Efficacy of ozonated autohemotherapy for improvement of myocardial injury following traumatic brain injury.

BACKGROUND: Traumatic brain injury is a kind of injury caused by external violence on the head. Its danger is not limited to life rescue in the early stage of the disease. Moreover, the subsequent inflammatory reaction and the change in its oxidative stress level will cause secondary myocardial injury. The purpose of this study is to explore the myocardial protective effect of ozone autohemotherapy (OA) in the progression of acute traumatic brain injury (TBI). METHODS: Forty patients with acute TBI were recruited and divided into The treatment group (Group OA, n = 18) and the Control group (Group C, n = 19). Patients in Group OA received OA before surgery and on the 1st and 2nd postoperative days, while patients in Group C underwent autologous blood transfusion. Venous blood was collected from all patients before (T0) and after 7 days (T1) days of surgery for measurement of cardiac troponin T (cTnT) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP). At T0 and T1, transthoracic cardiac ultrasound was performed to measure left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and venous blood was sampled to determine the contents of superoxide dismutase (SOD) and malondialdehyde (MDA). NIH Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores were calculated, and other clinical indexes were recorded. RESULTS: (1) The levels of cTnT at T1 were significantly higher as compared with that at T0 in both groups (p < 0.01). Compared with Group C, a remarkable decline in the content of NT-proBNP was found in Group OA at T1 (p = 0.021). (2) The LVEF (p = 0.002) and serum SOD (p = 0.015) at T1 were significantly increased in Group OA as compared with those in Group C. (3) The length of Intensive Care Unit and hospitalization time for patients in Group OA was distinctly shorter than that for patients in Group C (p = 0.021, p = 0.015, respectively). CONCLUSION: Perioperative OA treatment can alleviate the secondary myocardial injury during the disease course of TBI, which might be associated with its myocardial protective effect against oxidative stress. TRIAL REGISTRATION: This study was approved by the Ethical Committee of Changzhou NO.2 People's Hospital. The protocol was registered prospectively with the Chinese Clinical Trial Registry (ChiCTR2000029612) on February 02, 2020.

Mesenchymal Stromal Cell Implants for Chronic Motor Deficits After Traumatic Brain Injury: Post Hoc Analysis of a Randomized Trial.

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is frequently characterized by chronic motor deficits. Therefore, this clinical trial assessed whether intracranial implantation of allogeneic modified mesenchymal stromal (SB623) cells can improve chronic motor deficits after TBI. METHODS: Post hoc analysis of the double-blind, randomized, prospective, surgical sham-controlled, phase 2, STEMTRA clinical trial (June 2016 and March 2019) with 48 weeks of follow-up was conducted. In this international, multicenter clinical trial, eligible participants had moderate-to-severe TBI, were ≥12 months postinjury, and had chronic motor deficits. Participants were randomized in a 1:1:1:1 ratio to stereotactic surgical intracranial implantation of SB623 cells (2.5 × 106, 5.0 × 106, 10 × 106) or surgical sham-controlled procedure. The prespecified primary efficacy end point was significantly greater change from baseline of the Fugl-Meyer Motor Scale (FMMS) score, a measure of motor status, for the SB623 pooled vs control arm at 24 weeks. RESULTS: A total of 211 participants were screened, 148 were excluded, and 63 underwent randomization, of which 61 (97%; mean age, 34 [SD, 12] years; 43 men [70.5%]) completed the trial. Single participants in the SB623 2.5 × 106 and 5.0 × 106 cell dose groups discontinued before surgery. Safety and efficacy (modified intent-to-treat) were assessed in participants who underwent surgery (N = 61; SB623 = 46, controls = 15). The primary efficacy end point (FMMS) was achieved (least squares mean [SE] SB623: +8.3 [1.4]; 95% CI 5.5-11.2 vs control: +2.3 [2.5]; 95% CI -2.7 to 7.3; p = 0.04), with faster improvement of the FMMS score in SB623-treated groups than in controls at 24 weeks and sustained improvement at 48 weeks. At 48 weeks, improvement of function and activities of daily living (ADL) was greater, but not significantly different in SB623-treated groups vs controls. The incidence of adverse events was equivalent in SB623-treated groups and controls. There were no deaths or withdrawals due to adverse events. DISCUSSION: Intraparenchymal implantation of SB623 cells was safe and significantly improved motor status at 24 weeks in participants with chronic motor deficits after TBI, with continued improvement of function and ADL at 48 weeks. Cell therapy can modify chronic neurologic deficits after TBI. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02416492. Submitted to registry: April 15, 2015. First participant enrolled: July 6, 2016. Available at: classic.clinicaltrials.gov/ct2/show/NCT02416492. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that intracranial implantation of allogeneic stem (SB623) cells in adults with motor deficits from chronic TBI improves motor function at 24 weeks.

