American College of Surgeons Trauma Quality Improvement Best Practices recommends initial massive transfusion (MT) cooler delivery within 15 minutes of protocol activation, with a goal of 10 minutes. ...The current study sought to examine the impact of timing of first cooler delivery on patient outcomes.
Patients predicted to receive MT at 12 Level I trauma centers were randomized to two separate transfusion ratios as described in the PROPPR trial. Assessment of Blood Consumption score or clinician gestalt prediction of MT was used to randomize patients and call for initial study cooler. In this planned subanalysis, the time to MT protocol activation and time to delivery of the initial cooler were evaluated. The impact of these times on mortality and time to hemostasis were examined using both Wilcoxon rank sum and linear and logistic regression.
Among 680 patients, the median time from patient arrival to MT protocol activation was 9 minutes with a median time from MT activation call to delivery of first cooler of 8 minutes. An increase in both time to MT activation and time to arrival of first cooler were associated with prolonged time to achieving hemostasis (coefficient, 1.09; p = 0.001 and coefficient, 1.16; p < 0.001, respectively). Increased time to MT activation and time to arrival of first cooler were associated with increased mortality (odds ratio OR, 1.02; p = 0.009 and OR, 1.02; p = 0.012, respectively). Controlling for injury severity, physiology, resuscitation intensity, and treatment arm (1:1:1 vs. 1:1:2), increased time to arrival of first cooler was associated with an increased mortality at 24 hours (OR, 1.05; p = 0.035) and 30 days (OR, 1.05, p = 0.016).
Delays in MT protocol activation and delays in initial cooler arrival were associated with prolonged time to achieve hemostasis and an increase in mortality. Independent of products ratios, every minute from time of MT protocol activation to time of initial cooler arrival increases odds of mortality by 5%.
Prognostic, level II; Therapeutic, level III.
Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI.
To determine whether tranexamic acid ...treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI.
Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher.
Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309).
The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 moderate disability or good recovery) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 no disability to 30 death), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events.
Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 74% male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; 90% 1-sided confidence limit for benefit, -0.9%; P = .16; 97.5% 1-sided confidence limit for harm, 10.2%; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% 95% CI, -7.9% to 2.1%; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 95% CI, -2.5 to 0.7; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% 95% CI, -12.8% to 2.1%; P = .16).
Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended.
ClinicalTrials.gov Identifier: NCT01990768.
There is no consensus on reporting nonmortality trauma complications in a graded manner. The Clavien-Dindo scale of complications was originally for elective surgery and requires adaptation to ...provide meaningful data for trauma patients. In particular, the original score does not account for those treated without surgery. We report an adapted Clavien-Dindo in trauma (ACDiT) scale and apply it to patients managed operatively and nonoperatively.
A combined prospective and retrospective international multicenter observational study was undertaken to apply the ACDiT scale to 484 trauma patients at three university teaching hospitals (Birmingham, England (n = 303); Houston, Texas (n = 113); and Glasgow, Scotland (n = 68)). These included both intensive care unit (ICU) and non-ICU-managed patients. The Clavien-Dindo scoring system was adapted for trauma patients based on consensus amongst an international collaboration of trauma specialists at these sites. Data included whether initial patients were managed operatively or nonoperatively. Complication grades were compared with hospital-free and ICU-free days as other outcome measures of patient morbidity.
Two hundred seventeen (44.8%) of 484 patients experienced complications, of whom 61 (28.1%) of 217 died (grade V). The remainder consisted of grades I (n = 20), II (n = 60), III (n = 24), and IV (n = 52). There was a strong association between higher ACDiT grade category and lower number of hospital-free and ICU-free days (p < 0.01). Eighty-eight patients with complications did not require surgery, validating the score's usefulness in patients managed nonoperatively.
The ACDiT scale can be used to grade the severity of posttrauma complications in patients managed both operatively and nonoperatively. It provides clinically meaningful data for morbidity and mortality meetings and other quality improvement exercises.
Prognostic, level IV.
Missing doses of antibiotics in hospitalized patients is a well-described but inadequately recognized issue. We hypothesized that missing doses of antibiotics decreases quality of care.
