Fibroblast growth factor 15, induced by elevated bile acids, mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy.

BACKGROUND: Fibroblast growth factor (FGF) 15/19, which is expressed in and secreted from the distal ileum, can regulate hepatic glucose metabolism in an endocrine manner. The levels of both bile acids (BAs) and FGF15/19 are elevated after bariatric surgery. However, it is unclear whether the increase in FGF15/19 is induced by BAs. Moreover, it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery. AIM: To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy (SG). METHODS: By calculating and comparing the changes of body weight after SG with SHAM group, we examined the weight-loss effect of SG. The oral glucose tolerance test (OGTT) test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG. By detecting the glycogen content, expression and activity of glycogen synthase as well as the glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (Pepck), we evaluated the hepatic glycogen content and gluconeogenesis activity. We examined the levels of total BA (TBA) together with the farnesoid X receptor (FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery. Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4 (FGFR4) with its corresponding signal pathways involved in glucose metabolism were detected. RESULTS: After surgery, food intake and body weight gain of SG group was decreased compare with the SHAM group. The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG, while the expression of the key enzyme for hepatic gluconeogenesis: G6Pase and Pepck, were depressed. TBA levels in serum and portal vein were both elevated after SG, the FXR-agonistic BA subspecies: Chenodeoxycholic acid (CDCA), lithocholic acid (LCA) in serum and CDCA, DCA, LCA in portal vein were all higher in SG group than that in SHAM group. Consequently, the ileal expression of FXR and FGF15 were also advanced in SG group. Moreover, the hepatic expression of FGFR4 was stimulated in SG-operated rats. As a result, the activity of its corresponding pathway for glycogen synthesis: FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated, while the corresponding pathway for hepatic gluconeogenesis: FGFR4- cAMP regulatory element-binding protein- peroxisome proliferator-activated receptor γ coactivator-1α pathway was suppressed. CONCLUSION: Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR. Furthermore, the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.

Objective performance of emergency medical technicians in the use of mechanical cardiopulmonary resuscitation compared with subjective self-evaluation: a cross-sectional, simulation-based study.

OBJECTIVE: To evaluate the subjective and objective resuscitation performance of emergency medical technicians (EMTs) using mechanical cardiopulmonary resuscitation (MCPR) devices. DESIGN AND SETTING: This was a cross-sectional simulation-based study where participants installed the MCPR device on a training manikin. PARTICIPANTS: We assessed EMT-Intermediates (EMT-Is) and EMT-Paramedics (EMT-Ps) of the Emergency Medical Services (Ambulance) Division of the Taipei City Fire Department. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the gap between self-perceived (subjective) and actual (objective) no-flow time during resuscitation, which we hypothesised as statistically insignificant. The secondary outcome was the association between resuscitation performance and personal attributes like knowledge, attitude and self-confidence. RESULTS: Among 210 participants between 21 and 45 years old, only six were female. There were 144 EMT-Is and 66 EMT-Ps. During a simulated resuscitation lasting between four and a half and 5 min, EMTs had longer actual no-flow time compared with self-perceived no-flow time (subjective, 38 s; objective, 57.5 s; p value<0.001). This discrepancy could cause a 6.5% drop of the chest compression fraction in a resuscitation period of 5 min. Among the EMT personal factors, self-confidence was negatively associated with objective MCPR deployment performance (adjusted OR (aOR) 0.66, 95% CI 0.45 to 0.97, p=0.033) and objective teamwork performance (aOR 0.57, 95% CI 0.34 to 0.97, p=0.037) for EMT-Ps, whereas knowledge was positively associated with objective MCPR deployment performance (aOR 2.15, 95% CI 1.31 to 3.52, p=0.002) and objective teamwork performance (aOR 1.77, 95% CI 1.02 to 3.08, p=0.043) for EMT-Is. Moreover, regarding the self-evaluation of no-flow time, both self-satisfaction and self-abasement were associated with objectively poor teamwork performance. CONCLUSIONS: EMTs' subjective and objective performance was inconsistent during the MCPR simulation. Self-confidence and knowledge were personal factors associated with MCPR deployment and teamwork performance. Both self-satisfaction and self-abasement were detrimental to teamwork during resuscitation.

Influence of advanced life support response time on out-of-hospital cardiac arrest patient outcomes in Taipei.

