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1.
Int J Mol Sci ; 22(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34502537

RESUMO

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.

2.
Int J Mol Sci ; 22(16)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34445251

RESUMO

Exosomes secreted by adipose-derived stem cells (ADSC-exo) reportedly improve nerve regeneration after peripheral nerve injury. Herein, we investigated whether pretreatment of ADSCs with FK506, an immunosuppressive drug that enhances nerve regeneration, could secret exosomes (ADSC-F-exo) that further augment nerve regeneration. Designed exosomes were topically applied to injured nerve in a mouse model of sciatic nerve crush injury to assess the nerve regeneration efficacy. Outcomes were determined by histomorphometric analysis of semi-thin nerve sections stained with toluidine blue, mouse neurogenesis PCR array, and neurotrophin expression in distal nerve segments. Isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile potential exosomal proteins facilitating nerve regeneration. We observed that locally applied ADSC-exo and ADSC-F-exo significantly enhanced nerve regeneration after nerve crush injury. Pretreatment of ADSCs with FK506 failed to produce exosomes possessing more potent molecules for enhanced nerve regeneration. Proteomic analysis revealed that of 192 exosomal proteins detected in both ADSC-exo and ADSC-F-exo, histone deacetylases (HDACs), amyloid-beta A4 protein (APP), and integrin beta-1 (ITGB1) might be involved in enhancing nerve regeneration.


Assuntos
Tecido Adiposo/metabolismo , Exossomos , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/terapia , Nervos Periféricos/fisiologia , Células-Tronco/metabolismo , Tacrolimo/farmacologia , Animais , Exossomos/metabolismo , Exossomos/transplante , Camundongos , Traumatismos dos Nervos Periféricos/metabolismo
3.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445582

RESUMO

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.


Assuntos
Movimento Celular , Exossomos/fisiologia , Células Endoteliais da Veia Umbilical Humana/fisiologia , Lipopolissacarídeos/farmacologia , Células-Tronco Mesenquimais/fisiologia , Neovascularização Fisiológica , Proliferação de Células , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Transdução de Sinais
4.
J Cell Mol Med ; 25(15): 7436-7450, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34235869

RESUMO

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.

5.
Int J Med Sci ; 18(4): 1058-1066, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33456364

RESUMO

The heterogeneity of exosome populations presents a great challenge to their study. The current study was designed to investigate the potential heterogeneity miRNA contents in circulating exosomes purified via different exosomal markers. In this study, exosomes from the serum of C57BL/6 mice after cecum ligation and perforation (CLP) or sham operation were isolated by precipitation using ExoQuick-TC and affinity purified with anti-Rab5b, anti-CD9, anti-CD31, and anti-CD44 antibodies using the Exo-Flow Exosome Capture kit to collect exosome subpopulations. RNA extracted from the exosomes isolated by ExoQuick-TC were profiled by next-generation sequencing (NGS). Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was also employed to determine the expression profiles of four representative exosomal miRNAs (mmu-miR-486-5p, mmu-miR-10a-5p, mmu-miR-143-3p, and mmu-miR-25-3p) selected from the NGS analysis. The results revealed that the expression patterns of these miRNAs in exosomes isolated by ExoQuick-TC as determined by RT-qPCR and NGS were similar, showing upregulation of mmu-miR-10a-5p and mmu-miR-143-3p but downregulation of mmu-miR-25-3p and mmu-miR-486-5p following CLP when compared to the levels in exosomes from sham control mice. However, their expression levels in the antibody-captured exosome subpopulations varied. The miRNAs in the exosomes captured by anti-Rab5b or anti-CD9 antibodies were more similar to those isolated by ExoQuick-TC than to those captured by anti-CD44 antibodies. However, there were no significant differences in these four miRNAs in CD31-captured exosomes. This study demonstrated that purification with different exosomal markers allows the collection of different exosome subpopulations with various miRNA contents. The results of this study demonstrate the heterogeneity of circulating exosomes and suggest the importance of stratifying exosome subpopulations when using circulating exosomes as biomarkers or investigating exosome function. In addition, this study also emphasized the necessity of using a consistent exosome marker across different samples as detecting biomarkers.


