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Abstract Bone health screening is crucial before and during androgen deprivation therapy (ADT) for prostate cancer, yet changes in bone mineral density during ADT are often overlooked. To improve surveillance rates, we developed an auto-recruit path integrated into the outpatient system, where a pop-up reminder prompts physicians to arrange bone health screenings when ADT is prescribed without a dual-energy x-ray absorptiometry (DXA) screening in the past year. If selected, the system orders DXA and related examinations automatically. We retrospectively reviewed DXA screening rates from 2000 to 2018. During that period, only 286 out of 3,019 patients (9.5%) received DXA screenings. After implementing the auto-recruit system, 251 out of 747 eligible patients (33.6%) were screened from March 2021 to February 2022. Participants using ADT for over a year had worse T-scores and higher osteoporosis rates (34.5% vs. 23.2%) compared to those using ADT for less than a year. Post-screening, there was a significant increase in calcium supplement and bone protective agent use, highlighting improved patient awareness and proactive bone health management. In conclusion, bone health screening for prostate cancer patients on ADT remains an unmet need. The auto-recruit path in the outpatient system effectively increases screening rates and enhances bone health management.

Abstract Prostate cancer (PC) treatment, particularly androgen deprivation therapy (ADT), remains pivotal, albeit linked to increased fracture risk due to osteoporosis. The advent of novel hormonal agents (NHAs) has spurred inquiries into their influence on bone health. This study aimed to evaluate the impact of NHAs on bone health in patients receiving combination therapy. We conducted a retrospective analysis using Taiwan’s National Health Insurance Research Database, encompassing men aged 45 and above diagnosed with PC without bone metastasis and undergoing ADT between 2000 and 2018. The study involved 25,949 patients, categorized into those receiving standard ADT (n = 25,166) and those on NHA combination therapy (n = 783). Our analysis delved into fracture risk, comorbidities, and osteoporosis treatments. Patients on NHA combination therapy faced significantly higher risks of any osteoporotic fracture and major osteoporotic fracture than those on ADT alone (HR = 1.29, 95% CI 1.04–1.61; HR = 1.37, 95% CI 1.06–1.75, respectively). Notably, age emerged as a critical factor, with the highest risk observed in those aged 90 or above. The 5-year overall survival rates were lower for patients who experienced any osteoporotic fracture, major osteoporotic fracture, and hospitalization due to osteoporotic fracture compared to those who did not experience these fractures (51.5% vs. 56.5%, 47.1% vs. 56.7%, and 48.2% vs. 56.3%, respectively, p

Objective To investigate and compare the effects of basic preconditioning regimens Bu/Cy, Cy/TBI and Flu/Bu for the treatment of patients in allogeneic hematopoietic stem cell transplantation.Methods It comprised exploring the published literature in the databases of PubMed, EMBASE, Cochrane Library, and Web of Science, using suitable keywords pertaining to various basic pretreatments Bu/Cy, Cy/TBI, and Flu/Bu, prior to allogeneic hematopoietic stem cell transplantation, and then extracting the searched outcome indicators of Overall Survival (OS) and survival (herein represented as OS and survival). Further, the results were estimated with meta-analysis using R, where the incidence of GVHD was reported in odds ratio (OR) with its 95% confidence interval (95%CI).Results and Discussion A total of 14 papers were included in this study, including 1436 cases were treated with Bu/Cy, 1816 cases with Cy/TBI, and 549 cases with Flu/Bu in the preconditioning regimen. After OS was the outcome pooled, compared with Flu/Bu in the preconditioning group, the results (Cy/TBI HR = 1.12 (95% Cl:1.04,1.61), Bu/Cy HR = 1.24 (95% Cl. 1.13,2.06)) showed that Flu/Bu preconditioning regimen significantly improved the overall survival rate of allogeneic HSCT patients. With the incidence of GVHD as the outcome summary, compared with Flu/Bu in the pretreatment group, the results (Cy/TBI HR = 1.24 (95% Cl:1.12, 1.82), Bu/Cy HR = 1.14 (95% Cl. 1.03, 2.12)) indicated that Flu/Bu in the pretreatment regimen group also significantly reduced the incidence of GVHD after allogeneic HSCT.Conclusion Patients who received the basal preconditioning regimen Flu/Bu before allogeneic hematopoietic stem cell transplantation had the lowest hazard ratio for overall survival (OS) development. This indicates that the use of the basal preconditioning regimen Flu/Bu for the treatment of patients was the most effective, although the quality of the studies included needs to be confirmed by high-quality randomized controlled trials.

Background This study investigated drug–drug interactions in patients with atrial fibrillation taking both a direct oral anticoagulant (DOAC) and an antiarrhythmic drug. Methods and Results Using data from the National Health Insurance database (2012–2018), we identified 78 805 patients with atrial fibrillation on DOACs, with 24 142 taking amiodarone, 8631 taking propafenone, 2784 taking dronedarone, 297 taking flecainide, 177 taking sotalol, and 42 772 on DOACs alone. Patients with bradycardia, heart block, heart failure, mitral stenosis, prosthetic valves, or incomplete data were excluded. Propensity score matching compared those taking both DOACs and antiarrhythmic drugs with those on DOACs alone. There was an increased risk of major bleeding in patients concomitantly taking DOACs with amiodarone when compared with matched patients taking DOACs alone (hazard ratio [HR],1.13 [95% CI, 1.04–1.23]; P=0.0044), particularly in patients taking dabigatran (HR, 1.19 [95% CI, 1.03–1.38]; P=0.0175). No significant difference in bleeding risk was found for propafenone, dronedarone, flecainide, or sotalol. The small sample sizes in the flecainide and sotalol groups limit interpretation. Notably, intracranial bleeding risk was higher in patients on DOACs and amiodarone, regardless of age. Additionally, patients

