Acute Injury Research Articles

Marathon Health Pitfalls: What Every Runner Needs to Know

Introduction and Purpose: Long-distance running, especially marathons, tests human endurance and physical limits. While the benefits of marathon running are well-documented, the associated health risks often go unnoticed. This review aims to synthesize current knowledge on the health risks and complications faced by marathon runners, providing crucial insights for both amateur and professional athletes.State of Knowledge: Marathon running imposes significant stress on the cardiovascular system, musculoskeletal structure, and metabolic processes. Issues such as acute myocardial injury, overhydration leading to hyponatremia, and musculoskeletal injuries are prevalent. The review also examines less common but severe risks like rhabdomyolysis and marathon-related cardiac arrests. Despite the robust fitness levels of runners, these health risks remain a serious concern, necessitating preventive strategies and proper health monitoring.Summary: Marathon runners must be aware of the potential health risks associated with prolonged endurance activities. Precautionary measures, including tailored training programs, dietary adjustments, and regular medical check-ups, are essential to mitigate these risks. Additionally, further research is required to develop more effective interventions and guidelines that can safeguard the health of marathon participants. This review underscores the need for a balanced approach that respects the physiological demands of marathon running while ensuring the health and safety of the runners.

Temporal dynamics of gait function in acute cervical spinal cord injury

BackgroundFollowing spinal cord injury (SCI), gait function reaches a post-recovery plateau that depends on the paralysis severity. However, the plateau dynamics during the recovery period are not known. This study aimed to examine the gait function temporal dynamics after traumatic cervical SCI (CSCI) based on paralysis severity.MethodsThis retrospective cohort study included 122 patients with traumatic CSCI admitted to a single specialized facility within 2 weeks after injury. The Walking Index for Spinal Cord Injury II (WISCI II) was estimated at 2 weeks and 2, 4, 6, and 8 months postinjury for each American Spinal Injury Association Impairment Scale (AIS) grade, as determined 2 weeks postinjury. Statistical analysis was performed at 2 weeks to 2 months, 2–4 months, 4–6 months, and 6–8 months, and the time at which no significant difference was observed was considered the time at which the gait function reached a plateau.ResultsIn the AIS grade A and B groups, no significant differences were observed at any time point, while in the AIS grade C group, the mean WISCI II values continued to significantly increase up to 6 months. In the AIS grade D group, the improvement in gait function was significant during the entire observation period.ConclusionsThe plateau in gait function recovery was reached at 2 weeks postinjury in the AIS grade A and B groups and at 6 months in the AIS grade C group.

Acute Brain Injury Risk Prediction Models in Venoarterial Extracorporeal Membrane Oxygenation Patients with Tree-Based Machine Learning: An ELSO Registry Analysis

ObjectiveWe aimed to determine if machine learning (ML) can predict acute brain injury (ABI) and identify modifiable risk factors for ABI in venoarterial extracorporeal membrane oxygenation (VA-ECMO) patients. MethodsWe included adults (≥18 years) receiving VA-ECMO or extracorporeal cardiopulmonary resuscitation (ECPR) in the Extracorporeal Life Support Organization Registry (2009-2021). Our primary outcome was ABI: central nervous system (CNS) ischemia, intracranial hemorrhage (ICH), brain death, and seizures. We utilized Random Forest, CatBoost, LightGBM and XGBoost ML algorithms (10-fold leave-one-out cross-validation) to predict and identify features most important for ABI. We extracted 65 total features: demographics, pre-ECMO/on-ECMO laboratory values, and pre-ECMO/on-ECMO settings. ResultsOf 35,855 VA-ECMO (non-ECPR) patients (median age=57.8 years, 66%=male), 7.7% (n=2,769) experienced ABI. In VA-ECMO (non-ECPR), the area under the receiver-operator characteristics curves (AUC-ROC) to predict ABI, CNS ischemia, and ICH was 0.67, 0.67, and 0.62, respectively. The true positive, true negative, false positive, false negative, positive, and negative predictive values were 33%, 88%, 12%, 67%, 18%, and 94%, respectively for ABI. Longer ECMO duration, higher 24h ECMO pump flow, and higher on-ECMO PaO2 were associated with ABI. Of 10,775 ECPR patients (median age=57.1 years, 68%=male), 16.5% (n=1,787) experienced ABI. The AUC-ROC for ABI, CNS ischemia, and ICH was 0.72, 0.73, and 0.69, respectively. Longer ECMO duration, older age, and higher 24h ECMO pump flow were associated with ABI. ConclusionsIn the largest study predicting neurological complications with ML in ECMO, longer ECMO duration and higher 24h pump flow were associated with ABI in non-ECPR and ECPR VA-ECMO.

