Ovatodiolide and antrocin synergistically inhibit the stemness and metastatic potential of hepatocellular carcinoma via impairing ribosome biogenesis and modulating ERK/Akt-mTOR signaling axis.

Activation of mitogen-activated protein kinase (MAPK) and PI3K signaling confers resistance against sorafenib, a mainstay treatment for advanced hepatocellular carcinoma (HCC). Antrocin and ovatodiolide constitute as the most potent secondary metabolites isolated from Antrodia camphorata and Anisomeles indica, respectively. Both natural compounds have recently gained a lot of attention due to their putative inhibition of MAPK and PI3K signaling in various solid cancers. However, whether their combination is effective in HCC remains unknown. Here, we investigated their effect, alone or in various combinations, on MAPK and PI3K signaling pathways in HCC cells. An array of in vitro study were used to investigate anticancer and stemness effects to treat HCC, such as cytotoxicity, drug combination index, migration, invasion, colony formation, and tumor sphere formation. Drug effect in vivo was evaluated using mouse xenograft models. In this study, antrocin and ovatodiolide synergistically inhibited the SNU387, Hep3B, Mahlavu, and Huh7 cell lines. Sequential combination treatment of Huh7 and Mahlavu with ovatodiolide followed by antrocin resulted stronger cytotoxic effect than did treatment with antrocin followed by ovatodiolide, their simultaneous administration, antrocin alone, or ovatodiolide alone. In the Huh7 and Mahlavu cell lines, ovatodiolide→antrocin significantly suppressed colony formation and proliferation as well as markedly downregulated ERK1/2, Akt, and mTOR expression. Inhibition of ERK1/2 and Akt/mTOR signaling by ovatodiolide→antrocin suppressed ribosomal biogenesis, autophagy, and cancer stem cell-like phenotypes and promoted apoptosis in Huh7 and Mahlavu cells. The sorafenib-resistant clone of Huh7 was effectively inhibited by synergistic combination of both compound in vitro. Eventually, the ovatodiolide→antrocin combination synergistically suppressed the growth of HCC xenografts. Taken together, our findings suggested that ovatodiolide→antrocin combination may represent potential therapeutic approach for patients with advanced HCC.

Cancer-Associated Exosomal CBFB Facilitates the Aggressive Phenotype, Evasion of Oxidative Stress, and Preferential Predisposition to Bone Prometastatic Factor of Breast Cancer Progression.

Background: Despite therapeutic advancements, metastasis remains a major cause in breast cancer-specific mortality. Breast cancer cells are susceptible to oxidative damage and exhibit high levels of oxidative stress, including protein damage, DNA damage, and lipid peroxidation. Some breast cancer risk factors may change the level of endogenous oxidative stress. Circulating exosomes play critical roles in tumorigenesis, distant metastasis, and poor prognosis in patients with breast cancer. Methods: We used an online database to analyze the expression and prognostic value of core binding factor subunit ß (CBFB) and oxidative stress-related targets in patients with breast cancer. Serum from healthy controls and patients with primary breast cancer or bone metastatic breast cancer in the bone was collected. Exosomes were isolated from the sera or cell culture media. We used an MDA-MB-436-innoculated tumor xenograft mouse model for silencing CBFB. Results: Circulating exosomes from patients with breast cancer metastasis to the bone were rich in CBFB. The human mammary fibroblast cells HMF3A and fibroblasts derived from patient samples cocultured with exosomes had increased α-SMA and vimentin expression and IL-6 and OPN secretion. Similarly, nonmetastatic breast cancer cells cocultured with exosomes exhibited increased levels of certain markers, including vimentin, snail1, CXCR4, and Runx2, and the exosomes had high CBFB expression. Silencing CBFB in metastatic MDA-MB-436 and MDA-MB-157 cells resulted in suppressed migration and invasion and downregulation of vimentin, CXCR4, snail1, Runx2, CD44, and OPN. Conversely, CBFB overexpression resulted in upregulation of Runx2, vimentin, snail1, CD44, and OPN in nonmetastatic T47D and MCF12A cells. The CBFB-rich exosomes derived from MDA-MB-436 cells induced enhanced metastatic phenotypes in the low-metastatic T47D and MCF12A cell lines. Conclusion: Our results revealed that CBFB may promote bone metastasis in patients with breast cancer. Of therapeutic relevance, targeting CBFB resulted in decreased tumor burden and bone metastasis, downregulation of bone metastasis markers, and impaired regulation of oxidative stress-related proteins NAE1 and NOS1.