ObjectiveTo explore the functional characteristics of a patient of Bartter syndrome type III and compound heterozygous mutations in CLCNKB gene and explore the rescue effect of cystic fibrosis transmembrane conductance regulator modulator compound VX-809 on CLCNKB gene missense variant.MethodsA retrospective analysis was conducted for a hospitalized patient of Bartter syndrome type III on September 2, 2019. Clinical characteristics, growth and development status, laboratory findings and genetic data were reviewed. Wild-type and variant CLCNKB genes were separately transfected into human embryonic kidney 293 cells (HEK293) and the expression levels of ClC-Kb protein in each group detected by Western blot. The differences in protein expression between wild-type and variant type were compared by unpaired t-test. Additionally, immunofluorescent stain was utilized for examining the subcellular localization of ClC-Kb protein. And cystic fibrosis transmembrane conductance regulator modulator compound VX-809 was employed for treating cells after transfecting with a over-expressing variant in CLCNKB gene.ResultsThis 32-month-old girl presented with hypokalemia, hypochloremia, metabolic alkalosis, renal salt wasting and normal blood pressure in all four extremities. Genetic testing results revealed compound heterozygous variations in CLCNKB gene. Transfection of two variant plasmids (p.F213C & p. Y466Mfs13) into HEK293 cells indicated that the expression of variant ClC-Kb protein was significantly lower than that of wild-type (P

BackgroundPrevious studies have shown that global constructive work (CW) and wasted work (WW) predict response to cardiac resynchronization therapy (CRT). This study evaluated the predictive value of regional CW and WW for reverse remodeling and clinical outcomes after CRT.MethodsWe performed a prospective study involving 134 CRT candidates with left bundle branch block and left ventricular ejection fraction ≤35%. Global and regional CW and WW were calculated using pressure-strain loop analysis. CRT response was defined by reverse remodeling as a reduction of ≥15% in left ventricular end-systolic volume after six months.ResultsAt six-month follow-up, 92 (69%) patients responded to CRT. Of the regional CW and WW measures, lateral wall (LW) CW and septal WW were most strongly and significantly correlated with reverse remodeling. At multivariate analysis, LW CW and septal WW were both independent determinants of reverse remodeling. When LW CW and septal WW were included in the model, global CW and WW were not independently associated with reverse remodeling. LW CW and septal WW predicted reverse remodeling with an area under the curve (AUC) of 0.783 (95% CI: 0.700–0.866) and 0.737 (95% CI: 0.644–0.831), respectively. Using both variables increased the AUC to 0.832 (95% CI: 0.755–0.908). Both LW CW ≤878 mmHg% (HR 2.01; 95% CI: 1.07–3.79) and septal WW ≤181 mmHg% (HR 2.60; 95% CI: 1.38–4.90) were significant predictors of combined death and HF hospitalization at two-year follow-up.ConclusionLW CW and septal WW before CRT are important determinants of reverse remodeling and clinical outcomes.

Background: Premature ventricular complexes (PVCs) are common electrocardiographic abnormalities and may be a prognosticator in predicting mortality in patients with structurally normal hearts or chronic heart diseases. Whether PVC burden was associated with mortality in patients with chronic atrial fibrillation (AF) remained unknown. We investigated the prognostic value of PVC burden in patients with persistent AF. Methods: A retrospective analysis of 24 h Holter recordings of 1767 patients with persistent AF was conducted. Clinical characteristics, 24 h average heart rate (HR), and PVC measures, including 24 h PVC burden and the presence of consecutive PVCs (including any PVC couplet, triplet, or non-sustained ventricular tachycardia) were examined for the prediction of all-cause and cardiovascular mortality using the Cox proportional hazards model. Results: After a median follow-up time of 30 months, 286 (16%) patients died and 1481 (84%) patients survived. Multivariate analysis revealed that age, heart failure, stroke, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, digoxin, oral anticoagulant use, and estimated glomerular filtration rate were significant baseline predictors of all-cause mortality and cardiovascular mortality. Twenty-four-hour PVC burden and the presence of consecutive PVCs were significantly associated with all-cause and cardiovascular mortality after adjusting for significant clinical factors. When compared to the first quartile of PVC burden (0.3%/day) was significantly associated with an increased risk of all-cause mortality (hazard ratio, 2.46; 95% CI, 1.77–3.42) and cardiovascular mortality (hazard ratio: 2.67; 95% CI, 1.76–4.06). Conclusions: Twenty-four-hour PVC burden is independently associated with all-cause and cardiovascular mortality in patients with persistent AF.

Abstract Backgrounds Early integration of palliative care for terminally ill non-cancer patients improves quality of life. However, there are scanty data on Palliative Care Consultation Service (PCCS) among non-cancer patients. Methods In this 9-year observational study Data were collected from the Hospice-Palliative Clinical Database (HPCD) of Taichung Veterans General Hospital (TCVGH). Terminally ill non-cancer patients with 9 categories of diagnoses who received PCCS during 2011 to 2019 were enrolled. Trend analysis was performed to evaluate differences in categories of diagnosis throughout study period, duration of PCCS, patient outcomes, DNR declaration, awareness of disease by patients and families before and after PCCS. Results In total, 536 non-cancer patients received PCCS from 2011 to 2019 with an average age of 70.7 years. The average duration of PCCS was 18.4 days. The distributions of age, gender, patient outcomes, family’s awareness of disease before PCCS, and patient’s awareness of disease after PCCS were significantly different among the diagnoses. Organic brain disease and Chronic kidney disease (CKD) were the most prevalent diagnoses in patients receiving PCCS in 2019. For DNR declaration, the percentage of patients signing DNR before PCCS remained high throughout the study period (92.8% in 2019). Patient outcomes varied according to the disease diagnoses. Conclusion This 9-year observational study showed that the trend of PCCS among non-cancer patients had changed over the duration of the study. An increasing number of terminally ill non-cancer patients received PCCS during late life, thereby increasing the awareness of disease for both patients and families, which would tend to better prepare terminally ill patients for end-of-life as they may consider DNR consent. Early integration of PCCS into ordinary care for terminally non-cancer patients is essential for better quality of life.

