The Stress Index as a Predictor of Mortality in Patients with Isolated Moderate to Severe Traumatic Brain Injury.

BACKGROUND: The Stress Index (SI), calculated as the ratio of blood glucose to serum potassium levels, is a promising prognostic marker in various acute care settings. This study aimed to evaluate the utility of the SI for predicting mortality in patients with isolated moderate-to-severe traumatic brain injury (TBI). METHODS: This retrospective cohort study included adult trauma patients (aged ≥ 20 years) with isolated moderate to severe TBI (Abbreviated Injury Scale ≥ 3 for only head region) treated from 2009-2022. The SI was computed from the initial glucose and potassium levels upon arrival at the emergency department. Logistic regression models were used to assess the association between the SI and mortality after adjusting for relevant covariates. The most effective threshold value of the SI for predicting mortality was identified using receiver operating characteristic (ROC) analysis. RESULTS: Among the 4357 patients with isolated moderate and severe TBI, 463 (10.6%) died. Deceased patients had a significantly higher SI (61.7 vs. 44.1, p < 0.001). In multivariate analysis, higher SI independently predicted greater mortality risk (odds ratio (OR) 6.70, 95% confidence interval (CI) 1.66-26.99, p = 0.007). The optimal SI cutoff for predicting mortality was 48.50 (sensitivity 62.0%, specificity 71.4%, area under the curve 0.724). Patients with SI ≥ 48.5 had nearly two-fold higher adjusted mortality odds compared to those below the threshold (adjusted OR 1.94, 95% CI 1.51-2.50, p < 0.001). CONCLUSIONS: SI is a useful predictor of mortality in patients with isolated moderate-to-severe TBI. Incorporating SI with standard clinical assessments could enhance risk stratification and management approaches for this patient population.

Translational Potential of Baicalein in Mitigating RSL3-Induced Ferroptosis in Fibroblasts: Implications for Therapeutic Interventions.

Background: Ferroptosis is an iron-driven cell-death mechanism that plays a central role in various diseases. Recent studies have suggested that baicalein inhibits ferroptosis, making it a promising therapeutic candidate. Materials and Methods: Fibroblast cultures were treated with different agents to determine the effects of baicalein on ferroptosis. Ferroptosis-related gene expression, lipid peroxidation, and post-treatment cellular structural changes were measured using real-time quantitative polymerase chain reaction, C11-BODIPY dye, and transmission electron microscopy, respectively. Results: Baicalein significantly inhibited rat sarcoma virus selective lethal 3-induced ferroptosis in fibroblasts. Moreover, in baicalein-treated groups, reduced ferroptosis-related gene expression, decreased lipid peroxidation, and maintained cell structure was observed when compared with those of the controls. Discussion: The ability of baicalein to counteract RSL3-induced ferroptosis underscores its potential protective effects, especially in diseases characterized by oxidative stress and iron overload in fibroblasts. Conclusion: Baicalein may serve as a potent therapeutic agent against conditions in which ferroptosis is harmful. The compound's efficacy in halting RSL3-triggered ferroptosis in fibroblasts paves the way for further in vivo experiments and clinical trials.

Association of easy albumin-bilirubin score with increased mortality in adult trauma patients.

Introduction: The easy albumin-bilirubin (EZ-ALBI) score is calculated using the equation: total bilirubin (mg/dl) - 9 × albumin (g/dl), and is used to evaluate liver functional reserve. This study was designed to investigate whether the EZ-ALBI score serves as an independent risk factor for mortality and is useful for stratifying the mortality risk in adult trauma patients. Methods: We retrospectively reviewed data from the registered trauma database of the hospital and included 3,637 adult trauma patients (1,241 deaths and 2,396 survivors) due to all trauma caused between January 1, 2009, and December 31, 2021. The patients were allocated to the two study groups based on the best EZ-ALBI cutoff point (EZ-ALBI = -28.5), which was determined based on the area under the receiver operating characteristic curve. Results: Results revealed that the non-survivors had a significantly higher EZ-ALBI score than the survivors (-26.4 ± 6.5 vs. -31.5 ± 6.2, p < 0.001). Multivariate logistic regression analysis revealed that EZ-ALBI ≥ -28.5was an independent risk factor for mortality (odds ratio, 2.31; 95% confidence interval, 1.63-3.28; p < 0.001). Patients with an EZ-ALBI score ≥ -28.5 presented with 2.47-fold higher adjusted mortality rates than patients with an EZ-ALBI score < -28.5. A propensity score-matched pair cohort of 1,236 patients was developed to reduce baseline disparities in trauma mechanisms. The analysis showed that patients with an EZ-ALBI score ≥ -28.5 had a 4.12 times higher mortality rate compared to patients with an EZ-ALBI score < -28.5. Conclusion: The EZ-ALBI score was a significant independent risk factor for mortality and can serve as a valuable tool for stratifying mortality risk in adult trauma patients by all trauma causes.

Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages.

Circulating exosomes derived from polymicrobial sepsis contain various non-coding RNAs and proteins. Isobaric tags for a relative or absolute quantitation proteomic analysis of the exosomal content revealed 70 dysregulated proteins in the circulating exosomes from septic mice. Next-generation sequencing was used to profile the long non-coding RNA expression in primary cultured macrophages treated with exosomes obtained from the blood of septic C57BL/6 mice, and it was discovered that the nuclear factor-kappa B (NF-κB)/miR-17-92a-1 cluster host gene (MIR17HG) pathways were activated in the macrophages. The inhibition of MIR17HG expression by RNA interference resulted in significantly decreased cell viability. RNA pull-down assays of MIR17HG revealed that ten protein targets bind to MIR17HG. Interaction networks of proteins pulled down by MIR17HG were constructed using GeneMANIA, and their functions were mainly involved in ribonucleoprotein granules, type I interferons, the regulation of organelle assembly, the biosynthesis of acetyl coenzyme A, as a signal transducer and activator of transcription (STAT) protein phosphorylation, and mRNA splicing. Furthermore, RNA interference inhibited MIR17HG expression, resulting in significantly decreased cell survival. In conclusion, this work discovered considerable MIR17HG overexpression in macrophages treated with circulating exosomes from sepsis-affected animals. This study's findings assist us in comprehending the role of exosomes in modulating inflammatory responses and mediating pathogenic pathways in macrophages during sepsis.

The Influence of Hyponatremia and Hypokalemia on the Risk of Fractures in Various Anatomical Regions among Adult Trauma Patients: A Propensity Score-Matched Analysis.

BACKGROUND: Hyponatremia and hypokalemia are common electrolyte imbalances in trauma patients and have been identified to be risk factors for a fall. In addition, hyponatremia was reported to be related to osteoporosis and fragility fractures, while the association between hypokalemia and osteoporosis has only been reported in rare case reports. This study investigated the impact of hyponatremia and hypokalemia on the incidence of fractures in various body regions of adult trauma patients, using the propensity score-matched patient cohort to reduce the influence of patients' baseline characteristics. METHODS: The study analyzed data from 11,173 hospitalized adult trauma patients treated from 1 January 1998, to 31 December 2022. The study included 1968 patients with hyponatremia and 9205 without, and 1986 with hypokalemia and 9187 without. Different 1:1 propensity score-matched cohorts were generated to create the 1903 pairings of patients with or without hyponatremia, 1977 pairings of patients with or without hypokalemia, and 380 pairing of patients with both hyponatremia and hypokalemia vs. normal control patients. Analysis was conducted on the incidence of fracture in various anatomic regions. RESULTS: Hyponatremic patients had increased odds of thoracic vertebral fracture [odds ratio (95% confidence interval) 1.63 (1.10-2.42), p = 0.014], pelvic fracture [2.29 (1.12-4.67), p = 0.019], and femoral fracture [1.28 (1.13-1.45), p < 0.001] but decreased odds of radial and patella fractures. Hypokalemic patients showed no significant differences in fracture risk except for a decreased likelihood of radial fractures. The patients with both hyponatremia and hypokalemia showed a decreased likelihood of radial fractures and patella fractures. CONCLUSION: Hyponatremia may have a greater impact on the occurrence of bone fractures than hypokalemia in trauma patients who have suffered a fall. Electrolyte abnormalities should be taken into account while assessing the risk of fractures in trauma patients.

Evaluation of the Easy Albumin-Bilirubin Score as a Prognostic Tool for Mortality in Adult Trauma Patients in the Intensive Care Unit: A Retrospective Study.

