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Arterial Ischemic Stroke Secondary to Cardiac Disease in Neonates and Children.
Chung MG, Guilliams KP, Wilson JL, Beslow LA, Dowling MM, Friedman NR, Hassanein SMA, Ichord R, Jordan LC, Mackay MT, Rafay MF, Rivkin M, Torres M, Zafeiriou D, deVeber G, Fox CK, International Pediatric Stroke Study Investigators
(2019) Pediatr Neurol 100: 35-41
MeSH Terms: Brain Ischemia, Cardiac Surgical Procedures, Child, Child, Preschool, Female, Heart Diseases, Humans, Infant, Infant, Newborn, Infant, Newborn, Diseases, Intracranial Arterial Diseases, Intraoperative Complications, Male, Postoperative Complications, Registries, Stroke, Thromboembolism
Show Abstract · Added March 24, 2020
OBJECTIVE - We describe the risk factors for peri-procedural and spontaneous arterial ischemic stroke (AIS) in children with cardiac disease.
METHODS - We identified children with cardiac causes of AIS enrolled in the International Pediatric Stroke Study registry from January 2003 to July 2014. Isolated patent foramen ovale was excluded. Peri-procedural AIS (those occurring during or within 72 hours of cardiac surgery, cardiac catheterization, or mechanical circulatory support) and spontaneous AIS that occurred outside of these time periods were compared.
RESULTS - We identified 672 patients with congenital or acquired cardiac disease as the primary risk factor for AIS. Among these, 177 patients (26%) had peri-procedural AIS and 495 patients (74%) had spontaneous AIS. Among non-neonates, spontaneous AIS occurred at older ages (median 4.2 years, interquartile range 0.97 to 12.4) compared with peri-procedural AIS (median 2.4 years, interquartile range 0.35 to 6.1, P < 0.001). About a third of patients in both groups had a systemic illness at the time of AIS. Patients who had spontaneous AIS were more likely to have a preceding thrombotic event (16 % versus 9 %, P = 0.02) and to have a moderate or severe neurological deficit at discharge (67% versus 33%, P = 0.01) compared to those with peri-procedural AIS.
CONCLUSIONS - Children with cardiac disease are at risk for AIS at the time of cardiac procedures but also outside of the immediate 72 hours after procedures. Many have acute systemic illness or thrombotic event preceding AIS, suggesting that inflammatory or prothrombotic conditions could act as a stroke trigger in this susceptible population.
Copyright © 2019 Elsevier Inc. All rights reserved.
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17 MeSH Terms
Endothelial-Dependent Vasomotor Dysfunction in Infants After Cardiopulmonary Bypass.
Krispinsky LT, Stark RJ, Parra DA, Luan L, Bichell DP, Pietsch JB, Lamb FS
(2020) Pediatr Crit Care Med 21: 42-49
MeSH Terms: Acetylcholine, Biomarkers, Cardiac Surgical Procedures, Cardiopulmonary Bypass, Cardiovascular Diseases, Child, Child, Preschool, Cytokines, Endothelium, Vascular, Heart Defects, Congenital, Humans, Infant, Microcirculation, Nitric Oxide, Pilot Projects, Postoperative Complications, Prospective Studies, Severity of Illness Index, Vascular Resistance, Vasodilator Agents, Vasomotor System
Show Abstract · Added July 2, 2019
OBJECTIVES - Cardiopulmonary bypass-induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, alterations in circulating biomarkers, and postoperative capillary leak. Endothelial-dependent vasomotor dysfunction of the systemic vasculature has never been quantified in this setting. The objective of the present study was to quantify acute effects of cardiopulmonary bypass on endothelial vasomotor control and attempt to correlate these effects with postoperative cytokines, tissue edema, and clinical outcomes in infants.
DESIGN - Single-center prospective observational cohort pilot study.
SETTING - Pediatric cardiac ICU at a tertiary children's hospital.
