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We are reporting the successful treatment of a rare case of spontaneous suprachoroidal hemorrhage (SSCH) in a young refractory glaucoma patient with rhegmatogenous retinal detachment (RRD). The 34-year-old male was admitted to our hospital having experienced pain in his right eye for two days. The patient had a history of glaucoma and long axial length in the right eye with chronic poorly controlled intraocular pressure (IOP) and acute hypotony. Following clinical examinations, the patient was diagnosed with SSCH with RRD in the right eye. The patient underwent drainage of the suprachoroidal hemorrhage and vitrectomy combined with gas injection to address retinal and choroidal detachment. During the following two months, the patient's retina remained attached. Long axial length and persistent high IOP are two major risk factors of SSCH with RRD, while acute hypotony appeared to be a precipitating factor in this case. Surgeons can consider alternative tamponade options, such as gases, during vitrectomy to treat SSCH with RRD., Competing Interests: None., (AJTR Copyright © 2024.)

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death worldwide and in Taiwan. It is highly prevalent and has a tremendous impact on global health. Therefore, the Taiwan Society of Cardiology developed these best-evidence preventive guidelines for decision-making in clinical practice involving aspects of primordial prevention including national policies, promotion of health education, primary prevention of clinical risk factors, and management and control of clinical risk factors. These guidelines cover the full spectrum of ASCVD, including chronic coronary syndrome, acute coronary syndrome, cerebrovascular disease, peripheral artery disease, and aortic aneurysm. In order to enhance medical education and health promotion not only for physicians but also for the general public, we propose a slogan (2H2L) for the primary prevention of ASCVD on the basis of the essential role of healthy dietary pattern and lifestyles: " Healthy Diet and Healthy Lifestyles to Help Your Life and Save Your Lives ". We also propose an acronym of the modifiable risk factors/enhancers and relevant strategies to facilitate memory: " ABC 2 D 2 EFG-I'M 2 ACE" : Adiposity, Blood pressure, Cholesterol and Cigarette smoking, Diabetes mellitus and Dietary pattern, Exercise, Frailty, Gout/hyperuricemia, Inflammation/infection, Metabolic syndrome and Metabolic dysfunction-associated fatty liver disease, Atmosphere (environment), Chronic kidney disease, and Easy life (sleep well and no stress). Some imaging studies can be risk enhancers. Some risk factors/clinical conditions are deemed to be preventable, and healthy dietary pattern, physical activity, and body weight control remain the cornerstone of the preventive strategy., Competing Interests: Ting-Hsing Chao has been on the speaker bureau for Astrazeneca, Bayer, Eli Lilly, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Novartis, Pfizer, Sanofi, Tanabe, and TSH biopharm. All other authors report no potential conflicts of interest in relation to these guidelines.

Nitrile-containing insecticides can be converted into their amide derivatives by Pseudaminobacter salicylatoxidans . N -(4-trifluoromethylnicotinoyl) glycinamide (TFNG-AM) is converted to 4-(trifluoromethyl) nicotinoyl glycine (TFNG) using nitrile hydratase/amidase. However, the amidase that catalyzes this bioconversion has not yet been fully elucidated. In this study, it was discovered that flonicamid (FLO) is degraded by P. salicylatoxidans into the acid metabolite TFNG via the intermediate TFNG-AM. A half-life of 18.7 h was observed for P. salicylatoxidans resting cells, which transformed 82.8% of the available FLO in 48 h. The resulting amide metabolite, TFNG-AM, was almost all converted to TFNG within 19 d. A novel amidase-encoding gene was cloned and overexpressed in Escherichia coli . The enzyme, PmsiA, hydrolyzed TFNG-AM to TFNG. Despite being categorized as a member of the amidase signature enzyme superfamily, PsmiA only shares 20-30% identity with the 14 previously identified members of this family, indicating that PsmiA represents a novel class of enzyme. Homology structural modeling and molecular docking analyses suggested that key residues Glu247 and Met242 may significantly impact the catalytic activity of PsmiA. This study contributes to our understanding of the biodegradation process of nitrile-containing insecticides and the relationship between the structure and function of metabolic enzymes.

