bims-heshmo 2021-05-30 papers

bims-heshmo

Biomed News

on Trauma hemorrhagic shock — molecular basis

Issue of 2021–05–30
fiveteen papers selected by
Andreia Luís, Ludwig Boltzmann Institute

Disseminated intravascular coagulation immediately after trauma predicts a poor prognosis in severely injured patients.
ROLE OF ALBUMIN ON ENDOTHELIAL BASEMENT MEMBRANE AND HEMOSTASIS IN A RAT MODEL OF HEMORRHAGIC SHOCK.
Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma.
Prehospital End-Tidal CO2: A Superior Marker for Mortality Risk in the Acutely Injured Patient.
Association Between Hyperoxia, Supplemental Oxygen, and Mortality in Critically Injured Patients.
Potential protective effect of hesperidin on hypoxia/reoxygenation-induced hepatocyte injury.
Recommended Primary Outcomes for Clinical Trials Evaluating Hemostatic Blood Products and Agents in Patients with Bleeding: Proceedings of a National Heart Lung and Blood Institute and United States Department of Defense Consensus Conference.
Prehospital resuscitation.
Outcomes of Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome Following Traumatic Injury: A Propensity-Matched Analysis.
Pentoxifylline treatment alleviates kidney ischemia/reperfusion injury: Novel involvement of galectin-3 and ASK-1/JNK & ERK1/2/NF-κB/HMGB-1 trajectories.
Remote ischemic preconditioning improves tissue oxygenation in a porcine model of controlled hemorrhage without fluid resuscitation.
Intelligent prediction of RBC demand in trauma patients using decision tree methods.
5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis.
Acute Respiratory Distress Syndrome (ARDS) after trauma: Improving incidence, but increasing mortality.
Slounase, a Batroxobin Containing Activated Factor X Effectively Enhances Hemostatic Clot Formation and Reducing Bleeding in Hypocoagulant Conditions in Mice.

Sci Rep. 2021 May 26. 11(1): 11031

Disseminated intravascular coagulation immediately after trauma predicts a poor prognosis in severely injured patients.

Takeshi Wada, Atsushi Shiraishi, Satoshi Gando, Kazuma Yamakawa, Seitaro Fujishima, Daizoh Saitoh, Shigeki Kushimoto, Hiroshi Ogura, Toshikazu Abe, Toshihiko Mayumi, Junichi Sasaki, Joji Kotani, Naoshi Takeyama, Ryosuke Tsuruta, Kiyotsugu Takuma, Norio Yamashita, Shin-Ichiro Shiraishi, Hiroto Ikeda, Yasukazu Shiino, Takehiko Tarui, Taka-Aki Nakada, Toru Hifumi, Kohji Okamoto, Yuichiro Sakamoto, Akiyoshi Hagiwara, Tomohiko Masuno, Masashi Ueyama, Satoshi Fujimi, Yutaka Umemura, Yasuhiro Otomo.

Trauma patients die from massive bleeding due to disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype in the early phase, which transforms to DIC with a thrombotic phenotype in the late phase of trauma, contributing to the development of multiple organ dysfunction syndrome (MODS) and a consequently poor outcome. This is a sub-analysis of a multicenter prospective descriptive cross-sectional study on DIC to evaluate the effect of a DIC diagnosis on the survival probability and predictive performance of DIC scores for massive transfusion, MODS, and hospital death in severely injured trauma patients. A DIC diagnosis on admission was associated with a lower survival probability (Log Rank P < 0.001), higher frequency of massive transfusion and MODS and a higher mortality rate than no such diagnosis. The DIC scores at 0 and 3 h significantly predicted massive transfusion, MODS, and hospital death. Markers of thrombin and plasmin generation and fibrinolysis inhibition also showed a good predictive ability for these three items. In conclusion, a DIC diagnosis on admission was associated with a low survival probability. DIC scores obtained immediately after trauma predicted a poor prognosis of severely injured trauma patients.

