SHOCK最新文献

Abstract: Restoration of mesenteric lymphatic microcirculation is crucial for alleviating severe hemorrhagic shock-induced death. Exercise preconditioning (EP) enhances adaptability and resistance to injury and disease. The mitochondria-associated endoplasmic reticulum membrane (MAM) plays a crucial role in the energy and information exchange between the two organelles. Therefore, we hypothesized that EP ameliorates mesenteric lymphatic contractility through MAM in rats following hemorrhagic shock, aiming to confirm that EP enhances resistance to hemorrhagic shock and further popularizes the idea that exercise is beneficial for health. To test this hypothesis, we observed the effects of EP for 4 weeks on survival time and mesenteric lymphatic contractility in conscious rats following hemorrhagic shock and further explored the effects of MAM agonists and inhibitors. The results showed that EP prolonged the survival time and improved the mesenteric lymphatic contractility and reactivity in vivo and in vitro in rats underwent hemorrhagic shock, ameliorated the MAM ultrastructure in lymphatic smooth muscle cells (LSMCs) and reduced the voltage-dependent anion channel 1 (VDAC1, a vital protein of MAM) and IP3R1 expressions in mesenteric lymphatic tissue. Importantly, treatment with 2-APB (IP3R1 inhibitor) or VBIT-12 (VDAC1 inhibitor) prolonged the survival time, improved mesenteric lymphatic contractility in vivo , ameliorated the MAM ultrastructure injury, and decreased the IP3R1 or VDAC1 expressions in LSMCs in rats following hemorrhagic shock. In contrast, the administration of drinking water containing CdCl 2 (IP3R1 activator) abolished the beneficial effect of EP on hemorrhagic shock. Taken together, the protective effect of EP on lymphatic contractility following hemorrhagic shock was achieved by improving MAM in LSMCs.

Abstract: Aim: To identify and describe microcirculatory dysfunction (MD) in severe COVID-19 cases. Methods: This prospective, cohort study evaluated microvascular function in COVID-19 patients with acute respiratory failure not requiring mechanical ventilation and compared it with that of non-COVID-19 intensive care unit (ICU)-matched controls. A validation cohort included healthy, comorbidity-free patients. The primary outcome compared tissue oxygen resaturation slope (rStO 2 ) in COVID-19 patients and non-COVID ICU controls. rStO 2 was measured post a 3-min vaso-occlusive test during post-occlusive reactive hyperemia (PORH). Additionally, microvascular reactivity was assessed using perfusion index (PI) during PORH and laser speckle contrast imaging post iontophoresis with acetylcholine (ACH), sodium nitroprusside (SNP), and sublingual microcirculation. Results: Overall, 75 patients (25 per cohort) were included. COVID-19 patients exhibited greater severity than ICU controls, as indicated by their SOFA scores (4.0 [3.0; 4.0] vs. 1.0 [0; 1.0], P < 0.001) and PaO 2 /FiO 2 ratios (113 [82; 150] vs. 443 [348; 533], P < 0.001). No significant difference was observed in rStO 2 between the groups. COVID-19 patients showed longer time in reaching peak PI ( P = 0.025), reduced vasodilation with ACH and SNP ( P = 0.010 and P = 0.018, respectively), and increased microvascular density ( P = 0.019) compared to non-COVID-19 ICU controls. Conclusion: We observed evidence of MD in COVID-19 patients through various microcirculatory parameters. This study's reproducible multimodal approach facilitates acute MD detection across multiple clinical applications. Limitations included the observational design, limited statistical power, single-time microvascular measurements, varying illness severity among groups, and possible influences of treatments and vaccinations on MD. Trial registration : Clinical-Trials.gov (NCT04773899).

Abstract: Background: Recent observational studies have suggested that osteoporosis may be a risk factor for sepsis. To mitigate confounding factors and establish the causal relationship between sepsis and osteoporosis, we conducted a two-sample Mendelian randomization analysis using publicly available summary statistics. Methods: Utilizing summary data from FinnGen Biobank, we employed a two-sample Mendelian randomization (MR) analysis to predict the causal relationship between osteoporosis and sepsis. The MR analysis primarily utilized the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, weighted mode, and simple mode analyses, with Bayesian weighted MR (BWMR) analysis employed for result validation. Sensitivity analyses included MR-PRESSO, "leave-one-out" analysis, MR-Egger regression, and Cochran Q test. Results: In the European population, an increase of one standard deviation in osteoporosis was associated with an 11% increased risk of sepsis, with an odds ratio (OR) of 1.11 (95% CI, 1.06-1.16; P = 3.75E-06). BWMR yielded an OR of 1.11 (95% CI, 1.06-1.67; P = 1.21E-05), suggesting osteoporosis as a risk factor for sepsis. Conversely, an increase of one standard deviation in sepsis was associated with a 26% increased risk of osteoporosis, with an OR of 1.26 (95% CI, 1.11-1.16; P = 0.45E-03). BWMR yielded an OR of 1.26 (95% CI, 1.09-1.45; P = 1.45E-03), supporting sepsis as a risk factor for osteoporosis. Conclusion: There is an association between osteoporosis and sepsis, with osteoporosis serving as a risk factor for the development of sepsis, while sepsis may also promote the progression of osteoporosis.