Background: Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, is an epochal oral antidiabetic drug that improves cardiorenal outcomes. However, the effect of early dapagliflozin intervention on left ventricular (LV) remodeling in patients with type 2 diabetes free from cardiovascular disease remains unclear., Methods and Results: The ELUCIDATE trial was a prospective, open-label, randomized, active-controlled study that enrolled 76 patients with asymptomatic type 2 diabetes with LV ejection fraction ≥50%, randomized to the dapagliflozin 10 mg/day add-on or standard-of-care group. Speckle-tracking echocardiography-based measurements of the cardiac global longitudinal strain were performed at baseline and 24 weeks after treatment initiation. Patients who received dapagliflozin had a greater reduction in LV dimension (1.68 mm [95% CI, 0.53-2.84]; P =0.005), LV end-systolic volume (5.51 mL [95% CI, 0.86-10.17]; P =0.021), and LV mass index (4.25 g/m 2.7 [95% CI, 2.42-6.09]; P <0.0001) compared with standard of care in absolute mean differences. Dapagliflozin add-on therapy led to a significant LV global longitudinal strain increment (0.74% [95% CI, 1.00-0.49]; P <0.0001) and improved LV systolic and early diastolic strain rates (0.27/s [95% CI, 0.17-0.60]; and 0.11/s [95% CI, 0.06-0.16], respectively; both P <0.0001) but not in global circumferential strain. No significant changes were found in insulin resistance, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, or other biomarkers at 6 months after the dapagliflozin administration., Conclusions: Dapagliflozin add-on therapy could lead to more favorable cardiac remodeling accompanied by enhanced cardiac mechanical function among patients with asymptomatic type 2 diabetes. Our findings provide evidence of the efficacy of dapagliflozin use for the primary prevention of diabetic cardiomyopathy., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871621.

Reductive soil disinfestation (RSD) is an effective method for remediating degraded facility vegetable soils. However, the effectiveness of RSD using green manure as a carbon source in the field has not yet been clarified. We investigated the effects of RSD and organic fertilizer application on soil microbial community composition, diversity, and stability in a degraded facility vegetable soil. There were six treatments, including no fertilization (CK), no fertilization and soil flooded and mulched with plastic film (FF), soil amended with chicken manure (OM), soil amended with chicken manure and flooded and mulched with plastic film (OMR), soil amended with Sesbania cannabina (TF), and soil amended with S. cannabina and flooded and mulched with plastic film (TR). The results showed that the OMR and TR treatments significantly decreased bacterial Chao1 index, altered bacterial and fungal community structure, and increased the relative abundances of Bacillus , Rhodococcus , Clostridium , and Penicillium . The TR treatment significantly reduced the relative abundance of Fusarium . Results of redundancy analysis and Mantel test analysis suggested that soil ammonium nitrogen and dissolved organic carbon contents were the key factors influencing bacterial community composition, and soil pH was the key factor affecting fungal community composition. Results of cohesion analysis showed that the OMR and TR treatments significantly improved bacterial community stability, and that there was no difference between OMR and TR treatments. The TR treatment enhanced fungal community stability, which was significantly higher than the OMR treatment. Therefore, the RSD with green manure as carbon source could be effective remediation practice to improve soil health.