The easy albumin-bilirubin (EZ-ALBI) score is derived using the following equation: total bilirubin (mg/dL) - 9 × albumin (g/dL). This study aimed to determine whether the EZ-ALBI score predicted mortality risk in adult trauma patients in an intensive care unit (ICU). Data from a hospital's trauma database were retrospectively evaluated for 1083 adult trauma ICU patients (139 deaths and 944 survivors) between 1 January 2016 and 31 December 2021. Patients were classified based on the ideal EZ-ALBI cut-off of -26.5, which was determined via receiver operating characteristic curve analysis. The deceased patients' EZ-ALBI scores were higher than those of the surviving patients (-26.8 ± 6.5 vs. -30.3 ± 5.9, p = 0.001). Multivariate logistic analysis revealed that, in addition to age, the presence of end-stage renal disease, Glasgow Coma Scale scores, and injury severity scores, the EZ-ALBI score is an independent risk factor for mortality (odds ratio (OR), 1.10; 95% confidence interval (CI): 1.06-1.14; p = 0.001)). Compared with patients with EZ-ALBI scores < -26.5, those with scores ≥ -26.5 had a 2.1-fold higher adjusted mortality rate (adjusted OR, 2.14; 95% CI: 1.43-3.19, p = 0.001). In conclusion, the EZ-ALBI score is a substantial and independent predictor of mortality and can be screened to stratify mortality risk in adult trauma ICU patients.

Elevation of White Blood Cell Subtypes in Adult Trauma Patients with Stress-Induced Hyperglycemia.

BACKGROUND: Blood immune cell subset alterations following trauma can indicate a patient's immune-inflammatory status. This research explored the influence of stress-induced hyperglycemia (SIH) on platelet counts and white blood cell (WBC) subtypes, including the derived indices of the monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in trauma patients. METHODS: We studied 15,480 adult trauma patients admitted from 1 January 1998 to 31 December 2022. They were categorized into four groups: nondiabetic normoglycemia (NDN, n = 11,602), diabetic normoglycemia (DN, n = 1750), SIH (n = 716), and diabetic hyperglycemia (DH, n = 1412). A propensity score-matched cohort was formed after adjusting for age, sex, and comorbidities, allowing for comparing the WBC subtypes and platelet counts. RESULTS: Patients with SIH exhibited significantly increased counts of monocytes, neutrophils, and lymphocytes in contrast to NDN patients. However, no significant rise in platelet counts was noted in the SIH group. There were no observed increases in these cell counts in either the DN or DH groups. CONCLUSIONS: Our results demonstrated that trauma patients with SIH showed significantly higher counts of monocytes, neutrophils, and lymphocytes when compared to NDN patients, whereas the DN and DH groups remained unaffected. This underscores the profound association between SIH and elevated levels of specific WBC subtypes.

Cathelicidin Antimicrobial Peptide Acts as a Tumor Suppressor in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is associated with high rates of metastasis and recurrence, and is one of the most common causes of cancer-associated death worldwide. This study examined the protein changes within circulating exosomes in patients with HCC against those in healthy people using isobaric tags for a relative or absolute quantitation (iTRAQ)-based quantitative proteomics analysis. The protein levels of von Willebrand factor (VWF), cathelicidin antimicrobial peptide (CAMP), and proteasome subunit beta type-2 (PSMB2) were altered in HCC. The increased levels of VWF and PSMB2 but decreased CAMP levels in the serum of patients with HCC were validated by enzyme-linked immunosorbent assays. The level of CAMP (the only cathelicidin found in humans) also decreased in the circulating exosomes and buffy coat of the HCC patients. The serum with reduced levels of CAMP protein in the HCC patients increased the cell proliferation of Huh-7 cells; this effect was reduced following the addition of CAMP protein. The depletion of CAMP proteins in the serum of healthy people enhances the cell proliferation of Huh-7 cells. In addition, supplementation with synthetic CAMP reduces cell proliferation in a dose-dependent manner and significantly delays G1-S transition in Huh-7 cells. This implies that CAMP may act as a tumor suppressor in HCC.