DOI: https://doi.org/10.1038/s41598-021-90492-0
J Trauma Acute Care Surg. 2021 May 25.

ROLE OF ALBUMIN ON ENDOTHELIAL BASEMENT MEMBRANE AND HEMOSTASIS IN A RAT MODEL OF HEMORRHAGIC SHOCK.

Luciana N Torres, Christi L Salgado, Michael A Dubick, Andrew P Cap, Ivo P Torres Filho.

BACKGROUND: We sought to determine the extent of loss of endothelial basement membrane (BM), leukocyte recruitment and changes in coagulation after hemorrhagic shock (HS), followed by limited-volume resuscitation (LVR) with 5% albumin (ALB).
METHODS: Anesthetized rats were bled 40% of blood volume and assigned to treatment groups: untreated (n = 6); LVR with normal saline (NS; n = 8); or LVR with ALB (n = 8). Sham rats (n = 6) underwent all procedures except hemorrhage or resuscitation. Blood samples were assayed for active proteases, such as metalloproteinase-9 (MMP-9) and a disintegrin metalloproteinase 10 (ADAM-10), BM-type heparan sulfate proteoglycan (perlecan), cell count and coagulation function. Leukocyte transmigration was used to estimate the net efficiency of leukocyte recruitment in cremaster venules.
RESULTS: Hemorrhage significantly lowered red cell count, but white cell and platelet counts did not change (vs. sham) Ionized calcium in plasma were significantly reduced in untreated and remained so after NS. In contrast, ionized calcium was normalized after albumin. Plasma expansion after NS and ALB further reduced leukocyte and platelet counts. MMP-9, ADAM-10 and perlecan were significantly higher in untreated rats (vs. sham). ALB normalized MMP-9, ADAM-10 and perlecan levels, while NS further increased MMP-9, ADAM-10 and perlecan (vs. sham). Transmigrated leukocytes doubled in the untreated group and remained elevated after NS (vs. sham) but normalized after ALB. ALB reduced every stage of the leukocyte recruitment process to sham levels.
CONCLUSIONS: Despite similar plasma expansion, NS weakened platelet function contrary to ALB. Plasma expansion with ALB resulted in restoration of BM integrity and attenuation of leukocyte recruitment to tissues, in contrast to NS. ALB plays a critical role in restoring BM integrity, attenuating leukocyte recruitment to tissues, and optimizing hemostasis by increasing ionized calcium in plasma.

DOI: https://doi.org/10.1097/TA.0000000000003298
J Surg Res. 2021 May 20. pii: S0022-4804(21)00245-6. [Epub ahead of print]266 222-229

Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma.

Ben E Biesterveld, Ali Z Siddiqui, Rachel L O'Connell, Henriette Remmer, Aaron M Williams, Alizeh Shamshad, William M Smith, Michael T Kemp, Glenn K Wakam, Hasan B Alam.

   INTRODUCTION: Trauma is the leading cause of death among young people. These patients have a high incidence of kidney injury, which independently increases the risk of mortality. As valproic acid (VPA) treatment has been shown to improve survival in animal models of lethal trauma, we hypothesized that it would also attenuate the degree of acute kidney injury.
METHODS: We analyzed data from two separate experiments where swine were subjected to lethal insults. Model 1: hemorrhage (50% blood volume hemorrhage followed by 72-h damage control resuscitation). Model 2: polytrauma (traumatic brain injury, 40% blood volume hemorrhage, femur fracture, rectus crush and grade V liver laceration). Animals were resuscitated with normal saline (NS) +/- VPA 150 mg/kg after a 1-h shock phase in both models (n = 5-6/group). Serum samples were analyzed for creatinine (Cr) using colorimetry on a Liasys 330 chemistry analyzer. Proteomic analysis was performed on kidney tissue sampled at the time of necropsy.
RESULTS: VPA treatment significantly (P < 0.05) improved survival in both models. (Model 1: 80% vs 20%; Model 2: 83% vs. 17%). Model 1 (Hemorrhage alone): Cr increased from a baseline of 1.2 to 3.0 in NS control animals (P < 0.0001) 8 h after hemorrhage, whereas it rose only to 2.1 in VPA treated animals (P = 0.004). Model 2 (Polytrauma): Cr levels increased from baseline of 1.3 to 2.5 mg/dL (P = 0.01) in NS control animals 4 h after injury but rose to only 1.8 in VPA treated animals (P = 0.02). Proteomic analysis of kidney tissue identified metabolic pathways were most affected by VPA treatment.
CONCLUSIONS: A single dose of VPA (150 mg/kg) offers significant protection against acute kidney injury in swine models of polytrauma and hemorrhagic shock.

