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1.
Nat Commun ; 15(1): 314, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38182562

ABSTRACT

Cybermedical systems that regulate patient clotting in real time with personalized blood product delivery will improve treatment outcomes. These systems will harness popular viscoelastic assays of clot strength such as thromboelastography (TEG), which help evaluate coagulation status in numerous conditions: major surgery (e.g., heart, vascular, hip fracture, and trauma); liver cirrhosis and transplants; COVID-19; ICU stays; sepsis; obstetrics; diabetes; and coagulopathies like hemophilia. But these measurements are time-consuming, and thus impractical for urgent care and automated coagulation control. Because protein concentrations in a blood sample can be measured in about five minutes, we develop personalized, phenomenological, quick, control-oriented models that predict TEG curve outputs from input blood protein concentrations, to facilitate treatment decisions based on TEG curves. Here, we accurately predict, experimentally validate, and mechanistically justify curves and parameters for common TEG assays (Functional Fibrinogen, Citrated Native, Platelet Mapping, and Rapid TEG), and verify results with trauma patient clotting data.


Subject(s)
Blood Coagulation , Hemostatics , Female , Pregnancy , Humans , Blood Platelets , Biological Assay , Fibrinogen
2.
J Am Coll Surg ; 238(4): 417-422, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38235790

ABSTRACT

BACKGROUND: In-house calls contribute to loss of sleep and surgeon burnout. Although acknowledged to have an opportunity cost, home call is often considered less onerous, with minimal effects on sleep and burnout. We hypothesized home call would result in impaired sleep and increased burnout in acute care surgeons. STUDY DESIGN: Data from 224 acute care surgeons were collected for 6 months. Participants wore a physiological tracking device and responded to daily surveys. The Maslach Burnout Inventory was administered at the beginning and end of the study. Within-participant analyses were conducted to compare sleep, feelings of restedness, and burnout as a function of home call. RESULTS: One hundred seventy-one surgeons took 3,313 home calls, 52.5% were associated with getting called and 38.5% resulted in a return to the hospital. Home call without calls was associated with 3 minutes of sleep loss (p < 0.01), home call with 1 or more call resulted in a further 14 minutes of sleep loss (p < 0.0001), and home call with a return to the hospital led to an additional 70 minutes of sleep loss (p < 0.0001). All variations of home call resulted in decreased feelings of restedness (p < 0.0001) and increased feelings of daily burnout (p < 0.0001, Fig. 1). CONCLUSIONS: Home call is deleterious to sleep and burnout. Even home call without calls or returns to the hospital is associated with burnout. Internal assessments locally should incorporate frequency of calls and returns to the hospital when creating call schedules. Repeated nights of home call can result in cumulative sleep debt, with adverse effects on health and well-being.


Subject(s)
Burnout, Professional , Psychological Tests , Surgeons , Humans , Sleep/physiology , Self Report , Burnout, Professional/epidemiology , Surveys and Questionnaires
3.
J Trauma Acute Care Surg ; 97(1): 48-56, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38548690

ABSTRACT

INTRODUCTION: Smoking is a public health threat because of its well-described link to increased oxidative stress-related diseases including peripheral vascular disease and coronary artery disease. Tobacco use has been linked to risk of inpatient trauma morbidity including acute respiratory distress syndrome; however, its mechanistic effect on comprehensive metabolic heterogeneity has yet to be examined. METHODS: Plasma was obtained on arrival from injured patients at a Level 1 trauma center and analyzed with modern mass spectrometry-based metabolomics. Patients were stratified by nonsmoker, passive smoker, and active smoker by lower, interquartile, and upper quartile ranges of cotinine intensity peaks. Patients were substratified by high injury/high shock (Injury Severity Score, ≥15; base excess, <-6) and compared with healthy controls. p Value of <0.05 following false discovery rate correction of t test was considered significant. RESULTS: Forty-eight patients with high injury/high shock (7 nonsmokers [15%], 25 passive smokers [52%], and 16 active smokers [33%]) and 95 healthy patients who served as controls (30 nonsmokers [32%], 43 passive smokers [45%], and 22 active smokers [23%]) were included. Elevated metabolites in our controls who were active smokers include enrichment in chronic inflammatory and oxidative processes. Elevated metabolites in active smokers in high injury/high shock include enrichment in the malate-aspartate shuttle, tyrosine metabolism, carnitine synthesis, and oxidation of very long-chain fatty acids. CONCLUSION: Smoking promotes a state of oxidative stress leading to mitochondrial dysfunction, which is additive to the inflammatory milieu of trauma. Smoking is associated with impaired mitochondrial substrate utilization of long-chain fatty acids, aspartate, and tyrosine, all of which accentuate oxidative stress following injury. This altered expression represents an ideal target for therapies to reduce oxidative damage toward the goal of personalized treatment of trauma patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.


