A PROMPT Update on Partial REBOA: Initial Clinical Data and Overview of the DoD-Funded Partial REBOA Outcomes Multicenter ProspecTive (PROMPT) Study.

INTRODUCTION: Retrograde Endovascular Balloon Occlusion of the Aorta (REBOA) is an effective management for the transient responder, but the ischemic consequences of complete aortic occlusion currently limit its use. Multiple DoD-funded preclinical studies have clearly demonstrated that partial REBOA reduces distal ischemia to potentially extend safe occlusion times, while still providing effective temporization of noncompressible torso hemorrhage. Early versions of REBOA devices were designed to completely occlude the aorta and had little ability to provide partial occlusion. Recently, a new REBOA device (pREBOA-PRO) was designed specifically to allow for partial occlusion, with the hypothesis that this may reduce the complications of aortic occlusion and extend safe occlusion times while maintaining the benefits on cardiac and cerebrovascular circulation as well as reductions in resuscitation requirements. MATERIALS AND METHODS: To ascertain the impact of a new purpose-built partial REBOA device on the extension of safe occlusion time, the Partial REBOA Outcomes Multicenter ProspecTive (PROMPT) trial compared available data from the pREBOA-PRO with existing data from 200 clinical uses of pREBOA-PRO and available data in the AAST AORTA Registry were reviewed to design primary endpoints and clinical evidence for a prospective multi-center trial, the PROMPT Study. Together with the endpoints identified in preclinical studies of partial REBOA, primary endpoints for the PROMPT study were identified and power analyses were conducted to determine the target patient enrollment goals. RESULTS: Results from the clinical implementation of partial REBOA at a single trauma center were used to conduct the initial power analysis for the primary endpoint of Acute Kidney Injury (AKI) after prolonged occlusion. The rate of AKI after complete REBOA was 55% (12/20) compared to 33% (4/12) after partial REBOA (Madurska et al., 2021). With an alpha of 0.05 and power (ß) of 0.8, the projected sample size for comparison on a dichotomous outcome is 85 patients for the assessment of AKI. Initial power and endpoint analyses have been confirmed and extended with the ongoing analysis of partial and complete REBOA reported in the AORTA database. These analyses confirm preclinical findings which show that compared to complete REBOA, partial REBOA is associated with extended occlusion time in zone 1 (complete: 31 min vs. partial: 45 min, P = 0.003), lower rates of AKI after zone 1 occlusion (complete: 33% vs. partial: 19%, P = 0.05) and reduced resuscitation requirements (e.g., 25% reduction in pRBC administration: complete: 18 units vs. partial: 13 units, P = 0.02). CONCLUSIONS: The DoD-funded PROMPT study of partial REBOA will provide prospective observational clinical data on patients being treated with pREBOA-PRO. Outcomes will be stratified based on partial or complete occlusion to address whether partial REBOA has additional clinical benefits over complete REBOA, such as decreased distal ischemia, extension of safe occlusion time, improved hemodynamics during transition to and from occlusion, and reduced interoperative bleeding and blood product use. The results from this study are expected to confirm previous data demonstrating reduction of ischemic sequalae, improved transition to reperfusion, and reduced resuscitative requirements compared to complete REBOA.

Diagnosis and management of blunt cerebrovascular injuries: What you need to know.

ABSTRACT: Blunt cerebrovascular injuries are not as rare as they were once thought to be-but they still have the same potential for disastrous outcomes. They may occur following any trauma, but more common with higher energy transfer mechanisms. If stroke occurs, prompt recognition and treatment offers the best chance for optimal outcome. Early diagnosis and provision of antithrombotic therapy may prevent strokes, so screening of asymptomatic patients is recommended. Herein we will present what you need to know to diagnose and manage blunt cerebrovascular injury.

Markers of Futile Resuscitation in Traumatic Hemorrhage: A Review of the Evidence and a Proposal for Futility Time-Outs during Massive Transfusion.