ObjectiveThis study aimed to better understand the current situation involving work stressors and the coping styles of outpatient and emergency nurses in 29 pediatric specialty hospitals across China. The study analyzed this correlation to provide a reference for the occupational stress management of pediatric nurses.MethodsFrom June to September 2020, 1,457 outpatient and emergency nurses in 29 pediatric specialty hospitals across China were selected as study participants, and a questionnaire survey was conducted using the Basic Information Questionnaire, the Chinese version of the Work Stressor Scale for Nurses, and the Simple Coping Style Scale.ResultsThe assessed stress level of outpatient and emergency nurses in 29 tertiary pediatric specialty hospitals nationwide is lower than the results of the survey of the 2007 domestic norm, p

BackgroundSodium-glucose co-transporter 2 (SGLT2) inhibitors has been shown with cardiovascular benefit in type 2 diabetes mellitus (T2DM) patients. However, its osmotic diuresis still concern physicians who may look for possible electrolyte imbalance. We therefore aimed to investigate electrocardiographic (ECG) changes associated with SGLT2 inhibitors.MethodsElectronic medical records from Chang Gung Research Database between January 1, 2001 and January 31, 2019 were searched for patients with ECG reports and patients on an oral hypoglycemic agent (OHA). We then separate these T2DM patients with EKG into those taking either SGLT2 inhibitors or non-SGLT2 inhibitors. We excluded patients with OHA use 500 ms, and ECG showing atrial fibrillation or atrial flutter. Propensity score matching (PSM) was performed between groups by age, sex, comorbidities, and medications (including QT prolonging medications). Conditional logistic regression and Firth's logistic regression for rare events were employed to compare the difference between SGLT2 and non-SGLT2 inhibitor patients.ResultsAfter exclusion criteria and PSM, there remained 1,056 patients with ECG on SGLT2 inhibitors and 2,119 patients with ECG on non-SGLT2 inhibitors in the study. There were no differences in PR intervals, QT prolongations by Bazett's or Fridericia's formulas, new onset ST-T changes, new onset CRBBB or CLBBB, and ventricular arrhythmia between the group of patients on SGLT2 inhibitors and the group of patients on non-SGLT2 inhibitors. There were no differences between the two groups in terms of cardiovascular death and sudden cardiac death. In addition, there were no differences between the two groups in terms of electrolytes.ConclusionsCompared with T2DM patients on non-SGLT2 inhibitors, there were no differences in PR interval, QT interval, ST-T changes, bundle-branch block, or ventricular arrhythmia in the patients on SGLT2 inhibitors. There were no differences in cardiovascular mortality between these two groups. In addition, there were no electrolyte differences between groups. SGLT2 inhibitors appeared to be well-tolerated in terms of cardiovascular safety.

Background/purpose: In-hospital cardiac arrest is a serious issue for hospitalized patients. The documented initial rhythm and detected medical events have been reported to influence the survival of cardiopulmonary resuscitation. This study aimed to identify the effect of continuous real-time electrocardiogram (ECG) monitoring on the prognosis of resuscitated patients in a general cardiac ward. Methods: We conducted this retrospective study using medical records of hospitalized patients in a cardiovascular ward who experienced an in-hospital cardiac arrest and received cardiopulmonary resuscitation from February 2015 to December 2018. The patients who were considered to be at high risk of cardiac events such as ventricular arrhythmia would receive continuous ECG monitoring. A wireless ECG telemonitoring system was introduced to replace traditional bedside ECG monitors. The outcome measures were the initial success of resuscitation, 24-h survival after resuscitation, and survival to discharge. Results: We enrolled 115 patients with a cardiac arrest during hospitalization, of whom 73 (63%) patients received wireless ECG telemonitoring. Patients receiving continuous ECG monitoring were associated with higher opportunities of initial success of resuscitation and 24-h survival after resuscitation (67.1% vs. 40.5%, p = 0.005; and 49.3% vs. 26.2%, p = 0.015, respectively) when comparing to the non-monitoring group; but no significant difference in survival to discharge (21.9% vs. 16.7%, p = 0.498) was observed. With adjustment of the covariates, the monitoring group was associated with a higher likelihood to reach the initial success of resuscitation (odds ratios [ORs], 3.21; 95% confidence interval [CI], 1.03–9.98). However, the effect of monitoring on 24-h survival and survival to discharge was close to null after adjusting for covariates. Conclusion: A wireless ECG telemonitoring system were beneficial to the initial success of resuscitation for patients at high risk of cardiovascular events suffering an in-hospital cardiac arrest; but had less impact on 24-h survival and survival to discharge.