Peripheral artery disease (PAD) shares common clinical risk factors, for example, endothelial dysfunction, with preserved ejection fraction (LVEF) heart failure (HFpEF). Whether PAD is associated with preclinical systolic dysfunction and higher HF risk among individuals presenting preserved LVEF remains uncertain. We retrospectively included outpatients with at least one known or established cardiovascular (CV) risk factor with LVEF ≥ 50%. Patients were categorized into high risk and low risk of developing PAD (PAD vs Non-PAD) by ankle-brachial index (ABI) (≤ 0.90 or > 1.4) and further stratified based on their history of HFpEF (HFpEF vs. Non-HFpEF), resulting in the formation of four distinct strata. Preclinical systolic dysfunction was defined using dedicated speckle-tracking algorithm. A total of 2130 consecutive patients were enrolled in the study, with a median follow-up of 4.4 years. The analysis revealed a higher prevalence of high risk of developing PAD in patients with HFpEF compared to those without HFpEF (25.1% vs. 9.4%). Both high risk of developing PAD and HFpEF were independently associated with preclinical systolic dysfunction (global longitudinal strain, GLS ≥ - 18%) (odds ratio, OR: 1.38; 95% confidence interval, CI: 1.03-1.86). In comparison to patients at low risk of developing PAD without HFpEF (Non-PAD/Non-HFpEF group), those categorized as having a high risk of developing PAD with HFpEF (PAD/HFpEF group) exhibited the most impaired GLS and a heightened susceptibility to heart failure hospitalization (hazard ratio, HR: 6.51; 95% CI: 4.43-9.55), a twofold increased risk of all-cause mortality (HR: 2.01; 95% CI: 1.17-3.38), cardiovascular mortality (HR: 2.44; 95% CI: 1.08-5.51), and non-cardiovascular mortality (HR: 1.78; 95% CI: 0.82-3.84). A high risk of developing PAD was strongly linked to impaired preclinical systolic function and an increased likelihood for subsequent hospitalization for HF, all-cause mortality, CV mortality and non-CV mortality. There is a clear need for preventive strategies aimed at reducing hospitalizations for HF and mortality in this high-risk population., (© 2024. The Author(s).)

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Background The angiotensin receptor-neprilysin inhibitor (LCZ696) has emerged as a promising pharmacological intervention against renin-angiotensin system inhibitor in reduced ejection fraction heart failure (HFrEF). Whether the therapeutic benefits may vary among heterogeneous HFrEF subgroups remains unknown. Methods and Results This study comprised a pooled 2-center analysis including 1103 patients with symptomatic HFrEF with LCZ696 use and another 1103 independent HFrEF control cohort (with renin-angiotensin system inhibitor use) matched for age, sex, left ventricular ejection fraction, and comorbidity conditions. Three main distinct phenogroup clusterings were identified from unsupervised machine learning using 29 clinical variables: phenogroup 1 (youngest, relatively lower diabetes prevalence, highest glomerular filtration rate with largest left ventricular size and left ventricular wall stress); phenogroup 2 (oldest, lean, highest diabetes and vascular diseases prevalence, lowest highest glomerular filtration rate with smallest left ventricular size and mass), and phenogroup 3 (lowest clinical comorbidity with largest left ventricular mass and highest hypertrophy prevalence). During the median 1.74-year follow-up, phenogroup assignment provided improved prognostic discrimination beyond Meta-Analysis Global Group in Chronic Heart Failure risk score risk score (all net reclassification index P <0.05) with overall good calibrations. While phenogroup 1 showed overall best clinical outcomes, phenogroup 2 demonstrated highest cardiovascular death and worst renal end point, with phenogroup 3 having the highest all-cause death rate and HF hospitalization among groups, respectively. These findings were broadly consistent when compared with the renin-angiotensin system inhibitor control as reference group. Conclusions Phenomapping provided novel insights on unique characteristics and cardiac features among patients with HFrEF with sacubitril/valsartan treatment. These findings further showed potentiality in identifying potential sacubitril/valsartan responders and nonresponders with improved outcome discrimination among patients with HFrEF beyond clinical scoring.

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., Competing Interests: All authors declare no conflict of interest.

