Circadian Rhythm Disruption in Hepatocellular Carcinoma Investigated by Integrated Analysis of Bulk and Single-Cell RNA Sequencing Data.

Circadian rhythms are essential regulators of a multitude of physiological and behavioral processes, such as the metabolism and function of the liver. Circadian rhythms are crucial to liver homeostasis, as the liver is a key metabolic organ accountable for the systemic equilibrium of the body. Circadian rhythm disruption alone is sufficient to cause liver cancer through the maintenance of hepatic metabolic disorder. Although there is evidence linking CRD to hepatocarcinogenesis, the precise cellular and molecular mechanisms that underlie the circadian crosstalk that leads to hepatocellular carcinoma remain unknown. The expression of CRD-related genes in HCC was investigated in this study via bulk RNA transcriptomic analysis and single-cell sequencing. Dysregulated CRD-related genes are predominantly found in hepatocytes and fibroblasts, according to the findings. By using a combination of single-cell RNA sequencing and bulk RNA sequencing analyses, the dysregulated CRD-related genes ADAMTS13, BIRC5, IGFBP3, MARCO, MT2A, NNMT, and PGLYRP2 were identified. The survival analysis using the Kaplan-Meier method revealed a significant correlation between the expression levels of BIRC5 and IGFBP3 and the survival of patients diagnosed with HCC.

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.

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.

Profiling the Expression of Circulating Acute-Phase Proteins, Cytokines, and Checkpoint Proteins in Patients with Severe Trauma: A Pilot Study.

PURPOSE: Severe trauma may lead to the systemic release of inflammatory mediators into the circulation with profound acute-phase responses; however, the understanding of the expression of these mediators remains limited. This study aimed to characterize the alterations in the expression of circulating acute-phase proteins, cytokines, and checkpoint proteins in patients with severe trauma injuries. PATIENTS AND METHODS: The study population included trauma patients in the intensive care unit (ICU) with an injury severity score equal to or greater than 16 and who had used a ventilator for 48 hours. A total of 12 female and 28 male patients were recruited for the study; six patients died and 34 survived. Blood samples collected at acute stages were compared with those drawn at the subacute stage, the time when the patients were discharged from the ICU, or before the discharge of the patients from the hospital. RESULTS: The study identified that the expression of acute-phase proteins, such as alpha-1-acid glycoprotein and C-reactive protein, and cytokines, including granulocyte colony-stimulating factor, interleukin-6, and interleukin-1 receptor antagonist, was elevated in the circulation after severe trauma. In contrast, the levels of acute-phase proteins, such as alpha-2-macroglobulin, serum amyloid P, and von Willebrand factor, and cytokines, including interleukin-4 and interferon gamma-induced protein 10, were reduced. However, there were no significant differences in the expression of checkpoint proteins in the circulation. CONCLUSION: The dysregulated proteins identified in this study may serve as potential therapeutic targets or biomarkers for treating patients with severe trauma. However, the related biological functions of these dysregulated factors require further investigation to validate their functions.

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.

Association of Platelets and White Blood Cells Subtypes with Trauma Patients' Mortality Outcome in the Intensive Care Unit.

