A Deep Learning Approach to Classify Fabry Cardiomyopathy from Hypertrophic Cardiomyopathy Using Cine Imaging on Cardiac Magnetic Resonance.

A challenge in accurately identifying and classifying left ventricular hypertrophy (LVH) is distinguishing it from hypertrophic cardiomyopathy (HCM) and Fabry disease. The reliance on imaging techniques often requires the expertise of multiple specialists, including cardiologists, radiologists, and geneticists. This variability in the interpretation and classification of LVH leads to inconsistent diagnoses. LVH, HCM, and Fabry cardiomyopathy can be differentiated using T1 mapping on cardiac magnetic resonance imaging (MRI). However, differentiation between HCM and Fabry cardiomyopathy using echocardiography or MRI cine images is challenging for cardiologists. Our proposed system named the MRI short-axis view left ventricular hypertrophy classifier (MSLVHC) is a high-accuracy standardized imaging classification model developed using AI and trained on MRI short-axis (SAX) view cine images to distinguish between HCM and Fabry disease. The model achieved impressive performance, with an F1-score of 0.846, an accuracy of 0.909, and an AUC of 0.914 when tested on the Taipei Veterans General Hospital (TVGH) dataset. Additionally, a single-blinding study and external testing using data from the Taichung Veterans General Hospital (TCVGH) demonstrated the reliability and effectiveness of the model, achieving an F1-score of 0.727, an accuracy of 0.806, and an AUC of 0.918, demonstrating the model's reliability and usefulness. This AI model holds promise as a valuable tool for assisting specialists in diagnosing LVH diseases.

Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning.

BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are important prognostic factors for gastric cancer (GC) that indicate an increased risk of metastasis and poor outcomes. Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment decisions. However, prior models using conventional computed tomography (CT) images to predict LVI or PNI separately have had limited accuracy. Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion. We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients. AIM: To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately. METHODS: This study used a retrospective dataset involving 257 GC patients (training cohort, n = 172; validation cohort, n = 85). First, several clinical indicators, including serum tumor markers, CT-TN stages and CT-detected extramural vein invasion (CT-EMVI), were extracted, as were quantitative spectral CT parameters from the delineated tumor regions. Next, a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters. A logistic regression (LR)-based nomogram model was subsequently constructed to predict LVI/PNI status, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: In both the training and validation cohorts, CT T3-4 stage, CT-N positive status, and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant (P < 0.05). LR analysis of the training group showed preoperative CT-T stage, CT-EMVI, single-energy CT values of 70 keV of venous phase (VP-70 keV), and the ratio of standardized iodine concentration of equilibrium phase (EP-NIC) were independent influencing factors. The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824, respectively, which were slightly greater than those of CT-T and CT-EMVI (AUC = 0.793, 0.762). The nomogram combining CT-T stage, CT-EMVI, VP-70 keV and EP-NIC yielded AUCs of 0.918 (0.866-0.954) and 0.874 (0.784-0.936) in the training and validation cohorts, which are significantly higher than using each of single independent factors (P < 0.05). CONCLUSION: The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC, with accuracy boosted by integrating clinical markers.

Employing feature engineering strategies to improve the performance of machine learning algorithms on echocardiogram dataset.

