[Risk factors for acute respiratory distress syndrome in patients with traumatic hemorrhagic shock].

OBJECTIVE: To investigate the risk factors of acute respiratory distress syndrome (ARDS) after traumatic hemorrhagic shock. METHODS: This was a retrospective cohort study of 314 patients with traumatic hemorrhagic shock at Trauma Medicine Center, Peking University People's Hospital from December 2012 to August 2021, including 152 male patients and 162 female patients, with a median age of 63.00 (49.75-82.00) years. The demographic data, past medical history, injury assessment, vital signs, laboratory examination and other indicators of these patients during hospitalization were recorded. These patients were divided into two groups, ARDS group (n=89) and non-ARDS group (n=225) according to whether there was ARDS within 7 d of admission. Risk factors for ARDS were identified using Logistic regression. The C-statistic expressed as a percentage [area under curve (AUC) of the receiver operating characteristic (ROC) curve] was used to assess the discrimination of the model. RESULTS: The incidence of ARDS after traumatic hemorrhagic shock was 28.34%. Finally, Logistic regression model showed that the independent risk factors of ARDS after traumatic hemorrhagic shock included male, history of coronary heart disease, high acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, road traffic accident and elevated troponin Ⅰ. The OR and 95% confidence intervals (CI) were 4.01 (95%CI: 1.75-9.20), 5.22 (95%CI: 1.29-21.08), 1.07 (95%CI: 1.02-1.57), 2.53 (95%CI: 1.21-5.28), and 1.26 (95%CI: 1.02-1.57), respectively; the P values were 0.001, 0.020, 0.009, 0.014, and 0.034, respectively. The ROC curve was used to analyze the value of each risk factor in predicting ARDS. It was found that the AUC for predicting ARDS after traumatic hemorrhagic shock was 0.59 (95%CI: 0.51-0.68) for male, 0.55 (95%CI: 0.46-0.64) for history of coronary heart disease, 0.65 (95%CI: 0.57-0.73) for APACHE Ⅱ score, 0.58 (95%CI: 0.50-0.67) for road traffic accident, and 0.73 (95%CI: 0.66-0.80) for elevated troponin Ⅰ, with an overall predictive value of 0.81 (95%CI: 0.74-0.88). CONCLUSION: The incidence of ARDS in patients with traumatic hemorrhagic shock is high, and male, history of coronary heart disease, high APACHE Ⅱ score, road traffic accident and elevated troponin Ⅰ are independent risk factors for ARDS after traumatic hemorrhagic shock. Timely monitoring these indicators is conducive to early detection and treatment of ARDS after traumatic hemorrhagic shock.

EFFECT OF MIR-21-3P ON INTESTINAL INJURY IN RATS WITH TRAUMATIC HEMORRHAGIC SHOCK RESUSCITATED WITH THE SODIUM BICARBONATE RINGER'S SOLUTION.

ABSTRACT: Background : This study aims to determine the impact and mechanism of miR-21-3p on intestinal injury and intestinal glycocalyx during fluid resuscitation in traumatic hemorrhagic shock (THS), and the different impacts of sodium lactate Ringer's solution (LRS) and sodium bicarbonate Ringer's solution (BRS) for resuscitation on intestinal damage. Methods : A rat model of THS was induced by hemorrhage from the left femur fracture. The pathological changes of intestinal tissues and glycocalyx structure were observed by hematoxylin-eosin staining and transmission electron microscope. MiR-21-3p expression in intestinal tissues was detected by real-time quantitative polymerase chain reaction. The expression of glycocalyx-, cell junction-, and PI3K/Akt/NF-κB signaling pathway-related proteins was analyzed by western blot. Results : MiR-21-3p expression was increased in THS rats, which was suppressed by resuscitation with BRS. BRS or LRS aggravated the intestinal injury and damaged intestinal glycocalyx in THS rats. The expression of SDC-1, HPA, ß-catenin, MMP2, and MMP9 was upregulated, the expression of E-cad was downregulated, and the PI3K/Akt/NF-κB signaling pathway was activated in THS rats, which were further aggravated by BRS or LRS. The adverse effect of LRS was more serious than BRS. MiR-21-3p overexpression deteriorated the injury of intestinal tissues and intestinal glycocalyx; increased the expression of SDC-1, HPA, ß-catenin, MMP2, and MMP9 while decreasing E-cad expression; and activated the PI3K/Akt/NF-κB signaling pathway in BRS-resuscitated THS rats. Conclusion : MiR-21-3p aggravated intestinal tissue injury and intestinal glycocalyx damage through activating PI3K/Akt/NF-κB signaling pathway in rats with THS resuscitated with BRS.

