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155. Risks and Benefits Associated With Prestroke Antiplatelet Therapy Among Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator

Author

Hernandez, Adrian F., Laskowitz, Daniel T., Federspiel, Jerome J., Bhatt, Deepak L., Fonarow, Gregg C., Bettger, Janet Prvu, Webb, Laura, Grau-Sepulveda, Maria, Xian, Ying, Thomas, Laine, Schwamm, Lee H., Reeves, Mathew J., Peterson, Eric D., and Smith, Eric E.

Subjects
cardiovascular diseases
Abstract

IMPORTANCE: Intravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, many patients may have been receiving antiplatelet therapy before acute ischemic stroke and could face an increased risk for bleeding when treated with tPA. OBJECTIVE: To assess the risks and benefits associated with prestroke antiplatelet therapy among patients with ischemic stroke who receive intravenous tPA. DESIGN, SETTING, AND PARTICIPANTS: This observational study used data from the American Heart Association and American Stroke Association Get With the Guidelines-Stroke registry, which included 85 072 adult patients with ischemic stroke who received intravenous tPA in 1545 registry hospitals from January 1, 2009, through March 31, 2015. Data were analyzed during the same period. EXPOSURES: Prestroke antiplatelet therapy before tPA administration for acute ischemic stroke. MAIN OUTCOMES AND MEASURES: Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, discharge ambulatory status, and modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]). RESULTS: Of the 85 072 registry patients, 38 844 (45.7%) were receiving antiplatelet therapy before admission; 46 228 patients (54.3%) were not. Patients receiving antiplatelet therapy were older (median [25th-75th percentile] age, 76 [65-84] vs 68 [56-80] years) and had a higher prevalence of cardiovascular risk factors. The unadjusted rate of sICH was higher in patients receiving antiplatelet therapy (5.0% vs 3.7%). After risk adjustment, prior use of antiplatelet agents remained associated with higher odds of sICH compared with no use (adjusted odds ratio [AOR], 1.18 [95% CI, 1.10-1.28]; absolute difference, +0.68% [95% CI, 0.36%-1.01%]; number needed to harm [NNH], 147). Among patients enrolled on October 1, 2012, or later, the highest odds (95% CIs) of sICH were found in 15 116 patients receiving aspirin alone (AOR, 1.19 [1.06- 1.34]; absolute difference [95% CI], +0.68% [0.21%-1.20%]; NNH, 147) and 2397 patients receiving dual antiplatelet treatment of aspirin and clopidogrel (AOR, 1.47 [1.16-1.86]; absolute difference, +1.67% [0.58%-3.00%]; NNH, 60). The risk for in-hospital mortality was similar between those who were and were not receiving antiplatelet therapy after adjustment (8.0% vs 6.6%; AOR, 1.00 [0.94-1.06]; nonsignificant absolute difference, -0.01% [-0.37% to 0.36%]). However, patients receiving antiplatelet therapy had a greater risk-adjusted likelihood of independent ambulation (42.1% vs 46.6%; AOR, 1.13 [1.08-1.17]; absolute difference, +2.23% [1.55%-2.92%]; number needed to treat, 43) and better functional outcomes (modified Rankin Scale score, 0-1) at discharge (24.1% vs 27.8%; AOR, 1.14; 1.07-1.22; absolute difference, +1.99% [0.78%-3.22%]; number needed to treat, 50). CONCLUSIONS AND RELEVANCE: Among patients with an acute ischemic stroke treated with intravenous tPA, those receiving antiplatelet therapy before the stroke had a higher risk for sICH but better functional outcomes than those who were not receiving antiplatelet therapy.

Published
2016
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156. Genetic polymorphisms associated with the risk of concussion in 1056 college athletes: a multicentre prospective cohort study

Author

Terrell, Thomas Roland, primary, Abramson, Ruth, additional, Barth, Jeffery T, additional, Bennett, Ellen, additional, Cantu, Robert C, additional, Sloane, Richard, additional, Laskowitz, Daniel T, additional, Erlanger, David M, additional, McKeag, Douglas, additional, Nichols, Gregory, additional, Valentine, Verle, additional, and Galloway, Leslie, additional

Published
2017
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157. Preventing Episodic Migraine With Caloric Vestibular Stimulation: A Randomized Controlled Trial

