The Pathogenic Role of Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Nocardiosis with the Central Nervous System Involvement.

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. CONCLUSION: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.

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.

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.

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.

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.

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.

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.

Increased Angiogenesis by Exosomes Secreted by Adipose-Derived Stem Cells upon Lipopolysaccharide Stimulation.

Exosomes secreted by adipose-derived stem cells (ADSCs) enhance angiogenesis and wound healing. However, in clinical settings, wounds may be infected by various bacteria or pathogens. We investigated whether human ADSCs stimulated with lipopolysaccharide (LPS) secrete exosomes (ADSC-LPS-exo) that augment the angiogenesis of human umbilical vein endothelial cells (HUVECs). ExoQuick-TC exosome precipitation solution was used to purify exosomes from human ADSC culture media in the presence or absence of 1 µg/mL LPS treatment for 24 h. The uptake of ADSC-LPS-exo significantly induced the activation of cAMP response element binding protein (CREB), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) signaling pathways and increased the migration of and tube formation in HUVECs. RNA interference with CREB, AP-1, or NF-κB1 significantly reduced the migration of and tube formation in HUVECs treated with ADSC-LPS-exo. An experiment with an antibody array for 25 angiogenesis-related proteins revealed that only interleukin-8 expression was significantly upregulated in HUVECs treated with ADSC-LPS-exo. In addition, proteomic analysis revealed that eukaryotic translation initiation factor 4E, amyloid beta A4 protein, integrin beta-1, and ras-related C3 botulinum toxin substrate 1 may be potential candidates involved in ADSC-LPS-exo-mediated enhanced angiogenesis.

Identification and characterization of hADSC-derived exosome proteins from different isolation methods.

Exosomes are secreted into the extracellular space by most cell types and contain various molecular constituents, which play roles in many biological processes. Adipose-derived mesenchymal stem cells (ADSCs) can differentiate into a variety of cell types and secrete a series of paracrine factors through exosomes. ADSC-derived exosomes have shown diagnostic and therapeutic potential in many clinical diseases. The molecular components are critical for their mechanisms. Several methods have been developed for exosome purification, including ultracentrifugation, ultrafiltration, density gradient purification, size-based isolation, polymer precipitation and immuno-affinity purification. Thus, we employed four methods to isolate exosomes from the hADSC culture medium, including ultracentrifugation, size exclusion chromatography, ExoQuick-TC precipitation and ExoQuick-TC ULTRA isolation. Following exosome isolation, we performed quantitative proteomic analysis of the exosome proteins using isobaric tags for relative and absolute quantification (iTRAQ) labelling, combined with 2D-LC-MS/MS. There were 599 universal and 138 stably expressed proteins in hADSC-derived exosomes. We proved that these proteins were potential hADSC-derived exosomes markers, including CD109, CD166, HSPA4, TRAP1, RAB2A, RAB11B and RAB14. From the quantitative proteomic analysis, we demonstrated that hADSC-derived exosome protein expression varied, with lipopolysaccharide (LPS) treatment, in the different isolation methods. Pathway analysis and proliferation, migration and endothelial tube formation assays showed varying effects in cells stimulated with hADSC-derived exosomes from different isolation methods. Our study revealed that different isolation methods might introduce variations in the protein composition in exosomes, which reflects their effects on biological function. The pros and cons of these methods are important points to consider for downstream research applications.

Risk factors and complications contributing to mortality in elderly patients with fall-induced femoral fracture: A cross-sectional analysis based on trauma registry data of 2,407 patients.

BACKGROUND: This study aimed to identify the risk factors and complications associated with mortality in elderly patients with femoral fracture after a fall from the ground level. METHODS: This retrospective study reviewed data pertaining to elderly patients aged ≥65 years who were admitted into a Level I trauma center, between January 1, 2009 and December 31, 2017. Multivariate logistic regression analysis was performed to identify independent effects of univariate predictive variables on the occurrence of mortality. RESULTS: Of 2407 enrolled elderly patients, there were 42 mortal and 2365 survival patients. A greater percentage of fatal patients than survival patients had a head injury with abbreviated injury scale (AIS) score ≥ 2 in the head/neck region (4.8% vs. 0.7%, respectively; p = 0.042). Multivariate logistic regression analysis revealed that the age (odds ration [OR] 1.1, 95% confident interval [CI] 1.0-1.1, p < 0.001), pre-existence of end-stage renal disease (ESRD) (OR 3.2, 95% CI 1.2-8.7, p = 0.023), and subarachnoid hemorrhage (SAH) (OR 12.1, 95% CI 1.3-113.9, p = 0.029) were significant independent risk factors for mortality in elderly patients with a femoral fracture resulting from a ground level fall. The patients in mortality group had a significantly higher rates of pneumonia (OR 28.6, 95% CI 14.6-55.9, p < 0.001), respiratory failure (OR 68.7, 95% CI 32.2-146.4, p < 0.001), sepsis (OR 26.3, 95% CI 10.9-63.4, p < 0.001), and pulmonary embolism (OR 14.4, 95% CI 1.6-131.6, p = 0.002) than those in the survival groups. CONCLUSIONS: This study identified age, pre-existence of ESRD, and SAH as significant independent risk factors for mortality in elderly patients with femoral fracture in a fall. However, ESRD and SAH only contribute to the mortality in a small group of patients. In contrast, respiratory complications contributed greatly to mortality. Thus aggressive chest-protective measures are encouraged to decrease the respiratory complications associated with femoral fracture in elderly patients.