Lilrb4 ameliorates ileal injury in rats with hemorrhagic shock and suppresses the activation of NF-κB signaling pathway.

Hemorrhagic shock (HS) leads to intestinal damage and subsequent multiple organ dysfunction syndrome. Intestinal barrier dysfunction is the main cause of multiple organ failure associated with HS. Leukocyte immunoglobulin-like receptor B4 (Lilrb4) belongs to the Ig superfamily and is a vital natural immunomodulatory receptor. The purpose of this study was to identify the role and molecular mechanism of Lilrb4 in HS-induced ileal injury. In this work, HS was established by femoral artery cannula and 90 min of HS (blood pressure, 35-40 mmHg), followed by resuscitation. RNA sequencing analysis showed that Lilrb4 was highly expressed in the ileum of HS rats. As observed, HS rats exhibited severe ileal injury, characterized by enlarged subepithelial space, edema, exfoliation and extensive loss of villi. Whereas, lentivirus system-mediated Lilrb4 overexpression considerably mitigated these alterations. HS led to increased release of markers associated with intestinal injury, which was effectively reversed by Lilrb4 overexpression. In addition, after resuscitation, Lilrb4 overexpression inhibited HS-triggered inflammatory response, as evidenced by decreased levels of proinflammatory cytokines. Lilrb4 also inhibited the activation of NF-κB signal induced by HS. Notably, Lilrb4 modulated the balance of regulatory T (Treg)-T helper 17 (Th17) cells in the mesenteric lymph node (MLN), which may also contribute to its protective role in HS progression. In aggregate, these findings confirmed that Lilrb4 overexpression protected against ileal injury caused by HS, indicating that Lilrb4 may be a potential candidate for the treatment of HS.

Successful application of airway pressure release ventilation in a child with severe acute respiratory distress syndrome induced by trauma: a case report.

BACKGROUND: Trauma has been identified as one of the risk factors for acute respiratory distress syndrome. Respiratory support can be further complicated by comorbidities of trauma such as primary or secondary lung injury. Conventional ventilation strategies may not be suitable for all trauma-related acute respiratory distress syndrome. Airway pressure release ventilation has emerged as a potential rescue method for patients with acute respiratory distress syndrome and hypoxemia refractory to conventional mechanical ventilation. However, there is a lack of research on the use of airway pressure release ventilation in children with trauma-related acute respiratory distress syndrome. We report a case of airway pressure release ventilation applied to a child with falling injury, severe acute respiratory distress syndrome, hemorrhagic shock, and bilateral hemopneumothorax. We hope this case report presents a potential option for trauma-related acute respiratory distress syndrome and serves as a basis for future research. CASE PRESENTATION: A 15-year-old female with falling injury who developed severe acute respiratory distress syndrome, hemorrhagic shock, and bilateral hemopneumothorax was admitted to the surgical intensive care unit. She presented refractory hypoxemia despite the treatment of conventional ventilation with deep analgesia, sedation, and muscular relaxation. Lung recruitment was ineffective and prone positioning was contraindicated. Her oxygenation significantly improved after the use of airway pressure release ventilation. She was eventually extubated after 12 days of admission and discharged after 42 days of hospitalization. CONCLUSION: Airway pressure release ventilation may be considered early in the management of trauma patients with severe acute respiratory distress syndrome when prone position ventilation cannot be performed and refractory hypoxemia persists despite conventional ventilation and lung recruitment maneuvers.

[New research direction of organ dysfunction caused by hemorrhagic shock: mechanisms of mitochondrial quality control].

Hemorrhagic shock (HS) is one of the leading causes of death among young adults worldwide. Multiple organ dysfunction in HS is caused by an imbalance between tissue oxygen supply and demand, which is closely related to the poor prognosis of patient. Mitochondrial dysfunction is one of the key mechanisms contributing to multiple organ dysfunction in HS, while mitochondrial quality control regulates mitochondrial function through a series of processes, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial protein homeostasis. Modulating mitochondrial quality control can improve organ dysfunction. This review aims to summarize the effects of mitochondrial dysfunction on organ function in HS and discuss the potential mechanisms of mitochondrial quality control, providing insights into the injury mechanisms underlying HS and guiding clinical management.