Author

Wilkinson, David, primary, Ade, Kristen K., additional, Rogers, Lesco L., additional, Attix, Deborah K., additional, Kuchibhatla, Maragatha, additional, Slade, Martin D., additional, Smith, Lanty L., additional, Poynter, Kathryn P., additional, Laskowitz, Daniel T., additional, Freeman, Marshall C., additional, Hoffer, Michael E., additional, Saper, Joel R., additional, Scott, Dianne L., additional, Sakel, Mohamed, additional, Calhoun, Anne H., additional, and Black, Robert D., additional

Published
2017
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158. Neuroprotective pentapeptide CN-105 is associated with reduced sterile inflammation and improved functional outcomes in a traumatic brain injury murine model

Author

Laskowitz, Daniel T., primary, Wang, Haichen, additional, Chen, Tony, additional, Lubkin, David T., additional, Cantillana, Viviana, additional, Tu, Tian Ming, additional, Kernagis, Dawn, additional, Zhou, Guanen, additional, Macy, Gary, additional, Kolls, Bradley J., additional, and Dawson, Hana N., additional

Published
2017
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166. 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

Runqi Wangqin, Laskowitz, Daniel T., Yongjun Wang, Zixiao Li, Yilong Wang, Liping Liu, Li Liang, 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., Ying Xian, Wangqin, Runqi, Wang, Yongjun, and Li, Zixiao

Published
2018
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167. Transformative Impact of Proteomics on Cardiovascular Health and Disease

Author

Lindsey, Merry L., primary, Mayr, Manuel, additional, Gomes, Aldrin V., additional, Delles, Christian, additional, Arrell, D. Kent, additional, Murphy, Anne M., additional, Lange, Richard A., additional, Costello, Catherine E., additional, Jin, Yu-Fang, additional, Laskowitz, Daniel T., additional, Sam, Flora, additional, Terzic, Andre, additional, Van Eyk, Jennifer, additional, and Srinivas, Pothur R., additional

Published
2015
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168. APIXABAN FOLLOWING ACUTE CORONARY SYNDROMES AMONG PATIENTS WITH PRIOR STROKE: INSIGHTS FROM THE APPRAISE-2 TRIAL

Author

Sherwood, Matthew, primary, Lopes, Renato, additional, Sun, Jie-Lena, additional, Harrington, Robert, additional, Wallentin, Lars, additional, Laskowitz, Daniel T., additional, James, Stefan, additional, Goodman, Shaun, additional, Darius, Harald, additional, Lewis, Basil, additional, Liaw, Danny, additional, Gibson, C. Michael, additional, and Alexander, John, additional

Published
2015
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170. The Effect of Propofol vs. Isoflurane Anesthesia on Postoperative Changes in Cerebrospinal Fluid Cytokine Levels: Results from a Randomized Trial.

Author

Berger, Miles, Ponnusamy, Vikram, Greene, Nathaniel, Cooter, Mary, Nadler, Jacob W., Friedman, Allan, McDonagh, David L., Laskowitz, Daniel T., Newman, Mark F., Shaw, Leslie M., Warner, David S., Mathew, Joseph P., and James, Michael L.

Subjects
CEREBROSPINAL fluid, CYTOKINES, ISOFLURANE
Abstract

Introduction: Aside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. In vitro and mouse model studies suggest that propofol inhibits, while isoflurane increases, neuroinflammation. If these findings translate to humans, they could be clinically important since neuroinflammation has detrimental effects on neurocognitive function in numerous disease states. Materials and methods: To examine whether propofol and isoflurane differentially modulate neuroinflammation in humans, cytokines were measured in a secondary analysis of cerebrospinal fluid (CSF) samples from patients prospectively randomized to receive anesthetic maintenance with propofol vs. isoflurane (registered with http://www. clinicaltrials.gov, identifier NCT01640275). We measured CSF levels of EGF, eotaxin, G-CSF, GM-CSF, IFN-α2, IL-1RA, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α before and 24 h after intracranial surgery in these study patients. Results: After Bonferroni correction for multiple comparisons, we found significant increases from before to 24 h after surgery in G-CSF, IL-10, IL-1RA, IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α. However, we found no difference in cytokine levels at baseline or 24 h after surgery between propofol- (n = 19) and isoflurane-treated (n = 21) patients (p > 0.05 for all comparisons). Increases in CSF IL-6, IL-8, IP-10, and MCP-1 levels directly correlated with each other and with postoperative CSF elevations in tau, a neural injury biomarker. We observed CSF cytokine increases up to 10-fold higher after intracranial surgery than previously reported after other types of surgery. Discussion: These data clarify the magnitude of neuroinflammation after intracranial surgery, and raise the possibility that a coordinated neuroinflammatory response may play a role in neural injury after surgery. [ABSTRACT FROM AUTHOR]

Published
2017
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172. Phase 1 Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety, Tolerability, and Pharmacokinetics of a Single Escalating Dose and Repeated Doses of CN-105 in Healthy Adult Subjects.