The reduction in the blood supply following the 2019 coronavirus pandemic has been exacerbated by the increased use of balanced resuscitation with blood components including whole blood in urban trauma centers. This reduction of the blood supply has diminished the ability of blood banks to maintain a constant supply to meet the demands associated with periodic surges of urban trauma resuscitation. This scarcity has highlighted the need for increased vigilance through blood product stewardship, particularly among severely bleeding trauma patients (SBTPs). This stewardship can be enhanced by the identification of reliable clinical and laboratory parameters which accurately indicate when massive transfusion is futile. Consequently, there has been a recent attempt to develop scoring systems in the prehospital and emergency department settings which include clinical, laboratory, and physiologic parameters and blood products per hour transfused as predictors of futile resuscitation. Defining futility in SBTPs, however, remains unclear, and there is only nascent literature which defines those criteria which reliably predict futility in SBTPs. The purpose of this review is to provide a focused examination of the literature in order to define reliable parameters of futility in SBTPs. The knowledge of these reliable parameters of futility may help define a foundation for drawing conclusions which will provide a clear roadmap for traumatologists when confronted with SBTPs who are candidates for the declaration of futility. Therefore, we systematically reviewed the literature regarding the definition of futile resuscitation for patients with trauma-induced hemorrhagic shock, and we propose a concise roadmap for clinicians to help them use well-defined clinical, laboratory, and viscoelastic parameters which can define futility.

Admission Viscoelastic Hemostatic Assay Parameters Predict Poor Long-Term Intracerebral Hemorrhage Outcomes.

BACKGROUND: Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. METHODS: Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. RESULTS: Of 44 patients analyzed, the mean age was 64 years, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. CONCLUSIONS: Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA-guided treatments should be incorporated into ICH care.

Does preperitoneal packing increase venous thromboembolim risk among trauma patients? A prospective multicenter analysis across 17 level I trauma centers.

INTRODUCTION: Pelvic fractures are associated with a high risk of venous thromboembolism (VTE). Among treatment options, including pelvic angioembolization (PA), preperitoneal pelvic packing (PPP), and pelvic open reduction internal fixation (ORIF), PPP has been postulated as a VTE risk factor. We aimed to characterize the risk of VTE among pelvic fracture patients receiving PPP, PA or ORIF. METHODS: We used observational data from a 17-site Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT) study group, a US level I trauma center collaborative working to identify factors associated with posttraumatic VTE, deep venous thrombosis, pulmonary embolism, or pulmonary thrombosis. The CLOTT criteria included age 18 to 40 years with at least one independent VTE risk factor. We compared outcomes of PPP, PA, and pelvic ORIF to reference of no pelvic intervention. Our primary outcome was VTE. A competing risk analysis was performed. RESULTS: Among 1,387 pelvic fracture patients, VTE incidence was 5.6%. The ORIF patients were most likely to develop VTE (24.7%), while VTE incidence for PPP was 9.0% and 2.6% for PA. After multivariate, risk-competing analysis, none of the three treatment interventions for pelvic fractures were significantly associated with VTE. Initiation of VTE prophylaxis in the first 24 hours of admission independently halved VTE incidence (hazard ratio, 0.55; confidence interval, 0.33-0.91). CONCLUSION: Pelvic fracture interventions do not appear to be independent risk factors for VTE in our study. Initiation of VTE pharmacoprophylaxis within the first 24 hours of admission remains critical to significantly decreasing VTE formation in this high-risk population. LEVEL OF EVIDENCE: Therapeutic Study; Level III.

Increasing the Threshold to Perform Preperitoneal Pelvic Packing Decreases Morbidity Without Affecting Mortality.