Early versus delayed feeding after therapeutic endoscopic procedures: Meta-analysis of randomized controlled trials.

INTRODUCTION: Early feeding was previously considered to increase the risk of postprocedural bleeding. However, many trials have demonstrated the benefits of early feeding after therapeutic endoscopic procedures. We conducted a meta-analysis of randomized controlled trials to evaluate the safety and outcomes between early feeding and delayed feeding after therapeutic endoscopic procedures. METHODS: Medline (PubMed), Embase, Google Scholar, the Cochrane Library, and clinicaltrials.gov were searched to identify randomized controlled trials that met our inclusion criteria. The pooled data for the mortality rate, postprocedural bleeding rate, and length of hospital stay were analyzed. RESULTS: A total of seven trials consisting of 717 patients were reviewed. These seven trials examined various therapeutic endoscopic procedures. Three trials included patients undergoing endoscopic hemostasis for upper gastrointestinal bleeding, two included patients undergoing esophageal variceal ligation, and two included patients with gastric neoplasm treated with endoscopic submucosal dissection. Although no significant differences were observed in the postprocedural bleeding rate or the mortality rate between patients who received early feeding and those who received delayed feeding, early feeding resulted in shorter hospital stays (weighted mean difference -1.04, 95% confidence interval -1.45 to 0.63). CONCLUSION: Early feeding appears to be a safe management method for patients undergoing therapeutic endoscopic procedures. Therefore, we recommend early feeding for these patients.

Screening for Poor Self-Reported Sleep Quality at 12 Weeks in Post-Mild Traumatic Brain Injury Patients Using the HF-Age-Gender (HAG) Index.

To identify a screening tool for poor self-reported sleep quality at 12 weeks according to non-invasive measurements and patients' characteristics in the first week after mild traumatic brain injury (mTBI), data from 473 mTBI participants were collected and follow-ups were performed at 12 weeks. Patients with previous poor self-reported sleep quality prior to the injury were excluded. Patients were then divided into two groups at 12 weeks according to the Pittsburgh Sleep Quality Index based on whether or not they experienced poor sleep quality. The analysis was performed on personal profiles and heart rate variability (HRV) for 1 week. After analyzing the non-invasive measurements and characteristics of mTBI patients who did not complain of poor sleep quality, several factors were found to be relevant to the delayed onset of poor sleep quality, including age, gender, and HRV measurements. The HRV-age-gender (HAG) index was proposed and found to have 100% sensitivity (cut-off, 7; specificity, 0.537) to predicting whether the patient will experience poor sleep quality after mTBI at the 12-week follow-up. The HAG index helps us to identify patients with mTBI who have no sleep quality complaints but are prone to developing poor self-reported sleep quality. Additional interventions to improve sleep quality would be important for these particular patients in the future.

Comparison of Dizziness Factors for Mild Traumatic Brain Injury Patients with and without Dizziness: A Factor Analysis and Propensity Score Model Study.

Traumatic brain injury (TBI) causes major socioeconomic problems worldwide. In the United States, nearly three-quarters of patients with TBI have mild TBI (mTBI). 32% of these patients may develop dizziness. In this study, we analyzed the factor structure of the traditional Chinese version of the DHI and evaluate the differences in DHI factors between dizziness and nondizziness groups. In total, 315 patients with mTBI, comprising 158 with self-reported dizziness and 157 without dizziness, were recruited from three hospitals. The responses for Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Epworth Sleepiness Scale (ESS), and Pittsburgh Sleep Quality Index (PSQI) demonstrated between-group differences. The Chinese DHI had internal validity and had four factors that differed from the English version (3 aspects). The group effects for the physical subscale remained significantly different even after adjustments in the propensity score model. For the Chinese version, two of four factors remained significantly different in the effects between self-reported dizziness and nondizziness groups. The factors of our Chinese DHI differed from those of the original English version of DHI. After adjustments using the propensity score model, the physical subscale demonstrated significant differences between the self-reported dizziness and nondizziness groups. Only two factors from our Chinese DHI were significantly different; moreover, it contained only three physical, five functional, and three emotional items.