Systolic blood pressure lower than the heart rate indicates a poor outcome in patients with severe isolated traumatic brain injury: A cross-sectional study.

BACKGROUND: A systolic blood pressure (SBP) lower than the heart rate (HR) could indicate a poor condition in trauma patients. In such scenarios, the reversed shock index (RSI) is < 1, as calculated by the SBP divided by the HR. This study aimed to clarify whether RSI could be used to identify high-risk adult patients with isolated traumatic brain injury (TBI). METHODS: This retrospective study reviewed 1216 hospitalized adult patients with isolated TBI at a Level I trauma center between January 1, 2009 and December 31, 2015. The patients were grouped and analyzed according to RSI (<1 or ≥ 1). Subgroups of patients with severe TBI (Glasgow Coma Scale [GCS] ≤ 8) or non-severe TBI (GCS > 8) were also compared. The primary outcome was in-hospital mortality. The odds ratios (ORs) of categorical variables were calculated by chi-square tests with 95% confidence intervals (CIs). Mann-Whitney U-tests were used to analyze non-normally distributed continuous data. RESULTS: Among patients with isolated TBI, those with an RSI <1 had higher mortality (44.7% vs. 7.1%, OR: 10.5, 95% CI: 5.36-20.75; P < 0.001) than those with an RSI ≥1. An RSI <1 indicated a higher risk of mortality (OR: 5.1, 95% CI: 2.08-12.49; P < 0.001) in patients with severe isolated TBI but not in patients with non-severe isolated TBI (OR: 3.6, 95% CI: 0.45-28.71; P = 0.267). CONCLUSION: Patients with isolated TBI may be at risk for shock. In trauma patients with severe isolated TBI, an SBP lower than the HR indicates a poor outcome.

Artificial neural network approach to predict surgical site infection after free-flap reconstruction in patients receiving surgery for head and neck cancer.

BACKGROUND: The aim of this study was to develop an effective surgical site infection (SSI) prediction model in patients receiving free-flap reconstruction after surgery for head and neck cancer using artificial neural network (ANN), and to compare its predictive power with that of conventional logistic regression (LR). MATERIALS AND METHODS: There were 1,836 patients with 1,854 free-flap reconstructions and 438 postoperative SSIs in the dataset for analysis. They were randomly assigned tin ratio of 7:3 into a training set and a test set. Based on comprehensive characteristics of patients and diseases in the absence or presence of operative data, prediction of SSI was performed at two time points (pre-operatively and post-operatively) with a feed-forward ANN and the LR models. In addition to the calculated accuracy, sensitivity, and specificity, the predictive performance of ANN and LR were assessed based on area under the curve (AUC) measures of receiver operator characteristic curves and Brier score. RESULTS: ANN had a significantly higher AUC (0.892) of post-operative prediction and AUC (0.808) of pre-operative prediction than LR (both P<0.0001). In addition, there was significant higher AUC of post-operative prediction than pre-operative prediction by ANN (p<0.0001). With the highest AUC and the lowest Brier score (0.090), the post-operative prediction by ANN had the highest overall predictive performance. CONCLUSION: The post-operative prediction by ANN had the highest overall performance in predicting SSI after free-flap reconstruction in patients receiving surgery for head and neck cancer.

Association of Osteoporosis Self-Assessment Tool for Asians (OSTA) Score with Clinical Presentation and Expenditure in Hospitalized Trauma Patients with Femoral Fractures.