Assuntos
MicroRNA Circulante/análise , Exossomos/metabolismo , Sepse/diagnóstico , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , MicroRNA Circulante/sangue , MicroRNA Circulante/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Sepse/sangue , Sepse/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-31795322

RESUMO

Traumatic subarachnoid hemorrhage (SAH) is the second most frequent intracranial hemorrhage and a common radiologic finding in computed tomography. This study aimed to estimate the risk of mortality in adult trauma patients with traumatic SAH concurrent with other types of intracranial hemorrhage, such as subdural hematoma (SDH), epidural hematoma (EDH), and intracerebral hemorrhage (ICH), compared to the risk in patients with isolated traumatic SAH. We searched our hospital's trauma database from 1 January, 2009 to 31 December, 2018 to identify hospitalized adult patients ≥20 years old who presented with a trauma abbreviated injury scale (AIS) of ≥3 in the head region. Polytrauma patients with an AIS of ≥3 in any other region of the body were excluded. A total of 1856 patients who had SAH were allocated into four exclusive groups: (Group I) isolated traumatic SAH, n = 788; (Group II) SAH and one diagnosis, n = 509; (Group III) SAH and two diagnoses, n = 493; and (Group IV) SAH and three diagnoses, n = 66. One, two, and three diagnoses indicated occurrences of one, two, or three other types of intracranial hemorrhage (SDH, EDH, or ICH). The adjusted odds ratio with a 95% confidence interval (CI) of the level of mortality was calculated with logistic regression, controlling for sex, age, and pre-existing comorbidities. Patients with isolated traumatic SAH had a lower rate of mortality (1.8%) compared to the other three groups (Group II: 7.9%, Group III: 12.4%, and Group IV: 27.3%, all p < 0.001). When controlling for sex, age, and pre-existing comorbidities, we found that Group II, Group III, and Group IV patients had a 4.0 (95% CI 2.4-6.5), 8.9 (95% CI 4.8-16.5), and 21.1 (95% CI 9.4-47.7) times higher adjusted odds ratio for mortality, respectively, than the patients with isolated traumatic SAH. In this study, we demonstrated that compared to patients with isolated traumatic SAH, traumatic SAH patients with concurrent types of intracranial hemorrhage have a higher adjusted odds ratio for mortality.


Assuntos
Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Feminino , Humanos , Hemorragias Intracranianas/classificação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnoídea Traumática/etiologia , Hemorragia Subaracnoídea Traumática/mortalidade , Taiwan/epidemiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-31835629

RESUMO

BACKGROUND: In recent years, several versions of the Abbreviated Injury Scale (AIS) were updated and published. It was reported that the codeset in the dictionary of AIS-2005 had significant change from that of AIS-1998. This study was designed to evaluate the potential impact of adapting the AIS-2005 codeset from the AIS-1998 in an established trauma system of a single level I trauma center. The patients' outcome was measured in different Injury Severity Score (ISS) strata according to the double-coded injuries in a three-year period. METHODS: The double-coded injuries sustained by 7520 trauma patients between 1 January, 2016, and 31 December, 2018, in a level I trauma center were used to compare the patient injury characteristics and outcomes between AIS-1998 and AIS-2005 and under different ISS strata, defined as <16 (mild to moderate injury), 16-24 (severe injury), and >24 (critical injury). RESULTS: The mean ISS was significantly lower using AIS-2005 than using AIS-1998 (7.5 ± 6.3 vs. 8.3 ± 7.1, respectively, p < 0.001). AIS-2005 scores in the body regions of the head/neck (2.94 ± 1.08 vs. 3.40 ± 1.15, respectively, p < 0.001) and extremity (2.19 ± 0.56 vs. 2.24 ± 0.58, respectively, p < 0.001), but not in other body regions, were significantly lower than AIS-1998 scores. The critically injured patients (ISS >24), but not severely injured patients or patients with mild-to-moderate injury, coded by AIS-2005 had a significantly higher mortality rate (34.2% vs. 26.2%, respectively, p = 0.031) than did patients coded by AIS-1998. The rate of intensive care unit admission was significantly higher for patients in all ISS strata after adapting AIS-2005 as the scoring system than after adapting AIS-1998. Regarding patients with major trauma, which was defined as ISS > 15, the number of patients with major trauma in this study was 17.0% (n = 1276) for AIS-1998 and 9.7% (n = 733) for AIS-2005. As a consequence, the mortality rate of patients with major trauma was significantly higher in AIS-2005 than in AIS-1998 (15.4% vs. 9.1%, respectively, p < 000.1). CONCLUSIONS: In this study, we revealed that the adaptation of AIS-2005 from AIS-1998 had resulted in a significant decrease of severity scores in the measurement of the same injuries. The number of head/neck injuries classified as 16-24 was the key difference between AIS-1998 and AIS-2005. Furthermore, critically injured patients who had ISS > 24 coded by AIS-2005 had significantly higher mortality rates than did the patients coded by AIS-1998. This study also indicated that a direct comparison of the measurements that are generated from these two AIS versions can produce misleading results.


