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Introduction: Wünderlich syndrome (WS) refers to subcapsular, perirenal, or pararenal hemorrhage due to non-traumatic and iatrogenic conditions. Neoplasms, vascular disease, renal etiology, and anticoagulant use are underlying risk factors.Case Report: We describe a case of WS in a 79-year-old male who was undergoing hemodialysis, which resulted in hemorrhagic shock requiring multiple transfusions and embolization by interventional radiology.Conclusion: Most commonly, patients present with flank pain; a computed tomography with contrast of the abdomen is essential for diagnosis. Surgical intervention is considered in hemodynamically unstable patients. Conservative therapy and intravenous resuscitations with blood products are considered a priority in hemodynamically stable patients.

This study aims to investigate the effects of hypoxically stored Red Blood Cells (RBCs) in a rat model of traumatic brain injury followed by severe hemorrhagic shock (HS) and resuscitation. RBCs were made hypoxic using an O2 depletion system (Hemanext Inc. Lexington, MA) and stored for 3 weeks. Experimental animals underwent craniotomy and blunt brain injury followed by severe HS. Rats were resuscitated with either fresh RBCs (FRBCs), 3-week-old hypoxically stored RBCs (HRBCs), or 3-week-old conventionally stored RBCs (CRBCs). Resuscitation was provided via RBCs transfusion equivalent to 70 % of the shed blood and animals were followed for 2 h. The control group was comprised of healthy animals that were not instrumented or injured. Post-resuscitation hemodynamics and lactate levels were improved with FRBCs and HRBCs, and markers of organ injury in the liver (Aspartate aminotransferase [AST]), lung (chemokine ligand 1 [CXCL-1] and Leukocytes count), and heart (cardiac troponin, Interleukin- 6 [IL-6] and Tumor Necrosis Factor Alpha[TNF-α]) were lower with FRBCs and HRBCs resuscitation compared to CRBCs. Following reperfusion, biomarkers for oxidative stress, lipid peroxidation, and RNA/DNA injury were assessed. Superoxide dismutase [SOD] levels in the HRBCs group were similar to the FRBCs group and levels in both groups were significantly higher than CRBCs. Catalase levels were not different than control values in the FRBCs and HRBCs groups but significantly lower with CRBCs. Thiobarbituric acid reactive substances [Tbars] levels were higher for both CRBCs and HRBCs. Hypoxically stored RBCs show few differences from fresh RBCs in resuscitation from TBI + HS and decreased organ injury and oxidative stress compared to conventionally stored RBCs.

For the last two decades, the aromatic aldehyde 5‐hydroxymethyl‐furfural (5‐HMF) has been the subject of several investigations for its pharmacologic potential. In 2004, the Safo group reported that 5‐HMF has potent antisickling activity by targeting and ameliorating the primary pathophysiology of hypoxia‐induced sickling of erythrocytes (red blood cells [RBC]). Following the encouraging outcome of the preclinical and phase I/II clinical studies of 5‐HMF for the treatment of sickle cell disease (SCD), there have been multiple studies suggesting 5‐HMF has several other biological or pharmacologic activities, including anti‐allergic, antioxidant, anti‐hypoxic, anti‐ischemic, cognitive improvement, anti‐tyrosinase, anti‐proliferation, cytoprotective, and anti‐inflammatory activities. The wide range of its effects makes 5‐HMF a potential candidate for treating a variety of diseases including cognitive disorders, gout, allergic disorders, anemia, hypoxia, cancers, ischemia, hemorrhagic shock, liver fibrosis, and oxidative injury. Several of these therapeutic claims are currently under investigation and, while promising, vary in terms of the strength of their evidence. This review presents the research regarding the therapeutic potential of 5‐HMF in addition to its sources, physicochemical properties, safety, absorption, distribution, metabolism, and excretion (ADME) profiles. [ABSTRACT FROM AUTHOR]

Hemorrhagic shock and resuscitation (HSR) enhances the risk of acute lung injury (ALI). This study investigated the protective effect of carbamazepine (CBZ) on HSR-induced ALI in rats. Male Sprague-Dawley rats were allocated into five distinct groups through randomization: control (SHAM), saline + HSR (HSR), CBZ + HSR (CBZ/HSR), dimethyl sulfoxide (DMSO) + HSR (DMSO/HSR), and CBZ + chloroquine (CQ) + HSR (CBZ/CQ/HSR). Subsequently, HSR models were established. To detect tissue damage, we measured lung histological changes, lung injury scores, and wet/dry weight ratios. We measured neutrophil counts as well as assessed the expression of inflammatory factors using RT-PCR to determine the inflammatory response. We detected autophagy-related proteins LC3II/LC3I, P62, Beclin-1, and Atg12-Atg5 using western blotting. Pretreatment with CBZ improved histopathological changes in the lungs and reduced lung injury scores. The CBZ pretreatment group exhibited significantly reduced lung wet/dry weight ratio, neutrophil aggregation and number, and inflammation factor (TNF-α and iNOS) expression. CBZ changed the expression levels of autophagy-related proteins (LC3II/LC3I, beclin-1, Atg12-Atg5, and P62), suggesting autophagy activation. However, after injecting CQ, an autophagy inhibitor, the beneficial effects of CBZ were reversed. Taken together, CBZ pretreatment improved HSR-induced ALI by suppressing inflammation, at least in part, through activating autophagy. Thus, our study offers a novel perspective for treating HSR-induced ALI. [ABSTRACT FROM AUTHOR]

Summary Hepatic artery pseudoaneurysm (HAP) is a rare vascular complication following liver transplantation (LTx) with treatment choice frequently driven by institutional experience. Approximately, 10% of hepatic grafts are lost from this complication, requiring re‐transplantation and placing further demand on the already present organ shortage. Secondly, patients with HAP can present with catastrophic bleeding, with reported mortality of up to 78%. We aim to identify risk factors associated with HAP and assess the survival benefit of different treatment modalities used (endovascular and open surgical techniques). Early detection may facilitate semi‐elective management of this condition. A systematic search was performed in PubMed, Medline and Embase up to 1 October 2023. Case series with ≥5 patients focusing on adult patients who developed extrahepatic pseudoaneurysm following LTx were included. A total of 11 studies were pooled, comprising of 118 patients with survival data available in 61 patients. The most common presentation was haemorrhagic shock or luminal haemorrhage (75.5%). Bile leak was documented in 66.7% (28/42), 15.2% (18/118) associated foregut pathologies and 28.6% (14/49) of microbiology cultures grew a fungal organism. Flow preserving strategies (stenting, revascularization) trended towards better survival at 120 months compared to non‐flow preserving strategies (embolization, HAL); however, this was not statistically significant following log rank (Mantel–Cox) analysis (P 0.169). Any patient following LTx presenting with haemorrhagic shock or luminal bleeding needs HAP excluded urgently. HAP management is complex, requiring careful consideration of patient specific presentation, anatomic factors and associated pathologies. [ABSTRACT FROM AUTHOR]

This letter to the editor published in Leukemia & Lymphoma discusses a case of acute undifferentiated leukemia (AUL) successfully treated with a novel combination therapy of FLAG-IDA and venetoclax. A 55-year-old female with AUL and high-risk genetic features achieved complete remission after induction treatment with FLAG-IDA + VEN. The patient experienced a complicated course but responded well to treatment, highlighting the potential efficacy of this regimen in AUL cases. The study emphasizes the importance of individualized treatment strategies for rare leukemia subtypes like AUL, which often have poor outcomes and limited treatment options. [Extracted from the article]