The creation of a global neurotrauma registry.

The authors propose the generation of a multi-institutional TBI registry. Barriers to registry implementation include: (1) difficulties in acquiring ethical approval; (2) incomplete clinical data available; (3) lack of information and insufficient technology (IT) support; (4) limited available resources; (5) time constraints involving understaffing yet managing high patient volumes; (6) time constraints associated with entering patient data into the registry tool. The authors detail the current state of affairs on neurotrauma registries worldwide and propose the creation of a multi-institutional, global neurotrauma registries. This private-public partnership will enable appropriate balance among stakeholders while offering care to the largest number of citizens. This initiative will require coordinated efforts involving vetted members of organized neurosurgery. Support from these entities, such as fellowship program creation, provided funding through travel vouchers to LMICs, secured housing and transportation costs in LMI nations, facilitated meetings with global local stakeholders, and promotion of key developments via social media, will accelerate the creation of this global neurotrauma registry. We propose the creation of a global TBI registry, in partnership with large, academic medical centers. Several proposed limitations of registry implementation can be addressed with support from local stakeholders, including government officials and administrative members at key institutions. Several American institutions have well-established global health programs to support this initiative. Further, at Harvard Medical School, the program in Global Surgery and Social Change offers the Paul Farmer Global Surgery Fellowship that trains leaders in policy development and implementation. The fellowship consists of 2 separate tracks: a 2-year research fellow (PGY-5-PGY-6) and 1-year research associate (MD and MBBS, etc.). Funding could be allocated towards creating a year-long fellowship dedicated towards implementing a neurotrauma registry, with this selected scholar granted the resource and connections to network with government officials and healthcare groups in every nation within that jurisdiction. A scholar would be assigned a region of the world with the goal to generate a registry that would later be combined with those generated by peer scholars. In addition, we propose the creation of a fund, controlled by donors, as a funding model.

Race and Socio-Economic Status Impact Withdrawal of Treatment in Young Traumatic Brain Injury.

CONTEXT: Withdrawal of life-sustaining therapies (WDLST) in young individuals with traumatic brain injury (TBI) is an overwhelming situation often made more stressful by socioeconomic factors that shape health outcomes. Identifying these factors is crucial to developing equitable and goal-concordant care for patients and families. OBJECTIVES: We aimed to identify predictors of WDLST in young patients with 1-TBI. We hypothesized uninsured payment method, race, and co-morbid status are associated with WDLST. METHODS: We queried the 2021 Trauma Quality Improvement Program database for patients <45 years with TBI. Patients with WDLST were compared to patients without WDLST. Multivariable logistic regression (MLR) was performed. RESULTS: 61,115 patients were included, of whom 2,487 (4.1%) underwent WDLST. Patients in the WDLST cohort were older (29 vs 27, P<0.001), more likely to suffer from a penetrating mechanism (29% vs 11%, P<.0001), and have uninsured (22% vs 18%) or other payment method (5% vs 3%) when compared to the non-WDLST cohort. MLR identified age (AOR:1.019, 95% CI 1.014-1.024, P<.0001), non-Hispanic ethnicity (AOR:1.590, 95% CI 1.373-1.841, P<.0001), penetrating mechanism (AOR:3.075, 95% CI 2.727-3.467, P<.0001), systolic blood pressure (AOR: 0.992, 95% CI 0.990-0.993, P<0.0001), advanced directive (AOR:4.987, 95% CI 2.823-8.812, P<.0001), cirrhosis (AOR:3.854, 95% CI 2.641-5.625, P<.0001), disseminated cancer (AOR:6.595, 95% CI 2.370-18.357, P=0.0003), and interfacility transfer (AOR:1.457, 95% CI 1.295-1.640, P<0.0001) as factors associated with WDLST. Black patients were less likely to undergo WDLST when compared to white patients (AOR:0.687, 95% CI 0.603-0.782, P<.0001). CONCLUSION: The decision for WDLST in young patients with severe TBI may be influenced by cultural and socioeconomic factors in addition to clinical considerations.

