Publications by authors named "Nathan J Reinert"

5 Publications

  • Page 1 of 1

Predictive Factors of Perioperative Stroke-Related Mortality Following Vascular Surgery: A Retrospective Analysis.

J Stroke Cerebrovasc Dis 2021 Jul 5;30(7):105833. Epub 2021 May 5.

Departments of Neurology and Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States. Electronic address:

Objective: Vascular surgical procedures have one of the highest risks of perioperative stroke and stroke-related mortality, yet the independent risk factors contributing to this increased mortality have not been described. Perioperative strokes are thought to result from a combination of embolism and hypoperfusion mechanisms. The purpose of this study is to describe the independent predictors of perioperative stroke-related mortality in the vascular surgical population using the Pennsylvania Health Care Cost Containment Council (PHC4) database which collects cause of death data.

Methods: This retrospective, case-control study evaluated 4,128 patients aged 18-99 who underwent a vascular, non-carotid surgical procedure and subsequently suffered perioperative mortality. Common surgical comorbidities and risk factors for perioperative stroke, including carotid stenosis and atrial fibrillation, were evaluated in multivariate regression analysis.

Results: Patients with carotid stenosis were 2.6 (aOR, 95% CI 1.4-4.5) times more likely to suffer perioperative mortality from stroke than from other causes. Additionally, in-hospital stroke, history of stroke, admission from a healthcare facility, and cancer were all positive predictive factors, whereas atrial fibrillation, emergency admission, hypertension, and diabetes were associated with decreased risk of perioperative stroke-related mortality.

Conclusions: Identification of vascular surgical population-specific predictors of stroke-related mortality can help to enhance preoperative risk-stratification tools and guide perioperative management of identified high-risk patients. Increased neurophysiologic monitoring in the perioperative period to prevent delays in diagnosis of perioperative stroke offers a strategy to reduce risk of perioperative stroke-related mortality in vascular surgical patients.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105833DOI Listing
July 2021

The Role of Phosphodiesterase-5 Inhibitors in COVID-19: An Exploration of Literature From Similar Pathologies.

J Intensive Care Med 2021 Jan 10;36(1):3-8. Epub 2020 Sep 10.

The University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Coronavirus Disease 2019 (COVID-19) has had a devastating impact on the ability of highly trained healthcare providers to render sufficient care, due to both the significant demand on resources and the unique nature of this disease that make it resistant to traditional therapies. This review sought to determine the potential role of phosphodiesterase-5 inhibitors (PDE-5) in the management of COVID-19 by extrapolating relevant data and clinical studies from other related disease states, including acute respiratory distress syndrome, acute lung injury, and high altitude pulmonary edema. Following a literature search, 4 reports were analyzed and included in this review. While the heterogenicity of data and the small number of trials included limit the interpretation and applicability, it was consistently demonstrated that PDE-5 inhibitors lowered pulmonary arterial pressures. The overall benefit of these agents is seemingly dependent upon the etiology of the respiratory failure, which warrants expanded clinical investigation for COVID-19.
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http://dx.doi.org/10.1177/0885066620957951DOI Listing
January 2021

Perioperative stroke-related mortality after non-cardiovascular, non-neurological procedures: A retrospective risk factor evaluation of common surgical comorbidities.

J Perioper Pract 2021 Mar 17;31(3):80-88. Epub 2020 Apr 17.

Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Perioperative stroke-related mortality in the non-cardiovascular, non-neurological surgery population is an uncommon, yet devastating outcome. A combination of emboli and hypoperfusion may cause large vessel occlusions leading to perioperative strokes and mortality. Identifying independent risk factors for perioperative stroke-related mortality may enhance risk-stratification algorithms and preventative therapies.

Objectives: This study utilised cause-of-death data to determine independent risk scores for common surgical comorbidities that may lead to perioperative stroke-related mortality, including atrial fibrillation and asymptomatic carotid stenosis.

Methods: This retrospective, IRB-exempt, case-control study evaluated non-cardiovascular, non-neurological surgical patients in a claims-based database. ICD-10-CM and ICD-9-CM codes identified cause of death and comorbidity incidences, respectively. A multivariate regression analysis then established adjusted independent risk scores of each comorbidity in relation to perioperative stroke-related mortality.