Keywords:  AKI; HDACI; Histone deacetylase; Proteomics; VPA

DOI:  https://doi.org/10.1016/j.jss.2021.04.014
Am Surg. 2021 May 28. 31348211023401

Prehospital End-Tidal CO2: A Superior Marker for Mortality Risk in the Acutely Injured Patient.

Robert G Willis, Kyle W Cunningham, Paola A Troia, Ashley S Gutierrez, Ashley B Christmas, Rita Brintzenhoff, Ronald F Sing.

   BACKGROUND: Emergency medical personnel must expeditiously triage acutely injured patients to the appropriate medical facility. Efficient and objective variables to facilitate this process and provide information to the receiving trauma center are needed. Currently, multiple variables are used to prognosticate injury severity and risk of mortality including vital signs, mental status, lactate, and base excess. We investigated the prehospital use of end-tidal carbon dioxide (ETCO2) as a noninvasive physiologic measure that can be obtained in the acutely injured patient.
METHODS: We performed a retrospective analysis of 557 acutely injured patients over 2 years at a Level 1 trauma center. All patients arriving as trauma activations with ETCO2 measurements were included in analysis. End-tidal carbon dioxide measurements were categorized as low, normal, and high based on reference levels. Mortality was the primary outcome. Secondary receiver operator curves (ROC) for base excess, venous lactate, blood pressure, and venous pH were compared. We hypothesized ETCO2 levels would be able to predict mortality.
RESULTS: End-tidal carbon dioxide levels conferred a mortality rate of 38%, 17.3%, and 2.9% for low, normal, and high, respectively (P < .001). Receiver operator curve analysis produced an area under the curve predictive value for ETCO2 (.748) which was superior to lactate (.660), SBP (.578), pH (.560), and base excess (.497).
DISCUSSION: End-tidal carbon dioxide is a more sensitive and specific predictor of mortality in the acutely injured patient compared to venous lactate, base deficit, blood pressure, or venous pH. Additional studies are needed to determine if ETCO2 can be used as an effective prehospital adjunct to prevent mortality in acutely injured patients.

Keywords:  injury severity; resuscitation; shock; trauma; triage; vital signs

DOI:  https://doi.org/10.1177/00031348211023401
Crit Care Explor. 2021 May;3(5): e0418

Association Between Hyperoxia, Supplemental Oxygen, and Mortality in Critically Injured Patients.

David J Douin, Erin L Anderson, Layne Dylla, John D Rice, Conner L Jackson, Franklin L Wright, Vikhyat S Bebarta, Steven G Schauer, Adit A Ginde.