Exosomal miRNA-21 derived from umbilical cord mesenchymal stem cells inhibits microglial overactivation to counteract nerve damage.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of neurological disability, and current treatments have limited effectiveness. Recent studies have emphasized the potential of exosomes derived from umbilical cord mesenchymal stem cells (UC-MSCs-Exo) in TBI treatment, but the molecular mechanisms underlying their therapeutic effects are not fully understood. METHODS AND RESULTS: In this study, UC-MSCs-Exo was isolated using ultracentrifugation and intraventricularly injected to TBI rat model. The neurofunctional motor function of the rats was evaluated using the modified neurological severity score (mNSS), and the activation of microglia was assessed through immunofluorescence detection of IBA1 expression levels. Additionally, we established an in vitro neuroinflammatory model using BV2 microglia to investigate the effects of UC-MSCs-Exo and miRNA-21. Our findings indicate that UC-MSCs-Exo promote neurological recovery in TBI rats and inhibit excessive microglia activation. Furthermore, UC-MSCs-Exo highly expresses miRNA-21 and inhibited the proliferation, migration, and release of inflammatory mediators of BV2 microglia by transporting miRNA-21. CONCLUSIONS: The present study suggests that the promotion of neurological recovery in TBI rats by UC-MSCs-Exo may be attributed to the inhibition of excessive microglia activation through miRNA-21.

Effect of a seven-strain probiotic on dietary intake, inflammatory markers, and T-cells in severe traumatic brain injury patients: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Inflammatory processes are key factors in pathological events associated with severe traumatic brain injury (STBI). The aim of this trial was to determine the effect of probiotics on anthropometric measures, disease severity, inflammatory markers, and T cells in patients with STBI. METHODS: Forty adult patients with STBI were enrolled in this parallel randomized, double-blind, placebo-controlled trial. Energy and protein status, Acute Physiology and Chronic Health Evaluation (APACHE II) score, Sequential Organ Failure Assessment (SOFA), interleukin 10 (IL-10), interleukin 1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), transforming growth factor beta (TGF-ß), T-helper 17 (Th17), and T- Regulator (T-reg) cells were assessed at baseline (day 1), and week 2 (day 14) for each patient. RESULTS: Probiotic supplementation led to a substantial reduction in the serum levels of TNF-α (from 10.15 ± 6.52 to 5.05 ± 3.27) (P = 0.034), IL-1ß (from 11.84 ± 7.74 to 5.87 ± 3.77) (P < 0.001), and Th17 cells (from 5.19 ± 1.69 to 2.67 ± 1.89) (P < 0.001) and a substantial increase in the serum levels of IL-10 (from 3.35 ± 1.45 to 6.17 ± 2.04) (P = 0.038), TGF-ß (from 30.5 ± 15.27 to 46.25 ± 21.05) (P < 0.001), and T-reg cells (from 2.83 ± 1.43 to 4.29 ± 1.89) (P < 0.001) compared with the placebo group. Furthermore, no notable changes were observed in energy and protein intake and also, terms of SOFA and APACHE II scores following probiotic treatment compared with the placebo. CONCLUSIONS: Probiotics could reduce inflammation and improve cellular immunity and may be considered as an adjunctive therapy in STBI patients.

Wrapping stem cells with wireless electrical nanopatches for traumatic brain injury therapy.

Electrical stimulation holds promise for enhancing neuronal differentiation of neural stem cells to treat traumatic brain injury. However, once the stem cells leave the stimulating material and migrate post transplantation, electrical stimulation on them is diminished. Here, we wrap the stem cells with wireless electrical nanopatches, the conductive graphene nanosheets. Under electromagnetic induction, electrical stimulation can thus be applied in-situ to individual nanopatch-wrapped stem cells on demand, stimulating their neuronal differentiation through a MAPK/ERK signaling pathway. Consequently, 41% of the nanopatch-wrapped stem cells differentiate into functional neurons in 5 days, as opposed to only 16.3% of the unwrapped ones. The brain injury male mice implanted with the nanopatch-wrapped stem cells and exposed to a rotating magnetic field 30 min/day exhibit significant recovery of brain tissues, behaviors, and cognitions, within 28 days. This study opens up an avenue to individualized electrical stimulation of transplanted stem cells for treating neurodegenerative diseases.

Local Delivery of Dual Stem Cell-Derived Exosomes Using an Electrospun Nanofibrous Platform for the Treatment of Traumatic Brain Injury.

