Journal of Trauma and Acute Care Surgery最新文献

Background: Acute lung injury (ALI) after trauma is associated with alveolar dysfunction that causes significant morbidity with limited treatment options. We have shown that AR-R17779, a small molecule agonist of the α7 nicotinic acetylcholine receptor highly expressed on macrophages, prevents lung edema in preclinical models of injury. The mechanism by which AR-R17779 attenuates trauma-induced ALI is unknown. We hypothesized that AR-R17779 decreases trauma-induced ALI by limiting macrophage activation and preventing lung epithelial glycocalyx breakdown.

Methods: C57BL/6 mice underwent a polytrauma model consisting of lung contusion and liver crush injury with cohorts treated with an intraperitoneal dose of AR-R17779 (25 mg/kg) immediately following polytrauma. Lungs were harvested 24 hours postinjury for evaluation of ALI using histology and immunofluorescence of heparan sulfate (HS), a key component of the glycocalyx. In vitro coculture studies were performed to assess the impact of AR-R17779 on the activation of macrophages by lipopolysaccharide (LPS) and its effects on the lung epithelial glycocalyx by immunoblotting, enzyme-linked immunosorbent assay, and HS expression.

Results: AR-R17779 attenuated polytrauma-induced histological ALI and loss of HS from the lung epithelial glycocalyx. In vitro, AR-R17779 dose-dependently suppressed signal transducer and activator of transcription 3 phosphorylation and tumor necrosis factor release from LPS-treated macrophages. In coculture studies, treating LPS-stimulated macrophages with AR-R17779 decreased epithelial glycocalyx degradation compared with macrophages treated with LPS alone.

Conclusion: AR-R17779 attenuated trauma-induced ALI by preventing lung epithelial glycocalyx breakdown, which may result from the suppression of macrophage proinflammatory activity. Future research should test AR-R17779 as an adjunct to resuscitation aimed at limiting dysregulated macrophage activation and ALI after trauma.

Background: Health literacy (HL) is the ability to understand and use information for health decisions. Low HL is associated with poor surgical outcomes and disparities in care, but its impact on acute care surgery (ACS) populations is poorly understood. Health literacy is important in ACS populations where patients have complex medical needs, limited preoperative communication, and significant social vulnerabilities. We performed a systematic review aimed at assessing HL-related outcomes in ACS populations, evaluating the quality of existing evidence and examining equity-related variable collection using the PROGRESS+ framework.

Methods: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were queried up to May 25, 2023, and studies evaluating HL in ACS populations were included. Two reviewers independently extracted relevant articles and performed risk of bias analyses. Studies evaluating the association between HL and patient outcomes in ACS populations were included. Equity-related reporting within studies was evaluated with the PROGRESS+ checklist. Of 1,369 abstracts identified, 10 studies remained after full-text review.

Results: All included studies were observational with a median patient enrollment of 128 (interquartile range, 58-199). Low HL was associated with worse knowledge of injuries, decreased adherence, and poorer follow-up in seven studies (70%). Moderate to high risk of bias was found in six studies (60%). No study reported all 10 PROGRESS+ variables, and 4 studies (40%) reported 3 or fewer.

Conclusion: While studies evaluating HL-related outcomes in ACS populations are few, many found adverse outcomes related to low HL. However, these studies frequently lacked validated measures, comprehensive variable reporting, and consideration of social factors, with many at a high risk of bias. High-quality research using standardized HL instruments and improved equity data collection is needed to inform interventions and improve outcomes.

Level of evidence: Systematic Review/Meta analyses; Level IV.

Background: Chronic pain, anxiety, depression, and posttraumatic stress disorder (PTSD) are frequently seen after traumatic injury. Ketamine infusions used to treat acute pain may decrease the risk of chronic pain and improve psychological outcomes of injured patients. We hypothesized patients receiving ketamine would have a lower incidence of chronic pain, anxiety, depression, and PTSD.

Methods: A prospective, randomized, double-blind placebo-controlled trial of severely injured (Injury Severity Score ≥15) adult patients (age, 18-64 years) admitted to a Level 1 trauma center was conducted. Exclusion criteria included pregnancy and chronic opiate use. All patients were prescribed a patient-controlled analgesia and randomized to either adjustable dose ketamine (ADK) starting at 3 μg/kg/min or an equivalent rate of 0.9% normal saline. Quality of life (QoL) outcomes were measured using Depression and Anxiety (Depression Anxiety Stress Scales 21), PTSD (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-5), Trauma quality of life (TQOL), and pain (Brief Pain Inventory-Short Form) questionnaires at hospitalization, and 1, 3, and 6 months postdischarge. Linear regression analysis evaluated the relationship between groups and baseline pain and mental health outcomes at each follow-up.