Objectives: This study mainly uses machine learning (ML) to make predictions by inputting features during training and inference. The method of feature selection is an important factor affecting the accuracy of ML models, and the process includes data extraction, which is the collection of all data required for ML. It also needs to import the concept of feature engineering, namely, this study needs to label the raw data of the cardiac ultrasound dataset with one or more meaningful and informative labels so that the ML model can learn from it and predict more accurate target values. Therefore, this study will enhance the strategies of feature selection methods from the raw dataset, as well as the issue of data scrubbing. Methods: In this study, the ultrasound dataset was cleaned and critical features were selected through data standardization, normalization, and missing features imputation in the field of feature engineering. The aim of data scrubbing was to retain and select critical features of the echocardiogram dataset while making the prediction of the ML algorithm more accurate. Results: This paper mainly utilizes commonly used methods in feature engineering and finally selects four important feature values. With the ML algorithms available on the Azure platform, namely, Random Forest and CatBoost, a Voting Ensemble method is used as the training algorithm, and this study also uses visual tools to gain a clearer understanding of the raw data and to improve the accuracy of the predictive model. Conclusion: This paper emphasizes feature engineering, specifically on the cleaning and analysis of missing values in the raw dataset of echocardiography and the identification of important critical features in the raw dataset. The Azure platform is used to predict patients with a history of heart disease (individuals who have been under surveillance in the past three years and those who haven't). Through data scrubbing and preprocessing methods in feature engineering, the model can more accurately predict the future occurrence of heart disease in patients.

Transcatheter Edge-to-Edge Repair for a Patient With Severe Mitral Regurgitation of Carpentier IIIa Classification.

Whether patients diagnosed with mitral regurgitation of Carpentier class IIIa (rheumatic origin) can possibly be treated with balloon mitral commissurotomy followed by transcatheter edge-to-edge repair remains unclear. Here, we report on such a case who was successfully treated with balloon mitral commissurotomy and then transcatheter edge-to-edge repair without aggravating mitral stenosis. (Level of Difficulty: Intermediate.).

2023 Expert Consensus of the Taiwan Society of Cardiology on the Diagnosis and Treatment of Cardiac Amyloidosis.

Cardiac amyloidosis is one form of systemic amyloidosis caused by abnormal amyloid fibrils deposited in the extracellular space of the myocardium causing heart failure because of restrictive cardiomyopathy and conduction disturbances. The incidence and prevalence of cardiac amyloidosis are higher than previously noted, particularly among special populations. The most common forms of cardiac amyloidosis are light chain and transthyretin amyloid cardiomyopathy. Even though more than 70% of patients with systemic amyloidosis have cardiac amyloidosis, the diagnosis is often delayed, suggesting significant gaps in the knowledge of cardiac amyloidosis and a lack of multidisciplinary teamwork in our daily practice. The Taiwan Society of Cardiology Heart Failure Committee organized experts to draft the "Expert Consensus on the diagnosis and treatment of cardiac amyloidosis." This statement aims to help clinicians and healthcare professionals improve early diagnosis and management of cardiac amyloidosis in Taiwan. The expert panel met virtually to review the data and discuss the consensus statements. Our review provided practical information about diagnostic methods and algorithms, clinical clues and red-flag signs, cardiac amyloidosis per se and its comorbidities treatment modalities, and follow-up plans for asymptomatic transthyretin gene carriers. We especially innovate two acronyms, "HFpEF MUTED CALL" and "HFmrEF MUST COUNT", to help in the early diagnosis and screening of transthyretin amyloid cardiomyopathy as shown in the Central Illustration.

Real-World Analyses of the Treatment Conditions in Patients Initiating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitor in Taiwan.

AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is a powerful low density lipoprotein cholesterol (LDL-C)-lowering therapy, but this drug is expensive. This study aimed to describe the real-world treatment conditions in patients initiating PCSK9 inhibitor in Taiwan. METHODS: This was a multicenter, retrospective, and observational study. The clinical characteristics, baseline lipid-lowering therapy, and changes in the lipid profile of patients receiving PCSK9 inhibitor treatment were obtained from 11 major teaching hospitals in Taiwan. RESULTS: A total of 296 patients (age 57±13 years, male 73%) who received PCSK9 inhibitor treatments (73.3% alirocumab and 26.7% evolocumab) from 2017 to 2021 were included. Among the patients, 62.8% had history of coronary artery disease, and 27.7% had myocardial infarction. High intensity statin (HIS) monotherapy or HIS＋ezetimibe treatment was used in 32.5% when initiating PCSK9 inhibitor treatment. Among alirocumab users, 21.2% received 75 mg every 3 to 4 weeks, whereas among evolocumab users, 8.9% received 140 mg every 3 to 4 weeks. Almost all the non-standard-dosing PCSK9 inhibitors were paid by the patients themselves but were not reimbursed by the Taiwan National Health Insurance. Overall, the LDL-C levels at baseline and 12 weeks after treatment were 147.4±67.4 and 69.7±58.2 mg/dL (p＜0.01), corresponding to a 49.6%±31.8% LDL-C reduction. CONCLUSIONS: In the real-world practice in Taiwan, the LDL-C reduction efficacy of PCSK9 inhibitors was slightly lower than that reported in the clinical trials. The use of non-standard-dosing PCSK9 inhibitors was not uncommon in Taiwan.