Traumatic brain injury poses serious physical, psychosocial, and economic threats. Although systemic administration of stem cell-derived exosomes has recently been proven to be a promising modality for traumatic brain injury treatment, they come with distinct drawbacks. Luckily, various biomaterials have been developed to assist local delivery of exosomes to improve the targeting of organs, minimize nonspecific accumulation in vital organs, and ensure the protection and release of exosomes. In this study, we developed an electrospun nanofibrous scaffold to provide sustained delivery of dual exosomes derived from mesenchymal stem cells and neural stem cells for traumatic brain injury treatment. The electrospun nanofibrous scaffold employed a functionalized layer of polydopamine on electrospun poly(ε-caprolactone) nanofibers, thereby enhancing the efficient incorporation of exosomes through a synergistic interplay of adhesive forces, hydrogen bonding, and electrostatic interactions. First, the mesenchymal stem cell-derived exosomes and the neural stem cell-derived exosomes were found to modulate microglial polarization toward M2 phenotype, play an important role in the modulation of inflammatory responses, and augment axonal outgrowth and neural repair in PC12 cells. Second, the nanofibrous scaffold loaded with dual stem cell-derived exosomes (Duo-Exo@NF) accelerated functional recovery in a murine traumatic brain injury model, as it mitigated the presence of reactive astrocytes and microglia while elevating the levels of growth associated protein-43 and doublecortin. Additionally, multiomics analysis provided mechanistic insights into how dual stem cell-derived exosomes exerted its therapeutic effects. These findings collectively suggest that our novel Duo-Exo@NF system could function as an effective treatment modality for traumatic brain injury using sustained local delivery of dual exosomes from stem cells.

Synthesis of Lipidated Ligands and Formulation of Glia-Specific LNPs for RNAi-Mediated BBB Protection.

Pro-inflammatory polarization of microglia and astrocytes results in neuroinflammation and blood-brain barrier (BBB) disruption after a primary traumatic brain injury (TBI). Herein, we demonstrate that the dual-ligand functionalized lipid nanoparticles (AM31 LNPs) were actively and specifically internalized by microglia and astrocytes via mannose receptor (MR)- and adenosine receptor (AR)-mediated endocytosis, respectively, in a mouse model of TBI. Systemic administration of AM31 LNPs carrying siRNA against p65 resulted in internalization by the glial cells in the peri-infarct region and a robust knockdown of p65 at both mRNA and protein levels in these cells, leading to significant down-regulation of key pro-inflammatory cytokines and up-regulation of key anti-inflammatory cytokines. AM31 LNP-mediated silencing of p65 ameliorated TBI-induced BBB disruption. Our data proved that AM 31 LNP is a promising vehicle for RNA therapeutics for targeting microglia and astrocytes in neural disorder.

Transplantation of miR-193b-3p-Transfected BMSCs Improves Neurological Impairment after Traumatic Brain Injury through S1PR3-Mediated Regulation of the PI3K/AKT/mTOR Signaling Pathway.

The aim of the present study was to explore the molecular mechanisms by which miR-193b-3p-trans-fected bone marrow mesenchymal stem cells (BMSCs) transplantation improves neurological impairment after traumatic brain injury (TBI) through sphingosine-1-phosphate receptor 3 (S1PR3)-mediated regulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway at the cellular and animal levels. BMSCs were transfected with miR-193b-3p. A TBI cell model was established by oxygen-glucose deprivation (OGD)-induced HT22 cells, and a TBI animal model was established by controlled cortical impact (CCI). Cell apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL), and cell activity was detected by a cell counting kit 8 (CCK-8) assay. Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of related proteins and genes. In this study, transfection of miR-193b-3p into BMSCs significantly enhanced BMSCs proliferation and differentiation. Transfection of miR-193b-3p reduced the levels of the interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-alpha (TNF-α) inflammatory factors in cells and mouse models, and it inhibited neuronal apoptosis, which alleviated OGD-induced HT22 cell damage and neural function damage in TBI mice. Downstream experiments showed that miR-193b-3p targeting negatively regulated the expression of S1PR3, promoted the activation of the PI3K/AKT/mTOR signaling pathway, and inhibited the levels of apoptosis and inflammatory factors, which subsequently improved OGD-induced neuronal cell damage and nerve function damage in TBI mice. However, S1PR3 overexpression or inhibition of the PI3K/AKT/mTOR signaling pathway using the IN-2 inhibitor weakened the protective effect of miR-193b-3p-transfected BMSCs on HT22 cells. Transplantation of miR-193b-3p-transfected BMSCs inhibits neurological injury and improves the progression of TBI in mice through S1PR3-mediated regulation of the PI3K/AKT/mTOR pathway.

