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Our previous research revealed that androgen receptor (AR) activation reduces endothelial cell proliferation via non-genomic pathways. We hypothesized that AR activation might also affect endothelial cell migration, a critical step in angiogenesis. Our data demonstrates that treatment of human umbilical vein endothelial cells (HUVECs) with AR agonists, metribolone (R1881) or dihydrotestosterone (DHT), results in a dose-dependent reduction in migration, which can be reversed by AR antagonists or AR knockdown. Mechanistically, R1881 inhibits HUVEC migration by suppressing RhoA activity through the cSrc/FAK/paxillin pathway and promoting RhoA degradation via RhoA-p27 complex formation, ultimately resulting in RhoA ubiquitination. Transfection with constitutively active RhoA-V14 rescues the inhibitory effect of R1881 on HUVEC migration. Furthermore, R1881 elevates intracellular vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) levels but reduces VEGF secretion from HUVECs. This reduction is attributed to the formation of VEGF-CTGF complexes in the cytosol induced by R1881. Transfection with RhoA-V14 reduces CTGF levels and VEGF-CTGF complex formation, leading to enhanced VEGF secretion. Pre-treatment with WP631, a CTGF inhibitor, mitigates the R1881-induced reduction in VEGF secretion and HUVECs migration. In vivo assessments using zebrafish angiogenesis and mouse matrigel plug assays validate the anti-angiogenic effects of R1881. These findings provide insight into the molecular mechanisms through which AR activation modulates endothelial cell migration and angiogenesis.

Background: Second-generation antipsychotics increase the risk of atrial fibrillation. This study explores whether the atypical antipsychotic ziprasidone triggers inflammasome signaling, leading to atrial arrhythmia. Methods: Electromechanical and pharmacological assessments were conducted on the rabbit left atria (LA). The patch-clamp technique was used to measure ionic channel currents in single cardiomyocytes. Detection of cytosolic reactive oxygen species production was performed in atrial cardiomyocytes. Results: The duration of action potentials at 50 % and 90 % repolarization was dose-dependently shortened in ziprasidone-treated LA. Diastolic tension in LA increased after ziprasidone treatment. Ziprasidone-treated LA showed rapid atrial pacing (RAP) triggered activity. PI3K inhibitor, Akt inhibitor and mTOR inhibitor abolished the triggered activity elicited by ziprasidone in LA. The NLRP3 inhibitor MCC950 suppressed the ziprasidone-induced post-RAP-triggered activity. MCC950 treatment reduced the reverse-mode Na+/Ca2+ exchanger current in ziprasidone-treated myocytes. Cytosolic reactive oxygen species production decreased in ziprasidone-treated atrial myocytes after MCC950 treatment. Protein levels of inflammasomes and proinflammatory cytokines, including NLRP3, caspase-1, IL-1β, IL-18, and IL-6 were observed to be upregulated in myocytes treated with ziprasidone. Conclusions: Our findings suggest ziprasidone induces atrial arrhythmia, potentially through upregulation of the NLRP3 inflammasome and enhancement of reactive oxygen species production via the PI3K/Akt/mTOR pathway.

Background: Major depressive disorder (MDD) and dementia are both major contributors to the global burden of disease. Despite existing literature on the association between MDD and dementia, there is a lack of a nationwide longitudinal cohort study that considers the competing risk of death. Therefore, this study assessed the bidirectional associations between MDD and dementia over an 11-year period in population-based settings, accounting for death as a competing risk. Methods: We conducted two population-based retrospective cohort studies in Taiwan. We identified 80,742 patients diagnosed with MDD in 2009–2010 and matched them with patients without MDD by sex, age, and year of diagnosis to assess the relative risk of dementia. We also identified 80,108 patients diagnosed with dementia in 2009–2010 and matched them with patients without dementia by sex, age, and year of diagnosis to assess the relative risk of MDD. All patients were followed until they received a diagnosis of new onset MDD or new onset dementia, their death, or the end of 2019. Cause-specific hazards models were used to estimate adjusted hazard ratios (aHRs). Results: The incidence density (ID) of dementia was higher in patients with MDD than in patients without MDD (7.63 vs. 2.99 per 1000 person-years), with an aHR of 2.71 (95% confidence interval [CI]: 2.55–2.88). The ID of MDD was higher in patients with dementia than in patients without dementia (12.77 vs. 4.69 per 1000 person-years), with an aHR of 2.47 (95% CI: 2.35–2.59). Conclusions: This population-based study found a bidirectional association between MDD and dementia. Our findings suggest the need to identify dementia in patients with MDD and vice versa.

Background: Although extracorporeal life support (ECLS) can provide emergency systemic perfusion for acute fulminant myocarditis (AFM), the mortality rate remains extremely high, especially in those undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Temporary ventricular assist device (VAD) can provide a more physiological blood flow direction and better subsequent organ perfusion than ECLS. We investigated temporary VAD efficacy in ECPR-revived AFM patients. Methods: During January 2012–May 2019, we retrospectively recruited 22 AFM patients with hemodynamic collapse and ECPR; 11 underwent ECLS only and 11 underwent additional VAD support after ECLS. Systemic perfusion was compared via laboratory biochemistry at post-ECPR days 2 (D2) and 4 (D4). Consciousness and cardiac function were assessed through the Glasgow Coma Scale (GCS) and echocardiography, respectively. All major complications and causes of mortality were recorded; 30-day survival was analyzed and risk factors were predicted. Results: The VAD group had significantly better hemodynamic improvement; more inotropes being tapered at D2 and D4; better data representative of systemic perfusion, including albumin, pH, bicarbonate, and lactate levels at D4; and better 30-day survival (72.7% vs. 27.2%, p = 0.033). The causes of mortality included central failure, multiple organ failure, and bacteremia with sepsis. The risk factors included lethal dysrhythmia before ECLS, GCS

Vasoplegic syndrome (VS) is characterized by low systemic vascular resistance paired with relatively preserved cardiac output that may result in increased morbidity and mortality rate after open-heart surgery utilizing cardiopulmonary bypass. We report a case of a 61-year-old male who underwent redo open-heart surgery due to a paravalvular leak of the previous implanted mitral bioprosthesis and severe tricuspid regurgitation. The patient experienced the VS in the intensive care unit after the operation. He was resuscitated by vasopressors and recovered uneventfully.