PATIENTS - Children less than 1 year old requiring cardiopulmonary bypass for repair of a congenital heart lesion.
INTERVENTION - None.
MEASUREMENTS AND MAIN RESULTS - Laser Doppler perfusion monitoring was coupled with local iontophoresis of acetylcholine (endothelium-dependent vasodilator) or sodium nitroprusside (endothelium-independent vasodilator) to quantify endothelial-dependent vasomotor function in the cutaneous microcirculation. Measurements were obtained preoperatively, 2-4 hours, and 24 hours after separation from cardiopulmonary bypass. Fifteen patients completed all laser Doppler perfusion monitor (Perimed, Järfälla, Sweden) measurements. Comparing prebypass with 2-4 hours postbypass responses, there was a decrease in both peak perfusion (p = 0.0006) and area under the dose-response curve (p = 0.005) following acetylcholine, but no change in responses to sodium nitroprusside. Twenty-four hours after bypass responsiveness to acetylcholine improved, but typically remained depressed from baseline. Conserved endothelial function was associated with higher urine output during the first 48 postoperative hours (R = 0.43; p = 0.008).
CONCLUSIONS - Cutaneous endothelial dysfunction is present in infants immediately following cardiopulmonary bypass and recovers significantly in some patients within 24 hours postoperatively. Confirmation of an association between persistent endothelial-dependent vasomotor dysfunction and decreased urine output could have important clinical implications. Ongoing research will explore the pattern of endothelial-dependent vasomotor dysfunction after cardiopulmonary bypass and its relationship with biochemical markers of inflammation and clinical outcomes.
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21 MeSH Terms
Molecular and mechanical factors contributing to ductus arteriosus patency and closure.
Crockett SL, Berger CD, Shelton EL, Reese J
(2019) Congenit Heart Dis 14: 15-20
MeSH Terms: Cardiac Surgical Procedures, Ductus Arteriosus, Ductus Arteriosus, Patent, Hemodynamics, Humans, Infant, Newborn, Oxidative Stress
Show Abstract · Added November 26, 2018
Regulation of the ductus arteriosus, an essential fetal vessel connecting the pulmonary artery and aorta, is complex. Failure of this vessel to close after birth may result in a persistent left-to-right shunt through the patent ductus arteriosus, a condition associated with significant morbidities. Numerous factors contribute to the shift from fetal ductus patency to postnatal closure, requiring precise coordination of molecular cues with biomechanical forces and underlying genetic influences. Despite significant advances, questions remain regarding signaling dynamics and the natural time course of ductus closure, particularly in preterm neonates. This review highlights the contributions of early investigators and more recent clinician scientists to our understanding of the molecular and mechanical factors that mediate ductus patency and closure.
© 2019 Wiley Periodicals, Inc.
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7 MeSH Terms
Association Between Early Postoperative Acetaminophen Exposure and Acute Kidney Injury in Pediatric Patients Undergoing Cardiac Surgery.
Van Driest SL, Jooste EH, Shi Y, Choi L, Darghosian L, Hill KD, Smith AH, Kannankeril PJ, Roden DM, Ware LB
(2018) JAMA Pediatr 172: 655-663
MeSH Terms: Acetaminophen, Acute Kidney Injury, Antioxidants, Cardiac Surgical Procedures, Child, Preschool, Creatinine, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Infant, Male, Postoperative Care, Postoperative Complications, Postoperative Period, Retrospective Studies, Treatment Outcome
Show Abstract · Added March 24, 2020
Importance - Acute kidney injury (AKI) is a common and serious complication for pediatric cardiac surgery patients associated with increased morbidity, mortality, and length of stay. Current strategies focus on risk reduction and early identification because there are no known preventive or therapeutic agents. Cardiac surgery and cardiopulmonary bypass lyse erythrocytes, releasing free hemoglobin and contributing to oxidative injury. Acetaminophen may prevent AKI by reducing the oxidation state of free hemoglobin.