Anesthesia for traumatic brain injury.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) presents complex clinical challenges, requiring a nuanced understanding of its pathophysiology and current management principles to improve patient outcomes. Anesthetists play a critical role in care and need to stay updated with recent evidence and trends to ensure high-quality treatment. The Brain Trauma Foundation Guidelines, last updated in 2016, have shown moderate adherence, and much of the current management relies on expert opinions. This literature review synthesizes the current evidence and provides insights into the role of anesthetists in TBI management. RECENT FINDINGS: Recent literature has emphasized the importance of tailored anesthetic management principles in treating TBI, focusing on minimizing secondary brain injury during neurosurgical interventions or extracranial surgery. Emerging trends include individualized intracranial pressure approaches and multimodal neuromonitoring for comprehensive assessment of cerebral physiology. SUMMARY: Anesthesia for TBI patients requires a comprehensive approach that balances anesthetic goals with the unique pathophysiological factors of brain injury. Despite recent research expanding our understanding, challenges remain in standardizing protocols and addressing individual patient response variability. Adherence to established management principles, personalized approaches, and ongoing research is crucial for improving the outcomes.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) in the presence of associated severe traumatic brain injury: A propensity-score matched study.

BACKGROUND: Experimental work suggested that resuscitative Endovascular Balloon Occlusion of the aorta (REBOA) preserves cerebral circulation in animal models of traumatic brain injury. No clinical work has evaluated the role of REBOA in the presence of associated severe traumatic brain injury (TBI). We investigated the impacts of REBOA on neurological and survival outcomes. METHODS: Propensity-score matched study, using the American College of Surgeons Trauma Quality Improvement Program database. Patients with severe TBI patients (Abbreviated Injury Scale ≥3) receiving REBOA within 4 â€‹h from arrival were matched with similar patients not receiving REBOA. Neurological matching included head AIS, pupils, and midline shift. Clinical outcomes were compared between the two groups. RESULTS: 434 REBOA patients were matched with 859 patients without REBOA. Patients in the REBOA group had higher rates of in-hospital mortality (63.6 â€‹% vs 44.2 â€‹%, p â€‹< â€‹0.001), severe sepsis (4.4 â€‹% vs 2.2 â€‹%, p â€‹= â€‹0.029), acute kidney injury (10.1 â€‹% vs 6.6 â€‹%, p â€‹= â€‹0.029), and withdrawal of life support (25.4 â€‹% vs 19.6 â€‹%, p â€‹= â€‹0.020) despite of lower craniectomy/craniotomy rate (7.1 â€‹% vs 12.7 â€‹%, p â€‹< â€‹0.002). CONCLUSION: In patients with severe TBI, REBOA use is associated with an increased risk of in-hospital mortality, AKI, and infectious complications.

Elucidating the molecular mechanisms behind the therapeutic impact of median nerve stimulation on cognitive dysfunction post-traumatic brain injury.