Effect of lactobacillus rhamnosus DY801 on methionine metabolism and Th17 cells in the treatment of acute radiochemotherapy induced bowel injury.

e24099 Background: Radiation and chemotherapy are important treatments for patients with pelvic malignant tumors, and they will inevitably lead to the occurrence of radiochemotherapy-induced intestinal injury. Acute radiochemotherapy-induced intestinal injury reduces the quality of life and treatment compliance of patients, which ultimately affects overall survival. However, at present, the treatment of acute intestinal injury is limited. Therefore, alleviating acute radiochemotherapy-induced intestinal injury is an important scientific problem to be solved urgently in tumor treatment. Methods: The stool samples of patients before and after treatment were analyzed by 16S rRNA sequencing to explore the intestinal bacteria associated with radiochemotherapy-induced intestinal injury. The changes in intestinal bacteria and metabolism related to radiochemotherapy-induced intestinal injury were explored through mice in vivo experiments, metagenomics, and non-target metabolomics analysis. New strains of Lactobacillus were obtained from fresh human fecal samples. The molecular mechanism of the therapeutic effect of Lactobacillus rhamnosus DY801 was explored through in vivo experiments, RNA-sequencing, Crispr/cas9 gene knockout, immunohistochemistry, flow cytometry, LC/MS, and western blot. Results: 16S rRNA sequencing of stool samples from patients before and after treatment suggested that the abundance of Lactobacillus and Bacteroides decreased after radiotherapy and chemotherapy. In vivo experiments in mice showed that the decrease in abundance of Lactobacillus and Bacteroides, the decrease of methionine metabolism, and the increase of activated Th17 cells were related to the severity of radiochemotherapy-induced intestinal injury. Ten new strains of Lactobacillus were isolated, cultured, and identified from the feces of matched normal people. Among them, Lactobacillus rhamnosus DY801 had a resistance to acid and bile salt, and has the strongest ability to treat radiochemotherapy-induced intestinal injury. In vivo and in vitro experiments suggest that Lactobacillus rhamnosus DY801 inhibited the proinflammatory Th17 cells through methionine, a production of metB gene, and significantly improve acute intestinal injury. Conclusions: Lactobacillus rhamnosus DY801 regulated methionine metabolism and inhibited Th17 cells in the treatment of the acute radiochemotherapy-induced intestinal injury.

MLKL deficiency alleviates acute alcoholic liver injury via inhibition of NLRP3 inflammasome

Mixed lineage kinase domain-like protein (MLKL) is identified as the terminal executor of necroptosis. However, its role in acute alcoholic liver injury remains unclear. This study elucidates that MLKL can contribute to acute alcoholic liver injury independently of necroptosis. Although the expression of MLKL was upregulated, no significant increase in its phosphorylation or membrane translocation was observed in the liver tissues of mice treated with ethanol. This finding confirms that alcohol intake does not induce necroptosis in mouse liver tissue. Additionally, the deletion of Mlkl resulted in the downregulation of NLRP3 expression, which subsequently inhibited the activation of the NLRP3 inflammasome and the ensuing inflammatory response, thereby effectively mitigating liver injury induced by acute alcohol consumption. The knockout of Nlrp3 did not affect the expression of MLKL, further confirming that MLKL acts upstream of NLRP3. Mechanistically, inhibiting the nuclear translocation of MLKL reduced the nuclear entry of p65, the principal transcriptional regulator of NLRP3, thereby limiting the transcription of Nlrp3 mRNA and subsequent NLRP3 expression. Overall, this study unveils a novel mechanism of MLKL regulates the activation of NLRP3 inflammasomes in a necroptosis independent way in acute alcoholic liver injury