Retrospective ...study on patients admitted to the Shock Trauma ICU from February to June 2015. Patients prescribed a multidose course of antibiotics were evaluated. A missed antibiotic dose was one ordered but never given (a completely missed dose) or a dose that was not given within an hour before or after the planned time (an off-schedule missed dose). Patient outcomes included a positive culture, ventilator, ICU and hospital length of stay (LOS), and mortality. Multiple statistical methods were used as appropriate; significance was set as P < 0.05.
For the 5-mo study period, 280 patients were admitted and 200 met inclusion criteria. Eight percent of patients (16/200) did not miss any antibiotic doses, 39% (77/200) had only off-schedule doses, 2% (4/200) had only completely missed doses, and 51% (103/200) had both off-schedule and completely missed doses. For the 200 patients, 8167 doses were ordered and 2096 (26%) were missed. Adjusting for age, gender, BMI, injury severity score, and doses of antibiotics showed that those who miss doses off-schedule had longer LOS than those who do not miss doses of antibiotics. There was a significant nonlinear relationship between LOS and frequency of early (P-value = 0.02) and late (P-value = 0.01) doses.
To reduce length of hospital stay and optimize quality, methods to improve compliance with antibiotic dosing schedules should be investigated.
Background CXCL12/CXCR4 signaling may be involved in tumor growth and angiogenesis, and homing of cancer cells to bone and other organs. Our purpose was to determine whether inhibition of CXCR4 with ...a peptide-based antagonist would reduce tumor growth and metastasis of breast cancer. Methods We used two mouse models of breast cancer. In the first model, 1 × 106 MDA-MB-231 breast cancer cells transfected with luciferase were implanted into the inguinal mammary fat pad to produce primary tumors. In the second model, 1 × 105 MDA-231-BSC12 cells were injected into the left cardiac ventricle to produce bone metastases. CTCE-9908, a peptide analog of CXCL12 that competitively binds to CXCR4, was used to test the effect of inhibiting CXCR4. Five mice from each mouse model were treated with CTCE-9908 (25 mg/kg, injected subcutaneously 5 d/wk). All mice were assessed weekly using bioluminescent imaging to quantify relative volumes of tumor burden. Results Bioluminescencent imaging showed that the mice treated with CTCE-9908 had significantly less primary tumor burden than the control mice. At 5 and 6 wk, the mice treated with CTCE-9908 had a 7-fold reduction and 5-fold reduction in primary tumor burden, respectively. Treatment with CTCE-9908 also significantly inhibited the rate of metastases compared with the control group. At 5 and 6 wk, the mice treated with CTCE-9908 demonstrated a 9-fold reduction and 20-fold reduction in metastatic tumor burden, respectively. Conclusion Treatment with the CXCR4 antagonist CTCE-9908 significantly reduced metastasis as well as primary tumor growth in mouse models of breast cancer.
Background Cyclooxygenase-2 (COX-2) expression in primary breast cancer predicts tumor cell dissemination to bone marrow, which is a risk factor for recurrence and distant metastasis. “Stem-like” ...phenotype may be important in cancer metastasis. Methods To investigate the role of COX-2 protein in breast cancer stem-like cells, we analyzed it by co-immunofluorescence in tumorospheres derived from the MCF7 estrogen receptor-positive breast cancer cell line. To evaluate COX-2 function we utilized a COX-2 inhibitor in a clonogenicity assay performed with tumorospheres-derived cells. Results We detected rare cells in tumorospheres (one cell per tumorosphere) with very high COX-2 expression (COX-2high ). COX-2 transfected MCF7 cells were able to generate long-term tumorospheres culture, even though transfection efficiency was only one in a million cells. We detected expression of OCT4 in some COX-2high cells, supporting the hypothesis that these cells could be cancer stem-like cells. It is important that COX-2high cells showed less expression of Ki-67 than did neighboring cells, indicating that COX-2high cells may be progenitors of tumorospheres. Celecoxib inhibited the growth of tumorosphere cultures and the ability of tumorosphere-derived cells to form colonies in vitro , indicating an active role of COX-2 in these processes. However, 2 μM celecoxib failed to eradicate tumorosphere-initiating cells. Finally, we detected rare COX-2high cells among SUM149 inflammatory breast cancer cells growing on plastic in serum-containing medium; the SUM149 cell line produces a very high level of COX-2 protein. Conclusion Our results support a role for COX-2 in stem-like breast cancer cells and suggest a mechanism behind a role for COX-2 in disseminated tumor cells, which are known to exhibit characteristic biomarkers and functional properties of stem-like cells.
