Proteomics of Coagulopathy Following Injury Reveals Limitations of Using Laboratory Assessment to Define Trauma-Induced Coagulopathy to Predict Massive Transfusion.

Objective: Trauma-induced coagulopathy (TIC) is provoked by multiple mechanisms and is perceived to be one driver of massive transfusions (MT). Single laboratory values using prothrombin time (INR) or thrombelastography (TEG) are used to clinically define this complex process. We used a proteomics approach to test whether current definitions of TIC (INR, TEG, or clinical judgement) are sufficient to capture the majority of protein changes associated with MT. Methods: Eight level-I trauma centers contributed blood samples from patients available early after injury. TIC was defined as INR >1.5 (INR-TIC), TEG maximum amplitude <50mm (TEG-TIC), or clinical judgement (Clin-TIC) by the trauma surgeon. MT was defined as > 10 units of red blood cells in 24 hours or > 4 units RBC/hour during the first 4 hr. SomaLogic proteomic analysis of 1,305 proteins was performed. Pathways associated with proteins dysregulated in patients with each TIC definition and MT were identified. Results: Patients (n=211) had a mean injury severity score of 24, with a MT and mortality rate of 22% and 12%, respectively. We identified 578 SOMAscan analytes dysregulated among MT patients, of which INR-TIC, TEG-TIC, and Clin-TIC patients showed dysregulation only in 25%, 3%, and 4% of these, respectively. TIC definitions jointly failed to show changes in 73% of the protein levels associated with MT, and failed to identify 26% of patients that received a massive transfusion. INR-TIC and TEG-TIC patients showed dysregulation of proteins significantly associated with complement activity. Proteins dysregulated in Clin-TIC or massive transfusion patients were not significantly associated with any pathway. Conclusion: These data indicate there are unexplored opportunities to identify patients at risk for massive bleeding. Only a small subset of proteins that are dysregulated in patients receiving MT are statistically significantly dysregulated among patients whose TIC is defined based solely on laboratory measurements or clinical assessment.

COVID-19: All the wrong moves in all the wrong places.

In this Editorial, Barrett and Yaffe highlight shortcomings in our collective response to the COVID-19 pandemic and underscore the need for more basic research into this new disease.

Salvage use of tissue plasminogen activator (tPA) in the setting of acute respiratory distress syndrome (ARDS) due to COVID-19 in the USA: a Markov decision analysis.

BACKGROUND: COVID-19 threatens to quickly overwhelm our existing critical care infrastructure in the USA. Systemic tissue plasminogen activator (tPA) has been previously demonstrated to improve PaO2/FiO2 (mmHg) when given to critically ill patients with acute respiratory distress syndrome (ARDS). It is unclear to what extent tPA may impact population-based survival during the current US COVID-19 pandemic. METHODS: A decision analytic Markov state transition model was created to simulate the life critically ill COVID-19 patients as they transitioned to either recovery or death. Two patient groups were simulated (50,000 patients in each group); (1) Patients received tPA immediately upon diagnosis of ARDS and (2) patients received standard therapy for ARDS. Base case critically ill COVID-19 patients were defined as having a refractory PaO2/FiO2 of < 60 mmHg (salvage use criteria). Transition from severe to moderate to mild ARDS, recovery, and death were estimated. Markov model parameters were extracted from existing ARDS/COVID-19 literature. RESULTS: The use of tPA was associated with reduced mortality (47.6% [tTPA] vs. 71.0% [no tPA]) for base case patients. When extrapolated to the projected COVID-19 eligible for salvage use tPA in the USA, peak mortality (deaths/100,000 patients) was reduced for both optimal social distancing (70.5 [tPA] vs. 75.0 [no tPA]) and no social distancing (158.7 [tPA] vs. 168.8 [no tPA]) scenarios. CONCLUSIONS: Salvage use of tPA may improve recovery of ARDS patients, thereby reducing COVID-19-related mortality and ensuring sufficient resources to manage this pandemic.