Background: White blood cell (WBC) subtypes have been suggested to reflect patients' immune-inflammatory status. Furthermore, the derived ratio of platelets and WBC subtypes, including monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), is proposed to be associated with patient outcome. Therefore, this study aimed to identify the association of platelets and white blood cells subtypes with the mortality outcome of trauma patients in the intensive care unit (ICU). Method: The medical information from 2854 adult trauma patients admitted to the ICU between 1 January 2009 and 31 December 2019 were retrospectively retrieved from the Trauma Registry System and classified into two groups: the survivors group (n = 2524) and the death group (n = 330). The levels of monocytes, neutrophils, lymphocytes, platelets, and blood-drawn laboratory data detected upon patient arrival to the emergency room and the derived MLR, NLR, and PLR were calculated. Multivariate logistic regression analysis was used to determine the independent effects of univariate predictive variables on mortality occurrence. Result: The results revealed the patients who died had significantly lower platelet counts (175,842 ± 61,713 vs. 206,890 ± 69,006/µL, p < 0.001) but higher levels of lymphocytes (2458 ± 1940 vs. 1971 ± 1453/µL, p < 0.001) than the surviving patients. However, monocyte and neutrophil levels were not significantly different between the death and survivor groups. Moreover, dead patients had a significantly lower PLR than survivors (124.3 ± 110.3 vs. 150.6 ± 106.5, p < 0.001). However, there was no significant difference in MLR or NLR between the dead patients and the survivors. Multivariate logistic regression revealed that male gender, old age, pre-existing hypertension, coronary artery disease and end-stage renal disease, lower Glasgow Coma Scale (GCS), higher Injury Severity Score (ISS), higher level of lymphocytes and lower level of red blood cells and platelets, longer activated partial thromboplastin time (aPTT), and lower level of PLR were independent risk factors associated with higher odds of trauma patient mortality outcome in the ICU. Conclusion: This study revealed that a higher lymphocyte count, lower platelet count, and a lower PLR were associated with higher risk of death in ICU trauma patients.

Reply to Comment on Tsai, Y.-C., et al. Association of Stress-Induced Hyperglycemia and Diabetic Hyperglycemia with Mortality in Patients with Traumatic Brain Injury: Analysis of a Propensity Score-Matched Population. Int. J. Environ. Res. Public Health 2020, 17, 4266.

Thank you for Eduardo Mekitarian Filho's appreciation of our work on the study of stress-induced hyperglycemia (SIH) and diabetic hyperglycemia (DH) in patients with traumatic brain injuries [...].

Association between Geriatric Nutritional Risk Index and Mortality in Older Trauma Patients in the Intensive Care Unit.

The geriatric nutritional risk index (GNRI) is a simple and efficient tool to assess the nutritional status of patients with malignancies or after surgery. Because trauma patients constitute a specific population that generally acquires accidental and acute injury, this study aimed to identify the association between the GNRI at admission and mortality outcomes of older trauma patients in the intensive care unit (ICU). METHODS: The study population included 700 older trauma patients admitted to the ICU between 1 January 2009 and 31 December 2019. The collected data included age, sex, body mass index (BMI), albumin level at admission, preexisting comorbidities, injury severity score (ISS), and in-hospital mortality. Multivariate logistic regression analysis was conducted to identify the independent effects of univariate predictive variables resulting in mortality in our study population. The study population was categorized into four nutritional risk groups: a major-risk group (GNRI < 82; n = 128), moderate-risk group (GNRI 82 to <92; n = 191), low-risk group (GNRI 92-98; n = 136), and no-risk group (GNRI > 98; n = 245). RESULTS: There was no significant difference in sex predominance, age, and BMI between the mortality (n = 125) and survival (n = 575) groups. The GNRI was significantly lower in the mortality group than in the survival group (89.8 ± 12.9 vs. 94.2 ± 12.0, p < 0.001). Multivariate logistic regression analysis showed that the GNRI (odds ratio-OR, 0.97; 95% confidence interval (CI) 0.95-0.99; p = 0.001), preexisting end-stage renal disease (OR, 3.6; 95% CI, 1.70-7.67; p = 0.001), and ISS (OR, 1.1; 95% CI, 1.05-1.10; p < 0.001) were significant independent risk factors for mortality. Compared to the patients in group of GNRI > 98, those patients in group of GNRI < 82 presented a significantly higher mortality rate (26.6% vs. 13.1%; p < 0.001) and length of stay in hospital (26.5 days vs. 20.9 days; p = 0.016). CONCLUSIONS: This study demonstrated that GNRI is a significant independent risk factor and a promising simple screening tool to identify the subjects with malnutrition associated with higher risk for mortality in those ICU elderly trauma patients.

Performance of Prognostic Scoring Systems in Trauma Patients in the Intensive Care Unit of a Trauma Center.