Assuntos
Escala Resumida de Ferimentos , Escala de Gravidade do Ferimento , Centros de Traumatologia/organização & administração , Ferimentos e Lesões/diagnóstico , Adulto , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Centros de Traumatologia/normas , Ferimentos e Lesões/mortalidade
8.
BMC Musculoskelet Disord ; 20(1): 413, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488121

RESUMO

BACKGROUND: This study aimed to determine the influence of ageing on the incidence and site of femoral fractures in trauma patients, by taking the sex, body weight, and trauma mechanisms into account. METHODS: This retrospective study reviewed data from adult trauma patients aged ≥20 years who were admitted into a Level I trauma center, between January 1, 2009 and December 31, 2016. According to the femoral fracture locations, 3859 adult patients with 4011 fracture sites were grouped into five subgroups: proximal type A (n = 1359), proximal type B (n = 1487), proximal type C (n = 59), femoral shaft (n = 640), and distal femur (n = 466) groups. A multivariate logistic regression analysis was applied to identify independent effects of the univariate predictive variables on the occurrence of fracture at a specific site. A two-dimensional plot was presented visually with age and the propensity score accounts for the risk of a fracture at a specific femoral site. RESULTS: This analysis revealed that older age was an independent variable that could positively predict the occurrence of proximal type A (OR [95%CI]: 1.03 [1.03-1.04], p < 0.001) and B fractures (1.02 [1.01-1.02], p < 0.001), and negatively predict the occurrence of proximal type C (0.96 [0.94-0.98], p < 0.001), shaft (0.95 [0.95-0.96], p < 0.001), and distal fractures (0.98 [0.98-0.99], p < 0.001). DISCUSSION: Using the propensity scores which account for the risk of a fracture in a specific femoral site, this study revealed that the older patients were at a higher risk of developing proximal type A and type B fractures, while a lower risk of developing fractures in the shaft and distal femur. This incidence of fracture site can largely be explained by age-related factors, including a decrease in bone strength and falling being the most common mechanism of trauma in older patients. CONCLUSIONS: This study revealed a difference in the involvement of age in the incidence of femoral fracture sites in the trauma patients.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Envelhecimento/fisiologia , Fraturas do Fêmur/epidemiologia , Cabeça do Fêmur/lesões , Colo do Fêmur/lesões , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/fisiopatologia , Cabeça do Fêmur/fisiopatologia , Colo do Fêmur/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Centros de Traumatologia/estatística & dados numéricos
10.
PLoS One ; 14(7): e0220398, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31348811