Protective effect and mechanism of quercetin on acute liver injury induced by diquat poisoning in mice

To investigate the protective effect of quercetin (QR) on acute liver injury induced by diquat (DQ) poisoning in mice and its mechanism. Eighty healthy male C57BL/6 mice with SPF grade were randomly divided into control group, DQ model group, QR treatment group, and QR control group, with 20 mice in each group. The DQ poisoning model was established by a one-time intraperitoneal injection of DQ solution (40 mg/kg); the control and QR control groups received equivalent amounts of distilled water through intraperitoneal injection. Four hours after modeling, the QR treatment group and the QR control group received 0.5 mL QR solution (50 mg/kg) through gavage. Meanwhile, an equivalent amount of distilled water was given orally to the control group and the DQ model group. The treatments above were administered once daily for seven consecutive days. Afterwards, the mice were anesthetized, blood and liver tissues were collected for following tests: changes in the structure of mice liver tissue were observed using transmission electron microscopy; the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using enzyme linked immunosorbent assay (ELISA); the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured using the water-soluble tetrazolium-1 (WST-1) method, the thiobarbituric acid (TBA) method, and enzymatic methods, respectively; the protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues were detected using Western blotting. Severe mitochondrial damage was observed in the liver tissues of mice in the DQ model group using transmission electron microscopy, yet mitochondrial damage in the QR treatment group showed significant alleviation. Compared to the control group, the DQ model group had significantly increased levels of MDA in liver tissue, serum AST, and ALT, yet had significantly decreased levels of GSH and SOD in liver tissue. In comparison to the DQ model group, the QR treatment group exhibited significant reductions in serum levels of ALT and AST, as well as MDA levels in liver tissue [ALT (U/L): 52.60±6.44 vs. 95.70±8.00, AST (U/L): 170.45±19.33 vs. 251.10±13.09, MDA (nmol/mg): 12.63±3.41 vs. 18.04±3.72], and notable increases in GSH and SOD levels in liver tissue [GSH (μmol/mg): 39.49±6.33 vs. 20.26±3.96, SOD (U/mg): 121.40±11.75 vs. 81.67±10.01], all the differences were statistically significant (all P < 0.01). Western blotting results indicated that the protein expressions of Nrf2 and HO-1 in liver tissues of the DQ model group were significantly decreased compared to the control group. On the other hand, the protein expressions of Keap1 and activated caspase-9 were conspicuously higher when compared to the control group. In comparison to the DQ model group, the QR treatment group showed a significant increase in the protein expressions of Nrf2 and HO-1 in liver tissues (Nrf2/β-actin: 1.17±0.08 vs. 0.92±0.45, HO-1/β-actin: 1.53±0.17 vs. 0.84±0.09). By contrast, there was a notable decrease in the protein expressions of Keap1 and activated caspase-9 (Keap1/β-actin: 0.48±0.06 vs. 1.22±0.09, activated caspase-9/β-actin: 1.17±0.12 vs. 1.59±0.30), the differences were statistically significant (all P < 0.01). QR may reduce acute liver injury induced by DQ poisoning in mice via activating Keap1/Nrf2 signaling pathway.

