Health-related Quality of Life in Patients with Metastatic Spinal Cord Compression.

OBJECTIVE: Improvements in cancer treatment have resulted in an increased number of patients with metastatic spinal cord compression (MSCC). Because patients with MSCC often have a limited expected survival time, maintenance of a high functional level and quality of life are important. However, there is limited information about health-related quality of life (HRQoL) in patients with MSCC. The aim of this study was to examine the feasibility of routine assessment of HRQoL based on the Euroqol-5 dimensions (EQ-5D) questionnaire in a cohort of patients consecutively admitted for evaluation of acute symptoms of MSCC. METHODS: From 1 January to 31 December 2011, 544 patients diagnosed with acute symptoms of MSCC were consecutively enrolled in a cohort study. All patients were evaluated through a centralized referral system at one treatment facility. Data were prospectively registered, the variables age, sex, primary oncologic diagnosis, Tokuhashi Revised score, EQ-5D score and treatment modality being recorded on admission. The study patients were treated conservatively with radiotherapy alone or with surgery and subsequent radiotherapy. The EQ-5D questionnaire was administered on admission (baseline) and 6, 12, 26 and 52 weeks after admission. Response rates, completion rates and HRQoL scores were analyzed by relevant subgroups. Response rates were based on all questionnaires returned regardless of whether or not they had been completed, whereas completion rates were based on fully completed questionnaires (i.e., containing responses to all five questions. RESULTS: The mean age was 65 years (range, 20-95 years); 57% of the patients were men. The overall response rate to the Euroqol-5 dimensions (EQ-5D) questionnaires was 84% and the overall completion rate 72%. At baseline, mean EQ-5D scores were significantly lower for patients treated with surgery and subsequent radiotherapy 0.28 (95% CI, 0.19-0.36) than for those treated with radiotherapy alone 0.42 (95% CI, 0.38-0.46). At the one-year follow-up, the mean EQ-5D scores had improved to 0.71 (95% CI, 0.64-0.77) for patients treated with surgery and subsequent radiotherapy and 0.63 (95% CI, 0.56-0.70) for patients treated with radiotherapy alone. CONCLUSIONS: Measurement of HRQoL in patients consecutively admitted for evaluation of acute symptoms of MSCC is feasible and detects significant changes over time between treatment modalities and different strata of expected survival.

Platelet aggregation following trauma: a prospective study.

We aimed to elucidate platelet function in trauma patients, as it is pivotal for hemostasis yet remains scarcely investigated in this population. We conducted a prospective observational study of platelet aggregation capacity in 213 adult trauma patients on admission to an emergency department (ED). Inclusion criteria were trauma team activation and arterial cannula insertion on arrival. Blood samples were analyzed by multiple electrode aggregometry initiated by thrombin receptor agonist peptide 6 (TRAP) or collagen using a Multiplate device. Blood was sampled median 65 min after injury; median injury severity score (ISS) was 17; 14 (7%) patients received 10 or more units of red blood cells in the ED (massive transfusion); 24 (11%) patients died within 28 days of trauma: 17 due to cerebral injuries, four due to exsanguination, and three from other causes. No significant association was found between aggregation response and ISS. Higher TRAP values were associated with death due to cerebral injuries (P < 0.01, when corrected for ISS and platelet counts), whereas lower platelet counts were associated with massive transfusion (P < 0.01, when corrected for ISS and aggregation). An aggregation value of 145 IU by TRAP significantly identified death due to cerebral injury (sensitivity 71% and specificity 76%, P < 0.01) by receiver operating characteristic-curve analysis; the corresponding value of platelet counts for massive transfusion was 189 × 10/l (sensitivity 86%, specificity 75%, P < 0.01). We concluded there was no simple relationship between platelet aggregation and injury severity. Our results indicate that high platelet aggregation values are associated with fatality of cerebral injury.

Low hemorrhage-related mortality in trauma patients in a Level I trauma center employing transfusion packages and early thromboelastography-directed hemostatic resuscitation with plasma and platelets.

