Chin-Wang Hsu

Several observational studies have indicated a greater risk of cardiovascular diseases in cold weather. Cold-inducible RNA-binding protein (CIRP) is highly conserved and upregulated in response to various cellular stressors. Although CIRP provides protective effects against cold exposure, extracellular CIRP (eCIRP) is a danger-associated molecular pattern that can trigger inflammatory response. We aimed to explore the association between cold temperature and AD development, decipher the mechanistic links between cold stress and vascular cell injury, and provide a new therapeutic approach for cold stress-induced vascular emergencies. We used daily meteorological records obtained from the Taiwan Central Weather Administration and health insurance claims from the National Health Research Institute to examine the association between cold temperature and AD development. A murine AD model was established via treatment with the irreversible lysyl oxidase inhibitor 3-aminopropionitrile fumarate (BAPN). The mice were subjected to acute cold exposure (ACE) at 4 ± 1 °C. We found that cold stress and exogenous CIRP induced vascular inflammation and the overexpression of matrix metalloproteinase-2 through the Toll-like receptor 4 (TLR4) pathway in endothelial cells in vitro. There was a greater risk of AD at cold temperatures. ACE increased the aortic arch diameter and circulating CIRP and interleukin-6 levels in BAPN-fed, AD-susceptible mice. Exogenous recombinant CIRP exacerbated AD in BAPN-treated mice. C23, a competitive CIRP antagonist, ameliorated ACE-exacerbated AD in BAPN-treated mice. In conclusion, cold temperatures are associated with AD development in a subtropical/tropical monsoon climate. Cold stress could exacerbate AD development through the eCIRP/TLR4 pathway. Blocking eCIRP prevented cold-induced exacerbation of AD in AD-susceptible mice.

University neighborhoods in Taiwan have high-volume traffic, which may increase motorcyclists’ risk of injury. However, few studies have analyzed the environmental factors affecting motorcycle crash injury severity in university neighborhoods. In this multicenter cross-sectional study, we explored the factors that increase the severity of such injuries, especially among young adults. We retrospectively connected hospital data to the Police Traffic Accident Dataset. Areas within 500 m of a university were considered university neighborhoods. We analyzed 4751 patients, including 513 with severe injury (injury severity score ≥ 8). Multivariate analysis revealed that female sex, age ≥ 45 years, drunk driving, early morning driving, flashing signals, and single-motorcycle crashes were risk factors for severe injury. Among patients aged 18–24 years, female sex, late-night and afternoon driving, and flashing signals were risk factors. Adverse weather did not increase the risk. Time to hospital was a protective factor, reflecting the effectiveness of urban emergency medical services. Lifestyle habits among young adults, such as drunk driving incidents and afternoon and late-night driving, were also explored. We discovered that understanding chaotic traffic in the early morning, flashing signals at the intersections, and roadside obstacles is key for mitigating injury severity from motorcycle crashes in university neighborhoods.

Epidemiological studies have suggested the effects of ambient fine particles (PM_2.5) on asthma, but the effects of specific components of PM_2.5 on asthma remain to be explored. Here, we studied the effect of PM_2.5-bound polycyclic aromatic hydrocarbons (PAHs) on asthma acute exacerbation. The data on daily counts of emergency room visits (ERVs) were obtained from Wan Fang Medical Center, Taipei, Taiwan, from 2012 to 2015. The daily concentrations of PM_2.5 and pollutant gases were obtained from a local air quality monitoring station. The levels of PM_2.5-bound PAH were estimated by an established grid-scale model. Relative risks for ERVs as the increase in the level of ambient pollutants were calculated by using a generalized additive model of Poisson regression. In the present study, we observed statistically significant positive associations between PM_2.5 and asthma ERVs for all age groups. PM_2.5-bound PAH was also associated with asthma ERVs for all age groups. In the adult subgroup analysis, there was a significant association between PM_2.5-bound PAH and asthma ERVs at lags 1 and 2 (RR 1.289, 95% CI 1.050–1.582 and RR 1.242, 95% CI 1.039–1.485). The impacts of air pollution on the risk of pediatric asthma ERV were found to be significant for PM_2.5 at lag day 0 (RR 1.310, 95% CI 1.069–1.606). Moreover, pediatric asthma ERVs were significantly associated with the levels of PM_2.5-bound PAH at lag 1 and 2 days (RR 1.576, 95% CI 1.371–1.810 and RR 1.426, 95% CI 1.265–1.607). The study provides evidence that PM_2.5-bound PAHs were associated with an increased risk of asthma attacks. Our data further suggested that traffic exhaust is a primary source of PM_2.5-bound PAHs.

Introduction: Pneumonia is one of the leading causes of death worldwide, represents a potentially life-threatening condition. In recent studies, adjuvant corticosteroids therapy has been shown to improve outcome in severe community-acquired pneumonia (CAP); however, the treatment response to corticosteroids vary. It is important to select patients likely to benefit from the treatment. Currently, the optimal patient selection of corticosteroids treatment is not yet clearly defined. Methods: Sphingosine-1-phosphate and pneumonia (SOPN) trial is a double-blinded, randomized, placebo-controlled trial that will investigate if sphingosine-1-phosphate (S1P) can be an indicator for initiating adjuvant corticosteroids therapy in patients with severe CAP. Participants will be recruited from the emergency department and randomized to receive 20 mg of methylprednisolone twice daily or placebo for 5 days. The primary outcome will be “in-hospital mortality.” Secondary outcomes will include intensive care unit (ICU) admission, length of ICU stay, length of hospital stay, and clinical outcomes at Day 7 and Day 14. Conclusion: SOPN trial is the first randomized placebo-controlled trial to investigate whether S1P can be a predictive biomarker for adjuvant corticosteroids therapy in patients with severe CAP. The trial will add additional data for the appropriate use of adjuvant corticosteroids therapy in patients with severe CAP. Results from this clinical trial will provide foundational information supporting that if the S1P is appropriate for guiding the patient selection for corticosteroids adjuvant therapy.