Worsening of Dizziness Impairment Is Associated with Bone Marrow Kinase on Chromosome X Level in Patients after Mild Traumatic Brain Injury.

Over 2 million people suffer from mild traumatic brain injury (mTBI) each year. Predicting symptoms of mTBI and the characterization of those symptoms has been challenging. Biomarkers that correlate clinical symptoms to disease outcome are desired to improve understanding of the disease and optimize patient care. Bone marrow kinase on chromosome X (BMX), a member of the TEC family of nonreceptor tyrosine kinases, is up-regulated after traumatic neural injury in a rat model of mTBI. The aim of this investigation was to determine whether BMX serum concentrations can effectively be used to predict outcomes after mTBI in a clinical setting. A total of 63 patients with mTBI (Glasgow Coma Score [GCS] between 13 and 15) were included. Blood samples taken at the time of hospital admission were analyzed for BMX. Data collected included demographic and clinical variables. Outcomes were assessed using the Dizziness Handicap Inventory (DHI) questionnaire at baseline and 6 weeks postinjury. The participant was asssigned to the case group if the subject's complaints of dizziness became worse at the sixth week assessment; otherwise, the participant was assigned to the control group. A receiver operating characteristic curve was constructed to explore BMX level. Significant associations were found between serum levels of BMX and dizziness. Areas under the curve for prediction of change in DHI postinjury were 0.76 for total score, 0.69 for physical score, 0.65 for emotional score, and 0.66 for functional score. Specificities were between 0.69 and 0.77 for total score and emotional score, respectively. Therefore, BMX demonstrates potential as a candidate serum biomarker of exacerbating dizziness post-mTBI.

Risk Values of Weight and Body Mass Index for Chest Wall Thickness in Patients Requiring Needle Thoracostomy Decompression.

INTRODUCTION: Emergency decompression is needed in patients with tension pneumothorax, a life-threatening condition. The catheter-based needle thoracostomy was suggested using a 5 cm catheter inserted into the 2nd intercostal space (ICS) and 5th ICS according to the ninth and tenth editions of Advanced Trauma Life Support, respectively. A catheter of suitable length may not be available immediately or the muscle structure of the chest wall may be modified in pneumothorax. Furthermore, alternative sites for needle thoracostomy and reference values of chest wall thickness (CWT) should be explored and warranted. METHOD: CT scan data and medical data of 650 eligible patients from October 2016 to December 2016 were reviewed. CWT values at four ICSs as well as four variables, namely, age, weight, height, and body mass index (BMI) for both men and women were compared using a nonparametric method, namely, the Wilcoxon signed-rank test. The associations between CWT and the four variables were assessed using the Pearson correlation coefficient. The overall performance of BMI, weight, and height in predicting CWT > 5 cm was evaluated using the receiver-operating characteristic (ROC) curve. Finally, the prediction models were built by using the bootstrap method. RESULTS: Four variables, namely, age, height, weight, and BMI, were compared between the men and women groups. All four variables differed significantly between the two groups, and CWTs at all ICSs, except for the 3rd ICS, differed significantly between the two groups. Among the women, the area under the ROC curve (AUROC) of BMI for predicting CWT > 5 cm at 2nd ICS was larger than the AUROC of weight and height. Among the men, the AUROC of weight for predicting CWT > 5 cm at 2nd ICS was larger than that of BMI and height. The reference value tables were provided for five proposed models for women and men, respectively. Under emergencies, the variable, BMI, or even weight itself, could be used for predicting a failure performance of the needle decompression. For women, CWT at 5th ICS was predicted over 5 cm at BMI over 25.9 kg/m2 or weight over 103.1 kg. For men, CWT at 5th ICS was predicted over 5 cm at BMI over 25.5 kg/m2 or weight over 157.4 kg. CONCLUSION: Needle thoracostomy is the preferred first technique for many emergency providers for decompression. Therefore, a reference table for safe needle thoracostomy decompression at four usual sites, namely, 2nd ICS, 3rd CIS, 4th ICS, and 5th ICS, was recommended, which will enable paramedics and emergency specialists to rapidly determine CWT at the appropriate ICSs during emergencies.