Exploring the Regulatory Role of XIST-microRNAs/mRNA Network in Circulating CD4+ T Cells of Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC) is one of the most common cancers and the main cause of cancer-related death globally. Immune dysregulation of CD4+ T cells has been identified to play a role in the development of HCC. Nevertheless, the underlying molecular pathways of CD4+ T cells in HCC are not completely known. Thus, a better understanding of the dysregulation of the lncRNA-miRNA/mRNA network may yield novel insights into the etiology or progression of HCC. In this study, circulating CD4+ T cells were isolated from the whole blood of 10 healthy controls and 10 HCC patients for the next-generation sequencing of the expression of lncRNAs, miRNAs, and mRNAs. Our data showed that there were different expressions of 34 transcripts (2 lncRNAs, XISTs, and MIR222HGs; 29 mRNAs; and 3 other types of RNA) and 13 miRNAs in the circulating CD4+ T cells of HCC patients. The expression of lncRNA-XIST-related miRNAs and their target mRNAs was confirmed using real-time quantitative polymerase chain reaction (qPCR) on samples from 100 healthy controls and 60 HCC patients. The lncRNA-miRNA/mRNA regulation network was created using interaction data generated from ENCORI and revealed there are positive correlations in the infiltration of total CD4+ T cells, particularly resting memory CD4+ T cells, and negative correlations in the infiltration of Th1 CD4+ T cells.

The Addition of the Geriatric Nutritional Risk Index to the Prognostic Scoring Systems Did Not Improve Mortality Prediction in Trauma Patients in the Intensive Care Unit.

Background: Malnutrition is prevalent among critically ill patients and has been associated with a poor prognosis. This study sought to determine whether the addition of a nutritional indicator to the various variables of prognostic scoring models can improve the prediction of mortality among trauma patients in the intensive care unit (ICU). Methods: This study's cohort included 1,126 trauma patients hospitalized in the ICU between January 1, 2018, and December 31, 2021. Two nutritional indicators, the prognostic nutrition index (PNI), a calculation based on the serum albumin concentration and peripheral blood lymphocyte count, and the geriatric nutritional risk index (GNRI), a calculation based on the serum albumin concentration and the ratio of current body weight to ideal body weight, were examined for their association with the mortality outcome. The significant nutritional indicator was served as an additional variable in prognostic scoring models of the Trauma and Injury Severity Score (TRISS), the Acute Physiology and Chronic Health Evaluation (APACHE II), and the mortality prediction models (MPM II) at admission, 24, 48, and 72 h in the mortality outcome prediction. The predictive performance was determined by the area under the receiver operating characteristic curve. Results: Multivariate logistic regression revealed that GNRI (OR, 0.97; 95% CI, 0.96-0.99; p=0.007), but not PNI (OR, 0.99; 95% CI, 0.97-1.02; p=0.518), was independent risk factor for mortality. However, none of these predictive scoring models showed a significant improvement in prediction when the GNRI variable is incorporated. Conclusions: The addition of GNRI as a variable to the prognostic scoring models did not significantly enhance the performance of the predictors.

The Association of Albumin-Bilirubin (ALBI) Grade with Mortality Risk in Trauma Patients with Liver Injuries.

Introduction: The albumin-bilirubin (ALBI) grade objectively assesses liver function with better performance than the Child-Pugh and end-stage liver disease scores. However, the evidence is lacking on the ALBI grade in trauma cases. This study aimed to identify the association between the ALBI grade and mortality outcomes in trauma patients with liver injury. Methods: Data from 259 patients with traumatic liver injury at a level I trauma center between January 1, 2009, and December 31, 2021 were retrospectively analyzed. Independent risk factors for predicting mortality were identified using multiple logistic regression analysis. Participants were characterized by ALBI score into grade 1 (≤ -2.60, n = 50), grade 2 (-2.60 < and ≤ -1.39, n = 180), and grade 3 (> -1.39, n = 29). Results: Compared to survival (n = 239), death (n = 20) was associated with a significantly lower ALBI score (2.8±0.4 vs 3.4±0.7, p < 0.001). The ALBI score was a significant independent risk factor for mortality (OR, 2.79; 95% CI, 1.27-8.05; p = 0.038). Compared with grade 1 patients, grade 3 patients had a significantly higher mortality rate (24.1% vs 0.0%, p < 0.001) and a longer hospital stay (37.5 days vs 13.5 days, p < 0.001). Discussion: This study showed that ALBI grade is a significant independent risk factor and an useful clinical tool to discover liver injury patients who are more susceptible to death.

Deciphering the Divergent Gene Expression Landscapes of m6A/m5C/m1A Methylation Regulators in Hepatocellular Carcinoma Through Single-Cell and Bulk RNA Transcriptomic Analysis.