Abstract Aims This study aimed to compare the efficacy of angiotensin receptor–neprilysin inhibitor (ARNI) therapy with angiotensin receptor blocker (ARB) therapy for cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction. Methods and results Data were obtained from the Chang Gung Research Database. The cohort entry date of the ARB group was assigned as that of the ARNI group to avoid immortal time bias. Additionally, 1:1 propensity score matching based on age, sex, and baseline left ventricular ejection fraction was conducted. The expectation–maximization imputation method with inverse probability of treatment weighting was used to compare outcomes between the two groups. The primary outcome was a composite of cardiovascular death and hospitalization for worsening HF. Patients who received ARNI therapy had a significantly lower risk of the primary composite outcome occurring than patients who received ARBs (hazard ratio, 0.74; 95% confidence interval, 0.57–0.96). The reduction of hospitalization for worsening HF contributed most to the primary outcome benefits. In addition to the primary outcome, the ARNI group had a significantly lower risk of non‐fatal myocardial infarction. The improvement of ejection fraction was not significantly different between the groups. The medication doses of ARNI were lower than in clinical trials. Conclusions In patients with HF with reduced ejection fraction, sacubitril/valsartan was superior to ARB therapy in reducing the occurrence of the primary outcome endpoint of hospitalization for worsening HF and cardiovascular death.

Abstract Aims Recent studies indicated that sodium glucose cotransporter‐2 inhibitors (SGLT2i) reduced heart failure hospitalization in patients with type 2 diabetes mellitus (T2DM). However, whether SGTL2i can improve left ventricular (LV) systolic and diastolic function remained unclear. This study aimed to compare the change in echocardiographic parameters in T2DM patients receiving SGLT2i with a different baseline LV ejection fraction (LVEF). The change in echocardiographic parameters was also compared between T2DM patients treated with SGLT2i and those treated with dipeptidyl peptidase‐4 inhibitor (DPP4i). Methods and results This multicentre cohort study consecutively enrolled 665, 119, and 132 T2DM patients treated with SGLT2i with a preserved (≥50%), moderately reduced (40–50%), and reduced baseline LVEF (

Abstract Aims Patients with concomitant atrial fibrillation (AF) and reduced left ventricular ejection fraction (LVEF) have poor prognosis. Outcomes of novel oral anticoagulant (NOAC) in elderly AF patients with normal, mid‐range, and reduced LVEF were investigated. Methods and results Data were retrieved from Chang Gung Research Database during 2010–2017 for patients with AF. We excluded patients with venous thromboembolism within 6 months, total knee/hip replacement and heart valve replacement within 6 months, end‐stage renal disease, stroke/systemic embolism (SE)/death within 7 days, age

Abstract Background Studies specifically examining the association between glycated hemoglobin A1c (HbA1c) levels and ischemic stroke/systemic thromboembolism (IS/SE) risk in atrial fibrillation (AF) patients are limited. Here, we investigated the association between HbA1c levels and the risk of IS/SE, as well as major bleeding, among AF patients with or without oral anticoagulants (OACs). We also compared the effectiveness and safety of warfarin and direct oral anticoagulants (DOACs) in different HbA1c categories. Methods We utilized medical data from a multi-center healthcare provider in Taiwan, which included 34,036 AF patients with serum HbA1c data available within 3 months after AF being diagnosed. Patients were divided into seven study groups according to their HbA1c levels: 0.05). Conclusion For AF patients, IS/SE risk significantly increased once HbA1c levels exceeded 6.5%, and OACs may attenuate these associations. Compared with warfarin, DOACs were more effective and safer across broad HbA1c categories. Therefore, in addition to prescribing DOACs when indicated, more aggressive glycemic control to achieve an HbA1c level

Major bleeding risks associated with non-vitamin K oral anticoagulants (NOACs) used with and without concurrent antipsychotics in patients with non-valvular atrial fibrillation (AF) were assessed. A total of 98,863 patients with non-valvular AF receiving at least one NOAC prescription from Taiwan’s National Health Insurance database were enrolled. Major bleeding was defined as a primary diagnosis of intracranial or gastrointestinal hemorrhage or bleeding at other sites. The adjusted incidence rate difference (AIRD) per 1,000 person-years and adjusted rate ratio of major bleeding were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score. A total of 8,037 major bleeding events occurred during 705,521 person-quarters with NOAC prescriptions. Antipsychotics were used in 26.35% of NOAC-exposed patients. Compared to using NOAC alone, co-medication of either typical (AIRD: 79.18, 95% confidence interval [CI]: 70.63–87.72) or atypical (AIRD: 40.5, 95% CI: 33.64–47.35) antipsychotic with NOAC had a significant increase in the adjusted incidence rate per 1,000 person-years of major bleeding. The concomitant use of a NOAC with chlorpromazine (AIRD: 103.87, 95% CI: 51.22–156.52), haloperidol (AIRD: 149.52, 95% CI: 125.03–174.00), prochlorperazine (AIRD: 90.43, 95% CI: 78.55–102.32), quetiapine (AIRD: 44.6, 95% CI: 37.11–52.09), or risperidone (AIRD: 41.55, 95% CI: 22.86–60.24) (All p < 0.01) showed a higher adjusted incidence rate of major bleeding than using NOACs alone. The concomitant use of typical (chlorpromazine, haloperidol, or prochlorperazine) or atypical (quetiapine or risperidone) antipsychotic with NOACs was associated with a significantly increased risk of major bleeding.