Prevalence of genetically defined familial hypercholesterolemia and the impact on acute myocardial infarction in Taiwanese population: A hospital-based study.

Background: Familial hypercholesterolemia (FH) is a common genetic disorder with markedly increased risk of coronary artery diseases (CAD), especially acute myocardial infarction (AMI). However, genetic tests for FH are not always necessary in the current diagnostic criteria of FH, which might lead to underestimation of the prevalence of FH and a lack of awareness of FH-associated CAD and AMI. We aimed to explore the prevalence of genetically defined FH in the hospital-based population and to determine the impact of FH risk variants on CAD and AMI. Methods: The study participants were recruited between June 24, 2019 and May 12, 2021, at a medical center in Taiwan, in cooperation with the Taiwan Precision Medicine Initiative (TPMI) project. The prevalence of FH was calculated and the effects of FH pathogenic variants on CAD and AMI were analyzed by logistic regression models and shown as ORs and 95% CI. Results: The prevalence of genetically defined FH was 1.13% in the hospital-based population in Taiwan. Highest LDL and total cholesterol levels were observed in patients with LDLR rs28942084 (LDL 219.4±55.2; total cholesterol 295.8±55.4). There was an approximately 4-fold increased risk of hyperlipidemia in subjects with the LDLR rs769446356 polymorphism (OR, 4.42; 95% CI, 1.92-10.19) and AMI in individuals with the LDLR rs730882109 polymorphism (OR, 3.79; 95% CI, 2.26-6.35), and a 2-fold increased risk of CAD in those with the LDLR rs749038326 polymorphism (OR, 2.14; 95% CI, 1.31-3.50), compared with the groups without pathogenic variants of FH. Conclusions: The prevalence of genetically defined FH was 1.13% in the hospital-based population in Taiwan, which was higher than the rate observed in individuals with clinically defined FH. The risk of CAD and AMI was increased to varying degrees in subjects with different FH risk alleles. Close monitoring and risk stratification strategy are essential in high-risk patients with FH risk alleles to facilitate early detection and treatments.

Whole Exome Sequencing of Patients With Heritable and Idiopathic Pulmonary Arterial Hypertension in Central Taiwan.

Background: Genetic variants could be identified in subjects with idiopathic and heritable pulmonary arterial hypertension (PAH). The 6th World Symposium on Pulmonary Hypertension (WSPH) provided a list of genes with evidence of association with PAH. However, reports using whole exome sequencing (WES) from southeastern Asian PAH cohorts were scarce. Methods: Subjects with idiopathic and heritable PAH (N = 45) from two medical centers in central Taiwan were screened for PAH related gene variants. The genomic DNA was prepared from peripheral blood lymphocytes. We performed WES for all patients enrolled in this study. All identified gene variants were validated by polymerase-chain reaction and Sanger sequencing. The clinical and hemodynamic data were compared between bone morphogenetic protein receptor type-2 (BMPR2) gene variants carriers vs. non-carriers. Results: Eight patients (8/45 = 17.8%) was identified carrying BMPR2 gene variants and 8 patients (8/45 = 17.8%) had other WSPH-listed PAH-related gene variants (1 with ACVRL1, 1 with ENG, 1 with SMAD9, 1 with SMAD1, 1 with ATP13A3 and 3 with AQP1). In addition, a total of 14 non-WSPH-listed PAH-related genetic variant sites (ABCC8, NOTCH1, NOTCH2, NOTCH3, JAG1, BMP10, GGCX, FBLN2, ABCA3 and PTGIS) were found in this PAH cohort. Subjects carrying BMPR2 gene variant (N = 8) were younger at diagnosis of PAH (30 ± 11 vs 49 ± 13 years, p = 0.001) than the non-carrier group (N = 37). BMPR2 variant carriers had a trend toward having higher mean pulmonary arterial pressure (PAP) (61 ± 19 vs. 51 ± 13 mmHg, p = 0.076) than the non-carriers upon initial diagnosis. Pulmonary vascular resistance, right atrial pressure, cardiac output, as well as functional class were similar between BMPR2 variant carriers and non-carriers at initial diagnosis. Conclusions: We identified 17.8% of patients with BMPR2 gene variants and 17.8% subjects with other 6th WSPH-listed PAH-related gene variants in a Taiwanese idiopathic and heritable PAH cohort. PAH patients carrying BMPR2 variants presented at a younger age with a trend toward having higher mean PAP at initial diagnosis.