Introduction: RNA modifications mediated by the m6A, m1A, and m5C regulatory genes are crucial for the progression of malignancy. This study aimed to explore the expression of regulator genes for m6A/m5C/m1A methylation at the single-cell level and to validate their expression in cancerous and adjacent para-cancerous liver tissues of adult patients with HCC who underwent tumor resection. Methods: The bulk sequencing from The Cancer Genome Atlas (TCGA) database and the single-cell RNA sequencing (scRNA-seq) data obtained from the Gene Expression Omnibus (GEO) database were used to identify the dysregulated m6A/m5C/m1A genes for hepatocellular carcinoma (HCC). A real-time polymerase chain reaction (real-time PCR) was used to measure the expression of dysregulated m6A/m5C/m1A genes in collected human HCC tissues and compared with adjacent para-cancerous liver tissues. Immune cell infiltration with these significantly expressed methylation-related genes was evaluated using Timer2.0. Results: A discrepancy in m6A/m5C/m1A gene expression was observed between bulk sequencing and scRNA-seq. The clustered heatmap of the scRNA-seq-identified dysregulated m6A/m5C/m1A genes in TCGA cohort revealed heterogeneous expression of these methylation regulators within the cancer, whereas their expression in the adjacent liver tissues was more homogeneous. The real-time PCR validated the significant overexpression of DNMT1, NSUN5, TRMT6, IGF2BP1, and IGFBP3, which were identified using scRNA-seq, and IGFBP2, which was identified using bulk sequencing. These dysregulated methylation genes are mainly correlated with the infiltration of natural killer cells. Discussion: This study suggests that cellular diversity inside tumors contributes to the discrepancy in the expression of methylation regulator genes between traditional bulk sequencing and scRNA-seq. This study identified five regulatory genes that will be the focus of further studies regarding the function of m6A/m5C/m1A in HCC.

Using Second Measurement of De Ritis Ratio to Improve Mortality Prediction in Adult Trauma Patients in Intensive Care Unit.

The De Ritis ratio (DRR), the ratio of serum levels of aspartate aminotransferase/alanine aminotransferase, has been reported to be a valuable biomarker in risk stratification for many liver and non-liver diseases. This study aimed to explore whether the inclusion of DRR at the date of intensive care unit (ICU) admission or days after ICU admission improves the predictive performance of various prognosis prediction models. This study reviewed 888 adult trauma patients (74 deaths and 814 survivors) in the trauma registered database between 1 January 2009, and 31 December 2020. Medical information with AST and ALT levels and derived DRR at the date of ICU admission (1st DRR) and 3-7 day after ICU admission (2nd DRR) was retrieved. Logistic regression was used to build new probability models for mortality prediction using additional DRR variables in various mortality prediction models. There was no significant difference in the 1st DRR between the death and survival patients; however, there was a significantly higher 2nd DRR in the death patients than the survival patients. This study showed that the inclusion of the additional DRR variable, measured 3-7 days after ICU admission, significantly increased the prediction performance in all studied prognosis prediction models.

Delta De Ritis Ratio Is Associated with Worse Mortality Outcomes in Adult Trauma Patients with Moderate-to-Severe Traumatic Brain Injuries.

This study aimed to investigate whether changes in the De Ritis ratio (DRR) can be used to stratify the mortality risk of patients with moderate-to-severe traumatic brain injury (TBI). This retrospective study reviewed data for 1347 adult trauma patients (134 deaths and 1213 survival) with moderate-to-severe TBI between 1 January 2009, and 31 December 2020, from the registered trauma database. The outcomes of the patients allocated into the two study groups were compared based on the best Delta DRR (ΔDRR) cutoff point. The first and second DRR of patients who died were significantly higher than those of patients who survived. Elevation of DRR 72-96 h later was found for patients who died, but not for those who survived; the ΔDRR of the patients who died was significantly higher than that of those who survived (1.4 ± 5.8 vs. -0.1 ± 3.3, p = 0.004). Multivariate logistic regression analysis revealed that ΔDRR was a significant independent risk factor for mortality in these patients. Additionally, a ΔDRR of 0.7 was identified as the cutoff value for mortality stratification of adult trauma patients at high risk of mortality with moderate-to-severe TBI.

Association between Elevated De Ritis Ratio and Mortality Outcome in Adult Patients with Thoracoabdominal Trauma.

