728 results match your criteria: "Safar Center[Affiliation]"

Traumatic brain injury (TBI) and subsequent post-traumatic epilepsy (PTE) often impair daily activities and mental health (MH), which contribute to long-term TBI-related disability. PTE also affects driving capacity, which impacts functional independence, community participation, and satisfaction with life (SWL). However, studies evaluating the collective impact of PTE on multidimensional outcomes are lacking.

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Environmental enrichment-induced cognitive recovery after a moderate pediatric traumatic brain injury is associated with the gut microbiota and neuroinflammation.

Exp Neurol

December 2024

División de Neurociencias, Centro de Investigación Biomédica de Michoacán - Instituto Mexicano del Seguro Social, Morelia, Michoacán, Mexico. Electronic address:

Pediatric traumatic brain injury (TBI) is a significant health concern, yet access to rehabilitation therapies for children remains limited. Environmental enrichment (EE) is a preclinical model of neurorehabilitation that promotes behavioral recovery and reduces neuroinflammation after TBI. While the gut microbiota has recently emerged as a potential therapeutic target for treating TBI sequelae in adults, its role in recovery after pediatric TBI remains unclear.

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A New Clue on Diffuse Brain Swelling After Pediatric TBI.

JAMA Netw Open

November 2024

Department of Critical Care Medicine, Safar Center for Resuscitation Research, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

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Cognition and Behavior in the Aging Brain Following TBI: Surveying the Preclinical Evidence.

Adv Neurobiol

October 2024

Departments of Physical Medicine & Rehabilitation and Neurobiology, Center for Neuroscience, and Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA.

Article Synopsis
  • * Age-related factors such as inflammation, reduced neuroplasticity, and cellular changes significantly affect recovery from TBI and have not been adequately addressed in current research.
  • * There's a call for more targeted research and interventions that consider unique challenges faced by older adults after TBI to enhance treatment outcomes and prevent further neurodegenerative diseases.
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Pediatric Traumatic Brain Injury: Models, Therapeutics, and Outcomes.

Adv Neurobiol

October 2024

Departments of Physical Medicine & Rehabilitation, Critical Care Medicine, and Psychology, and Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, John G. Rangos Research Center, Pittsburgh, PA, USA.

Pediatric traumatic brain injury (TBI) is a significant healthcare issue, but potential treatments are absent despite robust investigation in several clinical trials. Factors attributed to clinical TBI, such as heterogeneity of injury and single-dose pharmacological treatments as well as timing of administration, may be reasons for the negative studies. Preclinical models of TBI can reduce some of the impediments by highlighting differences in injury depending on injury severity and location and by conducting dose response studies, thus providing better therapeutic targets and pharmacological profiles for clinical use.

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Delayed-and-abbreviated environmental enrichment after traumatic brain injury confers neurobehavioral benefits similar to immediate-and-continuous exposure.

Brain Res

January 2025

Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Environmental enrichment (EE) consists of increased living space, complex stimuli, and social interaction that collectively confer neurobehavioral benefits in preclinical models of traumatic brain injury (TBI). The typical EE approach entails implementation immediately after surgery and continual exposure, which is not clinically applicable, as TBI patients often only receive rehabilitation after critical care, and then only for a few hours per day. We are focused on developing a clinically relevant model of neurorehabilitation by refining the timing of initiation and duration of EE exposure after TBI.

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Introduction: Monitoring cell-free plasma hemoglobin (PHb) during extracorporeal therapies allows early intervention of significant hemolysis, but timely measurements are often challenging. We thus present an analysis of a rapid benchtop device's ability to detect clinically significant hemolysis (PHb ≥50 mg/dL).

Methods: PHb was measured in 419 plasma samples from 88 pediatric patients undergoing cardiopulmonary bypass via both the benchtop device (HemoCue® Plasma/Low Hb system) and the clinical laboratory at the Children's Hospital of Pittsburgh (reference standards).

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Pre-operative environmental enrichment does not yield a prophylactic effect against traumatic brain injury-induced neurobehavioral deficits.

Exp Neurol

January 2025

Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Article Synopsis
  • Environmental enrichment (EE) effectively improves neurobehavioral and cognitive functions following traumatic brain injury (TBI), but its preventative effects against TBI are uncertain.
  • The study hypothesized that EE before TBI surgery would protect against deficits and suggest additional benefits if EE was provided both before and after the injury.
  • Results showed that while pre-injury EE didn't provide a protective effect against TBI, rats with post-injury EE performed better in motor skills and cognitive tests compared to those without enrichment.
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Objective: To examine risk factors associated with homeboundness 1-year after traumatic brain injury (TBI) and to explore associations between homebound status and risk of future mortality and nursing home entry.

Design: Secondary analysis of a longitudinal prospective cohort study.

Setting: TBI Model Systems centers.

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Importance: Declining mortality in the field of pediatric critical care medicine has shifted practicing clinicians' attention to preserving patients' neurodevelopmental potential as a main objective. Earlier identification of critically ill children at risk for incurring neurologic morbidity would facilitate heightened surveillance that could lead to timelier clinical detection, earlier interventions, and preserved neurodevelopmental trajectory.

Objective: Develop machine-learning models for identifying acquired neurologic morbidity while hospitalized with critical illness and assess correlation with contemporary serum-based, brain injury-derived biomarkers.

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New insights into metabolism dysregulation after TBI.

J Neuroinflammation

July 2024

Department of Neurology, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA, 15213, USA.

Traumatic brain injury (TBI) remains a leading cause of death and disability that places a great physical, social, and financial burden on individuals and the health system. In this review, we summarize new research into the metabolic changes described in clinical TBI trials, some of which have already shown promise for informing injury classification and staging. We focus our discussion on derangements in glucose metabolism, cell respiration/mitochondrial function and changes to ketone and lipid metabolism/oxidation to emphasize potentially novel biomarkers for clinical outcome prediction and intervention and offer new insights into possible underlying mechanisms from preclinical research of TBI pathology.

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Enhancing survival after ionizing radiation exposure through mitigation of pyroptosis.

Biochim Biophys Acta Mol Basis Dis

October 2024

Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh School of Public Health, 130 Desoto St, Pittsburgh, PA 15261, USA; Safar Center for Resuscitation Research, Department of Critical Care Medicine, University of Pittsburgh Medical Center, 4401 Penn Ave, Pittsburgh, PA 15224, USA; Children's Neuroscience Institute, UPMC Children's Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA; Department of Pediatrics, Division of Critical Care and Hospital Medicine, Redox Health Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address:

• Pyroptosis, an inflammatory cell death, has been implicated in the pathogenesis of total body irradiation (TBI) so we investigated time course and cell type involvement of key mediators in a murine model. • Pyroptotic mediators were most highly expressed at day 3 post TBI with immune cells from ileum being preferentially activated. • We also investigated the effectiveness of MCC950, a potent pyroptosis inhibitor, in our murine model showing a survival benefit at 50 mg/kg regardless of sex.

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Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity.

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[This corrects the article DOI: 10.3389/fped.2024.

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Cholinergic disruptions underlie attentional deficits following traumatic brain injury (TBI). Yet, drugs specifically targeting acetylcholinesterase (AChE) inhibition have yielded mixed outcomes. Therefore, we hypothesized that galantamine (GAL), a dual-action competitive AChE inhibitor and α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator, provided chronically after injury, will attenuate TBI-induced deficits of sustained attention and enhance ACh efflux in the medial prefrontal cortex (mPFC), as assessed by microdialysis.

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A Comparison of the Anticoagulation Efficacy and Safety of Epoprostenol to Heparin and Citrate in Children Receiving Continuous Renal Replacement Therapy.

Blood Purif

October 2024

Division of Pediatric Critical Care, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Introduction: Anticoagulants are used in continuous renal replacement therapy (CRRT) to prolong filter life. There are no prior investigations directly comparing epoprostenol to more commonly used forms of anticoagulation in children. Therefore, the primary aim of this study was to assess the efficacy and safety of epoprostenol as compared to heparin and citrate anticoagulation in a pediatric cohort.

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Corrigendum to "Biomarkers for neuroprognostication after standard versus extracorporeal cardiopulmonary resuscitation - A sub-analysis of Prague-OHCA study" [Resuscitation 199 (2024) 110219].

Resuscitation

August 2024

Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine and UPMC, 200 Lothrop St, Pittsburgh, PA 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, John G. Rangos Research Center, 4401 Penn Avenue, Pittsburgh, PA 15224, United States. Electronic address:

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Article Synopsis
  • Neurological issues are prevalent in children hospitalized with SARS-CoV-2-related multisystem inflammatory syndrome (MIS-C), potentially leading to lasting cognitive and functional problems.
  • This study investigates how severe neurological symptoms during hospitalization relate to new cognitive and functional impairments upon discharge among children under 18.
  • Over 3,500 patients were examined, revealing that those with severe neurological manifestations had a higher likelihood of experiencing new morbidities at discharge compared to those without such issues.
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Uncontrolled neuroinflammation mediates traumatic brain injury (TBI) pathology and impairs recovery. Interleukin-6 (IL-6), a pleiotropic inflammatory regulator, is associated with poor clinical TBI outcomes. IL-6 operates via classical-signaling through membrane-bound IL-6 receptor (IL-6R) and trans-signaling through soluble IL-6 receptor (s)IL-6R.

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Temporal Profile of Serum Neurofilament Light (NF-L) and Heavy (pNF-H) Level Associations With 6-Month Cognitive Performance in Patients With Moderate-Severe Traumatic Brain Injury.

J Head Trauma Rehabil

November 2024

Author Affiliations: Brain Rehabilitation Research Center (BRRC), Malcom Randall VAMC, Gainesville, Florida (Drs Trifilio, Lamb, Wang, and Williamson and Ms Bottari); Department of Clinical and Health Psychology (Drs Trifilio and Williamson and Ms Bottari), College of Public Health and Health Professions, and Departments of Emergency Medicine (Dr Wang) and Psychiatry (Drs Lamb and Williamson), College of Medicine, University of Florida, Gainesville; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas (Dr Robertson); Department of Neurology, SUNY Downstate Health Sciences University, Brooklyn, New York (Dr Rubenstein); Department of Physical Medicine and Rehabilitation (Ms McQuillan and Dr Wagner), Department of Emergency Medicine (Dr Barton), Department of Neuroscience (Dr Wagner), Clinical and Translational Science Institute (Dr Wagner), and Safar Center for Resuscitation Research (Dr Wagner); University of Pittsburgh, Pittsburgh, Pennsylvania; and Department of Neurobiology, Center for Neurotrauma, Multiomics & Biomarkers (CNMB), Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia (Dr Wang).

Objective: Identification of biomarkers of cognitive recovery after traumatic brain injury (TBI) will inform care and improve outcomes. This study assessed the utility of neurofilament (NF-L and pNF-H), a marker of neuronal injury, informing cognitive performance following moderate-to-severe TBI (msTBI).

Setting: Level 1 trauma center and outpatient via postdischarge follow-up.

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Biomarkers for neuroprognostication after standard versus extracorporeal cardiopulmonary resuscitation - A sub-analysis of Prague-OHCA study.

Resuscitation

June 2024

Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine and UPMC, 200 Lothrop St, Pittsburgh PA 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, John G. Rangos Research Center, 4401 Penn Avenue, Pittsburgh, PA 15224, United States. Electronic address:

Background: Limited evidence exists for prognostic performance of biomarkers in patients resuscitated from out-of-hospital cardiac arrest (OHCA) with extracorporeal CPR (ECPR). We hypothesized that (1) the time course and (2) prognostic performance of biomarkers might differ between CPR and ECPR in a sub-analysis of Prague-OHCA study.

Methods: Patients received either CPR (n = 164) or ECPR (n = 92).

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Neurofilament-light chain (NF-L) and phosphorylated neurofilament-heavy chain (pNF-H) are axonal proteins that have been reported as potential diagnostic and prognostic biomarkers in traumatic brain injury (TBI). However, detailed temporal profiles for these proteins in blood, and interrelationships in the acute and chronic time periods post-TBI have not been established. Our objectives were: 1) to characterize acute-to-chronic serum NF-L and pNF-H profiles after moderate-severe TBI, as well as acute cerebrospinal fluid (CSF) levels; 2) to evaluate CSF and serum NF-L and pNF-H associations with each other; and 3) to assess biomarker associations with global patient outcome using both the Glasgow Outcome Scale-Extended (GOS-E) and Disability Rating Scale (DRS).

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The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St.

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Post-discharge outcomes of hospitalized children diagnosed with acute SARS-CoV-2 or MIS-C.

Front Pediatr

February 2024

Department of Psychiatry and Behavioral Sciences, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Introduction: Hospitalized children diagnosed with SARS-CoV-2-related conditions are at risk for new or persistent symptoms and functional impairments. Our objective was to analyze post-hospital symptoms, healthcare utilization, and outcomes of children previously hospitalized and diagnosed with acute SARS-CoV-2 infection or Multisystem Inflammatory Syndrome in Children (MIS-C).

Methods: Prospective, multicenter electronic survey of parents of children <18 years of age surviving hospitalization from 12 U.

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