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Abstract: Background : This systematic review and meta-analysis aims to detecting performance of muscular ultrasound for intensive care unit (ICU)-acquired weakness (ICUAW). Methods : We searched PubMed, Web of Science, Embase, Cochrane library, CNKI, VIP, and Wanfang databases for articles published before July 2024. A random-effects model was utilized to derive the summary estimates of sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). Additionally, the sources of heterogeneity were explored by subgroup analysis and meta-regression. Results : This meta-analysis comprised 10 prospective studies involving 561 participants, of whom 241 (42.96%) were diagnosed as ICUAW. Overall, muscular ultrasound exhibited good performance for detecting ICUAW, with the area of summary receiver operating characteristic (SROC) curve of 0.85 (95%CI 0.82-0.88), sensitivity of 0.76 (95%CI 0.70-0.81), specificity of 0.80 (95%CI 0.74-0.84), and DOR of 12.43 (95%CI 7.98-19.38). Upon predefined subgroup analysis, the rectus femoris exhibited significantly superior discriminatory ability in identifying ICUAW than the non-rectus femoris, with higher SROC (0.88 [95%CI 0.85-0.91] vs. 0.76 [95%CI 0.72-0.79], P < 0.01). Moreover, cross-sectional area was more effective than thickness, with higher specificity (0.86 [95%CI 0.80-0.91] vs. 0.74 [95%CI 0.68-0.79], P = 0.02) and SROC (0.89 [95%CI 0.86-0.92] vs. 0.76 [95%CI 0.72-0.80], P < 0.01). Furthermore, integrated analysis of these two indicators revealed that the cross-sectional area of rectus femoris was statistically superior to the thickness of rectus femoris, with higher sensitivity (0.82 [95%CI 0.74-0.87] vs. 0.75 [95%CI 0.65-0.83], P < 0.05) and AUC (0.91 [95%CI 0.88-0.93] vs. 0.80 [95%CI 0.76-0.83], P < 0.01). Conclusions : Muscular ultrasound could be a reliable tool for ICUAW detection. Compared with alternative indices, the cross-sectional area of the rectus femoris exhibits superior detection efficacy and may be considered as a valuable parameter for clinical application.

Abstract: Introduction: Gut ischemia and reperfusion (I/R) injury promotes the release of damage-associated molecular patterns (DAMPs) such as extracellular cold-inducible RNA-binding protein (eCIRP). Gut I/R often leads to acute lung injury (ALI), a major contributor to mortality. Milk fat globule-epidermal growth factor-factor VIII-derived oligopeptide-3 (MOP3) is a novel peptide that attenuates sepsis by opsonizing eCIRP and facilitating its phagocytic clearance. We hypothesized that MOP3 reduces inflammation, mitigates gut and lung injury, and improves survival in gut I/R injury. Methods: Phagocytosis of FITC-labeled eCIRP by intestinal epithelial cells was determined by confocal microscopy, and the cell supernatant was evaluated for cytokine expression by ELISA. Adult C57BL/6 mice underwent 60 min of gut ischemia via superior mesenteric artery occlusion followed by reperfusion. Mice were treated with MOP3 or vehicle via retro-orbital injection at the time of reperfusion. At 4 h post-I/R, blood, gut, and lungs were harvested for further assay. In additional mice, 36-h survival was assessed. Plasma levels of injury and inflammatory markers were measured with colorimetry and ELISA, respectively. Tissue mRNA expression was measured with qPCR. Myeloperoxidase (MPO), TUNEL, histologic injury, and ZO-1 immunohistochemistry assessments were performed. Results: MOP3 significantly increased eCIRP phagocytosis by intestinal epithelial cells ( P < 0.01) and decreased IL-6 release ( P < 0.001). Gut I/R caused elevated plasma eCIRP levels. MOP3 treatment significantly reduced plasma levels of IL-1β ( P < 0.01), IL-6 ( P < 0.05), and lactate dehydrogenase ( P < 0.05) along with a significant decrease in gut ( P < 0.05) and lung ( P < 0.001) injury scores as well as gut cell death ( P < 0.05). Moreover, MOP3 reduced pulmonary levels of chemokines and the granulocyte activation marker MPO after gut I/R. Mechanistically, ZO-1 expression in the gut was decreased following gut I/R injury, whereas MOP3 significantly reversed the decrease in ZO-1 mRNA expression ( P < 0.001). Finally, mice treated with MOP3 exhibited a significant decrease in mortality ( P < 0.05). Conclusions: Treatment with MOP3 effectively mitigates organ injury induced by gut I/R. This beneficial effect is attributed to the facilitation of eCIRP clearance, directing the potential of MOP3 as an innovative therapeutic approach for this critical and often fatal condition.

Abstract: Introduction : Improvements in combat casualty care have increased survival rates, but these patients are at particular risk of developing multiple organ failure (MOF). We investigated the incidence and severity of MOF in a cohort of severe combat casualties. Materials and Methods : This retrospective study included all on-duty French land army war casualties with a severe combat injury requiring intensive care unit admission during 2009-2023. Demographic data, advanced life support interventions, and outcomes were collected. Each organ failure was then analyzed during a 7-day trauma course according to the Sequential Organ Failure Assessment score. Results: Of the 100 patients who met the inclusion criteria, those with persistent MOF at day 4 (MOF group) represented 22% of the total population (median Sequential Organ Failure Assessment score 6.0 [5.3-8.0]). Compared to those without persistent MOF, these patients were more severely injured (median Military Injury Severity Score 38.0 [interquartile range 33.0-56.8] vs. 26.5 [20.0-34.0], P < 0.001) by an explosive mechanism (68.2%) and sustained more traumatic brain injury (40.9% vs. 14.1%, P = 0.013). The MOF group also received significantly more blood units (median 14.0 [8.3-24.8] vs. 6.0 [0.0-12.0], P < 0.001) and massive transfusions (68.2% vs. 32.1%, P = 0.002). Pulmonary and cardiovascular dysfunction were the most frequently observed trauma outcomes. A multivariable logistic regression model showed that MOF persistence at day 4 was significantly associated (odds ratios [95% confidence intervals]) with severe injuries (1.5 [1-2.3], P = 0.042). Conclusion : A high number of severe lesions significantly and independently increased risk of MOF persistence at day 4 after combat-related trauma. These findings are particularly relevant to current and anticipated large-scale combat operations that will challenge battlefield casualty care and evacuation.

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.