OBJECTIVE: Ferroptosis represents a form of regulated cellular death dependent upon iron and lipid peroxidation derivatives, holding considerable implications for cerebral and neurologic pathologies. In the present study, we endeavored to elucidate the molecular mechanisms governing ferroptosis and appraise the therapeutic value of electrical stimulation of median nerve in addressing cognitive impairments following traumatic brain injury (TBI), employing a rodent model. METHODS: In this study, we established a rat model to investigate the cognitive impairments resulting from TBI, followed by the application of median nerve stimulation (MNS). Initially, rats received an intraperitoneal injection of Erastin (2 mg/kg) prior to undergoing MNS. After 24 h of MNS treatment, the rats were subjected to an open field test to evaluate their cognitive and motor functions. Subsequently, we conducted biochemical assays to measure the serum levels of GSH, MDA and SOD. The structural integrity and cellular morphology of hippocampal tissue were examined through H&E staining, Nissl staining and transmission electron microscopy. Additionally, we assessed the expression levels of proteins crucial for neuronal health and function in the hippocampus, including VEGF, SLC7A11, GPX4, Nrf2, α-syn, NEUN and PSD95. RESULTS: Compared to the control group, rats in the stimulation group demonstrated enhanced mobility, reduced levels of tissue damage, a decrease in MDA concentration, and increased levels of GSH and SOD. Additionally, there was a significant upregulation in the expression of proteins critical for cellular defense and neuronal health, including GPX4, SLC7A11, Nrf2, VEGF, α-syn, NEUN, and PSD95 proteins. Conversely, rats in the Erastin group demonstrated decreased mobility, exacerbated pathological tissue damage, elevated MDA concentration, and decreased levels of GSH and SOD. There was also a notable decrease in the expression of GPX4, SLC7CA11, Nrf2, and VEGF proteins. The expression levels of α-syn, NEUN, and PSD95 were similarly diminished in the Erastin group. Each of these findings was statistically significant, indicating that MNS exerts neuroprotective effect in the hippocampal tissue of rats with TBI by inhibiting the ferroptosis pathway. CONCLUSION: (1) MNS may enhance the cognitive and behavioral performance of rats after TBI; (2) MNS can play a neuroprotective role by promoting the expression of nerve injury-related proteins, alleviating oxidative stress and ferroptosis process; (3) MNS may inhibit ferroptosis of neuronal cells by activating Nrf2/ GPX4 signaling pathway, thereby improving cognitive impairment in TBI rats.

Impact of Trauma Verification Level on Management and Outcomes of Combined Traumatic Brain and Solid Organ Injuries: An NTDB Retrospective Review.

BACKGROUND: Level-I and level-II trauma centers are required to offer equivalent resources since "The Orange Book." This study evaluates differences between level-I and level-II management of solid organ injury (SOI) with traumatic brain injury (TBI). METHODS: We conducted a retrospective review of the National Trauma Data Banks from 2013 to 2021 of adult (≥18 years), blunt trauma patients with both TBI and SOI treated at level-I or level-II trauma centers. RESULTS: 48,479 TBI and SOI patients were identified, 32,611 (67.3%) at level-I centers. Unadjusted incidence of laparotomy was higher at level I (14.5% vs 11.7%, P < 0.001), and angiography rates were similar (3.3% vs 3.4%, P 0.717). Sub-group analysis of stable patients (SBP ≥100) showed an increase in nonoperative management at level II (87.3% vs 88.7%, P < 0.001) and decrease in laparotomy (9.9% vs 8.3%, P < 0.001). On logistic regression (LR), severe TBI, high-grade SOI, and level I trauma status were predictors of laparotomy. Logistic regression showed mild/moderate TBI with high-grade SOI and level II were associated with use of angiography. Unadjusted mortality rates were slightly different (14.8% vs 13.4%, P < 0.001), but there was no association with trauma level on LR. DISCUSSION: Nonoperative management was seen more at level-II centers with laparotomy at level I. Subgroup analysis showed no difference in mortality in trauma levels. Matched patients for level I and II showed no statistical difference in management. Patients were treated similarly at both levels with similar outcomes and mortality.

[Effect of transnasal humidified rapid insufflation ventilatory exchange on cerebral oxygen saturation during induction of general anesthesia in patients undergoing traumatic brain injury emergency surgery].