Background: Extracorporeal membrane oxygenation (ECMO) can provide temporary circulatory support and vital organ oxygenation and is potentially useful as a bridge therapy in some trauma cases. We aimed to demonstrate the characteristics and outcomes of patients with trauma treated with veno-arterial ECMO (V-A ECMO) using data from a Japanese nationwide trauma registry. Methods: This retrospective descriptive study analyzed data from the Japan Trauma Data Bank between January 2019 and December 2021. Patients with severe trauma (injury severity score [ISS] ≥ 9) and treated using V-A ECMO were assessed. Results: Among the 72,439 patients with severe trauma, 51 received V-A ECMO. Sixteen patients (31.3%) survived until hospital discharge. On hospital arrival, six (37.5%) survivors and 15 (42.9%) non-survivors experienced cardiac arrest. The median ISS for the survivor and non-survivor group was 25 (range, 25–39) and 25 (range, 17–33), respectively. Thoracic trauma was the most common type of trauma in both groups. In the non-survivor group, open-chest cardiopulmonary resuscitation, aortic cross-clamping, and resuscitative endovascular balloon occlusion of the aorta were performed in 10 (28.6%), 5 (14.3%), and 4 (11.4%) patients, respectively. However, these procedures were not performed in the survivor group. Peripheral oxygen saturation tended to be lower in the survivor group both before and upon arrival at the hospital. Conclusions: The results of this study suggest the potential benefit of V-A ECMO in some challenging trauma cases. Further studies are warranted to assess the indications for V-A ECMO in patients with trauma. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Phase I clinical trial of an artificial oxygen carrier (liposome‐encapsulated hemoglobin vesicles [HbVs]) is safely completed, considering the other clinical application. Herein, we aimed to investigate the resuscitation effects of HbVs in cases of lethal hemorrhage, including the mechanisms involved.Optical mapping analysis (OMP) and electrophysiological studies (EPS), immunostaining pathological examination for hypoxia‐inducible factor‐1α (HIF1‐alpha) in the heart tissue, and blood troponin I (TnI) level measurements were performed in rats that underwent five rounds of spontaneous arterial bleeding with up to 65% hemorrhage.Ten rats in each group were resuscitated by a transvenous infusion of 5% albumin (ALB), washed erythrocytes (wRBC), HbVs (HbV), 50% HbV diluted by 5% albumin (50% HbV), and 66% HbV diluted by 5% albumin (66% HbV). The rats in the ALB and 50% HbV groups died, whereas those in the other groups survived. OMP showed impaired action potential duration dispersion (APDd) in the left ventricle in the ALB and 50% HbV groups, which was attenuated in the other groups. Lethal arrhythmias were provoked by EPS in the ALB and 50% HbV groups but not in the other groups. HIF1‐alpha was positively stained only in the ALB and 50% HbV groups. TnI levels were elevated in the ALB and 50% HbV groups.Acute lethal hemorrhage causes myocardial ischemia with hypoxia and arrhythmias, which may be induced by impaired APDd and myocardial damage, reflected in the increased levels of HIF1‐alpha and TnI. HbVs could be useful for resuscitation and may help save patients with injuries such as gunshot wounds. [ABSTRACT FROM AUTHOR]

Background: Aortoesophageal fistula (AEF) is a rare cause of upper gastrointestinal hemorrhage. Despite diagnostic and therapeutic advances, the mortality rate in AEF patients remains high because of its fulminant course, even with maximal intensive care. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a resuscitation technique to control life-threatening bleeding. It has become an important modality in the management of life-threatening, traumatic or non-traumatic, arterial bleeding. However, it's use in hemorrhagic shock caused by cancer has rarely been reported. Case presentation: A 51-year-old woman with a history of esophageal cancer presented to our emergency department with hematemesis. Computed tomography was performed because of a strong suspicion of hemorrhagic shock. With a diagnosis of AEF due to esophageal cancer, emergency thoracic endovascular aortic repair was performed while the bleeding was controlled using REBOA. Staged elective esophageal reconstruction was successfully performed. Conclusions: Hemostasis is crucial in patients who present with suspected hemorrhagic shock attributable to AEF. The timely implementation of REBOA has shown promise and potential effectiveness in such cases. [ABSTRACT FROM AUTHOR]

Introduction The United States Army has shifted doctrine to focus on large-scale combat operations against peer to near-peer adversaries. Future conflicts could result in a limited supply chain, leaving medical providers with only expired blood products for treatment of hemorrhagic shock. This study evaluated quality, function, and safety metrics of whole blood stored for 1 week past regulated expiration (i.e. 35 days, in CPDA-1). Materials and Methods Whole blood units (n  = 6) were collected in citrate phosphate dextrose adenine-1 (CPDA-1) anticoagulant and stored refrigerated for up to 42 days. Units were sampled on days 35, 37, 39, and 42 of storage and evaluated for the following: complete blood count, blood metabolism and chemistries, clotting dynamics, and presence of bacteria. Results The majority of evaluated parameters fell outside of normal clinical ranges beginning at day 35 of storage. At 42 days, blood pH was 6.58 ± 0.038, hemolysis was significantly increased (P  = .037 vs day 35), and bacterial contamination was not evident. Glucose levels continuously dropped during extended storage. K+ was significantly increased at day 42 compared to day 35 (P  = .010). A significant reduction in clot strength, factor V activity, and factor VIII activity was evident beginning at day 39 of storage. Conclusions Storage of whole blood out to 42 days results in a continuous decline in function, but further in vivo safety studies should be performed to determine if the benefits of expired blood outweigh the risks. Other methods to safely extend storage of whole blood that maintain hemostatic function and preserve safety should be investigated, with emphasis placed on methods that reduce potassium leak and/or hemolysis. [ABSTRACT FROM AUTHOR]

Introduction Achieving simultaneous cerebral blood flow (CBF) and oxygenation measures, specifically for point-of-care injury monitoring in prolonged field care, requires the implementation of appropriate methodologies and advanced medical device design, development, and evaluation. The near-infrared spectroscopy (NIRS) method measures the absorbance of light whose attenuation is related to cerebral blood volume and oxygenation. By contrast, diffuse correlation spectroscopy (DCS) allows continuous noninvasive monitoring of microvascular blood flow by directly measuring the degree of light scattering because of red blood cell (RBC) movement in tissue capillaries. Hence, this study utilizes these two optical approaches (DCS–NIRS) to obtain a more complete hemodynamic monitoring by providing cerebral microvascular blood flow, hemoglobin oxygenation and deoxygenation in hemorrhage, and hypoxia-induced injuries. Materials and Methods Piglet models of hemorrhage and hypoxia-induced brain injury were used with DCS and NIRS sensors placed over the preorbital to temporal skull regions. To induce hemorrhagic shock, up to 70% of the animal's total blood volume was withdrawn through graded hemorrhage serially via a syringe from a femoral artery cannula in 10 mL/kg aliquots over 1 minute every 10 minutes. A second group of animals was subjected to hypoxia for ∼1 hour through graded hypoxia by serial titration from normoxic fraction inspired oxygen of 21% to hypoxic fraction inspired oxygen of 6%. A subset of animals served as sham-controls undergoing anesthesia, instrumentation, and ventilation as the injury groups, yet experiencing no blood loss or hypoxia. Results We first investigated the relationship between hemorrhagic shock and no shock by using measured biomarkers, including blood flow index from DCS associated with CBF and oxygenated (HbO) and de-oxygenated hemoglobin from NIRS. The statistical analysis revealed a significant difference between no shock and hemorrhagic shock (P  < .01). The HbO decreased with each blood loss as expected, yet the de-oxygenated hemoglobin was slightly changed. During hypoxia-induced global hypoxic–ischemic injury tests, the CBF results from graded hypoxia were consistent with the response previously measured during hemorrhagic shock. Moreover, HbO decreased when the animal was hypoxic, as expected. A statistical analysis was also conducted to compare the results with those of the sham controls. Conclusions There is a consistency in blood flow measures in both injury mechanisms (hemorrhagic shock and hypoxia), which is significant as the new prototype system provides similar measures and trends for each brain injury type, suggesting that the optical system can be used in response to different injury mechanisms. Notably, the results support the idea that this optical system can probe the hemodynamic status of local cerebral cortical tissue and provide insight into the underlying changes of cerebral tissue perfusion at the microvascular level. These measurement capabilities can improve shock identification and monitoring of medical management of injuries, particularly hemorrhagic shock, in prolonged field care. [ABSTRACT FROM AUTHOR]