   OBJECTIVES: Hyperoxia is common among critically ill patients and may increase morbidity and mortality. However, limited evidence exists for critically injured patients. The objective of this study was to determine the association between hyperoxia and in-hospital mortality in adult trauma patients requiring ICU admission.
DESIGN SETTING AND PARTICIPANTS: This multicenter, retrospective cohort study was conducted at two level I trauma centers and one level II trauma center in CO between October 2015 and June 2018. All adult trauma patients requiring ICU admission within 24 hours of emergency department arrival were eligible. The primary exposure was oxygenation during the first 7 days of hospitalization.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Primary outcome was in-hospital mortality. Secondary outcomes were hospital-free days and ventilator-free days. We included 3,464 critically injured patients with a mean age of 52.6 years. Sixty-five percent were male, and 66% had blunt trauma mechanism of injury. The primary outcome of in-hospital mortality occurred in 264 patients (7.6%). Of 226,057 patient-hours, 46% were spent in hyperoxia (oxygen saturation > 96%) and 52% in normoxia (oxygen saturation 90-96%). During periods of hyperoxia, the adjusted risk for mortality was higher with greater oxygen administration. At oxygen saturation of 100%, the adjusted risk scores for mortality (95% CI) at Fio2 of 100%, 80%, 60%, and 50% were 6.4 (3.5-11.8), 5.4 (3.4-8.6), 2.7 (1.7-4.1), and 1.5 (1.1-2.2), respectively. At oxygen saturation of 98%, the adjusted risk scores for mortality (95% CI) at Fio2 of 100%, 80%, 60%, and 50% were 7.7 (4.3-13.5), 6.3 (4.1-9.7), 3.2 (2.2-4.8), and 1.9 (1.4-2.7), respectively.
CONCLUSIONS: During hyperoxia, higher oxygen administration was independently associated with a greater risk of mortality among critically injured patients. Level of evidence: Cohort study, level III.

Keywords:  critical care; hyperoxia; injuries; intensive care units; oxygenation; trauma

DOI:  https://doi.org/10.1097/CCE.0000000000000418
Exp Ther Med. 2021 Jul;22(1): 764

Potential protective effect of hesperidin on hypoxia/reoxygenation-induced hepatocyte injury.

Shilai Li, Jijin Zhu, Ling Pan, Peiqi Wan, Quanlin Qin, Daqing Luo, Wenhui Pan, Yuqing Wei, Yansong Xu, Liming Shang, Xinping Ye.

  Hesperidin (HDN) has been reported to have hydrogen radical- and hydrogen peroxide-removal activities and to serve an antioxidant role in biological systems. However, whether HDN protects hepatocytes (HCs) against hypoxia/reoxygenation (H/R)-induced injury remains unknown. The present study aimed to explore the role of HDN in H/R-induced injury. HCs were isolated and cultured under H/R conditions with or without HDN treatment. HC damage was markedly induced under H/R, as indicated by cell viability, supernatant lactate dehydrogenase levels and alanine aminotransferase levels; however, HDN treatment significantly reversed HC injury. Oxidative stress markers (malondialdehyde, superoxide dismutase, glutathioneand reactive oxygen species) were increased markedly during H/R in HCs; however, this effect was significantly attenuated after exposure to HDN. Compared with those of the control group, the mRNA expression levels of IL-6 and TNF-α in HCs and the concentrations of IL-6 and TNF-α in the supernatants increased significantly following H/R, and HDN significantly ameliorated these effects. Western blotting demonstrated that microtubule-associated protein 1 light chain 3α (MAP1LC3A, also known as LC3) and Beclin-1 protein expression levels increased, while sequestosome 1 levels decreased during H/R following exposure to HDN. The number of GFP-LC3 puncta in HCs following exposure to HDN was increased compared with that observed in HCs without HDN exposure under the H/R conditions after bafilomycin A1 treatment. In summary, the present study demonstrated that HDN attenuated HC oxidative stress and inflammatory responses while enhancing autophagy during H/R. HDN may have a potential protective effect on HCs during H/R-induced injury.

Keywords:  autophagy; hepatocyte; hesperidin; hypoxia/reoxygenation; oxidative stress

DOI:  https://doi.org/10.3892/etm.2021.10196
J Trauma Acute Care Surg. 2021 May 26.

Recommended Primary Outcomes for Clinical Trials Evaluating Hemostatic Blood Products and Agents in Patients with Bleeding: Proceedings of a National Heart Lung and Blood Institute and United States Department of Defense Consensus Conference.