Direct oral anticoagulants (DOACs) are commonly prescribed with antidepressants that may increase bleeding risk. Here we assessed the association between DOACs with and without concurrent antidepressants and major bleeding risk in patients with atrial fibrillation (AF) by a retrospective cohort study included patients with AF who received prescriptions of DOACs in Taiwan’s National Health Insurance database between 2012 and 2017. Adjusted rate ratio (ARR) of major bleeding was calculated by comparing incidence rate adjusted with Poisson regression and inverse probability of treatment weighting using the propensity score between patient-times with and without antidepressants. Among 98863 patients with AF, concurrent use of bupropion with DOACs increased the risks of all major bleeding (ARR: 1.49, 95% CI: 1.02–2.16) and gastrointestinal hemorrhage (ARR: 1.57, 95% CI: 1.04–2.33). An increased risk of intracerebral hemorrhage (ICH) was associated with the combinations of DOACs with selective serotonin reuptake inhibitors (SSRIs, ARR: 1.38, 95% CI: 1.08–1.76), particularly in paroxetine (ARR: 2.11, 95% CI: 1.17–3.81), and tetracyclic antidepressants (TeCAs, ARR: 1.34, 95% CI: 1.01–1.78). In subgroup analyses stratified by individual NOACs, SSRIs increased the risk of ICH in the dabigatran-treated patients (ARR: 1.55, 95% CI: 1.04–2.33). The combinations of apixaban and serotonin-norepinephrine reuptake inhibitors (SNRIs) were associated with a higher risk of all major bleeding (ARR: 1.63, 95% CI: 1.04–2.55). These results clearly indicate the drug–drug interactions between DOACs and antidepressants, which should be carefully considered when prescribing DOACs in adult patients. Careful monitoring for bleeding should be performed while concurrently prescribing DOACs with bupropion, SSRI, SNRI, and TeCA. Concomitant use of DOACs and TCAs may be a relatively safe strategy for patients with AF.

Background To evaluate the prognostic impact of lymph node dissection (LND) in patients who underwent radical nephroureterectomy (RNU) with bladder cuff excision (BCE) for clinically node-negative (cN0) upper urinary tract urothelial carcinoma (UTUC). Methods We retrospectively enrolled 520 patients with cN0 UTUC in a single tertiary referral center from 2000 to 2015. The patients were divided into three groups: patients with and without pathologically proved lymph node metastasis (pN1–3 and pN0, respectively) and patients without LND (pNx). We analyzed associations between overall survival (OS)/ disease-free survival (DFS)/ cancer-specific survival (CSS) and clinical characteristics. Results The patients were divided into three groups (pN1–3, pN0 and pNx with 20, 303, and 197 patients, respectively). OS/DFS/CSS in the pN1–3 group were significantly worse (all pConclusions In the pN0 group, LND for cN0 UTUC did not show therapeutic benefits in terms of DFS, CSS, and OS. However, LND with RNU allowed optimal tumor staging, through patients still had a poor prognosis. Clinically occult LN metastases were found in 6.2% of our patients.

Background: Patients with active peptic ulcer (PU) were excluded from direct oral anticoagulant (DOAC) trials for stroke prevention in patients with atrial fibrillation (AF). This study evaluated the safety and effectiveness of DOACs in AF patients with active, inactive and no peptic ulcer (PU).Methods: This study accessed electronic medical records from January 1, 2009 to May 31, 2019 at a multi-center healthcare provider in Taiwan and involved 2,955 AF patients who had undergone esophagogastroduodenoscopy ≤ 1 year before anticoagulation. Subjects were classified into 3 groups: active (n = 237), inactive (n = 828) and no-PU (n = 1,890) groups. We compared the risks of major bleeding, gastrointestinal bleeding, and ischemic stroke/systemic embolism (IS/SE) between DOACs and warfarin among the 3 groups.Results: In the active PU group, there were no significant differences in the risks of major bleeding [hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.08–4.98, p = 0.676], gastrointestinal bleeding (HR = 0.65, 95% CI 0.08–4.98, p = 0.676) and IS/SE (HR = 2.58; 95% CI 0.53–12.70, p = 0.243) between DOAC and warfarin (as the reference). In the inactive PU group, there were no significant differences in the risks of major bleeding (HR = 0.36, 95% CI 0.09–1.39, p = 0.138), gastrointestinal bleeding (HR = 0.21, 95% CI 0.02–1.80, p = 0.153), and IS/SE (HR = 1.04, 95% CI 0.39–2.82, p = 0.934) between DOAC and warfarin (as the reference). In the no-PU group, DOACs were associated with lower risk of major bleeding (HR = 0.26, 95% CI 0.12–0.53, p < 0.001), gastrointestinal bleeding (HR = 0.25, 95% CI 0.01–0.59, p = 0.002), and similar risk of IS/SE (HR = 0.92, 95% CI 0.55–1.54, p = 0.757) compared to warfarin.Conclusions: DOACs were as effective as warfarin in preventing IS/SE irrespective of PU status and safer than warfarin in reducing major bleeding in the no-PU group. In patients with active or inactive PUs, DOAC and warfarin were not significantly different in their effects on major bleeding or gastrointestinal bleeding.

Abstract Introduction Atrial fibrillation (AF) often occurs in patients with acute coronary syndrome (ACS). It remains unclear whether pre-existing or new-onset AF confers different risk in patients with ACS. Methods We conducted a retrospective cohort study using Taiwan’s National Health Insurance Research Database. Patients who were hospitalized with a primary diagnosis of ACS from 2005 to 2009 were studied. Major outcomes were mortality, heart failure, and combined ischemic stroke/systemic embolism (IS/SE). The date of the first ACS diagnosis was defined as the index date. Pre-existing AF was defined as AF occurring before the index date. New-onset AF was defined as AF that started after or at the same time as the ACS diagnosis. Results Among 6663 patients with ACS, 488 (7.3%) had pre-existing AF and 479 (7.2%) had new-onset AF. Compared to patients with pre-existing AF, those with new-onset AF were younger, less likely to have co-morbidities, and more likely to receive evidence-based therapy. The un-adjusted risks of adverse outcomes in both groups were similar. Compared to pre-existing AF, new-onset AF was significantly associated with a higher adjusted risk of death (hazard ratio 1.27, 95% confidence interval 1.06–1.52) and IS/SE (hazard ratio 1.49, 95% confidence interval 1.01–2.20). The significant associations between new-onset AF and adverse outcomes were more likely to be observed in elderly patients with ACS. Conclusions New-onset AF during ACS was associated with a significantly increased risk of adverse outcomes, especially in the elderly patients.