Objective - To test the hypothesis that early postoperative acetaminophen exposure is associated with reduced risk of AKI in pediatric patients undergoing cardiac surgery.
Design, Setting, and Participants - In this retrospective cohort study, the setting was 2 tertiary referral children's hospitals. The primary and validation cohorts included children older than 28 days admitted for cardiac surgery between July 1, 2008, and June 1, 2016. Exclusion criteria were postoperative extracorporeal membrane oxygenation and inadequate serum creatinine measurements to determine AKI status.
Exposures - Acetaminophen exposure in the first 48 postoperative hours.
Main Outcomes and Measures - Acute kidney injury based on Kidney Disease: Improving Global Outcomes serum creatinine criteria (increase by ≥0.3 mg/dL from baseline or at least 1.5-fold more than the baseline [to convert to micromoles per liter, multiply by 88.4]) in the first postoperative week.
Results - The primary cohort (n = 666) had a median age of 6.5 (interquartile range [IQR], 3.9-44.7) months, and 341 (51.2%) had AKI. In unadjusted analyses, those with AKI had lower median acetaminophen doses than those without AKI (47 [IQR, 16-88] vs 78 [IQR, 43-104] mg/kg, P < .001). In logistic regression analysis adjusting for age, cardiopulmonary bypass time, red blood cell distribution width, postoperative hypotension, nephrotoxin exposure, and Risk Adjustment for Congenital Heart Surgery score, acetaminophen exposure was protective against postoperative AKI (odds ratio, 0.86 [95% CI, 0.82-0.90] per each additional 10 mg/kg). Findings were replicated in the validation cohort (n = 333), who had a median age of 14.1 (IQR, 3.9-158.2) months, and 162 (48.6%) had AKI. Acetaminophen doses were 60 (95% CI, 40-87) mg/kg in those with AKI vs 70 (95% CI, 45-94) mg/kg in those without AKI (P = .03), with an adjusted odds ratio of 0.91 (95% CI, 0.84-0.99) for each additional 10 mg/kg.
Conclusions and Relevance - These results indicate that early postoperative acetaminophen exposure may be associated with a lower rate of AKI in pediatric patients who undergo cardiac surgery. Further analysis to validate these findings, potentially through a prospective, randomized trial, may establish acetaminophen as a preventive agent for AKI.
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Angiographic Efficacy of the Atriclip Left Atrial Appendage Exclusion Device Placed by Minimally Invasive Thoracoscopic Approach.
Ellis CR, Aznaurov SG, Patel NJ, Williams JR, Sandler KL, Hoff SJ, Ball SK, Whalen SP, Carr JJ
(2017) JACC Clin Electrophysiol 3: 1356-1365
MeSH Terms: Aged, Atrial Appendage, Atrial Fibrillation, Cardiac Surgical Procedures, Computed Tomography Angiography, Echocardiography, Transesophageal, Female, Humans, Intracranial Embolism, Male, Middle Aged, Minimally Invasive Surgical Procedures, Retrospective Studies, Surgical Instruments, Therapeutic Occlusion, Thoracoscopy, Thrombosis, Treatment Outcome, Wound Closure Techniques
Show Abstract · Added January 10, 2020
OBJECTIVES - This study sought to assess long-term left atrial appendage (LAA) closure efficacy of the Atriclip applied via totally thoracoscopic (TT) approach with computed tomographic angiography.
BACKGROUND - LAA closure is associated with a low risk for atrial fibrillation-related embolic stroke. The Atriclip exclusion device allows epicardial LAA closure, avoiding the need for post-operative oral anticoagulation. Previous data with Atriclip during open chest procedures show a high efficacy rate of closure >95%.
METHODS - Three-dimensional volumetric 2-phase computed tomographic angiography ≥90 days post-implantation was independently assessed by chest radiology for complete LAA closure on all consented subjects identified retrospectively as having had a TT-placed Atriclip at Vanderbilt University Medical Center from June 13, 2011, to October 6, 2015.