OBJECTIVES: To determine the effectiveness of an updated protocol that increased the transfusion threshold to perform preperitoneal pelvic packing in patients with pelvic ring injuries and hemodynamic instability (HDI). DESIGN: Retrospective review. SETTING: Urban level 1 trauma center. PATIENTS SELECTION CRITERIA: Severely injured (injury severity score > 15) patients with pelvic ring injuries treated before and after increasing the threshold to perform preperitoneal pelvic packing from 2 to 4 units of red blood cells (RBCs). HDI was defined as a systolic blood pressure <90 mm Hg. OUTCOME MEASURES AND COMPARISONS: Mortality from hemorrhage, anterior pelvic space infections, and venous thromboembolisms before and after increasing preperitoneal pelvic packing threshold. RESULTS: One hundred sixty-six patients were included: 93 treated under the historical protocol and 73 treated under the updated protocol. HDI was present in 46.2% (n = 43) of the historical protocol group and 49.3% (n = 36) of the updated protocol group (P = 0.69). The median age of patients with HDI was 35.0 years (interquartile range 26.0-52.0), 74.7% (n = 59) were men, and the median injury severity score was 41.0 (interquartile range 29.0-50.0). Patients with HDI in the updated protocol group had a lower heart rate on presentation (105.0 vs. 120.0; P = 0.004), required less units of RBCs over the first 24 hours (6.0 vs. 8.0, P = 0.03), and did not differ in age, injury severity score, systolic blood pressure on arrival, base deficit or lactate on arrival, resuscitative endovascular balloon occlusion of the aorta, resuscitative thoracotomy, angioembolization, or anterior pelvis open reduction internal fixation (P > 0.05). The number of PPPs performed decreased under the new protocol (8.3% vs. 65.1%, P < 0.0001), and there were fewer anterior pelvic infections (0.0% vs. 13.9%, P = 0.02), fewer VTEs (8.3% vs. 30.2%; P = 0.02), and no difference in deaths from acute hemorrhagic shock (5.6% vs. 7.0%, P = 1.00). CONCLUSIONS: Increasing the transfusion threshold from 2 to 4 units of red blood cells to perform pelvic packing in severely injured patients with pelvic ring injuries decreased anterior pelvic space infections and venous thromboembolisms without affecting deaths from acute hemorrhage. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Early GFAP and UCH-L1 point-of-care biomarker measurements for the prediction of traumatic brain injury and progression in patients with polytrauma and hemorrhagic shock.

OBJECTIVE: Traumatic brain injury (TBI) and hemorrhage are responsible for the largest proportion of all trauma-related deaths. In polytrauma patients at risk of hemorrhage and TBI, the diagnosis, prognosis, and management of TBI remain poorly characterized. The authors sought to characterize the predictive capabilities of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) measurements in patients with hemorrhagic shock with and without concomitant TBI. METHODS: The authors performed a secondary analysis on serial blood samples derived from a prospective observational cohort study that focused on comparing early whole-blood and component resuscitation. A convenience sample of patients was used in which samples were collected at three time points and the presence of TBI or no TBI via CT imaging was documented. GFAP and UCH-L1 measurements were performed on plasma samples using the i-STAT Alinity point-of-care platform. Using classification tree recursive partitioning, the authors determined the measurement cut points for each biomarker to maximize the abilities for predicting the diagnosis of TBI, Rotterdam CT imaging scores, and 6-month Glasgow Outcome Scale-Extended (GOSE) scores. RESULTS: Biomarker comparisons demonstrated that GFAP and UCH-L1 measurements were associated with the presence of TBI at all time points. Classification tree analyses demonstrated that a GFAP level > 286 pg/ml for the sample taken upon the patient's arrival had an area under the receiver operating characteristic curve of 0.77 for predicting the presence of TBI. The classification tree results demonstrated that a cut point of 3094 pg/ml for the arrival GFAP measurement was the most predictive for an elevated Rotterdam score on the initial and second CT scans and for TBI progression between scans. No significant associations between any of the most predictive cut points for UCH-L1 and Rotterdam CT scores or TBI progression were found. The predictive capabilities of UCH-L1 were limited by the range allowed by the point-of-care platform. Arrival GFAP cut points remained strong independent predictors after controlling for all potential polytrauma confounders, including injury characteristics, shock severity, and resuscitation. CONCLUSIONS: Early measurements of GFAP and UCH-L1 on a point-of-care device are significantly associated with CT-diagnosed TBI in patients with polytrauma and shock. Early elevated GFAP measurements are associated with worse head CT scan Rotterdam scores, TBI progression, and worse GOSE scores, and these associations are independent of other injury attributes, shock severity, and early resuscitation characteristics.