Introduction Many trauma patients die from hemorrhagic shock in the military and civilian settings. Although two-thirds of hemorrhagic shock victims die of reasons other than exsanguination, such as the consequent cytokine storm, anti-inflammatory therapies failed to be utilized. Apoptotic cell–based treatments enhance innate ability to exert systemic immunomodulation as demonstrated in several clinical applications and hence might present a novel approach in hemorrhagic shock treatment. Materials and Methods Twenty-two rats underwent a pressure-controlled hemorrhagic shock model and followed up for 24 hours. An infusion of apoptotic cells (Allocetra-OTS, Enlivex Therapeutics Ltd, Nes Ziona, Israel) was administered to the treatment group. Hemodynamics, blood counts, biochemistry findings, and cytokine profile were compared to a saline-resuscitated control group. Results The treatment group's mean arterial pressure decreased from 94.8 mmHg to 28.2 mmHg, resulting in an 8.13 mg/dL increase in lactate and a 1.9 g/L decrease in hemoglobin, similar to the control group. White blood cells and platelets decreased more profoundly in the treatment group. A similar cytokine profile after 24 hours was markedly attenuated in the treatment group 2 hours after bleeding. Levels of pro-inflammatory cytokines such as interleukin (IL)-1a (28.4 pg/mL vs. 179.1 pg/mL), IL-1b (47.4 pg/mL vs. 103.9 pg/mL), IL-6 (526.2 pg/mL vs. 3492 pg/mL), interferon γ (11.4 pg/mL vs. 427.9 pg/mL), and tumor necrosis factor α (19.0 pg/mL vs. 31.7 pg/mL) were profoundly lower in the treatment group. Conclusion In a pressure-control hemorrhagic shock model in rats, apoptotic cell infusion showed preliminary signs of a uniform attenuated cytokine response. Apoptotic cell–based therapies might serve as a novel immunomodulatory therapy for hemorrhagic shock. [ABSTRACT FROM AUTHOR]

Objective: To discuss the effect of fluid resuscitation on the occurrence of ferroptosis in vascular tissue and the structure of vascular cells in the rats with blast injury complicated with hemorrhagic shock, and to clarify its mechanism. Methods: A total of 54 healthy adult SD rats were randomly divided into normal group, blast injury complicated with hemorrhagic shock (model) group, and the fluid resuscitation (treatment) group, and there were 18 rats in each group. Among them, 10 rats were randomly selected to observe the surival status and another 8 rats were selected to detect the other indexes. The average survival time(ST), 24 h and 72 h survival rates of the rats in various groups were observed; the blood pressure (BP), heart rate (HR), and respiratory rate (RR) of the rats in various groups were observed ; the levels of serum creatinine (Scr), blood urea nitrogen (BUN), lactate (LAC), glucose (GLU), iron ions, glutathione (GSH), and malondialdehyde (MDA) and the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in serum of the rats in various groups were detected; Western blotting method was used to detect the expression levels of ferroptosis marker proteins glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and heme oxygenase 1(HO-1) proteins in superior mesenteric artery tissue of the rats in various groups; the pathomorphology of the superior mesenteric artery of the rats in various groups was observed. Results: All the rats in normal group survived for 72 h, while the longest ST of the rats in model group did not exceed 9 h. Compared with model group, the ST and 24 h survival rate (SR) of the rats in treatment group were significantly increased (P<0. 05). Compared with normal group, the BP, HR, and RR of the rats in model group were significantly decreased (P<0. 01). Compared with model group, the BP, HR, and RR of the rats in treatment group were significantly increased after fluid resuscitation (P< 0. 05). Compared with normal group, the activities of AST and ALT, and the levels of Scr and BUN in serum of the rats in model group were significantly increased (P<0. 01). Compared with model group, the serum levels of LAC and GLU of the rats in treatment group were significantly decreased (P<0. 01). Compared with normal group, the concentration of iron ion, GSH level, MDA level, LDH activity in serum of the rats in model group were significantly increased (P<0. 05); compared with model group, the concentration of iron ion and LDH activity in serum of the rats in treatment group was significantly decreased (P<0. 01). Compared with normal group, the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in model group were significantly decreased (P<0. 05); compared with model group, the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in treatment group were significantly increased (P<0. 05). Compared with normal group, the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in model group was increased (P<0. 01); compared with model group, the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in treatment group was increased (P<0. 01).The microscopic pathology results showed that the cell arrangement in the layers of the superior mesenteric artery tissue of the rats in model group was disordered, the swelling was significant and the thickness was increased; the pathological changes in superior mesenteric artery tissue of the rats in treatment group was alleviated. The ultramicroscopic pathology results showed that the endothelial cell structure of blood vessels of the rats in normal group was intact, and there was no swelling in the subendothelial matrix; the vascular endothelial cell membrane of the rats in model group was damaged, there were cytoplasmic dissolution and fragmentation, and the swelling of the subendothelial matrix was significant; the swelling of the vascular endothelial cells in treatment group was alleviated. Conclusion: Ferroptosis occurs in vascular tissue of the rats with blast injury complicated with hemorrhagic shock, and fluid resuscitation can alleviate the structural damage of the vascular cells by inhibiting the vascular tissue ferroptosis. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic shock is well documented as a leading cause of preventable fatalities among military casualties. During military operations plasma can be transfused while waiting for whole blood. This study was conducted to assess the safety and efficacy of two new freeze‐dried plasma formulations in a porcine model of traumatic hemorrhagic shock. Study Design and Methods: In the face of species‐specific transfusion, transfusible blood products were derived from porcine sources. The efficacy of three lyophilized plasma (LP) formulations was evaluated: lyophilized plasma (LP), concentrated lyophilized plasma (CLP), and platelet‐rich concentrated lyophilized plasma (PCLP). Pigs were subjected to multi‐trauma and hemorrhagic shock. Ninety minutes post‐shock induction, the animals were treated with one of the three lyophilized products. Monitoring included systolic blood pressure and cardiac output. Point‐of‐care and laboratory diagnostic tests were used to assess renal function, real‐time hemostasis (ROTEM), and coagulation. Histological examinations of kidney, lung, and muscle tissues were conducted 4 h after shock induction. Results: CLP and PCLP significantly improved systolic blood pressure and cardiac output and positively influenced base excess, creatinine, various ROTEM, and coagulation markers compared with standard LP without histologic modification. No adverse effect was associated with the transfusion of any of the plasma products throughout the experimental procedures. Conclusion: Both CLP and PCLP exhibit promising therapeutic potential for managing hemorrhagic shock in scenario where whole blood supplies are limited. However, the distinct physiological and coagulation characteristics of the swine model necessitate further investigation using humanized preclinical models to fully understand their clinical applicability and constraints. [ABSTRACT FROM AUTHOR]

Background: Cardiopulmonary resuscitation (CPR) is performed in cardiac arrests. There exist life support guidelines for individuals in performing effective CPR. CPR-related bleeding and hemothoraces are rare. Intercostal artery rupture leading up to shock and respiratory compromise in such situations is rare. Here, we present a unique case with a management dilemma while discussing challenges and guidance to regional centers. Case presentation: A 49-year-old Caucasian male experienced an out-of-hospital cardiac arrest which required bystander cardiopulmonary resuscitation from a colleague prior to commencement of lysis protocol at the local hospital. Transfer was later arranged to the nearest cardiac catheterization laboratory where a rescue percutaneous coronary intervention was performed in the left anterior descending artery that required strict dual antiplatelet use. Beneath the shroud of these events was a life-threatening right-sided hemothorax from rupture of intercostal arteries that occurred during initial resuscitation. Astute recognition of this post-percutaneous coronary intervention resulted in eventual transfer of the patient to a tertiary center where the source and the collection of the bleed was addressed. The patient's took a great trajectory to improvement. Conclusions: A regional center poses many challenges and limitations. Massive bleeding from intercostal arteries leading to hemorrhagic shock and respiratory compromise from an expanding hemothorax post-CPR is rare. Post-percutaneous coronary intervention use of dual antiplatelets posed a management dilemma that prompted assistance from tertiary counterparts. Clinicians should be astute and quick in assessing and providing care. [ABSTRACT FROM AUTHOR]

