SHOCK最新文献

Abstract: Background Sepsis is a life-threatening condition characterized by multiple organ dysfunction. Blood cells abnormalities play a significant role in the onset and progression of sepsis; however, the potential causal relationship between platelets and sepsis remains unclear, as does whether immune cells mediate the interaction between platelets and sepsis. This study aims to explore the potential causal relationship between platelets and sepsis and analyze the mediating effect of immune cells. In addition, cell-to-cell communication was analyzed to explore the interaction between blood cells and immune cells.Material and methods In this study, genome-wide association study (GWAS) data were utilized to examine the association between blood cells and sepsis. Two-sample mendelian randomisation (MR) and reverse MR were performed to investigate the potential causal relationship between blood cells and sepsis, with a specific focus on the relationship between platelets and sepsis. Subsequently, two-step MR was employed to identify the immune cells that mediate the interaction between platelets and sepsis and to assess their potential mediating effects. Cellchat software was used to analyze cell-to-cell communication.Results The results of two-sample MR indicated that platelets were negatively correlated with sepsis (OR = 0.976, 95% CI 0.959-0.993, p = 0.005), suggesting that platelets have a protective effect against sepsis. Additionally, reverse MR demonstrated that sepsis had no significant effect on platelets (OR = 0.909, 95% CI 0.156-5.296, p = 0.916). The mediating effect analysis revealed that monocytes and B cells were important mediators in the relationship between platelets and sepsis. Notably, the correlation between platelets and sepsis shifted from negative to positive with the involvement of monocytes and B cells. The number and strength of cell-cell interactions were decreased in sepsis. Monocytes and B cells primarily regulate platelets through the CLEC signaling pathway, contributing to the pathogenesis of sepsis.Conclusion This study confirmed the protective role of platelets in sepsis. Monocytes and B cells mediate changes in the genetic association between platelets and sepsis. Monocytes and B cells primarily interact with platelets via the CLEC pathway, thereby modulating the genetic association between platelets and sepsis. These findings indicate that thrombocytopenia, especially when accompanied by elevated monocytes and B cells, may serve as a potential marker for sepsis.

Aims: Brain injury occupies the predominant cause of neurological dysfunction and mortality after successful cardiopulmonary resuscitation (CPR) from cardiac arrest (CA). This study investigates the role and mechanism of Sirtuin 6 (SIRT6) in post-cardiac arrest brain injury in rats.

Methods: All rats were subjected to asphyxial CA followed by CPR. Two weeks before modeling, rats were infected with lentivirus containing oe-SIRT6 and oe-FOXO1 through lateral ventricular injection. qRT-PCR and Western blot quantified SIRT6 and FOXO1 expressions in brain tissues. Neurological deficit scores evaluated the neural function of rats at different time points, and water maze test assessed the changes in short-term learning and memory abilities. The survival status of rats 7 days after modeling was recorded. The pathological changes in brain tissues, inflammatory factors, and apoptosis were evaluated by H&E staining, ELISA, and TUNEL, respectively. Ch-IP measured the enrichment of SIRT6 and H3K9ac in the FOXO1 promoter.

Results: SIRT6 was poorly expressed while FOXO1 was highly expressed in CA/CPR rats. Elevation of SIRT6 expression alleviated neural function, behavioral ability, and survival rate, as well as abated pathological damage, inflammatory responses, and cell apoptosis in CA/CPR rats. Mechanistically, SIRT6 curbed FOXO1 transcription and expression by lowering the H3K9ac level in the FOXO1 promoter; FOXO1 overexpression abolished the improvement effect of SIRT6 overexpression on brain injury in CA/CPR rats.

Conclusions: Elevation of SIRT6 expression restrained the FOXO1 expression by diminishing the H3K9ac level in the FOXO1 promoter, thereby mitigating post-cardiac arrest brain injury in rats.

Background: Death in the early phase of trauma is primarily attributable to uncontrolled bleeding exacerbated by trauma-induced coagulopathy (TIC). A comprehensive synthesis of the available evidence on interventions for TIC is needed.

Methods: We conducted a systematic review and meta-analysis of blood component products and tranexamic acid administrations for severe trauma patients with TIC. We included randomized and non-randomized controlled trials. We included studies with patients who required transfusion with any coagulopathy associated with trauma and a detailed definition. The intervention was administration of blood component products and tranexamic acid. The primary outcome of the study was all-cause mortality and transfusion quantity.

Results: Four randomized controlled trials and seven observational studies were included in the qualitative synthesis. In this study, Fibrinogen concentrate (FC), Prothrombin coagulation cofactor (PCC), and Combination administrations of FC and PCC (FC + PCC) administration did not significantly reduce mortality rates. FC, PCC, and FC + PCC administrations significantly reduced RBC transfusions after admission. In addition, PCC administration reduced FFP transfusions during hospital admission. The incidence of thrombotic events was not significantly higher in the FC + PCC, PCC, and rFVIIa groups. Although statistically nonsignificant, multiple organ failure was lower in the FC and FC + PCC groups.