Association between Sleep Deprivation in Caregivers and Risk of Injury among Toddlers: A Propensity Score Analysis.

INTRODUCTION: Unintentional injury remains the leading cause of death in children worldwide. Adequate parental supervision is a crucial strategy for preventing injury. Many factors, such as a large family size, poor socioeconomic status, and the caregiver being a single mother, contribute to unintentional injury in children. In addition, sleep deprivation in caregivers might be associated with injury in children because sleep deprivation causes impaired daytime cognitive function, wake-state instability, and negative moods, thereby impairing caregiver supervision. Therefore, this study determines the association between injury in children and the sleep quality of their primary caregivers. METHOD: This is a retrospective case-control study on unintentional injury in children aged 0 to 4 years who visited the emergency department (case group) and an age- and sex-matched control group. Sleep quality in caregivers was assessed using the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was used to evaluate the association between aspects of the PSQI and injury. A propensity score model was used to generate a quasirandomized design. RESULTS: This case-control study recruiting 277 injured and 274 noninjured children was conducted in Taiwan. There was no statistically significant difference in child's age and primary caregiver's age between the injured and noninjured groups. The primary outcome, Pittsburgh sleep quality index, was not significantly different between the two groups. The average scores of sleep duration and habitual sleep efficiency in the control group were higher than those in the case group. However, there was no difference between the two groups after adjusting via a propensity score model, including the following potential confounders, child's age, child's sex, number of previous injury, caregiver mental status, caregiver's sex and caregiver's age, and the number of children living together. CONCLUSION: Our study was the first to examine the association between injury in children and the sleep quality of their primary caregivers. We observed that no PSQI component significantly affected the risk of injury among children.

Development of a fall-risk assessment profile for community-dwelling older adults by using the National Health Interview Survey in Taiwan.

BACKGROUND: Falls represent a global health issue among older adults and cause a considerable burden on medical systems. In this study, a fall-risk assessment profile was developed for community-dwelling older adults. METHOD: The data of survey participants aged > 65 years were obtained from three rounds (2005, 2009, and 2013) of the National Health Interview Survey in Taiwan. In total, 8356 older participants were included in this study. Logistic regression analyses were used to determine potential predictors associated with falls. The regression coefficients of the predictors in the final model were translated into scores (by multiplying by 5) and then summed to obtain a total risk-score for falls. A receiver operating characteristic (ROC) curve was used to evaluate the discriminative performance of the risk assessment profile. RESULT: Self-reported falls within 1 year accounted for 19.1% of the total falls. The predictors that were included in the risk profile according to the logistic regression analysis results were as follows: female sex (adjusted odds ratio = 1.57; risk-score = 2), living alone (adjusted odds ratio = 1.56; risk-score = 2), urinary incontinence (adjusted odds ratio = 1.36; risk-score = 2), perceived unhealthiness (adjusted odds ratio = 1.32; risk-score = 1), perceived pain (adjusted odds ratio = 1.51; risk-score = 2), hospital admission in the past year (adjusted odds ratio = 2.42; risk-score = 4), low activity of daily living (ADL) scores (adjusted odds ratio = 1.29; risk-score = 1), and low mobility function scores (adjusted odds ratio = 1.68; risk-score = 3). At a total risk-score cutoff point of 6 (range 0-17), the model predicted falls with a sensitivity and specificity of 75.16 and 52.75%, respectively (area under the ROC curve = 0.70). CONCLUSION: The fall-risk assessment profile comprising eight predictors-female sex, living alone, incontinence, perceived unhealthiness, perceived pain, hospital admission in the past year, low ADL scores, and low mobility function scores-may serve as an assessment tool for identification of older adults with a high risk of falling, and assessment results can be used to facilitate community-based intervention.