Background: Successful implementation of practice guidelines has been challenging in the treatment of acute coronary syndrome (ACS), leaving room for improvement. A nationwide registry can provide more information than that recorded in the National Health Insurance Research Database (NHIRD)., Methods: We conducted a prospective, nationwide, multi-center ACS full spectrum registry involving 3600 patients admitted to hospitals within 24 hours of the onset of myocardial infarction with ST-segment elevation or ACS without ST-segment elevation. In total, 41 sites including medical centers and regional hospitals were selected across Taiwan. The data for each patient are collected at 3 time points for the main study: during hospitalization, 6 months, and 12 months after the discharge. The milestone for first patient in was reached on January 7, 2022, and complete enrollment is expected before October 2023. The primary aims of the main study are to determine the degree of guideline-directed medical therapies and to identify prognostic predictors associated with 1-year composite outcomes, including death, myocardial infarction, stroke, and unplanned coronary revascularization in ACS patients. Thereafter, the patient data will be analyzed every 3 to 5 years for up to 20 years after discharge using the NHIRD in the extended study., Conclusions: We hypothesized that a greater increase in the implementation of guideline-directed medical therapies can be observed. The results of the current study will add new and important information regarding a broad spectrum of ACS to drive further investigations., Competing Interests: Ting-Hsing Chao have been on the speaker bureau for AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Pfizer, Sanofi, Tanabe, Orient EuroPharma, and TSH biopharm. Tzung-Dau Wang has been on the speaker bureau for AstraZeneca, Daiichi-Sankyo, Medtronic, Novartis, Pfizer, and Omron. All other authors declare no potential conflict of interest in relation to this work.

The prevalence of heart failure is increasing, causing a tremendous burden on health care systems around the world. Although mortality rate of heart failure has been significantly reduced by several effective agents in the past 3 decades, yet it remains high in observational studies. More recently, several new classes of drugs emerged with significant efficacy in reducing mortality and hospitalization in chronic heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). To integrate these effective therapies and prioritize them in the management of Asian patients, Taiwan Society of Cardiology has recently appointed a working group to formulate a consensus of pharmacological treatment in patients with chronic heart failure. Based on most updated information, this consensus provides rationales for prioritization, rapid sequencing, and in-hospital initiation of both foundational and additional therapies for patients with chronic heart failure., Competing Interests: Dr. C.-E. Chiang has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Menarini, MSD, Novartis, Pfizer, and Sanofi. Dr. C.-L. Hung has received honorarium from Astrazeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, and Sanofi. Dr. Y.-W. Wu has received honorarium from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Sanofi, and Takeda. Dr. T.-H. Lin has received honorarium from Astrazeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Sanofi, Bayer, Viatris, Menariri, Tanabe, and Takeda. Dr. K.-C. Ueng has received honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, and Sanofi. Dr. S.-H. Sung has received honorarium from Astrazeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, Sanofi, Abbott, and Edward. Dr. C.-K. Wu has received honorarium from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, Sanofi, and Abbott. Dr. T.-H. Chao has received honorarium from Bayer, AstraZeneca, Eli Lilly, Boehringer Ingelheim, Daiichi-Sankyo, Tanabe Taiwan, and Novartis. Dr. Y.-H. Lin has received honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Novartis, Pfizer, and Sanofi. Dr. M. YC Chen has received honorarium from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, and Pfizer. Dr. P.-L. Lin has received honorarium from AstraZeneca, Abbott, Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Eli Lilly, Novartis, Novo Nordisk, Pfizer, and Sanofi. Dr. T.-F. Chao has received speaker honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, and Sanofi. Dr. H.-M. Cheng has received honorarium from AstraZeneca, Pfizer, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, SERVIER, Sanofi, Takeda, and Eli Lilly. Dr. M.-E. Liu has received honorarium from Abbott, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Medtronic, MSD, Novartis, Pfizer, and Sanofi. Dr. H.-I. Yeh has received honorarium from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, MSD, Novartis, Novo Nordisk, Pfizer, and Sanofi. Dr. Y.-H. Li has received honorarium from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, and Sanofi. Dr. I.-C. Hsieh has received honorarium from AstraZeneca, Boehringer Ingelheim, Novartis, Bayer, MSD, Sanofi, Daiichi Sankyo, Pfizer, and Eli Lilly. Dr. C.-C. Wang has received honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, and Pfizer. Dr. C.-H. Chen reports honoraria from Novartis and Daiichi Sankyo. Dr. P.-H. Chu has received honorarium from AstraZeneca. Dr. S.-J. Yeh has received honorarium from Tanabe. Dr. W.-J. Chen has received honorarium from Astrazeneca, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Novartis, Pfizer, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome with multiple underlying mechanisms and comorbidities that leads to a variety of clinical phenotypes. The identification and characterization of these phenotypes are essential for better understanding the precise pathophysiology of HFpEF, identifying appropriate treatment strategies, and improving patient outcomes. Despite accumulating data showing the potentiality of artificial intelligence (AI)-based phenotyping using clinical, biomarker, and imaging information from multiple dimensions in HFpEF management, contemporary guidelines and consensus do not incorporate these in daily practice. In the future, further studies are required to authenticate and substantiate these findings in order to establish a more standardized approach for clinical implementation.