Background: A cross-sectional study to investigate the association of Osteoporosis Self-Assessment Tool for Asians (OSTA) score with clinical presentation and expenditure of hospitalized adult trauma patients with femoral fractures. Methods: According to the data retrieved from the Trauma Registry System between 1 January 2009 and 31 December 2015, a total of 2086 patients aged ≥40 years and hospitalized for treatment of traumatic femoral bone fracture were categorized as high-risk patients (OSTA < -4, n = 814), medium-risk patients (-1 ≥ OSTA ≥ -4, n = 634), and low-risk patients (OSTA > -1, n = 638). Two-sided Pearson's, chi-squared, or Fisher's exact tests were used to compare categorical data. Unpaired Student's t-test and Mann-Whitney U-test were used to analyze normally and non-normally distributed continuous data, respectively. Propensity-score matching in a 1:1 ratio was performed using Number Crunching Statistical Software (NCSS) software (NCSS 10; NCSS Statistical Software, Kaysville, UT, USA), with adjusted covariates including mechanism and Glasgow Coma Scale (GCS); injuries were assessed based on the Abbreviated Injury Scale (AIS), and Injury Severity Score (ISS) was used to evaluate the effect of OSTA-related grouping on a patient's outcome. Results: High-risk and medium-risk patients were predominantly female, presented with significantly older age and higher incidences of co-morbidity, and were injured in a fall accident more frequently than low-risk patients. High-risk patients and medium-risk patients had a different pattern of femoral fracture and a significantly lower ISS. Although high-risk and medium-risk patients had significantly shorter lengths hospital of stay (LOS) and less total expenditure than low-risk patients did, similar results were not found in the selected propensity score-matched patients, implying that the difference may be attributed to the associated injury severity of the patients with femoral fracture. However, the charge of surgery is significantly lower in high-risk and medium-risk patients than in low-risk patients, regardless of the total population or the selected propensity score-matched patients. This lower charge of surgery may be attributed to a less aggressive surgery applied for older patients with high or medium risk of osteoporosis. Conclusions: This study of hospitalized trauma patients with femoral fracture according to OSTA risk classification revealed that high-risk and medium-risk patients had significantly higher odds of sustaining injury in a fall accident than low-risk patients; they also present a different pattern of femoral bone fracture as well as a significantly lower ISS, shorter hospital LOS, and less total expenditure. In addition, the significantly lower charge of surgery in high-risk and medium-risk patients than in low-risk patients may be because of the preference of orthopedists for less aggressive surgery in dealing with older patients with osteoporotic femoral bone fracture.

Obese patients who fall have less injury severity but a longer hospital stay than normal-weight patients.

BACKGROUND: The effects of obesity on injury severity and outcome have been studied in trauma patients but not in those who have experienced a fall. The aim of this study was to compare injury patterns, injury severities, mortality rates, and in-hospital or intensive care unit (ICU) length of stay (LOS) between obese and normal-weight patients following a fall. METHODS: Detailed data were retrieved for 273 fall-related hospitalized obese adult patients with a body mass index (BMI) ≥30 kg/m(2) and 2357 normal-weight patients with a BMI <25 kg/m(2) but ≥18.5 kg/m(2) from the Trauma Registry System of a Level I trauma center between January 1, 2009, and December 31, 2013. We used the Pearson's chi-squared test, Fisher's exact test, the Mann Whitney U test, and independent Student's t-test to analyze differences between the two groups. RESULTS: Analysis of AIS scores and AIS severity scaling from 1 to 5 revealed no significant differences in trauma regions between obese and normal-weight patients. When stratified by injury severity (Injury Severity Score [ISS] of <16, 16-24, or ≥25), more obese patients had an ISS of <16 compared to normal-weight patients (90.5 % vs. 86.0 %, respectively; p = 0.041), while more normal-weight patients had an ISS between 16 and 24 (11.0 % vs. 6.6 %, respectively; p = 0.025). Obese patients who had experienced a fall had a significantly lower ISS (median (range): 9 (1-45) vs. 9 (1-50), respectively; p = 0.015) but longer in-hospital LOS than did normal-weight patients (10.1 days vs. 8.9 days, respectively; p = 0.049). Even after taking account of possible differences in comorbidity and ISS, the obese patients have an average 1.54 day longer LOS than that of normal-weight patients. However, no significant differences were found between obese and normal-weight patients in terms of the New Injury Severity Score (NISS), Trauma-Injury Severity Score (TRISS), mortality, percentage of patients admitted to the ICU, or LOS in the ICU. CONCLUSION: Obese patients who had experienced a fall did not have different injured body regions than did normal-weight patients. However, they had a lower ISS but a longer in-hospital LOS than did normal-weight patients.