Walking against or with traffic? Evaluating pedestrian fatalities and head injuries in Taiwan.

BACKGROUND: Allowing contraflow cycling on one-way streets has been reported to reduce crash risks in Belgium and the United Kingdom. Similarly, walking against traffic on roadways without sidewalks substantially improves pedestrian safety. This study examined fatalities and head injuries sustained by pedestrians in against-traffic and with-traffic crashes. METHODS: Using police-reported crash data in Taiwan between 2011 and 2016, fatalities and head injuries were compared for pedestrians involved in against-traffic and with-traffic crashes. RESULTS: Of the 14,382 pedestrians involved in crashes, 10,749 and 3633 pedestrians in with-traffic and against-traffic crashes, respectively, were reported. Compared with pedestrians involved in against-traffic crashes, those in with-traffic crashes were more likely to sustain fatalities and head injuries. Results of logistic regression models revealed several influential factors on pedestrian fatalities and head injuries, including elderly pedestrians, male drivers, intoxicated drivers, rural roadways, unlit streets in darkness, limited sight distance, adverse weather conditions, midnight hours, and a heavy vehicle as the crash partner. CONCLUSIONS: Pedestrians in with-traffic crashes were more likely to sustain fatalities and head injuries compared with those in against-traffic crashes. Furthermore, the negative effect of walking with traffic on injuries was more pronounced in reduced-visibility conditions.

Population-based case-control study of the effect of sun glare on pedestrian fatalities in Taiwan.

OBJECTIVES: Sun glare is a serious driving hazard and increases crash risks. Relatively few studies have examined the effects of sun glare on pedestrian fatalities, given that a crash has occurred. The primary objective of this study was to investigate the effect of sun glare on pedestrian fatalities. DESIGN: A population-based case-control study. SETTING: Taiwan. PARTICIPANTS: Using the Taiwan National Traffic Crash Data and sunrise and sunset data from the National Oceanic and Atmospheric Administration for the period 2003 to 2016, 100 411 pedestrians involved in crashes were identified. Of these crashes, 13 355 and 87 056 were glare-related (case) and non-glare-related (control) crashes, respectively. METHODS: To account for unobserved heterogeneity, mixed logit models were estimated to identify the determinants of pedestrian fatalities. MAIN OUTCOME MEASURES: Pedestrian fatalities. RESULTS: Pedestrians involved in glare-related crashes were more likely to be fatally injured than those in non-glare-related crashes (ß=0.527; t=3.21). Other contributory factors to fatal injuries among pedestrians were older pedestrians (ß=0.553; t=2.33), male drivers (ß=0.324; t=2.33), older drivers (ß=0.218; t=2.14), intoxicated motorists (ß=0.606; t=2.85), rural roadways (ß=0.985; t=3.92), overtaking manoeuvres (ß=0.472; t=3.58), heavy vehicle crash partners (ß=0.248; t=2.78) and sunset hours (ß=0.274; t=3.08). Walking against traffic appeared beneficial for decreasing injury severity (ß=-0.304; t=-2.76). CONCLUSIONS: Sun glare is associated with pedestrian fatalities. Older pedestrians, male drivers, older drivers and intoxicated motorists are prevalent determinants of pedestrian fatalities in glare-related crashes.

Collagen 1A1 (COL1A1) Is a Reliable Biomarker and Putative Therapeutic Target for Hepatocellular Carcinogenesis and Metastasis.