Background Benefits of patients with end‐stage renal disease and atrial fibrillation undergoing peritoneal dialysis (PD) or hemodialysis are unknown. Methods and Results Patients undergoing dialysis were retrieved from Taiwan National Health Insurance Research Database during 2001 to 2013 and separated into PD or hemodialysis. Primary outcomes were ischemic stroke/systemic embolism, major bleeding, and intracranial hemorrhage (ICH). An inverse probability of treatment weighting based on propensity score was used to reduce the confounding. The risk of outcomes between PD and hemodialysis was compared using Cox proportional hazard model for fatal outcomes or Fine and Gray subdistribution hazard model which considered death a competing risk, respectively. A total of 7916 patients with end‐stage renal disease with atrial fibrillation undergoing PD or hemodialysis during 2001 to 2013 were identified. After exclusion criteria, 363 patients receiving PD and 5302 patients receiving hemodialysis were analyzed. At 1‐year follow‐up, the risk of ICH was significantly lower in the PD group compared with the hemodialysis group (0.2% versus 0.9%; subdistribution hazard ratio [SHR], 0.31; 95% CI, 0.17–0.57). At 3‐year follow‐up, the risks of major bleeding and ICH were significantly lower in the PD group compared with the hemodialysis group (major bleeding: 1.8% versus 3.2%; SHR, 0.68; 95% CI, 0.53–0.87; ICH: 0.5% versus 2%; SHR, 0.32; 95% CI, 0.21–0.48). At 5‐year follow‐up, ischemic stroke/systemic embolism, major bleeding, and ICH were significantly lower in the PD group compared with the hemodialysis group (ischemic stroke/systemic embolism: 12.4% versus 17.7%, SHR, 0.87; 95% CI, 0.79–0.96; major bleeding: 2.6% versus 4.1%; SHR, 0.79; 95% CI, 0.64–0.97; ICH: 0.5% versus 2.6%; SHR, 0.25; 95% CI, 0.17–0.37). Conclusions In patients with end‐stage renal disease and atrial fibrillation, dialytic modalities by PD or hemodialysis impacted these patients differently. There were overall reduced ischemic stroke/systemic embolism, major bleeding, and ICH at 5‐year follow‐up in patients undergoing PD compared with hemodialysis.

Background: Dipeptidylpeptidase-4 inhibitors (DPP-4i′s) are considered to be safe for patients with type 2 diabetes mellitus (T2DM). However, little is known about drug–drug interactions between DPP-4i′s and concurrent medications.Methods: Data on patients using DPP-4i′s for T2DM during 2011–2017 were retrieved from Chang Gung Research database provided by Chang Gung Memorial Hospital. Patients were excluded if they were aged 90 years; had incomplete demographic data; had insulinoma; or had records of concomitant insulin use. A generalized estimating equation–based Poisson model was employed for statistical analysis. The primary outcome was hypoglycemia events.Results: We retrieved data on a total of 97,227 patients using DPP-4i′s. After patients were excluded according to the mentioned criteria, the remaining 77,047 DPP-4i users were studied (mean age 64 ± 12 years, men 54.4%). The most common medications coprescribed with DPP4is over all person-quarters were acetaminophen, simvastatin, fluvastatin, and colchicine (all >20,000 person-quarters). The combinations of a DPP-4i with bumetanide, captopril, colchicine, acetaminophen, cotrimoxazole, and pantoprazole were associated with an increased risk of hypoglycemia. Compared with the ratios observed for person-quarters of DPP-4i use alone (reference category), the adjusted prevalence ratios per 100 person-years of hypoglycemia for person-quarters of DPP-4i use in combination with bumetanide, captopril, colchicine, acetaminophen, cotrimoxazole, and pantoprazole were 2.44 (95% confidence interval [CI], 1.78–3.36), 2.97 (95% CI, 2.26–3.90), 1.87 (95% CI, 1.44–2.42), 2.83 (95% CI, 2.44–3.29), 2.27 (95% CI, 1.27–4.04), and 3.03 (95% CI, 1.96–4.68), respectively.Conclusion: Among patients taking DPP-4i′s for T2DM, concurrent use of such inhibitors with bumetanide, captopril, acetaminophen, and pantoprazole was associated with an increased risk of hypoglycemia compared with the use of DPP-4i′s alone. Physicians prescribing DPP-4i′s should consider the potential risks associated with their concomitant use with other drugs.

Background Surgery for tricuspid valve (TV) diseases is associated with poor prognosis, but few studies have described the long‐term outcomes by comparing TV repair and replacement in isolated and concomitant TV surgeries separately. Methods and Results Between 2000 and 2013, adult patients who underwent TV repair or replacement surgeries were identified from the Taiwan National Health Insurance Research Database. Outcomes of interest included all‐cause mortality, composite outcome, and readmission attributable to any cause. Inverse probability of treatment weighting was used to reduce confounding effects. A total of 2644 patients with a mean follow‐up of 4.9 years were included. Of them, 12.6% and 87.4% underwent isolated and concomitant TV surgery, respectively. The in‐hospital mortality rates for isolated and concomitant TV surgery were 8.7% and 8.6%, respectively, whereas all‐cause mortality rates were 41.7% and 36.8%, respectively. Compared with TV replacement, TV repair demonstrated significantly lower risks of all‐cause mortality (concomitant: hazard ratio [HR], 0.76; 95% CI, 0.59–0.99), composite outcome (isolated: subdistribution HR, 0.55; 95% CI, 0.35–0.89; concomitant: subdistribution HR, 0.63; 95% CI, 0.46–0.86), and readmission (isolated: subdistribution HR, 0.64; 95% CI, 0.46–0.91; concomitant: subdistribution HR, 0.72; 95% CI, 0.60–0.86), except insignificant difference in all‐cause mortality in isolated surgery. Conclusions Compared with replacement, TV repair is associated with better short‐ and long‐term outcomes in both isolated and concomitant TV surgery. However, further prospective clinical trials are warranted.