RESULTS - Complete LAA closure (defined by complete exclusion of the LAA with no exposed trabeculations, and clip within 1 cm from the left circumflex artery) was found in 61 of 65 subjects (93.9%). Four cases had incomplete closure (6.2%). Two clips were placed too distally, leaving a large stump with exposed trabeculae. Two clips failed to address a secondary LAA lobe. No major complications were associated with TT placement of the Atriclip. Follow-up over 183 patient-years revealed 1 stroke in a patient with complete LAA closure and no thrombus (hypertensive cerebrovascular accident).
CONCLUSIONS - Angiographic LAA closure efficacy with a TT-placed Atriclip is high (93.9%). The clinical significance of a remnant stump is unknown. Confirmation of complete LAA occlusion should be made before cessation of systemic anticoagulation.
Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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High-Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery.
Smith LE, Smith DK, Blume JD, Linton MF, Billings FT
(2017) J Am Heart Assoc 6:
MeSH Terms: Acute Kidney Injury, Aged, Aged, 80 and over, Atorvastatin, Cardiac Surgical Procedures, Cholesterol, HDL, Coronary Artery Disease, Dose-Response Relationship, Drug, Double-Blind Method, Female, Follow-Up Studies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Kidney Function Tests, Male, Middle Aged, Postoperative Complications, Postoperative Period, Preoperative Period, Risk Factors, Treatment Outcome
Show Abstract · Added April 10, 2018
BACKGROUND - Acute kidney injury (AKI) after cardiac surgery is associated with increased short- and long-term mortality. Inflammation, oxidative stress, and endothelial dysfunction and damage play important roles in the development of AKI. High-density lipoproteins (HDLs) have anti-inflammatory and antioxidant properties and improve endothelial function and repair. Statins enhance HDL's anti-inflammatory and antioxidant capacities. We hypothesized that a higher preoperative HDL cholesterol concentration is associated with decreased AKI after cardiac surgery and that perioperative statin exposure potentiates this association.
METHODS AND RESULTS - We tested our hypothesis in 391 subjects from a randomized clinical trial of perioperative atorvastatin to reduce AKI after cardiac surgery. A 2-component latent variable mixture model was used to assess the association between preoperative HDL cholesterol concentration and postoperative change in serum creatinine, adjusted for known AKI risk factors and suspected confounders. Interaction terms were used to examine the effects of preoperative statin use, preoperative statin dose, and perioperative atorvastatin treatment on the association between preoperative HDL and AKI. A higher preoperative HDL cholesterol concentration was independently associated with a decreased postoperative serum creatinine change (=0.02). The association between a high HDL concentration and an attenuated increase in serum creatinine was strongest in long-term statin-using patients (=0.008) and was further enhanced with perioperative atorvastatin treatment (=0.004) and increasing long-term statin dose (=0.003).
CONCLUSIONS - A higher preoperative HDL cholesterol concentration was associated with decreased AKI after cardiac surgery. Preoperative and perioperative statin treatment enhanced this association, demonstrating that pharmacological potentiation is possible during the perioperative period.
CLINICAL TRIAL REGISTRATION - URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00791648.
© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
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21 MeSH Terms
Cardiac repair in a mouse model of acute myocardial infarction with trophoblast stem cells.