Rupture of abdominal aortic aneurysms (AAAs) is one of the leading causes of sudden death in the elderly population. The osteogenic transcription factor runt-related gene (RUNX) encodes multifunctional mediators of intracellular signal transduction pathways in vascular remodeling and inflammation. We aimed to evaluate the roles of RUNX2 and its putative downstream target miR-424/322 in the modulation of several AAA progression-related key molecules, such as matrix metalloproteinases and vascular endothelial growth factor. In the GEO database, we found that male patients with AAAs had higher RUNX2 expression than did control patients. Several risk factors for aneurysm induced the overexpression of MMPs through RUNX2 transactivation, and this was dependent on Smad2/3 upregulation in human aortic smooth muscle cells. miR-424 was overexpressed through RUNX2 after angiotensin II (AngII) challenge. The administration of siRUNX2 and miR-424 mimics attenuated the activation of the Smad/RUNX2 axis and the overexpression of several AAA progression-related molecules in vitro. Compared to their littermates, miR-322 KO mice were susceptible to AngII-induced AAA, whereas the silencing of RUNX2 and the administration of exogenous miR-322 mimics ameliorated the AngII-induced AAA in ApoE KO mice. Overall, we established the roles of the Smad/RUNX2/miR-424/322 axis in AAA pathogenesis. We demonstrated the therapeutic potentials of miR-424/322 mimics and RUNX2 inhibitor for AAA progression.

Abstract This retrospective cohort study aimed to evaluate the association between acetylcholinesterase inhibitors (AChEI) usage and the risk of lung cancer. Data from 116,106 new users of AChEI and 348,318, at a ratio of 1:3, matched by age, sex, and index-year, between 2000 and 2015 controls were obtained from the Taiwan Longitudinal Health Insurance Database in this cohort study. The Cox regression model was used to compare the risk of lung cancer. The adjusted hazard ratio (aHR) of lung cancer for AChEI users was 1.198 (95% confidence interval [CI] = 0.765–1.774, p = 0.167). However, the adjusted HR for patients aged ≥ 65 was adjusted to HR: 1.498 (95% CI = 1.124–1.798, p

Introduction: Aim of this retrospective cohort study is to evaluate the prognostic value of tumor volume reduction rate status post-induction chemotherapy in locally advanced head and neck squamous cell carcinoma. Methods: Patients newly diagnosed from year 2007 to 2016 at a single center were included in this retrospective study. All patients had received induction Taxotere, Platinum, Fluorouracil followed by daily definitive intensity-modulated radiotherapy for 70 Gy in 35 fractions concurrent with or without cisplatin-based chemotherapy. Tumor volume reduction rate was measured and calculated by contrast-enhanced computed tomography images at diagnosis, and after at least 1 cycle of induction chemotherapy, and analyzed though a univariate and multivariate Cox regression model. Results: Ninety patients of the primary cancer sites at hypopharynx (31/90, 34.4%), oropharynx (29/90, 32.2%), oral cavity (19/90, 21.1%), and larynx (11/90, 12.2%) were included in this study, with a median follow-up time interval of 3.9 years. In multivariate Cox regression analysis, the tumor volume reduction rate of the primary tumor (TVRR-T) was also an independently significant prognostic factor for disease-free survival (DFS) (hazard ratio 0.77, 95% confidence interval 0.62-0.97; P -value = .02). Other factors including patient's age at diagnosis, the primary cancer site, and RECIST (Response Evaluation Criteria in Solid Tumors), were not significantly related. At a cutoff value using 50% in Kaplan–Meier survival analysis, the DFS was higher with TVRR-T ≥ 50% group (log-rank test, P = .024), and a trend of improved overall survival. (log-rank test, P = .069). Conclusion: TVRR-T is a probable prognostic factor for DFS. With a cut-off point of 50%, TVRR-T may indicate better DFS.

Abstract Background Emergency department (ED) overcrowding is a health services issue worldwide. Modern health policy emphasizes appropriate health services utilization. However, the relationship between accessibility, capability, and appropriateness of ED use is unknown. Thus, this study aimed to examine the effect of hospital ED regionalization policy and categorization of hospital emergency capability policy (categorization policy) on patient-appropriate ED use. Methods Taiwan implemented a nationwide three-tiered hospital ED regionalization and categorization of hospital emergency capability policies in 2007 and 2009, respectively. We conducted a retrospective observational study on the effect of emergency care policy intervention on patient visit. Between 2005 and 2011, the Taiwan National Health Insurance Research Database recorded 1,835,860 ED visits from 1 million random samples. ED visits were categorized using the Yang-Ming modified New York University-ED algorithm. A time series analysis was performed to examine the change in appropriate ED use rate after policy implementation. Results From 2005 to 2011, total ED visits increased by 10.7%. After policy implementation, the average appropriate ED visit rate was 66.9%. The intervention had no significant effect on the trend of appropriate ED visit rate. Conclusions Although regionalization and categorization policies did increase emergency care accessibility, it had no significant effect on patient-appropriate ED use. Further research is required to improve data-driven policymaking.

Abstract Background The association between palliative care and life-sustaining treatment following emergency department (ED) resuscitation is unclear. This study aims to analyze the usage of palliative care and life-sustaining treatments among ED triage level I resuscitation patients based on a nationally representative sample of patients in Taiwan. Methods A matched-pair retrospective cohort study was conducted to examine the association between palliative care and outcome variables using multivariate logistic regression and Kaplan–Meier survival analyses. Between 2009 and 2013, 336 ED triage level I resuscitation patients received palliative care services (palliative care group) under a universal health insurance scheme. Retrospective cohort matching was performed with those who received standard care at a ratio of 1:4 (usual care group). Outcome variables included the number of visits to emergency and outpatient departments, hospitalization duration, total medical expenses, utilization of life-sustaining treatments, and duration of survival following ED triage level I resuscitation. Results The mean survival duration following level I resuscitation was less than 1 year. Palliative care was administered to 15% of the resuscitation cohort. The palliative care group received significantly less life-sustaining treatment than did the usual care group. Conclusion Among patients who underwent level I resuscitation, palliative care was inversely correlated with the scope of life-sustaining treatments. Furthermore, triage level I resuscitation status may present a possible new field for starting palliative care intervention and reducing low-value care.

Though ionic circuits have been reported, previous technologies did not allow ionic output or operate at significant voltages. Here, the authors, inspired by concepts from electronics and biology, show an abiotic ionic circuit that functions at voltages below 1 V and amplifies sub-nA ion currents.

Abstract Background Hypofractionated whole-breast irradiation is a standard adjuvant therapy for early-stage breast cancer. This study evaluates the plan quality and efficacy of an in-house-developed automated radiotherapy treatment planning algorithm for hypofractionated whole-breast radiotherapy. Methods A cohort of 99 node-negative left-sided breast cancer patients completed hypofractionated whole-breast irradiation with six-field IMRT for 42.56 Gy in 16 daily fractions from year 2016 to 2018 at a tertiary center were re-planned with an in-house-developed algorithm. The automated plan-generating C#-based program is developed in a Varian ESAPI research mode. The dose-volume histogram (DVH) and other dosimetric parameters of the automated and manual plans were directly compared. Results The average time for generating an autoplan was 5 to 6 min, while the manual planning time ranged from 1 to 1.5 h. There was only a small difference in both the gantry angles and the collimator angles between the autoplans and the manual plans (ranging from 2.2 to 5.3 degrees). Autoplans and manual plans performed similarly well in hotspot volume and PTV coverage, with the autoplans performing slightly better in the ipsilateral-lung-sparing dose parameters but were inferior in contralateral-breast-sparing. The autoplan dosimetric quality did not vary with different breast sizes, but for manual plans, there was worse ipsilateral-lung-sparing (V4Gy) in larger or medium-sized breasts than in smaller breasts. Autoplans were generally superior than manual plans in CI (1.24 ± 0.06 vs. 1.30 ± 0.09, p

Secondary aortoenteric fistula is a rare yet fatal condition that may occur as a complication after abdominal aortic aneurysm repair. Here, we report a case of a 66-year-old male with abdominal discomfort and intermittent fever at 5 years after endovascular aortic repair of an infected abdominal mycotic aneurysm. Surgical treatment with extra-anatomic bypass for lower body revascularization, followed by exploratory laparotomy with explantation of the infected graft and aortic tissue and repair of the duodenum were performed. The patient was rescued from the septic condition and discharged uneventfully 2 months postoperatively.

The authors here report an ultrathin ionomer membrane as an artificial solid-electrolyte interphase filter that minimizes parasitic reactions and enables stable dendrite-free lithium plating-stripping cycles in a carbonate-based electrolyte. The protected anodes exhibit outstanding coulombic efficiencies at room and elevated (50 °C) temperatures.

A series of 3-substituted-4-chloro-thioxanthones and their corresponding S,S-dioxidethioxanthone derivatives were designed and synthesized. The effects of our synthesized compounds on cell viability toward the MCF-7 and MDA-MB-468 breast cancer cell lines were evaluated. The most active compound was 4f, which was active against the MCF-7 and MDA-MB-468 cell lines with respective IC50 values of 7.2 and 3.9 μM. Interestingly, compound 4f did not impair cell viability of the cardiac myoblast H9C2 cell line (IC50 > 25 μM), indicating that this compound might not exhibit cytotoxic effects on the normal cardiac cells. Further, compounds 4b, 4f, 4j, 4s, 5b, 5f, 5j, and 5s were characterized by the NCI screening system. Results revealed that compounds 4f and 4s had effective anticancer activities against various cancer cell lines. Finally, our results indicated that the 3-substituted-4-chloro-thioxanthone derivatives have the potential to be further developed as promising small molecules for anticancer applications. Keywords: Thioxanthone, Thioxanthen-9-one-10,10-dioxide, MCF-7, MDA-MB-468, NCI 60-cell panel assay

Acute renal infarction is an uncommon disease, which is frequently misdiagnosed or diagnosed late because of its nonspecific clinical presentation, and may result in irreversible damage to the renal parenchyma. Here, we present a case of acute renal infarction in a 51-year-old male, presenting with left flank pain and being diagnosed through computed tomography. We successfully performed catheter-directed thrombolysis to rescue the ischemic renal tissue and preserve the renal function.

Abstract Background Equity in medical resource utilization is a crucial concern in countries with national health insurance systems. From the perspective of an active aging framework, public health insurance is one of the pillars of economic security, as suggested by the World Bank, to achieve the goal of social security for older adults. This study thus sought to quantify income-related inequality in national health insurance systems, especially during the global economic crisis of 2007–2008. Methods By employing the Taiwan National Health Interview Surveys (2005 and 2009) datasets, we analyzed the socioeconomic inequality of outpatient service utilization for older Taiwanese adults during the financial crisis of 2007–2008. We used corrected concentration indices (CCIs) to examine inequalities over time. Furthermore, we decomposed socioeconomic inequalities to reveal the contributions of determinant factors. The dependent variables related to whether participants had used outpatient services in the previous month, and the independent factors included individual’s needs, enabling, predisposing, and environmental factors proposed by Andersen model. Results The sample consisted of 2415 observations in 2005 and 2554 observations in 2009. The income-related health care inequality was minor from pro-rich to pro-poor across the study duration, although the difference was insignificant (women: from a concentration index [CI] of 0.0256 in 2005 to a CI of − 0.0098 in 2009; men: from a CI of 0.0379 in 2005 to a CI of 0.0310 in 2009). We used a probit model to analyze the effect of explanatory factors on outpatient resource utilization by men and women. After other factors were controlled for, we found that that the income variable had a positive and significant effect on outpatient service utilization in 2009 and the absolute contribution of income to inequality notably increased from 0.0480 in 2005 to 0.3247 in 2009 for older women. Conclusions In conclusion, Taiwan’s National Health Insurance system guarantees the accessibility of health care services to older adults, but slight income-related inequality was maintained in the outpatient resource utilization of women during the 2007–2008 financial crisis. Close attention should be paid to the vulnerability of women during times of economic insecurity.

Background and aims: During coronary artery bypass graft (CABG) surgery, the residual hemostasis procedures, from weaning cardiopulmonary bypass to closing sternotomy, are always completed by residents and supervised by attending surgeons. We want to evaluate the teaching effectiveness for residents under the supervision of attending surgeons with different levels of seniority. Materials and methods: Between January 1st 2001 and December 31st 2010, 2279 consecutive CABG surgeries were performed in our medical center. In total, 83 patients underwent a reexploration for postoperative bleeding. All causes of bleeding were identified and recorded. Competent attending surgeons were defined as having >3 years' experience and young attending surgeons with ≦3 years' experience. We compared the reexploration rate and aimed to identify the common sources of bleeding by the two groups. We also assessed the impact of attending experience on the outcomes and major complications after reexploration. Results: There were 36 surgical bleeding and 17 non-surgical bleeding in the young group and 16 surgical bleeding and 14 non-surgical bleeding in the competent group. The young group experienced more mediastinal drainage before a reexploration and a longer time interval to a reexploration. However, both are without statistical significance. Furthermore, the young group has a significant longer hospital stay. The most common intra-pericardium surgical bleeding included two-stage cannulation, side branch of the left internal mammary artery (LIMA), and side branch of vein grafts. The most common extra-pericardium surgical bleeding included a puncture hole by sternal wires, LIMA bed, and fragile sternum. Conclusion: Young attending surgeons indeed had both higher incidence of reexploration and surgical bleeding after a CABG. However, the supervisor experience only impacted hospital stay, not major complications or mortality after a reexploration. This might imply the competent attending surgeons provide higher teaching effectiveness for the hemostasis procedure after CABG. Keywords: Reexploration, Resident training, Surgeon experience, Cardiac surgery, Coronary artery bypass grafting

Background: Atypical antipsychotics increase the risk of atrial arrhythmias and sudden cardiac death. This study investigated whether ziprasidone, a second-generation antipsychotic, affected intracellular Ca2+ and Na+ regulation and oxidative stress, providing proarrhythmogenic substrates in atriums. Methods: Electromechanical analyses of rabbit atrial tissues were conducted. Intracellular Ca2+ monitoring using Fluo-3, the patch-clamp method for ionic current recordings, and a fluorescence study for the detection of reactive oxygen species and intracellular Na+ levels were conducted in enzymatically dissociated atrial myocytes. Results: Ziprasidone-treated atriums showed sustained triggered activities after rapid pacing, which were inhibited by KN-93 and ranolazine. A reduced peak L-type Ca2+ channel current and enhanced late Na+ current were observed in ziprasidone-treated atrial myocytes, together with an increased cytosolic Na+ level. KN-93 suppressed the enhanced late Na+ current in ziprasidone-treated atrial myocytes. Atrial myocytes treated with ziprasidone showed reduced Ca2+ transient amplitudes and sarcoplasmic reticulum (SR) Ca2+ stores, and increased SR Ca2+ leakage. Cytosolic and mitochondrial reactive oxygen species production was increased in atrial myocytes treated with ziprasidone. TNF-α and NLRP3 were upregulated in ziprasidone-treated myocytes, and the level of phosphorylated calcium/calmodulin-dependent protein kinase II protein was increased. Conclusions: Our results suggest that ziprasidone increases the occurrence of atrial triggered activity and causes intracellular Ca2+ and Na+ dysregulation, which may result from enhanced oxidative stress and activation of the TNF-α/NLRP3 inflammasome pathway in ziprasidone-treated myocytes.

Objective The objectives of this study are to refine the measurement of appropriate emergency department (ED) use and to provide a natural observation of appropriate ED use rates based on professional versus patient perspectives.Setting Taiwan has a population of 23 million, with one single-payer universal health insurance scheme. Taiwan has no limitations on ED use, and a low barrier to ED use may be a surrogate for natural observation of users’ perspectives in ED use.Participants In 7 years, there were 1 835 860 ED visits from one million random samples of the National Health Insurance Database.Measures Appropriate ED use was determined according to professional standards, measured by the modified Billings New York University Emergency Department (NYU-ED) algorithm, and further analysed after the addition of prudent patient standards, measured by explicit process-based and outcome-based criteria.Statistical analyses The area under the receiver operating characteristic curve (AUC) was used to reflect the performance of appropriate ED use measures, and sensitivity analyses were conducted using different thresholds to determine the appropriateness of ED use. The generalised estimating equation model was used to measure the associations between appropriate ED use based on process and outcome criteria and covariates including sex, age, occupation, health status, place of residence, medical resources area, date and income level.Results Appropriate ED use based on professional criteria was 33.5%, which increased to 63.1% when patient criteria were added. The AUC, which combines both professional and patient criteria, was high (0.85).Conclusions The appropriate ED use rate nearly doubled when patient criteria were added to professional criteria. Explicit process-based and outcome-based criteria may be used as a supplementary measure to the implicit modified Billings NYU-ED algorithm when determining appropriate ED use.

Background: Lipotoxicity causes endoplasmic reticulum (ER) stress, leading to cell apoptosis. Sirtuin 1 (Sirt1) regulates gene transcription and cellular metabolism. In this study, we investigated the role of Sirt1 in palmitate-induced ER stress. Methods: Both H9c2 myoblasts and heart-specific Sirt1 knockout mice fed a palmitate-enriched high-fat diet were used. Results: The high-fat diet induced C/EBP homologous protein (CHOP) and activating transcription factor 4 (ATF4) expression in both Sirt1 knockout mice and controls. The Sirt1 knockout mice showed higher CHOP and ATF4 expression compared to those in the control. Palmitic acid (PA) induced ATF4 and CHOP expression in H9c2 cells. PA-treated H9c2 cells showed decreased cytosolic NAD+/NADH alongside reduced Sirt1′s activity. The H9c2 cells showed increased ATF4 and CHOP expression when transfected with plasmid encoding dominant negative mutant Sirt1. Sirt1 activator SRT1720 did not affect CHOP and ATF4 expression. Although SRT1720 enhanced the nuclear translocation of ATF4, the extent of the binding of ATF4 to the CHOP promoter did not increase in PA treated-H9c2 cells. Conclusion: PA-induced ER stress is mediated through the upregulation of ATF4 and CHOP. Cytosolic NAD+ concentration is diminished by PA-induced ER stress, leading to decreased Sirt1 activity. The Sirt1 activator SRT1720 promotes the nuclear translocation of ATF4 in PA-treated H9c2 cells.

Abstract Purpose The dosimetric leaf gap (DLG) and multileaf collimator (MLC) transmission are two important systematic parameters used to model the rounded MLC leaf ends effect when commissioning an Eclipse treatment planning system (TPS). Determining the optimal DLG is a time consuming process. This study develops a simple and reliable method for determining the DLG using the cross-field dose width. Methods and materials A Varian TrueBeam linac with 6 MV, 10 MV, 6 MV flattening filter free (FFF) and 10 MV FFF photon beams and equipped with the 120 Millennium MLC and the Eclipse™ TPS was used in this study. Integral sliding fields and static slit MLC field doses with different gap widths were measured with an ionization chamber and GAFCHROMIC EBT3 films, respectively. Measurements were performed for different beam energies and at depths of 5 and 10 cm. DLGs were derived from a linear extrapolation to zero dose and intercepting at the gap width axis. In the ion chamber measurements method, the average MLC leaf transmission to the gap reading for each gap (R gT ) were calculated with nominal and cross-field dose widths, respectively. The cross-field dose widths were determined according to the dose profile measured with EBT3 films. Additionally, the optimal DLG values were determined using plan dose measurements, as the value that produced the closest agreement between the planned and measured doses. DLGs derived from the nominal and cross-field dose width, the film measurements, and the optimal process, were obtained and compared. Results The DLG values are insensitive to the variations in depth (within 0.07 mm). DLGs derived from nominal gap widths showed a significantly lower values (with difference about 0.5 mm) than that from cross-field dose widths and from film measurements and from plan optimal values. The method in deriving DLGs by correcting the nominal gap widths to the cross-field dose widths has shown good agreements to the plan optimal values (with difference within 0.21 mm). Conclusions The DLG values derived from the cross-field dose width method were consistent with the values derived from film measurements and from the plan optimal process. A simple and reliable method to determine DLG for rounded leaf-end MLC systems was established. This method provides a referable DLG value required during TPS commissioning.

ObjectiveAortic calcification (AC) is associated with increased risks of cardiovascular events and mortality. Numerous studies have explored the association between calcification and abdominal artery aneurysm. However, evidence regarding the association between AC and acute aortic dissection (AAD) is limited. We aimed to evaluate the association between AC-related variables and the development of intimal tear (IT) in patients with AAD.MethodsWe conducted a retrospective observational study involving 64 patients with type A AAD and 32 patients with type B AAD from February, 2011 to January, 2017 at a tertiary referral medical center in Taiwan. We used the default analysis module "calcification score analysis" to calculate all the calcification variables, including AC scores and volume.ResultsWe identified an association between AC and AAD. Patients with AAD had a greater AC volume in the aortic arch and greater AC scores for both the ascending aorta and the aortic arch than did patients without AAD. However, hypertension and coronary artery disease, rather than AC remained to be the independent risk factor for AAD in multivariate analysis. Patients with type A AAD had greater mean and cumulative AC volumes in the aortic arch, greater cumulative AC volumes in the whole aorta and higher cumulative AC scores in the aortic arch than did patients with type B AAD. ACs were superimposed on ITs in nearly half of the patients with AAD. In patients with type A AAD, AC was more commonly located distal to the IT and farther from the IT.ConclusionsWe identified the associations between AC-related variables and the location of IT in patients with AAD. However, AC was not an independent risk factor for AAD. The distribution of AC was different between patients with type A and type B AAD.

BackgroundRecent studies have indicated that several critical illnesses are associated with an increased risk of cardiovascular diseases (CVDs). Nonetheless, studies of the association between heat-related illnesses (HRIs) and subsequent CVDs are still limited. We sought to evaluate whether heat stroke (HS) was associated with an increased CVD incidence.MethodsThe data from the nationwide, population-based, retrospective, cohort study described herein were obtained from the National Health Insurance Research Database in Taiwan. The outcome evaluated in this study was the cumulative incidence of CVDs, which was compared between patients with HS, patients with other HRIs and a control group during a 14-year follow-up period.ResultsOur analyses included 150 HS cases, 150 patients with other HRIs and 150 patients without HRIs. The HS patients had a significantly higher incidence of developing CVDs than the other HRI and control patients (32.67% vs. 23.33% vs. 16.67%, p = 0.005). Patients with HS had an increased incidence of acute myocardial infarction (AMI) compared with that of the controls (6% vs. 2.67%, p = 0.042) and an increased incidence of acute ischemic stroke (AIS) compared with those of the other HRI and control patients (12% vs. 6% vs. 4.67%, p = 0.038). An increased risk of chronic kidney disease (CKD) was also found in the patients with HS and other HRIs compared to that in the controls (17.33% vs. 14.67% vs. 6.67%, p = 0.016).ConclusionPrior HS was associated with an increased incidence of CVDs, particularly AMI and AIS, and an increased incidence of CKD.

Spinal cord ischemic injury and consequently permanent paraplegia remain the most devastating complications after open and endovascular thoracic or thoracoabdominal aortic aneurysm repair. Hemodynamic stability, which depends on a network of blood vessels around the cord, is most important not only during but also after stent-graft deployment to prevent spinal cord injury. Despite the use of various strategies to prevent spinal cord ischemia, including aggressive revascularization of the subclavian artery and cerebrospinal fluid drainage, this condition remains inevitable and difficult to predict before an operation. We present a rare case of a patient who presented with unilateral paraplegia that developed after thoracic endovascular aortic repair for aortic arch aneurysm and our subsequent salvage strategy.

Background: The aim of this study was to examine the utility of the vascular ring connector (VRC) and compare the clinical outcomes to conventional suture technique in the operation for acute type A aortic dissection (AAAD). Methods: We retrospectively enrolled 64 consecutive patients (mean age 57.4 ± 12.7 years, range 24-82 years) with AAAD who underwent emergent surgery in our institution from September 2010 to November 2014. Patients were divided into VRC group (55 patients) and conventional suture group (nine patients) based on the use of VRC during the operation. The preoperative characteristics, operative variables, and postoperative outcomes were collected and analyzed. Results: Male patients predominated in both groups. The mean times of cardiopulmonary bypass and aortic cross-clamp were 200.1 ± 99.9 and 193.6 ± 54.7 min (P = 0.425) and 107.5 ± 56.2 and 112.3 ± 40.8 min (P = 0.404) in the VRC group and suture group, respectively. There were more blood transfusions within 24 h (1513.3 ± 949.2 vs. 841.8 ± 801.1 ml) and more mediastinal drainage amount (1314.4 ± 650.3 ml vs. 942.1 ± 527.2 ml) in the suture group than in the VRC group. In the VRC group, 36.3% of patients did not require blood transfusion. Moreover, the pumping time and cardiac ischemic times were longer in the one-VRC group than in the two-VRC group. Operative mortality did not differ between the two groups (10.9% in VRC and 11.1% in suture group, P = 0.985). No dislodgement of VRC during or after operation and no bleeding from sutureless anastomosis site were noted. Conclusion: Use of VRC is associated with equivalent operative mortality and morbidity compared to suture group in patients with AAAD undergoing an emergent operation. This study demonstrates the clinical safety and efficacy of VRC in reducing the need of blood transfusion within 24 h and mediastinal drainage within 72 h. However, further randomized studies and long-term surveillance of the use of VRC in AAAD are still mandatory.

Background: Cardiopulmonary bypass (CPB) induces postoperative immunosuppression, including decreased T-cells and lower plasma regulated on activation, normal T-cell expressed and secreted (RANTES) concentrations. MicroRNA-125a negatively regulates RANTES expression in activated T-cells. The aims were to investigate microRNA-125a expression in T-cells and RANTES production following CPB. Materials and Methods: Twenty-eight patients undergoing elective cardiac surgery were included in this study. Arterial blood was sampled at six sequential points (before anesthesia induction, before CPB, at 2, 4, 6, and 24 h after beginning CPB) for plasma RANTES concentrations by enzyme-linked immunosorbent assay. T-lymphocytes were isolated from whole blood at four points (before anesthesia, before CPB, at 2 and 4 h after beginning CPB) for intracellular microRNA-125a expression by quantitative real-time reverse transcription polymerase chain reaction in 14 patients. Perioperative laboratory data and variables were also recorded. Results: The plasma RANTES concentrations decreased significantly at 2-24 h after beginning CPB, with concurrent reduction of postoperative lymphocyte counts, as compared with the preanesthesia level (P < 0.001). Intra-T-cell microRNA-125a expression was activated at 2 and 4 h, however, without significance (P = 0.078 and 0.124, respectively). The plasma RANTES levels at 4 h were not correlated with CPB time (P = 0.671), anesthesia time (P = 0.305), postoperative extubation time (P = 0.508), and Intensive Care Unit (ICU) stay (P = 0.756). Three patients expired with pneumonia- or mediastinitis-related septic shock in the ICU. Conclusion: Plasma RANTES concentrations were depressed till 24 h following CPB, with reduced lymphocytes after cardiac surgery. MicroRNA-125a expression in T-lymphocytes was not correlated with perioperative variables and its role in downregulation of RANTES production needs to be determined.

We report a case of delayed hemothorax resulted from diaphragmatic laceration after blunt chest trauma and its successful treatment. Initial chest X-ray and initial computed tomography (CT) scan revealed no hemothorax in this 19-year-old male with a stable hemodynamic condition although there were multiple contusion wounds with ecchymoses over the right chest wall, shoulder, back and right upper quadrant of abdomen. In the following day, he experienced progressive dyspnea and conscious disturbance. Massive hemothorax was verified through repeated chest X-ray and CT scan. A laceration wound about 3 cm in length with continuous oozing at the dome of the right hemidiaphragm was noted in emergent thoracotomy. The laceration was repaired, and the patient had an uneventful recovery after the surgery. We proposed that traumatic diaphragmatic injury should be considered in any patient who has sustained blunt trauma to the lower chest and upper abdomen regions, watchful observation and high index of suspicion are necessary.

Anomalous left coronary artery arising from the pulmonary artery (ALCAPA) is a rare type of congenital coronary abnormality that may be associated with early infant mortality and sudden adult cardiac death. We report a case regarding a 23-year-old male who collapsed during a marathon race and was resuscitated with cardiopulmonary resuscitation. Subsequent workups verified the diagnosis of ALCAPA. The patient underwent surgical intervention with obliteration of the ALCAPA orifice and coronary artery bypass grafting with left internal mammary artery to left anterior descending coronary artery. The procedure was done smoothly, and he was discharged uneventfully.

There are few studies on heparin-induced thrombocytopenia (HIT) reported from Taiwan and Asian countries. We conducted a prospective study to investigate the frequency of HIT in patients undergoing cardiopulmonary bypass surgeries. Methods: A cohort of 54 patients was enrolled from January 01, 2010 to October 31, 2011. Patients' clinical information was obtained for 4T score classification. Plasma (2–4 mL) was also collected before surgery and on Days 5 and 10 following heparin administration during the bypass procedure. This was tested for anti-heparin/PF4 antibodies and functional assay using flow cytometry (FC). Results: The mean platelet count for this cohort followed the expected pattern in the postoperative setting. Seven of the 54 (13%) patients had positive antibodies assays before bypass surgery. This increased to 32% on Day 5 and was markedly elevated to 63% on Day 10 after surgery. Only one of the 54 patients (1.8%) was found to have both positive antibody assay and platelet activation, but no clinical HIT/thrombosis developed. Conclusion: Our study is the first report on the rates of HIT in the setting of cardiopulmonary bypass surgery in Taiwan and demonstrated no clinical HIT occurrence, despite the high frequency of HIT antibody in our cohort.

As the shortcomings of deinstitutionalization become evident, models of institution-based therapeutic communities are starting to appear as promising alternatives. While institution-based therapy models produce desirable outcomes for some categories of mental illness, these lessons have not been applied to exploring community approaches to child mental health. To this end, we use an identity narrative approach to explore the relation between mental illnesses and childhood or adolescent development in narratives of patients treated under different therapeutic models for three conditions: severe mental illness (SMI), substance abuse and ADHD. Only the ADHD patients were children; the SMI and substance abuse treatment models were designed for adult patients. But all patient narratives showed the illness had roots in childhood. This secondary analysis examines patient narratives collected from three independent projects between 2005 and 2013. The oral history study of the Yu Li therapeutic model for SMI was conducted from 2005 to 2006. The project documenting a therapeutic model for substance abusers in the Tsao Tun Psychiatric Center was carried out from 2009 to 2010. Lastly, we took oral histories from participants in an ADHD family support group between 2011 and 2013. The development and nature of these models will be illustrated first, then contrasted, to identify the key elements of empowerment in each type of therapeutic community. We further apply the Jonsen’s four-topic approach to clinical decision making to clarify the ethical dilemmas in assignment of tasks and to distinguish how each division of labor affects patient empowerment. While considering the nature of illness or recovery for different categories of patients, we find narrative understandings are crucial for ascertaining the residual functioning of each patient, and for striking a balance between individual existence and social being. We conclude narrative medicine constitutes a specialized approach for building recovery models and promoting mental health.

Fungal endocarditis is a very rare entity and is associated with high morbidity and mortality rates. We report a 68-year-old man with fungal valvular endocarditis over the mitral valve with a large vegetation located over the anterior leaflet, presenting initially as acute limb ischemia of the left lower limb. Immediate embolectomy was performed for revascularization of the left lower limb. Pathologic section of the retrieved femoral embolectomy specimen revealed aggregated fungal spores and hyphae. Blood cultures were positive for Candida tropicalis. We should be alert to treat patients with acute arterial occlusion of the extremities and to investigate the underlying possible fatal etiology.

[This corrects the article DOI: 10.1371/journal.pone.0079452.].

Background: Coronary artery disease occurs frequently and is a major cause of morbidity and mortality in patients with chronic renal failure. Because the number of patients requiring dialysis for end-stage renal disease (ESRD) has increased, the number of patients in this population who require coronary artery bypass grafting (CABG) has increased. The aim of this study was to examine the effect of early hemodialysis (HD) on the early surgical outcomes of ESRD patients undergoing CABG. Materials and Methods: Fifty-nine dialysis-dependent patients who underwent isolated CABG with cardiopulmonary bypass (CPB) were enrolled in this study. These patients were divided into two groups based on the timing of the first postoperation HD session. In the early HD group, HD was performed within 6 h postoperation; in the scheduled HD group, HD was performed >6 h postoperation. The preoperative characteristics, operative variables, and postoperative outcomes were retrospectively analyzed. Results: The time to first HD after CABG was 2.43 ± 1.58 h in the early HD group and 20.68 ± 6.98 h in the scheduled HD group (P < 0.001). There were no significant differences in the operative variables, namely duration of operation, CPB time, and aortic cross-clamp time, between the two groups. The incidence of postoperative pneumonia was higher in the scheduled HD group (31.8%) than in the early HD group (2.7%). There was a trend of decreased incidence of postoperative pneumonia in the early HD group with marginal significance from the univariate analysis. The intensive care unit and hospital stay duration of both groups were similar. Nine patients died in the hospital, yielding an overall 30-day mortality of 8.47%. Conclusion: In dialysis-dependent patients who underwent CABG, the short-term outcomes and surgical mortality were acceptable. Dialysis-dependent renal failure should not be considered a contraindication for CABG. Early HD in the postoperative period demonstrated the trend to reduce the incidence of postoperative pneumonia; however, other parameters of surgical outcomes were insignificant.

Population-based evidence of the relative risk of cancer among heart, kidney, and liver transplant recipients from Asia is lacking. The Taiwan National Health Insurance Research Database was used to conduct a population-based cohort study of transplant recipients (n = 5396), comprising 801 heart, 2847 kidney, and 1748 liver transplant recipients between 2001 and 2012. Standardized incidence ratios and Cox regression models were used. Compared with the general population, the risk of cancer increased 3.8-fold after heart transplantation, 4.1-fold after kidney transplantation and 4.6-fold after liver transplantation. Cancer occurrence showed considerable variation according to transplanted organs. The most common cancers in all transplant patients were cancers of the head and neck, liver, bladder, and kidney and non-Hodgkin lymphoma. Male recipients had an increased risk of cancers of the head and neck and liver, and female kidney recipients had a significant risk of bladder and kidney cancer. The adjusted hazard ratio for any cancer in all recipients was higher in liver transplant recipients compared with that in heart transplant recipients (hazard ratio = 1.5, P = .04). Cancer occurrence varied considerably and posttransplant cancer screening should be performed routinely according to transplanted organ and sex.

Background. Cardiopulmonary bypass (CPB) causes release of matrix metalloproteinase- (MMP-) 9, contributing to pulmonary infiltration and dysfunction. The aims were to investigate MMP-9 production and associated perioperative variables and oxygenation following CPB. Methods. Thirty patients undergoing elective cardiac surgery were included. Arterial blood was sampled at 6 sequential points (before anesthesia induction, before CPB and at 2, 4, 6, and 24 h after beginning CPB) for plasma MMP-9 concentrations by ELISA. The perioperative laboratory data and variables, including bypass time, PaO2/FiO2, and extubation time, were also recorded. Results. The plasma MMP-9 concentrations significantly elevated at 2–6 h after beginning CPB (P

Neonates undergoing open-heart surgery are particularly at risk of postoperative bleeding requiring blood transfusion. Aprotinin has attained high efficacy in reducing the requirement for a blood transfusion following a cardiopulmonary bypass, but is seldom studied in the neonatal age group. The aim of this study was to compare the efficacy and adverse effects of aprotinin and tranexamic acid in neonates undergoing open-heart surgery at a single centre.Between October 2003 and March 2008, perioperative data of 552 consecutive neonatal patients undergoing open-heart surgery in Children's Hospital Boston were reviewed. Among them, 177 did not receive antifibrinolytic therapy (Group A); 100 were treated with tranexamic acid only (Group B); and 275 patients received aprotinin with or without tranexamic acid (Group C). Except for antifibrinolytic therapy, the anaesthesiological and surgical protocols remained identical. Postoperative complications and in-hospital mortality were the primary study endpoints.Body weight and Risk Adjustment for Congenital Heart Surgery (RACHS-1) scores were statistically comparable among the three groups. No statistically significant differences were observed between the duration of hospitalization, chest tube drainage, reexploration for bleeding, and kidney function impairment. In Group C, less blood was transfused within 24 hours than in GroupB. Operative mortality was similar among the three groups.No further risk and kidney injury were observed in the use of aprotinin in neonatal cardiac surgery, aprotinin demonstrated a reduced requirement for blood transfusion compared with tranexamic acid. Our data provide reasonable evidence that aprotinin and tranexamic acid are safe and efficacious as antifibrinolytic modalities in neonatal patients undergoing cardiac surgery.

Background: Thrombomodulin (TM) is a type of cell membrane-bound anticoagulant protein cofactor in the thrombin-mediated activation of protein C. Previous evidence has shown an association between TM polymorphisms and systemic inflammation. Conventional cardiopulmonary bypass (CPB), beating-heart CPB, and off-pump techniques have been widely used in cardiac surgery. However, these techniques may also cause systemic inflammatory responses in the patients. Whether TM polymorphisms are associated with systemic inflammation after cardiac surgery is still unclear. Methods: We analyzed the TM gene C1418T polymorphisms in 347 patients who underwent coronary artery bridge graft (CABG) surgery using allele-specific primers in a PCR assay. The clinical data during the hospital stay were collected and tested for correlations with the TM gene C1418T polymorphisms. Results: We separated the patients into two groups based on their TM C1418T genotype (CC genotype group and CT/TT genotype group). The days spent in an intensive care unit (ICU) and the incidence of fever in the ICU were significantly lower in the beating-heart CPB and off-pump groups than in the conventional CPB group. Additionally, the TM gene C1418T polymorphisms did not affect the early outcomes in patients in the beating-heart CPB and off-pump groups. Interestingly, in the conventional CPB group, patients with the CC genotype had a lower rate of fever, shorter duration of fever, and delay of ICU when compared with the CT/TT genotype. Conclusion: Surgeons may use a patient’s TM gene C1418T polymorphism to predict the strength of systemic inflammation and speculate on early outcomes during hospitalization before conventional CPB is performed.

Toll-like receptors (TLRs) plays a critical role in innate immunity. In 2004, Aslam R. and Shiraki R. first determined that murine and human platelets express functional TLRs. Additionally, Andonegui G. demonstrated that platelets express TLR4, which contributes to thrombocytopenia. However, the underlying mechanisms of TLR4 expression by platelets have been rarely explored until now. The aim of this study was to identify the mechanism of TLR4 expression underlying thrombin treatment. The human washed platelets were used in this study. According to flowcytometry and western blot analysis, the surface levels of TLR4 were significantly enhanced in thrombin-activated human platelets and decreased by TMB-8, calpeptin, and U73122, but not Y27632 (a Rho-associated protein kinase ROCK inhibitor) indicating that thrombin-mediated TLR4 expression was modulated by PAR/PLC pathway, calcium and calpain. Co-immunoprecipitation (co-IP) assay demonstrated that the interaction between TLR4 and myosin-9 (a substrate of calpain) was regulated by calpain; cleavage of myosin-9 enhanced TLR4 expression in thrombin treated platelets. Transmission electron microscope data indicated that human platelets used α-granules to control TLR4 expression; the co-IP experiment suggested that myosin-9 did not coordinate with Rab7b to negatively regulate TLR4 trafficking in thrombin treated platelets. In summary, phospholipase Cγ-calpain-myosin 9-Rab7b axis was responsible for the mechanism underlying the regulation of TLR4 containing α-granules trafficking in thrombin-stimulated platelets, which was involved in coagulation.

The tyrosine kinase receptor Axl is expressed in the vasculature, and growth arrest-specific protein 6 (Gas6) is its ligand. Plasma Gas6 levels have been shown to be associated with endothelial dysfunction markers and cardiovascular events. We set out to determine the plasma Gas6 levels in patients undergoing coronary artery bypass grafting (CABG) and investigate the expression of Gas6 and Axl in the aorta.Immunoassays were used to investigate plasma Gas6 levels in CABG patients (n = 19) and control subjects (n = 20). The expression of Gas6 and Axl in the injured aorta were examined by reverse transcription-polymerase chain reactions, real-time reverse transcription-polymerase chain reactions, western blotting, and immunohistochemical staining. Plasma Gas6 levels were significantly lower in CABG patients than in matched control subjects. In CABG patients, plasma Gas6 levels were negatively correlated with fasting glucose, E-selectin, and vascular cell adhesion molecule-1 levels. The levels predicted the operative mortality rate and were positively correlated with plasma soluble Axl (sAxl) levels and Gas6 expression in the aorta. Moreover, Gas6 expression was positively correlated with Axl expression in the aorta.We concluded that plasma Gas6 is associated with fasting glucose, endothelial dysfunction markers, sAxl values, and vascular Gas6 expression in CABG patients, and it predicts the operative mortality of these patients. These findings suggest that the Gas6/Axl system is crucial in vascular biology.

Migration of vascular smooth muscle cells (VSMCs) into the intima is considered to be a vital event in the pathophysiology of atherosclerosis. Despite substantial evidence supporting the pathogenic role of Toll-like receptor 4 (TLR4) in the progression of atherogenesis, its function in the regulation of VSMC migration remains unclear. The goal of the present study was to elucidate the mechanism by which TLR4 regulates VSMC migration. Inhibitor experiments revealed that TLR4-induced IL-6 secretion and VSMC migration were mediated via the concerted actions of MyD88 and TRIF on the activation of p38 MAPK and ERK1/2 signaling. Neutralizing anti-IL-6 antibodies abrogated TLR4-driven VSMC migration and F-actin polymerization. Blockade of p38 MAPK or ERK1/2 signaling cascade inhibited TLR4 agonist-mediated activation of cAMP response element binding protein (CREB). Moreover, siRNA-mediated suppression of CREB production repressed TLR4-induced IL-6 production and VSMC migration. Rac-1 inhibitor suppressed TLR4-driven VSMC migration but not IL-6 production. Importantly, the serum level of IL-6 and TLR4 endogenous ligand HMGB1 was significantly higher in patients with coronary artery diseases (CAD) than in healthy subjects. Serum HMGB1 level was positively correlated with serum IL-6 level in CAD patients. The expression of both HMGB1 and IL-6 was clearly detected in the atherosclerotic tissue of the CAD patients. Additionally, there was a positive association between p-CREB and HMGB1 in mouse atherosclerotic tissue. Based on our findings, we concluded that, upon ligand binding, TLR4 activates p38 MAPK and ERK1/2 signaling through MyD88 and TRIF in VSMCs. These signaling pathways subsequently coordinate an additive augmentation of CREB-driven IL-6 production, which in turn triggers Rac-1-mediated actin cytoskeleton to promote VSMC migration.

A 36-year-old male had congenitally corrected transposition of the great arteries (cc-TGA) with heart failure underwent heart transplantation. Due to the abnormal alignment of the great arteries in cc-TGA, the transplantation required technical modifications. When harvesting the donor heart, extra length of the pulmonary artery was preserved. The donor′s pulmonary artery was cut at its bifurcation. Anastomosis of the pulmonary artery followed anastomosis of the left and right atrium. Last, aortic anastomosis was performed. Preservation of extraordinary pulmonary artery of the donor′s heart may be necessary to achieve an acceptable anastomosis. Heart transplantation for cc-TGA is technically feasible.