BACKGROUND: Prediction of mortality outcomes in trauma patients in the intensive care unit (ICU) is important for patient care and quality improvement. We aimed to measure the performance of 11 prognostic scoring systems for predicting mortality outcomes in trauma patients in the ICU. METHODS: Prospectively registered data in the Trauma Registry System from 1 January 2016 to 31 December 2018 were used to extract scores from prognostic scoring systems for 1554 trauma patients in the ICU. The following systems were used: the Trauma and Injury Severity Score (TRISS); the Acute Physiology and Chronic Health Evaluation (APACHE II); the Simplified Acute Physiology Score (SAPS II); mortality prediction models (MPM II) at admission, 24, 48, and 72 h; the Multiple Organ Dysfunction Score (MODS); the Sequential Organ Failure Assessment (SOFA); the Logistic Organ Dysfunction Score (LODS); and the Three Days Recalibrated ICU Outcome Score (TRIOS). Predictive performance was determined according to the area under the receiver operator characteristic curve (AUC). RESULTS: MPM II at 24 h had the highest AUC (0.9213), followed by MPM II at 48 h (AUC: 0.9105). MPM II at 24, 48, and 72 h (0.8956) had a significantly higher AUC than the TRISS (AUC: 0.8814), APACHE II (AUC: 0.8923), SAPS II (AUC: 0.9044), MPM II at admission (AUC: 0.9063), MODS (AUC: 0.8179), SOFA (AUC: 0.7073), LODS (AUC: 0.9013), and TRIOS (AUC: 0.8701). There was no significant difference in the predictive performance of MPM II at 24 and 48 h (p = 0.37) or at 72 h (p = 0.10). CONCLUSIONS: We compared 11 prognostic scoring systems and demonstrated that MPM II at 24 h had the best predictive performance for 1554 trauma patients in the ICU.

Effect of Lowering the Blood Alcohol Concentration Limit to 0.03 Among Hospitalized Trauma Patients in Southern Taiwan: A Cross-Sectional Analysis.

BACKGROUND: In June 2013, the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.05 to 0.03 mg/mL in Taiwan. Thus, this study aimed to assess the epidemiological changes in terms of drinking among drivers in southern Taiwan before and after the law was imposed. METHODS: Only patients who had undergone the BAC test at the emergency room were included in the study. The patients during the study period before (n = 2735) and after (n = 2413) the implementation of the law were selected for comparison. Drunk patients were defined as those who had a BAC ≥0.005 and were considered as driving under the influence (DUI) of alcohol. Meanwhile, driving while intoxicated (DWI) was defined as a BAC ≥0.05, which was the level adopted in the new law. RESULTS: Since the BAC limit lowered to 0.03, the number of DUI patients significantly decreased from 340 (12.4%) to 171 (7.1%), and that of DWI patients significantly reduced from 273 (10.0%) to 146 (6.1%) based on the alcohol test. In addition, after the implementation of the law, the number of associated injuries did not significantly decrease from that before the law was implemented in patients involved in alcohol-related crashes. CONCLUSION: After lowering the legal BAC limit from 0.05 to 0.03, responsiveness to the change in law was observed among the studied population. However, such responsiveness may not be observed in some citizens who may need special interventions to help reduce their behavior of drinking and driving.

Association of Stress-Induced Hyperglycemia and Diabetic Hyperglycemia with Mortality in Patients with Traumatic Brain Injury: Analysis of a Propensity Score-Matched Population.