Ac2-26 reduced the liver injury after cardiopulmonary bypass in rats via AKT1/GSK3β/eNOS pathway

ObjectiveAbout 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to ameliorate organic injury by inhibiting inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 on acute liver injury after CPB.MethodsA total of 32 SD rats were randomized into sham, CPB, Ac, and Ac/AKT1 groups. The rats only received anesthesia, and rats in other groups received CPB. The rats in Ac/AKT1 were pre-injected with the shRNA to interfere with the expression of AKT1. The rats in CPB were injected with saline, and rats in Ac and Ac/AKT1 groups were injected with Ac2-26. After 12 h of CPB, all the rats were sacrificed and the peripheral blood and liver samples were collected to analyze. The inflammatory factors in serum and liver were detected. The liver function was tested, and the pathological injury of liver tissue was evaluated.ResultsCompared with the sham group, the inflammatory factors, liver function, and pathological injury were worsened after CPB. Compared with the CPB group, the Ac2-26 significantly decreased the pro-inflammatory factors and increased the anti-inflammatory factor, improved liver function, and ameliorated the pathological injury. All the therapeutic effects of Ac2-26 were notably attenuated by the shRNA of AKT1. The Ac2-26 increased the GSK3β and eNOS, and this promotion was inhibited by the shRNA.ConclusionThe Ac2-26 significantly treated the liver injury, inhibited inflammation, and improved liver function. The effect of Ac2-26 on liver injury induced by CPB was partly associated with the promotion of AKT1/GSK3β/eNOS.

Clinical characteristics and prognosis of acute gastrointestinal injury in patients with sepsis-associated acute respiratory distress syndrome

To observe the clinical characteristics and prognosis of patients with acute respiratory distress syndrome (ARDS) in sepsis combined with acute gastrointestinal injury (AGI) of different grades, and to further explore the risk factors associated with the poor prognosis of patients. The clinical data of patients with septic ARDS admitted to the intensive care unit (ICU) of Tianjin First Central Hospital from March to October 2023 were collected. According to the 2012 European Association of Critical Care Medicine AGI definition and grading criteria, the patients were categorized into AGI grade 0- IV groups. The clinical characteristics and 28-day clinical outcomes of the patients were observed; the risk factors related to the prognosis of patients with septic ARDS combined with AGI were analyzed by using univariate and multivariate Logistic regression; and the receiver operator characteristic curve (ROC curve) and calibration curves were plotted to evaluate the predictive value of each risk factor on the prognosis of patients with septic ARDS combined with AGI. A total of 92 patients with septic ARDS were enrolled, including 7 patients in the AGI 0 group, 20 patients in the AGI I group, 38 patients in the AGI II group, 23 patients in the AGI III group, and 4 patients in the AGI IV group. The incidence of AGI was 92.39%. With the increase of AGI grade, the ARDS grade increased, and acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), intra-abdominal pressure (IAP), white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), lymphocyte percentage (LYM%), and 28-day mortality all showed a significant increasing trend, while the oxygenation index (PaO2/FiO2) showed a significant decreasing trend (all P < 0.05). Pearson correlation analysis showed that APACHE II score, SOFA score, and ARDS classification were positively correlated with patients' AGI grade (Pearson correlation index was 0.386, 0.473, and 0.372, respectively, all P < 0.001), and PaO2/FiO2 was negatively correlated with patients' AGI grade (Pearson correlation index was -0.425, P < 0.001). Among the patients with septic ARDS combined with AGI, there were 68 survivors and 17 deaths at 28 days. The differences in APACHE II score, SOFA score, ARDS grade, AGI grade, PaO2/FiO2, IAP, AGI 7-day worst value, length of ICU stay, and total length of hospital stay between the survival and death groups were statistically significant. Univariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.350, 95% confidence interval (95%CI) was 1.071-1.702, P = 0.011], PaO2/FiO2 (OR = 0.964, 95%CI was 0.933-0.996, P = 0.027) and AGI 7-day worst value (OR = 2.103, 95%CI was 1.194-3.702, P = 0.010) were the risk factors for 28-day mortality in patients with septic ARDS combined with AGI. Multivariate Logistic regression analysis showed that SOFA score (OR = 1.384, 95%CI was 1.153-1.661, P < 0.001), PaO2/FiO2 (OR = 0.983, 95%CI was 0.968-0.999, P = 0.035) and AGI 7-day worst value (OR = 1.992, 95%CI was 1.141-3.478, P = 0.015) were the independent risk factors for 28-day mortality in patients with septic ARDS combined with AGI. ROC curve analysis showed that SOFA score, PaO2/FiO2 and AGI 7-day worst value had predictive value for the 28-day prognosis of patients with septic ARDS combined with AGI. The area under the ROC curve (AUC) was 0.824 (95%CI was 0.697-0.950), 0.760 (95%CI was 0.642-0.877) and 0.721 (95%CI was 0.586-0.857), respectively, all P < 0.01; when the best cut-off values of the above metrics were 5.50 points, 163.45 mmHg (1 mmHg≈0.133 kPa), and 2.50 grade, the sensitivities were 94.1%, 94.1%, 31.9%, respectively, and the specificities were 80.9%, 67.6%, 88.2%, respectively. The incidence of AGI in patients with septic ARDS is about 90%, and the higher the AGI grade, the worse the prognosis of the patients. SOFA score, PaO2/FiO2 and AGI 7-day worst value have a certain predictive value for the prognosis of patients with septic ARDS combined with AGI, among which, the larger the SOFA score and AGI 7-day worst value, and the smaller the PaO2/FiO2, the higher the patients' mortality.