Background Fragmented QRS (fQRS) morphology as a surrogate marker of the possible presence of myocardial scarring has been shown to confer a higher risk in patients with reduced ejection fraction heart failure. We aimed to investigate the pathophysiological correlates and prognostic implications of fQRS in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We consecutively studied 960 patients with HFpEF (76.4±12.7 years, men: 37.2%). fQRS was assessed using a body surface ECG during hospitalization. QRS morphology was available and classified into 3 categories among 960 subjects with HFpEF as non-fQRS, inferior fQRS, and anterior/lateral fQRS groups. Despite comparable clinical features in most baseline demographics among the 3 fQRS categories, anterior/lateral fQRS showed significantly higher B-type natriuretic peptide/troponin levels (both P <0.001), with both the inferior and anterior/lateral fQRS HFpEF groups demonstrating a higher degree of unfavorable cardiac remodeling, greater extent of myocardial perfusion defect, and slower coronary flow phenomenon (all P <0.05). Patients with anterior/lateral fQRS HFpEF exhibited significantly altered cardiac structure/function and more impaired diastolic indices (all P <0.05). During a median of 657 days follow-up, the presence of anterior/lateral fQRS conferred a doubled HF re-admission risk (adjusted hazard ratio 1.90, P <0.001), with both inferior and anterior/lateral fQRS having a higher risk of cardiovascular and all-cause death (all P <0.05) by using Cox regression models. Conclusions The presence of fQRS in HFpEF was associated with more extensive myocardial perfusion defects and worsened mechanics, which possibly denotes a more severe involvement of cardiac damage. Early recognition in such patients with HFpEF likely benefits from targeted therapeutic interventions.

Background: We tested the hypothesis that non-invasive pulse wave analysis (PWA)-derived systemic circulation variables can predict invasive hemodynamics of pulmonary circulation and the indicator of right heart function, N-terminal pro-brain natriuretic peptide (NT-proBNP), in patients with precapillary pulmonary hypertension (PH)., Methods: This prospective study enrolled patients with group 1 and 4 PH who had complete PWA, NT-proBNP, and hemodynamics data. Risk assessment-based "hemodynamic score (HS)" and principal component analysis-based PWA variable grouping were determined/performed. Models of hierarchical multiple linear regression (HMLR) and receiver operating characteristic (ROC) curves were used to determine the relationships of PWA variables with HS and NT-proBNP and to predict the latter parameters., Results: Fifty-three PWAs were included. PWA variables were classified into 4 eigenvalue principal components (representing 90% configuration). Univariate analysis showed that left ventricular ejection time (LVET) was significantly negatively associated with HS and NT-proBNP levels. HMLR analysis showed that LVET was still significantly, negatively, and independently associated with HS (B = -0.006 [-0.010~-0.001]) and NT-proBNP (B = -13.47 [-21.20~-5.73]). ROC curve analysis showed that LVET > 306.9 msec and > 313.2 msec predicted the low-risk group of HS (AUC: 0.802; p = 0.001; sensitivity: 100%; and specificity: 59%) and low-to-intermediate risk levels of NT-proBNP (AUC: 0.831; p < 0.001; sensitivity: 100%; and specificity: 59%)., Conclusions: The non-invasive PWA parameter, LVET, is an independent predictor of invasive right heart HS and NT-proBNP levels; it may serve as a novel biomarker of right ventricular function in patients with pre-capillary PH.