Aims: Seawater immersion significantly aggravated organ dysfunction following hemorrhagic shock, leading to higher mortality rate. However, the effective treatment is still unavailable in clinic. Mitochondria were involved in the onset and development of multiple organ function disorders; whether mitochondria participate in the cardiac dysfunction following seawater immersion combined with hemorrhagic shock remains poorly understood. Hence, we investigated the role and possible mechanism of mitochondria in seawater immersion combined with hemorrhage shock–induced cardiac dysfunction. Results: Mitochondrial fission protein dynamin-related protein 1 (Drp1) was activated and translocated from the cytoplasm to mitochondria in the heart following seawater immersion combined with hemorrhagic shock, leading to excessive mitochondrial fission. Excessive mitochondrial fission disrupted mitochondrial function and structure and activated mitophagy and apoptosis. At the same time, excessive mitochondrial fission resulted in disturbance of myocardial structure and hemodynamic disorders and ultimately provoked multiple organ dysfunction and high mortality. Further studies showed that the mitochondrial division inhibitor mitochondrial division inhibitor-1 can significantly reverse Drp1 mitochondrial translocation and inhibit mitochondrial fragmentation, reactive oxygen species (ROS) accumulation, mitophagy, and apoptosis and then protect circulation and vital organ functions, prolonging animal survival. Innovation: Our findings indicate that Drp1-mediated mitochondrial fission could be a novel therapeutic targets for the treatment of seawater immersion combined with hemorrhagic shock. Conclusion: Drp1 mitochondrial translocation played an important role in the cardiac dysfunction after seawater immersion combined with hemorrhage shock. Drp1-mediated excessive mitochondrial fission leads to cardiac dysfunction due to the mitochondrial structure and bioenergetics impairment. [ABSTRACT FROM AUTHOR]

Introduction: Road Traffic Accidents (RTAs) are the leading cause of premature death in young people aged 5–29. Globally, 186,300 children aged 9 years and under die from RTAs each year. Romania had the highest mortality rate in children aged 0 to 14 for 2018–2020. This study aimed to assess the involvement of children aged 0–17 years in fatal RTAs by analyzing medico-legal autopsy records in a 5-year period at Timisoara Institute of Legal Medicine (TILM), Romania. Materials and Methods: A retrospective analysis of medico-legal autopsy records of road fatalities in children aged 0–17 years, from TILM in a 5-year period (2017–2021), was conducted. Results: Of all medico-legal autopsies in the 5-year period, 23 cases (5.8%) involved road fatalities in children aged 17 and under. Preschoolers accounted for 10 cases, followed by the age group 15–17 years (n = 9). Most children sustained fatal injuries as passengers (n = 13), followed by child pedestrians (n = 7). This research follows four representative cases, each being a different type of child road fatality regarding the type of road user, the age of the victim, and the involvement of other risk factors. Conclusions: Our findings emphasize the tragedy of road fatalities in children and the need to determine risk factors and prevention strategies to reduce the enormous global crisis involving these vulnerable victims. [ABSTRACT FROM AUTHOR]

This study aimed to modify a laser Doppler flowmeter designed and assembled at our institute. After measuring sensitivity evaluation in ex vivo experiments, we confirmed the efficacy of this new device for monitoring real-time esophageal mucosal blood flow changes after thoracic stent graft implantation by simulating various clinical situations in an animal model. Thoracic stent graft implantation was performed in a swine model (n = 8). Esophageal mucosal blood flow decreased significantly from baseline (34.1 ± 18.8 ml/min/100 g vs. 16.7 ± 6.6 ml/min/100 g, P < 0.05) in the lower esophagus (Th6–Th8) where the stent graft covered the aorta. In the hemorrhagic shock model (shock index ≥ 1.0), esophageal mucosal blood flow showed a remarkable change from baseline in the upper esophagus (Th1–Th3), where the stent graft did not cover the aorta (20.8 ± 9.8 ml/min/100 g vs. 12.9 ± 8.6 ml/min/100 g, P < 0.01); however, it returned to the baseline value within a 30-min period. Mucosal blood flow remained stable in the esophagus, where the stent graft did not cover the aorta. After elevating the mean blood pressure to > 70 mmHg with continuous intravenous noradrenaline infusion, esophageal mucosal blood flow increased significantly in both regions; however, the reaction was different between the two regions. Our newly developed laser Doppler flowmeter could measure real-time esophageal mucosal blood flow changes in various clinical situations during thoracic stent graft implantation in a swine model. Hence, this device can be applied in many medical fields by downsizing it. [ABSTRACT FROM AUTHOR]

Abstract Background Extracorporeal membrane oxygenation (ECMO) can provide temporary circulatory support and vital organ oxygenation and is potentially useful as a bridge therapy in some trauma cases. We aimed to demonstrate the characteristics and outcomes of patients with trauma treated with veno-arterial ECMO (V-A ECMO) using data from a Japanese nationwide trauma registry. Methods This retrospective descriptive study analyzed data from the Japan Trauma Data Bank between January 2019 and December 2021. Patients with severe trauma (injury severity score [ISS] ≥ 9) and treated using V-A ECMO were assessed. Results Among the 72,439 patients with severe trauma, 51 received V-A ECMO. Sixteen patients (31.3%) survived until hospital discharge. On hospital arrival, six (37.5%) survivors and 15 (42.9%) non-survivors experienced cardiac arrest. The median ISS for the survivor and non-survivor group was 25 (range, 25–39) and 25 (range, 17–33), respectively. Thoracic trauma was the most common type of trauma in both groups. In the non-survivor group, open-chest cardiopulmonary resuscitation, aortic cross-clamping, and resuscitative endovascular balloon occlusion of the aorta were performed in 10 (28.6%), 5 (14.3%), and 4 (11.4%) patients, respectively. However, these procedures were not performed in the survivor group. Peripheral oxygen saturation tended to be lower in the survivor group both before and upon arrival at the hospital. Conclusions The results of this study suggest the potential benefit of V-A ECMO in some challenging trauma cases. Further studies are warranted to assess the indications for V-A ECMO in patients with trauma.

Adenomyosis is a chronic disease associated with abnormal uterine bleeding and debilitating pain with severely reduced quality of life in many affected women. Primary strategies for its management encompass surgical interventions, hormonal therapy, or a synergistic blend of these therapeutic modalities. Dienogest (DNG), a new progestin, is primarily utilized to treat adenomyosis due to its exceptional selectivity for the progesterone receptor. In this uncommon case report, we introduce a 42-year-old woman who experienced hemorrhagic shock as a result of uterine bleeding and pulmonary embolism that occurred while a patient was undergoing dienogest therapy for uterine adenomyosis. This situation necessitated blood transfusion and introduction of drugs then an emergency hysterectomy was scheduled followed by the initiation of anticoagulation. We hypothesize that the emergence of pulmonary embolism was intimately tied to adenomyosis, and the occurrence of hemorrhagic shock was likely due to the intake of dienogest.

Abstract Background Aortoesophageal fistula (AEF) is a rare cause of upper gastrointestinal hemorrhage. Despite diagnostic and therapeutic advances, the mortality rate in AEF patients remains high because of its fulminant course, even with maximal intensive care. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a resuscitation technique to control life-threatening bleeding. It has become an important modality in the management of life-threatening, traumatic or non-traumatic, arterial bleeding. However, it’s use in hemorrhagic shock caused by cancer has rarely been reported. Case presentation A 51-year-old woman with a history of esophageal cancer presented to our emergency department with hematemesis. Computed tomography was performed because of a strong suspicion of hemorrhagic shock. With a diagnosis of AEF due to esophageal cancer, emergency thoracic endovascular aortic repair was performed while the bleeding was controlled using REBOA. Staged elective esophageal reconstruction was successfully performed. Conclusions Hemostasis is crucial in patients who present with suspected hemorrhagic shock attributable to AEF. The timely implementation of REBOA has shown promise and potential effectiveness in such cases.

Breast trauma in elderly patients with multiple comorbidities can result in severe complications such as hemorrhagic shock due to the highly vascular nature of breast tissue. This case involves a 65-year-old female with a history of rheumatoid arthritis and prior breast cancer who developed a significant breast hematoma following a motor vehicle accident. Initially stable, she rapidly deteriorated with hypotension and altered mental status after imaging revealed a large hematoma with active hemorrhage. Immediate intervention, including blood transfusion and intubation, was essential for stabilization. While spontaneous cessation of bleeding and hematoma stabilization can negate the need for further intervention, persistent bleeding requires prompt action. Options include surgical exploration, hematoma evacuation, vessel ligation, interventional radiology for embolization, additional blood transfusions, and pharmacological hemostatic agents. Breast hematoma can lead to hemorrhagic shock if severe enough in elderly patients with reduced physiological reserve.