Author

Guptill, Jeffrey T., Raja, Shruti M., Boakye‐Agyeman, Felix, Noveck, Robert, Ramey, Sarah, Tu, Tian Ming, and Laskowitz, Daniel T.

Subjects
APOLIPOPROTEINS, CEREBRAL hemorrhage, MEDICAL protocols, PHARMACOKINETICS, RANDOMIZED controlled trials, NEUROPROTECTIVE agents, BLIND experiment, DISEASE complications
Abstract

Spontaneous intracranial hemorrhage (ICH) remains a devastating stroke subtype, affecting as many as 80,000 people annually in the United States and associated with extremely high mortality. In the absence of any pharmacological interventions demonstrated to improve outcome, care for patients with ICH remains largely supportive. Thus, despite advances in the understanding of ICH and brain injury, there remains an unmet need for interventions that improve neurologic recovery and outcomes. Recent research suggesting inflammation and APOE genotype play a role in modifying neurologic outcome after brain injury has led to the development of an APOE-derived peptide agent (CN-105). Preclinical studies have demonstrated that CN-105 effectively downregulates the inflammatory response in acute brain injury, including ICH. Following Investigational New Drug (IND) enabling studies in murine models, this first-in-human single escalating dose and multiple dose placebo-controlled clinical trial was performed to define the safety and pharmacokinetics (PK) of CN-105. A total of 48 subjects (12 control, 36 active) were randomized in this study; all subjects completed the study. No significant safety issues were identified with both dosing regimens, and PK analysis revealed linearity without significant drug accumulation. The median half-life in the terminal elimination phase of CN-105 following a single or repeated dosing regimen did not change (approximately 3.6 hours). With the PK and preliminary safety of CN-105 established, the drug is now poised to begin first-in-disease phase 2 clinical trials in patients with ICH who urgently need new therapeutic options. [ABSTRACT FROM AUTHOR]

Published
2017
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174. Neighborhood Socioeconomic Status and the Prevalence of Stroke and Coronary Heart Disease in Rural China: A Population-Based Study

Author

Tang, Xun, primary, Laskowitz, Daniel T., additional, He, Liu, additional, Østbye, Truls, additional, Bettger, Janet Prvu, additional, Cao, Yang, additional, Li, Na, additional, Li, Jingrong, additional, Zhang, Zongxin, additional, Liu, Jianjiang, additional, Yu, Liping, additional, Xu, Haitao, additional, Hu, Yonghua, additional, and Goldstein, Larry B., additional

Published
2014
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175. Statins and Delirium During Critical Illness

Author

Morandi, Alessandro, primary, Hughes, Christopher G., additional, Thompson, Jennifer L., additional, Pandharipande, Pratik P., additional, Shintani, Ayumi K., additional, Vasilevskis, Eduard E., additional, Han, Jin H., additional, Jackson, James C., additional, Laskowitz, Daniel T., additional, Bernard, Gordon R., additional, Ely, E. Wesley, additional, and Girard, Timothy D., additional

Published
2014
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179. Abstract 7: Risk of Intracranial Hemorrhage Among Acute Ischemic Stroke Patients Receiving Prior Antiplatelet Therapy and Treated with Intravenous Tissue Plasminogen Activator

Author

Xian, Ying, primary, Grau-Spulveda, Maria, additional, Schwamm, Lee H, additional, Bhatt, Deepak L, additional, Smith, Eric E, additional, Reeves, Mathew J, additional, Federspiel, Jerome, additional, Thomas, Laine, additional, Bettger, Janet P, additional, Laskowitz, Daniel T, additional, Hernandez, Adrian F, additional, Fonarow, Gregg C, additional, and Peterson, Eric D, additional

Published
2014
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185. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