Background: Sutureless aortic valve replacement (SU-AVR) has emerged as a promising alternative for the treatment of patients with aortic valve stenosis. This study aims to assess the safety and efficacy of SU-AVR in an elderly Asian population. Methods: From June 2015 to May 2016, 15 adults with severe aortic stenosis (9 females) with a median age of 79 years underwent Perceval sutureless bioprosthesis (LivaNova, UK) implantation in a single Taiwanese institution; peri-operative recovery, clinical improvement, and valve performance were analyzed. Results: Three (20%) patients underwent concomitant procedures (coronary artery bypass grafting, 1 patient; maze, 2 patients) and 6/12 (50%) patients underwent J-ministernotomy for isolated SU-AVR. Median cardiopulmonary bypass and cross-clamp time were 105 min and 69 min, respectively. All sutureless bioprosthesis were implanted successfully without conversion to a traditional valve, but 2 patients (13.3%) need intraoperative valve repositioning because of paravalvular leakage. Median extubation time and intensive care unit stay were 5 h and 2 days, respectively. One patient experienced in-hospital mortality due to sudden collapse thought secondary to high degree atrioventricular block. Serial echocardiographic evaluations were performed preoperatively and at 1, 3, and 6 months postoperatively. The final echocardiographic exams showed nothing greater than mild aortic insufficiency and the median mean trans-valvular gradient was 13.2 (range, 6.0–26.3) mmHg. Conclusions: By simplified procedure and improved hemodynamics, SU-AVR can be implanted safely in elderly Asian population with excellent valvular performance. Keywords: Aortic valve replacement, Sutureless bioprosthesis, Minimally invasive cardiac surgery

Effects of subculture conditions on the mycelium growth and antioxidant capacity assessment of Cordyceps militaris trains AG-1 and PSJ-1 were carried out in laboratory during the autumn-winter season of 2015. Different temperature regimes and nutrition, vitamins levels, grain in substrate were evaluated for optimization on mycelium growth. The results showed that two strains AG-1 and PSJ-1 can grow the maximum mycelium radial at the temperature of 24 °C. The mycelium growth was improved by carbon sources such as glucose, dextrose, fructose, and maltose at 30 g/L concentration. Whereas glucose achieved the highest value of mycelium colony diameter in strains AG-1 and PSJ-1. Vitamins B1 concentrations at 0.03 g/L also gave the great values in mycelium colony diameter of both strains AG-1 and PSJ-1. The studies depicted that a substrate mixed with various grains sources (brown rice, white rice, and wheat, black glutinous rice Vietnam, and corn) cultured at 24 °C, for 12 days supported maximum mycelia growth of the two strains AG-1 and PSJ-1 of C. militaris. The effect of liquid culture medium (MYPS and PD) with mycelium on the anti-oxidation capacity was assessed. The results showed that the increasing of DPPH radical scavenging capacity with the extract concentration exist a proportional relation and Fe2+-chelating capacity as well. The cultured Cordyceps mycelium of two strains AG-1 and PSJ-1had the equally strong antioxidant capacity. Keywords: Cordyceps militaris, Mycelium growth, Nutritional condition, Temperature, Vitamins, Anti-oxidation activity

Abstract Tumor local invasion is the first step of metastasis cascade which remains the key obstacle for cancer therapy. Collective cell migration plays a critical role in tumor invading into surrounding tissues. In vitro assays fail to assess collective invasion in a real time manner. Herein we aim to develop a three-dimensional (3D) microfluidic cell invasion model to determine the dynamic process. In this model, collective invasion of breast cancer cells is induced by the concentration gradient of fetal bovine serum. We find that breast cancer cells adopt a collective movement rather than a random manner when the cells invade into extracellular matrix. The leading cells in the collective movement exhibit an increased expression of an Aurora kinase family protein - AURKA compared with the follower cells. Inhibition of AURKA kinase activity by VX680 or AKI603 significantly reduces the phosphorylation of ERK1/2 (Thr202/Tyr204) and collective cohort formation. Together, our study illustrates that AURKA acts as a potential therapeutic target for suppressing the process of tumor collective invasion. The 3D microfluidic cell invasion model is a reliable, measurable and dynamic platform for exploring potential drugs to inhibit tumor collective invasion.