BACKGROUND: The association between out-of-hospital cardiac arrest patient survival and advanced life support response time remained controversial. We aimed to test the hypothesis that for adult, non-traumatic, out-of-hospital cardiac arrest patients, a shorter advanced life support response time is associated with a better chance of survival. We analyzed Utstein-based registry data on adult, non-traumatic, out-of-hospital cardiac arrest patients in Taipei from 2011 to 2015. METHODS: Patients without complete data, witnessed by emergency medical technicians, or with response times of ≥ 15 minutes, were excluded. We used logistic regression with an exposure of advanced life support response time. Primary and secondary outcomes were survival to hospital discharge and favorable neurological outcomes (cerebral performance category ≤ 2), respectively. Subgroup analyses were based on presenting rhythms of out-of-hospital cardiac arrest, bystander cardiopulmonary resuscitation, and witness status. RESULTS: A total of 4,278 cases were included in the final analysis. The median advanced life support response time was 9 minutes. For every minute delayed in advanced life support response time, the chance of survival to hospital discharge would reduce by 7% and chance of favorable neurological outcome by 9%. Subgroup analysis showed that a longer advanced life support response time was negatively associated with the chance of survival to hospital discharge among out-of-hospital cardiac arrest patients with shockable rhythm and pulse electrical activity groups. CONCLUSIONS: In non-traumatic, adult, out-of-hospital cardiac arrest patients in Taipei, a longer advanced life support response time was associated with declining odds of survival to hospital discharge and favorable neurologic outcomes, especially in patients presenting with shockable rhythm and pulse electrical activity.

Effect of Placement of a Supraglottic Airway Device vs Endotracheal Intubation on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest in Taipei, Taiwan: A Cluster Randomized Clinical Trial.

Importance: Prehospital advanced airway management with either initial endotracheal intubation (ETI) or initial supraglottic airway (SGA) insertion in patients with out-of-hospital cardiac arrest (OHCA) remains controversial. Objective: To compare the effectiveness of ETI and SGA in patients with nontraumatic OHCA. Design, Setting, and Participants: The Supraglottic Airway Device vs Endotracheal intubation (SAVE) trial was a multicenter cluster randomized clinical trial conducted in Taipei City, Taiwan. Individuals aged 20 years or older who experienced nontraumatic OHCA requiring advanced airway management and were treated by participating emergency medical service agencies were enrolled from November 11, 2016, to December 31, 2019. The final day of follow-up was February 19, 2020. Interventions: Four advanced life support ambulance teams were divided into 2 randomization clusters, with each cluster assigned to either ETI or SGA in a biweekly period. Main Outcomes and Measures: The primary outcome of the SAVE trial was sustained return of spontaneous circulation (ROSC) (≥2 hours) after resuscitation. Secondary outcomes included prehospital ROSC, survival to hospital discharge, and favorable neurologic outcome, defined as a cerebral performance category score less than or equal to 2. Prespecified subgroups and the association between time to advanced airways were explored. Per protocol and intention-to-treat analysis were performed. Results: A total of 936 patients (517 in the ETI group and 419 in the SGA group) were included in the primary analysis (median age, 77 [IQR, 62-85] years; 569 men [60.8%]). The first-attempt airway success rates were 77% with ETI (n = 413) and 83% with SGA (n = 360). Sustained ROSC was 26.9% (n = 139) in the ETI group vs 25.8% (n = 108) in the SGA group. The odds ratio of sustained ROSC was 1.02 (95% CI, 0.98-1.06) in the ETI group vs SGA group. The odds ratio of ETA vs SGA was 1.04 (95% CI, 1.02-1.07) for prehospital ROSC, 1.00 (95% CI, 0.94-1.06) for survival to hospital discharge, and 0.99 (95% CI, 0.94-1.03) for cerebral performance category scores less than or equal to 2. Conclusions and Relevance: In this randomized clinical trial, among patients with OHCA, initial airway management with ETI did not result in a favorable outcome of sustained ROSC compared with SGA device insertion. Trial Registration: ClinicalTrials.gov Identifier: NCT02967952.

Outcomes of out-of-hospital cardiac arrests after a decade of system-wide initiatives optimising community chain of survival in Taipei city.