Results: Forty-four of 82 patients (54%) were randomized to ADK. Both groups were similar in demographics, injury mechanisms/severity, and baseline QOL measures. Patients in the ketamine group had significantly less anxiety symptom severity ( p < 0.05) and PTSD ( p < 0.05), with significantly less re-experiencing symptoms (subscale of PTSD) at 3 and 6 months ( p < 0.05).

Conclusion: Ketamine infusion for acute pain treatment in severe traumatic injury may significantly reduce anxiety and PTSD 6 months after injury. This effect may be specific to the memory processes responsible for re-experiencing symptoms. Further research should explore the effects of acute ketamine administration on the neurobiological mechanisms implicated in the development of PTSD, as this could be a novel preventative intervention to improve QoL for injured patients.

Level of evidence/study type: Therapeutic/Care Management; Level I.

Background: Trauma-induced coagulopathy (TIC) has distinct fibrinolytic phenotypes based on viscoelastic testing. The underlying mechanisms behind differences in fibrinolytic responses to trauma are unclear. We hypothesized that plasma proteins crosslinked into fibrin clots by the transglutaminase activity of factor XIII (FXIII) may explain tissue-type plasminogen activator (tPA) responsiveness observed in fibrinolysis shutdown.

Methods: Plasma samples from trauma patients were categorized into four fibrinolytic phenotypes (hyperfibrinolysis, hypofibrinolysis, fibrinolysis shutdown, and physiologic fibrinolysis) based on rapid thromboelastography and tPA-enhanced thromboelastography. Plasma underwent liquid chromatography-mass spectrometry proteomics for substrates of FXIII, evaluation for FXIII concentration/activity, and Western blotting to confirm proteomic findings. In vitro studies assessed cysteine cathepsin-mediated proteolysis of fibrinolytic and clot-related proteins.

Results: Plasma proteomic analysis identified differences in levels of four proteins known to be crosslinked into fibrin in fibrinolysis shutdown patients. Patients with shutdown exhibited significantly higher plasma FXIII activity compared with other phenotypes. Because FXIII crosslinks protease inhibitors to fibrin, we studied inflammatory cysteine cathepsins' ability to degrade fibrinolytic proteins. Cysteine cathepsins degraded coagulation and fibrinolytic proteins in vitro, including plasminogen, tPA, and fibrinogen. Cathepsin L exposure completely disrupted ex vivo fibrin clot formation and impaired fibrinolytic enzyme function, highlighting its potential multifaceted role in TIC pathophysiology.

Conclusion: Elevated FXIII activity and protease inhibitor incorporation into fibrin clots may regulate fibrinolysis shutdown in trauma patients with fibrinolysis shutdown by inhibiting cysteine cathepsin activity. These findings identify FXIII and cysteine cathepsins as possible contributors to TIC that should be studied further.

Introduction: Compensation disparities significantly impact junior faculty, especially trauma surgeons (TSs) facing complex compensation structures. Only 20.3% of TSs think that their compensation is determined objectively, highlighting the importance of understanding compensation metrics. We aim to measure the worth of different trauma-related specialties through total cash compensation (TCC), work relative value units (wRVUs), and TCC/wRVU.

Methods: Total cash compensation, wRVU, and TCC/wRVU data were obtained from Medical Group Management Association from 2010 to 2023 for critical care specialists, orthopedic surgeons, general surgeons, and TSs in academic (Ac) and nonacademic (non-Ac) settings. Z test compared mean values between Ac VERSUS non-Ac annually. Ac/non-Ac ratios were calculated to assess compensation trends.

Results: Academic physicians consistently earned less TCC than non-Ac counterparts, with TSs showing the highest mean difference in 2023 (-$132,941). Academic TSs generated significantly more wRVUs than non-Ac counterparts (2,169-2,886 more annually) through 2018, but this advantage disappeared by 2023. Academic TSs consistently earned less per wRVU, with the most dramatic disadvantage in 2010 (Ac/non-Ac ratio of 0.50). While this improved to 0.82 by 2023, it remained the lowest among all trauma-related specialties (compared with 0.89 for orthopedic surgeons, 1.39 for critical care specialists, and 0.96 for general surgeons).

Conclusion: Our longitudinal study demonstrates that Ac physicians receive lower TCC and TCC/wRVU, even while historically maintaining higher clinical productivity. The traditional justification that lower Ac compensation reflects reduced clinical activity is challenged by our finding that Ac trauma clinicians historically generated more wRVUs. Trauma surgeons face a "double disadvantage," which is being undercompensated relative to both non-Ac TSs and other Ac specialists. Rectifying these compensation inequities is critical to preserving the Ac mission and ensuring excellence in trauma care, education, and research.

Level of evidence: Economic and Value Based Evaluations; Level III.