Conclusions: FC and PCC administrations did not significantly reduce mortality. However, FC, PCC, and FC + PCC reduced transfusion rates and complications in patients with coagulopathy-associated trauma. However, the definition of TIC is quite heterogeneous. Thus, the definition of TIC should be defined universally. Furthermore, due to the lack of high certainty of evidence, further well-constructed trials are warranted to investigate the efficacy of blood component products, specifically FC and PCC supplementation for TIC.

Background: Sepsis-associated encephalopathy (SAE) represents a severe complication of sepsis, substantially elevating both mortality and healthcare costs for patients. Gastrodin (GAS), a principal bioactive constituent of Gastrodia elata Blume, is neuroprotective in various neurological disorders, including ischemic stroke, epilepsy, Alzheimer's disease, and neuropathic pain. In this study, we sought to investigate whether GAS could serve as a protective agent against SAE.

Methods: Mice were subjected to cecal ligation and puncture (CLP) or the murine brain microvascular endothelial cell bEnd.3 was exposed to lipopolysaccharide (LPS) and subsequently treated with GAS. We assessed neurological deficits, blood-brain barrier (BBB) integrity, neuroinflammation, and the state of ferroptosis to evaluate the regulation of GAS on SAE. Mechanistically, we utilized glutathione peroxidase 4 (GPX4) knockout mice to delineate the crucial role of GPX4 and examined the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway to uncover the upstream signaling of GPX4.

Results: GAS mitigated neurological deficits in SAE mice and reduced BBB disruption and neuroinflammation both in vivo and in vitro. Functionally, the neuroprotective effects of GAS were realized through the inhibition of ferroptosis. Furthermore, we demonstrated that GPX4 played a pivotal role in this process. Lastly, we found that the COX-2/PGE2 pathway was activated following GAS treatment in SAE mice, thereby increasing the expression level of GPX4.

Conclusions: Our study elucidated that GAS offers protection against SAE by suppressing ferroptosis through the activation of the COX-2/PGE2/GPX4 axis. This research validates the therapeutic potential of GAS and provides novel insights into potential therapeutic strategies for the management of SAE.

Background: The relationship between the partial pressure of oxygen in arterial blood (PaO2) and the prognosis of sepsis patients, and its potential variation over time, remains unclear. The optimal PaO2 range for sepsis patients has always been a contentious issue, with no consensus. We aimed to explore the association between different levels of PaO2 exposure over time and the 28-day mortality of sepsis patients, and to identify the optimal PaO2 range for sepsis patients within a specific time frame.

Methods: We retrieved data on adult patients diagnosed with sepsis within 24 hours before or after ICU admission from the Medical Information Mart for Intensive Care IV (MIMIC-IV; version 2.2) database. We excluded patients who were not admitted to the ICU for the first time, those with ICU stay <24 hours, and those without PaO2 results during their ICU stay. We calculated the time-weighted average (TWA) of PaO2 and used piece-wise exponential additive mixed models (PAMMs) to estimate the time-dependent changes in the association between TWA-PaO2 and patient prognosis.

Results: A total of 16,880 sepsis patients were included in the MIMIC cohort. Results indicated that patients' TWA-PaO2 correlates with increased 28-day mortality after intensive care unit (ICU) admission in sepsis patients, and this association was mainly manifested in the early course of the disease. With a time window of the first 1-7 days after ICU admission, the optimal TWA-PaO2 range for sepsis patients was ≥130 mmHg and ≤ 160 mmHg. Increased exposure time, proportion of exposure time, and exposure dose of high-risk PaO2 outside the range were all associated with an increased risk of 28-day mortality.

Conclusion: PaO2 in sepsis patients should be closely monitored. During the first 1-7 days of ICU admission, PaO2 should be maintained within the range of ≥130 mmHg and ≤ 160 mmHg. A dose-dependent relationship exists between high-risk PaO2 outside the range and patient outcome.

Background: Loss of muscle mass and strength in patients who have experienced severe burns is dramatic and associated with subsequent functional impairment. Past work has shown that exercise and oxandrolone, an anabolic steroid, individually improve muscle function and muscle mass in severely burned patients. This study aims to evaluate the effect of oxandrolone treatment combined with resistance exercise on muscle atrophy and investigate the protein synthesis and mitochondrial biogenesis pathways in a hindlimb suspension model.