Author

Kashani, Kianoush, 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, Kellum, John A, Kashani, Kianoush, 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

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 <0.002), none of which achieved an AUC >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

Published
2013

187. Genetic polymorphisms associated with the risk of concussion in 1056 college athletes: a multicentre prospective cohort study

Author

Terrell, Thomas Roland, Abramson, Ruth, Barth, Jeffery T, Bennett, Ellen, Cantu, Robert C, Sloane, Richard, Laskowitz, Daniel T, Erlanger, David M, McKeag, Douglas, Nichols, Gregory, Valentine, Verle, and Galloway, Leslie

Abstract

Background/aimTo evaluate the association of genetic polymorphisms APOE, APOEG-219T promoter, microtubule associated protein(MAPT)/tauexon 6 Ser53Pro, MAPT/tauHist47Tyr, IL-6572 G/C and IL-6RAsp358Alawith the risk of concussion in college athletes.MethodsA 23-centre prospective cohort study of 1056 college athletes with genotyping was completed between August 2003 and December 2012. All athletes completed baseline medical and concussion questionnaires, and post-concussion data were collected for athletes with a documented concussion.ResultsThe study cohort consisted of 1056 athletes of mean±SD age 19.7±1.5 years,89.3% male, 59.4% Caucasian, 35.0% African-American, 5.6% other race. The athletes participated in American football, soccer, basketball, softball, men’s wrestling and club rugby. A total of 133 (12.1% prevalence) concussions occurred during an average surveillance of 3 years per athlete. We observed a significant positive association between IL-6RCC (p=0.001) and a negative association between APOE4 (p=0.03) and the risk of concussion. Unadjusted and adjusted logistic regression analysis showed a significant association between IL-6RCC and concussion (OR 3.48; 95% CI 1.58 to 7.65; p=0.002) and between the APOE4 allele and concussion (OR 0.61; 95% CI 0.38 to 0.96; p=0.04), which persisted after adjustment for confounders.ConclusionsIL-6RCC was associated with a three times greater concussion risk and APOE4 with a 40% lower risk.

Published
2018
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193. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

Author

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

Published
2013
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194. Apolipoprotein E modifies the CNS response to injury via a histamine-mediated pathway.

Author

UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, Mace, Brian E, Wang, Haichen, Lynch, John R, Moss, Jason, Sullivan, Patrick, Colton, Heidi, Morgan, Kevin, Renauld, Jean-Christophe, Laskowitz, Daniel T, UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, Mace, Brian E, Wang, Haichen, Lynch, John R, Moss, Jason, Sullivan, Patrick, Colton, Heidi, Morgan, Kevin, Renauld, Jean-Christophe, and Laskowitz, Daniel T

Abstract

Recent evidence demonstrates that apolipoprotein E (apoE) influences the central nervous system (CNS) response to both acute and chronic injury. To address the mechanisms by which apoE influences neurological disease, we examined differential gene expression in the brains of apoE transgenic mice after closed head injury. Apart from confirming the knockout of apoE, the largest differential gene expression occurred for the interleukin-9 receptor (IL-9R), which was > 100-fold up-regulated in apoE-deficient versus wild-type mice. We observed a similar pattern of posttraumatic IL-9R up-regulation in APOE4 targeted replacement mice as compared with their APOE3 counterparts. This difference in gene expression was associated with increased neuronal protein expression of IL-9R in E4 animals compared with E3 as demonstrated by immunohistochemistry. The consequence of IL-9R binding in mast cells is the induction of proliferation and differentiation. This indirectly favors degranulation and release of histamine and inflammatory mediators, which have previously been demonstrated to exacerbate secondary neuronal injury. We found that apoE-deficient animals had increased levels of systemic histamine after injury and that pre-treatment with antihistamines improved functional outcomes in apoE-deficient but not wild-type animals after head injury. These results suggest that apoE modifies secondary neuronal injury caused by histamine release and are consistent with previous observations that apoE affects the CNS inflammatory response in an isoform-specific manner.

Published
2007

195. The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial.

Author

Berger, Miles, Nadler, Jacob W., Friedman, Allan, McDonagh, David L., Bennett, Ellen R., Cooter, Mary, Wenjing Qi, Laskowitz, Daniel T., Ponnusamy, Vikram, Newman, Mark F., Shaw, Leslie M., Warner, David S., Mathew, Joseph P., and James, Michael L.