Introduction: Hemorrhagic shock demands swift intervention. Management involves the rapid infusion of blood products to restore circulation and uphold tissue perfusion. The aim of this study was to evaluate the effectiveness of prehospital plasma administration in trauma patients, comparing outcomes with normal saline. This was a meta-analysis of randomized controlled trials. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, searches were conducted in PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials from August 1, 2018, to April 4, 2023. The PubMed search string included terms related to blood plasma, prehospital care, emergency medical services, and hemorrhagic shock: (Blood Plasma [MeSH Terms] OR fresh frozen plasma [MeSH Terms] OR plasma OR fresh frozen plasma OR FFP) AND (Prehospital OR emergency care, prehospital [MeSH Terms] OR prehospital emergency care [MeSH Terms] OR prehospital OR prehospital OR EMS OR emergency medical service [MeSH Terms]) AND (hemorrhagic shock [MeSH Terms] OR hemorrhage OR hemorrhage OR hemorrhagic shock OR hemorrhagic shock). Results from the trials were pooled using a random effects model, presented as risk ratios with 95% confidence intervals. Results: In the analysis of 760 patients from three studies, outcomes included mortality at 24 h and 28 days, multi-organ failure (MOF), acute lung injury, and vasopressor use within 24 h. Patients were divided into plasma (363) and normal saline (397) groups. Conclusion: There is no distinction between prehospital plasma administration and normal saline concerning mortality at 24 and 28 days or the need for vasopressors within 24 h. Moreover, plasma administration did not appear to influence rates of acute lung injury or MOF.

Timely and effective blood resuscitation is very important for patients with severe blood loss. The resuscitation fluids for hemorrhagic shock have evolved from whole blood to crystalloid/colloid solutions, crystalloid combined with red blood cells, to balanced blood components. In the past 20 years, it is a growing trend that low titer antibody group O whole blood (LTOWB) is used as the preferred universal bridging resuscitation fluid for emergent blood resuscitation. Herein we provide a review of the history and current status of whole blood for patients with severe bleeding and make a suggestion to launch a national implementation research program of LTOWB in China.

Abstract To study the degradation of lncRNAs in EPMI in rat brain tissue, this study provides a new direction for the estimation of EPMI. LncRNA high-throughput sequencing was performed on the brain tissues of hemorrhagic shock model rats at 0 h and 24 h, and the target lncRNAs were screened. Samples at 0, 1, 3, 6, 12, 18 and 24 h after death were collected, and miRNA-9 and miRNA-125b were used as reference genes. The relative expression levels of lncRNAs at each PMI were detected by RT–qPCR, and a functional model involving lncRNAs and EPMI was established. Samples were collected at 6, 9, 15, and 21 h after death for functional model verification. The expression of several lncRNAs decreased with the prolongation of EPMI, and the mathematical model established by several lncRNA indices exhibited good fit. The verification results of the multi-index joint function model are significantly better than those of the single-index function model, and the established model is more practical. There is a linear relationship between lncRNAs and EPMI, and the multi-index function model is significantly better than the single-index function model, which is important for EPMI inference in forensic pathology practice.

Abstract Background No standard treatment guidelines have been established for postpartum hemorrhage (PPH). We aimed to assess the differences in outcomes and prognoses between patients with PPH who underwent surgical and non-surgical treatment. Methods This retrospective study included 230 patients diagnosed with PPH at two referral hospitals between August 2013 and October 2023. The patients were divided into non-surgical (group 1, n = 159) and surgical intervention groups (group 2, n = 71). A subgroup analysis was performed by dividing the surgical intervention group into immediate (n = 45) and delayed surgical intervention groups (n = 26). Results Initial lactic acid levels and shock index were significantly higher in group 2 (2.85 ± 1.37 vs. 4.54 ± 3.63 mmol/L, p = 0.001, and 0.83 ± 0.26 vs. 1.10 ± 0.51, p

Lei Tan,1,2,&ast; Han She,1,2,&ast; Yi Wang,1,2,&ast; Yuanlin Du,1 Jun Zhang,1 Yunxia Du,1 Yinyu Wu,1 Wei Chen,1 Bingqiang Huang,1 Duanyang Long,1 Xiaoyong Peng,2 Qinghui Li,2 Qingxiang Mao,1 Tao Li,2 Yi Hu1 1Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Li; Yi Hu, Email lt200132@163.com; huyi921@sina.comBackground: Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer’s (AR) and Lactate Ringer’s solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear.Methods: The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury.Results: TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats’ survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity.Conclusion: The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis.Keywords: myocardial injury, hemorrhagic shock, mitochondria, ferroptosis

Xiaowei Zhou, Liyong Zou, Haoyue Deng, Yuanqun Zhou, Yue Wu, Xingnan Ouyang, Liangming Liu, Li Wang,&ast; Tao Li&ast; Department of Shock and Transfusion, Army Medical Center of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang; Tao Li, Department of Shock and Transfusion, Army Medical Center of Army Medical University, Chongqing, People’s Republic of China, Email wangli8134@163.com; lt200132@tmmu.edu.cnPurpose: Cold seawater immersion aggravates hemorrhagic shock-induced homeostasis imbalance and organ dysfunction, leading to increased mortality. Previous studies have shown that treatments targeting oxidative stress and mitochondrial dysfunction have limited efficacy for cold seawater immersion combined with hemorrhagic shock (SIHS). Thus, the mechanisms responsible for SIHS need further investigation.Methods and Results: Data from the hemorrhagic shock transcriptome and cold seawater immersion targets used for bioinformatics analysis revealed the involvement of endoplasmic reticulum stress (ERS) in SIHS occurrence and progression. Based on these findings, the effects and possible mechanism of inhibiting ERS in SIHS rats were investigated. SIHS causes a lethal triad and impairment of vital organ function, leading to death. Compared to lactated Ringer’s solution, the ERS inhibitor 4-phenylbutyric acid (PBA)significantly ameliorated acidosis and coagulopathy and protected vital organ function while prolonging survival and the golden treatment time. Through target screening and validation, 7 targets were identified for the ERS inhibitor PBA for the treatment of SIHS, among which S1PR1, MMP8 and CFTR may play more important roles.Conclusion: ERS plays a crucial role in the progression of SIHS. Inhibition of ERS caused by SIHS alleviates the lethal triad, protects organ function, and prolongs survival and the golden treatment time. The ERS inhibitor PBA may be an effective therapeutic measure for treating SIHS.Keywords: cold seawater immersion, hemorrhagic shock, lethal triad, organ function, ER stress, 4-phenylbutyric acid

BACKGROUND AND OBJECTIVE: We compared the overall clinical outcome in formula-based protocol (1:1:1) and thromboelastogram (TEG)-guided goal-based massive transfusion (MT) in the resuscitation of patients with hemorrhagic shock. MATERIALS AND METHODS: This was a retro-prospective case–control study conducted over a period of 2 years among the patients who received MT using a 1:1:1 fixed ratio protocol (controls, Group A) and goal-based protocol (cases, Group B) guided through TEG. Patients were matched for the type and severity of the clinical conditions. Utilization of blood components, clinical outcomes, transfusion-related complications, and total mortality rates were compared between the groups. RESULTS: There were 113 patients in the formula-based group and 109 patients in the goal-based transfusion group who were matched for injury severity scores. The total blood components utilized were 1867 and 1560, respectively, with a 17.7% reduction associated with the use of TEG. Patients were divided into normal, hypo, and hypercoagulable based on TEG, and a higher transfusion rate was associated with hypocoagulable TEG (942 vs. 610). The prothrombin time, activated partial thromboplastin time, R time, and K time had a significant positive correlation with the need to transfuse more than 20 blood components, whereas platelet count, base excess, alpha angle, MA, and CI had a negative correlation (r = 0.268, P < 0.001). At the end of goal-directed transfusion, 75% of the patients were free of transfusion support (vs. 65.4%) and only 6.9% of the patients had coagulopathy (vs. 31.8%) compared to formula-based resuscitation with a 10% reduction in mortality. CONCLUSION: TEG-guided goal-based approach helped to reduce blood component utilization with a reduced incidence of coagulopathy at the end of the MT while improving patient survival.