Exception from informed consent (EFIC) allows clinician scientists to perform much needed emergency research. Obtaining this exception, however, requires many meetings with community groups for ...consultation, which can make the process time-consuming and expensive. We aim to determine the impact of using social media in lieu of some community meetings in an effort to obtain an EFIC.
An economic analysis of four randomized clinical trials was performed. Costs were conservatively estimated using personnel costs, social media costs, and adjusted to 2016 US dollars. People were considered reached if they attended a community meeting or were directed to the study website by social media and spent ≥1 min.
The Early Whole Blood study required 14 meetings, reached 272 people, and cost $8260 ($30/person reached). The Pragmatic, Randomized Optimal Platelet and Plasma Ratios study required 14 meetings, reached 260 people, and cost $7479 overall ($29/person reached). The Prehospital Tranexamic Acid Use for Traumatic Brain Injury study required 12 meetings, reached 198 people, and cost $6340 ($32/person reached). Only the damage control laparotomy trial utilized social media in lieu of some community meetings. The damage control laparotomy trial required six meetings at which 137 people were reached. The $1000 social media campaign reached 229 people. The cost was $3977 overall and $11/person reached.
Including a social media campaign during the EFIC process increased the number of potential patients reached and reduced total and per person costs reached costs. Obtaining an EFIC for future emergency clinical trials may be facilitated by the inclusion of a social media campaign.
Abstract Background Reliable, accurate, noninvasive, and continuous determination of hemoglobin would be an important advance in the care of trauma patients. The aim of this study was to evaluate the ...utility of the Masimo Radical 7 device in severely injured trauma patients. Methods Highest level trauma activation patients were enrolled over a 1-year period. Laboratory hemoglobin values were compared with Masimo hemoglobin values using Bland-Altman analysis. Results A total of 525 patients were enrolled in the study. Comparison of 861 paired values from 418 patients showed a variance of 3.89 to −3.84 g/dL, showing a nonsignificant correlation between Masimo hemoglobin and laboratory hemoglobin values. Conclusions The Masimo Radical 7 system evaluated in this study holds promise, but it is not ready to be used as an initial noninvasive evaluation tool in the acute treatment of severely injured trauma patients. There was a poor correlation between Masimo hemoglobin and laboratory hemoglobin and large numbers of missing data. On the basis of the poor correlation, the Masimo Radical 7 device cannot currently be used to guide transfusion therapy.
Background and Objectives
There is no international consensus for management of early‐stage cervical cancer (ESCC). This study aimed to retrospectively investigate disease‐free survival (DFS) and ...overall survival (OS) in patients with ESCC according to the therapeutic strategy used, surgery alone versus preoperative radiation following by surgery.
Methods
Data were retrospectively collected from 1998 to 2015 using the Gynecological Cancer Registry of the Côte d'Or. The inclusion criteria were FIGO 2018 ≤ IB2; squamous cell carcinoma, adenocarcinoma or adenosquamous type. Survival curves were compared using the log‐rank test.
Results
One hundred twenty‐six patients were included. Median survival was 90 months. There was no significant difference in DFS (HR = 0.91, 95%CI 0.32–2.53, p = 0.858) or in OS between surgery alone versus preoperative radiation following by surgery (HR = 0.97, 95%CI 0.31–2.99, p = 0.961). In the subgroup of patients with stage ≥IB1, there was no significant difference in DFS (HR = 3.26, p = 0.2) or in OS (HR = 3.87, p = 0.2).
Conclusion
Our study did not identify any difference in survival according to the treatment strategy. Preoperative radiation following by surgery can be an alternative to surgery alone for ESCC.
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