus 62 [49-85] minutes). Adherence to early and discharge antithrombotics, smoking cessation counseling, and dysphagia screening were relatively high (eg >80%) in both countries. Large gaps existed between China and the United States with regard to the administration of thrombolytics within 3 hours (18.3% versus 83.6%), door-to-needle time ≤60 minutes (14.6% versus 48.0%), deep venous thrombosis prophylaxis (65.0% versus 97.8%), anticoagulation for atrial fibrillation (21.0% versus 94.4%), lipid treatment (66.3% versus 95.8%), and rehabilitation assessment (58.8% versus 97.4%). Conclusions We found significant differences in clinical characteristics and gaps in adherence for certain performance measures between China and the United States. Additional efforts are needed for continued improvements in acute stroke care and secondary prevention in both nations, especially China.

Published
2018

14. Early Beta-Blocker Utilization in Critically Ill Patients With Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

Author

Kelly-Hedrick, Margot, Liu, Sunny Yang, Komisarow, Jordan, Hatfield, Jordan, Ohnuma, Tetsu, Treggiari, Miriam M., Colton, Katharine, Arulraja, Evangeline, Vavilala, Monica S., Laskowitz, Daniel T., Mathew, Joseph P., Hernandez, Adrian, James, Michael L., Raghunathan, Karthik, and Krishnamoorthy, Vijay

Subjects
CRITICALLY ill patient care, BRAIN injuries, ADRENERGIC beta blockers, RETROSPECTIVE studies, LENGTH of stay in hospitals, TREATMENT effectiveness
Abstract

Background: There is limited evidence that beta-blockers may provide benefit for patients with moderate-severe traumatic brain injury (TBI) during the acute injury period. Larger studies on utilization patterns and impact on outcomes in clinical practice are lacking. Objective: The present study uses a large, national hospital claims-based dataset to examine early beta-blocker utilization patterns and its association with clinical outcomes among critically ill patients with moderate-severe TBI. Methods: We conducted a retrospective cohort study of the administrative claims Premier Healthcare Database of adults (≥17 years) with moderate-severe TBI admitted to the intensive care unit (ICU) from 2016 to 2020. The exposure was receipt of a beta-blocker during day 1 or 2 of ICU stay (BB+). The primary outcome was hospital mortality, and secondary outcomes were: hospital length of stay (LOS), ICU LOS, discharge to home, and vasopressor utilization. In a sensitivity analysis, we explored the association of beta-blocker class (cardioselective and noncardioselective) with hospital mortality. We used propensity weighting methods to address possible confounding by treatment indication. Results: A total of 109 665 participants met inclusion criteria and 39% (n = 42 489) were exposed to beta-blockers during the first 2 days of hospitalization. Of those, 42% received cardioselective only, 43% received noncardioselective only, and 14% received both. After adjustment, there was no association with hospital mortality in the BB+ group compared to the BB− group (adjusted odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94, 1.04). The BB+ group had longer hospital stays, lower chance of discharged home, and lower risk of vasopressor utilization, although these difference were clinically small. Beta-blocker class was not associated with hospital mortality. Conclusion: In this retrospective cohort study, we found variation in use of beta-blockers and early exposure was not associated with hospital mortality. Further research is necessary to understand the optimal type, dose, and timing of beta-blockers for this population. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Association of Early Dexmedetomidine Utilization With Clinical Outcomes After Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

Author

Sunny Yang Liu, Kelly-Hedrick, Margot, Komisarow, Jordan, Hatfield, Jordan, Tetsu Ohnuma, Treggiari, Miriam M., Colton, Katharine, Arulraja, Evangeline, Vavilala, Monica S., Laskowitz, Daniel T., Mathew, Joseph P., Hernandez, Adrian, James, Michael L., Raghunathan, Karthik, and Krishnamoorthy, Vijay

Published
2024
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18. Intravenous tPA (Tissue-Type Plasminogen Activator) in Patients With Acute Ischemic Stroke Taking Non–Vitamin K Antagonist Oral Anticoagulants Preceding Stroke

Author

Jin, Chen, Huang, Ryan J, Peterson, Eric D, Laskowitz, Daniel T, Hernandez, Adrian F, Federspiel, Jerome J, Schwamm, Lee H, Bhatt, Deepak L, Smith, Eric E, Fonarow, Gregg C, and Xian, Ying