Background: Hyperglycemia at the time of hospital admission is associated with higher morbidity and mortality rates in patients with traumatic brain injury (TBI). Using data from the Chang Gung Research Database (CGRD), this study aimed to compare mortality outcomes between patients with stress-induced hyperglycemia (SIH), diabetic hyperglycemia (DH), and nondiabetic normoglycemia (NDN). The study occurred at Keelung, Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals (CGMHs). Methods: A total of 1166, 6318, 3622, and 5599 health records from Keelung, Linkou, Chiayi, and Kaohsiung CGMHs, respectively, were retrieved from the CGRD for hospitalized patients with TBI between January 2001 and December 2015. After propensity score matching for sex, age, and Glasgow Coma Scale (GCS) score, the matched cohorts were compared to evaluate differences in the primary outcome between patients with SIH, DH, and NDN. In-hospital mortality was the primary outcome. Results: The analysis of matched patient populations revealed that at the Kaohsiung CGMH, patients with SIH had 1.63-fold (95% CI: 1.09-2.44; p = 0.017) and 1.91-fold (95% CI: 1.12-3.23; p = 0.017) higher odds of mortality than patients with NDN and DH, respectively. Similar patterns were found at the Linkou CGMH; patients with SIH had higher odds of mortality than patients with NDN and DH. In contrast, at the Keelung CGMH, patients with SIH had significantly higher odds of mortality than those with NDN (OR: 3.25; 95% CI: 1.06-9.97; p = 0.039). At the Chiayi CGMH, there were no significant differences in mortality rates among all groups. Conclusions: This study's results suggest that SIH and DH differ in their effect on the outcomes of patients with TBI. The results were similar between medical centers but not nonmedical centers; in the medical centers, patients with SIH had significantly higher odds of mortality than patients with either NDN or DH.

Effect of Height of Fall on Mortality in Patients with Fall Accidents: A Retrospective Cross-Sectional Study.

BACKGROUND: Accidental falls are a common cause of injury and deaths. Both ground-level falls (GLF) and non-GLF may lead to significant morbidity or mortality. This study aimed to explore the relationship between height of falls and mortality. METHOD: This is a retrospective study based on the data from a registered trauma database and included 8699 adult patients who were hospitalized between 1 January 2009 and 31 December 2017 for the treatment of fall-related injuries. Study subjects were divided into three groups of two categories based on the height of fall: GLF (group I: < 1 m) and non-GLF (group II: 1-6 m and group III: > 6 m). The primary outcome was in-hospital mortality. The adjusted odds ratio (AOR) of mortality adjusted for age, sex, and comorbidities with or without an injury severity score (ISS) was calculated using multiple logistic regression. RESULTS: Among the 7001 patients in group I, 1588 in group II, and 110 in group III, patients in the GLF group were older, predominantly female, had less intentional injuries, and had more pre-existing comorbidities than those in the non-GLF group. The patients in the non-GLF group had a significantly lower Glasgow Coma Scale (GCS), a higher injury severity score (ISS), worse physiological responses, and required more procedures performed in the emergency department. The mortality rate for the patients in group I, II, and III were 2.5%, 3.5%, and 5.5%, respectively. After adjustment by age, sex, and comorbidities, group II and group III patients had significantly higher adjusted odds of mortality than group I patients (AOR 2.2, 95% CI 1.64-2.89, p < 0.001 and AOR 2.5, 95% CI 1.84-3.38, p < 0.001, respectively). With additional adjustment by ISS, group II did not have significantly higher adjusted odds of mortality than group I patients (AOR 1.4, 95% CI 0.95-2.22, p = 0.082), but group III patients still had significantly higher adjusted odds of mortality than group I patients (AOR 10.0, 95% CI 2.22-33.33, p = 0.002). CONCLUSION: This study suggested that patients who sustained GLF and non-GLF were distinct groups of patients, and the height of fall did have an impact on mortality in patients of fall accidents. A significantly higher adjusted odds of mortality was found in the GLF group than in the non-GLF group after adjusting for age, sex, and comorbidities.

Impact of Adapting the Abbreviated Injury Scale (AIS)-2005 from AIS-1998 on Injury Severity Scores and Clinical Outcome.

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.

Concurrent Types of Intracranial Hemorrhage are Associated with a Higher Mortality Rate in Adult Patients with Traumatic Subarachnoid Hemorrhage: A Cross-Sectional Retrospective Study.

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.

Impact of stress-induced hyperglycemia on the outcome of children with trauma: A cross-sectional analysis based on propensity score-matched population.

