Previously, we demonstrated that sog9 cells, a murine L cell mutant, are deficient in the expression of C4ST (chondroitin 4-O-sulfotransferase)-1 and that they synthesize fewer and shorter CS (chondroitin sulfate) chains. These results suggested that C4ST-1 regulates not only 4-O-sulfation of CS, but also the length and amount of CS chains; however, the mechanism remains unclear. In the present study, we have demonstrated that C4ST-1 regulates the chain length and amount of CS in co-operation with ChGn-2 (chondroitin N-acetylgalactosaminyltransferase 2). Overexpression of ChGn-2 increased the length and amount of CS chains in L cells, but not in sog9 mutant cells. Knockdown of ChGn-2 resulted in a decrease in the amount of CS in L cells in a manner proportional to ChGn-2 expression levels, whereas the introduction of mutated C4ST-1 or ChGn-2 lacking enzyme activity failed to increase the amount of CS. Furthermore, the non-reducing terminal 4-O-sulfation of N-acetylgalactosamine residues facilitated the elongation of CS chains by chondroitin polymerase consisting of chondroitin synthase-1 and chondroitin-polymerizing factor. Overall, these results suggest that the chain length of CS is regulated by C4ST-1 and ChGn-2 and that the enzymatic activities of these proteins play a critical role in CS elongation.

BackgroundTrauma management requires a multidisciplinary approach, but coordination of staff and procedures is challenging in patients with severe trauma. In October 2014, we implemented a streamlined trauma management system involving emergency physicians trained in severe trauma management, surgical techniques, and interventional radiology. We evaluated the impact of streamlined trauma management on patient management and outcomes (study 1) and evaluated determinants of mortality in patients with severe trauma (study 2).MethodsWe conducted a retrospective cohort study of 125 patients admitted between January 2011 and 2019 with severe trauma (Injury Severity Score ≥16) and persistent hypotension (≥2 systolic blood pressure measurements <90 mm Hg). Patients were divided into a Before cohort (January 2011 to September 2014) and an After cohort (October 2014 to January 2019) according to whether they were admitted before or after the new approach was implemented. The primary outcome was in-hospital mortality.ResultsCompared with the Before cohort (n=59), the After cohort (n=66) had a significantly lower in-hospital mortality (36.4% vs. 64.4%); required less time from hospital arrival to initiation of surgery/interventional radiology (median, 41.0 vs. 71.5 minutes); and was more likely to undergo resuscitative endovascular balloon occlusion of the aorta (24.2% vs. 6.8%). Plasma administration before initiating hemostasis (adjusted OR 1.49 (95% CI 1.04 to 2.14)), resuscitative endovascular balloon occlusion of the aorta (9.48 (95% CI 1.25 to 71.96)), and shorter time to initiation of surgery/interventional radiology (0.97 (95% CI 0.96 to 0.99)) were associated with significantly lower mortality.DiscussionImplementing a streamlined trauma management protocol improved outcomes among hemodynamically unstable patients with severe multiple trauma.Level of evidenceLevel III.

BACKGROUND:Advances in medical equipment have resulted in changes in the management of severe trauma. The role of resuscitative endovascular balloon occlusion of the aorta (REBOA) in this scenario is still unclear. This study aimed to evaluate the usage of REBOA and utility of computed tomography (CT) in the setting of aortic occlusion in our current trauma management. METHODS:This Japanese single-tertiary center, retrospective, and observational study analyzed 77 patients who experienced severe trauma and persistent hypotension between October 2014 and March 2020. RESULTS:All patients required urgent hemostasis. Twenty patients underwent REBOA, 11 underwent open aortic cross-clamping, and 46 did not undergo aortic occlusion. Among patients who underwent aortic occlusion, 19 patients underwent prehemostasis CT, and 7 patients underwent operative exploration without prehemostasis CT for identifying active bleeding sites. The 24-hour and 28-day survival rates in patients who underwent CTwere not inferior to those in patients who did not undergo CT (24-hour survival rate, 84.2% vs. 57.1%; 28-day survival rate, 47.4% vs. 28.6%). Moreover, the patients who underwent CT had less discordance between primary hemostasis site and main bleeding site compared with patients who did not undergo CT (5% vs. 71.4%, p = 0.001).In the patients who underwent prehemostasis CT, REBOA was the most common approach of aortic occlusion. Most of the bleeding control sites were located in the retroperitoneal space. There were many patients who underwent interventional radiology for hemostasis. CONCLUSION:In a limited number of patients whose cardiac arrests were imminent and in whom no active bleeding sites could be clearly identified without CT findings, REBOA for CT diagnosis may be effective; however, further investigations are needed.

This study aimed to evaluate the effect of plasma transfusion before urgent hemostasis initiation on in-hospital mortality in hemodynamically unstable patients with severe trauma. Methods: This retrospective observational study of patients admitted to hospital between January 2011 and January 2019 grouped patients according to whether plasma transfusion was initiated before (Before group) or after (After group) hemostasis initiation. Patients with severe trauma who were unable to wait for plasma transfusion and had started hemostasis before the plasma infusion were excluded. We used multivariable logistic regression analysis to determine the effect of plasma transfusion before the initiation of urgent hemostasis on in-hospital mortality. Results: We included 47 and 73 patients in the Before and After groups, respectively. Blunt trauma was more common, and the Ddimer levels and Injury Severity Score were significantly higher in the Before group than in the After group (median D-dimer, 57.5 versus 38.1 lg/mL; P = 0.040; median Injury Severity Score, 50 versus 34; P < 0.001). Plasma given before hemostasis initiation was associated with significantly lower in-hospital mortality (adjusted odds ratio, 0.27; 95% confidence interval, 0.078-0.900; P = 0.033) in contrast with the total plasma volume given in the first 6 or 24 h. Conclusion: Plasma transfusion before hemostasis initiation could be an important factor for improving outcomes in hemodynamically unstable patients with blunt trauma, high D-dimer levels, or a high Injury Severity Score.