Increasing evidence shows that hepatocellular carcinoma (HCC) is a principal cause of cancer-related mortality globally, especially among Asian and African populations. Collagen type I α1 (COL1A1) is the major component of type I collagen. While aberrant expression of COL1A1 and COL1A2 is implicated in numerous cancers, the differential role of COL1A1 in malignant, premalignant and normal tissues remains unclear, and its clinical significance in HCC has not been elucidated. In this study, using bioinformatics analysis of publicly-available HCC microarray data from Gene Expression Omnibus (GEO) and RNAseq data from The Cancer Genome Atlas (TCGA) database, we determined that COL1A1 is significantly upregulated in HCC tumor tissues in comparison to normal tissues. Our analysis also revealed that COL1A1 confers survival advantage and enhanced oncogenicity on HCC cells. Interestingly, the siRNA-mediated silencing of COL1A1 expression (siCOLIA1) suppressed HCC cells clonogenicity, motility, invasiveness and tumorsphere formation. Concomitantly, siCOL1A1 abrogated Slug-dependent epithelial-to-mesenchymal transition (EMT) and HCC stemness gene-signature, by attenuating expression of stemness markers SOX2, OCT4 and CD133. The present study provides some mechanistic insight into COL1A1 activity in HCC and highlights its putative role as an important diagnostic biomarker and potential therapeutic target in early development and metastasis of HCC.

Psychometric Evaluation of Anxiety, Depression, and Sleep Quality after a Mild Traumatic Brain Injury: A Longitudinal Study.

Introduction. Over 1 million mild traumatic brain injury (mTBI) cases are reported annually worldwide and may result in cognitive, physical, and emotional deterioration; depression; anxiety; and sleep problems. However, studies on long-term mTBI effects are limited. This study included 440 patients, and regular follow-ups of psychological assessments were performed for 2 years. Four questionnaires, including the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), Beck's anxiety inventory (BAI), and Beck's depression inventory (BDI), were used to evaluate sleep problems, daytime sleepiness, anxiety, and depression, respectively. Results show that BAI and BDI scores considerably improved at the 6th-week, 1st-year, and 2nd-year follow-ups compared to baseline, yet these remained significantly different. In addition, anxiety and depression were prominent symptoms in a select subgroup of patients with poor initial evaluations, which improved over the 2 years. However, the ESS and PSQI scores fluctuated only mildly over the same time span. In conclusion, the mTBI patients showed a gradual improvement of anxiety and depression over the 2 years following injury. While anxiety and depression levels for mTBI patients in general did not return to premorbid status, improvements were observed. Sleep disorders persisted and were consistent with initial levels of distress.

Correction: Increased long-term risk of major adverse cardiovascular events in patients with carbon monoxide poisoning: A population-based study in Taiwan.

[This corrects the article DOI: 10.1371/journal.pone.0176465.].

Training or Battling a Monster of a Location-Based Augmented-Reality Game While Descending Stairs: An Observational Study of Inattentional Blindness and Deafness and Risk-Taking Inclinations.

Several emerging smartphone location-based augmented-reality (AR) games require three primary tasks: training or battling a monster, capturing a monster, and searching for a monster, which involve different levels of perceptual load. Using the AR game originated from Japan as a single case study, this study examined inattentional blindness and deafness and risk-taking inclinations among participants concurrently descending stairs and engaging in these three tasks. Participants descending stairs in Taipei Medical University were observed through recordings obtained from Wi-Fi cameras to determine whether they engaged in risk-taking behaviors such as hopping, not using the handrail, and stopping suddenly. After the participants descended the stairs, they were interviewed to obtain additional information regarding demographics, game tasks (training or battling a monster, capturing a monster, or searching for a monster), data plan, and screen size. Inattentional blindness and deafness were investigated by determining whether participants saw something unusual, a police ascending the stairs, and heard the national anthem played by the police, respectively. In total, 1036 participants descended the stairs and underwent the interview between August 2016 and July 2018. Logistic regression models revealed that training or battling a monster was most associated with inattentional blindness, deafness, not using the handrail, and stopping suddenly, whereas hopping behavior was the commonest among those capturing a monster. Other contributory factors include a large smartphone screen (≥5 in), unlimited mobile data, being an undergraduate student, and an increase in the daily gaming hours. Development of smartphone apps toward detection of stair locomotion may be beneficial for curbing phone use in general and AR game playing in particular.