Hemostasis Trials Outcomes Working Group

DOI: https://doi.org/10.1097/TA.0000000000003300
Trauma Surg Acute Care Open. 2021 ;6(1): e000729

Prehospital resuscitation.

Alexandra M P Brito, Martin Schreiber.

  Traumatic injury is the leading cause of death in young people in the USA. Our knowledge of prehospital resuscitation is constantly evolving and is often informed by research based on military experience. A move toward balanced blood product resuscitation and away from excessive crystalloid use has led to improvements in outcomes for trauma patients. This has been facilitated by new technologies allowing more front-line use of blood products as well as use of tranexamic acid in the prehospital setting. In this article, we review current practices in prehospital resuscitation and the studies that have informed these practices.

Keywords:  heorrhagic; multiple trauma; shock

DOI:  https://doi.org/10.1136/tsaco-2021-000729
Crit Care Explor. 2021 May;3(5): e0421

Outcomes of Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome Following Traumatic Injury: A Propensity-Matched Analysis.

Nasim Ahmed, Yen-Hong Kuo, Abimbola Pratt.

   OBJECTIVES: The purpose of this study is to evaluate the overall occurrence of inhospital mortality in trauma patients who were placed on extracorporeal membrane oxygenation following the complication of the acute respiratory distress syndrome.
DESIGN: Observational cohort study.
SETTING: The data of all patients who were traumatically injured and developed the complication of acute respiratory distress syndrome were accessed from the Trauma Quality Improvement Program database from the calendar years of 2013 to 2016.
PATIENTS: Patients 16 years old and less than 90 years old were included in the study. Variables included patient demography, Injury Severity Score, Glasgow Coma Scale score, Abbreviated Injury Scale score, and outcomes.
INTERVENTIONS: Extracorporeal membrane oxygenation.
MEASUREMENTS AND MAIN RESULTS: Propensity-matched analysis was performed between two groups: patients placed on extracorporeal membrane oxygenation and patients placed on conventional mode of ventilation. The primary outcome was inhospital mortality. Out of 6,121 patients who developed acute respiratory distress syndrome, 118 patients (1.93%) were placed on extracorporeal membrane oxygenation. The pair matched analysis showed significant difference between the two groups (extracorporeal membrane oxygenation vs conventional mode of ventilation) for overall inhospital mortality (35.6% vs 14.4%; p < 0.001). There were significant differences found between the two groups for the median hospital length of stay (41 [35-49] vs 27 [24-33]), ICU days (35 [30-41] vs 19 [17-24]), and ventilator days (30 [27-34] vs 15 [13-18]). All p values are less than 0.001.
CONCLUSIONS: Approximately 2% of acute respiratory distress syndrome patients were placed on extracorporeal membrane oxygenation. The overall inhospital mortality remained high despite patients being placed on extracorporeal membrane oxygenation.

Keywords:  extracorporeal membrane oxygenator; mortality; severe acute respiratory distress syndrome; trauma

DOI:  https://doi.org/10.1097/CCE.0000000000000421
J Pharmacol Sci. 2021 Jul;pii: S1347-8613(21)00031-1. [Epub ahead of print]146(3): 136-148

Pentoxifylline treatment alleviates kidney ischemia/reperfusion injury: Novel involvement of galectin-3 and ASK-1/JNK & ERK1/2/NF-κB/HMGB-1 trajectories.

Hagar M El-Sadek, Muhammad Y Al-Shorbagy, Magdy M Awny, Dalaal M Abdallah, Hanan S El-Abhar.

