Refining the criteria for immediate total-body CT after severe trauma

Objectives: Initial trauma care could potentially be improved when conventional imaging and selective CT scanning is omitted and replaced by immediate total-body CT (iTBCT) scanning. Because of the potentially increased radiation exposure by this diagnostic approach, proper selection of the severely injured patients is mandatory. Methods: In the REACT-2 trial, severe trauma patients were randomized to iTBCT or conventional imaging and selective CT based on predefined criteria regarding compromised vital parameters, clinical suspicion of severe injuries, or high-risk trauma mechanisms in five trauma centers. By logistic regression analysis with backward selection on the 15 study inclusion criteria, a revised set of criteria was derived and subsequently tested for prediction of severe injury and shifts in radiation exposure. Results: In total, 1083 patients were enrolled with median ISS of 20 (IQR 9–29) and median GCS of 13 (IQR 3–15). Backward logistic regression resulted in a revised set consisting of nine original and one adjusted criteria. Positive predictive value improved from 76% (95% CI 74–79%) to 82% (95% CI 80–85%). Sensitivity decreased by 9% (95% CI 7–11%). The area under the receiver operating characteristics curve remained equal and was 0.80 (95% CI 0.77–0.83), original set 0.80 (95% CI 0.77–0.83). The revised set retains 8.78 mSv (95% CI 6.01–11.56) for 36% of the non-severely injured patients. Conclusions: Selection criteria for iTBCT can be reduced from 15 to 10 clinically criteria. This improves the positive predictive value for severe injury and reduces radiation exposure for less severely injured patients. Key Points: • Selection criteria for iTBCT can be reduced to 10 clinically useful criteria. • This reduces radiation exposure in 36% of less severely injured patients. • Overall discriminative capacity for selection of severely injured patients remained equal

Cost-effectiveness of immediate total-body CT in patients with severe trauma (REACT-2 trial)

Background: The effect of immediate total-body CT (iTBCT) on health economic aspects in patients with severe trauma is an underreported issue. This study determined the cost-effectiveness of iTBCT compared with conventional radiological imaging with selective CT (standard work-up (STWU)) during the initial trauma evaluation. Methods: In this multicentre RCT, adult patients with a high suspicion of severe injury were randomized in-hospital to iTBCT or STWU. Hospital healthcare costs were determined for the first 6 months after the injury. The probability of iTBCT being cost-effective was calculated for various levels of willingness-to-pay per extra patient alive. Results: A total of 928 Dutch patients with complete clinical follow-up were included. Mean costs of hospital care were (sic)25 809 (95 per cent bias-corrected and accelerated (bca) c.i. (sic)22 617 to (sic)29 137) for the iTBCT group and (sic)26 155 ((sic)23 050 to (sic)29 344) for the STWU group, a difference per patient in favour of iTBCT of (sic)346 ((sic)4987 to (sic)4328) (P = 0.876). Proportions of patients alive at 6 months were not different. The proportion of patients alive without serious morbidity was 61.6 per cent in the iTBCT group versus 66.7 per cent in the STWU group (difference -5.1 per cent; P = 0.104). The probability of iTBCT being cost-effective in keeping patients alive remained below 0.56 for the whole group, but was higher in patients with multiple trauma (0.8-0.9) and in those with traumatic brain injury (more than 0.9). Conclusion: Economically, from a hospital healthcare provider perspective, iTBCT should be the diagnostic strategy of first choice in patients with multiple trauma or traumatic brain injury

High rates of clinically relevant incidental findings by total-body CT scanning in trauma patients; results of the REACT-2 trial

To determine whether there is a difference in frequency and clinical relevance of incidental findings detected by total-body computed tomography scanning (TBCT) compared to those by the standard work-up (STWU) with selective computed tomography (CT) scanning. Trauma patients from five trauma centres were randomized between April 2011 and January 2014 to TBCT imaging or STWU consisting of conventional imaging with selective CT scanning. Incidental findings were divided into three categories: 1) major finding, may cause mortality; 2) moderate finding, may cause morbidity; and 3) minor finding, hardly relevant. Generalized estimating equations were applied to assess differences in incidental findings. In total, 1083 patients were enrolled, of which 541 patients (49.9 %) were randomized for TBCT and 542 patients (50.1 %) for STWU. Major findings were detected in 23 patients (4.3 %) in the TBCT group compared to 9 patients (1.7 %) in the STWU group (adjusted rate ratio 2.851; 95%CI 1.337-6.077; p <0.007). Findings of moderate relevance were detected in 120 patients (22.2 %) in the TBCT group compared to 86 patients (15.9 %) in the STWU group (adjusted rate ratio 1.421; 95%CI 1.088-1.854; p <0.010). Compared to selective CT scanning, more patients with clinically relevant incidental findings can be expected by TBCT scanning. aEuro cent Total-body CT scanning in trauma results in 1.5 times more incidental findings. aEuro cent Evaluation by TBCT in trauma results in more patients with incidental findings. aEuro cent In every category of clinical relevance, TBCT detects more incidental findings