Results: Patients with atrial fibrillation were more likely (1.7 aOR, 95% CI (1.1, 2.8) p = 0.02) to die from perioperative stroke-related mortality than from other causes. No association was found with asymptomatic carotid stenosis. Further, in-hospital strokes (25.9 aOR, 95% CI (16.0, 41.8) p < 0.001) or diabetes (1.8 aOR, 95% CI (1.1, 2.9) p = 0.02) may increase perioperative stroke-related mortality risk.

Conclusions: Atrial fibrillation, diabetes and in-hospital strokes may be independent risk factors for perioperative stroke-related mortality in the non-cardiovascular, non-neurological surgery population.
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http://dx.doi.org/10.1177/1750458920911830DOI Listing
March 2021

Independent Predictors of Perioperative Stroke-Related Mortality after Cardiac Surgery.

J Stroke Cerebrovasc Dis 2020 May 14;29(5):104711. Epub 2020 Mar 14.

Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address:

Background And Purpose: Perioperative stroke remains a devastating complication after cardiac surgery and is associated with significant morbidity and mortality. Despite the significant contribution of stroke to perioperative mortality, risk factors for perioperative stroke-related mortality have not been well characterized. Our aim was to identify independent predictors of perioperative stroke-related mortality after cardiac surgery, using the Pennsylvania Health Care Cost Containment Council (PHC4) database which provides information on cause of death.

Methods: We retrospectively examined patient medical records from 2012 to 2014 of 3345 patients (ages 18-99) who underwent a cardiac surgical procedure and suffered perioperative (30-day) mortality. Perioperative stroke-related mortality was identified by International Classification of Diseases, Tenth Revision, Clinical Modification cause of death codes. We performed Fisher's exact test and multivariate analysis to identify comorbidities that independently predict perioperative stroke-related mortality.

Results: After controlling for all variables with multivariate analysis, we found that patients with carotid stenosis were 4.9 (adjusted odds ratio [aOR], 95% confidence interval [CI] 1.8-12.8) times more likely to die from a stroke than from other causes, when compared to patients without carotid stenosis. Other independent predictors of perioperative stroke-related mortality included in-hospital stroke (aOR 108.8, 95%CI 48.2-245.9), history of stroke (aOR 17.1, 95%CI 3.3-88.4), and age ≥ 80 (aOR 4.9, 95%CI 2.1-11.2).

Conclusions: This is the first study to establish carotid stenosis, among other comorbidities, as an independent predictor of perioperative stroke-related mortality after cardiac surgery. Understanding risk factors for mortality from stroke will help enhance the efficacy of preoperative screening, intraoperative neurophysiological monitoring, and potential treatments for stroke. Interventions to manage carotid stenosis and other identified risk factors prior to, during, or immediately after surgery may have the potential to reduce perioperative stroke-related mortality after cardiac surgery.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104711DOI Listing
May 2020

Functional Human α7 Nicotinic Acetylcholine Receptor (nAChR) Generated from Escherichia coli.

J Biol Chem 2016 08 6;291(35):18276-82. Epub 2016 Jul 6.

From the Departments of Anesthesiology, Pharmacology and Chemical Biology, and Computational & Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260

Human Cys-loop receptors are important therapeutic targets. High-resolution structures are essential for rational drug design, but only a few are available due to difficulties in obtaining sufficient quantities of protein suitable for structural studies. Although expression of proteins in E. coli offers advantages of high yield, low cost, and fast turnover, this approach has not been thoroughly explored for full-length human Cys-loop receptors because of the conventional wisdom that E. coli lacks the specific chaperones and post-translational modifications potentially required for expression of human Cys-loop receptors. Here we report the successful production of full-length wild type human α7nAChR from E. coli Chemically induced chaperones promote high expression levels of well-folded proteins. The choice of detergents, lipids, and ligands during purification determines the final protein quality. The purified α7nAChR not only forms pentamers as imaged by negative-stain electron microscopy, but also retains pharmacological characteristics of native α7nAChR, including binding to bungarotoxin and positive allosteric modulators specific to α7nAChR. Moreover, the purified α7nAChR injected into Xenopus oocytes can be activated by acetylcholine, choline, and nicotine, inhibited by the channel blockers QX-222 and phencyclidine, and potentiated by the α7nAChR specific modulators PNU-120596 and TQS. The successful generation of functional human α7nAChR from E. coli opens a new avenue for producing mammalian Cys-loop receptors to facilitate structure-based rational drug design.
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http://dx.doi.org/10.1074/jbc.M116.729970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000075PMC
August 2016