BACKGROUND: Hemorrhage accounts for most preventable trauma deaths, but still the optimal strategy for hemostatic resuscitation remains debated. STUDY DESIGN AND METHODS: This was a prospective study of adult trauma patients admitted to a Level I trauma center. Demography, Injury Severity Score (ISS), transfusion therapy, and mortality were registered. Hemostatic resuscitation was based on a massive transfusion protocol encompassing transfusion packages and thromboelastography (TEG)-guided therapy. RESULTS: A total of 182 patients were included (75% males, median age 43 years, ISS of 17, 92% with blunt trauma). Overall 28-day mortality was 12% with causes of death being exsanguinations (14%), traumatic brain injury (72%, two-thirds expiring within 24 hr), and other (14%). One-fourth, 16 and 15% of the patients, received red blood cells (RBCs), plasma, or platelets (PLTs) within 2 hours from admission and 68, 71, and 75%, respectively, of patients transfused within 24 hours received the respective blood products within the first 2 hours. In patients transfused within 24 hours, the median number of blood products at 2 hours was 5 units of RBCs, 5 units of plasma, and 2 units of PLT concentrates. Nonsurvivors had lower clot strength by kaolin-activated TEG and TEG functional fibrinogen and lower kaolin-tissue factor-activated TEG α-angle and lysis after 30 minutes compared to survivors. None of the TEG variables were independent predictors of massive transfusion or mortality. CONCLUSION: Three-fourths of the patients transfused with plasma or PLTs within 24 hours received these in the first 2 hours. Hemorrhage caused 14% of the deaths. We introduced transfusion packages and early TEG-directed hemostatic resuscitation at our hospital 10 years ago and this may have contributed to reducing hemorrhagic trauma deaths.

Elderly trauma patients have high circulating noradrenaline levels but attenuated release of adrenaline, platelets, and leukocytes in response to increasing injury severity.

OBJECTIVE: High patient age is a strong predictor of poor outcome in trauma patients. The present study investigated the effect of age on mortality and biomarkers of sympathoadrenal activation, tissue, endothelial, and glycocalyx damage, coagulation activation/inhibition, fibrinolysis, and inflammation in trauma patients at admission. DESIGN: Prospective observational study. SETTING: Single level I trauma center. PATIENTS: Eighty adult trauma patients (≥18 yrs) who met criteria for full trauma team activation and had an arterial cannula. INTERVENTION: Blood sampling a median of 68 min (interquartile range 48-88) post injury. MEASUREMENTS: Data on demography, biochemistry, Injury Severity Score, and 30-day mortality were recorded and plasma/serum was analyzed for biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), tissue/endothelial cell/glycocalyx damage (histone-complexed DNA fragments, annexin V, thrombomodulin, syndecan-1), platelet activation (soluble CD40 ligand), coagulation activation/inhibition (prothrombin fragment 1.2, thrombin/antithrombin complex, antithrombin, protein C, activated protein C, protein S, soluble endothelial protein C receptor, tissue factor pathway inhibitor, von Willebrand factor, fibrinogen, factor XIII), fibrinolysis (D-dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1), and inflammation (interleukin-6, terminal complement complex). Patients were stratified according to the median age (46 yrs) of the full cohort. RESULTS: Older trauma patients had markedly higher noradrenaline (p < .001) but an attenuated increase in adrenaline with increasing Injury Severity Score and lower platelets and leukocytes (both p < .05) compared to the younger patients. Older patients displayed a biomarker profile suggestive of enhanced release, activation, and consumption of the natural anticoagulants (low antithrombin, high activated protein C, protein S, and tissue factor pathway inhibitor) and hyperfibrinolysis (high tissue-type plasminogen activator) (all p < .05 vs. younger patients). Age was an independent predictor of mortality (hazard ratio 1.04 [95% confidence interval 1.01-1.07], p = .005) after adjusting for Injury Severity Score, prehospital Glasgow Coma Scale, and plasma catecholamines. CONCLUSIONS: In trauma patients, the association between age and mortality was confirmed. Older patients had high plasma noradrenaline but attenuated adrenaline release with higher Injury Severity Score, impaired platelet and leukocyte mobilization, enhanced consumption of anticoagulants, and hyperfibrinolysis, which may all contribute to the poor outcome in these patients.

High levels of soluble VEGF receptor 1 early after trauma are associated with shock, sympathoadrenal activation, glycocalyx degradation and inflammation in severely injured patients: a prospective study.

