Pilot Randomized trial of Fibrinogen in Trauma Haemorrhage (PRooF-iTH): study protocol for a randomized controlled trial.

BACKGROUND: Haemorrhage remains a leading cause of morbidity and mortality in trauma patients. Fibrinogen is an essential endogenous component of haemostasis and the plasma level is associated with bleeding, transfusion and outcome. Fibrinogen concentrate is widely used to correct acquired hypofibrinogenaemia, recommended by several international guidelines for the treatment of trauma patients, but evidence is lacking regarding the treatment safety and efficacy. We aim to assess the efficacy and safety of an immediate pre-emptive first-line treatment with fibrinogen concentrate in patients with trauma haemorrhage in need of haemostatic resuscitation. METHODS/DESIGN: This is a single-centre, randomized (1:1, active:placebo), placebo-controlled, double-blinded, investigator-initiated phase II trial. The trial population consists of 40 adult patients (>18 years) with traumatic, critical bleeding admitted to the Level 1 Trauma Centre at Rigshospitalet in Copenhagen, with immediate need for blood transfusion on arrival and an expected need for haemostatic resuscitation with multiple transfusions during the initial resuscitation. Patients will receive either pre-emptive administration of a bolus dose of 60-70 mg/kg fibrinogen concentrate (Riastap®) or placebo 0.9 % saline in equal volume to active treatment, both given as intravenous infusion blinded for the person administering the infusion. The primary end point is the change in thrombelastograph (TEG®) functional fibrinogen maximum amplitude in millimetres at 15 min after the intervention. The follow-up period on safety events and mortality will be until day 30. To detect a difference in the change from baseline to the 15-minute post-randomization measurement of 6-8 mm in TEG® functional fibrinogen maximum amplitude with a power of 0.90 and alpha of 0.05, we require 19 patients in each group. We have chosen to include 40 patients, 20 evaluable patients in each randomization group in case of attrition, in the present trial. DISCUSSION: Patients considered to be included in the trial will temporarily have a compromised consciousness because of the acute, critical bleeding related to trauma, so scientific guardians will co-sign the informed consent form. Next of kin and the patients' general practitioner or the patients will co-sign as soon as possible. This trial will test whether immediate pre-emptive fibrinogen concentrate administered to adult trauma patients as first-line treatment of trauma haemorrhage will increase the clot strength as evaluated by thrombelastography, transfusion requirements and survival in patients receiving haemostatic resuscitation according to current standard of care. TRIAL REGISTRATION: EudraCT no. 2014-003978-16 (22/1 2015); ClinicalTrials.gov: NCT02344069 . Registered on 14 January 2015. Trial protocol version 4.2 (23-12-2014).

Low level of procoagulant platelet microparticles is associated with impaired coagulation and transfusion requirements in trauma patients.

BACKGROUND: Following activation, platelets release small vesicles called platelet-derived microparticles (PMPs). PMPs accelerate thrombin generation and thus clot formation at sites of injury by exposing the procoagulant membrane phospholipid phosphatidylserine (PS). The role of PMPs in coagulopathy and hemorrhage following trauma remains elusive. We hypothesized that low levels of PS-positive PMPs (PS + PMPs) would be associated with impaired clot formation. METHODS: This is a prospective observational study of 210 trauma patients admitted directly to a Level 1 trauma center. Plasma levels of PS + PMPs were determined by flow cytometry. Coagulation status was assessed by rotational thrombelastometry, and impaired clot formation was defined by an α angle less than 63 degrees using the tissue factor-based EXTEM reagent. Transfusion requirement was assessed by number of units of red blood cells (RBCs) transfused within 24 hours of admission; platelet aggregation capacity was evaluated by the Multiplate assay; and injury severity was determined by the Injury Severity Score (ISS). RESULTS: The median ISS was 17, and blood samples were obtained after a median of 65 minutes following injury. Significantly lower levels of PS + PMPs were found in patients with impaired clot formation (p < 0.001). A low level of PS + PMPs was associated with a higher number of RBCs transfused during the initial 24 hours after admission (p < 0.03) when corrected for risk factors, for example, platelet count, hemoglobin level, and ISS. Platelet aggregation and PS + PMPs did not correlate significantly. CONCLUSION: Low levels of PMPs were associated with impaired clot formation in trauma patients at admission and also with the number of RBC transfusions. This suggests that PMPs may play an important and not previously investigated role in trauma-induced coagulopathy. LEVEL OF EVIDENCE: Prognostic study, level III.

Moderate precision of prognostic scoring systems in a consecutive, prospective cohort of 544 patients with metastatic spinal cord compression.