Association Between Acid-Sensing Ion Channel 3 Gene Variants and Balance Impairment in People With Mild Traumatic Brain Injury.

Introduction: Dizziness and balance impairment are common symptoms of mild traumatic brain injury (mTBI). Acid-sensing ion channel 3 (ASIC3) is expressed in the vestibular and proprioceptive systems and associated with balance functions. However, whether the genetic variants of ASIC3 are associated with people who suffer dizziness and balance impairment after mTBI remained unknown. Materials and methods: A total of 200 people with mTBI and 109 non-mTBI controls were recruited. Dizziness, balance functions, and the ability to perform daily activities were assessed by Dizziness Handicap Inventory (DHI), and objective balance functions were investigated by the postural stability test. Three diseases-related genetic variants of ASIC3 were determined through polymerase chain reaction and followed by restriction fragment length polymorphism. The Student's t-test and Mann-Whitney U-test were used for normal and abnormal distributed data, respectively. The regression was applied to adjust gender and age. The normality of continuous data was evaluated by Shapiro-Wilk test. Results: In the mTBI people, the rs2288645-A allele carriers exhibited a significantly worse physical domain DHI score (A-allele carriers: 11.39 ± 8.42, non-A carriers: 8.76 ± 7.87, p = 0.03). The rs4148855-GTC deletion carriers an exhibited significantly worse overall postural stability (GTC deletion carriers: 0.53 ± 0.33, non-carriers: 0.46 ± 0.20, p = 0.03). In the controls, rs2288646-A allele carriers were significant worse in the medial-to-lateral postural stability (A-allele carriers: 0.31 ± 0.17, non-A carriers: 0.21 ± 0.10, p = 0.01). Conclusion: The present study demonstrated that ASIC3 genetic variants were associated with certain aspects of balance functions and dizziness questionnaires in people of mTBI and non-mTBI. It provides a possible evidence that ASIC3 could be a new target for the management of the balancing disorders. However, further investigations are warranted to elucidate the underlying mechanisms and clinical significance.

Characteristics and outcomes of "Do Not Resuscitate" patients admitted to the emergency department-Intensive care unit.

BACKGROUND: Appropriate utilization of intensive care unit (ICU) beds are essential. Patients with critical illness who have do not resuscitate (DNR) have a reduced priority of intensive care. However, the possibility of recovery/survival is ambiguous and multifactorial. OBJECTIVE: To deliberate the characteristics and outcomes of critical illness in patients with prior DNR who were admitted to the emergency department (ED)-ICU. METHOD: This was a retrospective cohort study conducted between April 2015 and November 2015 in a university-based hospital. Non-traumatic patients with DNR admitted to ED-ICU from ED were included. RESULTS: Seventy-eight non-trauma patients with prior DNR status were included in the final analysis. 51.3% (40/78) patients were male with median age 83 (IQR: 75-89) years. The median APACHE II score was 24.5 (IQR: 20-30). 50% (39/78) of the DNR patients survived to discharge. Patients who survived to discharge had lower APACHE II score (23 (IQR: 20-28) vs. 28 (18-38), p = 0.028). There was no significant difference in age, gender, and Charlson index. ROC curves were constructed, generating a cut-off of the APACHE II score at 29.5 for determining survival to discharge (AUC = 0.644, p = 0.028). In multivariate Cox proportional model, APACHE II score above 29.5 was an independent predictor for mortality. (Hazard ratio = 2.46; 95% confidence interval: 1.04-5.83, p = 0.042). CONCLUSION: Our study found that 50% of patients with prior DNR on ICU admission survived to discharge, indicating that aggressive care is not definitely futile. Further prospective studies are required to evaluate the cost-effectiveness and patients' and/or families' satisfaction of the ICU admission of DNR patients.

Incidences of Hypothyroidism Associated With Surgical Procedures for Thyroid Disorders: A Nationwide Population-Based Study.