RESUMO

OBJECTIVE: To establish the composition of bacteria in mice following cecum ligation and puncture (CLP) through metagenomic analysis and investigate the role of TLRs on the composition of bacteria. METHODS: Total DNA extraction was done from the ascites, blood, and fecal samples from C57BL/6 mice sacrificed at 0, 4, 8, and 16 h, as well as from Tlr2-/-, Tlr4-/-, Tlr5-/-, and NF-κB-/-mice sacrificed at 16 h following CLP. Amplification of the V3-V4 regions of the bacterial 16S rRNA genes by PCR and the Illumina MiSeq sequencer was used for deep sequencing. Hierarchical clustering of the isolates was performed with Ward's method using Euclidean distances. The relative abundance according to operational taxonomic unit (OTU) number or taxa was used to compare the richness among subgroups in the experiments. RESULTS: There were 18 taxa that had significantly different abundances among the different samples of the C57BL/6 mice at 16 h following CLP. Various dynamic changes in the infectious bacteria inside the peritoneal cavity after CLP were found. While knockout of Tlr5 and NF-κB impaired the ability of bacterial clearance inside the peritoneal cavity for some kinds of bacteria found in the C57BL/6 mice, the knockout of Tlr4 enhanced clearance for other kinds of bacteria, and they presented excessive abundance in the peritoneal cavity despite their scarce abundance in the stool. CONCLUSION: NF-κB and TLRs are involved in bacterial clearance and in the expression pattern of the bacterial abundance inside the peritoneal cavity during polymicrobial infection.


Assuntos
Bactérias/classificação , Metagenômica/métodos , Cavidade Peritoneal/microbiologia , Receptores Toll-Like/genética , Animais , Ascite/microbiologia , Bactérias/genética , Sangue/microbiologia , DNA Bacteriano , DNA Ribossômico/genética , Fezes/microbiologia , Técnicas de Silenciamento de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Filogenia , RNA Ribossômico 16S/genética
11.
J Clin Med ; 8(6)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195670

RESUMO

BACKGROUND: We aimed to build a model using machine learning for the prediction of survival in trauma patients and compared these model predictions to those predicted by the most commonly used algorithm, the Trauma and Injury Severity Score (TRISS). METHODS: Enrolled hospitalized trauma patients from 2009 to 2016 were divided into a training dataset (70% of the original data set) for generation of a plausible model under supervised classification, and a test dataset (30% of the original data set) to test the performance of the model. The training and test datasets comprised 13,208 (12,871 survival and 337 mortality) and 5603 (5473 survival and 130 mortality) patients, respectively. With the provision of additional information such as pre-existing comorbidity status or laboratory data, logistic regression (LR), support vector machine (SVM), and neural network (NN) (with the Stuttgart Neural Network Simulator (RSNNS)) were used to build models of survival prediction and compared to the predictive performance of TRISS. Predictive performance was evaluated by accuracy, sensitivity, and specificity, as well as by area under the curve (AUC) measures of receiver operating characteristic curves. RESULTS: In the validation dataset, NN and the TRISS presented the highest score (82.0%) for balanced accuracy, followed by SVM (75.2%) and LR (71.8%) models. In the test dataset, NN had the highest balanced accuracy (75.1%), followed by the TRISS (70.2%), SVM (70.6%), and LR (68.9%) models. All four models (LR, SVM, NN, and TRISS) exhibited a high accuracy of more than 97.5% and a sensitivity of more than 98.6%. However, NN exhibited the highest specificity (51.5%), followed by the TRISS (41.5%), SVM (40.8%), and LR (38.5%) models. CONCLUSIONS: These four models (LR, SVM, NN, and TRISS) exhibited a similar high accuracy and sensitivity in predicting the survival of the trauma patients. In the test dataset, the NN model had the highest balanced accuracy and predictive specificity.

12.
BMJ Open ; 9(4): e026481, 2019 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-31005931

RESUMO

OBJECTIVES: We aimed to profile the epidemiological changes of driving under the influence (DUI) in southern Taiwan after the legal blood alcohol concentration (BAC) limit was lowered from 50 to 30 mg/dL in 2013. SETTING: Level 1 trauma medical centre in southern Taiwan. PARTICIPANTS: Data from 7447 patients (4375 males and 3072 females) were retrieved from the trauma registry system of a single trauma centre to examine patient characteristics (gender, age and BAC), clinical outcome variables (Abbreviated Injury Score, Injury Severity Score and mortality) and vehicular crash-related factors (vehicle type, airbag use in car crashes, helmet use in motorcycle crashes and time of crash) before and after the BAC limit change. RESULTS: Our results indicated that the percentage of DUI patients significantly declined from 10.99% (n=373) to 6.64% (n=269) after the BAC limit was lowered. Airbag use in car crashes (OR: 0.30, 95% CI 0.10 to 0.88, p=0.007) and helmet use in motorcycle crashes (OR: 0.20, 95% CI 0.15 to 0.26, p<0.001) was lower in DUI patients compared with non-DUI patients after the BAC limit change, with significant negative correlation. DUI behaviour increased crash mortality risk before the BAC limit change (OR: 4.33, 95% CI 2.20 to 8.54), and even more so after (OR: 5.60, 95% CI 3.16 to 9.93). The difference in ORs for mortality before and after the change in the BAC legal limit was not significant (p=0.568). CONCLUSION: This study revealed that lowering the BAC limit to 30 mg/dL significantly reduced the number of DUI events, but failed to result in a significant reduction in mortality in these trauma patients.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Concentração Alcoólica no Sangue , Dirigir sob a Influência/legislação & jurisprudência , Dirigir sob a Influência/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan , Adulto Jovem
13.
Int J Surg ; 66: 48-52, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31026517