Human hepatic HepaRG cells maintain high intrinsic CYP450 activity/metabolism and significantly outperform standard HepG2/C3A cells used in drug pharmacology applications

Introduction: Conventional in vitro human hepatic models for drug testing are based on the use of cell lines or primary human hepatocytes (PHHs). However, limited availability, inter-donor functional variability and early phenotypic alterations of PHHs in vitro restrict their use; whilst cell lines such as HepG2/C3As lack a substantial and variable set of liver-specific functions, specifically, CYP450 activity. In this study we compared CYP450 activity/ metabolism between HepG2/C3A and human HepaRG cells as hepatic models for pre-clinical drug testing. Methods: Human hepatic cell lines [HepG2/C3A or HepaRG] were grown to >80% confluence on collagen-I-coated plates and treated (in triplicates) 24 h with prototypical inducers rifampicin (CYP3A4) and omeprazole (CYP1A2), [n=3]. 50μM testosterone or phenacetin were added and supernatant and cell samples taken after 2 hours of incubation at 37°C. CYP1A2/3A4 activity [P450-Glo™-Luminometry; Promega] was determined (Figure 1). Relative turnover of testosterone [HPLC] and phenacetin [LC-MS/MS] metabolites was also measured. Cell phenotype was assessed by light-microscopy, histology (PAS-Glycogen), CYP3A4, F-actin/phalloidin, and JC-1 fluorescent-staining. Results: Figure 1 shows HepaRG CYP1A2/3A4 activity was 40-80x fold >> HepG2/C3A cells [P<0.001]; Drug profiling revealed HepaRGs had both enhanced production of major metabolites of phenacetin and testosterone and more intact drug metabolism compared with HepG2/C3A. In contrast with HepG2/C3A, HepaRGs displayed a more intact hepatic phenotype, including: Strong positive glycogen, CYP3A4 staining, high JC-1-positive intrinsic metabolic activity (ΔΨm) and organotypic gross morphology. Discussion / Conclusion: HepaRG cells may represent a more physiologically-relevant pre-clinical platform for CYP450 activation/ inhibition, safety pharmacology, as well as drug-drug interaction studies

Refining the criteria for immediate total-body CT after severe trauma

Objectives Initial trauma care could potentially be improved when conventional imaging and selective CT scanning is omitted and replaced by immediate total-body CT (iTBCT) scanning. Because of the potentially increased radiation exposure by this diagnostic approach, proper selection of the severely injured patients is mandatory. Methods In the REACT-2 trial, severe trauma patients were randomized to iTBCT or conventional imaging and selective CT based on predefined criteria regarding compromised vital parameters, clinical suspicion of severe injuries, or high-risk trauma mechanisms in five trauma centers. By logistic regression analysis with backward selection on the 15 study inclusion criteria, a revised set of criteria was derived and subsequently tested for prediction of severe injury and shifts in radiation exposure. Results In total, 1083 patients were enrolled with median ISS of 20 (IQR 9-29) and median GCS of 13 (IQR 3-15). Backward logistic regression resulted in a revised set consisting of nine original and one adjusted criteria. Positive predictive value improved from 76% (95% CI 74-79%) to 82% (95% CI 80-85%). Sensitivity decreased by 9% (95% CI 7-11%). The area under the receiver operating characteristics curve remained equal and was 0.80 (95% CI 0.77-0.83), original set 0.80 (95% CI 0.77-0.83). The revised set retains 8.78 mSv (95% CI 6.01-11.56) for 36% of the non-severely injured patients. Conclusions Selection criteria for iTBCT can be reduced from 15 to 10 clinically criteria. This improves the positive predictive value for severe injury and reduces radiation exposure for less severely injured patients

Clinical and economic impact of HeartLogic (TM) compared with standard care in heart failure patients