  Despite the documented renoprotective effect of pentoxifylline (PTX), a non-selective phosphodiesterase-4 inhibitor, the studies appraised only its anti-inflammatory/-oxidant/-apoptotic capacities without assessment of the possible involved trajectories. Here, we evaluated the potential role of galectin-3 and the ASK-1/NF-κB p65 signaling pathway with its upstream/downstream signals in an attempt to unveil part of the cascades involved in the renotherapeutic effect using a renal bilateral ischemia/reperfusion (I/R) model. Rats were randomized into sham-operated, renal I/R (45 min/72 h) and I/R + PTX (100 mg/kg; p.o). Post-treatment with PTX improved renal function and abated serum levels of cystatin C, creatinine, BUN and renal KIM-1 content, effects that were reflected on an improvement of the I/R-induced renal histological changes. On the molecular level, PTX reduced renal contents of galectin-3, ASK-1 with its downstream molecule JNK and ERK1/2, as well as NF-κB p65 and HMGB1. This inhibitory effect extended also to suppress neutrophil infiltration, evidenced by diminishing ICAM-1 and MPO, as well as inflammatory cytokines (TNF-α/IL-18), oxidative stress (MDA/TAC), and caspase-3. The PTX novel renotherapeutic effect involved in part the inhibition of galectin-3 and ASK-1/JNK and ERK1/2/NF-κB/HMGB-1 trajectories to mitigate renal I/R injury and to provide basis for its anti-inflammatory, antioxidant, and anti-apoptotic impacts.

Keywords:  ASK-1; ERK; Galectin-3; HMGB1; JNK

DOI:  https://doi.org/10.1016/j.jphs.2021.03.011
Sci Rep. 2021 May 24. 11(1): 10808

Remote ischemic preconditioning improves tissue oxygenation in a porcine model of controlled hemorrhage without fluid resuscitation.

Gal Yaniv, Arik Eisenkraft, Lilach Gavish, Linn Wagnert-Avraham, Dean Nachman, Jacob Megreli, Gil Shimon, Daniel Rimbrot, Ben Simon, Asaf Berman, Matan Cohen, David Kushnir, Ruth Shaylor, Baruch Batzofin, Shimon Firman, Amir Shlaifer, Michael Hartal, Yuval Heled, Elon Glassberg, Yitshak Kreiss, S David Gertz.

Remote ischemic preconditioning (RIPC) involves deliberate, brief interruptions of blood flow to increase the tolerance of distant critical organs to ischemia. This study tests the effects of limb RIPC in a porcine model of controlled hemorrhage without replacement therapy simulating an extreme field situation of delayed evacuation to definitive care. Twenty-eight pigs (47 ± 6 kg) were assigned to: (1) control, no procedure (n = 7); (2) HS = hemorrhagic shock (n = 13); and (3) RIPC + HS = remote ischemic preconditioning followed by hemorrhage (n = 8). The animals were observed for 7 h after bleeding without fluid replacement. Survival rate between animals of the RIPC + HS group and those of the HS group were similar (HS, 6 of 13[46%]-vs-RIPC + HS, 4 of 8[50%], p = 0.86 by Chi-square). Animals of the RIPC + HS group had faster recovery of mean arterial pressure and developed higher heart rates without complications. They also had less decrease in pH and bicarbonate, and the increase in lactate began later. Global oxygen delivery was higher, and tissue oxygen extraction ratio lower, in RIPC + HS animals. These improvements after RIPC in hemodynamic and metabolic status provide essential substrates for improved cellular response after hemorrhage and reduction of the likelihood of potentially catastrophic consequences of the accompanying ischemia.

DOI: https://doi.org/10.1038/s41598-021-90470-6
Mil Med Res. 2021 May 24. 8(1): 33

Intelligent prediction of RBC demand in trauma patients using decision tree methods.

Yan-Nan Feng, Zhen-Hua Xu, Jun-Ting Liu, Xiao-Lin Sun, De-Qing Wang, Yang Yu.