Group B or not group B? An association between ABO, early mortality, and organ dysfunction in major trauma patients with shock.

BACKGROUND: ABO blood group alters coagulation profiles in the general population and may influence outcomes after trauma. The relationship between trauma-induced coagulopathy, severe injury with hemorrhagic shock, and survival with respect to ABO group is unknown. OBJECTIVES: In severe hemorrhagic trauma, we aimed to characterize the association of ABO group with admission coagulation profiles, mortality, and immune-mediated complications. METHODS: Clinical and laboratory variables were examined from severely injured adult patients enrolled in a perpetual observational cohort study at a UK Major Trauma Center. Univariate and multivariate analyses were performed to determine differences in clinical outcomes (mortality, organ dysfunction, and critical care support). In a shock subgroup, we performed an exploratory analysis of rotational thromboelastometry parameters and coagulation biomarkers. RESULTS: In 1119 trauma patients, we found no difference in mortality between ABO groups. In patients with shock, 24-hour mortality was significantly lower in group B vs non-B groups (7% vs 16%, adjusted odds ratio [aOR], 0.19; P = .030), but there were increased rates of invasive ventilation (aOR, 3.34; P = .033), renal replacement therapy (aOR, 2.55; P = .037), and a trend for infection (aOR, 1.85; P = .067). Comparing patients with shock, group B vs non-B patients had 40% higher fibrinogen, 65% higher factor (F) VIII, 36% higher FIX, 20% higher FXIII, and 19% higher von Willebrand factor. CONCLUSION: In this observational study limited by single time-point sampling and subgroup analysis of trauma hemorrhage with shock, group B patients have enhanced hemostatic capability associated with early survival but with increased risk of immune-mediated complications.

International registry on aortic balloon occlusion in major trauma: Partial inflation does not improve outcomes in abdominal trauma.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a method for temporary hemorrhage control used in haemodynamically unwell patients with severe bleeding. In haemodynamically unwell abdominal trauma patients, laparotomy remains the initial procedure of choice. Using REBOA in patients as a bridge to laparotomy is a novel option whose feasibility and efficacy remain unclear. We aimed to assess the clinical outcome in patients with abdominal injury who underwent both REBOA placement and laparotomy. METHODS: This is a retrospective study, including trauma patients with an isolated abdominal injury who underwent both REBOA placement and laparotomy, during the period 2011-2019. All data were collected via the Aortic Balloon Occlusion Trauma Registry database. RESULTS: One hundred and three patients were included in this study. The main mechanism of trauma was blunt injury (62.1%) and the median injury severity score (ISS) was 33 (14-74). Renal failure and multi-organ dysfunction syndrome (MODS) occurred in 15.5% and 35% of patients, respectively. Overall, 30-day mortality was 50.5%. Post balloon inflation systolic blood pressure (SBP) >80 mmHg was associated with lower 24-h mortality (p = 0.007). No differences in mortality were found among patients who underwent partial occlusion vs. total occlusion of the aorta. CONCLUSIONS: Our results support the feasibility of REBOA use in patients with isolated abdominal injury, with survival rates similar to previous reports for haemodynamically unstable abdominal trauma patients. Post-balloon inflation SBP >80 mmHg was associated with a significant reduction in 24-h mortality rates, but not 30-day mortality. Total aortic occlusion was not associated with increased mortality, MODS, and complication rates compared with partial occlusion.

Sodium bicarbonate Ringer's solution for hemorrhagic shock: A meta-analysis comparing crystalloid solutions.