BACKGROUND: Hemorrhagic shock (HS) causes severe organ damage, worsened by high-altitude conditions with lower oxygen and temperatures. Existing research lacks specific insights on brain and heart damage under these conditions. This study hypothesizes that high-altitude and cold (HAC) environments exacerbate HS-induced damage in the brain and heart, aiming to improve treatment strategies. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley (SD) rats (200–250 g of weight) were randomly assigned into sham, HS + normal, HS + HAC (4,000 m), and HS + HAC (6,000 m). The HS model was established in SD rats (35% loss of total blood volume), and histopathological injuries of the brain and heart were detected using hematoxylin and eosin staining, Sirius red staining, and immunohistochemistry. Apoptosis of the brain and heart tissues was detected by terminal transferase-mediated dUTP nick end labeling (TUNEL) immunofluorescence staining. To determine the levels of tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (Mcp-1), BCL2-associated X (BAX), and myeloid cell leukemia-1 (Mcl-1) protein, western blotting assay was used. RESULTS: The HAC environment induced pathological damage to the brain and heart and aggravated the degree of cardiac fibrosis in HS rats. However, it did not cause apoptosis of the brain and heart. In addition, it upregulated TNF-α, IFN-γ, Mcp-1, and BAX protein levels, but downregulated Mcl-1 protein levels (P < 0.05). CONCLUSIONS: The HAC environment aggravated the degree of brain and heart damage in HS rats, which may be related to neuron nucleus pyknosis, myocardial fibrosis, and inflammatory and apoptosis activation.

Abstract Background The purpose of the study was to evaluate the mortality of patients who received Resuscitative Endovascular Balloon Occlusion of The Aorta (REBOA) in severe pelvic fracture with hemorrhagic shock. Methods The American College of Surgeon Trauma Quality Improvement Program (ACS-TQIP) database for the calendar years 2017–2019 was accessed for the study. The study included all patients aged 15 years and older who sustained severe pelvic fractures, defined as an injury with an abbreviated injury scale (AIS) score of ≥ 3, and who presented with the lowest systolic blood pressure (SBP) of

Abstract Background Traumatic shock is the leading cause of preventable death with most patients dying within the first six hours from arriving to the hospital. This underscores the importance of prehospital interventions, and growing evidence suggests prehospital transfusion improves survival. Optimizing transfusion triggers in the prehospital setting is key to improving outcomes for patients in hemorrhagic shock. Our objective was to identify factors associated with early in-hospital transfusion requirements available to prehospital clinicians in the field to develop a simple algorithm for prehospital transfusion, particularly for patients with occult shock. Methods We included trauma patients transported by a single critical care transport service to a level I trauma center between 2012 and 2019. We used logistic regression, Fast and Frugal Trees (FFTs), and Bayesian analysis to identify factors associated with early in-hospital blood transfusion as a potential trigger for prehospital transfusion. Results We included 2,157 patients transported from the scene or emergency department (ED) of whom 207 (9.60%) required blood transfusion within four hours of admission. The mean age was 47 (IQR = 28 – 62) and 1,480 (68.6%) patients were male. From 13 clinically relevant factors for early hospital transfusions, four were incorporated into the FFT in following order: 1) SBP, 2) prehospital lactate concentration, 3) Shock Index, 4) AIS of chest (sensitivity = 0.81, specificity = 0.71). The chosen thresholds were similar to conventional ones. Using conventional thresholds resulted in lower model sensitivity. Consistently, prehospital lactate was among most decisive factors of hospital transfusions identified by Bayesian analysis (OR = 2.31; 95% CI 1.55 – 3.37). Conclusions Using an ensemble of frequentist statistics, Bayesian analysis and machine learning, we developed a simple, clinically relevant prehospital algorithm to help identify patients requiring transfusion within 4 h of hospital arrival.

Abstract Background Patients with hemorrhagic shock and trauma (HS/T) are vulnerable to the endotheliopathy of trauma (EOT), characterized by vascular barrier dysfunction, inflammation, and coagulopathy. Cellular therapies such as mesenchymal stem cells (MSCs) and MSC extracellular vesicles (EVs) have been proposed as potential therapies targeting the EOT. In this study we investigated the effects of MSCs and MSC EVs on endothelial and epithelial barrier integrity in vitro and in vivo in a mouse model of HS/T. This study addresses the systemic effects of HS/T on multiorgan EOT. Methods In vitro, pulmonary endothelial cell (PEC) and Caco-2 intestinal epithelial cell monolayers were treated with control media, MSC conditioned media (CM), or MSC EVs in varying doses and subjected to a thrombin or hydrogen peroxide (H2O2) challenge, respectively. Monolayer permeability was evaluated with a cell impedance assay, and intercellular junction integrity was evaluated with immunofluorescent staining. In vivo, a mouse model of HS/T was used to evaluate the effects of lactated Ringer’s (LR), MSCs, and MSC EVs on endothelial and epithelial intercellular junctions in the lung and small intestine as well as on plasma inflammatory biomarkers. Results MSC EVs and MSC CM attenuated permeability and preserved intercellular junctions of the PEC monolayer in vitro, whereas only MSC CM was protective of the Caco-2 epithelial monolayer. In vivo, both MSC EVs and MSCs mitigated the loss of endothelial adherens junctions in the lung and small intestine, though only MSCs had a protective effect on epithelial tight junctions in the lung. Several plasma biomarkers including MMP8 and VEGF were elevated in LR- and EV-treated but not MSC-treated mice. Conclusions In conclusion, MSC EVs could be a potential cell-free therapy targeting endotheliopathy after HS/T via preservation of the vascular endothelial barrier in multiple organs early after injury. Further research is needed to better understand the immunomodulatory effects of these products following HS/T and to move toward translating these therapies into clinical studies.

Abstract The timely detection and management of hemorrhagic shock hold paramount importance in clinical practice. This study was designed to establish a nomogram that may facilitate early identification of hemorrhagic shock in pediatric patients with multiple-trauma. A retrospective study was conducted utilizing a cohort comprising 325 pediatric patients diagnosed with multiple-trauma, who received treatment at the Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China. For external validation, an additional cohort of 144 patients from a children's hospital in Taizhou was included. The model's predictor selection was optimized through the application of the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Subsequently, a prediction nomogram was constructed using multivariable logistic regression analysis. The performance and clinical utility of the developed model were comprehensively assessed utilizing various statistical metrics, including Harrell's Concordance Index (C-index), receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Multivariate logistic regression analysis identified systolic blood pressure (ΔSBP), platelet count, activated partial thromboplastin time (APTT), and injury severity score (ISS) as independent predictors for hemorrhagic shock. The nomogram constructed using these predictors demonstrated robust predictive capabilities, as evidenced by an impressive area under the curve (AUC) value of 0.963. The model's goodness-of-fit was assessed using the Hosmer–Lemeshow test (χ2 = 10.023, P = 0.209). Furthermore, decision curve analysis revealed significantly improved net benefits with the model. External validation further confirmed the reliability of the proposed predictive nomogram. This study successfully developed a nomogram for predicting the occurrence of hemorrhagic shock in pediatric patients with multiple trauma. This nomogram may serve as an accurate and effective tool for timely and efficient management of children with multiple trauma.