Background: Pulmonary arterial hypertension (PAH), defined as the presence of a mean pulmonary artery pressure > 20 mmHg, pulmonary artery wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance (PVR) > 2 Wood units based on expert consensus, is characterized by a progressive and sustained increase in PVR, which may lead to right heart failure and death. PAH is a well-known complication of connective tissue diseases (CTDs), such as systemic sclerosis, systemic lupus erythematosus, Sjogren's syndrome, and other autoimmune conditions. In the past few years, tremendous progress in the understanding of PAH pathogenesis has been made, with various novel diagnostic and screening methods for the early detection of PAH proposed worldwide., Objectives: This study aimed to obtain a comprehensive understanding and provide recommendations for the management of CTD-PAH in Taiwan, focusing on its clinical importance, prognosis, risk stratification, diagnostic and screening algorithm, and pharmacological treatment., Methods: The members of the Taiwan Society of Cardiology (TSOC) and Taiwan College of Rheumatology (TCR) reviewed the related literature thoroughly and integrated clinical trial evidence and real-world clinical experience for the development of this consensus., Conclusions: Early detection by regularly screening at-risk patients with incorporations of relevant autoantibodies and biomarkers may lead to better outcomes of CTD-PAH. This consensus proposed specific screening flowcharts for different types of CTDs, the risk assessment tools applicable to the clinical scenario in Taiwan, and a recommendation of medications in the management of CTD-PAH.

Objective: To compare the postoperative recovery of primary pterygium excision combined with either limbal stem cell transplantation (LSCT) or amniotic membrane transplantation (AMT)., Methods: All relevant studies on the primary pterygium excision combined with either LSCT or AMT conducted before August 2022 were extracted from PubMed, EMBASE, Web of Science, and Cochrane Library databases. The main outcomes compared were tear film stability at 1, 3, and 6 months after surgery, postoperative corneal epithelial healing time, recurrence rate, and complications., Results: Sixteen randomized controlled trials (RCTs) with 1390 eye cases were included in this meta-analysis. We found that patients of the AMT group improved significantly in the results of the tear break-up time (BUT) and Schirmer I test at 1 month after surgery (BUT: MD=-0.37, 95% CI: -0.62, -0.12, P <0.05; Schirmer I test: MD=-0.32, 95% CI: -0.57, -0.07, P <0.05) compared with those of the LSCT group, suggesting that the early stage of tear film stability after primary pterygium excision combined with AMT was superior to the LSCT combination. However, according to the Schirmer I test result, the patients in the LSCT group showed increased tear production compared to the AMT group at 3 and 6 months after surgery (3 months: MD=0.36, 95% CI: 0.08, 0.64, P <0.05; 6 months: MD=0.33, 95% CI: 0.07, 0.60, P <0.05), suggesting that the LSCT combination was superior to the AMT combination in long-term postoperative tear film stability. As for postoperative corneal epithelial healing time, the LSCT group exhibited shorter time than the AMT group (MD=-1.17, 95% CI: -2.15, -0.19, P <0.05). Furthermore, the recurrence rate was lower in the LSCT group than in the AMT group (RR=0.42, 95% CI: 0.30, 0.59, P <0.05). Lastly, there was no statistical difference in BUT and complication rate at 3 and 6 months after surgery between the LSCT and AMT groups., Conclusions: Our analysis suggests that primary pterygium excision combined with LSCT may be a better choice compared to the combination with AMT in postoperative recovery., Competing Interests: None., (AJTR Copyright © 2023.)