Subjects
Stroke, Clinical Research, Neurosciences, Brain Disorders, Hematology, Good Health and Well Being, Administration, Intravenous, Administration, Oral, Antibodies, Monoclonal, Humanized, Anticoagulants, Antidotes, Antithrombins, Brain Ischemia, Dabigatran, Factor Xa Inhibitors, Fibrinolytic Agents, Humans, Intracranial Hemorrhages, Odds Ratio, Practice Guidelines as Topic, Pyrazoles, Pyridones, Rivaroxaban, Tissue Plasminogen Activator, apixaban, dabigatran, humans, intracranial hemorrhages, rivaroxaban, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and Purpose- Although there are no trials or large cohorts to inform clinical care, current guidelines caution against giving intravenous tPA (tissue-type plasminogen activator) to patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). We performed a literature review of intravenous tPA in patients treated with NOACs preceding stroke. Methods- A literature search of PubMed was performed encompassing January 2010 to March 2018. Patient characteristics, timing of last medication intake, laboratory testing, use of reversal, and outcomes ≤3 months after discharge were summarized. Results- We identified 55 studies with 492 NOAC patients receiving tPA (dabigatran, 181; rivaroxaban, 215; apixaban, 40; and unspecified NOAC, 56). Among patients with complete data, the median time from the last NOAC intake to symptom onset was 8 hours (interquartile range, 2.5-14.5), with 55.2% (80/145) within 12 hours. Few patients underwent sensitive laboratory tests, such as thrombin time, diluted thrombin time, or anti-Xa assays before tPA administration. The overall observed rates of symptomatic intracranial hemorrhage, mortality, and favorable outcomes (National Institutes of Health Stroke Scale score, ≤1; modified Rankin Scale score, 0-2; or neurological improvement in the National Institutes of Health Stroke Scale score, ≥8 points) were 4.3% (20/462), 11.3% (48/423), and 43.7% (164/375), respectively. Among dabigatran-treated patients, reversal with idarucizumab was associated with fewer symptomatic intracranial hemorrhage (4.5% [2/44] versus 7.4% [8/108]; unadjusted odds ratio, 0.60; 95% CI, 0.12-2.92), death (4.5% [2/44] versus 12.0% [13/108]; unadjusted odds ratio, 0.35; 95% CI, 0.08-1.61), and more favorable outcomes (79.1% [34/43] versus 39.2% [29/74]; unadjusted odds ratio, 5.86; 95% CI, 2.45-14.00), although the differences were not statistically significant for symptomatic intracranial hemorrhage and death. Conclusions- These preliminary observations suggest that tPA may be reasonably well tolerated without prohibitive risks of bleeding complications in selected patients on NOACs. Reversal of anticoagulant effects by idarucizumab for dabigatran-treated patients before tPA is an emerging strategy that was associated with more favorable outcomes.

Published
2018

23. Association of Early Dexmedetomidine Utilization With Clinical and Functional Outcomes Following Moderate-Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

Author

Sunny Yang Liu, Kelly-Hedrick, Margot, Temkin, Nancy, Barber, Jason, Komisarow, Jordan, Hatfield, Jordan, Tetsu Ohnuma, Manley, Geoffrey, Treggiari, Miriam M., Colton, Katharine, Vavilala, Monica S., Grandhi, Ramesh, Laskowitz, Daniel T., Mathew, Joseph P., Hernandez, Adrian, James, Michael L., Raghunathan, Karthik, Goldstein, Ben, Markowitz, Amy, and Krishnamoorthy, Vijay

Published
2024
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25. A Randomized, Placebo-Controlled, Phase II Trial of Intravenous Allogeneic Non-HLA Matched, Unrelated Donor, Cord Blood Infusion for Ischemic Stroke

Author

Laskowitz, Daniel T, primary, Troy, Jesse, additional, Poehlein, Emily, additional, Bennett, Ellen R, additional, Shpall, Elizabeth J, additional, Wingard, John R, additional, Freed, Brian, additional, Belagaje, Samir R, additional, Khanna, Anna, additional, Jones, William, additional, Volpi, John J, additional, Marrotte, Eric, additional, and Kurtzberg, Joanne, additional

Published
2023
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33. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

Author

Kashani, Kianoush, Al-Khafaji, Ali, Ardiles, Thomas, Artigas, Antonio, Bagshaw, Sean M, Bell, Max, Bihorac, Azra, Birkhahn, Robert, Cely, Cynthia M, Chawla, Lakhmir S, Davison, Danielle L, Feldkamp, Thorsten, Forni, Lui G, Gong, Michelle, Gunnerson, Kyle J, Haase, Michael, Hackett, James, Honore, Patrick M, Hoste, Eric AJ, Joannes-Boyau, Olivier, Joannidis, Michael, Kim, Patrick, Koyner, Jay L, Laskowitz, Daniel T, Lissauer, Matthew E, Marx, Gernot, McCullough, Peter A, Mullaney, Scott, Ostermann, Marlies, Rimmelé, Thomas, Shapiro, Nathan I, Shaw, Andrew D, Shi, Jing, Sprague, Amy M, Vincent, Jean-Louis, Vinsonneau, Christophe, Wagner, Ludwig, Walker, Michael G, Wilkerson, R Gentry, Zacharowski, Kai, and Kellum, John A

Abstract

Abstract Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P 0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration ClinicalTrials.gov number NCT01209169.

Published
2013

39. Intravenous Lidocaine Does Not Improve Neurologic Outcomes after Cardiac Surgery: A Randomized Controlled Trial

Author

Klinger, Rebecca Y., Cooter, Mary, Bisanar, Tiffany, Terrando, Niccolò, Berger, Miles, Podgoreanu, Mihai V., Stafford-Smith, Mark, Newman, Mark F., Mathew, Joseph P., Blumenthal, James A., Karhausen, Jorn A., Kertai, Miklos D., Krishnamoorthy, Vijay, Li, Yi-Ju, Swaminathan, Madhav, Warner, David S., Funk, Bonita L., Brassard, Rachele, Toulgoat-Dubois, Yanne, Waweru, Peter, Babyak, Michael A., Blumenthal, James A., Browndyke, Jeffrey N., Welsh-Bohmer, Kathleen A., Sketch, Michael H., Jr., Bennett, Ellen R., Graffagnino, Carmelo, Laskowitz, Daniel T., Strittmatter, Warren J., Collins, Kevin, Smigla, Greg, Shearer, Ian, D’Amico, Thomas A., Daneshmand, Mani A., Gaca, Jeffrey G., Glower, Donald D., Haney, Jack, Harpole, David, Hartwig, Mathew G., Hughes, G. Chad, Klapper, Jacob A., Lin, Shu S., Lodge, Andrew J., Milano, Carmelo A., Plichta, Ryan P., Schroeder, Jacob N., Smith, Peter K., and Tong, Betty C.

Published
2019
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41. List of Contributors

Author

Alves, Timothy I., primary, Alves, Wayne M., additional, Bakken, Hans, additional, Balcer, Laura J., additional, Berk, Thomas, additional, Bladin, Christopher F., additional, Bleck, Thomas P., additional, Campbell, Bruce C.V., additional, Chakraborty, Shamik, additional, Davis, Stephen M., additional, Donnan, Geoffrey A., additional, Draghic, Nicole, additional, Ecklund, James, additional, Glushakov, Alexander V., additional, Glushakova, Olena Y., additional, Goyal, Mayank, additional, Greenberg, Jared A., additional, Grimes, Jamie, additional, Hainline, Clotilde, additional, Hayes, Ronald L., additional, Herman, Susan T., additional, Hill, Michael D., additional, Holodinsky, Jessalyn K., additional, Johnson, Steven B., additional, Kolls, Brad J., additional, Laskowitz, Daniel T., additional, Levy, Howard, additional, Ling, Geoffrey, additional, Lloyd-Smith, Alexandra, additional, Maas, Andrew I.R., additional, Macdonald, Robert Loch, additional, Mannix, Rebekah, additional, Marshall, Lawrence F., additional, Mayer, Stephan A., additional, Menon, David K., additional, Miller, Emmy R., additional, Narayan, Raj K., additional, Palesch, Yuko Y., additional, Rincon, Fred, additional, Rucker, Janet C., additional, Silberstein, Stephen D., additional, Skolnick, Brett E., additional, Tamhankar, Madhura A., additional, Temkin, Nancy, additional, Valadka, Alex B., additional, Wintermark, Max, additional, Yeatts, Sharon D., additional, and Zerna, Charlotte, additional

Published
2018
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42. Utilization and Outcomes of Extracorporeal Membrane Oxygenation Following Traumatic Brain Injury in the United States

