PEAL Score to Predict the Mortality Risk of Cardiogenic Shock in the Emergency Department: An Observational Study.

BACKGROUND: The in-hospital mortality of cardiogenic shock (CS) remains high (28% to 45%). As a result, several studies developed prediction models to assess the mortality risk and provide guidance on treatment, including CardShock and IABP-SHOCK II scores, which performed modestly in external validation studies, reflecting the heterogeneity of the CS populations. Few articles established predictive scores of CS based on Asian people with a higher burden of comorbidities than Caucasians. We aimed to describe the clinical characteristics of a contemporary Asian population with CS, identify risk factors, and develop a predictive scoring model. METHODS: A retrospective observational study was conducted between 2014 and 2019 to collect the patients who presented with all-cause CS in the emergency department of a single medical center in Taiwan. We divided patients into subgroups of CS related to acute myocardial infarction (AMI-CS) or heart failure (HF-CS). The outcome was all-cause 30-day mortality. We built the prediction model based on the hazard ratio of significant variables, and the cutoff point of each predictor was determined using the Youden index. We also assessed the discrimination ability of the risk score using the area under a receiver operating characteristic curve. RESULTS: We enrolled 225 patients with CS. One hundred and seven patients (47.6%) were due to AMI-CS, and ninety-eight patients among them received reperfusion therapy. Forty-nine patients (21.8%) eventually died within 30 days. Fifty-three patients (23.55%) presented with platelet counts < 155 × 103/µL, which were negatively associated with a 30-day mortality of CS in the restrictive cubic spline plot, even within the normal range of platelet counts. We identified four predictors: platelet counts < 200 × 103/µL (HR 2.574, 95% CI 1.379-4.805, p = 0.003), left ventricular ejection fraction (LVEF) < 40% (HR 2.613, 95% CI 1.020-6.692, p = 0.045), age > 71 years (HR 2.452, 95% CI 1.327-4.531, p = 0.004), and lactate > 2.7 mmol/L (HR 1.967, 95% CI 1.069-3.620, p = 0.030). The risk score ended with a maximum of 5 points and showed an AUC (95% CI) of 0.774 (0.705-0.843) for all patients, 0.781 (0.678-0.883), and 0.759 (0.662-0.855) for AMI-CS and HF-CS sub-groups, respectively, all p < 0.001. CONCLUSIONS: Based on four parameters, platelet counts, LVEF, age, and lactate (PEAL), this model showed a good predictive performance for all-cause mortality at 30 days in the all patients, AMI-CS, and HF-CS subgroups. The restrictive cubic spline plot showed a significantly negative correlation between initial platelet counts and 30-day mortality risk in the AMI-CS and HF-CS subgroups.

Analyzing Financial Efficiency of Public-Private Partnerships Hospitals in Taiwan.

This study evaluates the management capacity ability and profitable capacity of eight public-private partnership hospitals in Taiwan from 2015 to 2020. By conducting various ratio analyses of the financial statement, this study found these hospitals have achieved a balance between management efficiency and profitability, thereby confirming the viability of the PPP model for hospital management. In addition, the subject hospitals play a vital role as isolation hospitals during the COVID-19 pandemic. Beyond offering medical assistance to infected individuals, these hospitals contribute to the integrity of Taiwan's medical network, mitigating the impact of the pandemic. Overall, establishing and managing hospitals with PPP partnership is a feasible solution as it alleviates governmental financial burdens related to medical welfare and achieves profitability.

Predictive Performance of Scoring Systems for Mortality Risk in Patients with Cryptococcemia: An Observational Study.