Detecting supraventricular tachycardia with smartwatches facilitates the decision for catheter ablation: A case series.

Smartwatch allows easy detection of arrhythmia. Such an approach is widely used for detecting atrial fibrillation. However, there has been no consensus on the diagnostic power of smartwatch-detected supraventricular tachycardia (SVT). We reported three patients of SVT presenting with infrequent palpitations. Their SVTs were not documented with single-lead or standard ECG in hospital before, but only recorded by the single-lead ECG on smartwatches. Electrophysiological studies confirmed the mechanisms of these SVTs and led to successful catheter ablations. In conclusion, in patients with recurrent symptomatic tachycardia and a smartwatch-detected SVT, an electrophysiological study is indicated rather than to wait for a standard ECG for clinical decision. This approach might prevent the delay for successful treatment.

Transcarotid Transcatheter Aortic Valve Replacement in an Octogenarian With Complex Type B Aortic Dissection and Aneurysm: A Case Report.

We report the case of an octogenarian with severe aortic valve stenosis, chronic kidney disease (CKD) and heart failure. Due to advanced CKD, we used a 3-dimensional transesophageal echocardiogram for sizing the device before transcatheter aortic valve replacement (TAVR). Noncontrast computed tomography found complex aortic dissection involving the arch, descending thoracic aorta, and abdominal aorta. TAVR was approached via the right carotid artery using a CoreValve. There was no cerebral vascular event. Renal function was well preserved. Transcarotid TAVR can be performed safely with complex type B aortic dissection. Three-dimensional transesophageal echocardiogram provides an alternative sizing solution in advanced CKD.

Nous décrivons ici le cas d'un octogénaire présentant une sténose sévère de la valve aortique, une néphropathie chronique et une insuffisance cardiaque. En raison de sa néphropathie chronique de stade avancé, nous avons eu recours à l'échocardiographie tridimensionnelle par voie transœsophagienne pour déterminer la taille du dispositif devant être utilisé avant le remplacement valvulaire aortique par cathéter (RVAC). Une tomodensitométrie sans contraste a révélé une dissection aortique complexe touchant l'arc aortique, l'aorte thoracique descendante et l'aorte abdominale. Le RVAC a été effectué par l'artère carotide droite à l'aide du système CoreValve. Il n'y a pas eu d'accident vasculaire cérébral. La fonction rénale a été bien préservée. Le RVAC par voie transcarotidienne peut être réalisé sans danger dans le cas d'une dissection aortique de type B complexe. L'échocardiographie tridimensionnelle par voie transœsophagienne constitue une solution de rechange pour déterminer la taille du dispositif chez les patients atteints de néphropathie chronique à un stade avancé.

Case Report: Leaflet Thrombosis After Transcatheter Aortic Valve Replacement With Worsening Heart Failure-A Successful Resolution Using Non-vitamin K Antagonist Oral Anti-coagulant.