Strategies to prevent blood loss and reduce transfusion in emergency general surgery, WSES-AAST consensus paper.

Emergency general surgeons often provide care to severely ill patients requiring surgical interventions and intensive support. One of the primary drivers of morbidity and mortality is perioperative bleeding. In general, when addressing life threatening haemorrhage, blood transfusion can become an essential part of overall resuscitation. However, under all circumstances, indications for blood transfusion must be accurately evaluated. When patients decline blood transfusions, regardless of the reason, surgeons should aim to provide optimal care and respect and accommodate each patient's values and target the best outcome possible given the patient's desires and his/her clinical condition. The aim of this position paper was to perform a review of the existing literature and to provide comprehensive recommendations on organizational, surgical, anaesthetic, and haemostatic strategies that can be used to provide optimal peri-operative blood management, reduce, or avoid blood transfusions and ultimately improve patient outcomes.

Versatile, in-line optical oxygen tension sensors for continuous monitoring during ex vivo kidney perfusion.

Integration of physiological sensing modalities within tissue and organ perfusion systems is becoming a steadily expanding field of research, aimed at achieving technological breakthrough innovations that will expand the sites and clinical settings at which such systems can be used. This is becoming possible in part due to the advancement of user-friendly optical sensors in recent years, which rely both on synthetic, luminescent sensor molecules and inexpensive, low-power electronic components for device engineering. In this article we report a novel approach towards enabling automated, continuous monitoring of oxygenation during ex vivo organ perfusion, by combining versatile flow cell components and low-power, programmable electronic readout devices. The sensing element comprises a 3D printed, miniature flow cell with tubing connectors and an affixed oxygen-sensing thin film material containing in-house developed, brightly-emitting metalloporphyrin phosphor molecules embedded within a polymer matrix. Proof-of-concept validation of this technology is demonstrated through integration within the tubing circuit of a transportable medical device for hypothermic oxygenated machine perfusion of extracted kidneys as a model for organs to be preserved as transplants.

The management of complicated colorectal cancer in older patients in a global perspective after COVID-19: the CO-OLDER WSES project.

BACKGROUND: Colorectal (CRC) cancer is becoming a disease of the elderly. Ageing is the most significant risk factor for presenting CRC. Early diagnosis of CRC and management is the best way in achieving good outcomes and longer survival but patients aged ≥75 years are usually not screened for CRC. This group of patients is often required to be managed when they are symptomatic in the emergency setting with high morbidity and mortality rates. Our main aim is to provide clinical data about the management of elderly patients presenting complicated colorectal cancer who required emergency surgical management to improve their care. METHODS: The management of complicated COlorectal cancer in OLDER patients (CO-OLDER; ClinicalTrials.gov ID: NCT05788224; evaluated by the local ethical committee CPP EST III-France with the national number 2023-A01094-41) in the emergency setting project provides carrying out an observational multicenter international cohort study aimed to collect data about patients aged ≥75 years to assess modifiable risk factors for negative outcomes and mortality correlated to the emergency surgical management of this group of patients at risk admitted with a complicated (obstructed and perforated) CRC. The CO-OLDER protocol was approved by Institutional Review Board and released. Each CO-OLDER collaborator is asked to enroll ≥25 patients over a study period from 1st January 2018 to 30th October 2023. Data will be analyzed comparing two periods of study: before and after the COVID-19 pandemic. A sample size of 240 prospectively enrolled patients with obstructed colorectal cancer in a 5-month period was calculated. The secured database for entering anonymized data will be available for the period necessary to achieve the highest possible participation. RESULTS: One hundred eighty hospitals asked to be a CO-OLDER collaborator, with 36 potentially involved countries over the world. CONCLUSIONS: The CO-OLDER project aims to improve the management of elderly people presenting with a complicated colorectal cancer in the emergency setting. Our observational global study can provide valuable data on the effectiveness of different management strategies in improving primary assessment, management and outcomes for elderly patients with obstructed or perforated colorectal cancer in the emergency setting, guiding clinical decision-making. This information can help healthcare providers make informed decisions about the best course of action for these patients.