Cryptococcal infection is usually diagnosed in immunocompromised individuals and those with meningeal involvement, accounting for most cryptococcosis. Cryptococcemia indicates a poor prognosis and prolongs the course of treatment. We use the scoring systems to predict the mortality risk of cryptococcal fungemia. This was a single hospital-based retrospective study on patients diagnosed with cryptococcal fungemia confirmed by at least one blood culture collected from the emergency department covering January 2012 and December 2020 from electronic medical records in the Taichung Veterans General Hospital. We enrolled 42 patients, including 28 (66.7%) males and 14 (33.3%) females with a mean age of 63.0 ± 19.7 years. The hospital stay ranged from 1 to 170 days (a mean stay of 44.4 days), and the overall mortality rate was 64.3% (27/42). In univariate analysis, the AUC of ROC for MEWS, RAPS, qSOFA, MEWS plus GCS, REMS, NEWS, and MEDS showed 0.833, 0.842, 0.848, 0.846, 0.846, 0.878, and 0.905. In the multivariate Cox regression analysis, all scoring systems, older age, lactate, MAP, and DBP, indicated significant differences between survivor and non-survivor groups. Our results show that all scoring systems could apply in predicting the outcome of patients with cryptococcal fungemia, and the MEDS displays the best performance. We recommend a further large-scale prospective study for patients with cryptococcal fungemia.

Risk Stratification for Hepatitis B Virus Reactivation in Kidney Transplant Recipients With Resolved HBV Infection.

The prophylaxis strategy for hepatitis B virus (HBV) reactivation in kidney transplant recipients (KTRs) with resolved HBV infection remains unclear. In this hospital-based retrospective cohort study, consecutive KTRs with resolved HBV infection were screened from the years 2000 through 2020. After excluding confounding conditions, 212 and 45 patients were respectively recruited into Anti-HBs positive and Anti-HBs negative groups. Cumulative incidences of, and subdistribution hazard ratios (SHRs) for HBV reactivation were analyzed after adjusting the competing risk. During a median 8.3 (mean 8.4 ± 4.9) years of follow-up, the 10-year cumulative incidence of HBV reactivation was significantly higher in Anti-HBs negative group when compared to that in Anti-HBs positive group (15.2%, 95% CI: 3.6-26.7 vs. 1.3%, 95% CI: 0.0-3.0; p < 0.001). In multivariable regression analysis, absence of anti-HBs (SHR 14.2, 95% CI: 3.09-65.2; p < 0.001) and use of high-dose steroids, i.e., steroid dose ≥20 mg/day of prednisolone equivalent over 4 weeks (SHR 8.96, 95% CI: 1.05-76.2; p = 0.045) were independent risk factors related to HBV reactivation. Accordingly, the 10-year cumulative incidence of HBV reactivation occurring in patients with two, one and zero risk factors was 42.7% (95% CI: 0.0-87.1), 7.9% (95% CI: 1.2-14.7) and 0%, respectively (p < 0.001). In conclusion, the strategy of HBV antiviral prophylaxis may be defined according to the risk stratification.

Educational Videos to Reduce Parental Rejection of Pediatric Cardiac Catheterization during the COVID-19 Pandemic.

During the COVID-19 pandemic, people voluntarily reduced their necessary healthcare. We examined whether supplying educational digital versatile discs (DVDs) before admission can reduce parental rejection of pediatric cardiac catheterization for congenital heart disease (CHD). Parents of 70 children with CHD selected for cardiac catheterization were randomly allocated to the DVD (received pre-admission DVDs in the outpatient department; 70 parents of 35 children) or non-DVD groups (did not receive the DVDs; 70 parents of 35 children). The parents could reject the admission of their children within 7 days. Cardiac catheterization was rejected by 14 (20.0%) and 26 (37.1%) parents in the DVD and non-DVD groups, respectively (p = 0.025). Parent Perceptions of Uncertainty Scale scores were lower in the DVD (128.3 ± 8.9 points) than in the non-DVD group (134.1 ± 7.3 points; p < 0.001). Decreased uncertainty due to pre-admission DVD watching could have contributed to the increased parental willingness for cardiac catheterization. The effects of pre-admission educational DVDs were more significant among parents with a lower education, rural residence, with only one child, female child, or younger child. Offering educational DVDs to parents of children selected for cardiac catheterization for CHD may decrease the parental rejection rate of the treatment.

Impact of educational videos on maternal anxiety caused by children's heart surgery.