BackgroundLittle is known about the effects of anticoagulation in patients with atrial fibrillation (AF) and left atrial enlargement (LAE).MethodsData of patients with AF were retrieved from Chang Gung Research Database during 2007-2016. We excluded patients who were not using oral anticoagulants, used anticoagulants for ResultsWe identified 40,777 patients who received a diagnosis of AF. After the exclusion criteria were applied, 6,445 patients remained, 4,922 with LAE, and they were followed up for 2.4 ±1.9 years. The mean age of the patients was 77.32 ± 0.18 in the NOAC group and 76.58 ± 6.91 in the warfarin group (p < 0.0001); 48.24% of patients in the NOAC group and 46.98% of patients in the warfarin group were men (p > 0.05). The mean CHA2DS2-VASc score was 3.26 ± 1.05 in the NOAC group and 3.07 ± 1.12 in the warfarin group (p < 0.0001). The mean HAS-BLED score was 3.87 ± 3.81 in the NOAC group and 3.86 ± 3.80 in the warfarin group (p > 0.05). Furthermore, the mean LA diameter was 4.75 ± 0.63 cm in the warfarin group and 4.79 ± 0.69 cm in the warfarin group (p > 0.05). Among patients with LAE, NOAC was associated with significantly reduced IS/SE events (CRR = 0.63, 95% CI = 0.52-0.77), no difference in major bleeding (CRR = 0.91, 95% CI = 0.78-1.05), and significantly reduced death from any cause (aHR = 0.65, 95% CI = 0.52-0.80) compared with warfarin.ConclusionsIn elderly patients with AF and LAE, NOAC was associated with reduced IS/SE and death from any cause compared with warfarin, whereas no difference in major bleeding was observed between these treatments.

Background The ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) evaluated rivaroxaban (20/15 mg/d) versus warfarin in patients with atrial fibrillation. A separate trial, J‐ROCKET AF (Japanese ROCKET AF), compared rivaroxaban (15/10 mg/d) and warfarin in Japanese patients with atrial fibrillation. Data about rivaroxaban following J‐ROCKET AF criteria compared with warfarin and ROCKET AF dosage were limited. Methods and Results This retrospective study used medical data from a multicenter healthcare provider in Taiwan that included 3162 patients taking rivaroxaban. Among 2320 patients with an estimated glomerular filtration rate (eGFR) ≥50 mL/min per 1.73 m2, 384 and 1936 patients followed the ROCKET AF (20 mg/d) and J‐ROCKET AF (15 mg/d) recommendation, respectively. Among 842 patients with an eGFR

Background Major randomized trials assessing non–vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation generally excluded patients with hemoglobin

Remyelination plays a key role in functional recovery of axons after spinal cord injury. Glial cells are the most abundant cells in the central nervous system. When spinal cord injury occurs, many glial cells at the lesion site are immediately activated, and different cells differentially affect inflammatory reactions after injury. In this review, we aim to discuss the core role of oligodendrocyte precursor cells and crosstalk with the rest of glia and their subcategories in the remyelination process. Activated astrocytes influence proliferation, differentiation, and maturation of oligodendrocyte precursor cells, while activated microglia alter remyelination by regulating the inflammatory reaction after spinal cord injury. Understanding the interaction between oligodendrocyte precursor cells and the rest of glia is necessary when designing a therapeutic plan of remyelination after spinal cord injury.

Background Patients with impaired liver function (ILF) were excluded from clinical trials that investigated non–vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation. The aim of this study was to evaluate the efficacy and safety of NOACs in atrial fibrillation patients with ILF. Methods and Results A cohort study based on electronic medical records was conducted from 2009 to 2016 at a multicenter healthcare provider in Taiwan and included 6451 anticoagulated atrial fibrillation patients (aged 76.7±7.0 years, 52.5% male). Patients were classified into 2 subgroups: patients with normal liver function (n=5818) and patients with ILF (n=633, 9.8%). Cox regression analysis was performed to investigate the risks of thromboembolism, bleeding, and death associated with use of NOACs and warfarin in patients with normal liver function and ILF, respectively. In patients with normal liver function, compared with warfarin therapy (n=2928), NOAC therapy (n=4048) was associated with significantly lower risks of stroke or systemic embolism (adjusted hazard ratio: 0.75; 95% confidence interval, 0.65–0.88; P

BackgroundWhether non–vitamin K antagonist oral anticoagulants (NOACs) are superior to warfarin among Asians with nonvalvular atrial fibrillation remains unclear. Methods and ResultsIn this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, there were 5843, 20 079, 27 777, and 19 375 nonvalvular atrial fibrillation patients taking apixaban, dabigatran, rivaroxaban and warfarin, respectively, from June 1, 2012 to December 31, 2016. Propensity‐score weighting was used to balance covariates across study groups. Patients were followed until the first occurrence of any efficacy or safety outcome or the end date of study. Hazard ratios (95% confidence intervals) comparing apixaban, dabigatran, and rivaroxaban with warfarin were: ischemic stroke/systemic embolism (IS/SE), 0.55 (0.43–0.69), 0.82 (0.68–0.98), and 0.81 (0.67–0.97); major bleeding, 0.41 (0.31–0.53), 0.65 (0.53–0.80), and 0.58 (0.46–0.72); and all‐cause mortality, 0.58 (0.51–0.66), 0.61 (0.54–0.68), and 0.57 (0.51–0.65). A total of 3623 (62%), 17 760 (88%), and 26 000 (94%) patients were taking low‐dose apixaban (2.5 mg twice daily), dabigatran (110 mg twice daily), and rivaroxaban (10–15 mg once daily), respectively. Similar to all‐dose NOACs, all low‐dose NOACs had lower risk of IS/SE, major bleeding, and mortality when compared with warfarin. In contrast to other standard‐dose NOACs, apixaban was associated with lower risks of IS/SE (0.45 [0.31–0.65]), major bleeding (0.29 [0.18–0.46]), and mortality (0.23 [0.17–0.31]) than warfarin. ConclusionsAll NOACs were associated with lower risk of IS/SE, major bleeding, and mortality compared with warfarin in the largest real‐world practice among Asians with nonvalvular atrial fibrillation. All low‐dose NOACs had lower risk of IS/SE, major bleeding, and mortality when compared with warfarin. Standard‐dose apixaban caused a lower risk of IS/SE, major bleeding, and mortality compared with warfarin.