BACKGROUND: The level of soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is increased in sepsis and strongly associated with disease severity and mortality. Endothelial activation and damage contribute to both sepsis and trauma pathology. Therefore, this study measured sVEGFR1 levels in trauma patients upon hospital admission hypothesizing that sVEGFR1 would increase with higher injury severity and predict a poor outcome. METHODS: Prospective observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry, Injury Severity Score (ISS), transfusions and 30-day mortality were recorded and plasma/serum (sampled a median of 68 min (IQR 48-88) post-injury) was analyzed for sVEGFR1 and biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), tissue injury (histone-complexed DNA fragments, hcDNA), endothelial activation and damage (von Willebrand Factor Antigen, Angiopoietin-2, soluble endothelial protein C receptor, syndecan-1, soluble thrombomodulin (sTM)), coagulation activation/inhibition and fibrinolysis (prothrombinfragment 1 + 2, protein C, activated Protein C, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer) and inflammation (interleukin-6). Spearman correlations and regression analyses to identify variables associated with sVEGFR1 and its predictive value. RESULTS: Circulating sVEGFR1 correlated with injury severity (ISS, rho = 0.46), shock (SBE, rho = -0.38; adrenaline, rho = 0.47), tissue injury (hcDNA, rho = 0.44) and inflammation (IL-6, rho = 0.54) (all p < 0.01) but by multivariate linear regression analysis only lower SBE and higher adrenaline and IL-6 were independent predictors of higher sVEGFR1. sVEGFR1 also correlated with biomarkers indicative of endothelial glycocalyx degradation (syndecan-1, rho = 0.67), endothelial cell damage (sTM, rho = 0.66) and activation (Ang-2, rho = 0.31) and hyperfibrinolysis (tPA, rho = 0.39; D-dimer, rho = 0.58) and with activated protein C (rho = 0.31) (all p < 0.01). High circulating sVEGFR1 correlated with high early and late transfusion requirements (number of packed red blood cells (RBC) at 1 h (rho = 0.27, p = 0.016), 6 h (rho = 0.27, p = 0.017) and 24 h (rho = 0.31, p = 0.004) but was not associated with mortality. CONCLUSIONS: sVEGFR1 increased with increasing injury severity, shock and inflammation early after trauma but only sympathoadrenal activation, hypoperfusion, and inflammation were independent predictors of sVEGFR1 levels. sVEGFR1 correlated strongly with other biomarkers of endothelial activation and damage and with RBC transfusion requirements. Sympathoadrenal activation, shock and inflammation may be critical drivers of endothelial activation and damage early after trauma.

Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? An observational study.

INTRODUCTION: It is debated whether early trauma-induced coagulopathy (TIC) in severely injured patients reflects disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype, acute coagulopathy of trauma shock (ACoTS) or yet other entities. This study investigated the prevalence of overt DIC and ACoTS in trauma patients and characterized these conditions based on their biomarker profiles. METHODS: An observational study was carried out at a single Level I Trauma Center. Eighty adult trauma patients (≥18 years) who met criteria for full trauma team activation and had an arterial cannula inserted were included. Blood was sampled a median of 68 minutes (IQR 48 to 88) post-injury. Data on demography, biochemistry, injury severity score (ISS) and mortality were recorded. Plasma/serum was analyzed for biomarkers reflecting tissue/endothelial cell/glycocalyx damage (histone-complexed DNA fragments, Annexin V, thrombomodulin, syndecan-1), coagulation activation/inhibition (prothrombinfragment 1+2, thrombin/antithrombin-complexes, antithrombin, protein C, activated protein C, endothelial protein C receptor, protein S, tissue factor pathway inhibitor, vWF), factor consumption (fibrinogen, FXIII), fibrinolysis (D-dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1) and inflammation (interleukin (IL)-6, terminal complement complex (sC5b-9)). Comparison of patients stratified according to the presence or absence of overt DIC (International Society of Thrombosis and Hemostasis (ISTH) criteria) or ACoTS (activated partial thromboplastin time (APTT) and/or international normalized ratio (INR) above normal reference). RESULTS: No patients had overt DIC whereas 15% had ACoTS. ACoTS patients had higher ISS, transfusion requirements and mortality (all P < 0.01) and a biomarker profile suggestive of enhanced tissue, endothelial cell and glycocalyx damage and consumption coagulopathy with low protein C, antithrombin, fibrinogen and FXIII levels, hyperfibrinolysis and inflammation (all P < 0.05). Importantly, in non-ACoTS patients, apart from APTT/INR, higher ISS correlated with biomarkers of enhanced tissue, endothelial cell and glycocalyx damage, protein C activation, coagulation factor consumption, hyperfibrinolysis and inflammation, that is, resembling that observed in patients with ACoTS. CONCLUSIONS: ACoTS and non-ACoTS may represent a continuum of coagulopathy reflecting a progressive early evolutionarily adapted hemostatic response to the trauma hit and both are parts of TIC whereas DIC does not appear to be part of this early response.