BACKGROUND: Mothers of children undergoing surgery for congenital heart disease experience significant stress. Therefore, finding a strategy to decrease this is vital. AIMS: To examine whether adding educational digital video discs to routine education can reduce maternal anxiety and depression when their children undergo heart surgery and when surgical or post-surgical complications occur. STUDY DESIGN: In a teaching hospital, 120 mothers whose children underwent elective heart surgery were randomly and equally divided into two groups: mothers receiving routine education plus a digital video disc before surgery and mothers receiving only routine education. Mothers' anxiety and depression levels were compared before education, after education (before surgery), and on discharge day. The effect of watching the digital video disc on maternal anxiety and depression on discharge day was evaluated for the participants whose children had surgical or post-surgical complications. RESULTS: Compared with only routine education, mothers' anxiety after education and on the discharge day decreased more if digital video disc was added. Depression decreased more after education, but no difference was found on the discharge day. Anxiety levels of mothers whose children had surgical or post-surgical complications on the discharge day decreased more if they watched the digital video disc, compared with those receiving only routine education (Beck anxiety inventory score 3.4 ± 1.9 and 6.1 ± 2.4 respectively; p-value .001). CONCLUSIONS: Compared with only routine education, adding digital video disc could decrease mothers' anxiety, and until the day of discharge. Compared with only routine education, adding digital video disc could decrease mothers' anxiety on the discharge day if their child had surgical or post-surgical complications. RELEVANCE TO CLINICAL PRACTICE: Adding educational digital video disc to routine education could decrease mothers' anxiety until the day of discharge. It could also decrease mothers' anxiety if their child had surgical or post-surgical complications.

Designing Mobile Epidemic Prevention Medical Stations for the COVID-19 Pandemic and International Medical Aid.

The demand for mobile epidemic prevention medical stations originated from the rapid spread of the COVID-19 pandemic. In order to reduce the infection risk of medical practitioners and provide flexible medical facilities in response to the variable needs of the pandemic, this research aimed to design mobile medical stations for COVID-19 epidemic prevention, the emergence of which began in February 2020. The mobile medical stations include a negative pressure isolation ward, a positive pressure swabbing station, a fever clinic and a laboratory. In Taiwan, many medical institutions used the mobile swabbing station design of this study to practice COVID-19 screening pre-tests. Internationally, this study assisted Palau in setting up medical stations to provide anti-epidemic goods and materials. The design of this study not only provides a highly flexible and safe medical environment but the benefits of screening can also be used as resources for medical research, forming an economic circulation for operation sustainability. In addition, the design of this study can also be used during the non-epidemic period as a healthcare station for rural areas or as a long-term community medical station.

Validation of a high-throughput method for simultaneous determination of areca nut and tobacco biomarkers in hair using microwave-assisted extraction and isotope dilution liquid chromatography tandem mass spectrometry.

For people with habits of chewing betel nuts and smoking, the probability of suffering from oral cancer is ten to a hundred times higher than others. Due to the serious health consequences of areca nut and tobacco, a reliable cessation program is needed. Hair is the best option to document long-term exposure. Unfortunately, the research on betel nut in hair did not attract much attention. In this study, a high-throughput method based on microwave-assisted extraction (MAE) and isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed to measure the four biomarkers of betel nuts and cigarettes, including areca alkaloids (arecoline), tobacco alkaloids (nicotine), and their metabolites (arecaidine and cotinine). The hair sample was washed, cut, weighed, and incubated for 3 min MAE with methanol/trifluoroacetic acid, then evaporated and reconstituted for LC-MS/MS analysis. The total experiment time was 50 min. The lower limits of quantification (LOQ) were 5-10 pg/mg. The intra-day and inter-day precision were 2.2-7.6%. Intra-day and inter-day accuracy were - 6.1-8.2%. The method showed good linearity (r2 > 0.995) over LOQ - 1000 pg/mg concentration ranges. It was successfully applied to analyze 11 subjects of regular areca nut chewers, also smokers. Eight samples were black hair; three samples were naturally black hair with partially gray hair. Measured concentrations in black hair were in the range 56.9 pg/mg to 3.2 ng/mg for arecoline, 12.8 pg/mg to 222.2 pg/mg for arecaidine, 3.8 ng/mg to 33.4 ng/mg for nicotine and 1.1 ng/mg to 6.1 ng/mg for cotinine. The results showed lower levels in gray hair. This method was utilized successfully to analyze pg/mg levels of arecoline, arecaidine, nicotine, and cotinine, and good recoveries were obtained. The mean concentration of arecaidine and cotinine in hair was 15% and 20% of arecoline and nicotine, respectively. A good positive correlation was found between the concentrations of these compounds and self-report. This method improved extraction speed, concentration, and analysis of samples and is useful for monitoring betel nut and smoking cessation programs.