   BACKGROUND: The vital signs of trauma patients are complex and changeable, and the prediction of blood transfusion demand mainly depends on doctors' experience and trauma scoring system; therefore, it cannot be accurately predicted. In this study, a machine learning decision tree algorithm [classification and regression tree (CRT) and eXtreme gradient boosting (XGBoost)] was proposed for the demand prediction of traumatic blood transfusion to provide technical support for doctors.
METHODS: A total of 1371 trauma patients who were diverted to the Emergency Department of the First Medical Center of Chinese PLA General Hospital from January 2014 to January 2018 were collected from an emergency trauma database. The vital signs, laboratory examination parameters and blood transfusion volume were used as variables, and the non-invasive parameters and all (non-invasive + invasive) parameters were used to construct an intelligent prediction model for red blood cell (RBC) demand by logistic regression (LR), CRT and XGBoost. The prediction accuracy of the model was compared with the area under the curve (AUC).
RESULTS: For non-invasive parameters, the LR method was the best, with an AUC of 0.72 [95% confidence interval (CI) 0.657-0.775], which was higher than the CRT (AUC 0.69, 95% CI 0.633-0.751) and the XGBoost (AUC 0.71, 95% CI 0.654-0.756, P < 0.05). The trauma location and shock index are important prediction parameters. For all the prediction parameters, XGBoost was the best, with an AUC of 0.94 (95% CI 0.893-0.981), which was higher than the LR (AUC 0.80, 95% CI 0.744-0.850) and the CRT (AUC 0.82, 95% CI 0.779-0.853, P < 0.05). Haematocrit (Hct) is an important prediction parameter.
CONCLUSIONS: The classification performance of the intelligent prediction model of red blood cell transfusion in trauma patients constructed by the decision tree algorithm is not inferior to that of the traditional LR method. It can be used as a technical support to assist doctors to make rapid and accurate blood transfusion decisions in emergency rescue environment, so as to improve the success rate of patient treatment.

Keywords:  Decision tree; Intelligent prediction; Invasive parameters; Mathematical model; Non-invasive parameters; Transfusion; Trauma

DOI:  https://doi.org/10.1186/s40779-021-00326-3
Sci Rep. 2021 May 27. 11(1): 11100

5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via a BLTR1 signaling axis.

Jong Min Choi, Seung Eun Baek, Ji On Kim, Eun Yeong Jeon, Eun Jeong Jang, Chi Dae Kim.

Monocyte chemoattractant protein-1 (MCP-1) plays an important role in initiating vascular inflammation; however, its cellular source in the injured vasculatures is unclear. Given the importance of high mobility group box 1 (HMGB1) in tissue injury, we investigated the role of vascular smooth muscle cells (VSMCs) in MCP-1 production in response to HMGB1. In primary cultured rat aortic VSMCs stimulated with HMGB1, the expression of MCP-1 and 5-lipoxygenase (LO) was increased. The increased MCP-1 expression in HMGB1 (30 ng/ml)-stimulated cells was significantly attenuated in 5-LO-deficient cells as well as in cells treated with zileuton, a 5-LO inhibitor. Likewise, MCP-1 expression and production were also increased in cells stimulated with exogenous leukotriene B4 (LTB4), but not exogenous LTC4. LTB4-induced MCP-1 expression was attenuated in cells treated with U75302, a LTB4 receptor 1 (BLTR1) inhibitor as well as in BLTR1-deficient cells, but not in 5-LO-deficient cells. Moreover, HMGB1-induced MCP-1 expression was attenuated in BLTR1-deficient cells or by treatment with a BLTR1 inhibitor, but not other leukotriene receptor inhibitors. In contrast to MCP-1 expression in response to LTB4, the increased MCP-1 production in HMGB1-stimulated VSMC was markedly attenuated in 5-LO-deficient cells, indicating a pivotal role of LTB4-BLTR1 signaling in MCP-1 expression in VSMCs. Taken together, 5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via BLTR1 signaling, suggesting the LTB4-BLTR1 signaling axis as a potential therapeutic target for vascular inflammation in the injured vasculatures.

DOI: https://doi.org/10.1038/s41598-021-90636-2
J Crit Care. 2021 May 13. pii: S0883-9441(21)00082-4. [Epub ahead of print]64 213-218

Acute Respiratory Distress Syndrome (ARDS) after trauma: Improving incidence, but increasing mortality.