Background: Transcatheter aortic valve replacement (TAVR) is indicated for treating symptomatic severe aortic valve stenosis (AS) with intermediate-to-high surgical risks. Few reports are available on managing leaflet thrombosis after TAVR with worsening heart failure. Case Summary: A 77-year-old man with severe AS and coronary artery disease (CAD) received a successful TAVR with Edwards Sapien 3 valve. A year later, the patient developed a worsening heart failure with pulmonary edema, new-onset atrial fibrillation (Af), an increase in mean trans-aortic valve pressure gradient to 48 mmHg, worsening mitral regurgitation (MR), and pulmonary hypertension (PH). The response of the patient to intravenous diuretics and inotropic treatments was poor. Multi-slice CT (MDCT) revealed hypo-attenuated thrombus and thickened transcatheter heart valve leaflets. A non-vitamin K antagonist oral anti-coagulant (NOAC) was added to treat the new-onset Af and leaflet thrombosis on top of the con-current single antiplatelet for CAD. A series of follow-up echocardiograms showed a progressive decrease in trans-aortic valve pressure gradient to 17 mmHg and reductions in MR and PH. Three months after the NOAC treatment, MDCT revealed the resolution of hypo-attenuated thrombus and thickened leaflets. Symptoms of heart failure were also improved gradually. Discussion: Worsening heart failure or an increase in trans-aortic valve pressure gradient after TAVR warranted further MDCT studies. Leaflet thrombosis can be resolved after using NOAC as in our present case.

[Pollution and Ecological Risk Assessment and Source Apportionment of Heavy Metals in Sediments of Qingliangshan Reservoir in the Meijiang Basin].

Reservoir sediment is an important sink for pollutants such as heavy metals. Under the changes in acid-base and redox conditions, there is a potential risk of heavy metals release into the water environment, which are transmitted through the food chain and threaten human health. Therefore, this study investigates the Qingliangshan Reservoir in the Meijiang River Basin, and conducts research concerning the contents and speciation of heavy metals in the sediments, potential ecological risks, and source apportionment. This study found that the content of heavy metals in the sediments of the reservoir area was in the order:Xitian tributary > dam front and reservoir center > Xintian-Baishui tributary. There is a large difference in the speciation of heavy metals in the sediments. Zn is mainly acid-soluble and in the residual state, Pb is mainly in an Fe/Mn oxide bound state, Cd is mainly in an acid-soluble state, and Cu, Ni, and Cr are in the residual state. Mainly, the percentage of bioavailable states are Cd(89%) > Pb(76%) > Zn(54%) > Cu(43%) > Ni(28%) > Cr(10%). The geoaccumulation index method shows that the pollution degree of heavy metal elements in reservoir sediments is in the order Cd > Pb > Zn > Cu > Cr > Ni, and the potential hazard ecological index method shows that the pollution degree of heavy metals is Cd > Pb > Cu > Ni > Zn > Cr. The potential ecological risk of Cd in the reservoir sediments is the largest, and the biological impact is greatest. Correlation analysis and principal component analysis results show that heavy metals Cu, Zn, Pb, and Cd in reservoir sediments are mainly from agricultural pollution, and Ni and Cr are mainly from natural background. Combined with the analysis of soil heavy metal content in the watershed, heavy metal pollution in the Qingliangshan Reservoir sediments originates from the effect of rainfall runoff and the use of agricultural chemical fertilizers before flooding in the upstream of the reservoir tributaries. There are significant spatial differences in heavy metal pollution in the sediments of the reservoir area. The Xintian-Baishui River recharge area is the least polluted, and it is closely related to the land use in the controlled watershed, which is mainly forest land, with fewer sources of pollution. The Xitian River replenishment area has the heaviest pollution. It controls many tea gardens and farmlands in the watershed, and the load of external fertilizer pollution is the largest. The pollution degree of heavy metals in front of the dam and the center of the reservoir area is between the two tributary replenishment areas, showing an obvious mixing effect.