Background and Aim: Limited information available about different types of thyroid surgeries with risk for postoperative hypothyroidism. This study aimed to investigate the risk of developing early and late-onset postoperative hypothyroidism in patients with thyroid disorders. Methods: We used a large cohort data from the Taiwan National Health Insurance Research Data Base (NHIRDB) and identified 9,693 (9, 348) patients from January 1998 to December 2010, admitted for thyroid disorder surgeries. We used the surgical procedures time as the index date. Our observational retrospective cohort study excluded the subjects diagnosed with hypoparathyroidism and hypothyroidism before any surgeries. We analyzed the data using the Cox regression model to calculate the hazard ratio. Result: Postoperative hypothyroidism associated with bilateral-total (HR, 4.27; 95% CI, 3.32-5.50), one-side total and another subtotal (HR, 3.16; 95% CI, 2.59-3.86), bilateral-subtotal (HR, 1.65; 95% CI, 1.37-1.98), and unilateral-total (HR, 1.17; 95% CI, 0.95-1.44) surgical procedures. The time intervals for thyroid disorders were 320 cases developed postoperative hypoparathyroidism in eight weeks, 480 cases the second month, and 1000 cases in the first year after surgery. Conclusion: Findings suggest that thyroidectomy was associated with transient postoperative hypothyroidism in thyroid disorder patients. The bilateral-total surgical procedure was strongly associated with temporary postoperative hypothyroidism.

Emergency Tracheal Intubation in an Ankylosing Spondylitis Patient in a Sitting Position Using an Airway Scope Combined with Face-to-Face and Digital Intubation.

BACKGROUND: Emergency intubation in a patient with advanced ankylosing spondylitis (AS) who presents with severe thoracic kyphosis deformity, rigid cervical flexion deformity of the neck, and an inability to achieve the supine position is particularly challenging to emergency physicians. CASE REPORT: This study reports on an AS patient presenting with these difficult airway characteristics and acute respiratory failure who was successfully intubated using video laryngoscope-assisted inverse intubation (II) and blind digital intubation (BDI). By using Pentax AirwayScope-assisted inverse intubation, the tracheal tube tip was passed through the glottic opening, but an unexpected resistance occurred during tube advancement, which was overcome by subsequent BDI. By using laryngoscope-assisted II complemented by the BDI technique, the patient was successfully intubated without complications. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case demonstrated that these two emergency airway management techniques are valuable backup methods and complement each other when applied to certain unstable airways, especially when the traditional patient position is not easily accomplished. Unexpected difficulty is not rare during airway management; emergency physicians should always be well prepared both mentally and practically.

Red blood cell distribution width is associated with mortality in elderly patients with sepsis.

INTRODUCTION: RDW is a prognostic biomarker and associated with mortality in cardiovascular disease, stroke and metabolic syndrome. For elderly patients, malnutrition and multiple comorbidities exist, which could affect the discrimination ability of RDW in sepsis. The main purpose of our study was to evaluate the prognostic value of RDW in sepsis among elderly patients. METHODS: This was a retrospective cohort study conducted in emergency department intensive care units (ED-ICU) between April 2015 and November 2015. Elderly patients (≥65years old) who were admitted to the ED-ICU with a diagnosis of severe sepsis and/or septic shock were included. The demographic data, biochemistry data, qSOFA, and APACHE II score were compared between survivors and nonsurvivors. RESULTS: A total of 117 patients was included with mean age 81.5±8.3years old. The mean APACHE II score was 21.9±7.1. In the multivariate Cox proportional hazards model, RDW level was an independent variable for mortality (hazard ratio: 1.18 [1.03-1.35] for each 1% increase in RDW, p=0.019), after adjusting for CCI, any diagnosed malignancy, and eGFR. The AUC of RDW in predicting mortality was 0.63 (95% confidence interval [CI]: 0.52-0.74, p=0.025). In subgroup analysis, for qSOFA <2, nonsurvivors had higher RDW levels than survivors (17.0±3.3 vs. 15.3±1.4%, p=0.044). CONCLUSIONS: In our study, RDW was an independent predictor of in-hospital mortality in elderly patients with sepsis. For qSOFA scores <2, higher RDW levels were associated with poor prognosis. RDW could be a potential parameter used alongside the clinical prediction rules.