BACKGROUND: The choice of fluid resuscitation in Traumatic Hemorrhagic shock (THS) remains a critical aspect of patient management. Bicarbonated Ringers solution (BRS) has shown promise due to its composition resembling human Extracellular Fluid and its potential benefits on hemodynamics. OBJECTIVE: To evaluate the efficacy, mortality rates, hemodynamic effects, and adverse outcomes of Sodium Bicarbonate Ringer's Solution in the treatment of hemorrhagic shock, as compared to other relevant interventions. METHOD: A comprehensive examination of the available literature was performed by conducting systematic searches in prominent databases such as Cochrane, EMBASE, MEDLINE, and PubMed. The process employed predefined criteria to extract relevant data and evaluate the quality of the studies. The outcome measures considered encompassed survival rates, mortality, mean arterial pressure (MAP), heart rate (HR), and adverse events. RESULT: The meta-analysis of three studies showed that compared to the other crystalloids, the use of BRS had an odds ratio for survival of 1.86 (95% CI: 0.94, 3.71; p = 0.08; I2 = 0%), an odds ratio for total adverse events of 0.14 (95% CI: 0.06, 0.35; p < 0.0001; I2 = 22%), a mean difference in heart rate of -4.49 (95% CI: -7.55, -1.44; p = 0.004; I2 = 13%), and a mean difference in mean arterial pressure of 2.31 (95% CI: -0.85, 5.47; p = 0.15; I2 = 66%). CONCLUSION: BRS demonstrated a significant reduction in complications, including adult respiratory distress syndrome (ARDS), Multiple Organ Dysfunction (MODS), and Total Adverse Effects, when compared to other solutions in the treatment of THS. Additionally, THS patients resuscitated with BRS experienced a notable decrease in heart rate. The findings suggest BRS may contribute to organ stability and potential survival improvement due to its similarity to human Extracellular Fluid and minimal impact on the liver.

Multicompartmental Trauma Induces Persistent Inflammation and Organ Injury.

INTRODUCTION: Previous preclinical models of multicompartmental injury have investigated its effects for durations of less than 72 h and the long-term effects have not been defined. We hypothesized that a model of multicompartmental injury would result in systemic inflammation and multiorgan dysfunction that persists at 1 wk. METHODS: Male and proestrus female Sprague-Dawley rats (n = 16/group) underwent polytrauma (PT) (unilateral right lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofractures) and were compared to naive controls. Weight, hemoglobin, plasma neutrophil gelatinase-associated lipocalin, and plasma toll-like receptor 4 were evaluated on days two and seven. Bilateral lungs were sectioned, stained and assessed for injury at day seven. Comparisons were performed in Graphpad with significance defined as ∗P <0.05. RESULTS: Rats who underwent PT had significant weight loss and anemia at day 2 (P = 0.001) compared to naïve rats which persisted at day 7 (P = 0.001). PT rats had elevated plasma neutrophil gelatinase-associated lipocalin at day 2 compared to naïve (P <0.0001) which remained elevated at day 7 (P <0.0001). Plasma toll-like receptor 4 was elevated in PT compared to naïve at day 2 (P = 0.03) and day 7 (P = 0.01). Bilateral lungs showed significant injury in PT cohorts at day 7 compared to naïve (P <0.0004). PT males had worse renal function at day seven compared to females (P = 0.02). CONCLUSIONS: Multicompartmental trauma induces systemic inflammation and multiorgan dysfunction without recovery by day seven. However, females demonstrate improved renal recovery compared to males. Long-term assessment of preclinical PT models are crucial to better understand and evaluate future therapeutic immunomodulatory and anti-inflammatory treatments.

Mesenchymal stem cells overexpressing PBX1 alleviates haemorrhagic shock-induced kidney damage by inhibiting NF-κB activation.

Mesenchymal stem cells (MSCs) have favourable outcomes in the treatment of kidney diseases. Pre-B-cell leukaemia transcription factor 1 (PBX1) has been reported to be a regulator of self-renewal of stem cells. Whether PBX1 is beneficial to MSCs in the treatment of haemorrhagic shock (HS)-induced kidney damage is unknown. We overexpressed PBX1 in rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human bone marrow-derived mesenchymal stem cells (hBMSCs) to treat rats with HS and hypoxia-treated human proximal tubule epithelial cells (HK-2), respectively. The results indicated that PBX1 enhanced the homing capacity of rBMSCs to kidney tissues and that treatment with rBMSCs overexpressing PBX1 improved the indicators of kidney function, alleviated structural damage to kidney tissues. Furthermore, administration with rBMSCs overexpressing PBX1 inhibited HS-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and the release of proinflammatory cytokines, and further attenuated apoptosis. We then determined whether NF-κB, an important factor in NLRP3 activation and the regulation of inflammation, participates in HS-induced kidney damage, and we found that rBMSCs overexpressing PBX1 inhibited NF-κB activation by decreasing the p-IκBα/IκBα and p-p65/p65 ratios and inhibiting the nuclear translocation and decreasing the DNA-binding capacity of NF-κB. hBMSCs overexpressing PBX1 also exhibited protective effects on HK-2 cells exposed to hypoxia, as shown by the increase in cell viability, the mitigation of apoptosis, the decrease in inflammation, and the inhibition of NF-κB and NLRP3 inflammasome activation. Our study demonstrates that MSCs overexpressing PBX1 ameliorates HS-induced kidney damage by inhibiting NF-κB pathway-mediated NLRP3 inflammasome activation and the inflammatory response.