Effect of Weight-Reduction in Obese Mice Lacking Toll-Like Receptor 5 and C57BL/6 Mice Fed a Low-Fat Diet.

BACKGROUND: This study aims to investigate the effect of feeding low-fat diet (LFD) to diet-induced obesity (DIO) mice lacking TLR5 (TLR5(-/-)), which have a tendency to develop glucose intolerance with increased adiposity, compared to that in C57BL/6 mice. RESULTS: TLR5(-/-) and C57BL/6 male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5 kcal%) diet for 12 weeks; (2) DIO, mice were fed a 58 kcal% high-fat diet (HFD) for 12 weeks; and (3) diet, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10.5 kcal% LFD for 4 weeks. The glucose intolerance in DIO TLR5(-/-) mice was more significant than that in DIO C57BL/6 mice and was not attenuated by a switch to the LFD. Weight-reduction with LFD had significantly decreased the epididymal fat mass in C57BL/6 mice but not in TLR5(-/-) mice. In addition, the LFD-fed TLR5(-/-) mice showed significantly higher expression of ghrelin in the serum and resistin in the epididymal fat than that in C57BL/6 mice. CONCLUSIONS: This study demonstrated that TLR5 gene knockout impairs some effects of weight-reduction in DIO.

Alcohol-related hospitalizations of adult motorcycle riders.

OBJECTIVE: To provide an overview of the demographic characteristics of adult motorcycle riders with alcohol-related hospitalizations. METHODS: Data obtained from the Trauma Registry System were retrospectively reviewed for trauma admissions at a level I trauma center between January 1, 2009 and December 31, 2013. Out of 16,548 registered patients, detailed information was retrieved regarding 1,430 (8.64%) adult motorcycle riders who underwent a blood alcohol concentration (BAC) test. A BAC level of 50 mg/dL was defined as the cut-off value for alcohol intoxication. RESULTS: In this study, alcohol consumption was more frequently noted among male motorcycle riders, those aged 30-49 years, those who had arrived at the hospital in the evening or during the night, and those who did not wear a helmet. Alcohol consumption was associated with a lower percentage of sustained severe injury (injury severity score ≥25) and lower frequencies of specific body injuries, including cerebral contusion (0.6; 95% confidence interval [CI] = 0.42-0.80), lung contusion (0.5; 95% CI = 0.24-0.90), lumbar vertebral fracture (0.1; 95% CI = 0.01-0.80), humeral fracture (0.5; 95% CI = 0.27-0.90), and radial fracture (0.6; 95% CI = 0.40-0.89). In addition, alcohol-intoxicated motorcycle riders who wore helmets had significantly lower frequencies of cranial fracture (0.4; 95% CI = 0.29-0.67), epidural hematoma (0.5; 95% CI = 0.29-0.79), subdural hematoma (0.4; 95% CI = 0.28-0.64), subarachnoid hemorrhage (0.5; 95% CI = 0.32-0.72), and cerebral contusion (0.4; 95% CI = 0.25-0.78). CONCLUSIONS: Motorcycle riders who consumed alcohol presented different characteristics and bodily injury patterns relative to sober patients, suggesting the importance of helmet use to decrease head injuries in alcohol-intoxicated riders.

Lipopolysaccharide-induced microRNA-146a targets CARD10 and regulates angiogenesis in human umbilical vein endothelial cells.

This aim of this study was to explore the role of miRNA-146a (miR-146a) and its target genes in endothelial cells. We demonstrated that lipopolysaccharide (LPS) induced the upregulation of miR-146a in human umbilical vein endothelial cells (HUVECs), and that the induction was blocked by silencing toll-like receptors, the adaptor molecule MyD88, and the nonspecific NF-κB inhibitor BAY 11-7082. In addition, knockdown of miR-146a by transfection of the locked nucleic acid antimiR-146a significantly inhibited LPS-induced cell migration and tube formation. A combined analysis of bioinformatics miRanda algorithms and a whole genome expression microarray of immunoprecipitated Ago2 ribonucleoprotein complexes identified 14 potential target genes. Subsequent transfection with the miR-146a precursor pre-miR-146a into HUVECs validated that CARD10 was the target gene of the miR-146a, both at the mRNA and protein levels. Silencing CARD10 inhibited p65 nuclear translocation in the cells receiving LPS stimulation and increased angiogenesis. Therefore, miR-146a may play a role in regulating the angiogenesis in HUVECs by downregulating CARD10, which acts in a negative feedback regulation loop to inhibit the activation of NF-κB that normally impairs angiogenesis.