This was a retrospective study of pediatric trauma patients and were hospitalized in a level-1 trauma center from January 1, 2009 to December 31, 2016. Stress-induced hyperglycemia (SIH) was defined as a hyperglycemia level ≥200 mg/dL upon arrival at the emergency department without any history of diabetes or a hemoglobin A1c level ≥6.5% upon arrival or during the first month of admission. The results demonstrated that the patients with SIH (n = 36) had a significantly longer length of stay (LOS) in hospital (16.4 vs. 7.8 days, p = 0.002), higher rates of intensive care unit (ICU) admission (55.6% vs. 20.9%, p < 0.001), and higher in-hospital mortality rates (5.6% vs. 0.6%, p = 0.028) compared with those with non-diabetic normoglycemia (NDN). However, in the 24-pair well-balanced propensity score-matched patient populations, in which significant difference in sex, age, and injury severity score were eliminated, patient outcomes in terms of LOS in hospital, rate of ICU admission, and in-hospital mortality rate were not significantly different between the patients with SIH and NDN. The different baseline characteristics of the patients, particularly injury severity, may be associated with poorer outcomes in pediatric trauma patients with SIH compared with those with NDN. This study also indicated that, upon major trauma, the response of pediatric patients with SIH is different from that of adult patients.

Higher Mortality Rate in Moderate-to-Severe Thoracoabdominal Injury Patients with Admission Hyperglycemia Than Nondiabetic Normoglycemic Patients.

BACKGROUND: Hyperglycemia at admission is associated with an increase in worse outcomes in trauma patients. However, admission hyperglycemia is not only due to diabetic hyperglycemia (DH), but also stress-induced hyperglycemia (SIH). This study was designed to evaluate the mortality rates between adult moderate-to-severe thoracoabdominal injury patients with admission hyperglycemia as DH or SIH and in patients with nondiabetic normoglycemia (NDN) at a level 1 trauma center. METHODS: Patients with a glucose level ≥200 mg/dL upon arrival at the hospital emergency department were diagnosed with admission hyperglycemia. Diabetes mellitus (DM) was diagnosed when patients had an admission glycohemoglobin A1c ≥6.5% or had a past history of DM. Admission hyperglycemia related to DH and SIH was diagnosed in patients with and without DM. Patients who had a thoracoabdominal Abbreviated Injury Scale score <3, a polytrauma, a burn injury and were below 20 years of age were excluded. A total of 52 patients with SIH, 79 patients with DH, and 621 patients with NDN were included from the registered trauma database between 1 January 2009, and 31 December 2018. To reduce the confounding effects of sex, age, comorbidities, and injury severity of patients in assessing the mortality rate, different 1:1 propensity score-matched patient populations were established to assess the impact of admission hyperglycemia (SIH or DH) vs. NDN, as well as SIH vs. DH, on the outcomes. RESULTS: DH was significantly more frequent in older patients (61.4 ± 13.7 vs. 49.8 ± 17.2 years, p < 0.001) and in patients with higher incidences of preexisting hypertension (2.5% vs. 0.3%, p < 0.001) and congestive heart failure (3.8% vs. 1.9%, p = 0.014) than NDN. On the contrary, SIH had a higher injury severity score (median [Q1-Q3], 20 [15-22] vs. 13 [10-18], p < 0.001) than DH. In matched patient populations, patients with either SIH or DH had a significantly higher mortality rate than NDN patients (10.6% vs. 0.0%, p = 0.022, and 5.3% vs. 0.0%, p = 0.043, respectively). However, the mortality rate was insignificantly different between SIH and DH (11.4% vs. 8.6%, odds ratio, 1.4; 95% confidence interval, 0.29-6.66; p = 0.690). CONCLUSION: This study revealed that admission hyperglycemia in the patients with thoracoabdominal injuries had a higher mortality rate than NDN patients with or without adjusting the differences in patient's age, sex, comorbidities, and injury severity.

Machine Learning Models of Survival Prediction in Trauma Patients.

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.

Risk Factors Contributing to Higher Mortality Rates in Elderly Patients with Acute Traumatic Subdural Hematoma Sustained in a Fall: A Cross-Sectional Analysis Using Registered Trauma Data.

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.