Thrombelastography and biomarker profiles in acute coagulopathy of trauma: a prospective study.

BACKGROUND: Severe injury induces an acute coagulopathy associated with increased mortality. This study compared the Thrombelastography (TEG) and biomarker profiles upon admission in trauma patients. METHODS: Prospective observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry including standard coagulation tests, hematology, transfusions, Injury Severity Score (ISS) and TEG were recorded. Retrospective analysis of thawed plasma/serum for biomarkers reflecting tissue injury (histone-complexed DNA fragments), sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (sCD40L, protein C, activated Protein C, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer, prothrombinfragment 1+2, plasmin/α2-antiplasmin complex, thrombin/antithrombin complex, tissue factor pathway inhibitor, antithrombin, von willebrand factor, factor XIII). Comparison of patients stratified according to ISS/TEG maximum clot strength. Linear regression analysis of variables associated with clot strength. RESULTS: Trauma patients had normal (86%), hypercoagulable (11%) or hypocoagulable (1%) TEG clot strength; one had primary hyperfibrinolysis. Hypercoagulable patients had higher age, fibrinogen and platelet count (all p < 0.05), none had increased activated partial thromboplastin time (APTT) or international normalized ratio (INR) and none required massive transfusion (> 10 red blood cells the initial 24 h). Patients with normal or hypercoagulable TEG clot strength had comparable biomarker profiles, but the few patients with hypocoagulable TEG clot strength and/or hyperfibrinolysis had very different biomarker profiles.Increasing ISS was associated with higher levels of catecholamines, histone-complexed DNA fragments, sCD40L, activated protein C and D-dimer and reduced levels of non-activated protein C, antithrombin, fibrinogen and factor XIII (all p < 0.05). Fibrinogen and platelet count were associated independently with clot strength in patients with ISS ≤ 26 whereas only fibrinogen was associated independently with clot strength in patients with ISS > 26. In patients with ISS > 26, adrenaline and sCD40L were independently negatively associated with clot strength. CONCLUSIONS: Trauma patients displayed different coagulopathies by TEG and variables independently associated with clot strength changed with ISS. In the highest ISS group, adrenaline and sCD40L were independently negatively associated with clot strength indicating that these may contribute to acute coagulopathy.

Guidelines for the conduction of follow-up studies measuring injury-related disability.

BACKGROUND: Scientific knowledge on functional outcome after injury is limited. During the past decade, a variety of measures have been used at various moments in different study populations. Guidelines are needed to increase comparability between studies. METHODS: A working group of the European Consumer Safety Association conducted a literature review of empirical studies into injury-related disability (1995-2005). We included injury from all levels of severity and selected studies using generic health status measures with both short-term and long-term follow up. The results were used as input for a consensus procedure toward the development of guidelines for defining the study populations, selecting the health status measures, selecting the timings of the assessments, and data collection procedures. RESULTS: The group reached consensus on a common core of health status measures and assessment moments. The group advises to use a combination of EuroQol-5D and Health Utilities Mark III in all studies on injury-related disability. This combination covers all relevant health domains, is applicable in all kinds of injury populations and in widely different age ranges, provides a link with utility scores, and has several practical advantages (e.g., brevity, availability in different languages). For specific types of injury, the common core may be supplemented by injury-specific measures. The group advises a common core of assessments at 1, 2, 4, and 12 months after injury. CONCLUSIONS: Our guidelines should be tested and may lead to improved and more consistent epidemiologic data on the incidence, severity, and duration of injury-related disability.