RESUMO

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.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Fraturas do Fêmur/complicações , Idoso , Idoso de 80 Anos ou mais , Traumatismos Craniocerebrais/mortalidade , Estudos Transversais , Feminino , Fraturas do Fêmur/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Escala de Gravidade do Ferimento , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Masculino , Traumatismo Múltiplo/mortalidade , Pneumonia/complicações , Pneumonia/mortalidade , Embolia Pulmonar/complicações , Embolia Pulmonar/mortalidade , Sistema de Registros , Insuficiência Respiratória/complicações , Insuficiência Respiratória/mortalidade , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/mortalidade , Taiwan/epidemiologia , Centros de Traumatologia
14.
PLoS One ; 14(4): e0216153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31022295

RESUMO

BACKGROUND: The shock index (SI) is defined as the ratio of heart rate/systolic blood pressure. This study aimed to determine the performance of delta shock index (ΔSI), a difference between SI upon arrival at the emergency room (ER) and that in the field, in predicting the need for massive transfusion (MT) among adult trauma patients with stable blood pressure. METHODS: This study included registered data from all trauma patients aged 20 years and above who were hospitalized from January 1, 2009 to December 31, 2016. Only patients who were transferred by emergency medical service from the accident site with a systolic blood pressure ≥ 90 mm Hg at the ER were included. The 7,957 enrolled trauma patients were divided into 2 groups, those who had received blood transfusion ≥ 10 U (MT, n = 82) and those who had not (non-MT, n = 7,875). The odds ratios with 95% confidence intervals for the need for MT by a given ΔSI were measured. The plot of specific receiver operating characteristic (ROC) curves was used to evaluate the best cutoff point of ΔSI that could predict the patient's probability of receiving MT. RESULTS: ROC curve analysis showed that a ΔSI of 0.06 as the cutoff point had the highest AUC of 0.61, with a sensitivity of 0.415 and specificity of 0.841. Patients with a ΔSI ≥ 0.00 had a significant 1.8-fold increase in need for MT than those patients with a ΔSI less than 0.00 (1.4% vs. 0.8%, p = 0.01). The larger the ΔSI, the higher the odds of need for an MT. Using the cutoff point of ΔSI of 0.06, patients with a ΔSI ≥ 0.06 had a significant 3.7-fold increase in need for MT than those patients with a ΔSI less than 0.06 (2.7% vs. 0.7%, p < 0.001). CONCLUSIONS: This study indicated that, in trauma patients with stable blood pressure at the ER, the accuracy of prediction of the requirement for MT by ΔSI is low. However, the size of the delta is significantly associated with need for MT and a lack of improvement in the patient's SI at the ER compared to that in the field significantly increases the odds of a need for MT.


Assuntos
Pressão Sanguínea , Transfusão de Sangue , Serviço Hospitalar de Emergência , Choque/complicações , Choque/fisiopatologia , Ferimentos e Lesões/complicações , Ferimentos e Lesões/fisiopatologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Curva ROC , Fatores de Risco
15.
Int J Surg ; 61: 48-52, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30543949

RESUMO

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.