Development of a rapid and sensitive LC-MS/MS assay for the quantification of commonly abused drugs in Asia in a micro-segment of a single hair using microwave-assisted extraction and dansyl chloride derivatization.

A high-throughput method using microwave-assisted extraction, chemical derivatization and liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) was developed for the simultaneous analysis of illicit drugs and their metabolites, including amphetamine (AMP), methamphetamine (MA), methylenedioxy- amphetamine (MDA), methylenedioxy-methamphetamine (MDMA), morphine (MOR), 6-acetylmorphine (6-AM), ketamine (K), and norketamine (NK) in a micro-segment of a single hair (0.4 mm). In order to elevate the throughput and sensitivities of selected compounds, 3 min microwave-assisted extraction and 10 min derivatization with dansyl chloride (DC) were employed. After derivatization, all compounds except ketamine and norketamine were derivatized and enhanced the sensitivities significantly. Derivatives showed intense fragment ions and low background noise on DC-MOR, DC-6-AM, and four DC-amphetamine-type stimulants. The total sample preparation and analysis time was 50 min. The calibration range was from LOQ to 5000 pg/mg, the coefficient of determination was better than 0.997. Intra-assay precision and accuracy were generally less than 15%. Limits of detection ranged from 15 to 50 pg/mg, limits of quantitation ranged between 45 and 125 pg/mg. The matrix effect was better than 90%. The method was successfully applied to the analysis of actual hair samples collected from multi-drug abusers. This advanced method showed practicality in hair analysis and was suitable for the extremely insufficient sample.

Maternal Exposure to Air Pollution Is Associated with Neonatal Jaundice: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the association between maternal ambient pollutant exposure and neonatal jaundice in multiple pollutant species and examine sex differences. STUDY DESIGN: Epidemiologic study: Records of 13 297 newborns (6153 male, 7144 female) born in Taichung, Taiwan were obtained from a national database. Average concentrations of prenatal air pollutants 3 months prior to birth were divided into low, middle, and high levels. Neonatal jaundice phototherapy rates between mothers who suffered varying air pollutant levels were compared. Clinical study: Three hundred seventy-six newborns (189 male, 187 female) born and received jaundice treatment with phototherapy in a hospital in Taichung, Taiwan were recruited. The correlation between prenatal exposure to air pollutants 3 months prior to birth, newborn's serum bilirubin, and serum hemoglobin were calculated. RESULTS: Epidemiologic study: Male newborns born to mothers exposed to high carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO2), and methane (CH4) levels had higher phototherapy rates. In female newborns, the same was noted for CO and CH4. Clinical study: Male newborns had a positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO, NO2, nonmethane hydrocarbon, and CH4 exposure 3 months prior to birth and serum bilirubin levels. Female newborns had a positive correlation for CH4. A positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO2, nonmethane hydrocarbon, CH4 exposure, and serum hemoglobin levels was noted in male newborns. CONCLUSION: Maternal exposure to air pollutants may increase neonatal jaundice treatment rates for phototherapy and higher neonatal serum total bilirubin level. Higher hemoglobin levels because of higher pollutant exposures may explain our findings. The association was more obvious in male newborns.

Evaluating the renal safety of tenofovir disoproxil fumarate in hepatitis B patients without chronic kidney disease.