Siglec-H-/- Plasmacytoid Dendritic Cells Protect Against Acute Liver Injury by Suppressing IFN-γ/Th1 Response and Promoting IL-21+ CD4 T Cells

Siglec-H is a receptor specifically expressed in mouse plasmacytoid dendritic cells (pDCs), which functions as a negative regulator of interferon-α production and plays a critical role in pDC maturation to become antigen-presenting cells. The function of pDCs in autoimmune and inflammatory diseases has been reported. However, the effect of Siglec-H expression in pDCs in liver inflammation and diseases remains unclear. Using the model of concanavalin A-induced acute liver injury (ALI), we investigated the Siglec-H/pDCs axis during ALI in BDCA2 transgenic mice and Siglec-H-/- mice. Anti-BDCA2 antibody, anti-interleukin (IL)-21R antibody, and Stat3 inhibitor were used to specifically deplete pDCs, block IL21 receptor, and inhibit Stat3 signaling, respectively. Splenocytes and purified naive CD4 T cells and bone marrow FLT3L-derived pDCs were cocultured and stimulated with phorbol myristate acetate/ionomycin and CD3/CD28 beads, respectively. Data showed that specific depletion of pDCs aggravated concanavalin A-induced ALI. Remarkably, alanine aminotransferase, hyaluronic acid, and proinflammatory cytokines IL6 and tumor necrosis factor-α levels were lower in the blood and liver of Siglec-H knockout mice. This was associated with attenuation of both interferon-γ/Th1 response and Stat1 signaling in the liver of Siglec-H knockout mice while intrahepatic IL21 and Stat3 signaling pathways were upregulated. Blocking IL21R or Stat3 signaling in Siglec-H knockout mice restored concanavalin A-induced ALI. Finally, we observed that the Siglec-H-null pDCs exhibited immature and immunosuppressive phenotypes (CCR9LowCD40Low), resulting in reduction of CD4 T-cell activation and promotion of IL21+CD4 T cells in the liver. During T-cell-mediated ALI, Siglec-H-null pDCs enhance immune tolerance and promote IL21+CD4 T cells in the liver. Targeting Siglec-H/pDC axis may provide a novel approach to modulate liver inflammation and disease.

The Combination of Zhuli Decoction and N-butylphthalide Inhibits Cell Apoptosis Induced by CO Poisoning through the PI3K/AKT/GSK-3β Signaling Pathway.