George Kasotakis, Brent Stanfield, Krista Haines, Cory Vatsaas, Amy Alger, Steven N Vaslef, Kelli Brooks, Suresh Agarwal.

   PURPOSE: Acute Respiratory Distress Syndrome (ARDS) is an infrequent, yet morbid inflammatory complication in injury victims. With the current project we sought to estimate trends in incidence, determine outcomes, and identify risk factors for ARDS and related mortality.
MATERIALS & METHODS: The national Trauma Quality Improvement Program dataset (2010-2014) was queried. Demographics, injury characteristics and outcomes were compared between patients who developed ARDS and those who did not. Logistic regression models were fitted for the development of ARDS and mortality respectively, adjusting for relevant confounders.
RESULTS: In the studied 808,195 TQIP patients, incidence of ARDS decreased over the study years (3-1.1%, p < 0.001), but related mortality increased (18.-21%, p = 0.001). ARDS patients spent an additional 14.7 ± 10.3 days in the hospital, 9.7 ± 7.9 in the ICU, and 6.6 ± 9.4 on mechanical ventilation (all p < 0.001). Older age, male gender, African American race increased risk for ARDS. Age, male gender, lower GCS and higher ISS also increased mortality risk among ARDS patients. Several pre-existing comorbidities including chronic alcohol use, diabetes, smoking, and respiratory disease also increased risk.
CONCLUSION: Although the incidence of ARDS after trauma appears to be declining, mortality is on the rise.

Keywords:  Acute lung injury; Acute respiratory distress syndrome; Mortality; Trauma quality improvement program; Traumatic injury

DOI:  https://doi.org/10.1016/j.jcrc.2021.05.003
Clin Appl Thromb Hemost. 2021 Jan-Dec;27:27 10760296211018510

Slounase, a Batroxobin Containing Activated Factor X Effectively Enhances Hemostatic Clot Formation and Reducing Bleeding in Hypocoagulant Conditions in Mice.

Reheman Adili, Madeline Jackson, Livia Stanger, Xiangrong Dai, Mandy Li, Benjamin Xiaoyi Li, Michael Holinstat.

  Uncontrolled bleeding associated with trauma and surgery is the leading cause of preventable death. Batroxobin, a snake venom-derived thrombin-like serine protease, has been shown to clot fibrinogen by cleaving fibrinopeptide A in a manner distinctly different from thrombin, even in the presence of heparin. The biochemical properties of batroxobin and its effect on coagulation have been well characterized in vitro. However, the efficacy of batroxobin on hemostatic clot formation in vivo is not well studied due to the lack of reliable in vivo hemostasis models. Here, we studied the efficacy of batroxobin and slounase, a batroxobin containing activated factor X, on hemostatic clot composition and bleeding using intravital microcopy laser ablation hemostasis models in micro and macro vessels and liver puncture hemostasis models in normal and heparin-induced hypocoagulant mice. We found that prophylactic treatment in wild-type mice with batroxobin, slounase and activated factor X significantly enhanced platelet-rich fibrin clot formation following vascular injury. In heparin-treated mice, batroxobin treatment resulted in detectable fibrin formation and a modest increase in hemostatic clot size, while activated factor X had no effect. In contrast, slounase treatment significantly enhanced both platelet recruitment and fibrin formation, forming a stable clot and shortening bleeding time and blood loss in wild-type and heparin-treated hypocoagulant mice. Our data demonstrate that, while batroxobin enhances fibrin formation, slounase was able to enhance hemostasis in normal mice and restore hemostasis in hypocoagulant conditions via the enhancement of fibrin formation and platelet activation, indicating that slounase is more effective in controlling hemorrhage.

Keywords:  batroxobin; bleeding; coagulation; fibrin; hemostasis; platelet

DOI:  https://doi.org/10.1177/10760296211018510