The De Ritis ratio is widely used to differentiate various causes of liver disease and serves as an independent prognostic predictor for different malignancies and non-malignant illnesses. This retrospective study aimed to identify the association between the De Ritis ratio on admission and mortality outcomes in adult thoracoabdominal trauma patients. A total of 2248 hospitalized adult trauma patients with thoracoabdominal injury, defined as an abbreviated injury scale (AIS) score ≥ 1 in the thoracic and abdominal regions, between 1 January 2009, and 31 December 2019, were included. They were categorized into three tertile groups according to the De Ritis ratio. A 1:1 propensity score-matched study group was established to attenuate the confounding effect of patient characteristics on the mortality outcome assessment. The AST levels of the tertile 1, 2, and 3 groups were 115.8 ± 174.9, 115.7 ± 262.0, and 140.5 ± 209.7 U/L, respectively. Patients in the tertile 3 group had a significantly higher level of AST than those in the tertile 1 group (p = 0.032). In addition, patients in the tertile 1 group had a significantly higher level of ALT than those in the tertile 2 and 3 groups (115.9 ± 158.1 U/L vs. 74.5 ± 107.0 U/L and 61.9 ± 86.0 U/L, p < 0.001). The increased De Ritis ratio in trauma patients with thoracoabdominal injuries was mainly attributed to elevated AST levels. The propensity score-matched patient cohorts revealed that the patients in the tertile 3 group presented a 3.89-fold higher risk of mortality than the patients in the tertile 2 group. In contrast, the patients in the tertile 1 group did not have a significantly different mortality rate than those in the tertile 2 group. This study suggests that a De Ritis ratio > 1.64 may be a useful biomarker to identify patients with a higher risk for mortality.

A new technique for separating platelet-rich plasma by a copolymer device － without a centrifugation process.

BACKGROUND: Platelet-rich plasma (PRP) is beneficial for clinical applications in various medical fields. Although commercial PRP preparation kits are already available in the market, most of these kits employ centrifugation. METHODS: We used a new cationic copolymer coating on a polyurethane (PU) sponge to promote platelet separation from the blood. This copolymer showed no cytotoxicity against cell viability or hemolysis. We further evaluated the efficiency of the new PRP preparation device by comparing it with that of a commercially available kit (RegenKit-THT). RESULTS: We demonstrated that PRP obtained using copolymer device contains high concentrations of platelets and angiogenic growth factors (epidermal growth factor, vascular endothelial growth factor-A, growth differentiation factor 2, and interleukin-8). The separated PRP also displayed beneficial effects on cell migration, angiogenesis, and matrix metalloproteinase gene expression. CONCLUSION: Based on these results, we developed a cationic copolymer-coated PU sponge as a PRP preparation device without the need for any centrifugation.

The Network of miRNA-mRNA Interactions in Circulating T Cells of Patients Following Major Trauma - A Pilot Study.

Purpose: Following major trauma, genes involved in adaptive immunity are downregulated, which accompanies the upregulation of genes involved in systemic inflammatory responses. This study investigated microRNA (miRNA)-mRNA interactome dysregulation in circulating T cells of patients with major trauma. Patients and Methods: This study included adult trauma patients who had an injury severity score ≥16 and required ventilator support for more than 48 h in the intensive care unit. Next-generation sequencing was used to profile the miRNAs and mRNAs expressed in CD3+ T cells isolated from patient blood samples collected during the injury and recovery stages. Results: In the 26 studied patients, 9 miRNAs (hsa-miR-16-2-3p, hsa-miR-16-5p, hsa-miR-185-5p, hsa-miR-192-5p, hsa-miR-197-3p, hsa-miR-23a-3p, hsa-miR-26b-5p, hsa-miR-223-3p, and hsa-miR-485-5p) were significantly upregulated, while 58 mRNAs were significantly downregulated in T cells following major trauma. A network consisting of 8 miRNAs and 22 mRNAs interactions was revealed by miRWalk, with three miRNAs (hsa-miR-185-5p, hsa-miR-197-3p, and hsa-miR-485-5p) acting as hub genes that regulate the network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that "chemokine signaling pathway" was the predominant pathway. Conclusion: The study revealed a miRNA-mRNA interactome consisting of 8 miRNAs and 22 mRNAs that are predominantly involved in chemokine signaling in circulating T cells of patients following major trauma.

Association of White Blood Cell Subtypes and Derived Ratios with a Mortality Outcome in Adult Patients with Polytrauma.