Carbon monoxide poisoning (COP) represents a significant global health burden, characterized by its morbidity and high mortality rates. The pathogenesis of COP-induced brain injury is complex, and effective treatment modalities are currently lacking. In this study, we employed network pharmacology to identify therapeutic targets and associated signaling pathways of Zhuli Decoction (ZLD) for COP. Subsequently, we conducted both in vitro and in vivo experiments to validate the therapeutic efficacy of ZLD in combination with N-butylphthalide (NBP) for acute COP-induced injury. Our network pharmacology analysis revealed that the primary components of ZLD exerted therapeutic effects through the modulation of multiple targets and pathways. The in vitro and in vivo experiments demonstrated that the combination of NBP and ZLD effectively inhibited apoptosis and up-regulated the activities of P-PI3K (Tyr458), P-AKT (Ser473), P-GSK-3β (Ser9), and Bcl-2, thus leading to the protection of neuronal cells and improvement in cognitive function in rats following COP, which was better than the effects observed with NBP or ZLD alone. The rescue experiment further showed that LY294002, a PI3K inhibitor, significantly attenuated the therapeutic efficacy of NBP + ZLD. The neuroprotection effects of NBP and ZLD against COP-induced brain injury are closely linked to the activation of the PI3K/AKT/GSK-3β signaling pathway.

The predictive value of point-of-care ultrasonography versus magnetic resonance imaging in assessing medial meniscal tears in patients with acute knee injury.

Musculoskeletal ultrasound is increasingly used as the modality of choice in diagnosing many medical situations. The present study aimed to compare the accuracy of point-of-care ultrasonography (POCUS) and magnetic resonance imaging (MRI) to detect acute medial meniscus tears in knee. The prospective study was conducted on patients with suspected medial meniscus tears in knee. in the emergency department. In the absence of a knee fracture on x-ray, POCUS on the knee was performed. All patients underwent POCUS and MRI of the knee followed by arthroscopy. POCUS findings were then compared to MRI findings to diagnose medial meniscus tears. A final total of 157 patients with a mean age of 25.04±7.41 years was included. Out of 157 patients, 94 (59.9%) were male. Medial meniscus tears were detected in 89 patients (56.7%) using arthroscopy as the gold standard. The sensitivity, specificity, positive and negative predictive values, and accuracy of POCUS to detect medial meniscus tears were 88.8% (95% confidence interval [CI], 80.3%-94.5%), 89.7% (95% CI, 79.9%-95.8%), 91.9% (95% CI, 84.8%-95.8%), 85.9% (95% CI, 77.2%-91.7%), and 89.2% (95% CI, 83.3%-93.6%), respectively. The diagnostic accuracy of MRI to detect medial meniscus injury was 93.0% (95% CI, 87.8%- 96.4%). The present study demonstrated that POCUS is an accurate and reliable diagnostic tool alternative to MRI in detecting medial meniscal tears. POCUS had acceptable sensitivity, specificity, and accuracy in detecting meniscal injuries and could be performed as an effective immediate investigation to guide further modalities in patients with acute knee trauma.

Contrast-enhanced US in Renal Transplant Complications: Overview and Imaging Features.

Renal transplant is the first-line treatment of end-stage renal disease. The increasing number of transplants performed every year has led to a larger population of transplant patients. Complications may arise during the perioperative and postoperative periods, and imaging plays a key role in this scenario. Contrast-enhanced US (CEUS) is a safe tool that adds additional value to US. Contrast agents are usually administered intravenously, but urinary tract anatomy and complications such as stenosis or leak can be studied using intracavitary administration of contrast agents. Assessment of the graft and iliac vessels with CEUS is particularly helpful in identifying vascular and parenchymal complications, such as arterial or venous thrombosis and stenosis, acute tubular injury, or cortical necrosis, which can lead to graft loss. Furthermore, infectious and malignant graft involvement can be accurately studied with CEUS, which can help in detection of renal abscesses and in the differentiation between benign and malignant disease. CEUS is also useful in interventional procedures, helping to guide percutaneous aspiration of collections with better delimitation of the graft boundaries and to guide renal graft biopsies by avoiding avascular areas. Potential postprocedural vascular complications, such as pseudoaneurysm, arteriovenous fistula, or active bleeding, are identified with CEUS. In addition, newer quantification tools such as CEUS perfusion are promising, but further studies are needed to approve its use for clinical purposes. ©RSNA, 2024 Supplemental material is available for this article.