Syndecan-1 as the Effect or Effector of the Endothelial Inflammatory Response?

INTRODUCTION: Syndecan-1 is a heparan sulfate proteoglycan found in the glycocalyx of vascular endothelial cells. Serum levels of syndecan-1 have repeatedly been demonstrated to increase following traumatic injury and shock, but it is unclear whether syndecan-1 plays an active role in the inflammatory response or is simply a biomarker of a state of hypoperfusion. The aim of this study was to identify the role of syndecan-1 role in the inflammatory process in the absence of trauma. METHODS: Male mice were randomized into five groups (n = 3). Four groups received increasing concentrations of syndecan-1 (1, 10, 100, and 1000pg/mL per blood volume) and a fifth group was given normal saline as a control via intravenous injection. These concentrations were selected based on previous syndecan-1 enzyme-linked immunosorbent assay data acquired following induced hemorrhagic shock in mice resulting in serum levels of 10-6000 pg/mL. Mice from each group were sacrificed at 1-, 4-, and 24-h time points for serum biomarker evaluation. A multiplex enzyme-linked immunosorbent assay was performed to analyze proinflammatory cytokines and chemokines including interleukin (IL)-1a, IL-1b, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, IL-17, monocyte chemoattractant protein-1, TNF-α, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor, and normal T cell expressed and presumably secreted levels. Whole blood was analyzed via rotational thromboelastometry in a separate group of mice dosed with syndecan-1 at 1000 pg/mL and compared to sham mice at 1 h. RESULTS: Tumor necrosis factor-α was significantly elevated in the 1000 pg/mL group compared to sham animals. There were no significant changes in IL-1a, IL-1b, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, monocyte chemoattractant protein--1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor, or normal T cell expressed and presumably secretedat 1, 4, and 24 h for any group when compared to mice receiving saline alone. No significant differences were noted in coagulability between the 1000 pg/mL syndecan-1 group and shams at 1 h CONCLUSIONS: Inflammatory cytokine concentrations did not change with increasing dosage of syndecan-1 within mice at any timepoint, except for an acute change in tumor necrosis factor-α which was transient. Based on our results, syndecan-1 appears to be a biomarker for inflammation rather than an active participant in eliciting an inflammatory response. Further research will focus on the role of syndecan-1 following hemorrhagic shock.

Availability and use of resources for emergency fracture care of pelvic trauma associated with haemorrhagic shock in Latin America: A cross-sectional study.

Determining the true availability of resources and understanding the level of training of surgeons involved in the treatment of patients with pelvic fractures and haemorrhagic shock is critical. In the herein study, the availability of technical, technological, and human resources for the care of this injury in Latin America region was analysed, and the preferences of orthopaedic trauma surgeons when performing interventions for the diagnosis and treatment of patients with pelvic trauma and associated haemorrhagic shock was described. A cross sectional web-based survey containing questions on knowledge, attitudes, and practices with respect to imaging resources, emergency pelvic stabilization methods, and interventions used for bleeding control was sent to 948 Latin America orthopaedic trauma surgeons treating pelvic fractures in the emergency department. Differences between regional clusters, level of training, type of hospital, and pelvic surgery volume were assessed. 368 responses were obtained, with 37.5% of respondents reporting formal training in pelvic surgery and 36.0% having available protocol for managing these patients. The most frequently used interventions were the supra-acetabular pelvic external fixator and pelvic packing. Limited hospital and imaging resources are available for the care of patients with pelvic trauma and associated haemorrhagic shock throughout Latin America. In addition, the training of orthopaedic trauma surgeons dealing with this type of injury and the volume of pelvic surgeries per year is heterogeneous. It should be urgently considered to develop management protocols adapted to Latin America according to the availability of resources, as well as to promote training in this severe life-threatening traumatic condition.

Shear Stress and Endothelial Mechanotransduction in Trauma Patients with Hemorrhagic Shock: Hidden Coagulopathy Pathways and Novel Therapeutic Strategies.