The role of RObotic surgery in EMergency setting (ROEM): protocol for a multicentre, observational, prospective international study on the use of robotic platform in emergency surgery.

BACKGROUND: Robotic surgery has gained widespread acceptance in elective interventions, yet its role in emergency procedures remains underexplored. While the 2021 WSES position paper discussed limited studies on the application of robotics in emergency general surgery, it recommended strict patient selection, adequate training, and improved platform accessibility. This prospective study aims to define the role of robotic surgery in emergency settings, evaluating intraoperative and postoperative outcomes and assessing its feasibility and safety. METHODS: The ROEM study is an observational, prospective, multicentre, international analysis of clinically stable adult patients undergoing robotic surgery for emergency treatment of acute pathologies including diverticulitis, cholecystitis, and obstructed hernias. Data collection includes patient demographics and intervention details. Furthermore, data relating to the operating theatre team and the surgical instruments used will be collected in order to conduct a cost analysis. The study plans to enrol at least 500 patients from 50 participating centres, with each centre having a local lead and collaborators. All data will be collected and stored online through a secure server running the Research Electronic Data Capture (REDCap) web application. Ethical considerations and data governance will be paramount, requiring local ethical committee approvals from participating centres. DISCUSSION: Current literature and expert consensus suggest the feasibility of robotic surgery in emergencies with proper support. However, challenges include staff training, scheduling conflicts with elective surgeries, and increased costs. The ROEM study seeks to contribute valuable data on the safety, feasibility, and cost-effectiveness of robotic surgery in emergency settings, focusing on specific pathologies. Previous studies on cholecystitis, abdominal hernias, and diverticulitis provide insights into the benefits and challenges of robotic approaches. It is necessary to identify patient populations that benefit most from robotic emergency surgery to optimize outcomes and justify costs.

pREBOA vs ER-REBOA impact on blood utilization and resuscitation requirements: A pilot analysis.

BACKGROUND: Partial occlusion of the aorta is a resuscitation technique designed to maximize proximal perfusion while allowing a graduated amount of distal flow to reduce the ischemic sequelae associated with complete aortic occlusion. The pREBOA catheter affords the ability to titrate perfusion as hemodynamics allows, however, the impact of this new technology for REBOA on blood use and other resuscitative requirements is currently unknown. We hypothesize pREBOA's ability to provide partial occlusion, when appropriate, decreases overall resuscitative requirements when compared to ER-REBOA. METHODS: The entire AAST AORTA Registry was used to compare resuscitation requirements between all ER-REBOA and pREBOA. Unpaired t-tests were used to compare resuscitation strategies including packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, cryoprecipitate, crystalloids, and need for pressors. RESULTS: When comparing ER-REBOA (n=800) use to pREBOA (n=155), initial patient presentations were similar except for age (44 vs 40 p=0.026) and rates of blunt injury (78.4% vs 78.7% p<0.010). Zone-1 occlusion was used less often in ER-REBOA (65.8 vs 71.7 p=0.046). Partial occlusion was performed in 85% of pREBOA compared to 11% in ER-REBOA (p<0.050). Vitals at the time of REBOA were worse in ER-REBOA, and received significantly more units of PRBCs, FFP, platelets, and liters of crystalloids than pREBOA (p<0.05). Rates of ARDS and septic shock were lower in pREBOA (p<0.05). CONCLUSION: When comparing pREBOA to ER-REBOA, there has been a rise in Zone-1 and partial occlusion. In our pilot analysis of the AORTA Registry, there was a reduction in administration of pRBC, FFP, platelets, and crystalloids. Though further prospective studies are required, this is the first to demonstrate an association between pREBOA, partial occlusion, and reduced blood use and resuscitative requirements.

Management of inflammatory bowel disease in the emergency setting: the MIBODI international survey and evidence-based practices.