Assuntos
Pressão Sanguínea , Lesões Encefálicas Traumáticas/diagnóstico , Frequência Cardíaca , Medição de Risco/métodos , Adulto , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/mortalidade , Estudos Transversais , Feminino , Mortalidade Hospitalar , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Choque/etiologia , Centros de Traumatologia
16.
PLoS One ; 13(11): e0207192, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30412613

RESUMO

BACKGROUND: The purpose of this study was to build a model of machine learning (ML) for the prediction of mortality in patients with isolated moderate and severe traumatic brain injury (TBI). METHODS: Hospitalized adult patients registered in the Trauma Registry System between January 2009 and December 2015 were enrolled in this study. Only patients with an Abbreviated Injury Scale (AIS) score ≥ 3 points related to head injuries were included in this study. A total of 1734 (1564 survival and 170 non-survival) and 325 (293 survival and 32 non-survival) patients were included in the training and test sets, respectively. RESULTS: Using demographics and injury characteristics, as well as patient laboratory data, predictive tools (e.g., logistic regression [LR], support vector machine [SVM], decision tree [DT], naive Bayes [NB], and artificial neural networks [ANN]) were used to determine the mortality of individual patients. The predictive performance was evaluated by accuracy, sensitivity, and specificity, as well as by area under the curve (AUC) measures of receiver operator characteristic curves. In the training set, all five ML models had a specificity of more than 90% and all ML models (except the NB) achieved an accuracy of more than 90%. Among them, the ANN had the highest sensitivity (80.59%) in mortality prediction. Regarding performance, the ANN had the highest AUC (0.968), followed by the LR (0.942), SVM (0.935), NB (0.908), and DT (0.872). In the test set, the ANN had the highest sensitivity (84.38%) in mortality prediction, followed by the SVM (65.63%), LR (59.38%), NB (59.38%), and DT (43.75%). CONCLUSIONS: The ANN model provided the best prediction of mortality for patients with isolated moderate and severe TBI.


Assuntos
Lesões Encefálicas Traumáticas/mortalidade , Aprendizado de Máquina , Escala Resumida de Ferimentos , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Árvores de Decisões , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Valor Preditivo dos Testes , Curva ROC , Máquina de Vetores de Suporte , Taiwan/epidemiologia , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-30388747

RESUMO

BACKGROUND: We aimed to explore the risk factors that contribute to the mortality of elderly trauma patients with acute subdural hematoma (SDH) resulting from a fall. Mortality rates of the elderly were compared to those of young adults. METHODS: A total of 444 patients with acute traumatic subdural hematoma resulting from a fall, admitted to a level I trauma center from 1 January 2009 to 31 December 2016 were enrolled in this study. Patients were categorized into two groups: elderly patients (n = 279) and young adults (n = 165). The primary outcome of this study was patient mortality in hospital. The adjusted odds ratio (AOR) with 95% confidence interval (CI) for mortality was calculated according to gender and pre-existing comorbidities. Univariate and multivariate logistic regression analyses were performed to identify factors related to mortality in the elderly. RESULTS: The odds ratio for mortality caused by falls in the elderly patients was four-fold higher than in the young adults, after adjusting for gender and pre-existing comorbidities. In addition, the presence of pre-existing coronary artery disease (OR 3.2, 95% CI 1.09⁻9.69, p = 0.035), end-stage renal disease (OR 4.6, 95% CI 1.48⁻14.13, p = 0.008), hematoma volume (OR 1.2, 95% CI 1.11⁻1.36, p < 0.001), injury severity score (OR 1.3, 95% CI 1.23⁻1.46, p < 0.001), and coagulopathy (OR 4.0, 95% CI 1.47⁻11.05, p = 0.007) were significant independent risk factors for mortality in patients with acute traumatic SDH resulting from a fall. CONCLUSIONS: In this study, we identified that pre-existing CAD, ESRD, hematoma volume, ISS, and coagulopathy were significant independent risk factors for mortality in patients with acute traumatic SDH. These results suggest that death following acute SDH is influenced both by the extent of neurological damage and the overall health of the patient at the time of injury.