Mifepristone protects acetaminophen induced liver injury through NRF2/GSH/GST mediated ferroptosis suppression

Ferroptosis is a form of iron-dependent cell death that has attracted significant attention for its potential role in numerous diseases. Targeted inhibition of ferroptosis could be of potential use in treating diseases: such as drug induced liver injury (DILI). Ferroptosis can be antagonized by the xCT/GSH/GPX4, FSP1/CoQ10, DHODH/CoQ10, GCH1/BH4, and NRF2 pathways. Identifying novel anti-ferroptosis pathways will further promote our understanding of the biological nature of ferroptosis and help discover new drugs targeting ferroptosis related human diseases. In this study, we identified the clinically used drug mifepristone (RU486) as a novel ferroptosis inhibitor. Mechanistically, RU486 inhibits ferroptosis by inducing GSH synthesis pathway, which supplies GSH for glutathione-S-transferase (GST) mediated 4-HNE detoxification. Furthermore, RU486 induced RLIP76 and MRP1 export 4-HNE conjugate contributes to its anti-ferroptosis activity. Interestingly, RU486 induced GSH/GSTs/RLIP76&MRP1 anti-ferroptosis pathway acts independent of classic anti-ferroptosis systems: including xCT/GSH/GPX4, FSP1, DHODH, GCH1, SCD1 and FTH1. Moreover, NRF2 was identified to be important for RU486’s anti-ferroptosis activity by inducing downstream gene expression. Importantly, in mouse model, RU486 showed strong protection effect on acetaminophen (APAP)-induced acute liver injury, evidenced by decreased ALT, AST level and histological recovery after APAP treatment. Interestingly, RU486 also decreased oxidative markers, including 4-HNE and MDA, and induced NRF2 activation as well as GSTs, MRP1 expression. Together, these data suggest NRF2/GSH/GST/RLIP76&MRP1 mediated detoxification pathway as an important independent anti-ferroptosis pathway act both in vitro and in vivo.

Prognostication in Neurocritical Care.

This article synthesizes the current literature on prognostication in neurocritical care, identifies existing challenges, and proposes future research directions to reduce variability and enhance scientific and patient-centered approaches to neuroprognostication. Patients with severe acute brain injury often lack the capacity to make their own medical decisions, leaving surrogate decision makers responsible for life-or-death choices. These decisions heavily rely on clinicians' prognostication, which is still considered an art because of the previous lack of specific guidelines. Consequently, there is significant variability in neuroprognostication practices. This article examines various aspects of neuroprognostication. It explores the cognitive approach to prognostication, highlights the use of statistical modeling such as Bayesian models and machine learning, emphasizes the importance of clinician-family communication during prognostic disclosures, and proposes shared decision making for more patient-centered care. This article identifies ongoing challenges in the field and emphasizes the need for future research to ameliorate variability in neuroprognostication. By focusing on scientific methodologies and patient-centered approaches, this research aims to provide guidance and tools that may enhance neuroprognostication in neurocritical care.

Does Ileus Represent the Forgotten End Organ Failure in Critical Illness?

This review evaluates the current literature on ileus, impaired gastrointestinal transit (IGT), and acute gastrointestinal injury (AGI) and its impact on multiple organ dysfunction syndrome. Ileus is often under recognized in critically ill patients and is associated with significant morbidity and is potentially a marker of disease severity as seen in other organs like kidneys (ATN).

Evaluation of liver function using Cordyceps militaris extract powder in Sprague-Dawley rat with acute hepatic injury induced by dimethylnitrosamine

Evaluation of liver function using Cordyceps militaris extract powder in Sprague-Dawley rat with acute hepatic injury induced by dimethylnitrosamine

Inflammatory bowel disease increases the severity of myocardial infarction after acute ischemia-reperfusion injury in mice

Inflammatory bowel disease increases the severity of myocardial infarction after acute ischemia-reperfusion injury in mice

Management of Meniscus Pathology with Concomitant Anterior Cruciate Ligament Injury.