AIM: This study aimed to evaluate the impact of the WSES-AAST guidelines in clinical practice and to investigate the knowledge, attitudes, and practices of emergency surgeons in managing the complications of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: The MIBODI survey is a cross-sectional study among WSES members designed as an international web-based survey, according to the Checklist for Reporting Results of Internet E-Surveys, to collect data on emergency surgeons' knowledge, attitudes, and practices concerning the management of patients presenting with acute complications of CD and UC. The questionnaire was composed of 30 questions divided into five sections: (1) demographic data, (2) primary evaluation, (3) non-operative management, (4) operative management, and (5) perianal sepsis management. RESULTS: Two hundred and forty-two surgeons from 48 countries agreed to participate in the survey. The response rate was 24.2% (242/1000 members on WSES mail list). Emergency surgeons showed high adherence to recommendations for 6 of the 21 assessed items, with a "correct" response rate greater than or equal to 60%, according to WSES-AAST recommendations. Nine critical issues were highlighted, with correct answers at a rate of less than 50%. CONCLUSIONS: Inflammatory bowel disease is a complex disease that requires a multidisciplinary approach with close collaboration between gastroenterologists and surgeons. Emergency surgeons play a crucial role in managing complications related to IBD. One year after publication, the MIBODI study showed significant global implementation of the WSES-AAST guidelines in clinical practice, offering an imperative tool in the improved management of IBD in emergency and urgent settings.

The 2023 WSES guidelines on the management of trauma in elderly and frail patients

The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patient's directives, family feelings and representatives' desires, and all decisions should be shared. The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.

Neutrophil-mediated Inflammatory Plasminogen Degradation, Rather Than High Plasminogen-Activator Inhibitor-1, May Underly Failures and Inefficiencies of Intrapleural Fibrinolysis.

BACKGROUND: Complex pleural space infections often require treatment with multiple doses of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease, with treatment failure frequently necessitating surgery. Pleural infections are rich in neutrophils, and neutrophil elastase degrades plasminogen, the target substrate of tPA, that is required to generate fibrinolysis. We hypothesized that pleural fluid from patients with pleural space infection would show high elastase activity, evidence of inflammatory plasminogen degradation, and low fibrinolytic potential in response to tPA that could be rescued with plasminogen supplementation. RESEARCH QUESTION: Does neutrophil elastase degradation of plasminogen contribute to intrapleural fibrinolytic failure? STUDY DESIGN AND METHODS: We obtained infected pleural fluid and circulating plasma from hospitalized adults (n = 10) with institutional review board approval from a randomized trial evaluating intrapleural fibrinolytics vs surgery for initial management of pleural space infection. Samples were collected before the intervention and on days 1, 2, and 3 after the intervention. Activity assays, enzyme-linked immunosorbent assays, and Western blot analysis were performed, and turbidimetric measurements of fibrinolysis were obtained from pleural fluid with and without exogenous plasminogen supplementation. Results are reported as median (interquartile range) or number (percentage) as appropriate, with an α value of .05. RESULTS: Pleural fluid elastase activity was more than fourfold higher (P = .02) and plasminogen antigen levels were more than threefold lower (P = .04) than their corresponding plasma values. Pleural fluid Western blot analysis demonstrated abundant plasminogen degradation fragments consistent with elastase degradation patterns. We found that plasminogen activator inhibitor 1 (PAI-1), the native tPA inhibitor, showed high antigen levels before the intervention, but the overwhelming majority of this PAI-1 (82%) was not active (P = .003), and all PAI-1 activity was lost by day 2 after the intervention in patients receiving intrapleural tPA and deoxyribonuclease. Finally, using turbidity clot lysis assays, we found that the pleural fluid of 9 of 10 patients was unable to generate a significant fibrinolytic response when challenged with tPA and that plasminogen supplementation rescued fibrinolysis in all patients. INTERPRETATION: Our findings suggest that inflammatory plasminogen deficiency, not high PAI-1 activity, is a significant contributor to intrapleural fibrinolytic failure. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03583931; URL: www. CLINICALTRIALS: gov.