The nephrotoxicity of tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients without chronic kidney disease (CKD) remains controversial. We aimed to evaluate nephrotoxicity of TDF in this population. In this hospital-based cohort study, CHB patients who received either TDF or entecavir (ETV) therapy, and did not have underlying CKD, were retrospectively recruited from January, 2008 to January, 2019. After excluding those with confounding conditions, 257 TDF-treated patients were matched through propensity scores with 514 ETV-treated patients. Cumulative incidences of, and hazard ratios (HRs) for the CKD guideline-defined renal dysfunction, were analysed. The mean decline in glomerular filtration rate was similar over 60 months (TDF vs. ETV: 10.1 ml/min/1.73 m2 , 95% confidence interval [CI]: 7.4-12.7 vs. 8.0 ml/min/1.73 m2 , 95% CI: 6.4-9.6; p = .34). The 5-year cumulative incidence of renal dysfunction was not significantly different (TDF vs. ETV: 10.4%, 95% CI: 5.6-18.0 vs. 5.8%, 95% CI: 3.6-9.0; p = .18). However, in multivariable stratified analysis, TDF was associated with an increased risk of renal dysfunction in the elderly (age ≥60 years), when compared to ETV (HR 2.86, 95% CI: 1.02-8.01; p < .05). For confirming the effect of TDF amongst the elderly, 61 TDF-treated patients were further matched with 183 ETV-treated patients, with 5-year cumulative incidence of renal dysfunction being significantly higher in TDF users (TDF vs. ETV: 34.4%, 95% CI: 17.7-59.8 vs. 15.5%, 95% CI: 9.4-25.1; p < .05). TDF use was independently related to renal dysfunction (HR 2.71, 95% CI: 1.19-6.14; p < .05). Although TDF is generally safe for CHB patients without CKD, it is best to be avoided in the elderly.

Clinical features, management, and outcome of iliopsoas abscess associated with cardiovascular disorders: a hospital-based observational case series study.

BACKGROUND: Iliopsoas abscess (IPA) is a rare clinical entity and is difficult to diagnose due to its insidious onset and nonspecific symptoms. The association between IPA and cardiovascular disorders (CVD) has been rarely reported. Computed tomographic (CT) scan can provide a definitive diagnosis of IPA and associated foci of adjacent structures. IPA is a life-threatening condition, especially when associated with CVD. MATERIALS AND METHODS: We conducted a hospital-based observational study of IPA associated with CVD. Data were collected from the electronic clinical database of Taichung Veterans General Hospital (1520-bed tertiary referral hospital in central Taiwan) between July 2007 and December 2017. The diagnosis of IPA associated with CVD was confirmed by classical findings on CT and transesophageal echocardiography with compatible clinical presentation and cultures from pus/tissue and blood. RESULTS: Fifteen patients of IPA associated with CVD were studied. They included 12 males (80%) and 3 females (20%), with a mean age 63.2 ± 16.9 years (31-85 years). CVD included stent-graft/endograft infection of abdominal aortic aneurysm (AAA) (40%), primary mycotic AAA (33.3%), and infective endocarditis (26.7%). Staphylococcus aureus is the most common microorganism in pus/tissue cultures (n = 3, 37.5%) and in blood cultures (n = 6, 40%). The average length of hospital stay was 33.1 ± 20.5 days (range, 3-81 days; median, 33 days). Hospital stay lasted 42.6 ± 19.2 days in the survival group and 19.0 ± 14.1 days (P = 0.018) in the non-survival group. Incidence of patients staying in the intensive care unit (ICU) with intubation > 3 days was 33% in the survival group and 100% (P = 0.028) in the non-survival group. Intra-hospital mortality rate was 40%. Poor prognostic factors in the non-survival group were hypoalbuminemia, hyponatremia, involved disc/vertebral body and/or epidural abscess, and ICU stay with intubation > 3 days. Cumulative survival rate was 25% under conservative treatments and 66.3% under aggressive treatments (P = 0.038). CONCLUSION: Due to high mortality rates, clinicians should keep a high suspicion index for IPA associated with CVD through clinical presentation, physical examination, and imaging study. Timely empiric antibiotics for common bacteria, drainage for IPA, endovascular repair, or vascular reconstruction by graft replacement or bypass with intensive care should be mandatory to shorten the hospital stay, reduce medical costs, and lower mortality rate.

Thymoquinone suppresses the proliferation of renal cell carcinoma cells via reactive oxygen species-induced apoptosis and reduces cell stemness.