Aims The implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator-based HeartLogic (TM) algorithm has recently been developed for early detection of impending decompensation in heart failure (HF) patients; but whether this novel algorithm can reduce HF hospitalizations has not been evaluated. We investigated if activation of the HeartLogic algorithm reduces the number of hospital admissions for decompensated HF in a 1 year post-activation period as compared with a 1 year pre-activation period.Methods and results Heart failure patients with an implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator with the ability to activate HeartLogic and willingness to have remote device monitoring were included in this multicentre non-blinded single-arm trial with historical comparison. After a HeartLogic alert, the presence of HF symptoms and signs was evaluated. If there were two or more symptoms and signs apart from the HeartLogic alert, lifestyle advices were given and/or medication was adjusted. After activation of the algorithm, patients were followed for 1 year. HF events occurring in the 1 year prior to activation and in the 1 year after activation were compared. Of the 74 eligible patients (67.2 +/- 10.3 years, 84% male), 68 patients completed the 1 year follow-up period. The total number of HF hospitalizations reduced from 27 in the pre-activation period to 7 in the post-activation period (P = 0.003). The number of patients hospitalized for HF declined from 21 to 7 (P = 0.005), and the hospitalization length of stay diminished from average 16 to 7 days (P = 0.079). Subgroup analysis showed similar results (P = 0.888) for patients receiving cardiac resynchronization therapy during the pre-activation period or not receiving cardiac resynchronization therapy, meaning that the effect of hospitalizations cannot solely be attributed to reverse remodelling. Subanalysis of a single-centre Belgian subpopulation showed important reductions in overall health economic costs (P = 0.025).Conclusion Activation of the HeartLogic algorithm enables remote monitoring of HF patients, coincides with a significant reduction in hospitalizations for decompensated HF, and results in health economic benefits.Cardiolog

Emergency Bleeding Control Interventions After Immediate Total-Body CT Scans in Trauma Patients

Background: Immediate total-body CT (iTBCT) is often used for screening of potential severely injured patients. Patients requiring emergency bleeding control interventions benefit from fast and optimal trauma screening. The aim of this study was to assess whether an initial trauma assessment with iTBCT is associated with lower mortality in patients requiring emergency bleeding control interventions. Methods: In the REACT-2 trial, patients who sustained major trauma were randomized for iTBCT or for conventional imaging and selective CT scanning (standard workup; STWU) in five trauma centers. Patients who underwent emergency bleeding control interventions following their initial trauma assessment with iTBCT were compared for mortality and clinically relevant time intervals to patients that underwent the initial trauma assessment with the STWU. Results: In the REACT-2 trial, 1083 patients were enrolled of which 172

Erratum to: High rates of clinically relevant incidental findings by total-body CT scanning in trauma patients: Results of the REACT-2 trial

A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows: K. Treskes1, S.A. Bos1, L.F.M. Beenen2, J.C. Sierink1, M.J.R. Edwards3, B.J

Fibrinogen production is enhanced in an in-vitro model of non-alcoholic fatty liver disease: An isolated risk factor for cardiovascular events?

BACKGROUND: Cardiovascular disease (CVD) remains the major cause of excess mortality in patients with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the individual contribution of NAFLD to CVD risk factors in the absence of pathogenic influences from other comorbidities often found in NAFLD patients, by using an established in-vitro model of hepatic steatosis. METHODS: Histopathological events in non-alcoholic fatty liver disease were recapitulated by focused metabolic nutrient overload of hepatoblastoma C3A cells, using oleate-treated-cells and untreated controls for comparison. Microarray and proteomic data from cell culture experiments were integrated into a custom-built systems biology database and proteogenomics analysis performed. Candidate genes with significant dysregulation and concomitant changes in protein abundance were identified and STRING association and enrichment analysis performed to identify putative pathogenic pathways. RESULTS: The search strategy yielded 3 candidate genes that were specifically and significantly up-regulated in nutrient-overloaded cells compared to untreated controls: fibrinogen alpha chain (2.2 fold), fibrinogen beta chain (2.3 fold) and fibrinogen gamma chain (2.1 fold) (all rank products pfp <0.05). Fibrinogen alpha and gamma chain also demonstrated significant concomitant increases in protein abundance (3.8-fold and 2.0-fold, respectively, p <0.05). CONCLUSIONS: In-vitro modelling of NAFLD and reactive oxygen species formation in nutrient overloaded C3A cells, in the absence of pathogenic influences from other comorbidities, suggests that NAFLD is an isolated determinant of CVD. Nutrient overload-induced up-regulation of all three fibrinogen component subunits of the coagulation cascade provides a possible mechanism to explain the excess CVD mortality observed in NAFLD patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12944-015-0069-3) contains supplementary material, which is available to authorized users