Cytoprotective 3K3A-activated protein C and plasma: A comparison of therapeutics for the endotheliopathy of trauma.

BACKGROUND: Both healthy plasma and cytoprotective aPC (3K3A-aPC) have been shown to mitigate the endotheliopathy of trauma (EoT), but optimal therapeutics remain unknown. Our aim was therefore to determine optimal therapies to mitigate EoT by investigating the effectiveness of 3K3A-aPC with and without plasma-based resuscitation strategies. METHODS: Electric cell-substrate impedance sensing (ECIS) was used to measure real-time permeability changes in endothelial cells. Cells were treated with a 2 µg/mL solution of aPC 30 minutes prior to stimulation with plasma taken from severely injured trauma patients (ISS > 15 and BD < -6) (TP). Healthy plasma, or plasma frozen within 24 hours (FP24), was added concomitantly with TP. Cells treated with thrombin and untreated cells were included in this study as control groups. RESULTS: A dose-dependent difference was found between the 5% and 10% plasma-treated groups when HUVECs were simultaneously stimulated with TP (µd 7.346 95%CI 4.574 to 10.12). There was no difference when compared to TP alone in the 5% (µd 5.713 95%CI -1.751 to 13.18) or 10% group (µd -1.633 95%CI -9.097 to 5.832). When 3K3A-aPC was added to plasma and TP, the 5% group showed improvement in permeability compared to TP alone (µd 10.11 95%CI 2.642 to 17.57), but there was no difference in the 10% group (µd -1.394 95%CI -8.859 to 6.070). The combination of 3K3A-aPC, plasma, and TP at both the 5% plasma (µd -28.52 95%CI-34.72 to -22.32) and 10% plasma concentrations (µd -40.02 95%CI -46.22 to -33.82) had higher inter-cellular permeability than the 3K3A-aPC pre-incubation group. CONCLUSION: Our data shows that FP24, in a post-trauma environment, pre-treatment with 3K3A-aPC can potentially mitigate the EoT to a greater degree than FP24 with or without 3K3A-aPC. Although further exploration is needed, this represents a potentially ideal and perhaps superior therapeutic treatment for the dysregulated thromboinflammation of injured patients. LEVEL OF EVIDENCE: Prognostic/Epidemiological, Therapeutic/Care Management, Level III.

Trauma patients with type O blood exhibit unique multi-omics signature with decreased lectin pathway of complement levels.

BACKGROUND: Patients with type O blood may have an increased risk of hemorrhagic complications due to lower baseline levels of von Willebrand Factor (vWF) and factor VIII, but the transition to a mortality difference in trauma is less clear. We hypothesized that type O trauma patients will have differential proteomic and metabolomic signatures in response to trauma beyond vWF and FVIII alone. METHODS: Patients meeting the highest level of trauma activation criteria were prospectively enrolled. Blood samples were collected upon arrival to the emergency department. Proteomic and metabolomic (multi-omics) analyses of these samples were performed using liquid chromatography-mass spectrometry. Demographic, clinical, and multi-omics data were compared between patients with type O blood versus all other patients. RESULTS: There were 288 patients with multi-omics data; 146 (51%) had type O blood. Demographics, injury patterns, and initial vital signs and laboratory measurements were not different between groups. Type O patients had increased lengths of stay (7 vs. 6 days, p = 0.041) and a trend towards decreased mortality secondary to traumatic brain injury compared to other causes (TBI, 44.4 % vs. 87.5%, p = 0.055). Type O patients had decreased levels of mannose-binding lectin (MBL) and MBL associated serine proteases 1 and 2 which are required for the initiation of the lectin pathway of complement activation. Type O patients also had metabolite differences signifying energy metabolism and mitochondrial dysfunction. CONCLUSION: Blood type O patients have a unique multi-omics signature, including decreased levels of proteins required to activate the lectin complement pathway. This may lead to overall decreased levels of complement activation and decreased systemic inflammation in the acute phase possibly leading to a survival advantage, especially in TBI. However, this may later impair healing. Future work will need to confirm these associations, and animal studies are needed to test therapeutic targets. LEVEL OF EVIDENCE: Retrospective Comparative Study, Level IV.