Thymoquinone is a phytochemical compound isolated from Nigella sativa and has various biological effects, including anti-inflammation, antioxidation, and anticancer. Here, we further investigated the anticancer effects and associated molecular mechanism of 2-methyl-5-isopropyl-1,4-benzoquinone (thymoquinone) on human renal carcinoma cell lines 786-O and 786-O-SI3 and transitional carcinoma cell line BFTC-909. Results showed that thymoquinone significantly reduced cell viability, inhibited the colony formation of renal cancer cells, and induced cell apoptosis and mitochondrial membrane potential change in both cancer cells. In addition, thymoquinone also triggered the production of reactive oxygen species (ROS) and superoxide and the activation of apoptotic and autophagic cascade. ROS inhibition suppressed the caspase-3 activation and restored the decreased cell viability of 786-O-SI3 in response to thymoquinone. Autophagy inhibition did not restore the cell viability of 786-O-SI3 suppressed by thymoquinone. Moreover, thymoquinone suppressed the cell sphere formation and the expression of aldehyde dehydrogenase, Nanog, Nestin, CD44, and Oct-4 in 786-O-SI3 cells. The tumor-bearing model showed that thymoquinone in vivo inhibited the growth of implanted 786-O-SI3 cell. All these findings indicate that thymoquinone inhibits the proliferation of 786-O-SI3 and BFTC-909 cell possibly due to the induction of ROS/superoxide and the consequent apoptosis, suggesting that thymoquinone may be a potential anticancer supplement for genitourinary cancer.

Thymoquinone inhibits metastasis of renal cell carcinoma cell 786-O-SI3 associating with downregulation of MMP-2 and u-PA and suppression of PI3K/Src signaling.

Phytochemicals represent an important source of novel anticancer and chemotherapeutic agents. Thymoquinone (TQ) is the major bioactive phytochemical derived from the seeds of Nigella sativa and has shown potent anticancer activities. In this study, we aimed to investigate the anticancer activity of Thymoquinone on the human renal carcinoma cell 786-O-SI3 and the underlying mechanism. By using cell proliferation assay, wound healing, and invasion assay, we found that Thymoquinone did not affect the viability of 786-O-SI3 and human kidney-2, but clearly inhibited the migration and invasion of 786-O-SI3. Further zymography and immunoblotting analysis showed that Thymoquinone downregulated the activity and expression of matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA) and attenuated the adhesion of 786-O-SI3 to type I and type IV collagen. Kinase cascade assay indicated that Thymoquinone inhibited the phosphorylation of phosphatidylinositol 3-kinase, Akt, Src, and Paxillin. In addition, Thymoquinone also decreased the level of fibronectin, N-cadherin, and Rho A. In parallel, Thymoquinone dose-dependently suppressed the transforming growth factor (TGF)-ß-promoted u-PA activity and expression, as well as the cell motility and invasion of 786-O-SI3. Furthermore, tumor xenograft model revealed that Thymoquinone in vivo inhibited the 786-O-SI3 metastasizing to the lung. Collectively, these findings indicate that Thymoquinone inhibits the metastatic ability of 786-O-SI3, suggesting that Thymoquinone might be beneficial to promote the chemotherapy for renal cell carcinoma.

Statins improve the long-term prognosis in patients who have survived sepsis: A nationwide cohort study in Taiwan (STROBE complaint).