Li G, Chen J, Zhang X, He G, Tan W, Wu H, Li R, Chen Y, Gu R, Xie J, Xu B
(2017) Sci Rep 7: 44376
MeSH Terms: Animals, Cardiac Surgical Procedures, Cell Differentiation, Disease Models, Animal, Humans, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Mice, Myocardial Infarction, Myocardium, Myocytes, Cardiac, Trophoblasts
Show Abstract · Added September 11, 2017
Various stem cells have been explored for the purpose of cardiac repair. However, any individual stem cell population has not been considered as the ideal source. Recently, trophoblast stem cells (TSCs), a newly described stem cell type, have demonstrated extensive plasticity. The present study evaluated the therapeutic effect of TSCs transplantation for heart regeneration in a mouse model of myocardial infarction (MI) and made a direct comparison with the most commonly used mesenchymal stem cells (MSCs). Transplantation of TSCs and MSCs led to a remarkably improved cardiac function in contrast with the PBS control, but only the TSCs exhibited the potential of differentiation into cardiomyocytes in vivo. In addition, a significantly high proliferation level of both transplanted stem cells and resident cardiomyocytes was observed in the TSCs group. These findings primary revealed the therapeutic potential of TSCs in transplantation therapy for MI.
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12 MeSH Terms
Statins to Reduce Acute Kidney Injury After Cardiac Surgery--Reply.
Billings FT, Brown NJ
(2016) JAMA 316: 349-50
MeSH Terms: Acute Kidney Injury, Atorvastatin, Cardiac Surgical Procedures, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male
Added April 6, 2017
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Augmenting Surgery via Multi-scale Modeling and Translational Systems Biology in the Era of Precision Medicine: A Multidisciplinary Perspective.
Kassab GS, An G, Sander EA, Miga MI, Guccione JM, Ji S, Vodovotz Y
(2016) Ann Biomed Eng 44: 2611-25
MeSH Terms: Cardiac Surgical Procedures, Computer Simulation, Humans, Patient-Specific Modeling, Precision Medicine, Translational Medical Research, Wound Healing, Wounds and Injuries
Show Abstract · Added July 23, 2018
In this era of tremendous technological capabilities and increased focus on improving clinical outcomes, decreasing costs, and increasing precision, there is a need for a more quantitative approach to the field of surgery. Multiscale computational modeling has the potential to bridge the gap to the emerging paradigms of Precision Medicine and Translational Systems Biology, in which quantitative metrics and data guide patient care through improved stratification, diagnosis, and therapy. Achievements by multiple groups have demonstrated the potential for (1) multiscale computational modeling, at a biological level, of diseases treated with surgery and the surgical procedure process at the level of the individual and the population; along with (2) patient-specific, computationally-enabled surgical planning, delivery, and guidance and robotically-augmented manipulation. In this perspective article, we discuss these concepts, and cite emerging examples from the fields of trauma, wound healing, and cardiac surgery.
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Bridging translation for acute kidney injury with better preclinical modeling of human disease.
Skrypnyk NI, Siskind LJ, Faubel S, de Caestecker MP
(2016) Am J Physiol Renal Physiol 310: F972-84
MeSH Terms: Acute Kidney Injury, Animals, Antineoplastic Agents, Cardiac Surgical Procedures, Cisplatin, Contrast Media, Disease Models, Animal, Humans, Sepsis, Translational Medical Research
Show Abstract · Added October 23, 2018
The current lack of effective therapeutics for patients with acute kidney injury (AKI) represents an important and unmet medical need. Given the importance of the clinical problem, it is time for us to take a few steps back and reexamine current practices. The focus of this review is to explore the extent to which failure of therapeutic translation from animal studies to human studies stems from deficiencies in the preclinical models of AKI. We will evaluate whether the preclinical models of AKI that are commonly used recapitulate the known pathophysiologies of AKI that are being modeled in humans, focusing on four common scenarios that are studied in clinical therapeutic intervention trials: cardiac surgery-induced AKI; contrast-induced AKI; cisplatin-induced AKI; and sepsis associated AKI. Based on our observations, we have identified a number of common limitations in current preclinical modeling of AKI that could be addressed. In the long term, we suggest that progress in developing better preclinical models of AKI will depend on developing a better understanding of human AKI. To this this end, we suggest that there is a need to develop greater in-depth molecular analyses of kidney biopsy tissues coupled with improved clinical and molecular classification of patients with AKI.
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