Knowledge, attitudes and practices of using Indocyanine Green (ICG) fluorescence in emergency surgery: an international web-based survey in the ARtificial Intelligence in Emergency and trauma Surgery (ARIES)-WSES project.

Fluorescence imaging is a real-time intraoperative navigation modality to enhance surgical vision and it can guide emergency surgeons while performing difficult, high-risk surgical procedures. The aim of this study is to assess current knowledge, attitudes, and practices of emergency surgeons in the use of indocyanine green (ICG) in emergency settings. Between March 08, 2023 and April 10, 2023, a questionnaire composed of 27 multiple choice and open-ended questions was sent to 200 emergency surgeons who had previously joined the ARtificial Intelligence in Emergency and trauma Surgery (ARIES) project promoted by the WSES. The questionnaire was developed by an emergency surgeon with an interest in advanced technologies and artificial intelligence. The response rate was 96% (192/200). Responders affirmed that ICG fluorescence can support the performance of difficult surgical procedures in the emergency setting, particularly in the presence of severe inflammation and in evaluating bowel viability. Nevertheless, there were concerns regarding accessibility and availability of fluorescence imaging in emergency settings. Eighty-seven out of 192 (45.3%) respondents have a fluorescence imaging system of vision for both elective and emergency surgical procedures; 32.3% of respondents have this system solely for elective procedures; 21.4% of respondents do not have this system, 15% do not have experience with it, and 38% do not use this imaging in emergency surgery. Less than 1% (2/192) affirmed that ICG fluorescence changed always their intraoperative decision-making. Precision surgery effectively tailors surgical interventions to individual patient characteristics using advanced technology, data analysis and artificial intelligence. ICG fluorescence can serve as a valid and safe tool to guide emergency surgery in different scenarios, such as intestinal ischemia and severe acute cholecystitis. Due to the lack of high-level evidence within this field, a consensus of expert emergency surgeons is needed to encourage stakeholders to increase the availability of fluorescence imaging systems and to support emergency surgeons in implementing ICG fluorescence in their daily practice.

The 2023 WSES guidelines on the management of trauma in elderly and frail patients.

BACKGROUND: The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. METHODS: Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. RESULTS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patient's directives, family feelings and representatives' desires, and all decisions should be shared. CONCLUSIONS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.

Brodifacoum contamination of synthetic cannabinoid causing unexplained coagulopathy in multiple trauma: A case report.

An 18-year-old female presented to the emergency department after a motor vehicle collision. Initial imaging revealed a liver laceration. Subsequent labs showed significantly elevated prothrombin time, international normalized ratio, and activated partial thromboplastin time. Thromboelastography demonstrated a flatline tracing. The patient denied use of anticoagulation but admitted to synthetic cannabinoid use. It was believed the patient had taken synthetic cannabinoid contaminated by brodifacoum. She was therefore given prothrombin complex concentrate and vitamin K with blood products. The patient underwent sequential embolization, laparotomy, thoracotomy, and repair of the vena cava with a shunt. Thirty minutes postoperatively, her coagulation tests and thromboelastography were much improved. Two and a half hours postoperatively, it was determined she had sustained non-survivable injuries. The patient experienced brain death due to prolonged hypotension as a result of hemorrhagic shock with bleeding exacerbated by brodifacoum. To our knowledge, this is the first case reported of a trauma-induced coagulopathy exacerbated by brodifacoum-contaminated synthetic cannabinoid. Her coagulopathy was clearly not due to trauma alone and contributed greatly to the difficulty in controlling hemorrhage. The synthetic cannabinoid-associated coagulopathy rendered her otherwise potentially survivable injuries fatal. Given the frequency of multiple trauma and the recent increase in the prevalence of synthetic cannabinoid, it can be expected that the incidence of trauma complicated by synthetic cannabinoid-associated coagulopathy will increase in the near future. For patients that present with prolonged prothrombin time and/or activated partial thromboplastin time, it is important to inquire about recent synthetic cannabinoid use.