Introducing the Study of Life and Death Education to Support the Importance of Positive Psychology: An Integrated Model of Philosophical Beliefs, Religious Faith, and Spirituality.

Life education, also known as life and death education, is an important subject in Taiwan with institutions (e.g., high school) offering degree programs and courses that focus on quality learning and implementation of life education. What is interesting from the perspective of Taiwanese education is that the teaching of life education also incorporates a number of Eastern-derived and conceptualized tenets, for example, Buddhist teaching and the importance of spiritual wisdom. This premise contends then that life education in Taiwan, in general, is concerned with the promotion, fulfillment, and cherishing of quality life experiences (e.g., personal contentment, happiness). One example of life education, which resonates with other spiritual beliefs and religious faiths (e.g., Hinduism), is related to spiritual cultivation and the enlightenment of life wisdom. Our own teaching of the subject, likewise, places emphasis on the goal of teaching students to seek meaningful understanding of and appreciation for three major, interrelated components of life education: life wisdom, life practice, and life care. It has been acknowledged, to a certain degree, that life education has made meaningful contributions, such as the creation and facilitation of a civil, vibrant society, and that many Taiwanese individuals show dignity, respect for elders, and reverence for spiritual and religious faiths. For example, aside from high-quality hospice care, many Taiwanese engage in different types of benevolent acts (e.g., providing spiritual advice to someone who is dying), where possible. Life education is a beneficial subject for teaching and learning as its theoretical understanding may help individuals cope with pathologies and negative conditions and life experiences. One negative life experience, in this case, is the ultimate fate of humankind: death. Approaching death and/or the onset of grief is something that we all have to experience. How does one approach death? It is not easy feat, and of course, grief for a loved one is personal, and some of us struggle with this. We contend that spiritual cultivation and enlightenment, arising from life education, may assist us with the topic of death (e.g., the possibility of transcendence beyond the realm of life). More importantly however, from our own teaching experiences and research development, we strongly believe and rationalize that the subject of life education could, indeed, coincide with and support the paradigm of positive psychology (Seligman, 1999, 2010; Seligman and Csíkszentmihályi, 2000). Forming the premise of the present conceptual analysis article, we propose that a person's "spiritual and enlightened self," reflecting the convergence of three major aspects of life education (i.e., philosophical reflection, enrichment of personal well-being, and spiritual cultivation), would result in the initiation and creation of a number of virtues and positive characteristics, for example, having a positive outlook in life, having a perceived sense of spirituality, showing compassion, forgiveness, etc. These virtues and quality characteristics, from our philosophical reasoning, are equivalent to those qualities that the paradigm of positive psychology advocates for. In summary, we conceptualize that the subject of life education, from the perspective of Taiwanese education, may intertwine with the paradigm of positive psychology. A person's spiritual and enlightened self, or his/her "holistic self," from our rationalization, is the ultimate optimal life experience that he/she may have, enabling him/her to address the gamut of life conditions and experiences. The distinctive nature of life education in this case, as a point of summary, is that it incorporates spiritual beliefs and religious faiths (e.g., Buddhist faith), encouraging a person to seek nature and divine-human relationships, as well as to contemplate and to explore the complex nature of his/her inner self. The notion of Buddhist samsâra, for example, as "evidence" of spirituality, entailing the endless cycle of birth, rebirth, and redeath, may provide a person with hope into the afterlife. Such esoteric discourse, we contend, is positive and optimistic, allowing individuals to discard the dividing line between life and death.

Ventricular divergence correlates with epicardial wavebreaks and predicts ventricular arrhythmia in isolated rabbit hearts during therapeutic hypothermia.