Subject(s)
Metabolomics , Wounds and Injuries , Humans , Male , Female , Adult , Wounds and Injuries/metabolism , Wounds and Injuries/blood , Wounds and Injuries/complications , Middle Aged , Metabolomics/methods , Smoking/adverse effects , Smoking/metabolism , Smoking/blood , Oxidative Stress/physiology , Case-Control Studies , Injury Severity Score , Trauma Centers , Cotinine/blood , Cotinine/metabolism , Biomarkers/blood , Biomarkers/metabolism
4.
Article in English | MEDLINE | ID: mdl-38745347

ABSTRACT

BACKGROUND: Patients with type O blood may have an increased risk of hemorrhagic complications due to lower baseline levels of von Willebrand Factor (vWF) and factor VIII, but the transition to a mortality difference in trauma is less clear. We hypothesized that type O trauma patients will have differential proteomic and metabolomic signatures in response to trauma beyond vWF and FVIII alone. METHODS: Patients meeting the highest level of trauma activation criteria were prospectively enrolled. Blood samples were collected upon arrival to the emergency department. Proteomic and metabolomic (multi-omics) analyses of these samples were performed using liquid chromatography-mass spectrometry. Demographic, clinical, and multi-omics data were compared between patients with type O blood versus all other patients. RESULTS: There were 288 patients with multi-omics data; 146 (51%) had type O blood. Demographics, injury patterns, and initial vital signs and laboratory measurements were not different between groups. Type O patients had increased lengths of stay (7 vs. 6 days, p = 0.041) and a trend towards decreased mortality secondary to traumatic brain injury compared to other causes (TBI, 44.4 % vs. 87.5%, p = 0.055). Type O patients had decreased levels of mannose-binding lectin (MBL) and MBL associated serine proteases 1 and 2 which are required for the initiation of the lectin pathway of complement activation. Type O patients also had metabolite differences signifying energy metabolism and mitochondrial dysfunction. CONCLUSION: Blood type O patients have a unique multi-omics signature, including decreased levels of proteins required to activate the lectin complement pathway. This may lead to overall decreased levels of complement activation and decreased systemic inflammation in the acute phase possibly leading to a survival advantage, especially in TBI. However, this may later impair healing. Future work will need to confirm these associations, and animal studies are needed to test therapeutic targets. LEVEL OF EVIDENCE: Retrospective Comparative Study, Level IV.

5.
Am J Surg ; 238: 115887, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39163762

ABSTRACT

BACKGROUND: The risks associated with blood product administration and venous thromboembolic events remains unclear. We sought to determine which blood products were associated with the development of deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: We analyzed data from patients ≥18 years of age in the Trauma Quality Improvement Program (TQIP) database that received ≥1 blood product and survived ≥24 â€‹h. RESULTS: There were 42,399 that met inclusion, of whom, 2086 had at least one VTE event. In our multivariable logistic regression model, we found that WB had a unit odds ratio (uOR) of 1.05 (95 â€‹% CI 1.02-1.08) for DVT and 1.08 (1.05-1.12) for PE. Compared to WB, platelets had a higher uOR for DVT of 1.09 (1.04-1.13) but similar uOR for PE of 1.08 (1.03-1.14). CONCLUSIONS: We found an association of both DVT and PE with early whole blood and platelets.

6.
Article in English | MEDLINE | ID: mdl-38764145

ABSTRACT

BACKGROUND: Platelets are well known for their roles in hemostasis, but they also play a key role in thromboinflammatory pathways by regulating endothelial health, stimulating angiogenesis, and mediating host defense through both contact dependent and independent signaling. When activated, platelets degranulate releasing multiple active substances. We hypothesized that the soluble environment formed by trauma platelet releasates attenuates thromboinflammation via mitigation of trauma induced endothelial permeability and metabolomic reprogramming. METHODS: Blood was collected from injured and healthy patients to generate platelet releasates and plasma in parallel. Permeability of endothelial cells when exposed to trauma platelet releasates (TPR) and plasma (TP) was assessed via resistance measurement by Electric Cell-substrate Impedance Sensing (ECIS). Endothelial cells treated with TPR and TP were subjected to mass spectrometry-based metabolomics. RESULTS: TP increased endothelial permeability, whereas TPR decreased endothelial permeability when compared to untreated cells. When TP and TPR were mixed ex vivo, TPR mitigated TP-induced permeability, with significant increase in AUC compared to TP alone. Metabolomics of TPR and TP demonstrated disrupted redox reactions and anti-inflammatory mechanisms. CONCLUSION: TPRs provide endothelial barrier protection against TP-induced endothelial permeability. Our findings highlight a potential beneficial action of activated platelets on the endothelium in injured patients through disrupted redox reactions and increased antioxidants. Our findings support that soluble signaling from platelet degranulation may mitigate the endotheliopathy of trauma. The clinical implications of this are that activated platelets may prove a promising therapeutic target in the complex integration of thrombosis, endotheliopathy, and inflammation in trauma. LEVEL OF EVIDENCE: Prognostic/Epidemiological, Level III.

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