Surgical wound assessment by sonography in the prediction of surgical wound infections.

BACKGROUND: Surgical site infections (SSIs) are important sources of morbidity, prolonged hospital stays, and readmissions, so they have become a major economic burden. We hypothesized that surgical wound assessment by sonography (SWATS) used at the bedside would detect wound fluid collections and that the presence of such collections would predict SSI better than standard clinical examination. If so, SWATS might be used to indicate early intervention that could prevent SSI morbidity. METHODS: A prospective, single-institution observational study was conducted on adult inpatients following open abdominal surgery for trauma, gastrointestinal pathology, or biliary pathology at high risk (>5%) for SSI using traditional wound classifications. After informed consent was obtained, SWATS was performed using a smartphone-based ultrasound system on postoperative Day 2 to 4 and again before discharge or at postoperative Day 30, whichever came first. Primary treating physicians delivered standard wound care and were blinded to SWATS. SSI was diagnosed if treatment was implemented for suspected or documented wound infection by the treating physician. Results were analyzed by χ test and two-sample pooled variance t test where appropriate, with significance set at p < 0.05. RESULTS: Forty-nine patients were studied. Nineteen patients had peri-incisional fluid collections found by SWATS. Eight of these patients went on to develop an SSI. SSI was significantly associated with the presence of fluid collections on SWATS (p = 0.009). SWATS had a sensitivity of 72.7% (0.43-0.92), a specificity of 71.1% (0.62-0.77), a positive predictive value of 42.1% (0.25-0.53), and a negative predictive value of 90.0% (0.79-0.97). CONCLUSION: SWATS has a high negative predictive value that may allow it be an effective screening tool for developing SSI in high-risk surgical wounds. SWATS has the potential to be a useful and cost-effective adjunct to the clinician by objectively suggesting need for early therapy. Further study with larger sample sizes and randomized, SWATS-based interventions are required to validate this small study and determine its place in clinical care. LEVEL OF EVIDENCE: Diagnostic study, level IV.

A material cost-minimization analysis for hernia repairs and minor procedures during a surgical mission in the Dominican Republic.

INTRODUCTION: Expenditures on material supplies and medications constitute the greatest per capita costs for surgical missions. We hypothesized that supply acquisition at non-profit organization (NPO) costs would lead to significant cost-savings compared with supply acquisition at US academic institution costs from the provider perspective for hernia repairs and minor procedures during a surgical mission in the Dominican Republic. METHODS: Items acquired for a surgical mission were uniquely QR-coded for accurate consumption accounting. Both NPO and US academic institution unit costs were associated with each item in an electronic inventory system. Medication doses were recorded and QR codes for consumed items were scanned into a record for each sampled procedure. Mean material costs and cost-savings ± SDs were calculated in US dollars for each procedure type. Cost-minimization analyses between the NPO and the US academic institution platforms for each procedure type ensued using a two-tailed Wilcoxon matched-pairs test with α = 0.05. Item utilization analyses generated lists of most frequently used materials by procedure type. RESULTS: The mean cost-savings of supply acquisition at NPO costs for each procedure type were as follows: $482.86 ± $683.79 for unilateral inguinal hernia repair (n = 13); $332.46 ± $184.09 for bilateral inguinal hernia repair (n = 3); $127.26 ± $13.18 for hydrocelectomy (n = 9); $232.92 ± $56.49 for femoral hernia repair (n = 3); $120.90 ± $30.51 for umbilical hernia repair (n = 8); $36.59 ± $17.76 for minor procedures (n = 26); and $120.66 ± $14.61 for pediatric inguinal hernia repair (n = 7). CONCLUSION: Supply acquisition at NPO costs leads to significant cost-savings compared with supply acquisition at US academic institution costs from the provider perspective for inguinal hernia repair, hydrocelectomy, umbilical hernia repair, minor procedures, and pediatric inguinal hernia repair during a surgical mission in the Dominican Republic. Item utilization analysis can generate minimum-necessary material lists for each procedure type to reproduce cost-savings for subsequent missions.