Background: Postoperative vomiting and pain are common, unpleasant phenomena in pediatric patients undergoing ophthalmic surgery. Clonidine has antiemetic and analgesic properties and thus may be used as premedication to reduce postoperative vomiting and pain.Aim: To assess whether clonidine premedication may safely decrease postoperative vomiting and postoperative pain in pediatric patients who received an ophthalmic surgery.Methods: We systematically searched PubMed, EMBASE, Cochrane Library, and Scopus databases from their inception to September 2018. Randomized clinical trials comparing clonidine premedication with a placebo or an active comparator that investigated postoperative vomiting or postoperative pain in pediatric patients undergoing ophthalmic surgery were included. The primary outcome was postoperative vomiting. The secondary outcome was postoperative pain. We also evaluated the safety of clonidine premedication by tracking hemodynamic instability associated with its use.Results: Ten studies with 979 patients were eligible for inclusion. Clonidine achieved a significantly lower incidence of postoperative vomiting within 6 hours postoperatively, 6‐24 hours postoperatively, and at the end of the study (risk difference: −0.15; 95% confidence interval: −0.32 to −0.05; risk difference: −0.15; 95% confidence interval: −0.29 to 0.01; and risk difference: −0.23; 95% confidence interval: −0.34 to −0.12, respectively) than placebo. For the subgroup of patients who received strabismus surgery, clonidine produced a lower incidence of postoperative vomiting than placebo (risk difference: −0.19; 95% confidence interval: −0.29 to −0.05). Compared to benzodiazepine, clonidine achieved a lower incidence of postoperative vomiting at the end of the study (risk difference: −0.19; 95% confidence interval: −0.31 to −0.07); the effect was only observed in patients receiving clonidine 4 μg/kg. Furthermore, children receiving clonidine had lower postoperative pain scores, lower analgesic requirements, and more of them were pain‐free compared to those who received a placebo. No patient using clonidine had any major hemodynamic instability.Conclusion: Compared to placebo or benzodiazepine, clonidine premedication was effective in reducing postoperative vomiting in pediatric patients undergoing ophthalmic surgery. Clonidine premedication also provided more reduction in postoperative pain when compared to placebo. The use of clonidine premedication was not associated with adverse hemodynamic events.

Early determination of the severity of Community-Acquired Pneumonia (CAP) is essential for better disease prognosis. Current predictors are suboptimal, and their clinical utility remains to be defined, highlighting the need for developing biomarkers with efficacious prognostic value. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid with a documented regulatory role in immune defense and maintenance of endothelial barrier integrity. For early diagnose of CAP and recognition of severe CAP patients, we conduct this pilot study to access the potential utility of the circulating S1P in an Emergency department setting. In the prospective study, plasma S1P levels were quantified in healthy controls and patients with CAP. Also, their discriminating power was assessed by receiver operating characteristic analysis. The association between S1P levels and disease severity indices was assessed by Spearman correlation and logistic regression tests. Patients with CAP had significantly higher plasma S1P levels than healthy individuals (CAP: 27.54 ng/ml, IQR = 14.37–49.99 ng/ml; Controls: 10.58 ng/ml, IQR = 4.781–18.91 ng/ml; p < 0.0001). S1P levels were inversely correlated with disease severity in patients with CAP. Based on multivariate logistic regression analysis, the plasma S1P concentrations showed significant predicting power for mortality (OR: 0.909; CI: 0.801–0.985; p < 0.05), intensive care unit admission (OR: 0.89; CI: 0.812–0.953; p < 0.005) and long hospital stay (OR: 0.978; CI: 0.961–0.992; p < 0.005). Interestingly, significantly elevated levels of S1P were noted in patients who received methylprednisolone treatment during hospitalization. These results suggest that S1P may be associated with the pathogenesis of CAP and may have prognostic utility in CAP and its therapy, especially in the Emergency Department setting.

The effect of glycemic control on the prognosis of nondiabetic patients after acute myocardial infarction (AMI) remains uncertain. We investigated whether glycated hemoglobin (HbA1c) is associated with adverse outcomes after AMI in nondiabetic patients. In this observational study, we enrolled nondiabetic patients with AMI in the emergency department of 2 medical centers from January 2011 to September 2014. All patients received primary percutaneous coronary intervention and were divided into 4 groups according to the interquartile range of average HbA1c level (Group I, ≤5.6%; Group II, 5.6%–5.8%; Group III, 5.8%–6.0%; and Group IV, >6.0%). Multivariate logistic analysis was performed to estimate the correlation of HbA1c with major adverse cardiac events (MACEs) after AMI. In total, 267 eligible patients were enrolled; 48 patients (18%) developed MACEs within a median follow-up of 178 days. Univariate analysis showed HbA1c > 6.0%, with a higher risk of MACEs in Group IV than in Group I (odds ratio [OR]: 2.733; 95% confidence interval [CI]: 1.123–6.651 vs OR: 1.511; 95% CI: 0.595–3.835). Multivariate analysis revealed an approximately 3.8 times higher risk of MACEs in Group IV than in Group I (OR: 3.769; 95% CI: 1.30–10.86). The HbA1 level is a significant predictor of MACEs after AMI in nondiabetic patients.