INTRODUCTION: High beat-to-beat morphological variation (divergence) on the ventricular electrogram during programmed ventricular stimulation (PVS) is associated with increased risk of ventricular fibrillation (VF), with unclear mechanisms. We hypothesized that ventricular divergence is associated with epicardial wavebreaks during PVS, and that it predicts VF occurrence. METHOD AND RESULTS: Langendorff-perfused rabbit hearts (n = 10) underwent 30-min therapeutic hypothermia (TH, 30°C), followed by a 20-min treatment with rotigaptide (300 nM), a gap junction modifier. VF inducibility was tested using burst ventricular pacing at the shortest pacing cycle length achieving 1:1 ventricular capture. Pseudo-ECG (p-ECG) and epicardial activation maps were simultaneously recorded for divergence and wavebreaks analysis, respectively. A total of 112 optical and p-ECG recordings (62 at TH, 50 at TH treated with rotigaptide) were analyzed. Adding rotigaptide reduced ventricular divergence, from 0.13±0.10 at TH to 0.09±0.07 (p = 0.018). Similarly, rotigaptide reduced the number of epicardial wavebreaks, from 0.59±0.73 at TH to 0.30±0.49 (p = 0.036). VF inducibility decreased, from 48±31% at TH to 22±32% after rotigaptide infusion (p = 0.032). Linear regression models showed that ventricular divergence correlated with epicardial wavebreaks during TH (p<0.001). CONCLUSION: Ventricular divergence correlated with, and might be predictive of epicardial wavebreaks during PVS at TH. Rotigaptide decreased both the ventricular divergence and epicardial wavebreaks, and reduced the probability of pacing-induced VF during TH.

Recombinant Lactococcus lactis Expressing Ling Zhi 8 Protein Ameliorates Nonalcoholic Fatty Liver and Early Atherogenesis in Cholesterol-Fed Rabbits.

Atherosclerosis is an inflammatory disease characterized by lipid deposits in the subendothelial space leading to severe inflammation. Nonalcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis, including dyslipidemia, type 2 diabetes mellitus, and metabolic syndrome, all of which lead to lipid deposition in the liver causing inflammation and fibrosis. Several clinical trials have shown that certain Chinese herbal medicines with anti-inflammatory effects can be used as adjuvant therapy to prevent the development of cardiovascular events and liver disease. Ling Zhi 8 (LZ8) is an immunomodulatory protein isolated from a medicinal mushroom and has been well documented to possess a broad range of pharmacological properties. This study aimed to evaluate the protective effects of recombinant Lactococcus lactis expressing LZ8 protein on NAFLD and atherogenesis in a cholesterol-fed rabbit model. Twelve rabbits were divided into three groups and fed with syrup only, L. lactis vehicle, or recombinant L. lactis-LZ8 once a day on weekdays for five weeks, respectively. The gene expression of IL-1ß in the aorta was significantly suppressed after oral administration of L. lactis-LZ8. Moreover, in hematoxylin and eosin staining of the aorta, the intima-medial thickness was decreased, and foam cells were significantly reduced in the subendothelial space. LZ8 also inhibited the expression of IL-1ß in the liver, decreased fat droplet deposits and infiltration of inflammatory cells, and improved liver function by decreasing liver enzymes in an animal model. Our results suggest that the Lactococcus-expressing LZ8 appears to be a promising medicine for improving both NAFLD and early atherogenesis owing to its anti-inflammatory effect. Furthermore, it is available as a low-cost food-grade product.

Isolated Right Ventricular Metastasis in a Woman with Advanced Hepatocellular Carcinoma after Palliative Therapy.

Hepatocellular carcinoma (HCC) with cardiac metastasis represents a group of rarity and poor prognosis. Few case reports have described this patient entity, and it remains unclear regarding the optimal treatment and predicted outcome for these patients. In our case, we represented a 67-year-old female patient with presentations of dyspnea and heart murmur, which conducted to the diagnosis of advanced HCC with isolated right ventricular metastasis. Because of multiple comorbidities regarding cardiac and pulmonary systems, she received best supportive care and survived 2 months after initial diagnosis. A systemic literature review of 80 published cases (including our patient) since the 1950s was also performed from PubMed, and the data were gathered from the medical record and literature reviews. In our review, patients with advanced HCC and cardiac metastasis involved the right heart mainly with a predominance of right atrium (53%). Meanwhile the overall 3-month survival rate in our review was 70.7%. In subgroup analysis, the overall 3-month survival was highest (97%) in patients treated with surgery and other therapies, and lowest (27%) in patients with best supportive care. To our knowledge, this is the first comprehensive literature review addressing the epidemiology, optimal treatment, and prognosis for advanced-stage HCC with cardiac metastasis. We suggest that abnormal cardiac murmur in patients with history of HCC should prompt investigation for tumor involvement of the heart. We also emphasize individualized treatment as well as prognostic measurement accordingly.