PURPOSE: Improved survival among cancer patients and diverse conclusions from recent studies make it relevant to reassess the performance of the Tokuhashi Revised score and the Tomita score. The aim of this study was to validate and compare these two scoring systems in a recent and unselected cohort of patients with metastatic spinal cord compression (MSCC). METHODS: In 2011, we conducted a prospective cohort study of 544 patients who were consecutively admitted with MSCC to one treatment facility. Patients estimated survival were assessed with the Tokuhashi Revised score and the Tomita score and compared to the observed survival. We assessed how precise the scoring systems predicted survival with McNemar's test. The prognostic value was illustrated with Kaplan-Meier curves, and the individual prognostic components were analyzed with Cox regression analysis. RESULTS: The mean age was 65 years (range 20-95), and 57 % of the patients were men. The majority of tumors were lung (23 %), prostate (21 %), and breast tumors (18 %). The overall precision of predicted survival was 58.7 % for the Tokuhashi Revised score and 52.9 % for the Tomita score. The observed survival in each of the scoring groups categorized by the scoring systems was statistically significantly different (p < 0.0001). CONCLUSIONS: The Tokuhashi Revised score and the Tomita score are useful in categorizing patients into prognostic groups, and the individual components have important prognostic values. The Tokuhashi Revised score was most precise in predicting survival. However, due to the relatively low precision, we suggest that a modification of both scoring systems is necessary.

Impact of the severity of trauma on early retirement.

OBJECTIVE: To assess the association between Injury Severity Score (ISS) and subsequent risk of early retirement. DESIGN: Observational cohort study with follow-up based on prospectively collected data. Hospital-based data were linked to national register data on pension reception and vital status. SETTING: Level-one urban trauma centre. PARTICIPANTS: Patients aged 18-64 years entering the trauma centre in Copenhagen during 1999-2007 who were alive after three days were followed until early retirement, death or emigration. MAIN OUTCOME MEASURES: Primary outcome was early retirement, defined as receiving disability pension (unintentional) or voluntary early retirement pension (intentional) before the regular age of retirement (65 years). Relative risk of early retirement according to ISS (low, ISS 1-15 vs. high, ISS 16-75) was assessed using Cox proportional hazards regression, adjusted for age and gender. RESULTS: Of all 6687 patients admitted to the trauma centre, a total of 1722 trauma patients were included and followed for a median of 6.2 years (interquartile range (IQR) 3.7-9.1). Of these, 1305 (75.8%) were males, median age was 35.0 years (IQR 25.4-46.5), and median ISS was 16 (IQR 9-25). Three hundred and twenty-two patients retired during follow-up. Patients with high ISS, compared to patients with low ISS, had an increased risk of early retirement, adjusted hazard ratio 2.60 (95% confidence interval (CI) 2.05-3.30; p<0.001). Relative increase in retirement risk was 1.04 (95% CI 1.03-1.05) per ISS point and 1.03 (95% CI 1.03-1.04) per year older. Gender was not found to be a significant risk factor (p=0.69). Five-year absolute risks of early retirement were 9.9% (95% CI 7.8-12.0%) for the low ISS group and 24.6% (95% CI 21.6-27.5%) for the high ISS group. CONCLUSIONS: The risk of early retirement is 2.6 times higher in severely injured patients (ISS 16-75) than the risk in low to moderately injured patients (ISS 1-15) and they have a high absolute 5-year risk as well. Early, targeted interventions to assist with return to work might be able to reduce this risk.

Prognosis in patients with symptomatic metastatic spinal cord compression: survival in different cancer diagnosis in a cohort of 2321 patients.

STUDY DESIGN: A retrospective cohort study of 2321 patients consecutively admitted to one center and diagnosed with acute symptoms of metastatic spinal cord compression (MSCC). OBJECTIVE: To assess the possible change in 1-year survival for patients with MSCC from year 2005 through 2010 with respect to the primary cancer diagnosis. SUMMARY OF BACKGROUND DATA: An increasing number of patients are offered surgical treatment for MSCC. Among the reasons for this development are high evidence clinical studies, improved surgical techniques, and an increasing number of patients being treated for an oncological condition. Preoperative scoring systems are routinely used in the evaluation of these patients, and the primary oncological diagnosis is an important variable in all these systems. To our knowledge, no studies in a large group of patients have assessed the change in survival in these patients. This is of relevance because such changes in survival could have implications on the scoring systems used in the preoperative evaluation. METHODS: All patients referred to the university hospital, Rigshospitalet, suspected of acute symptoms caused by spinal metastases and diagnosed with MSCC from January 1, 2005, to December 31, 2010, were included in a retrospective cohort, n = 2321. For all patients primary tumor, treatment, and 1-year survival was registered. RESULTS: The overall 1-year survival did not change significantly from 2005 to 2010, but there was a significant increase in 1-year survival for the subgroups of patients with lung cancer hazard ratio = 0.93 (P = 0.008, 95% CI: 0.83-0.98) and renal cancer hazard ratio = 0.77 (P = 0.004, 95% CI: 0.56-0.92). CONCLUSION: Patients with MSCC from pulmonary and renal cancers experienced improved survival in the study period. No improvement was seen for patients with other oncological diagnoses. This corresponds to reports from oncological studies and could affect preoperative scoring systems.

Trauma-induced coagulopathy: standard coagulation tests, biomarkers of coagulopathy, and endothelial damage in patients with traumatic brain injury.