N6-methyladenosine (m6A) modification is a common epigenetic modification. It is reported that lncRNA can be regulated by m6A modification. Previous studies have shown that lncRNAs associated with m6A regulation (m6A-lncRNAs) serve as ideal prognostic biomarkers. However, whether lncRNAs are involved in m6A modification in colon adenocarcinoma (COAD) needs further exploration. The objective of this study was to construct an m6A-lncRNAs-based signature for patients with COAD. We obtained the RNA sequencing data and clinical information from The Cancer Genome Atlas (TCGA). Pearson correlation analysis was employed to recognize lncRNAs associated with m6A regulation (m6A-lncRNAs). 24 prognostic m6A-lncRNAs was identified by univariate Cox regression analysis. Gene set enrichment analysis (GSAE) was used to investigate the potential cellular pathways and biological processes. We have also explored the relationship between immune infiltrate levels and m6A-lncRNAs. Then, a predictive signature based on the expression of 13 m6A-lncRNAs was constructed by the Lasso regression algorithm, including UBA6-AS1, AC139149.1, U91328.1, AC138207.5, AC025171.4, AC008760.1, ITGB1-DT, AP001619.1, AL391422.4, AC104532.2, ZEB1-AS1, AC156455.1, and AC104819.3. ROC curves and K M survival curves have shown that the risk score has a well-predictive ability. We also set up a quantitative nomogram on the basis of risk score and prognosis-related clinical characteristics. In summary, we have identified some m6A-lncRNAs that correlated with prognosis and tumor immune microenvironment in COAD. In addition, a potential alternative signature based on the expression of m6A-lncRNAs was provided for the management of COAD patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Su-Zhe Zhou et al.)

Coronary artery disease (CAD) covers a wide spectrum from persons who are asymptomatic to those presenting with acute coronary syndromes (ACS) and sudden cardiac death. Coronary atherosclerotic disease is a chronic, progressive process that leads to atherosclerotic plaque development and progression within the epicardial coronary arteries. Being a dynamic process, CAD generally presents with a prolonged stable phase, which may then suddenly become unstable and lead to an acute coronary event. Thus, the concept of "stable CAD" may be misleading, as the risk for acute events continues to exist, despite the use of pharmacological therapies and revascularization. Many advances in coronary care have been made, and guidelines from other international societies have been updated. The 2023 guidelines of the Taiwan Society of Cardiology for CAD introduce a new concept that categorizes the disease entity according to its clinical presentation into acute or chronic coronary syndromes (ACS and CCS, respectively). Previously defined as stable CAD, CCS include a heterogeneous population with or without chest pain, with or without prior ACS, and with or without previous coronary revascularization procedures. As cardiologists, we now face the complexity of CAD, which involves not only the epicardial but also the microcirculatory domains of the coronary circulation and the myocardium. New findings about the development and progression of coronary atherosclerosis have changed the clinical landscape. After a nearly 50-year ischemia-centric paradigm of coronary stenosis, growing evidence indicates that coronary atherosclerosis and its features are both diagnostic and therapeutic targets beyond obstructive CAD. Taken together, these factors have shifted the clinicians' focus from the functional evaluation of coronary ischemia to the anatomic burden of disease. Research over the past decades has strengthened the case for prevention and optimal medical therapy as central interventions in patients with CCS. Even though functional capacity has clear prognostic implications, it does not include the evaluation of non-obstructive lesions, plaque burden or additional risk-modifying factors beyond epicardial coronary stenosis-driven ischemia. The recommended first-line diagnostic tests for CCS now include coronary computed tomographic angiography, an increasingly used anatomic imaging modality capable of detecting not only obstructive but also non-obstructive coronary plaques that may be missed with stress testing. This non-invasive anatomical modality improves risk assessment and potentially allows for the appropriate allocation of preventive therapies. Initial invasive strategies cannot improve mortality or the risk of myocardial infarction. Emphasis should be placed on optimizing the control of risk factors through preventive measures, and invasive strategies should be reserved for highly selected patients with refractory symptoms, high ischemic burden, high-risk anatomies, and hemodynamically significant lesions. These guidelines provide current evidence-based diagnosis and treatment recommendations. However, the guidelines are not mandatory, and members of the Task Force fully realize that the treatment of CCS should be individualized to address each patient's circumstances. Ultimately, the decision of healthcare professionals is most important in clinical practice.

