Mechanism matters: mortality and endothelial cell damage marker differences between blunt and penetrating traumatic injuries across three prehospital clinical trials

Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to characterize clinical and endothelial cell damage marker differences across blunt and penetrating injured patients enrolled in three large, prehospital randomized trials which focused on hemorrhagic shock. In this secondary analysis, patients with systolic blood pressure 108 were included. In addition, patients with both blunt and penetrating injuries were excluded. The primary outcome was 30-day mortality. Mortality was characterized using Kaplan–Meier and Cox proportional-hazards models. Generalized linear models were used to compare biomarkers. Chi squared tests and Wilcoxon rank-sum were used to compare secondary outcomes. We characterized data of 696 enrolled patients that met all secondary analysis inclusion criteria. Blunt injured patients had significantly greater 24-h (18.6% vs. 10.7%, log rank p = 0.048) and 30-day mortality rates (29.7% vs. 14.0%, log rank p = 0.001) relative to penetrating injured patients with a different time course. After adjusting for confounders, blunt mechanism of injury was independently predictive of mortality at 30-days (HR 1.84, 95% CI 1.06–3.20, p = 0.029), but not 24-h (HR 1.65, 95% CI 0.86–3.18, p = 0.133). Elevated admission levels of endothelial cell damage markers, VEGF, syndecan-1, TM, S100A10, suPAR and HcDNA were associated with blunt mechanism of injury. Although there was no difference in multiple organ failure (MOF) rates across injury mechanism (48.4% vs. 42.98%, p = 0.275), blunt injured patients had higher Denver MOF score (p < 0.01). The significant increase in 30-day mortality and endothelial cell damage markers in blunt injury relative to penetrating injured patients highlights the importance of considering mechanism of injury within the inclusion and exclusion criteria of future clinical trials. © 2024, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Reciprocal effects of interleukin-4 and interferon-γ on immunoglobulin E-mediated mast cell degranulation: a role for nitric oxide but not peroxynitrite or cyclic guanosine monophosphate

We report that cultured rat peritoneal cells spontaneously synthesize nitric oxide and this is associated with active suppression of mast cell secretory function. Addition of interleukin-4 (IL-4) or the nitric oxide synthase inhibitor N-monomethyl-l-arginine to peritoneal cells inhibited nitric oxide synthesis and enhanced anti-IgE-mediated mast cell degranulation, measured as serotonin release. Interferon-γ (IFN-γ) completely overcame the enhancement of serotonin release and suppression of nitrite production induced by IL-4. Over several experiments, with or without IL-4 and/or IFN-γ, serotonin release correlated inversely with nitrite production. On a cell-for-cell basis, non-mast cells produced ≈30 times more nitrite than mast cells in peritoneal cell populations, with or without IFN-γ stimulation. The nitric oxide donor S-nitrosoglutathione inhibited anti-IgE-induced serotonin release from purified mast cells, whereas 8-bromo-cyclic GMP, the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, superoxide dismutase and the peroxynitrite scavenger uric acid, were without effect. We conclude that IL-4 and IFN-γ reciprocally regulate mast cell secretory responsiveness via control of nitric oxide synthesis by accessory cells; the nitric oxide effect on mast cells is direct but does not involve cyclic GMP or peroxynitrite

Proximal Splenic Artery Embolization In Blunt Splenic Trauma

Proximal embolization of the splenic artery (PSAE) has recently been reported for traumatic splenic injury. The suggested mechanism of action entails a decrease in the splenic blood pressure without ischemia due to collateral blood supply. The main complications of selective embolization are continuous bleeding, splenic infarcts and splenic abscesses. The main complications of observation alone are continuous bleeding and formation of splenic pseudoaneurysms. Our aim was to assess the efficacy of PSAE in the cessation of bleeding without formation of pseudoaneurysms, and the outcome of the spleen after such intervention. A prospective observational study of all patients undergoing PSAE for traumatic splenic injury in our institution over a 33-month period. Clinical and Doppler sonographic examinations were performed to assess cessation of bleeding, splenic blood flow, and formation of splenic pseudoaneurysms, infarcts or abscesses. During 33 months, 11 patients with blunt abdominal trauma and tomographic evidence of either high grade or actively bleeding splenic injuries were treated by PSAE. During follow-up, no patient underwent surgery or repeated embolization. Preserved blood flow was found on Doppler sonography in 82% of the patients and no pseudoaneurysms were demonstrated. A perisplenic collection was found in one patient and responded well to percutaneous drainage. Proximal embolization of the splenic artery for severe splenic injury is highly successful in cessation of bleeding while preserving splenic architecture. There were minimal complications in this series demonstrated by clinical and Doppler examinations

Nonoperative Management of Blunt Splenic Trauma: Also Feasible and Safe in Centers with Low Trauma Incidence and in the Presence of Established Risk Factors

Background: Treatment of blunt splenic trauma has undergone dramatic changes over the last few decades. Nonoperative management (NOM) is now the preferred treatment of choice, when possible. The outcome of NOM has been evaluated. This study evaluates the results following the management of blunt splenic injury in adults in a Swedish university hospital with a low blunt abdominal trauma incidence. Method: Fifty patients with blunt splenic trauma were treated at the Department of Surgery, Lund University Hospital from January 1994 to December 2003. One patient was excluded due to a diagnostic delay of > 24 h. Charts were reviewed retrospectively to examine demographics, injury Severity score (ISS), splenic injury grade, diagnostics, treatment and outcome measures. Results: Thirty-nine patients (80%) were initially treated nonoperatively (NOM), and ten (20%) patients underwent immediate surgery (operative management, OM). Only one (3%) patient failed NOM and required surgery nine days after admission (failure of NOM, FNOM). The patients in the OM group had higher ISS (p < 0.001), higher grade of splenic injury (p < 0.001), and were hemodynamically unstable to a greater extent (p < 0.001). This was accompanied by increased transfusion requirements (p < 0.001), longer stay in the ICU unit (p < 0.001) and higher costs (p = 0.001). Twenty-seven patients were successfully treated without surgery. No serious complication was found on routine radiological follow-up. Conclusion: Most patients in this study were managed conservatively with a low failure rate of NOM. NOM of blunt splenic trauma could thus be performed in a seemingly safe and effective manner, even in the presence of established risk factors. Routine follow-up with CT scan did not appear to add clinically relevant information affecting patient management