It remains to be debated whether traumatic brain injury (TBI) induces a different coagulopathy than does non-TBI. This study investigated traditional coagulation tests, biomarkers of coagulopathy, and endothelial damage in trauma patients with and without TBI. Blood from 80 adult trauma patients was sampled (median of 68 min [IQR 48-88] post-injury) upon admission to our trauma center. Plasma/serum were retrospectively analyzed for biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (protein C, activated protein C, tissue factor pathway inhibitor, antithrombin, prothrombin fragment 1+2, thrombin/antithrombin complex, von Willebrand factor, factor XIII, d-dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1), immunology (interleukin [IL]6), endothelial cell/glycocalyx damage (soluble thrombomodulin, syndecan-1), and vasculogenesis (angiopoietin-1, -2). Patients were stratified according to: (1) isolated severe head/neck injuries (Abbreviated injury score [AIS]-head/neck ≥ 3, AIS-other<3) (isoTBI); (2) severe head/neck and extracranial injuries (AIS-head/neck ≥ 3, AIS-other>3) (sTBI+other); and (3) injuries without significant head/neck injuries (AIS-head/neck<3, including all AIS-other scores) (non-TBI). Twenty-three patients presented with isoTBI, 15 with sTBI+other and 42 with non-TBI. Acute coagulopathy of trauma shock, defined as activated partial thromboplastin time (APTT) and/or international normalized ratio (INR)>35 sec and>1.2, was found in 13%, 47%, and 5%, respectively (p=0.000). sTBI+other had significantly higher plasma levels of adrenaline, noradrenaline, annexin V, d-dimer, IL-6, syndecan-1, soluble thrombomodulin, and reduced protein C and factor XIII levels (all p<0.05). No significant biomarker differences were found between isoTBI and non-TBI patients. Injury severity scale (ISS) rather than the presence or absence of head/neck injuries determined the hemostatic and biomarker response to the injury. The coagulopathy identified thus reflected the severity of injury rather than its localization.

[Parental presence during treatment of injured and acutely ill children]. / Forældretilstedeværelse ved modtagelse og behandling af tilskadekomne og akut syge børn er formentlig hensigtsmæssig.

This review studies the literature on the effects of parental presence during treatment of injured and acutely ill children. Parents wish to stay with their child, and clinicians increasingly find it beneficial, probably correlated with increased experience. Studies indicate that the treatment of the child is not compromised by parental presence but only a few quasi-randomised, quantitative studies have been published, and many circumstances concerning parental presence have not been investigated sufficiently.

[Prehospital treatment of severely injured patients with focus on damage control-surgery]. / Præhospital behandling af svært tilskadekomne patienter med fokus på damage control-kirurgi.

The majority of patients undergoing damage control surgery initially receive prehospital treatment. Bleeding causes 40% of trauma deaths, half of which happen in the prehospital setting. Future research and improved treatment before hospital admission should focus on control of the bleeding, avoidance of hypothermia, minimising the time to definitive surgery, and a restrictive and goal directed therapy with regard to the intake of fluids. On occasion, lifesaving procedures could be performed during transport to the hospital.

Advanced trauma life support, 8th edition, the evidence for change.

The American College of Surgeons Committee on Trauma's Advanced Trauma Life Support Course is currently taught in 50 countries. The 8th edition has been revised following broad input by the International ATLS subcommittee. Graded levels of evidence were used to evaluate and approve changes to the course content. New materials related to principles of disaster management have been added. ATLS is a common language teaching one safe way of initial trauma assessment and management.

Bone grafting the scaphoid nonunion: a systematic review of 147 publications including 5,246 cases of scaphoid nonunion.

In order to elucidate the history of scaphoid nonunion and to evaluate whether or not the problem has been solved, we have reviewed the literature from 1928 to 2003 for union rates, postoperative immobilization periods and complications of the different scaphoid bone grafting procedures. The outcomes of 5 246 scaphoid nonunions were evaluated in three treatment groups. In the first group involving nonvascularized bone grafting without internal fixation, we found a union rate of 80% (95% CI: 78-82) after an average immobilization period of 15 weeks. In the second group involving nonvascularized bone grafting with internal fixation, the figures were 84% (CI: 82-85) and 7 weeks, respectively. In the last group involving vascularized bone grafting with or without internal fixation, the figures were 91% (CI: 87-94) and 10 weeks, respectively. We found no prospective randomized studies comparing different operative treatments of scaphoid nonunion. We conclude that there still is a need for improvement in the treatment of scaphoid nonunion.

The epidemiology of hand injuries in The Netherlands and Denmark.

Little is known about the magnitude of hand injuries at national levels. This paper quantifies and characterises the incidence of hand injuries that require acute medical attention at Emergency Departments in The Netherlands and Denmark. Except for the incidence rate and the referral after treatment, the overall picture of hand injuries is similar for both countries: hand injuries show a peak for teenagers, result mainly from home and leisure accidents, are mainly caused by objects and falls, the majority affect fingers and result mainly in superficial injuries, open wounds and fractures, a small proportion of the victims is admitted into hospital. We conclude that hand injuries are a real burden to society and are worthwhile to be prevented with special attention for home and leisure accidents and occupational accidents. Data recording on the backgrounds of accidents and their long term consequences should be improved.