Massive trauma remains a leading cause of death and a global public health burden. Post-traumatic coagulopathy may be present even before the onset of resuscitation, and correlates with severity of trauma. Several mechanisms have been proposed to explain the development of abnormal coagulation processes, but the heterogeneity in injuries and patient profiles makes it difficult to define a dominant mechanism. Regardless of the pattern of death, a significant role in the pathophysiology and pathogenesis of coagulopathy may be attributed to the exposure of endothelial cells to abnormal physical forces and mechanical stimuli in their local environment. In these conditions, the cellular responses are translated into biochemical signals that induce/aggravate oxidative stress, inflammation, and coagulopathy. Microvascular shear stress-induced alterations could be treated or prevented by the development and use of innovative pharmacologic strategies that effectively target shear-mediated endothelial dysfunction, including shear-responsive drug delivery systems and novel antioxidants, and by targeting the venous side of the circulation to exploit the beneficial antithrombogenic profile of venous endothelial cells.

Adipose tissue-derived mesenchymal stromal cells attenuate acute lung injury induced by trauma and haemorrhagic shock.

BACKGROUND: Mesenchymal stromal cells (MSCs) have shown promising therapeutic options for acute lung injury (ALI) caused by multiple factors. Here, we evaluated the therapeutic potential of adipose tissue-derived mesenchymal stromal cells (ADSCs) in trauma and hemorrhagic shock (THS)-induced ALI. METHODS: ALI model induced by THS was constructed by fractures plus abdominal trauma plus acute hemorrhage plus fluid resuscitation. The ADSCs group rats were generated by injecting 2 × 106 ADSCs at 0 and 1 h after THS. The sham, ALI, and ADSCs group rats were sacrificed at 24 h after resuscitation. The changes in lung histopathology, total protein in bronchoalveolar lavage fluid (BALF), mRNA expression of pro-inflammatory/anti-inflammatory cytokines, antioxidant, and anti-apoptotic indicator, and the activity of Toll-like receptor 4 (TLR4) signaling in lung tissues were evaluated. RESULTS: Administration of the ADSCs reversed ALI induced by THS, including lung histopathological changes/scores, and BALF total protein concentration. Additionally, ADSCs therapy also significantly down-regulated mRNA expression of pro-inflammatory TNF-α, IL-1ß, and IL-6, up-regulated mRNA expression of anti-inflammatory IL-10, anti-apoptotic molecule Bcl-2, and anti-oxidative molecule HO-1 in THS rats. Furthermore, ADSCs suppressed the expression of TLR4 in lung tissue. CONCLUSION: Our data show that ADSCs administration can exert therapeutic effects on THS-induced ALI in rats and may provide beneficial in preventative strategies for ALI.

Pachymic Acid Prevents Hemorrhagic Shock-Induced Cardiac Injury by Suppressing M1 Macrophage Polarization and NF-[Formula: see text]B Signaling Pathway.

Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos, has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15[Formula: see text]mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor [Formula: see text] (TNF-[Formula: see text]) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86[Formula: see text]) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206[Formula: see text]) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF-[Formula: see text]B pathway activation via inhibiting NF-[Formula: see text]B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF-[Formula: see text]B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.

Stercoral Ulcer Presenting in a Patient with Cauda Equina Syndrome Secondary to Postoperative Epidural Hematoma.

Chronic constipation can lead to fecal impaction in the large bowel, which can cause pressure necrosis followed by perforation, known as a stercoral ulcer. In extensive posterior thoracolumbar surgery, a long operation time, large blood loss, and perioperative narcotic use may aggravate constipation. Moreover, sacral root palsy due to cauda equina syndrome (CES) can lead to the deterioration of fecal impaction. This report describes the case of a 77-year-old woman with CES who presented with saddle anesthesia, neurogenic bladder, bowel incontinence, and paraplegia. Five days prior, she had undergone extended posterior lumbar interbody fusion from L1 to L5. Lumbar magnetic resonance imaging (MRI) showed an extended epidural hematoma. After urgent neural decompression, she gradually recovered from the saddle anesthesia, leg pain, and paraplegia over 3 weeks. Thereafter, the patient suddenly developed massive hematochezia and hemorrhagic shock. Urgent colonoscopy was performed, and a stercoral ulcer in the sigmoid colon was diagnosed. After 4 weeks of intensive care for hemorrhagic shock, pneumonia, and systemic sepsis, the patient was transferred to a general ward for intensive rehabilitation. One year after the operation, she was able to walk with assistance, and her urinary and bowel incontinence completely recovered. Chronic constipation, a common clinical problem, can sometimes cause relatively obscure but potentially life-threatening complications such as stercoral ulceration. Possible factors including advanced age, extensive spinal surgeries, prolonged operation time, significant blood loss, perioperative narcotic use, and the presence of spinal cord injury might contribute to the development of this condition. It highlights the importance of recognizing the potential development of stercoral ulcers in patients with CES and emphasizes the need for prompt diagnosis and management to avert catastrophic complications.