Subjects
PROPOFOL, ISOFLURANE, ANESTHESIA, CEREBROSPINAL fluid examination, ALZHEIMER'S patients, NEUROSURGERY complications, THERAPEUTICS
Abstract

Background: Preclinical studies have found differential effects of isoflurane and propofol on the Alzheimer's disease (AD)- associated markers tau, phosphorylated tau (p-tau) and amyloid-β (Aβ). Objective: We asked whether isoflurane and propofol have differential effects on the tau/Aβ ratio (the primary outcome), and individual AD biomarkers. We also examined whether genetic/intraoperative factors influenced perioperative changes in AD biomarkers. Methods: Patients undergoing neurosurgical/otolaryngology procedures requiring lumbar cerebrospinal fluid (CSF) drain placement were prospectively randomized to receive isoflurane (n = 21) or propofol (n = 18) for anesthetic maintenance. We measured perioperative CSF sample AD markers, performed genotyping assays, and examined intraoperative data from the electronic anesthesia record. A repeated measures ANOVA was used to examine changes in AD markers by anesthetic type over time. Results: The CSF tau/A ratio did not differ between isoflurane- versus propofol-treated patients (p = 1.000). CSF tau/Aβ ratio and tau levels increased 10 and 24 h after drain placement (p = 2.002×10-6 and p = 1.985×10--6, respectively), mean CSF p-tau levels decreased (p = 0.005), and Aβ levels did not change (p = 0.152). There was no interaction between anesthetic treatment and time for any of these biomarkers. None of the examined genetic polymorphisms, including ApoE4, were associated with tau increase (n = 9 polymorphisms, p > 0.05 for all associations). Conclusion: Neurosurgery/otolaryngology procedures are associated with an increase in the CSF tau/A ratio, and this increase was not influenced by anesthetic type. The increased CSF tau/A ratio was largely driven by increases in tau levels. Futurework should determine the functional/prognostic significance of these perioperative CSF tau elevations. [ABSTRACT FROM AUTHOR]

Published
2016
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200. Intraoperative Magnesium Administration Does Not Improve Neurocognitive Function After Cardiac Surgery

Author

Mathew, Joseph P., White, William D., Schinderle, David B., Podgoreanu, Mihai V., Berger, Miles, Milano, Carmelo A., Laskowitz, Daniel T., Stafford-Smith, Mark, Blumenthal, James A., Newman, Mark F., Mathew, Joseph P., Blumenthal, James A., Fontes, Manuel A., Kertai, Miklos D., Lombard, Frederick W., Mathew, Joseph P., McDonagh, David L., Monk, Terri G., Newman, Mark F., Podgoreanu, Mihai V., Stafford-Smith, Mark, Swaminathan, Madhav, Warner, David S., Funk, Bonita L., Balajonda, Narai, Hall, Roger L., Bisanar, Tiffany, Clemmons, Karen L., Li, Yi-Ju, Pecora, Greg, Phillips-Bute, Barbara, Toulgoat-Dubois, Yanne, Waweru, Peter, White, William D., Babyak, Michael A., Blumenthal, James A., Browndyke, Jeffrey N., Welsh-Bohmer, Kathleen A., Mark, Daniel B., Sketch, Michael H., Bennett, Ellen R., Graffagnino, Carmelo, Laskowitz, Daniel T., Strittmatter, Warren J., Alexander, Stanlin, Collins, Kevin, Smigla, Greg, Shearer, Ian, Berry, Mark F., D’Amico, Thomas A., Daneshmand, Mani A., Davis, R. Duane, Gaca, Jeffrey G., Glower, Donald D., Harpole, R. David, Hughes, G. Chad, Jaquiss, Robert D.B., Lin, Shu S., Lodge, Andrew J., Milano, Carmelo A., Onaitis, Mark W., Schroeder, Jacob N., Smith, Peter K., and Tong, Betty C.

Abstract

Neurocognitive decline occurs frequently after cardiac surgery and persists in a significant number of patients. Magnesium is thought to provide neuroprotection by preservation of cellular energy metabolism, blockade of the N-methyl-D-aspartate receptor, diminution of the inflammatory response, and inhibition of platelet activation. We therefore hypothesized that intraoperative magnesium administration would decrease postoperative cognitive impairment.

Published
2013
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