Abstract: Pelvic fractures are severe traumatic injuries often accompanied by potentially fatal massive bleeding. Rapid control of hemorrhages in prehospital emergency settings is critical for improving outcomes in traumatic bleeding. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a promising technique for controlling active bleeding from pelvic fractures. By inserting a balloon catheter into the aorta, REBOA helps maintain blood flow to vital organs such as the brain and heart. This paper provides a comprehensive overview of the initial management of noncompressive trunk hemorrhage caused by pelvic fractures, introduces the technical principles and developments of REBOA, and explores its extensive application in prehospital emergency care. It delves into the operational details and outlines strategies for effectively managing potential complications. We aim to offer a theoretical framework for the future utilization of REBOA in managing uncontrollable hemorrhage associated with pelvic fractures in prehospital emergencies.

Abstract: Objective : Vascular endothelial cells (ECs) sense and respond to both trauma factors (histone proteins) and sepsis signals (bacterial lipopolysaccharide, LPS) with elevations in calcium (Ca 2+ ), but it is not clear if the patterns of activation are similar or different. We hypothesized that within seconds of exposure, histones but not LPS would produce a large EC Ca 2+ response. We also hypothesized that histones would produce different spatio-temporal patterns of Ca 2+ events in veins than in arteries. Methods : We studied cultured ECs (EA.hy926) and native endothelial cells from surgically opened murine blood vessels. High-speed live cell imaging of Ca 2+ events were acquired for 5 min before and after stimulation of cultured ECs with histones or LPS alone or in combination. Histone-induced EC Ca 2+ events were also compared in native endothelial cells from resistance-sized arteries and veins. Ca 2+ activity was quantified as "Ca 2+ prevalence" using custom spatiotemporal analysis. Additionally, cultured ECs were collected after 6 h of exposure to histones or LPS for RNA sequencing. Results : ECs-both in culture and in blood vessels-rapidly increased Ca 2+ activity within seconds of histone exposure. In contrast, LPS exposure produced only a slight increase in Ca 2+ activity in cultured ECs and no effect on blood vessels over 5-min recording periods. Histones evoked large aberrant Ca 2+ events (>30 s in duration) in both veins and arteries, but with different spatio-temporal patterns. Ca 2+ activity in arterial ECs often appeared as "rosettes", with Ca 2+ events that propagated from one cell to all adjacent surrounding cells. In veins, ECs responded individually without spreading. Surprisingly, exposure of cultured ECs to LPS for 5 min before histones potentiated EC Ca 2+ activity by an order of magnitude. Exposure of ECs to histones or LPS both increased gene expression, but different mRNAs were induced. Conclusions : LPS and histones activate ECs through mechanisms that are distinct and additive; only histones produce large aberrant Ca 2+ events. ECs in arteries and veins display different patterns of Ca 2+ responses to histones.

Abstract: Background : This study sought to predict time to patient hemodynamic stabilization during trauma resuscitations of hypotensive patient encounters using electronic medical record (EMR) data. Methods: This observational cohort study leveraged EMR data from a nine-hospital academic system composed of Level I, Level II, and nontrauma centers. Injured, hemodynamically unstable (initial systolic blood pressure, <90 mm Hg) emergency encounters from 2015 to 2020 were identified. Stabilization was defined as documented subsequent systolic blood pressure of >90 mm Hg. We predicted time to stabilization testing random forests, gradient boosting, and ensembles using patient, injury, treatment, EPIC Trauma Narrator, and hospital features from the first 4 hours of care. Results: Of 177,127 encounters, 1,347 (0.8%) arrived hemodynamically unstable; 168 (12.5%) presented to Level I trauma centers, 853 (63.3%) to Level II, and 326 (24.2%) to nontrauma centers. Of those, 747 (55.5%) were stabilized with a median of 50 min (interquartile range, 21-101 min). Stabilization was documented in 94.6% of unstable patient encounters at Level I, 57.6% at Level II, and 29.8% at nontrauma centers ( P < 0.001). Time to stabilization was predicted with a C-index of 0.80. The most predictive features were EPIC Trauma Narrator measures, documented patient arrival, provider examination, and disposition decision. In-hospital mortality was highest at Level I, 3.0% vs. 1.2% at Level II, and 0.3% at nontrauma centers ( P < 0.001). Importantly, nontrauma centers had the highest retriage rate to another acute care hospital (12.0%) compared to Level II centers (4.0%, P < 0.001). Conclusion: Time to stabilization of unstable injured patients can be predicted with EMR data.