Cryptotanshinone ameliorates hemorrhagic shock-induced liver injury via activating the Nrf2 signaling pathway.

INTRODUCTION: Hemorrhagic shock (HS) is an important cause of high mortality in traumatized patients. Cryptotanshinone (CTS) is a bioactive compound extracted from Salvia miltiorrhiza Bunge (Danshen). The current study aimed to explore the effect and underlying mechanism of CTS on the liver injury induced by HS. MATERIAL AND METHODS: Male Sprague-Dawley rats were used to establish the HS model by hemorrhaging and monitoring mean arterial pressure (MAP). CTS was intravenously administered at concentration of 3.5 mg/kg, 7 mg/kg, or 14 mg/kg 30 minutes before resuscitation. Twenty-four hours after resuscitation, the liver tissue and serum samples were collected for the following examinations. Hematoxylin and eosin (H&E) staining was used to evaluate hepatic morphology changes. The myeloperoxidase (MPO) activity in liver tissue and the serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined to reveal the extent of liver injury. The protein expression of Bax and Bcl-2 in liver tissue was detected by western blot. The TUNEL assay determined the apoptosis of hepatocytes. Oxidative stress of liver tissue was assessed by the examination of reactive oxygen species (ROS) generation. The content of malondialdehyde (MDA), glutathione (GSH), and adenosine triphosphate (ATP), the activity of superoxide dismutase (SOD) and oxidative chain complexes (complex I, II, III, IV), as well as cytochrome c expression in cytoplasm and mitochondria, were also used to determine the extent of oxidative injury in the liver. Immunofluorescence (IF) was employed to estimate nuclear factor E2-related factor 2 (Nrf2) expression. The mRNA and protein levels of heme oxygenase 1 (HO-1), NAD(P)H: quinone oxidoreductases 1 (NQO1), cyclooxygenase-2 (COX-2), and nitric oxide synthase (iNOS) were assessed by real-time qPCR, western blot to investigate the mechanism of CTS regulating HS-induced liver injury. RESULTS: H&E staining and a histological score of rat liver suggested that HS induced liver injury. The activity of ALT, AST, and MPO was significantly increased by HS treatment. After CTS administration the ALT, AST, and MPO activities were suppressed, which indicates the liver injury was alleviated by CTS. The HS-induced upregulation of the TUNEL-positive cell rate was suppressed by various doses of CTS. HS-induced ROS production was decreased and the protein expression of Bax and Bcl-2 in the HS-induced rat liver was reversed by CTS administration. In the liver of HS-induced rats, the upregulation of MDA content and the downregulation of GSH content and SOD activitywere suppressed by CTS. Additionally, CTS increases ATP content and mitochondrial oxidative complexes activities and suppressed the release of cytochrome c from mitochondria to the cytoplasm. Moreover, IF and western blot demonstrated that the activation of Nrf2 blocked by HS was recovered by different doses of CTS in liver tissue. The expression of downstream enzymes of the Nrf2 pathway, including HO-1, NQO1, COX-2, and iNOS, was reversed by CTS in the HS rat model. CONCLUSIONS: The current study for the first time revealed the protective effect of CTS in HS-induced liver injury. CTS effectively recovered hepatocyte apoptosis, oxidative stress, and mitochondria damage induced by HS in the rat liver partly via regulating the Nrf2 signaling pathway.

[Resuscitative Endovascular Balloon Occlusion of the Aorta: Implementation and Nursing Care].