OBJECTIVE: To evaluate the effect of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) on regional cerebral oxygen saturation (rScO2) during induction of general anesthesia in patients undergoing traumatic brain injury (TBI) emergency surgery. METHODS: A prospective randomized controlled trial was conducted. The TBI emergency general anesthesia patients who underwent intracranial hematoma removal surgery at the Northern Jiangsu People's Hospital from January to July in 2023 were enrolled. The patients were divided into a conventional mask ventilation group and a THRIVE group using a random number table method. The patients in the conventional mask ventilation group were anesthetized and induced to pre oxygenate without positive pressure ventilation in the front mask for 10 minutes, with an oxygen flow rate of 8 L/min and an fraction of inspired oxygen (FiO2) of 1.00. After anesthesia induction for about 90 s, tracheal intubation was performed after the muscle relaxant took effect (patient's jaw muscle was relaxed). The patients in the THRIVE group were pre oxygenated with THRIVE for 10 minutes, with an oxygen flow rate of 30 L/min and a FiO2 of 1.00. During anesthesia induction, the oxygen flow rate was increased to 50 L/min, and anesthesia induction medication was used. The lower jaw of patient was supported with both hands to maintain airway patency, and the patient's mouth was kept closed throughout the process. After the muscle relaxant took effect (the patient's jaw muscle was relaxed), tracheal intubation was performed. At the time of patient entering the operating room, 10 minutes of pre oxygenation, and immediately after successful intubation, rScO2 was measured on the surgical and non-surgical sides. At the same time, ultrasound was used to measure the cross-sectional area (CSA) of the gastric antrum and arterial blood gas analysis was performed. The partial pressure of end-tidal carbon dioxide (PETCO2) during the first mechanical ventilation after successful tracheal intubation, the incidence of hypoxemia [pulse oxygen saturation (SpO2) < 0.95] during tracheal intubation, as well as prognostic indicators such as the length of intensive care unit (ICU) stay, total length of hospital stay, and Glasgow outcome scale (GOS) score at discharge were recorded. RESULTS: During the study period, a total of 70 TBI patients underwent emergency general anesthesia surgery, of which 2 patients died postoperatively, 2 patients were unable to cooperate with closed mouth breathing, and 3 patients had poor ultrasound image acquisition in the gastric antrum, all of whom were excluded. A total of 63 patients were ultimately enrolled, including 32 in the conventional mask ventilation group and 31 in the THRIVE group. There were no statistically significant differences in gender, age, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, Glasgow coma scale (GCS) score, optic nerve sheath diameter (ONSD), baseline vital signs, fasting situation, anesthesia time, surgical time, and intraoperative blood loss between the patients in the two groups, indicating comparability. When entering the operating room, there was no statistically significant difference in rScO2 on the surgical and non-surgical sides, and blood gas analysis indexes arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2) between the patients in the two groups. When pre oxygenated for 10 minutes, both the surgical and non-surgical sides rScO2 levels in the THRIVE group were significantly higher than those in the conventional mask ventilation group (surgical side: 0.709±0.036 vs. 0.636±0.028, non-surgical side: 0.791±0.016 vs. 0.712±0.027, both P < 0.01), and the PaO2 was significantly increased [mmHg (1 mmHg ≈ 0.133 kPa): 450.23±60.99 vs. 264.88±49.33, P < 0.01], PaCO2 was significantly reduced (mmHg: 37.81±3.65 vs. 43.59±3.76, P < 0.01), and the advantage continues tilled immediately after successful intubation. There was no statistically significant difference in CSA at each time point of ultrasound examination between the two groups. Compared with the conventional mask ventilation group, the patients in the THRIVE group showed a significant decrease in PETCO2 during the first mechanical ventilation after successful tracheal intubation (mmHg: 43.10±2.66 vs. 49.22±3.31, P < 0.01), and the incidence of hypoxemia during tracheal intubation was also significantly reduced [0% (0/31) vs. 28.12% (9/32), P < 0.01]. In terms of prognostic indicators, there was no statistically significant difference in the length of ICU stay and total length of hospital stay between the patients in the conventional mask ventilation group and the THRIVE group [length of ICU stay (days): 10 (9, 10) vs. 10 (9, 11), total length of hospital stay (days): 28.00 (26.00, 28.75) vs. 28.00 (27.00, 29.00), both P > 0.05]. However, the proportion of patients in the THRIVE group with a good prognosis at discharge (GOS score > 3) was significantly higher than that in the conventional mask ventilation group [35.5% (11/31) vs. 12.5% (4/32), P < 0.05]. CONCLUSIONS: THRIVE can significantly increase rScO2 during anesthesia induction in TBI emergency surgery patients and improve their neurological function prognosis.

Temporal Delays in the Management of Traumatic Brain Injury: A Comparative Meta-Analysis of Global Literature.