The purpose of this review is to summarize current clinical knowledge on the prevalence and types of meniscus pathology seen with concomitant anterior cruciate ligament (ACL) injury, as well as surgical techniques, clinical outcomes, and rehabilitation following operative management of these pathologies. Meniscus pathology with concomitant ACL injury is relatively common, with reports of meniscus pathology identified in 21-64% of operative ACL injuries. These concomitant injuries have been associated with increased age and body mass index. Lateral meniscus pathology is more common in acute ACL injury, while medial meniscus pathology is more typical in chronic ACL deficiency. Meniscus tear patterns associated with concomitant ACL injury include meniscus root tears, lateral meniscus oblique radial tears of the posterior horn (14%), and ramp lesions of the medial meniscus (8-24%). These meniscal pathologies with concomitant ACL injury are associated with increased rotational laxity and meniscal extrusion. There is a paucity of comparative studies to determine the optimal meniscus repair technique, as well as rehabilitation protocol, depending on specific tear pattern, location, and ACL reconstruction technique. There has been a substantial increase in recent publications demonstrating the importance of meniscus repair at the time of ACL repair or reconstruction to restore knee biomechanics and reduce the risk of progressive osteoarthritic degeneration. Through these studies, there has been a growing understanding of the meniscus tear patterns commonly identified or nearly missed during ACL reconstruction. Surgical management of meniscal pathology with concomitant ACL injury implements the same principles as utilized in the setting of isolated meniscus repair alone: anatomic reduction, biologic preparation and augmentation, and circumferential compression. Advances in repair techniques have demonstrated promising clinical outcomes, and the ability to restore and preserve the meniscus in pathologies previously deemed irreparable. Further research to determine the optimal surgical technique for specific tear patterns, as well as rehabilitation protocols for meniscus pathology with concomitant ACL injury, is warranted.

Neonatal Seizures.

Neonatal seizures are common among patients with acute brain injury or critical illness and can be difficult to diagnose and treat. The most common etiology of neonatal seizures is hypoxic-ischemic encephalopathy, with other common causes including ischemic stroke and intracranial hemorrhage. Neonatal clinicians can use a standardized approach to patients with suspected or confirmed neonatal seizures that entails laboratory testing, neuromonitoring, and brain imaging. The primary goals of management of neonatal seizures are to identify the underlying cause, correct it if possible, and prevent further brain injury. This article reviews recent evidence-based guidelines for the treatment of neonatal seizures and discusses the long-term outcomes of patients with neonatal seizures.

Treatment of Knee Chondral Defects in Athletes.

Cartilage lesions of the knee are a challenging problem, especially for active individuals and athletes who desire a return to high-load activities. They occur both through chronic repetitive loading of the knee joint or through acute traumatic injury and represent a major cause of pain and time lost from sport. They can arise as isolated lesions or in association with concomitant knee pathology. Management of these defects ultimately requires a sound understanding of their pathophysiologic underpinnings to help guide treatment. Team physicians should maintain a high index of suspicion for underlying cartilage lesions in any patient presenting with a knee effusion, whether painful or not. A thorough workup should include a complete history and physical examination. MRI is the most sensitive and specific imaging modality to assess these lesions and can provide intricate detail not only of the structure and composition of cartilage, but also of the surrounding physiological environment in the joint. Treatment of these lesions consists of both conservative or supportive measures, as well as surgical interventions designed to restore or regenerate healthy cartilage. Because of the poor inherent capacity for healing associated with hyaline cartilage, the vast majority of symptomatic lesions will ultimately require surgery. Surgical treatment options range from simple arthroscopic debridement to large osteochondral reconstructions. Operative decision-making is based on numerous patient- and defect-related factors and requires open lines of communication between the athlete, the surgeon, and the rest of the treatment team. Ultimately, a positive outcome is based on the creation of a durable, resistant repair that allows the athlete to return to pain-free sporting activities.