Uncontrolled hemorrhagic shock is the main cause of death in patients with traumatic injuries. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a rapidly performed and less-invasive treatment to stop bleeding. The REBOA balloon may be placed at the location of bleeding to achieve hemostasis. Prior to balloon placement, the indications for placement must be evaluated, including non-thoracic aortic trauma and non-traumatic patients with postpartum hemorrhage, and the appropriate sheath size (from 5 to 8 French) must be selected based on the bleeding site. As vascular injury of aortic dissection, rupture, or perforation may occur during the procedure, changes in hemodynamic parameters should be monitored. After balloon placement, ischemic complications due to blood flow occlusion such as lower extremity ischemia and acute renal failure should be tracked. After balloon removal, reperfusion injuries may occur, which can result in multiple organ failure, and should be observed closely. When caring for patients receiving REBOA, physicians should explain the procedure to their families to obtain informed consent. Also, nurses should prepare supplies and closely monitor changes in critical life signs to minimize the risks of hypotension, arrhythmia, and changes in consciousness during the procedure. After placement, the neurovascular and peripheral limbs "5P" (pain, pallor, paresthesia, pulselessness and paralysis) condition should be evaluated and recorded in detail. This treatment approach requires further study and research to assess the long-term impacts of placement and improve quality of care in these patients.

Bradykinin release following trauma and hemorrhagic shock causes pulmonary alveolar leak in a rodent model.

BACKGROUND: Hemorrhage accounts for 40% of the preventable death following severe injury. Activation of systemic coagulation produces bradykinin (BK), which may cause leak from the plasma to the extravascular space and to the tissues, which is part of the complex pathophysiology of trauma-induced end-organ injury. We hypothesize that BK, released during activation of coagulation in severe injury, induces pulmonary alveolar leak. METHODS: Isolated neutrophils (PMNs) were pretreated with a specific BK receptor B2 antagonist HOE-140/icatibant and BK priming of the PMN oxidase was completed. Rats underwent tissue injury/hemorrhagic shock (TI/HS), TI/icatibant/HS, and controls (no injury). Evans blue dye was instilled, and the percentage leak from the plasma to the lung was calculated from the bronchoalveolar lavage fluid (BALF). CINC-1 and total protein were measured in the BALF, and myeloperoxidase was quantified in lung tissue. RESULTS: The BK receptor B2 antagonist HOE140/icatibant inhibited (85.0 ± 5.3%) BK priming of the PMN oxidase ( p < 0.05). The TI/HS model caused activation of coagulation by increasing plasma thrombin-antithrombin complexes ( p < 0.05). Versus controls, the TI/HS rats had significant pulmonary alveolar leak: 1.46 ± 0.21% versus 0.36 ± 0.10% ( p = 0.001) and increased total protein and CINC-1 in the BALF ( p < 0.05). Icatibant given after the TI significantly inhibited lung leak and the increase in CINC-1 in the BALF from TI/icatibant/HS rats versus TI/HS ( p < 0.002 and p < 0.05) but not the total protein. There was no PMN sequestration in the lungs. Conclusions: This mixed injury model caused systemic activation of hemostasis and pulmonary alveolar leak likely due to BK release. CONCLUSION: This mixed injury model caused systemic activation of hemostasis and pulmonary alveolar leak likely due to BK release. LEVEL OF EVIDENCE: Original Article, Basic Science.

Omics Signatures of Tissue Injury and Hemorrhagic Shock in Swine.

OBJECTIVE: Advanced mass spectrometry methods were leveraged to analyze both proteomics and metabolomics signatures in plasma upon controlled tissue injury (TI) and hemorrhagic shock (HS)-isolated or combined-in a swine model, followed by correlation to viscoelastic measurements of coagulopathy via thrombelastography. BACKGROUND: TI and HS cause distinct molecular changes in plasma in both animal models and trauma patients. However, the contribution to coagulopathy of trauma, the leading cause of preventable mortality in this patient population remains unclear. The recent development of a swine model for isolated or combined TI+HS facilitated the current study. METHODS: Male swine (n=17) were randomized to either isolated or combined TI and HS. Coagulation status was analyzed by thrombelastography during the monitored time course. The plasma fractions of the blood draws (at baseline; end of shock; and at 30 minutes, 1, 2, and 4 hours after shock) were analyzed by mass spectrometry-based proteomics and metabolomics workflows. RESULTS: HS-isolated or combined with TI-caused the most severe omic alterations during the monitored time course. While isolated TI delayed the activation of coagulation cascades. Correlation to thrombelastography parameters of clot strength (maximum amplitude) and breakdown (LY30) revealed signatures of coagulopathy which were supported by analysis of gene ontology-enriched biological pathways. CONCLUSION: The current study provides a comprehensive characterization of proteomic and metabolomic alterations to combined or isolated TI and HS in a swine model and identifies early and late omics correlates to viscoelastic measurements in this system.