Abstract: Postpartum hemorrhage is the leading cause of preventable maternal illness and death globally and carries a disproportionately high burden of mortality in low- to middle-income countries. Tranexamic acid, an antifibrinolytic drug, has been widely adopted to control bleeding in trauma and other surgical conditions. Within the last decade, the World Health Organization updated their guidelines for the treatment of postpartum hemorrhage to include the use of tranexamic acid in all cases of postpartum hemorrhage. However, despite these guidelines and the proven utility of tranexamic acid to treat postpartum hemorrhage, widespread adoption of tranexamic acid into global standards of care across professional organizations has not been achieved. It is important for healthcare providers to understand the etiologies of postpartum hemorrhage, the mechanism of action and adverse effect profile of tranexamic acid, and the available literature regarding the use of tranexamic acid to prevent and treat postpartum hemorrhage to provide the best care for the pregnant patient.

Abstract: Background : Trauma and blood loss are frequently associated with organ failure, immune dysfunction, and a high risk of secondary bacterial lung infections. We aim to test if plasma metabolomic flux and monocyte bioenergetics are altered in association with trauma and related secondary infections. Methods : Plasma samples were collected from trauma patients at three time points: days 0, 3, and 7 postadmission. Metabolites (140) were measured in plasma from trauma survivors ( n = 24) and healthy control individuals (HC, n = 10). Further analysis within the trauma cohort included subsets of trauma/infection-negative (TIneg, n = 12) and trauma/infection-positive patients (TIpos, n = 12). The bioenergetic profile in monocytes was determined using mitochondrial and glycolytic stress tests. Results : In the trauma cohort, significant alterations were observed in 29 metabolites directly affecting 11 major metabolic pathways, while 34 metabolite alterations affected 8 pathways in 9, versus TIneg patients. The most altered metabolic pathways included protein synthesis, the urea cycle/arginine metabolism, phenylalanine, tyrosine, tryptophan biosynthesis, and carnitine compound family. In monocytes from trauma patients, reduced mitochondrial indices and loss of glycolytic plasticity were consistent with an altered profile of plasma metabolites in the tricarboxylic acid cycle and glycolysis. Conclusions : Our study highlights that the metabolic profile is significantly and persistently affected by trauma and related infections. Among trauma survivors, metabolic alterations in plasma were associated with reduced monocyte bioenergetics. These exploratory findings establish a groundwork for future clinical studies aimed at enhancing our understanding of the interplay between metabolic/bioenergetic alterations associated with trauma and secondary bacterial infections.

Abstract: Background: Sepsis, a complex and life-threatening disease, poses a significant global burden affecting over 48 million individuals. Recently, it has been reported that programmed death-ligand 1 (PD-L1) expressed on neutrophils is involved in both inflammatory organ dysfunction and immunoparalysis in sepsis. However, there is a dearth of strategies to specifically target PD-L1 in neutrophils in vivo . Methods: We successfully developed two lipid nanoparticles (LNPs) specifically targeting neutrophils by delivering PD-L1 siRNA via neutrophil-specific antibodies and polypeptides. In vivo and in vitro experiments were performed to detect lipid nanoparticles into neutrophils. A mouse cecal ligation and puncture model was used to detect neutrophil migration, neutrophil extracellular traps level, and organ damage. Result: The PD-L1 siRNA-loaded LNPs that target neutrophils suppressed inflammation, reduced the release of neutrophil extracellular traps, and inhibited T-lymphocyte apoptosis. This approach could help maintain homeostasis of both the immune and inflammatory responses during sepsis. Furthermore, the PD-L1 siRNA-loaded LNPs targeting neutrophils have the potential to ameliorate the multiorgan damage and lethality resulting from cecal ligation and puncture. Conclusions: Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy.