Publications by authors named "Chen-Yu Huang"

76 Publications

Clinical implementation of kVCT-guided tomotherapy with ClearRT.

Phys Eng Sci Med 2022 Aug 4. Epub 2022 Aug 4.

Medical Physics Department, Hong Kong Sanatorium & Hospital, 2 Village Road, Happy Valley, Hong Kong, China.

A helical fan-beam kilovoltage computed tomography (kVCT) was recently introduced into Tomotherapy units. This study aims to share the initial experience of kVCT in clinical workflow, compare its performance with that of the existing megavoltage computed tomography (MVCT), and explore its potential in adaptive planning. We retrospectively enrolled 23 patients who underwent both MVCT and kVCT scans. The clinical performance data regarding image acquisition time, nominal dose length product (DLP), registration time and registration corrections were extracted and compared. Image quality was scored by six experienced radiation therapists and quantified based on phantom measurements. CT number stability and the implementation of adaptive radiotherapy were dosimetrically evaluated by performing the dose recalculation on kVCT. Compared to MVCT, kVCT significantly reduced DLP (except the highest kVp protocol), image acquisition and registration time. KVCT obtained higher scores than MVCT on all criteria except artifacts. Phantom measurements also revealed a better image performance characterization of kVCT except for image uniformity. The CT number variation could lead to a dose difference of 0.5% for D95% of target and D of organ-at-risk. For the treatment planning with kVCT, a systematic dose difference (> 1%) in PTV dose metrics was observed at regions with large longitudinal density discontinuities compared to the reference plans. The new kVCT imaging provides enhanced soft-tissue visualization. The improved efficiency with kVCT-guided treatment will allow more patients to be treated each day. In most cases, the dose calculation accuracy of kVCT images is acceptable except for regions with severe artifacts.
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http://dx.doi.org/10.1007/s13246-022-01162-yDOI Listing
August 2022

Out-of-field dose and its constituent components for a 1.5 T MR-Linac.

Phys Med Biol 2021 11 15;66(22). Epub 2021 Nov 15.

Medical Physics Department, Hong Kong Sanatorium & Hospital, 2 Village Road, Happy Valley, Hong Kong, People's Republic of China.

This study aims to quantify the relative contributions of phantom scatter, collimator scatter and head leakage to the out-of-field doses (OFDs) of both static fields and clinical intensity-modulated radiation therapy (IMRT) treatments in a 1.5 T MR-Linac. The OFDs of static fields were measured at increasing distances from the field edge in an MR-conditional water phantom. Inline scans at depths of dmax (14 mm), 50 and 100 mm were performed for static fields of 5 × 5, 10 × 10 and 15 × 15 cmunder three different conditions: full scatter, with phantom scatter prevented, and head leakage only. Crossline scans at isocenter and offset positions were performed in full scatter condition. EBT3 radiochromic films were placed at 100 mm depth of solid water phantom to measure the OFD of clinical IMRT plans. All water tank data were normalized to Dmax of a 10 × 10 cmfield and the film results were presented as a fraction of the target mean dose.The OFD in the inline direction varied from 3.5% (15 × 15 cm, 100 mm depth, 50 mm distance) to 0.014% (5 × 5 cm, dmax, 400 mm distance). For all static fields, the collimator scatter was higher than the phantom scatter and head leakage at a distance of 100-400 mm. Head leakage remained the smallest among the three components, except at long distances (>375 mm) with small field size. Compared to the inline scans, the crossline scans at the isocenter showed higher doses at distances longer than 80 mm. All crossline profiles at longitudinal offset positions showed a cone shape with laterally shifted maxima. The OFD of IMRT deliveries varied with different target size. For prostate stereotactic body radiation therapy (SBRT) treatment, the OFD decreased from 2% to 0.03% at a distance of 50-500 mm. The OFDs have been measured for a 1.5 T MR-Linac. The presented dosimetric data are valuable for radiation safety assessments on patients treated with the MR-Linac, such as evaluating carcinogenic risk and radiation exposure to cardiac implantable electronic devices.
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http://dx.doi.org/10.1088/1361-6560/ac3346DOI Listing
November 2021

Magnetic Resonance-Guided Radiation Therapy of Patients With Cardiovascular Implantable Electronic Device on a 1.5 T Magnetic Resonance-Linac.

Pract Radiat Oncol 2022 Jan-Feb;12(1):e56-e61. Epub 2021 Sep 11.

Medical Physics and Research Department, Happy Valley, Hong Kong, China.

Magnetic resonance-guided radiation therapy is reported for treating patients with an insertable cardiac monitor and implantable cardiac pacemakers. All treatments were delivered using a 1.5 T MR-Linac. Among the 4 patients, 2 were treated with stereotactic body radiation therapy at a dose of 40 Gy in 5 fractions. A clinical safety protocol was developed to address the decision-making and patient selection, as well as the clarified responsibilities of different parties for management of patients with cardiovascular implantable electronic devices. Dose estimation based on out-of-field dose data are necessary for cardiovascular implantable electronic devices located outside the treatment fields.
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http://dx.doi.org/10.1016/j.prro.2021.08.011DOI Listing
January 2022

Structural and biochemical insights into a hyperthermostable urate oxidase from Thermobispora bispora for hyperuricemia and gout therapy.

Int J Biol Macromol 2021 Oct 14;188:914-923. Epub 2021 Aug 14.

Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan; Department of Agricultural Chemistry, National Taiwan University, Taipei 10617, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei 10617, Taiwan. Electronic address:

Microbial urate oxidase has emerged as a potential source of therapeutic properties for hyperuricemia in arthritic gout and renal disease. The thermostability and long-term thermal tolerance of the enzyme need to be established to prolong its therapeutic effects. Here, we present the biochemical and structural aspects of a hyperthermostable urate oxidase (TbUox) from the thermophilic microorganism Thermobispora bispora. Enzymatic characterization of TbUox revealed that it was active over a wide range of temperatures, from 30 to 70 °C, with optimal activity at 65 °C and pH 8.0, which suggests its applicability under physiological conditions. Moreover, TbUox exhibits high thermostability from 10 to 65 °C, with Tm of 70.3 °C and near-neutral pH stability from pH 7.0 to 8.0 and high thermal tolerance. The crystal structures of TbUox revealed a distinct feature of the C-terminal loop extensions that may help with protein stability via inter-subunit interactions. In addition, the high thermal tolerance of TbUox may be contributed by the extensive inter-subunit contacts via salt bridges, hydrogen bonds, and hydrophobic interactions. The findings in this study provide a molecular basis for the thermophilic TbUox urate oxidase for application in hyperuricemia and gout therapy.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.081DOI Listing
October 2021

Molecular Elucidation of a Urate Oxidase from for Hyperuricemia and Gout Therapy.

Int J Mol Sci 2021 May 25;22(11). Epub 2021 May 25.

Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 115024, Taiwan.

Urate oxidase initiates the uric acid degradation pathways and is extensively used for protein drug development for gout therapy and serum uric acid diagnosis. We first present the biochemical and structural elucidation of a urate oxidase from the extremophile microorganism (DrUox). From enzyme characterization, DrUox showed optimal catalytic ability at 30 °C and pH 9.0 with high stability under physiological conditions. Only the Mg ion moderately elevated its activity, which indicates the characteristic of the cofactor-free urate oxidase family. Of note, DrUox is thermostable in mesophilic conditions. It retains almost 100% activity when incubated at 25 °C and 37 °C for 24 h. In this study, we characterized a thermostable urate oxidase, DrUox with high catalytic efficiency and thermal stability, which strengthens its potential for medical applications.
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http://dx.doi.org/10.3390/ijms22115611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199477PMC
May 2021

Long Term Outcome of Postoperative Atrial Fibrillation After Cardiac Surgery-A Propensity Score-Matched Cohort Analysis.

Front Cardiovasc Med 2021 27;8:650147. Epub 2021 Apr 27.

Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Postoperative atrial fibrillation (POAF) results in a longer hospital stay and excess mortality. However, whether POAF would increase stroke rate has been debated for years. When and how long should anticoagulation be used to prevent stroke are unknown. In the study, we planned to investigate the clinical demographics and long-term outcomes of POAF after cardiac surgery in a single-center cohort. The cohort study used a database from National Taiwan University Hospital, a single tertiary medical center in Taiwan, between 2007 and 2017, to identify patients with prior normal sinus rhythm developing POAF after cardiac surgery. Patients without POAF after cardiac surgery were used as controls. Propensity score matching with 1:1 ratio and Cox regression models were employed to estimate the risk of transient ischemic accident (TIA) or ischemic stroke. From 2007 to 2017, a total of 8,374 patients received open-heart surgery, in which 1,585 patients with a history of AF were excluded. The overall incidence of TIA/ischemic stroke was 3.9% in a median 9.2-years of follow-up. After propensity matching, 1,965 matched paired subjects were included for analysis. Postoperative atrial fibrillation was associated with an increased risk of future AF [Hazard ratio (HR) 1.40, 95% confidence interval (95%CI) = 1.09-1.79, = 0.008] and heart failure (HF) hospitalization (HR 1.58, 95%CI 1.23-2.04, < 0.001); however, POAF did not significantly correlate with the risk of TIA/ischemic stroke (HR 1.17, 95%CI 0.85-1.60, = 0.043). Kaplan-Meier analysis showed that POAF was a significant predictor for future AF, HF hospitalization, and overall mortality, but not for TIA/ischemic stroke. In the Asian population, POAF after cardiac surgery increased the risk of future AF, HF, and overall mortality, but was not associated with future TIA/ischemic stroke.
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http://dx.doi.org/10.3389/fcvm.2021.650147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112811PMC
April 2021

Reproductive outcomes of microdissection testicular sperm extraction in hypogonadotropic hypogonadal azoospermic men after gonadotropin therapy.

J Assist Reprod Genet 2021 Oct 12;38(10):2601-2608. Epub 2021 May 12.

Department of Urology, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 11217, Taiwan.

Purpose: Male infertility caused by hypogonadotropic hypogonadism (HH) is not common. The main treatment is gonadotropins for 12 months or longer. If the patient is still azoospermic, conventional or microdissection testicular sperm extraction (mTESE) may further help in sperm retrieval. We aimed to analyze the fertility outcomes of HH men treated at our institute.

Methods: From 2008 to 2020, infertile men with hormone profile showing HH were enrolled. Gonadotropin therapy was prescribed if parenthood was being considered. Assisted reproductive technology was available to help patients attain fertility depending on the results of sperm analysis. Patient outcomes, including sperm retrieval, pregnancy and live birth rates, were analyzed.

Results: Seventeen initially azoospermic patients were administered gonadotropins for an average of 11.1 months, and sperm was subsequently found in the ejaculate of seven patients (41%). mTESE was performed on the other ten (59%) who were still azoospermic. For these 10 patients, they had collectively undergone an average 12.1 months (range 6-23 months) of gonadotropin therapy. Sperm was retrieved in nine (90.0%) cases. After 11 cycles of TESE-ICSI, six (54.5%) successful pregnancies were recorded, resulting in five (55.6%) cases with live-born babies, including two sets of twins, and one case of missed abortion at 9 weeks of gestation.

Conclusion: Gonadotropin therapy reversed azoospermia in a portion of the HH male patients studied. Of men who were still azoospermic after gonadotropin treatment, a majority could still have testicular sperm retrieved by mTESE for use in assisted reproductive technology, subsequently resulting in live births.
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http://dx.doi.org/10.1007/s10815-021-02211-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581149PMC
October 2021

Developing a Web-Based Shared Decision-Making Tool for Fertility Preservation Among Reproductive-Age Women With Breast Cancer: An Action Research Approach.

J Med Internet Res 2021 03 17;23(3):e24926. Epub 2021 Mar 17.

MacKay Medical College, Department of Nursing, New Taipei City, Taiwan.

Background: The pregnancy rate after cancer treatment for female survivors is lower than that of the general population. Future infertility is a significant concern for patients with breast cancer and is associated with a poor quality of life. Reproductive-age patients with breast cancer have safe options when choosing a type of fertility preservation method to be applied. Better information and support resources aimed at women to support their decision making are needed.

Objective: The objective of this study was to develop a web-based shared decision-making tool for helping patients with breast cancer make decisions on fertility preservation.

Methods: We used the action research cycle of observing, reflecting, planning, and acting to develop a web-based shared decision-making tool. The following four phrases were applied: (1) observe and reflect-collect and analyze the decision-making experiences of patients and health care providers; (2) reflect and plan-apply the initial results to create a paper design and modify the content; (3) plan and act-brainstorm about the web pages and modify the content; (4) act and observe-evaluate the effectiveness and refine the website's shared decision-making tool. Interviews, group meetings, and constant dialogue were conducted between the various participants at each step. Effectiveness was evaluated using the Preparation for Decision-Making scale.

Results: Five major parts were developed with the use of the action research approach. The Introduction (part 1) describes the severity of cancer treatment and infertility. Options (part 2) provides the knowledge of fertility preservation. The shared decision-making tool was designed as a step-by-step process (part 3) that involves the comparison of options, patient values, and preferences; their knowledge regarding infertility and options; and reaching a collective decision. Resources (part 4) provides information on the hospitals that provide such services, and References (part 5) lists all the literature cited in the website. The results show the web-based shared decision-making meets both patients' and health providers' needs and helps reproductive-age patients with breast cancer make decisions about fertility preservation.

Conclusions: We have created the first web-based shared decision-making tool for making fertility preservation decisions in Taiwan. We believe female patients of reproductive age will find the tool useful and its use will become widespread, which should increase patient autonomy and improve communication about fertility preservation with clinicians.

Trial Registration: Clinicaltrials.gov NCT04602910; https://clinicaltrials.gov/ct2/show/NCT04602910.
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http://dx.doi.org/10.2196/24926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074988PMC
March 2021

Effects on skin dose from unwanted air gaps under bolus in an MR-guided linear accelerator (MR-linac) system.

Phys Med Biol 2021 03 12;66(6):065021. Epub 2021 Mar 12.

Medical Physics and Research Department, Hong Kong Sanatorium and Hospital, Hong Kong SAR, People's Republic of China.

Bolus is commonly used in MV photon radiotherapy to increase superficial dose and improve dose uniformity for treating shallow lesions. However, irregular patient body contours can cause unwanted air gaps between a bolus and patient skin. The resulting dosimetric errors could be exacerbated in MR-Linac treatments, as secondary electrons generated by photons are affected by the magnetic field. This study aimed to quantify the dosimetric effect of unwanted gaps between bolus and skin surface in an MR-Linac. A parallel-plate ionization chamber and EBT3 films were utilized to evaluate the surface dose under bolus with various gantry angles, field sizes, and different air gaps. The results of surface dose measurements were then compared to Monaco 5.40 Treatment Planning System (TPS) calculations. The suitability of using a parallel-plate chamber in MR-Linac measurement was validated by benchmarking the percentage depth dose and output factors with the microDiamond detector and air-filled ionization chamber measurements in water. A non-symmetric response of the parallel-plate chamber to oblique beams in the magnetic field was characterized. Unwanted air gaps significantly reduced the skin dose. For a frontal beam, skin dose was halved when there was a 5 mm gap, a much larger difference than in a conventional linac. Skin dose manifested a non-symmetric pattern in terms of gantry angle and gap size. The TPS overestimated skin dose in general, but shared the same trend with measurement when there was no air gap, or the gap size was larger than 5 mm. However, the calculated and measured results had a large discrepancy when the bolus-skin gap was below 5 mm. When treating superficial lesions, unwanted air gaps under the bolus will compromise the dosimetric goals. Our results highlight the importance of avoiding air gaps between bolus and skin when treating superficial lesions using an MR-Linac system.
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http://dx.doi.org/10.1088/1361-6560/abe837DOI Listing
March 2021

Molecular Mechanisms of Laparoscopic Ovarian Drilling and Its Therapeutic Effects in Polycystic Ovary Syndrome.

Int J Mol Sci 2020 Oct 31;21(21). Epub 2020 Oct 31.

Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei 112, Taiwan.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and multiple small subcapsular cystic follicles in the ovary during ultrasonography, and affects 5-10% of women of reproductive age. PCOS is frequently associated with insulin resistance (IR) accompanied by compensatory hyperinsulinemia and, therefore, presents an increased risk of type 2 diabetes mellitus (DM). The pathophysiology of PCOS is unclear, and many hypotheses have been proposed. Among these hypotheses, IR and hyperandrogenism may be the two key factors. The first line of treatment in PCOS includes lifestyle changes and body weight reduction. Achieving a 5-15% body weight reduction may improve IR and PCOS-associated hormonal abnormalities. For women who desire pregnancy, clomiphene citrate (CC) is the front-line treatment for ovulation induction. Twenty five percent of women may fail to ovulate spontaneously after three cycles of CC treatment, which is called CC-resistant PCOS. For CC-resistant PCOS women, there are many strategies to improve ovulation rate, including medical treatment and surgical approaches. Among the various surgical approaches, one particular surgical method, called laparoscopic ovarian drilling (LOD), has been proposed as an alternative treatment. LOD results in an overall spontaneous ovulation rate of 30-90% and final pregnancy rates of 13-88%. These benefits are more significant for women with CC-resistant PCOS. Although the intra- and post-operative complications and sequelae are always important, we believe that a better understanding of the pathophysiological changes and/or molecular mechanisms after LOD may provide a rationale for this procedure. LOD, mediated mainly by thermal effects, produces a series of morphological and biochemical changes. These changes include the formation of artificial holes in the very thick cortical wall, loosening of the dense and hard cortical wall, destruction of ovarian follicles with a subsequently decreased amount of theca and/or granulosa cells, destruction of ovarian stromal tissue with the subsequent development of transient but purulent and acute inflammatory reactions to initiate the immune response, and the continuing leakage or drainage of "toxic" follicular fluid in these immature and growth-ceased pre-antral follicles. All these factors contribute to decreasing local and systemic androgen levels, the following apoptosis process with these pre-antral follicles to atresia; the re-starting of normal follicular recruitment, development, and maturation, and finally, the normalization of the "hypothalamus-pituitary-ovary" axis and subsequent spontaneous ovulation. The detailed local and systematic changes in PCOS women after LOD are comprehensively reviewed in the current article.
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http://dx.doi.org/10.3390/ijms21218147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663012PMC
October 2020

Endometriosis of the Paralumbar Muscles: A Case Report and Literature Review.

Gynecol Minim Invasive Ther 2020 Jul-Sep;9(3):170-174. Epub 2020 Aug 1.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.

The objective of this study is to report a case of deep endometriosis of the paralumbar muscles (psoas, multifidus, and erector spinae) and review existing literature on its management. A 34-year-old female with a history of endometriosis was seen for infertility. Paralumbar muscle masses seen on computed tomography (CT) scan were sampled, confirming endometriosis. Gonadotropin-releasing hormone agonist was given for 2 months. The patient was primed for assisted reproduction. A literature review was conducted to provide an understanding of paralumbar muscle endometriosis. To our knowledge, this is the first reported case of multifidus and erector spinae muscle endometriosis and fifth case of psoas muscle endometriosis. Because the available information is scarce, data from the existing literature on deep endometriosis may aid in the diagnosis and management. Magnetic resonance imaging and CT scan are essential imaging techniques to map lesions. Excision seems prudent, but the approach should be individualized depending on the patient's presentation and her preferences.
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http://dx.doi.org/10.4103/GMIT.GMIT_81_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545041PMC
August 2020

Asymptomatic Striatocapsular slit-like Hemorrhage as a Severity Marker in Patients with Hypertensive Angiopathy.

J Stroke Cerebrovasc Dis 2020 Oct 29;29(10):105153. Epub 2020 Jul 29.

Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan; Departments of Medical Imaging, National Taiwan University Hospital Hsin-Chu Branch, HsinChu, Taiwan. Electronic address:

Background: Concomitant asymptomatic striatocapsular slit-like hemorrhage (SSH) is occasionally found in patients of spontaneous intracerebral hemorrhage (ICH), but was seldomly described in the literature. In this study, we described the clinico-radiological features of asymptomatic SSH in ICH patients with hypertensive microangiopathy.

Methods And Results: 246 patients with strictly deep or mixed deep and lobar ICH/microbleeds were included. SSH was defined as hypointense lesions involving the lateral aspect of lentiform nucleus or external capsule in slit shape (>1.5 cm) on susceptibility-weighted imaging without history of associated symptoms. Demographics and neuroimaging markers were compared between patients with SSH and those without. Patients with SSH (n=24, 10%) and without SSH had comparable age (62.0 ± 12.6 vs. 62.3 ± 13.5, p = 0.912) and vascular risk factor profiles including the diagnosis of chronic hypertension, diabetes, and dyslipidemia (all p>0.05). SSH was associated with more common lobar microbleeds (79.2% vs 48.2%, p = 0.005), lacunes (75% vs. 41.4%, p = 0.002) and higher white matter hyperintensity (WMH) volumes (24.1 [10.4-46.3] vs. 13.9 [7.0-24.8] mL, p = 0.012) on MRI, as well as more frequent left ventricular hypertrophy (LVH) (50.0% vs. 20.5%, p = 0.004) and albuminuria (41.7% vs. 19.4%, p = 0.018). In multivariable analyses, SSH remains independently associated with LVH (p = 0.017) and albuminuria (p = 0.032) after adjustment for age, sex, microbleed, lacune and WMH volume.

Conclusions: Asymptomatic SSH is associated with more severe cerebral small vessel disease-related change on brain MRI, and hypertensive cardiac and renal injury, suggesting a more advanced stage of chronic hypertension.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105153DOI Listing
October 2020

Sodium-glucose co-transporter-2 inhibitors and major adverse limb events: A trial-level meta-analysis including 51 713 individuals.

Diabetes Obes Metab 2020 12 9;22(12):2348-2355. Epub 2020 Sep 9.

Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Aim: To analyse large-scale cardiovascular outcome trials of sodium-glucose co-transporter-2 (SGLT-2) inhibitors to evaluate whether there are safety concerns with respect to major adverse limb events overall or among various high-risk subgroups of patients.

Methods: We performed a quantitative meta-analysis of randomized, placebo-controlled, cardiovascular outcome trials of SGLT-2 inhibitors in patients with type 2 diabetes. We searched the PubMed, Embase and Cochrane databases for trials published up until 30 June 2020. The efficacy outcomes analysed included amputations and were stratified by several subgroup variables, including age, duration of diabetes, glucose control, renal function, established peripheral artery disease and diabetes microvascular complications. This review was registered before completing the analysis.

Results: Among 383 records identified, six studies assessing the following three SGLT-2 inhibitors met our inclusion criteria: empagliflozin (EMPA-REG OUTCOME study), canagliflozin (CANVAS Program and CREDENCE study), dapagliflozin (DECLARE-TIMI 58 and DAPA-HF trials) and ertugliflozin (VERTIS CV study). Of a total of 51 713 participants, 858 required amputation operations. The event rates of amputation were 2.0% (535/26 778) and 1.3% (323/24 927) in the SGLT-2 inhibitor and control groups, respectively. The random effects model revealed that SGLT-2 inhibitors were not significantly associated with an increased risk of amputation with substantial heterogeneity (pooled risk ratio, 1.24; 95% confidence interval, 0.96 to 1.60; I = 67.5%). This neutral effect of SGLT-2 inhibitors was also consistent across different levels of subgroups, including subgroups with or without established peripheral artery disease (PAD).

Conclusions: SGLT-2 inhibitors are not associated with increased risks of amputation operations even among various high-risk subgroups, including patients with PAD. The amputation events primarily arise from critical limb ischaemia and infection instead of acute limb ischaemia. A multi-centre study focused on major adverse limb events with a longer follow-up is needed to confirm these results and provide guidelines for clinical practice.
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http://dx.doi.org/10.1111/dom.14159DOI Listing
December 2020

Subsequent Development of Epithelial Ovarian Cancer After Ovarian Surgery for Benign Ovarian Tumor: A Population-Based Cohort Study.

Clin Epidemiol 2020 18;12:637-649. Epub 2020 Jun 18.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.

Purpose: The goal of the current study is to determine the risk of subsequent development of epithelial ovarian cancer (EOC) in women after ovarian surgery for benign ovarian tumors.

Patients And Methods: We conducted the nationwide population-based historic cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan. Eleven thousand six hundred twenty women who underwent ovarian surgery for ovarian benign diseases were analyzed. The collected data included age, types of ovarian surgery, medical history by Charlson comorbidity index (CCI), infertility (yes/no), pelvic inflammatory disease (PID) (yes/no), tubal ligation (yes/no), total/subtotal hysterectomy (TH/STH) (yes/no), and endometrioma (yes/no). We used the Kaplan-Meier method and the Log-rank test to evaluate the risk factors. Cox proportional hazard methods were used to evaluate risk factors for the subsequent development of EOC. Multivariate analysis using Cox stepwise forward regression was conducted for the covariate selected in univariate analysis. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using the Wald test.

Results: Subsequent EOC incidence rate (IR, incidence per 10,000 person-years) of women after ovarian surgery for benign ovarian tumors was 2.98. Separating into four groups based on different age, IR of EOC was 1.57 (<30 years), 4.71 (30-39 years), 3.59 (40-49 years) and 0.94 (≥50 years), respectively. Univariate and multivariate analyses identified only high level of CCI (≥2 or more) as an independent risk factor for subsequent development of EOC in women after ovarian surgery for benign ovarian tumors (HR 59.17, 95% CI 7.50-466.80 in women with CCI level of 2 and HR 190.68, 95% CI 24.33-2494.19, in women with CCI level ≥3, respectively).

Conclusion: Our results, if confirmed, suggest that women with other comorbidities (CCI) should be well informed that they may have a higher risk of subsequent development of EOC when ovarian surgery is planned even though the final pathology showed a benign ovarian tumor.
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http://dx.doi.org/10.2147/CLEP.S199349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308129PMC
June 2020

Validating the Use of Corifollitropin Alfa in Progestin-Primed Ovarian Stimulation Protocol on Normal and High Responders by Comparing with Conventional Antagonist Protocol: A Retrospective Study.

Life (Basel) 2020 Jun 21;10(6). Epub 2020 Jun 21.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, 201, Shih-Pai Road Section 2, Taipei 112, Taiwan.

Our previous study showed a satisfactory reproductive outcome resulting from the patient-friendly ovarian stimulation protocol using long-acting follicle stimulation hormone (FSH) plus oral medroxyprogesterone acetate (MPA). The present retrospective study aims to compare the efficacy of the patient-friendly ovarian stimulation protocol with that of the antagonist protocol on normal and high responders aged between 24 and 39 years in a tertiary fertility center in Taiwan. To prevent premature luteinizing hormone (LH) surge, oral MPA was given to patients in group 1 ( = 57), whereas antagonist protocol was applied to group 2 ( = 53). Duration and dosage of stimulation, number of injections and visits before trigger, incidence of premature LH surge, number of oocytes retrieved, fertilization rate, cleavage rate, rate of good embryos available, incidence of ovarian hyperstimulation syndrome, cumulative clinical pregnancy rate and live birth rate per retrieval were compared between groups. We conclude that our patient-friendly ovarian stimulation protocol with MPA demonstrates satisfactory stimulation and reproductive outcomes that are comparable to those of an antagonist protocol.
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http://dx.doi.org/10.3390/life10060090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344689PMC
June 2020

Crosslinked Hyaluronic Acid Gels for the Prevention of Intrauterine Adhesions after a Hysteroscopic Myomectomy in Women with Submucosal Myomas: A Prospective, Randomized, Controlled Trial.

Life (Basel) 2020 May 15;10(5). Epub 2020 May 15.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan.

Intrauterine adhesion (IUA), fibrosis, and scarring resulting from damage to the endometrium is a rare but serious clinical disease, contributing to a significant impairment of reproductive function. Uterine instrumentation, especially that of a hysteroscopic myomectomy, has become the main cause of IUA. Therefore, a prospective randomized controlled study to assess the effectiveness and short-term safety of the use of hyaluronic acid gels in the prevention of IUA after a hysteroscopic myomectomy and an evaluation of the characteristics of IUA observed at follow-up are presented here. A total of 70 patients were analyzed at the end of 16 March 2020. The results show that the incidence of IUA in women who underwent a hysteroscopic myomectomy is 21.4% (15/70), overall. Women treated with hyaluronic acid gels have a statistically significantly lower incidence of IUAs than non-treated women (12.8% vs. 39.1%, = 0.012). In addition, women in the anti-adhesive gel treatment group had a dramatically reduced severity of IUA than women in the no-treatment group ( = 0.002). Further analysis shows that the International Federation of Gynecology and Obstetrics (FIGO) classification type and the use of anti-adhesive gels are independent factors associated with moderate and severe degrees of IUA formation. The results here highlight the significant therapeutic benefits of the application of hyaluronic acid gels in women undergoing a hysteroscopic myomectomy, especially for those patients with a uterine myoma classified as FIGO type 2. Since the risk of IUA after a hysteroscopic myomectomy is high, especially for patients who have not received prophylactic anti-adhesive gels, the application of hyaluronic acid gels as a prevention strategy is highly recommended. More studies are encouraged to confirm our observation.
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http://dx.doi.org/10.3390/life10050067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280993PMC
May 2020

The negative correlation between osteoporosis and hyperlipidemia: Is it real?

Taiwan J Obstet Gynecol 2020 05;59(3):471-472

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, and Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.tjog.2020.03.029DOI Listing
May 2020

Risk factors associated with epithelial ovarian cancer in women with endometriosis.

Taiwan J Obstet Gynecol 2020 May;59(3):353-355

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.tjog.2020.03.002DOI Listing
May 2020

Dose-dense chemotherapy: A possible high cost-effectiveness treatment for ovarian cancer.

Taiwan J Obstet Gynecol 2020 May;59(3):351-352

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, and Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.tjog.2020.03.001DOI Listing
May 2020

Viromimetic STING Agonist-Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus.

Adv Funct Mater 2019 Jul 12;29(28):1807616. Epub 2019 Apr 12.

Institute of Biomedical Sciences Academia Sinica Taipei 11529 Taiwan.

The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV) calls for the development of novel vaccine technology that offers safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus-like fashion. STING agonists are first encapsulated into capsid-like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH-responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen-specific T cell responses in mice immunized with a MERS-CoV nanoparticle vaccine candidate. Using a MERS-CoV-permissive transgenic mouse model, it is shown that mice immunized with this nanoparticle-based MERS-CoV vaccine are protected against a lethal challenge of MERS-CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.
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http://dx.doi.org/10.1002/adfm.201807616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161765PMC
July 2019

Comparing Paclitaxel-Carboplatin with Paclitaxel-Cisplatin as the Front-Line Chemotherapy for Patients with FIGO IIIC Serous-Type Tubo-Ovarian Cancer.

Int J Environ Res Public Health 2020 03 26;17(7). Epub 2020 Mar 26.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan.

The use of weekly chemotherapy for the treatment of patients with advanced-stage serous-type epithelial Tubo-ovarian cancer (ETOC), and primary peritoneal serous carcinoma (PPSC) is acceptable as the front-line postoperative chemotherapy after primary cytoreductive surgery (PCS). The main component of dose-dense chemotherapy is weekly paclitaxel (80 mg/m), but it would be interesting to know what is the difference between combination of triweekly cisplatin (20 mg/m) or triweekly carboplatin (carboplatin area under the curve 5-7 mg/mL per min [AUC 5-7]) in the dose-dense paclitaxel regimen. Therefore, we compared the outcomes of women with Gynecology and Obstetrics (FIGO) stage IIIC ETOC and PPSC treated with PCS and a subsequent combination of dose-dense weekly paclitaxel and triweekly cisplatin (paclitaxel-cisplatin) or triweekly carboplatin using AUC 5 (paclitaxel-carboplatin). Between January 2010 and December 2016, 40 women with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC EOC, FTC, or PPSC were enrolled, including 18 treated with paclitaxel-cisplatin and the remaining 22 treated with paclitaxel-carboplatin. There were no statistically significant differences in disease characteristics of patients between two groups. Outcomes in paclitaxel-cisplatin group seemed to be little better than those in paclitaxel-carboplatin (median progression-free survival [PFS] 30 versus 25 months as well as median overall survival [OS] 58.5 versus 55.0 months); however, neither reached a statistically significant difference. In terms of adverse events (AEs), patients in paclitaxel-carboplatin group had more AEs, with a higher risk of neutropenia and grade 3/4 neutropenia, and the need for a longer period to complete the front-line chemotherapy, and the latter was associated with worse outcome for patients. We found that a period between the first-time chemotherapy to the last dose (6 cycles) of chemotherapy >21 weeks was associated with a worse prognosis in patients compared to that ≤21 weeks, with hazard ratio (HR) of 81.24 for PFS and 9.57 for OS. As predicted, suboptimal debulking surgery (>1 cm) also contributed to a worse outcome than optimal debulking surgery (≤1 cm) with HR of 14.38 for PFS and 11.83 for OS. Based on the aforementioned findings, both regimens were feasible and effective, but maximal efforts should be made to achieve optimal debulking surgery and following the on-schedule administration of dose-dense weekly paclitaxel plus triweekly platinum compounds. Randomized trials validating the findings are warranted.
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http://dx.doi.org/10.3390/ijerph17072213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177627PMC
March 2020

Stress Echocardiography-Derived E/e' Predicts Abnormal Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction.

Front Physiol 2019 3;10:1470. Epub 2019 Dec 3.

Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.

Background: The correlation between echocardiographic parameters and hemodynamics data in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. It is important to find a non-invasive echocardiographic parameter for predicting exercise pulmonary capillary wedge pressure (PCWP).

Aim: This study sought to determine the correlation between echocardiographic parameters and hemodynamics data at rest and during exercise in HFpEF patients.

Methods And Results: This study was a cross-sectional cohort exploratory analysis of baseline data from the ILO-HOPE trial. A total of 34 HFpEF patients were enrolled. The average age was 70 ± 12 years, and most (74%) were women. The patients underwent invasive cardiac catheterization and expired gas analysis at rest and during exercise. Echocardiography including tissue Doppler imaging was performed, and global longitudinal strain and other novel diastolic function indexes were analyzed at rest and during exercise. At rest, no significant correlation was noted between resting PCWP and echocardiographic parameters. However, a significant correlation was observed between post-exercise PCWP and stress E/e' (septal, lateral, and mean) ratio ( = 0.003, 0.031, 0.012). Moreover, post-exercise ΔPCWP showed a good correlation with stress E/e' (septal, lateral, and mean; all ≤ 0.001) and global longitudinal strain (GLS) during exercise ( = 0.03). After multivariate regression analysis with adjustment for possible confounding factors including age and sex, there was still a significant correlation between post-exercise ΔPCWP and E/e' ( = 0.62, < 0.001 for E/e').

Conclusion: Only stress echocardiography derived tissue Doppler E/e' ratio is closely correlated with abnormal exercise hemodynamics (PCWP and post-exercise ΔPCWP) in HFpEF. This echocardiographic marker is substantially more sensitive than other novel echocardiographic parameters during exercise, and may have significant diagnostic utility for ambulatory HFpEF patients with dyspnea.

Clinical Trial Registration: https://www.clinicaltrials.gov, identifier NCT03620526.
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http://dx.doi.org/10.3389/fphys.2019.01470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901703PMC
December 2019

Enhancement of human iPSC-derived cardiomyocyte maturation by chemical conditioning in a 3D environment.

J Mol Cell Cardiol 2020 01 23;138:1-11. Epub 2019 Oct 23.

Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD, USA. Electronic address:

Recent advances in the understanding and use of pluripotent stem cells have produced major changes in approaches to the diagnosis and treatment of human disease. An obstacle to the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for regenerative medicine, disease modeling and drug discovery is their immature state relative to adult myocardium. We show the effects of a combination of biochemical factors, thyroid hormone, dexamethasone, and insulin-like growth factor-1 (TDI) on the maturation of hiPSC-CMs in 3D cardiac microtissues (CMTs) that recapitulate aspects of the native myocardium. Based on a comparison of the gene expression profiles and the structural, ultrastructural, and electrophysiological properties of hiPSC-CMs in monolayers and CMTs, and measurements of the mechanical and pharmacological properties of CMTs, we find that TDI treatment in a 3D tissue context yields a higher fidelity adult cardiac phenotype, including sarcoplasmic reticulum function and contractile properties consistent with promotion of the maturation of hiPSC derived cardiomyocytes.
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http://dx.doi.org/10.1016/j.yjmcc.2019.10.001DOI Listing
January 2020

Rapid Prototyping of an Open-Surface Microfluidic Platform Using Wettability-Patterned Surfaces Prepared by an Atmospheric-Pressure Plasma Jet.

ACS Omega 2019 Oct 26;4(15):16292-16299. Epub 2019 Sep 26.

Department of Applied Chemistry, Institute of Biomedical Engineering, and Center for Emergent Functional Matter Science, National Chiao Tung University, 1001 Ta Hsueh Road, Hsinchu 30049, Taiwan.

Open-surface microfluidics is promising in terms of enabling economical and rapid biochemical analysis for addressing challenges associated with medical diagnosis and food safety. To this end, we present a simple and economical approach to develop an open-surface microfluidic platform suitable for facile liquid transport and mixing. Customizable patterns with tailored wettability are deposited using a plasma-assisted deposition technique under atmospheric pressure. The flow of the dispensed liquid is driven by gravity, and the tilting angle of the device determines the extent of mixing. First, a hexamethyldisiloxane film was deposited to create hydrophobic patterns on glass, and then, hydrophilic acrylic acid was deposited by a patterned cardboard mask to construct a channel suitable for forming channels to transport aqueous liquids without the need of an external energy input; the liquid can be confined to designated pathways. Several designs including Y-junctions, serpentine-shaped patterns, splitting channels, and concentration gradient generation patterns are presented. The proposed method can spatially pattern a surface with a hydrophobic/hydrophilic area, which can function as a microfluidic channel, and the surface can be applied in microfluidic devices with other types of substrates.
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http://dx.doi.org/10.1021/acsomega.9b01317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788040PMC
October 2019

Long-term Prognostic Value of Estimated Plasma Volume in Heart Failure with Preserved Ejection Fraction.

Sci Rep 2019 10 7;9(1):14369. Epub 2019 Oct 7.

Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.

Plasma volume, estimated by several indirect methods, has been viewed as a biological surrogate for intravascular fluid status. The clinical implication of estimated plasma volume status (ePVS) for long term outcomes in heart failure with preserved ejection fraction (HFpEF) remains unclear. We investigate the prognostic value of ePVS calculated by Strauss formula and its association with cardiovascular events and mortality in a prospective HFpEF cohort. There were 449 individuals met the inclusion criteria of our cohort. Estimated plasma volume variation (ΔePVS) and its instantaneous derivatives were calculated by the Strauss formula. Our study endpoints were events of heart failure hospitalization and mortality. Kaplan-Meier estimates and Cox regression analysis were applied to determine the power of ΔePVS and baseline ePVS in predicting long term cardiovascular outcomes. Both baseline ePVS and ΔePVS were independent predictors of heart failure hospitalization and mortality. Kaplan-Meier estimates of these outcomes stratified by optimal cut-off value showed that HFpEF individuals with higher baseline ePVS and ΔePVS were associated with elevated risk of composite endpoint of heart failure hospitalization and mortality. This study demonstrated the prognostic value of a novel biological surrogate, instantaneous derivatives ePVS, in predicting long term cardiovascular outcomes in HFpEF population. Monitoring instantaneous plasma volume may assist in identifying patients at high risk for future cardiovascular events. Further prospective studies validating the role of ePVS in predicting long-term prognosis in patients with HFpEF are warranted.
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http://dx.doi.org/10.1038/s41598-019-50427-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779908PMC
October 2019

Inhaled Prostacyclin on Exercise Echocardiographic Cardiac Function in Preserved Ejection Fraction Heart Failure.

Med Sci Sports Exerc 2020 02;52(2):269-277

Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, TAIWAN.

Purpose: Treatments that improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) have shown no benefits for those with heart failure with preserved ejection fraction (HFpEF). Our study aimed to investigate the effect of inhaled iloprost on myocardial performance during exercise in HFpEF.

Methods: The study participants were enrolled from the ILO-HOPE trial (NCT03620526), a prospective randomized, double-blind, placebo-controlled study that was designed to investigate the effects of iloprost on cardiovascular hemodynamics during exercise in patients with HFpEF. Subjects were randomized 1:1 to inhalation of iloprost or placebo for 5 min. Two-dimensional transthoracic echocardiography with high temporal resolution was implemented to measure left ventricular (LV) longitudinal strain, LV diastolic function, and RV function both at rest and during supine exercise at 20-W workload.

Results: LV global longitudinal strain (GLS) in response to exercise increased more in the iloprost group (LV GLS, -24.96 ± 1.20 vs -20.75 ± 3.00, P < 0.001). Iloprost also resulted in greater increment of LV GLS during exercise (ΔLV GLS, +6.02 ± 1.39 vs +3.44 ± 0.80, P < 0.001). Moreover, iloprost use was associated with enhancement of LV diastolic function, RV systolic function, and relief of pulmonary hypertension during exercise.

Conclusions: In patients with HFpEF, inhaled iloprost favorably improved myocardial performance during exercise by increasing LV GLS reserve, decreasing LV diastolic filling load, and reducing stress-induced pulmonary hypertension and thereby improving RV systolic function. Larger studies are needed to validate the result and long-term benefits of iloprost in patients with HFpEF.
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http://dx.doi.org/10.1249/MSS.0000000000002145DOI Listing
February 2020

Microangiopathy underlying mixed-location intracerebral hemorrhages/microbleeds: A PiB-PET study.

Neurology 2019 02 23;92(8):e774-e781. Epub 2019 Jan 23.

From the Department of Neurology (H.H.T.), National Taiwan University Hospital Bei-Hu Branch, Taipei; Departments of Neurology (H.H.T., L.-K.T., S.-C.T., J.-S.J.), Medical Imaging (Y.-F.C., B.-C.L.), and Nuclear Medicine (R.-F.Y.), National Taiwan University Hospital, Taipei; Department of Neurology (M.P., P.F., M.E.G.), Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA; Graduate Institute of Clinical Medicine (H.H.T.) and Division of Cardiology (C.-Y.H.), Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei.

Objective: To test the hypothesis that patients with concomitant lobar and deep intracerebral hemorrhages/microbleeds (mixed ICH) have predominantly hypertensive small vessel disease (HTN-SVD) rather than cerebral amyloid angiopathy (CAA), using in vivo amyloid imaging.

Methods: Eighty Asian patients with primary ICH without dementia were included in this cross-sectional study. All patients underwent brain MRI and C-Pittsburgh compound B (PiB)-PET imaging. The mean cortical standardized uptake value ratio (SUVR) was calculated using cerebellum as reference. Forty-six patients (57.5%) had mixed ICH. Their demographic and clinical profile as well as amyloid deposition patterns were compared to those of 13 patients with CAA-ICH and 21 patients with strictly deep microbleeds and ICH (HTN-ICH).

Results: Patients with mixed ICH were younger (62.8 ± 11.7 vs 73.3 ± 11.9 years in CAA, = 0.006) and showed a higher rate of hypertension than patients with CAA-ICH ( < 0.001). Patients with mixed ICH had lower PiB SUVR than patients with CAA (1.06 [1.01-1.13] vs 1.43 [1.06-1.58], = 0.003). In a multivariable logistic regression model, mixed ICH was associated with hypertension (odds ratio 8.9, 95% confidence interval 1.4-58.4, = 0.02) and lower PiB SUVR (odds ratio 0.03, 95% confidence interval 0.001-0.87, = 0.04) compared to CAA after adjustment for age. Compared to HTN-ICH, mixed ICH showed a similar mean age (62.8 ± 11.7 vs 60.1 ± 14.5 years in HTN-ICH) and risk factor profile (all > 0.1). Furthermore, PiB SUVR did not differ between mixed ICH (values presented above) and HTN-ICH (1.10 [1.00-1.16], = 0.45).

Conclusions: Patients with mixed ICH have much lower amyloid load than patients with CAA-ICH, while being similar to HTN-ICH. Overall, mixed ICH is probably caused by HTN-SVD, an important finding with clinical relevance.
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http://dx.doi.org/10.1212/WNL.0000000000006953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396971PMC
February 2019

Reply: further studies needed before using renin-angiotensin-aldosterone system blockade for atrial fibrillation prevention in hypertrophic cardiomyopathy.

Heart 2018 12;104(23):1985-1986

Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.

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http://dx.doi.org/10.1136/heartjnl-2018-314000DOI Listing
December 2018

3D and 4D Bioprinting of the Myocardium: Current Approaches, Challenges, and Future Prospects.

Biomed Res Int 2018 22;2018:6497242. Epub 2018 Apr 22.

Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.

3D and 4D bioprinting of the heart are exciting notions in the modern era. However, myocardial bioprinting has proven to be challenging. This review outlines the methods, materials, cell types, issues, challenges, and future prospects in myocardial bioprinting. Advances in 3D bioprinting technology have significantly improved the manufacturing process. While scaffolds have traditionally been utilized, 3D bioprinters, which do not require scaffolds, are increasingly being employed. Improved understanding of the cardiac cellular composition and multiple strategies to tackle the issues of vascularization and viability had led to progress in this field. studies utilizing small animal models have been promising. 4D bioprinting is a new concept that has potential to advance the field of 3D bioprinting further by incorporating the fourth dimension of time. Clinical translation will require multidisciplinary collaboration to tackle the pertinent issues facing this field.
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http://dx.doi.org/10.1155/2018/6497242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937623PMC
October 2018

Effect of nickel diffusion and oxygen behavior on heterojunction Schottky diodes of Au/NiO/ZnO with a NiO interlayer prepared by radio-frequency magnetron sputtering.

Nanotechnology 2018 Jul 3;29(29):295705. Epub 2018 May 3.

Department of Electrophysics, National Chiayi University, No. 300 Syuefu Rd., Chiayi 60004, Taiwan.

The rectifying characteristic of Au/ZnO Schottky diodes (SDs) was remarkably improved by introducing a NiO layer in-between the Au and ZnO layers. Compared with the Au/ZnO SDs, the introduction of the NiO layer significantly enhanced the rectification ratio from 1.38 to 1300, and reduced the ideality factor from 5.78 to 2.14. The NiO and ZnO layers were deposited on an indium-tin-oxide/glass substrate by radio-frequency magnetron sputtering. Secondary ion mass spectroscopy showed that Ni atoms diffused from NiO to ZnO, leading to a graded distribution of Ni in ZnO. X-ray diffraction demonstrated that the diffusion of Ni atoms increased the grain size and electron concentration of ZnO. X-ray photoelectron spectroscopy showed that the interstitial oxygen (O) atoms in NiO and ZnO compensated the oxygen vacancies (O) at the NiO/ZnO interface; the amount of O was significantly reduced, while O vanished at the interface. The band diagram revealed a potential drop in the bulk ZnO, owing to the graded distribution of Ni in ZnO, which accelerated the carriers, collected by the outer circuit. The carriers at the NiO/ZnO interface easily crossed over the barrier height, instead of being recombined by O, owing to the lower amount of O at the interface.
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http://dx.doi.org/10.1088/1361-6528/aac230DOI Listing
July 2018
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