Most patients diagnosed with sepsis died during their first episode, with the long-term survival rate upon post-sepsis discharge being low. Major adverse cardiovascular events and recurrent infections were regarded as the major causes of death. No definite medications had proven to be effective in improving the long-term prognosis. We aimed to examine the benefits of statins on the long-term prognosis of patients who had survived sepsis.Between 1999 and 2013, a total of 220,082 patients who had been hospitalized due to the first episode of sepsis were included, with 134,448 (61.09%) of them surviving to discharge. The surviving patients who were subsequently prescribed statins at a concentration of more than 30 cumulative Defined Daily Doses (cDDDs) during post-sepsis discharge were defined as the users of statin.After a propensity score matching ratio of 1:5, a total of 7356 and 36,780 surviving patients were retrieved for the study (statin users) and comparison cohort (nonstatin users), respectively. The main outcome was to determine the long-term survival rate during post-sepsis discharge.HR with 95% CI was calculated using the Cox regression model to evaluate the effectiveness of statins, with further stratification analyses according to cDDDs.The users of statins had an adjusted HR of 0.29 (95% CI, 0.27-0.31) in their long-term mortality rate when compared with the comparison cohort. For the users of statins with cDDDs of 30-180, 180-365, and >365, the adjusted HRs were 0.32, 0.22, and 0.16, respectively, (95% CI, 0.30-0.34, 0.19-0.26, and 0.12-0.23, respectively), as compared with the nonstatins users (defined as the use of statins <30 cDDDs during post-sepsis discharge), with the P for trend <.0001. In the sensitivity analysis, after excluding the surviving patients who had died between 3 and 6 months after post-sepsis discharge, the adjusted HR for the users of statins remained significant (0.35, 95% CI 0.32-0.37 and 0.42, 95% CI 0.39-0.45, respectively).Statins may have the potential to decrease the long-term mortality of patients who have survived sepsis. However, more evidence, including clinical and laboratory data, is necessary in order to confirm the results of this observational cohort study.Trial registration: CMUH104-REC2-115.

Liraglutide protects against glucolipotoxicity-induced RIN-m5F ß-cell apoptosis through restoration of PDX1 expression.

Prolonged exposure to high levels of glucose and fatty acid (FFA) can induce tissue damage commonly referred to as glucolipotoxicity and is particularly harmful to pancreatic ß-cells. Glucolipotoxicity-mediated ß-cell failure is a critical causal factor in the late stages of diabetes, which suggests that mechanisms that prevent or reverse ß-cell death may play a critical role in the treatment of the disease. Transcription factor PDX1 was recently reported to play a key role in maintaining ß-cell function and survival, and glucolipotoxicity can activate mammalian sterile 20-like kinase 1 (Mst1), which, in turn, stimulates PDX1 degradation and causes dysfunction and apoptosis of ß-cells. Interestingly, previous research has demonstrated that increased glucagon-like peptide-1 (GLP-1) signalling effectively protects ß cells from glucolipotoxicity-induced apoptosis. Unfortunately, few studies have examined the related mechanism in detail, especially the role in Mst1 and PDX1 regulation. In the present study, we investigate the toxic effect of high glucose and FFA levels on rat pancreatic RINm5F ß-cells and demonstrate that the GLP-1 analogue liraglutide restores the expression of PDX1 by inactivating Mst1, thus ameliorating ß-cell impairments. In addition, liraglutide also upregulates mitophagy, which may help restore mitochondrial function and protect ß-cells from oxidative stress damage. Our study suggests that liraglutide may serve as a potential agent for developing new therapies to reduce glucolipotoxicity.

Effective compounds in the fruit of Muntingia calabura Linn. cultivated in Taiwan evaluated with scavenging free radicals and suppressing LDL oxidation.

Scavenging effect of 2,2-diphenyl -2-picrylhydrazyl hydrate (DPPH) radicals, inhibitory effect of low-density lipoprotein (LDL) oxidation, Trolox equivalent antioxidant capacity (TEAC), and phenolic contents were used for the activity-guided separation to identify the effective compounds of Muntingia calabura Linn. fruit. Its ethanol extract with higher phenolic content and antioxidant activities was subjected to silica gel column chromatographic separation, which was sequentially eluted with n-hexane, 10-90% ethyl acetate (EA) in n-hexane, EA, EA/acetone (50/50, v/v), acetone, acetone/methanol (MeOH) (50/50, v/v), and MeOH; fifteen fractions (Fr. 1-15) were obtained. Fractions 13 and 14 with better antioxidant effects were mixed followed by purification of the effective compounds using HPLC. Two major compounds were isolated and identified as gallic acid and 1,2-benzenedicarboxylic acid diisooctyl ester through high performance liquid chromatography-mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR) measurements. Their amounts in the fruit were 3.76 and 4.62 mg g-1. This study is the first report to clarify the effective antioxidant compounds of M. calabura Linn. fruit.

Trends of CT utilisation in an emergency department in Taiwan: a 5-year retrospective study.