Background. After trauma, the subtypes of white blood cells (WBCs) in circulation and the derived neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) may undergo relative changes and reflect the patients' immune-inflammatory status and outcome. This retrospective study was designed to investigate the relationship between these variables and the mortality outcomes in adult patients with polytrauma, which is defined as an abbreviated injury scale (AIS) score ≥ 3 in two or more different body regions. Methods. A comparison of the expression of subtypes of WBCs, NLR, MLR, and PLR upon arrival to the emergency department was performed in selected propensity score-matched patient cohorts created from 479 adult patients with polytrauma between 1 January 2015 and 31 December 2019. A multivariate logistic regression analysis was used to identify the independent risk factors for mortality. Results. There were no significant differences in monocyte, neutrophil, and platelet counts, as well as in MLR, NLR, and PLR, between deceased (n = 118) and surviving (n = 361) patients. In the propensity score-matched patient cohorts, which showed no significant differences in sex, age, comorbidities, and injury severity, deceased patients had significantly higher lymphocyte counts than survivors (2214 ± 1372 vs. 1807 ± 1162 [106/L], respectively, p = 0.036). In addition, the multivariate logistic regression analysis revealed that the lymphocyte count (OR, 1.0; 95% confidence interval [CI], 1.00-1.06; p = 0.043) was a significant independent risk factor for mortality in these patients. Conclusions. This study revealed that there was no significant difference in the counts of monocytes, neutrophils, and platelets, as well as in MLR, NLR, and PLR, between deceased and surviving patients with polytrauma. However, a significantly higher lymphocyte count may be associated with a worse mortality.

The Association between Skull Bone Fractures and the Mortality Outcomes of Patients with Traumatic Brain Injury.

Introduction: Skull fractures are often found in patients with traumatic brain injury (TBI). Although skull fractures may indicate greater force impact and are associated with local or diffuse brain injuries, the prognostic value of skull fractures remains unclear. This retrospective study aimed to assess the association between skull fractures and mortality in patients with TBI. Methods: This study included 5,430 TBI patients registered in the trauma registry system from January 2009 to December 2018. Clinical and demographic data including age, sex, trauma mechanisms, comorbidities, Glasgow Coma Scale (GCS) score, abbreviated injury score (AIS)-head, injury severity score (ISS), and in-hospital mortality were acquired. Multiple logistic regression and propensity score matching were used to elucidate the effect of skull fractures on mortality outcomes of TBI patients. Results: Compared to TBI patients without skull fracture, patients with skull fractures were predominantly male, younger, had lower GCS upon arrival at the emergency room, and had higher AIS-head, ISS, and in-hospital mortality. The patients with skull fracture had 1.7-fold adjusted odds of mortality (95% confidence interval (CI): 1.27-2.25; p < 0.001) than those without skull fracture, controlling for age, sex, comorbidities, and AIS-head. Additionally, the propensity score-matched analysis of 1,023 selected paired patients revealed that skull fracture was significantly associated with increased 1.4-fold odds of risk for mortality (95% CI: 1.02-1.88; p=0.036). Conclusions: Using a propensity score-matched cohort to attenuate the confounding effect of age, comorbidities, and injury severity, skull fracture was identified as a significant independent risk factor for mortality in patients with TBI.

Exosomes Secreted by Adipose-Derived Stem Cells Following FK506 Stimulation Reduce Autophagy of Macrophages in Spine after Nerve Crush Injury.

Macrophages emerge in the milieu around innervated neurons after nerve injuries. Following nerve injury, autophagy is induced in macrophages and affects the regulation of inflammatory responses. It is closely linked to neuroinflammation, while the immunosuppressive drug tacrolimus (FK506) enhances nerve regeneration following nerve crush injury and nerve allotransplantation with additional neuroprotective and neurotrophic functions. The combined use of FK506 and adipose-derived stem cells (ADSCs) was employed in cell therapy for organ transplantation and vascularized composite allotransplantation. This study aimed to investigate the topical application of exosomes secreted by ADSCs following FK506 treatment (ADSC-F-exo) to the injured nerve in a mouse model of sciatic nerve crush injury. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile the potential exosomal proteins involved in autophagy. Immunohistochemical analysis revealed that nerve crush injuries significantly induced autophagy in the dorsal root ganglia and dorsal horn of the spinal segments. Locally applied ADSC-F-exo significantly reduced autophagy of macrophages in the spinal segments after nerve crush injury. Proteomic analysis showed that of the 22 abundant exosomal proteins detected in ADSC-F-exo, heat shock protein family A member 8 (HSPA8) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) are involved in exosome-mediated autophagy reduction.