Methods: Twenty-four Sprague Dawley rats received 40% total body surface area (%TBSA) scald burns and were then placed for hindlimb unloading. All animals were randomly grouped into vehicle (corn oil) without exercise (V/NEX), oxandrolone administration (0.1 mg/kg/day) without exercise (OX/NEX), vehicle with exercise (V/EX), or oxandrolone with exercise (OX/EX). (n = 6/group). On day 14 isometric forces of the left plantaris and soleus muscle were measured by using a muscle lever system with dynamic muscle control and analysis software. Fatigue measurement was only performed in the soleus muscle. The tissue of the muscle was then collected for protein extraction. Western blots were performed to study signal alternations and mitochondrial biogenesis pathways.

Results: Tetanic force (Po) was significantly increased in the plantaris with exercise, rather than with oxandrolone treatment. Fatigue index (FI) was lower and integration was significantly elevated in the soleus with exercise but not with oxandrolone treatment. Fatigue curve in the soleus further revealed the average maximum force were achieved in soleus with either oxandrolone treatment or exercise alone independently. Raptor and p-Akt levels are elevated in the OX/EX group while PGC1a expression was not altered.

Conclusion: Oxandrolone and resistance exercise have independent positive effects on muscle function recovery in this clinically relevant rodent model of severe burn. Both treatments combined increased signaling pathways by increasing protein synthesis.

Background: While acute myocardial infarction (AMI) is widely recognized as the primary cause of Cardiogenic Shock (CS), Non-AMI related CS has been excluded from the majority of CS studies. Information on its prognostic factors remains largely understudied, and it is necessary to focus on these patients to identify the specific risk factors. In this study, we aimed to build and validate a predictive nomogram and risk classification system.

Methods: 1298 patients and 548 patients with CS from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and MIMIC-III databases were included in the study after excluding patients with acute myocardial infarction. Lasson and logistic regression analysis were used to identify statistically significant predictors which were finally involved in the nomogram. The predictive performance of the nomogram was validated by calibration plots and was compared with other scoring systems by AUC and DCA curves.

Results: Age, heart rate, WBC count, albumin level, lactic acid level, GCS Score, 24 h urine output, and vasopressor use were identified as the most critical factors for in-hospital death. Based on these results, a nomogram was established for predicting in-hospital mortality. The AUC value of the nomogram was 0.806 in the training group and 0.814 and 0.730 in the internal and external validation sets, respectively, which were significantly higher than those of other commonly used Intensive Care Unit scoring systems (SAPSII, APSIII, and SOFA).In addition, the survival curve showed significant differences in the 30-day survival of the three risk subgroups divided by the nomogram.

Conclusion: For non-AMI associated CS, a predictive nomogram and risk classification system were developed and validated, and the nomogram demonstrated good performance in prognostic prediction and risk stratification.

Background: Intestinal ischemia-reperfusion injury is associated with both macrocirculatory and microcirculatory failure. Association of a vasoconstrictor in combination with a vasodilator such as ilomedin may improve macrocirculation parameters, microcirculation perfusion and reduce endothelial dysfunction. The primary objective was to demonstrate a difference in mean arterial pressure (MAP) after intestinal reperfusion with the concomitant administration of norepinephrine and ilomedin during ischemia compared with traditional hemodynamic treatment strategies (fluid resuscitation and vasopressors only). Secondary objectives were to demonstrate an improvement in peripheral and intestinal microcirculatory perfusion and endothelial dysfunction after intestinal reperfusion using this association.

Methods: We conducted a randomized preclinical trial in twenty-one large white pigs, in which a 2-hour small bowel ischemia was performed using a segmental mesenteric occlusion model, followed by a 2-hour reperfusion. Pigs were randomized into 3 groups: goal directed fluid therapy, early administration of norepinephrine before reperfusion and early administration of ilomedin and norepinephrine before reperfusion. Macrocirculatory (MAP and Cardiac Index (CI)), microcirculatory (Sublingual with SideStream Dark Field system and intestinal hemoglobin oxygen saturation with hyperspectral imaging (HSI)) measurements and biological analysis (biomarkers of endothelial dysfunction) were performed.

Results: There were no significant differences in the MAP (p = 0.499) and the CI (p = 0.659) between the 3 groups. Perfused Vessel Density (PVD) in sublingual microcirculation was significantly higher immediately after reperfusion and 2 hours after reperfusion in the early administration of ilomedin and norepinephrine group compared with the other 2 groups (p < 0.05). Hemoglobin oxygen saturation measured at the intestinal level was significantly higher immediately after reperfusion in the early administration of ilomedin and norepinephrine group compared with the other 2 groups (p < 0.01). There were no significant differences in biomarkers of endothelial dysfunction between the 3 groups. Creatinine, AST and alkaline phosphatases increased significantly 2 hours after reperfusion in the early administration of ilomedin and norepinephrine group compared with baseline (p < 0.05).

Conclusions: Early administration of norepinephrine and ilomedin during ischemia improved short-term post-reperfusion sublingual and intestinal microcirculation without worsening macrocirculatory parameters in an intestinal ischemia-reperfusion injury model. However, use of this strategy seemed to worsen both liver and kidney function.