A5072850769- Sepsis Diagnosis and Treatment
- Immune Response and Inflammation
- Neonatal Respiratory Health Research
- Trauma and Emergency Care Studies
- Respiratory Support and Mechanisms
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Traumatic Brain Injury and Neurovascular Disturbances
- Immune cells in cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Vitamin C and Antioxidants Research
- Birth, Development, and Health
- Thermal Regulation in Medicine
- Pregnancy-related medical research
- Cardiac Arrest and Resuscitation
- Metabolomics and Mass Spectrometry Studies
- Intensive Care Unit Cognitive Disorders
- Liver Disease Diagnosis and Treatment
- Fatty Acid Research and Health
- Childhood Cancer Survivors' Quality of Life
- IL-33, ST2, and ILC Pathways
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Health, psychology, and well-being
- Anesthesia and Neurotoxicity Research
University of Pittsburgh
2015-2024
McGowan Institute for Regenerative Medicine
2012-2023
Indiana University – Purdue University Indianapolis
2020
University of Pennsylvania
2020
University of Southern California
2020
Methodist Hospital
2020
Orthopaedic Trauma Association
2020
Inova Health System
2020
Division of Chemistry
2012
Novem (Netherlands)
2012
Severe traumatic injury can lead to immune dysfunction that renders trauma patients susceptible nosocomial infections (NI) and prolonged intensive care unit (ICU) stays. We hypothesized early circulating biomarker patterns following would correlate with sustained dysregulation associated NI remote organ failure.In a cohort of 472 blunt survivors studied over an 8-year period, 127 (27%) were diagnosed versus 345 without NI. To perform pairwise, case-control study 1:1 matching, 44 the compared...
Alterations in lipid metabolism have the potential to be markers as well drivers of pathobiology acute critical illness. Here, we took advantage temporal precision offered by trauma a common cause illness identify dynamic patterns circulating lipidome critically ill humans. The major findings include an early loss all classes lipids followed delayed and selective lipogenesis patients destined remain ill. previously reported survival benefit thawed plasma administration was associated with...
The translation of in vitro findings to clinical outcomes is often elusive. Trauma/hemorrhagic shock (T/HS) results hepatic hypoxia that drives inflammation. We hypothesize silico methods would help bridge hepatocyte data and T/HS, which the liver a primary site Primary mouse hepatocytes were cultured under (1% O2) or normoxia (21% for 1–72 h, both cell supernatants protein lysates assayed 18 inflammatory mediators by Luminex™ technology. Statistical analysis data-driven modeling employed...
Background The immunosuppression and immune dysregulation that follows severe injury includes type 2 responses manifested by elevations in interleukin (IL) 4, IL5, IL13 early after injury. We hypothesized IL33, an alarmin released tissue a known regulator of immunity, contributes to the systemic Methods findings Blunt trauma patients admitted intensive care unit level I center were enrolled observational study included frequent blood sampling. Dynamic changes IL33 soluble suppression...
A mathematical model of the human response to trauma replicates individual patient outcomes but predicts unexpected results in populations.
Blunt trauma patients may present with similar demographics and injury severity yet differ regard to survival. We hypothesized that this divergence was due different trajectories of systemic inflammation utilized computational analyses define these differences.Retrospective clinical study experimental in mice.Level 1 center laboratory.From a cohort 493 victims blunt trauma, we conducted pairwise, retrospective, case-control who survived over 24 hours but ultimately died (nonsurvivors; n =...
Clinical outcomes following trauma depend on the extent of injury and host's response to injury, along with medical care. We hypothesized that dynamic networks systemic inflammation manifest differently as a function severity in human blunt trauma.From cohort 472 survivors studied institutional review board approval, three Injury Severity Score (ISS) subcohorts were derived after matching for age sex: mild ISS (49 patients [33 males 16 females, aged 42 ± 1.9 years; 9.5 0.4]); moderate 1.9;...
To define the impact of prehospital hypotension on dynamic, systemic acute inflammatory response to blunt trauma.Retrospective study.Tertiary care institution.Twenty-two hypotensive trauma patients matched with 28 normotensive patients.None.From a cohort 472 survivors studied following institutional review board approval, two stringently subcohorts were derived. Twenty-two who sustained (15 males and 7 females; age, 45 ± 3.8; Injury Severity Score, 20.7 1.8) (20 8 46.1 2.5; 20.8 1.3). Serial...
Objective: Blunt trauma and traumatic spinal cord injury induce systemic inflammation that contributes to morbidity. Dysregulated neural control of postinjury is likely exaggerated in patients with injury. We used silico methods discern dynamic inflammatory networks could distinguish from blunt trauma. Design: Retrospective study. Settings: Tertiary care institution. Patients: Twenty-one severely injured thoracocervical matched 21 without Intervention: None. Measurements Main Results: Serial...
Trauma/hemorrhagic shock is associated with morbidity and mortality due to dysregulated inflammation, which driven in part by monocytes/macrophages stimulated injury-induced release of damage-associated molecular pattern (DAMP) molecules. MRP8/MRP14 an endogenous DAMP involved various inflammatory diseases, though its mechanism action unclear. Circulating levels human blunt trauma nonsurvivors were significantly lower than those survivors (P < 0.001). Human monocytic THP-1 cells expressed...
Optimizing resuscitation to reduce inflammation and organ dysfunction following human trauma-associated hemorrhagic shock is a major clinical hurdle. This limited by the short duration of pre-clinical studies sparsity early data in setting.
Improper compartmentalization of the inflammatory response leads to systemic inflammation in sepsis. Hemoadsorption (HA) is an emerging approach modulate sepsis-induced inflammation. We sought define effects HA on Escherichia coli-induced fibrin peritonitis rats. Hypothesis: both reprograms and recompartmentalizes Sprague Dawley male rats were subjected E. coli and, after 24 h, randomized or sham treatment (sepsis alone). Venous blood samples collected at 0, 1, 3 6 h (that is, 24–30 total...
Immune dysfunction is an important factor driving mortality and adverse outcomes after trauma but remains poorly understood, especially at the cellular level. To deconvolute trauma-induced immune response, we applied single-cell RNA sequencing to circulating bone marrow mononuclear cells in injured mice patients. In mice, greatest changes gene expression were seen monocytes across both compartments. After systemic injury, pattern of markedly deviated from steady state with corresponding...
Extremity and soft tissue injuries contribute significantly to inflammation adverse in-hospital outcomes for trauma survivors; accordingly, we examined the complex association between clinical inflammatory responses in this setting using silico tools. Two stringently propensity-matched, moderately/severely injured (Injury Severity Score > 16) patient sub-cohorts of ~30 patients each were derived retrospectively from a cohort 472 blunt survivors segregated based on their degree extremity...
We hypothesized that elevated base deficit (BD) ≥ 4 mEq/L upon admission could be associated with an altered inflammatory response, which in turn may impact differential clinical trajectories. Using and biobank data from 472 blunt trauma survivors, 154 patients were identified after excluding who received prehospital IV fluids or had alcohol intoxication. From this subcohort, 84 a BD 70 < mEq/L. Three samples within the first 24 h obtained all then daily up to day 7 injury. Twenty-two...
Trauma is the leading cause of death and disability for individuals under age 55. Many severely injured trauma patients experience complicated clinical courses despite appropriate initial therapy. We sought to identify novel circulating metabolomic signatures associated with outcomes following trauma.Untargeted metabolomics plasma immune mediator analysis was performed on collected during 3 post-injury time periods (<6 hours [h], 6 h-24h, day 2-day 5) in critically ill enrolled between April...
Clinical research characterizing the mechanisms responsible for sex-based outcome differences postinjury remain conflicting. We sought to characterize an X chromosome-linked IRAK-1 (IL-1 receptor-associated kinase) polymorphism as alternative mechanism sex postinjury. is key intermediate in toll-like receptor (TLR) pathway thought drive inflammation postinjury.A prospective cohort study was performed over a 24-month period. Bluntly injured patients requiring intensive care unit admission...
Clinical research characterizing the mechanisms responsible for sex-based outcome differences after injury remains conflicting. Currently lacking is an understanding of early sex hormone milieu injured patient and effects these have on clinical outcomes innate immune response following injury.A prospective cohort study was performed over a 20-month period. Blunt patients requiring intensive care unit admission were enrolled. Samples collected within 6 hours at 24 analyzed total testosterone...