Abstract Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases. Graphical Abstract

Cases and studies of protruding early gastric cancer (EGC) combined with spontaneous bleeding are relatively rare. The current study present a female patient aged 70 to 75 years old with hemorrhagic shock caused by spontaneous bleeding from EGC type 0-Isp, which was successfully cured by rapid emergency endoscopic submucosal dissection (ESD). [ABSTRACT FROM AUTHOR]

To study the degradation of lncRNAs in EPMI in rat brain tissue, this study provides a new direction for the estimation of EPMI. LncRNA high-throughput sequencing was performed on the brain tissues of hemorrhagic shock model rats at 0 h and 24 h, and the target lncRNAs were screened. Samples at 0, 1, 3, 6, 12, 18 and 24 h after death were collected, and miRNA-9 and miRNA-125b were used as reference genes. The relative expression levels of lncRNAs at each PMI were detected by RT–qPCR, and a functional model involving lncRNAs and EPMI was established. Samples were collected at 6, 9, 15, and 21 h after death for functional model verification. The expression of several lncRNAs decreased with the prolongation of EPMI, and the mathematical model established by several lncRNA indices exhibited good fit. The verification results of the multi-index joint function model are significantly better than those of the single-index function model, and the established model is more practical. There is a linear relationship between lncRNAs and EPMI, and the multi-index function model is significantly better than the single-index function model, which is important for EPMI inference in forensic pathology practice. [ABSTRACT FROM AUTHOR]

Introduction: Surgical management of intertrochanteric hip fractures is a common surgery with low rates of intraoperative complications. Vascular injuries are exceptionally rare when placing an intramedullary nail without open reduction. There are very few reported cases of direct arterial injury and active bleed at the level of the distal interlocking screw following closed reduction and intramedullary nailing of a hip fracture. We report one such case. Case Presentation: An 88‐year‐old female presented to the emergency department with a left intertrochanteric hip fracture. Closed reduction with a cephalomedullary nail fixation of the left hip fracture occurred as planned without any obvious intraoperative technical issues. The patient remained stable intraoperatively. No open reduction was required. Postoperatively, the patient developed hemorrhagic shock and required massive transfusion protocol. Angiography demonstrated an intramuscular hematoma at the level of the distal intramedullary nail interlocking screw with active extravasation. The patient subsequently required embolization. Nine days following surgery, she began Eliquis for DVT prophylaxis and was ambulating independently with signs of hematoma resolution. Discussion: Profunda femoris artery injury can stem from various mechanisms during surgery. Atherosclerosis places patients at a higher risk of complication due to rigid vessels. In this case, it is believed that drilling beyond the medial femoral cortex led to the arterial injury. Conclusion: Care should be taken to prevent drills from plunging beyond the medial femoral cortex during surgery. Cautious observation of patient's vitals and clinical course can allow for early detection of vascular complication. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Blood transfusions save lives and improve health every day. Despite the matching of blood types being stricter than it ever has been, emergency transfusions among incompatible blood types are still inevitable in the clinic when there is a lack of acceptable blood types for recipients. Here to overcome this, a counter measure nanoplatform consisting of a polymeric core coated by a red blood cell (RBC) membrane is developed. With A‐type or B‐type RBC membrane camouflaging, the nanoplatform is capable of specifically capturing anti‐A or anti‐B IgM antibodies within B‐type or A‐type whole blood, thereby decreasing the corresponding IgM antibody levels and then allowing the incompatible blood transfusions. In addition to IgM, the anti‐RBC IgG antibody in a passive immunization murine model can likewise be neutralized by this nanoplatform, leading to prolonged circulation time of incompatible donor RBCs. Noteworthily, nanoplatform made by expired RBCs (>42 days stored hypothermically) and then subjected to lyophilization does not impair their effect on antibody neutralization. Most importantly, antibody‐captured RBC‐NP do not exacerbate the risk of inflammation, complement activation, and coagulopathy in an acute hemorrhagic shock murine model. Overall, this biomimetic nanoplatform can safely neutralize the antibody to enable incompatible blood transfusion. [ABSTRACT FROM AUTHOR]

This article explores the challenges in developing effective interventions for sepsis, a life-threatening condition caused by an abnormal immune response to infection. Despite numerous clinical trials, there is currently no proven medication for sepsis. The authors argue that a new approach is needed, focusing on predictive biomarkers and trial enrichment rather than prognosis. They propose studying host genetics and deep phenotyping to identify different types of sepsis and develop targeted treatments. The article also suggests learning from other diseases like COVID-19 and non-infectious inflammatory conditions to find commonalities and potential therapies. The concept of "treatable traits" is introduced, which are specific features that can be targeted with interventions to improve outcomes. The TRAITS adaptive platform trial is mentioned as an example of this approach in critical care. Overall, the article emphasizes the importance of a fresh perspective in understanding and treating sepsis. It highlights the significance of early recognition, intervention, and a multidisciplinary approach to care. [Extracted from the article]

Background: No standard treatment guidelines have been established for postpartum hemorrhage (PPH). We aimed to assess the differences in outcomes and prognoses between patients with PPH who underwent surgical and non-surgical treatment. Methods: This retrospective study included 230 patients diagnosed with PPH at two referral hospitals between August 2013 and October 2023. The patients were divided into non-surgical (group 1, n = 159) and surgical intervention groups (group 2, n = 71). A subgroup analysis was performed by dividing the surgical intervention group into immediate (n = 45) and delayed surgical intervention groups (n = 26). Results: Initial lactic acid levels and shock index were significantly higher in group 2 (2.85 ± 1.37 vs. 4.54 ± 3.63 mmol/L, p = 0.001, and 0.83 ± 0.26 vs. 1.10 ± 0.51, p < 0.001, respectively). Conversely, initial heart rate and body temperature were significantly lower in group 2 (92.5 ± 21.0 vs. 109.0 ± 28.1 beat/min, p < 0.001, and 37.3 ± 0.8 °C vs. 37.0 ± 0.9 °C, p = 0.011, respectively). Logistic regression analysis identified low initial body temperature, high lactic acid level, and shock index as independent predictors of surgical intervention (p = 0.029, p = 0.027, and p = 0.049, respectively). Regarding the causes of PPH, tone was significantly more prevalent in group 1 (57.2% vs. 35.2%, p = 0.002), whereas trauma was significantly more prevalent in group 2 (24.5% vs. 39.4%, p = 0.030). Group 2 had worse overall outcomes and prognoses than group 1. The subgroup analysis showed significantly higher rates of uterine atony combined with other causes, hysterectomy, and disseminated intravascular coagulopathy in the delayed surgical intervention group than the immediate surgical intervention group (42.2% vs. 69.2%, p = 0.027; 51.1% vs. 73.1%, p = 0.049; and 17.8% vs. 46.2%, p = 0.018, respectively). Conclusions: Patients with PPH presenting with increased lactic acid levels and shock index and decreased body temperature may be surgical candidates. Additionally, immediate surgical intervention in patients with uterine atony combined with other causes of PPH could improve prognosis and reduce postoperative complications. [ABSTRACT FROM AUTHOR]

Mid-regional proadrenomedullin (MR-proADM) reflects the adrenomedullin level, which has vasodilatory activity, decreases endothelial permeability, and downregulates proinflammatory cytokines. Sepsis diagnosis in these patients is difficult, and MR-proADM is a widely studied sepsis biomarker. This study evaluates MR-proADM levels during the resuscitation phase, considering the potential influence of haemodynamic changes and its usefulness for the early sepsis detection in burn patients. A prospective observational study performed in the Critical Burn Unit. Demographic data, burn characteristics, comorbidities, prognostic/severity scales, and haemodynamic parameters were collected. The resuscitation protocol guided by diuresis, transpulmonary thermodilution, and lactate levels was followed. Blood samples were collected at various time points for biomarker measurement. Biomarker levels, including MR-proADM, C-reactive protein, and procalcitonin were measured during the resuscitation phase and septic episodes. Twenty-seven patients were included, with a mean age of 51 years, a mean total body surface area burn of 41.8%, a mean Abbreviated Burn Severity Index of 9.7, and a mean Baux score of 92. MR-proADM levels were elevated on admission (0.9 ± 0.5 nmol/l) and continued to increase slightly during the resuscitation phase (2.4 ± 2.2 nmol/l). Haemodynamic changes during resuscitation did not significantly affect MR-proADM levels. Twelve of the 27 patients developed sepsis, whose MR-proADM levels were significantly elevated on the day of clinical diagnosis (3.91 ± 2.99 nmol/l) and even the day before (2.57 ± 3.37). Higher MR-proADM levels were associated with greater severity as measured by the Sequential Organ Failure Assessment score. The mean MR-proadrenomedullin values during resuscitation in the patients who died was 3.51 ± 2.30 nmol/l, whereas in the survivors it was 1.28 ± 1.10 nmol/l (p = 0.0001). MR-proadrenomedullin values are elevated after thermal injury but are not affected by haemodynamic changes. During septic episodes in burn patients, MR-proADM rises early (the day before sepsis diagnosis). Higher levels of MR-proADM are associated with greater organ dysfunction and mortality. • MR-proADM is elevated after thermal injury. • MR-proADM is not affected by hemodynamic changes during the resuscitation phase in critical burn patients. • MR-proADM rises early (the day before sepsis diagnosis) during septic episodes in burned patients. • Higher levels of MR-proADM are associated with greater organ dysfunction and higher mortality. [ABSTRACT FROM AUTHOR]