Author

Hatfield, Jordan, primary, Ohnuma, Tetsu, additional, Soto, Alexandria L., additional, Komisarow, Jordan M., additional, Vavilala, Monica S., additional, Laskowitz, Daniel T., additional, James, Michael L., additional, Mathew, Joseph P., additional, Hernandez, Adrian F., additional, Goldstein, Benjamin A., additional, Treggiari, Miriam, additional, Raghunathan, Karthik, additional, and Krishnamoorthy, Vijay, additional

Published
2022
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44. Surgical Considerations to Improve Recovery in Acute Spinal Cord Injury

Author

Tabarestani, Troy Q., primary, Lewis, Nicholle E., additional, Kelly-Hedrick, Margot, additional, Zhang, Nina, additional, Cellini, Brianna R., additional, Marrotte, Eric J., additional, Williamson, Theresa, additional, Wang, Haichen, additional, Laskowitz, Daniel T., additional, Faw, Timothy D., additional, and Abd-El-Barr, Muhammad M., additional

Published
2022
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46. Analysis of Prescriptions for Dual Antiplatelet Therapy After Acute Ischemic Stroke

Author

Xian, Ying, primary, Xu, Haolin, additional, Matsouaka, Roland, additional, Laskowitz, Daniel T., additional, Maisch, Lesley, additional, Hannah, Deidre, additional, Smith, Eric E., additional, Fonarow, Gregg C., additional, Bhatt, Deepak L., additional, Schwamm, Lee H., additional, Mac Grory, Brian, additional, Feng, Wuwei, additional, Fosbøl, Emil Loldrup, additional, Peterson, Eric D., additional, and Johnson, Mark, additional

Published
2022
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50. 18F-florbetapir Positron Emission Tomography–determined Cerebral β-Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery

Author

Klinger, Rebecca Y., James, Olga G., Borges-Neto, Salvador, Bisanar, Tiffany, Li, Yi-Ju, Qi, Wenjing, Berger, Miles, Terrando, Niccolò, Newman, Mark F., Doraiswamy, P. Murali, Mathew, Joseph P., Weiner, Michael W., Aisen, Paul, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Shaw, Leslie M., Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, David, Mesulam, M. Marcel, Potter, William, Snyder, Peter, Schwartz, Adam, Green, Robert C., Montine, Tom, Petersen, Ronald, Aisen, Paul, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Balasubramanian, Archana B., Mason, Jennifer, Sim, Iris, Beckett, Laurel, Harvey, Danielle, Donohue, Michael, Jack, Clifford R., Jr., Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCArli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Jagust, William, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Morris, John C., Cairns, Louis Nigel J., Franklin, Erin, Taylor-Reinwald, Lisa, Shaw, Leslie M., Trojanowki, John Q., Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Toga, Arthur W., Crawford, Karen, Neu, Scott, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Weiner, Michael W., Thal, Lean, Khachaturian, Zaven, Thal, Leon, Buckholtz, Neil, Weiner, Michael W., Snyder, Peter J., Potter, William, Paul, Steven, Albert, Marilyn, Frank, Richard, Khachaturian, Zaven, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Silbert, Lisa, Lind, Betty, Carter, Raina, Dolen, Sara, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L., Lord, Joanne L., Petersen, Ronald, Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Pavlik, Valory, Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Ances, Beau, Morris, John C., Carroll, Maria, Creech, Mary L., Franklin, Erin, Mintun, Mark A., Schneider, Stacy, Oliver, Angela, Marson, Daniel, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, Shah, Raj C., deToledo-Morrell, Leyla, Duara, Ranjan, Greig-Custo, Maria T., Barker, Warren, Albert, Marilyn, Onyike, Chiadi, D’Agostino, Daniel, II, Kielb, Stephanie, Sadowski, Martin, Sheikh, Mohammed O., Ulysse, Anaztasia, Gaikwad, Mrunalini, Petrella, Jeffrey R., Wong, Terence Z., Coleman, Edward, Arnold, Steven E., Karlawish, Jason H., Wolk, David A., Clark, Christopher M., Smith, Charles D., Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Goldstein, Bonnie S., Martin, Kim, Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H.S., Lu, Po H., Bartzokis, George, Graff-Radford, Neill R, Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van Dyck, Christopher H., Carson, Richard E., MacAvoy, Martha G., Varma, Pradeep, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Ging-Yuek, Hsiung, Robin, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternack, Stephen, Rachisky, Irina, Trost, Dick, Kertesz, Andrew, Bernick, Charles, Munic, Donna, Mesulam, Marek-Marsel, Rogalski, Emily, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Yesavage, Jerome, Taylor, Joy L., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N., Belden, Christine M., Jacobson, Sandra A., Sirrel, Sherye A., Kowall, Neil, Killiany, Ronald, Budson, Andrew E., Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O., Wolday, Saba, Allard, Joanne, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Olichney, John, DeCarli, Charles, Carmichael, Owen, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Burke, Anna, Milliken, Ann Marie, Trncic, Nadira, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W., Kataki, Maria, Kelley, Brendan, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Sink, Kaycee M., Gordineer, Leslie, Williamson, Jeff D., Garg, Pradeep, Watkins, Franklin, Ott, Brian R., Tremont, Geoffrey, Daiello, Lori A., Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Perry, David, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Rogers, John, Kertesz, Andrew, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K., Smith, Karen Ekstam, Koleva, Hristina, Nam, Ki Won, Shim, Hyungsub, Relkin, Norman, Chiang, Gloria, Lin, Michael, Ravdin, Lisa, Smith, Amanda, Ashok Raj, Balebail, Fargher, Kristin, Weiner, Michael W., Aisen, Paul, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Green, Robert C., Harvey, Danielle, Jack, Clifford R., Jr., Jagust, William, Morris, John C., Saykin, Andrew J., Shaw, Leslie M., Toga, Arthur W., Trojanowki, John Q., Neylan, Thomas, Grafman, Jordan, Grafman, Jordan, Green, Robert C., Montine, Tom, Weiner, Michael, Petersen, Ronald, Aisen, Paul, Thomas, Ronald G., Donohue, Michael, Gessert, Devon, Sather, Tamie, Davis, Melissa, Morrison, Rosemary, Jiminez, Gus, Neylan, Thomas, Hayes, Jacqueline, Finely, Shannon, Harvey, Danielle, Donohue, Michael, Jack, Clifford R., Jr., Bernstein, Matthew, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Kantarci, Kejal, Ward, Chad, Jagust, William, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Landau, Susan, Morris, John C., Cairns, Nigel J., Householder, Erin, Shaw, Leslie M., Trojanowki, John Q., Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Toga, Arthur W., Crawford, Karen, Neu, Scott, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Weiner, Michael W., Friedl, Karl, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Brewer, James, Vanderswag, Helen, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Fleischman, Debra, Arfanakis, Konstantinos, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Greig, Maria T, Petrella, Jeffrey R., Porsteinsson, Anton P., Goldstein, Bonnie, Martin, Kimberly S., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Mintzer, Jacobo, Massoglia, Dino, Brawman-Mintzer, Olga, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Jagust, William, Landau, Susan, Rosen, Howard, Perry, David, Turner, Raymond Scott, Behan, Kelly, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Sabbagh, Marwan N., Jacobson, Sandra A., Sirrel, Sherye A., Obisesan, Thomas O., Wolday, Saba, Allard, Joanne, Johnson, Sterling C., Fruehling, J. Jay, Harding, Sandra, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Yesavage, Jerome A., Taylor, Joy L., Furst, Ansgar J., Chao, Steven, Relkin, Norman, Chiang, Gloria, Ravdin, Lisa, Blumenthal, James A., Karhausen, Jorn A., Kertai, Miklos D., Podgoreanu, Mihai V., Stafford-Smith, Mark, Swaminathan, Madhav, Warner, David S., Funk, Bonita L., Balajonda, Narai, Brassard, Rachele, Cooter, Mary, Toulgoat-Dubois, Yanne, Waweru, Peter, Babyak, Michael A., Blumenthal, James A., Browndyke, Jeffrey N., Welsh-Bohmer, Kathleen A., Sketch, Michael H., Jr., Bennett, Ellen R., Graffagnino, Carmelo, Laskowitz, Daniel T., Strittmatter, Warren J., Collins, Kevin, Smigla, Greg, Shearer, Ian, D’Amico, Thomas A., Daneshmand, Mani A., Gaca, R. Jeffrey G., Glower, Donald D., Haney, Jack, Harpole, R. David, Hartwig, Mathew G., Hughes, G. Chad, Klapper, Jacob A., Lin, Shu S., Lodge, Andrew J., Milano, Carmelo A., Plichta, Ryan P., Schroeder, Jacob N., Smith, Peter K., and Tong, Betty C.

Published
2018
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