OBJECTIVE: A meta-analysis was conducted to compare: 1) time from traumatic brain injury (TBI) to the hospital, and 2) time within the hospital to intervention or surgery, by country-level income, World Health Organization region, and healthcare payment system. METHODS: A comprehensive literature search was conducted and followed by a meta-analysis comparing duration of delays (prehospital and intrahospital) in TBI management. Means and standard deviations were pooled using a random effects model and subgroup analysis was performed using R software. RESULTS: Our analysis comprised 95,554 TBI patients from 45 countries. BY COUNTRY-LEVEL INCOME: From 23 low- and middle-income countries, a longer mean time from injury to surgery (862.53 minutes, confidence interval [CI]: 107.42-1617.63), prehospital (217.46 minutes, CI: -27.34-462.25), and intrahospital (166.36 minutes, 95% CI: 96.12-236.60) durations were found compared to 22 high-income countries. BY WHO REGION: African Region had the greatest total (1062.3 minutes, CI: -1072.23-3196.62), prehospital (256.57 minutes [CI: -202.36-715.51]), and intrahospital durations (593.22 minutes, CI: -3546.45-4732.89). BY HEALTHCARE PAYMENT SYSTEM: Multiple-Payer Health Systems had a greater prehospital duration (132.62 minutes, CI: 54.55-210.68) but greater intrahospital delays were found in Single-Payer Health Systems (309.37 minutes, CI: -21.95-640.69). CONCLUSION: Our study concludes that TBI patients in low- and middle-income countries within African Region countries face prolonged delays in both prehospital and intrahospital management compared to high-income countries. Additionally, patients within Single-Payer Health System experienced prolonged intrahospital delays. An urgent need to address global disparities in neurotrauma care has been highlighted.

Four-factor prothrombin complex concentrate is not inferior to andexanet alfa for the reversal or oral factor Xa inhibitors: An Eastern Association for the Surgery of Trauma multicenter study.

BACKGROUND: Andexanet alfa (AA) is the only FDA-approved reversal agent for apixaban and rivaroxaban (DOAC). There are no studies comparing its efficacy with four-factor prothrombin complex concentrate (PCC). This study aimed to compare PCC to AA for DOAC reversal, hypothesizing noninferiority of PCC. METHODS: We performed a retrospective, noninferiority multicenter study of adult patients admitted from July 1, 2018, to December 31, 2019, who had taken a DOAC within 12 hours of injury, were transfused red blood cells (RBCs) or had traumatic brain injury, and received AA or PCC. Primary outcome was PRBC unit transfusion. Secondary outcome with intensive care unit length of stay. MICE imputation was used to account for missing data and zero-inflated Poisson regression was used to account for an excess of zero units of RBC transfused. Two units difference in RBC transfusion was selected as noninferior. RESULTS: Results: From 263 patients at 10 centers, 77 (29%) received PCC and 186 (71%) AA. Patients had similar transfusion rates across reversal treatment groups (23.7% AA vs. 19.5% PCC) with median transfusion in both groups of 0 RBC. According to the Poisson component, PCC increases the amount of RBC transfusion by 1.02 times (95% confidence interval, 0.79-1.33) compared with AA after adjusting for other covariates. The average amount of RBC transfusion (nonzero group) is 6.13. Multiplying this number by the estimated rate ratio, PCC is estimated to have an increase RBC transfusion by 0.123 (95% confidence interval, 0.53-2.02) units compared with AA. CONCLUSION: PCC appears noninferior to AA for reversal of DOACs for RBC transfusion in traumatically injured patients. Additional prospective, randomized trials are necessary to compare PCC and AA for the treatment of hemorrhage in injured patients on DOACs. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Variability in Standardized Mortality Rates Among Pediatric Traumatic Brain Injury Patients: A Comparative Analysis of Trauma Centers.

INTRODUCTION: Traumatic brain injury (TBI) causes significant morbidity and mortality in pediatric patients and care is highly variable. Standardized mortality ratio (SMR) summarizes the mortality rate of a specific center relative to the expected rates across all centers, adjusted for case-mix. This study aimed to evaluate variations in SMRs among pediatric trauma centers for TBI. METHODS: Patients aged 1-18 diagnosed with TBI within the National Trauma Data Bank (NTDB) from 2017 to 2019 were included. Center-specific SMRs and 95% confidence intervals identified centers with mortality rates significantly better or worse than the median SMR for all centers. RESULTS: 316 centers with 10,598 patients were included. SMRs were risk-adjusted for patient risk factors. Unadjusted mortality ranged from 16.5 to 29.5%. Three centers (1.5%) had significantly better SMR (SMR <1) and three centers (1.5%) had significantly worse SMR (SMR >1). Significantly better centers had a lower proportion of neurosurgical intervention (2.4% vs. 11.8%, p < 0.001), a higher proportion of supplemental oxygen administration (93.7% vs. 83.5%, p = 0.004) and venous thromboembolism prophylaxis (53.2% vs. 40.6%, p < 0.001) compared to significantly worse centers. CONCLUSIONS: This study identified centers that have significantly higher and lower mortality rates for pediatric TBI patients relative to the overall median rate. These data provide a benchmark for pediatric TBI outcomes and institutional quality improvement. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Retrospective Comparative Study.