OBJECTIVES: To investigate the association between the trends of CT utilisation in an emergency department (ED) and changes in clinical imaging practice and patients' disposition. SETTING: A hospital-based retrospective observational study of a public 1520-bed referral medical centre in Taiwan. PARTICIPANTS: Adult ED visits (aged ≥18 years) during 2009-2013, with or without receiving CT, were enrolled as the study participants. MAIN OUTCOME MEASURES: For all enrolled ED visits, we retrospectively analysed: (1) demographic characteristics, (2) triage categories, (3) whether CT was performed and the type of CT scan, (4) further ED disposition, (5) ED cost and (6) ED length of stay. RESULTS: In all, 269 239 adult ED visits (148 613 male patients and 120 626 female patients) were collected during the 5-year study period, comprising 38 609 CT scans. CT utilisation increased from 11.10% in 2009 to 17.70% in 2013 (trend test, p<0.001). Four in 5 types of CT scan (head, chest, abdomen and miscellaneous) were increasingly utilised during the study period. Also, CT was increasingly ordered annually in all age groups. Although ED CT utilisation rates increased markedly, the annual ED visits did not actually increase. Moreover, the subsequent admission rate, after receiving ED CT, declined (59.9% in 2009 to 48.2% in 2013). CONCLUSIONS: ED CT utilisation rates increased significantly during 2009-2013. Emergency physicians may be using CT for non-emergent studies in the ED. Further investigation is needed to determine whether increasing CT utilisation is efficient and cost-effective.

Up-regulation of nicotinamide phosphoribosyltransferase and increase of NAD+ levels by glucose restriction extend replicative lifespan of human fibroblast Hs68 cells.

Calorie restriction (CR) extends lifespan in a remarkable range of organisms. However, the mechanisms of CR related to the longevity effects are not fully elucidated to date. Using human fibroblast Hs68 (Hs68) cells cultured at a lower level of medium glucose (i.e., glucose restriction; GR) to mimic CR, we investigated the crucial role of nicotinamide phosphoribosyltransferase (Nampt), nicotinamide adenine dinucleotide (NAD(+)), and nicotinamide (NAM) in GR-extended replicative lifespan of Hs68 cells. We found that GR extended the lifespan of Hs68 cells, in parallel to significantly increased expression of Nampt, intracellular NAD(+) levels, and SIRT1 activities, and to significantly decreased NAM levels. The lifespan-extending effects of GR were profoundly diminished by FK866 (a noncompetitive inhibitor of Nampt) and blocked by sirtinol (a noncompetitive inhibitor of sirtuins). However, the steady-state intracellular NAM level (averaged 2.5 µM) was much lower than the IC50 of NAM on human SIRT1 (about 50 µM). All these results suggest that up-regulation of Nampt play an important role in GR-extended lifespan of Hs68 cells by increasing the intracellular NAD(+) levels followed by activating SIRT1 activity in Hs68 cells. In contrast, the role of NAM depletion is limited.

Pine (Pinus morrisonicola Hayata) needle extracts sensitize GBM8901 human glioblastoma cells to temozolomide by downregulating autophagy and O(6)-methylguanine-DNA methyltransferase expression.

Pine needle extracts of Pinus morrisonicola (Hayata) are commonly used as a functional health beverage. However, it remains unclear what the mechanism is underlying the antitumor activity of pine needle extract. The aims of present study were to investigate the anti-glioblastoma effects of pine needle extracts as well as its bioactive compounds. From three different solvent extracts of pine needles, the water extract displayed the strongest cytotoxicity effects on GBM8901 glioblastoma cells. The isolated compounds were identified as pinocembrin, chrysin, and tiliroside. Chrysin was the most active ingredient of pine needle extract for the induction of apoptosis and suppression of migration and invasion. It also markedly inhibited temozolomide (TMZ)-induced autophagy and O(6)-methylguanine-DNA methyltransferase (MGMT) expression. Because both autophagy and MGMT overexpression have been implicated to TMZ-induced drug resistance in glioblastoma, our results showed that pine needle extract and chrysin may serve as a potential anticancer agent against glioblastoma, especially with regard to sensitizing glioblastoma cells resistant to TMZ.