Assuntos
Acidentes por Quedas/mortalidade , Acidentes por Quedas/estatística & dados numéricos , Hematoma Subdural Agudo/mortalidade , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Centros de Traumatologia/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Taiwan , Adulto Jovem
18.
Artigo em Inglês | MEDLINE | ID: mdl-30340313

RESUMO

Background: For elderly trauma patients, a prognostic tool called the Geriatric Trauma Outcome Score (GTOS), where GTOS = (age) + (ISS × 2.5) + (22 if any packed red blood cells (pRBCs) were transfused within 24 h after admission), was developed for predicting mortality. In such calculation, a score of 22 was added in the calculation of GTOS regardless of the transfused units of blood. This study aimed to assess the effect of transfused blood units on the mortality outcomes of the elderly trauma patients who received blood transfusion (BT). Methods: Detailed data of 687 elderly trauma patients aged ≥65 years who were transfused with pRBCs within 24 h after admission into a level I trauma center between 1 January 2009 and 31 December 2016 were retrieved from the Trauma Registry System database. Based on the units of pRBCs transfused, the study population was divided into two groups to compare the mortality outcomes between these groups. Adjusted odds ratios (AORs) with its 95% confidence intervals (CIs) for mortality were calculated by adjusting sex, pre-existing comorbidities, and GTOS. Results: When the cut-off value of BT was set as 3 U of pRBCs, patients who received BT ≥ 3 U had higher odds of mortality than those who received BT < 3 U (OR, 3.0; 95% CI, 1.94⁻4.56; p < 0.001). Patients who received more units of pRBCs still showed higher odds of mortality than their counterparts. After adjusting for sex, pre-existing comorbidities, and GTOS, comparison revealed that the patients who received BT of 3 U to 6 U had a 1.7-fold adjusted odds of mortality than their counterparts. The patients who received BT ≥ 8 U and 10 U had a 2.1-fold (AOR, 2.1; 95% CI, 1.09⁻3.96; p < 0.001) and 4.4-fold (AOR, 4.4; 95% CI, 2.04⁻9.48; p < 0.001) adjusted odds of mortality than those who received BT < 8 U and <10 U, respectively. Conclusions: This study revealed that the units of BT did matter in determining the probability of mortality. For those who received more units of blood, the mortality may be underestimated according to the GTOS.


Assuntos
Transfusão de Eritrócitos/estatística & dados numéricos , Mortalidade , Pacientes/estatística & dados numéricos , Prognóstico , Centros de Traumatologia/estatística & dados numéricos , Ferimentos e Lesões/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Probabilidade , Taiwan/epidemiologia , Ferimentos e Lesões/diagnóstico
19.
Artigo em Inglês | MEDLINE | ID: mdl-30355971

RESUMO

The reverse shock index (rSI) multiplied by Glasgow Coma Scale (GCS) score (rSIG), calculated by multiplying the GCS score with systolic blood pressure (SBP)/hear rate (HR), was proposed to be a reliable triage tool for identifying risk of in-hospital mortality in trauma patients. This study was designed to externally validate the accuracy of the rSIG in the prediction of mortality in our cohort of trauma patients, in comparison with those that were predicted by the Revised Trauma Score (RTS), shock index (SI), and Trauma and Injury Severity Score (TRISS). Adult trauma patients aged ≥20 years who were admitted to the hospital from 1 January 2009 to 31 December 2017, were included in this study. The rSIG, RTS, and SI were calculated according to the initial vital signs and GCS scores of patients upon arrival at the emergency department (ED). The end-point of primary outcome is in-hospital mortality. Discriminative power of each score to predict mortality was measured using area under the curve (AUC) by plotting the receiver operating characteristic (ROC) curve for 18,750 adult trauma patients, comprising 2438 patients with isolated head injury (only head Abbreviated Injury Scale (AIS) ≥ 2) and 16,312 without head injury (head AIS ≤ 1). The predictive accuracy of rSIG was significantly lower than that of RTS in all trauma patients (AUC 0.83 vs. AUC 0.85, p = 0.02) and in patients with isolated head injury (AUC 0.82 vs. AUC 0.85, p = 0.02). For patients without head injury, no difference was observed in the predictive accuracy between rSIG and RTS (AUC 0.83 vs. AUC 0.83, p = 0.97). Based on the cutoff value of 14.0, the rSIG can predict the probability of dying in trauma patients without head injury with a sensitivity of 61.5% and specificity of 94.5%. The predictive accuracy of both rSIG and RTS is significantly poorer than that of TRISS, in all trauma patients (AUC 0.93) or in patients with (AUC 0.89) and without head injury (AUC 0.92). In addition, SI had the significantly worse predictive accuracy than all of the other three models in all trauma patients (AUC 0.57), and the patients with (AUC 0.53) or without (AUC 0.63) head injury. This study revealed that rSIG had a significantly higher predictive accuracy of mortality than SI in all of the studied population but a lower predictive accuracy of mortality than RTS in all adult trauma patients and in adult patients with isolated head injury. In addition, in the adult patients without head injury, rSIG had a similar performance as RTS to the predictive risk of mortality of the patients.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Escala de Coma de Glasgow/estatística & dados numéricos , Mortalidade Hospitalar , Choque/diagnóstico , Ferimentos e Lesões/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Estudos Transversais , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia , Ferimentos e Lesões/classificação , Ferimentos e Lesões/etiologia , Adulto Jovem
20.
Nutrients ; 10(10)2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30304787