Lauryl Gallate Induces Apoptotic Cell Death through Caspase-dependent Pathway in U87 Human Glioblastoma Cells In Vitro.

BACKGROUND/AIM: The treatment of human glioma tumor is still an unmet medical need. Natural products are always promising resources for discovery of anticancer drugs. Lauryl gallate (LG) is one of the derivatives of gallic acid, widely present in plants, that has been shown to induce anticancer activities in many human cancer cell lines; however, it has not been studied in human glioma cell lines. Thus, the effects of LG on human glioblastoma U87 cells were investigated in the present in vitro study. MATERIALS AND METHODS: Cell morphology and viability were examined by phase-contrast microscopy. Annexin V/Propidium iodide (PI) double staining were performed and assayed by flow cytometry to confirm that viable cell number reduction was due to the induction of apoptosis. Furthermore, U87 cells were exposed to LG in various concentrations and were analyzed by caspase activity assay. To further confirm that LG induced apoptotic cell death, the expression of apoptosis-associated proteins in LG-treated U87 cells was tested by western blot. RESULTS: LG induced morphological changes and decreased viability in U87 cells. Annexin V/PI double staining revealed that LG induced apoptotic cell death in U87 cells in a dose-dependent manner. The increased activities of caspase-2, -3, -8 and -9 demonstrated that LG induced U87 cell apoptosis through a caspase-dependent pathway. In terms of molecular level, LG increased pro-apoptotic proteins Bax and Bak and decreased anti-apoptotic protein Bcl-2 in U87 cells. Furthermore, LG also suppressed the expression of p-Akt, Pak1, Hif-1α and Hif-2α, ß-catenin and Tcf-1 in U87 cells. CONCLUSION: These results suggest that LG induced apoptotic cell death via the caspase-dependent pathway in U87 cells.

Antitumorigenic Effects of ZAKß, an Alternative Splicing Isoform of ZAK.

Sterile alpha motif (SAM)- and leucine-zipper-containing kinase (ZAK) plays a role in the regulation of cell cycle progression and oncogenic transformation. The ZAK gene generates two transcript variants, ZAKα and ZAKß, through alternative splicing. In this study, we identified that ZAKα proteins were upregulated in tumor tissues, whereas ZAKß proteins were mostly expressed in corresponding normal tissues. The ectopically expressed ZAKß proteins in cancer cells inhibited cancer cell proliferation as well as anchorage-independent growth. The ZAKß:ZAKα protein ratio played a role in the regulation of the cyclic adenosine monophosphate (cAMP) signaling pathway, whereas high ZAKß protein levels led to the activation of cAMP response element binding protein 1 (CREB1) and exerted antitumor properties. Overexpression of ZAKß or CREB1 cDNAs in cancer cells inhibited anchorage-independent growth and also reduced the levels of cyclooxygenase 2 (Cox2) and ß-catenin proteins. Cancer cells treated with doxorubicin (Doxo) resulted in the switching from the expression of ZAKα to ZAKß and also inhibited cancer cell growth in soft agar, demonstrating that pharmacological drugs could be used to manipulate endogenous reprogramming splicing events and resulting in the activation of endogenous antitumorigenic properties. We showed that the two ZAK transcript variants, ZAKα and ZAKß, had opposite biological functions in the regulation of tumor cell proliferation in that ZAKß had powerful antitumor properties and that ZAKα could promote tumor growth.