The article explores the concept of damage control resuscitation (DCR) and its importance in preventing deaths from uncontrolled bleeding in both combat and civilian injuries. It discusses various strategies and principles of DCR, such as permissive hypotension and early transfusion of blood products, as well as the management of specific challenges like hypothermia and acidosis. The article also highlights potential solutions for improving DCR, including the use of clinical decision support systems, behavioral insights, and machine learning algorithms. It emphasizes the need for coordination among healthcare providers and adherence to DCR guidelines, while also acknowledging the need for further research and validation of new technologies. [Extracted from the article]

Tuberculosis is still an endemic in many parts of the world. Vascular complications have been described in patients with tuberculosis and in aggressive chest infections such as actinomycoses. Etiology of internal mammary artery pseudoaneurysms includes iatrogenic causes or a complication of infection (mycotic aneurysm). Early diagnosis and treatment of these aneurysms are key to prevent complications such as hemorrhage, hemothorax, and hemorrhagic shock. In this case report, we describe the presentation and management of a 11-year-old patient with tuberculosis, who developed an internal mammary artery pseudoaneurysm during the course of treatment. We describe the case of a 11-year-old girl with known tuberculosis who developed a left internal mammary artery pseudoaneurysm, and treated with percutaneous ultrasound-guided glue embolization. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to utilize a hemorrhagic shock pig model to compare two hemodynamic monitoring methods, pulse index continuous cardiac output (PiCCO) and spectral carotid artery Doppler ultrasound (CDU). Additionally, we sought to explore the feasibility of employing CDU as a non-invasive hemodynamic monitoring tool in the context of hemorrhagic shock and fluid resuscitation. Design: Animal experiments. Setting and subjects: Female pigs were selected, and hemorrhagic shock was induced by rapid bleeding through an arterial sheath. Interventions: Hemodynamic monitoring was conducted using both PiCCO and CDU during episodes of hemorrhagic shock and fluid resuscitation. Measurements and main results: Among the 10 female pigs studied, CDU measurements revealed a significant decrease in carotid velocity time integral (cVTI) compared to baseline values under shock conditions. During the resuscitation phase, after the mean arterial pressure (MAP) returned to its baseline level, there was no significant difference between cVTI and baseline values. A similar trend was observed for carotid peak velocity (cPV). The corrected flow time (FTc) exhibited a significant difference only at the time of shock compared to baseline values. In comparison to PiCCO, there was a significant correlation between cVTI and MAP (r = 0.616, P < 0.001), stroke volume (SV) (r = 0.821, P < 0.001), and cardiac index (CI) (r = 0.698, P < 0.001). The carotid Doppler shock index (cDSI) displayed negative correlations with MAP (r = − 0.593, P < 0.001), SV (r = − 0.761, P < 0.001), and CI (r = − 0.548, P < 0.001), while showing a positive correlation with the shock index (SI) (r = 0.647, P < 0.001). Conclusions: Compared to PiCCO, CDU monitoring can reliably reflect the volume status of hemorrhagic shock and fluid resuscitation. CDU offers the advantages of being non-invasive, providing real-time data, and being operationally straightforward. These characteristics make it a valuable tool for assessing and managing hemorrhagic shock, especially in resource-limited settings. [ABSTRACT FROM AUTHOR]

Purpose: Hypocalcaemia upon arrival (HUA) to hospital is associated with morbidity and mortality in the trauma patient. It has been hypothesised that there is an increased incidence of HUA in patients receiving prehospital transfusion as a result of citrated blood products. This research aimed to determine if there was a difference in arrival ionised calcium (iCa) levels in trauma patients who did and did not receive prehospital transfusion. Methods: We conducted a systematic review and meta-analysis of patients with an Injury Severity Score (ISS) > / = 15 and an iCa measured on hospital arrival. We then derived mean iCa levels and attempted to compare between-group variables across multiple study cohorts. Results: Nine studies reported iCa on arrival to ED, with a mean of 1.08 mmol/L (95% CI 1.02–1.13; I2 = 99%; 2087 patients). Subgroup analysis of patients who did not receive prehospital transfusion had a mean iCa of 1.07 mmol/L (95% CI 1.01–1.14; I2 = 99%, 1661 patients). Transfused patients in the 3 comparative studies had a slightly lower iCa on arrival compared to those who did not receive transfusion (mean difference − 0.03 mmol/L, 95% CI − 0.04 to − 0.03, I2 = 0%, p = 0.001, 561 patients). Conclusion: HUA is common amongst trauma patients irrespective of transfusion. Transfused patients had a slightly lower initial iCa than those without transfusion, though the clinical impact of this remains to be clarified. These findings question the paradigm of citrate-induced hypocalcaemia alone in trauma. There is a need for consensus for the definition of hypocalcaemia to provide a basis for future research into the role of calcium supplementation in trauma. [ABSTRACT FROM AUTHOR]

Hemorrhage is the leading cause of preventable death in civilian trauma centers and on the battlefield. One of the emerging treatment options for hemorrhage in austere environments is tranexamic acid (TXA). However, the landscape is not amenable to the current delivery standard. This study compared the pharmacokinetics of TXA via a standard 10-minute intravenous infusion (IV infusion), intravenous rapid push over 10 s (IV push), and intramuscular injection (IM) in a swine polytrauma and hemorrhagic shock model (trauma group) compared to uninjured controls (control group). Thirty swine were randomized to the trauma or control group. Following anesthesia, the trauma group experienced a simulated blast injury and 40% controlled hemorrhage. Subjects in both groups were then randomized to receive 1 g/10 mL TXA via IV infusion, IV push, or IM. Animals were monitored for four hours with serial blood sampling. Serum TXA concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and analyzed. The time to maximum TXA concentration (Tmax) was not affected by trauma in IV infusion or IV push, but was affected in the IM administration with Tmax significantly slower than the control group (p = 0.016). The minimum effective serum concentration of TXA (Ceff, 10 µg/mL) was reached in less than one minute with IV infusion and instantaneously with IV push. Despite lower bioavailability, the time to reach Ceff (Teff) was achieved via IM administration in less than 10 min for both groups (6.4 min trauma vs. 2.1 min control). In austere prehospital environments, an alternative to intravenous infusion of a life-saving medication is desired. Administration of TXA via all three methods reached the level needed to cause substantial inhibition of fibrinolysis within 10 min. The IV push method showed similar pharmacokinetics to IV infusion of TXA but can be delivered quickly without sacrificing an access site for 10 min. [ABSTRACT FROM AUTHOR]

To evaluate the Shock Index (SI) as a predictive tool for triage of gastrointestinal bleeding (GI) in the prehospital setting, assessing its correlation with mortality, admission rates, and hospital length of stay. In this retrospective cohort study, we analyzed data from the ESO Data Collaborative encompassing EMS records from the year 2022, focusing on 1525 patients with a primary GI bleeding diagnosis. The primary measure was the SI, calculated at initial contact and highest recorded prior to ED arrival. Statistical analysis included t-tests, linear regression, and ROC curves, performed using SPSS v29. A significantly higher mean SI was observed in patients who died (mean SI 0.997) compared to survivors (mean SI 0.795), p < 0.001. Admission rates also correlated with higher SI values, p < 0.001. However, SI was not predictive of the hospital length of stay. ROC analysis for mortality prediction yielded an AUC of 0.656 for the initial SI and 0.739 for the highest SI. The standard SI cutoff of 0.9 predicted mortality with a sensitivity of 74.14% and specificity of 55.35% for the highest SI. The SI is a valuable predictive tool for mortality among prehospital patients with GI bleeding. Its application may improve the triage process, potentially influencing transport decisions and initial hospital care. Despite its predictive capability for mortality, the SI should be supplemented with other clinical assessments to make comprehensive prehospital care decisions. Further research into SI as part of a comprehensive assessment which includes end-title CO2, mentation, and heaviness of bleeding. [ABSTRACT FROM AUTHOR]