RESUMO

Background: This study aimed at assessing the effect of a low-fat diet (LFD) in obese mice lacking toll⁻like receptors (Tlr) and understanding the expression and regulation of microRNAs during weight reduction. Methods: C57BL/6, Tlr5-/-, Tlr2-/- and Tlr4-/- mice were used in this study. A group of mice were fed with a high-fat diet (HFD) (58% kcal) for 12 weeks to induce obesity (diet-induced obesity, DIO). Another group that had been fed with HFD for eight weeks (obese mice) were switched to a low-fat diet (LFD) (10.5% kcal) for the next four weeks to reduce their body weight. The control mice were fed with a standard AIN-76A diet for the entire 12 weeks. The body weight of the mice was measured weekly. At the end of the experiment, epididymal fat weight and adipocyte size were measured. The differentially expressed miRNAs in the fat tissue was determined by next-generation sequencing with real-time quantitative reverse transcription polymerase chain reaction (RT⁻qPCR). Target prediction and functional annotation of miRNAs were performed using miRSystem database. Results: Switching to LFD significantly reduced the body weight and epididymal fat mass in the HFD-fed C57BL/6 and Tlr5-/- mice but not in Tlr2-/- and Tlr4-/- mice. Weight reduction significantly decreased the size of adipocytes in C57BL/6 but not in the Tlr knockout mice. In Tlr2-/- and Tlr4-/- mice, feeding with HFD and the subsequent weight reduction resulted in an aberrant miRNA expression in the epididymal fat tissue unlike in C57BL/6 and Tlr5-/-. However, target prediction and functional annotation by miRSystem database revealed that all the top 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathways of the dysregulated miRNAs during weight reduction in the C57BL/6 mice were also found in the regulated pathways of Tlr5-/-, Tlr2-/-, and Tlr4-/- strains. However, among these pathways, gene sets involved in arginine and proline metabolism and glutathione metabolism were mainly involved in the Tlr knockout mice but not in the C57BL/6 mice. Conclusions: In this study, we demonstrated that feeding of LFD leads to significant body weight reduction in C57BL/6 and Tlr5-/- mice, but not in Tlr2-/- and Tlr4-/- mice. Significant reduction in the size of adipocytes of epididymal fat was only found in C57BL/6, but not in Tlr5-/-, Tlr2-/-, and Tlr4-/- mice. The dysregulated miRNAs in Tlr2-/- and Tlr4-/- mice were different from those in C57BL/6 and Tlr5-/- strains. Among those miRNA-regulated pathways, arginine and proline metabolism as well as glutathione metabolism may have important roles in the Tlr knockout mice rather than in C57BL/6 mice.


Assuntos
Tecido Adiposo/metabolismo , Dieta com Restrição de Gorduras , MicroRNAs/metabolismo , Obesidade/genética , Receptores Toll-Like/genética , Adipócitos/patologia , Animais , Dieta Hiperlipídica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Obesidade/etiologia , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Receptor 5 Toll-Like/genética , Perda de Peso
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