OBJECTIVE: A strengthened chain of survival benefits patient outcomes after out-of-hospital cardiac arrest (OHCA).2 Over the past decade, the Taipei Fire Department (TFD) has continuously implemented system-wide initiatives on this issue.We hypothesised that for adult, non-trauma OHCA patients, the bundle of these system-wide initiatives are associated with better outcomes. METHODS: We conducted a registry-based, retrospective study to examine the association between consecutive system-level initiatives and OHCA survival on a two-yearly basis using trend analysis and multivariable logistic regression. The primary outcome was survival to hospital discharge (STHD) and favourable neurological status. RESULTS: We analysed 18,076 cases from 2008 to 2017. The numbers of two-yearly cases of OHCA with resuscitation attempts from 2008 to 2017 were 3,576, 3,456, 3,822, 3,811, and 3,411. There was a significant trend of improved STHD (Two-fold) and favourable neurological outcome (Six-fold) over the past decade. Similar trends were observed in the shockable and non-shockable groups. Considering the first 2 years as baseline, the odds of STHD and favourable neurological status in the end of the initiatives increased significantly after adjusting for universally recognised predictors for OHCA survival. CONCLUSION: For non-trauma adult OHCA in Taipei, continuous, multifaceted system-wide initiatives on the community chain of survival were associated with improved odds of STHD and favourable neurologic outcomes.

The Effect of Successful Intubation on Patient Outcomes After Out-of-Hospital Cardiac Arrest in Taipei.

STUDY OBJECTIVE: The effect of out-of-hospital intubation in patients with out-of-hospital cardiac arrest remains controversial. The Taipei City paramedics are the earliest authorized to perform out-of-hospital intubation among Asian areas. This study evaluates the association between successful intubation and out-of-hospital cardiac arrest survival in Taipei. METHODS: We analyzed 6 years of Utstein-based registry data from nontrauma adult patients with out-of-hospital cardiac arrest who underwent out-of-hospital airway management including intubation, laryngeal mask airway, or bag-valve-mask ventilation. The primary analysis was intubation success on patient outcomes. The primary outcome was survival to discharge and the secondary outcomes included sustained return of spontaneous circulation and favorable neurologic survival. Sensitivity analysis was performed with intubation attempts rather than intubation success. Subgroup analysis of advanced life support-serviced districts was also performed. RESULTS: A total of 10,853 cases from 2008 to 2013 were analyzed. Among out-of-hospital cardiac arrest patients receiving airway management, successful intubation, laryngeal mask airway, and bag-valve-mask ventilation was reported in 1,541, 3,099, and 6,213 cases, respectively. Compared with bag-valve-mask device use, successful out-of-hospital intubation was associated with improved chances of sustained return of spontaneous circulation (adjusted odds ratio [aOR] 1.91; 95% confidence interval [CI] 1.66 to 2.19), survival to discharge (aOR 1.98; 95% CI 1.57 to 2.49), and favorable neurologic outcome (aOR 1.44; 95% CI 1.03 to 2.03). The results were comparable in sensitivity and subgroup analyses. CONCLUSION: In nontrauma adult out-of-hospital cardiac arrest in Taipei, successful out-of-hospital intubation was associated with improved odds of sustained return of spontaneous circulation, survival to discharge, and favorable neurologic outcome.

The effect of the number and level of emergency medical technicians on patient outcomes following out of hospital cardiac arrest in Taipei.

AIM: The effect of the number and level of on-scene emergency medical technicians (EMTs) on the outcomes of patients with out-of-hospital cardiac arrest (OHCA) remains unclear. We aimed to test the association between the number and level of EMTs and the outcomes of patients with OHCA. METHODS: We analysed Utstein-based registry data on OHCA in Taipei from 2011 to 2015. The eligible patients were adults, aged ≥20 years, with non-traumatic OHCA who underwent resuscitation attempts. The exposures were the total number of EMTs or the EMT-Paramedic (EMT-P) ratio >50%. The outcome of interest was survival to discharge. RESULTS: During study period, total 8262 OHCA cases were included, of which 1085 (13.1%) were approached by crews with an EMT-P ratio >50%. While an increase in the number of EMTs on-scene was not associated with better chances of survival (adjusted odds ratio [aOR] 0.98, 95% confidence interval [CI] 0.89-1.08), an EMT-P ratio >50% was significantly associated with improved outcome (aOR 1.36, 95% CI 1.06-1.76). Subgroup analyses showed that EMT-P >50% significantly benefited survival in witnessed OHCA cases with non-shockable rhythm (aOR 1.69, 95% CI 1.01-2.58). Survival was the highest among cases seen by four EMTs with an EMT-P ratio >50% (aOR 2.54, 95% CI 1.43-4.50). CONCLUSION: An on-scene EMT-P ratio >50% was associated with improved survival to discharge of OHCA cases, especially in those with witnessed, non-shockable rhythm. The presence of four EMTs with an EMT-P ratio >50% at the scene of OHCA was associated with the best outcome.