Background: Epicardial adipose tissue (EAT) as a marker of metabolic disorders has been shown to be closely associated with a variety of unfavorable cardiovascular events and cardiac arrhythmias. Data on regional-specific visceral adiposity outside the heart and its modulation on autonomic dysfunction, particularly heart rate recovery after exercise, remain obscure., Methods: We studied 156 consecutive subjects (mean age: 49.3 ± 8.0 years) who underwent annual health surveys and completed treadmill tests. Multi-detector computed tomography-based visceral adiposity, including EAT and peri-aortic fat (PAF) tissue, was quantified using dedicated software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). We further correlated EAT and PAF with blood pressure and heart rate (HR) recovery information from an exercise treadmill test. Metabolic abnormalities were scored by anthropometrics in combination with biochemical data., Results: Increased EAT and PAF were both associated with a smaller reduction in systolic blood pressure during the hyperventilation stage before exercise compared to supine status (β-coefficient (coef.): -0.19 and -0.23, respectively, both p < 0.05). Both visceral adipose tissue mediated an inverted relationship with heart rate recovery at 3 (EAT: β-coef.: -0.3; PAF: β-coef.: -0.36) and 6 min (EAT: β-coef.: -0.32; PAF: β-coef.: -0.34) after peak exercise, even after adjusting for baseline clinical variables and body fat composition (all p < 0.05)., Conclusion: Excessive visceral adiposity, whether proximal or distal to the heart, may modulate the autonomic response by lowering the rate of HR recovery from exercise after accounting for clinical metabolic index. Cardiac autonomic dysfunction may partly explain the increase in cardiovascular morbidity and mortality related to both visceral fats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chang, Chu, Tsai, Kuo, Tsai, Hung, Hou, Lai, Liu, Huang, Yun, Yeh and Hung.)

Visceral adipose tissue (VAT) is associated with central obesity, insulin resistance and metabolic syndrome. However, the association of body-site specific adiposity and non-alcoholic fatty liver disease (NAFLD) has not been well characterized. We studies 704 consecutive subjects who underwent annual health survey in Taiwan. All subjects have been divided into three groups including normal (341), mild (227) and moderate and severe (136) NAFLD according to ultrasound finding. Pericardial (PCF) and thoracic peri-aortic adipose tissue (TAT) burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3DWorkstation, TeraRecon, SanMateo, CA, USA). We explored the relationship between PCF/TAT, NAFLD and cardiometabolic risk profiles. Patients with moderate and mild NAFLD have greater volume of PCF (100.7 ± 26.3vs. 77.1 ± 21.3 vs. 61.7 ± 21.6 ml, P < 0.001) and TAT (11.2 ± 4.1 vs. 7.6 ± 2.6 vs. 5.5 ± 2.6 ml, P < 0.001) when compared to the normal groups. Both PCF and TAT remained independently associated with NAFLD after counting for age, sex, triglyceride, cholesterol and other cardiometabolic risk factors. In addition, both PCF and TAT provided incremental prediction value for NAFLD diagnosis. (AUROC: 0.85 and 0.87, 95%, confidence interval: 0.82-0.89 and 0.84-0.90). Both visceral adipose tissues strongly correlated with the severity of NAFLD. Compared to PCF, TAT is more tightly associated with NAFLD diagnosis in a large Asian population., (© 2022. The Author(s).)

Background: This study aims to explore the clinical correlates of myocardial deformations using speckle-tracking algorithm and to determine the prognostic utility of such measures in asymptomatic ethnic Chinese population., Methods: Global longitudinal (GLS), circumferential strain (GCS), and torsion were analyzed using featured tissue-tracking algorithm among 4049 symptom-free ethnic Chinese population. Hypertrophy (LVH) was classified into 4 tiers: indeterminate, dilated, thick and thick/dilated, by gender-stratified partition of end-diastolic volume index (EDVi) and LV mass/EDV0.67., Results: LVH (7.3%) showed substantially lower GLS (-20.3 ± 1.82% vs. -18.9 ± 2.08%) yet higher torsion (2.20 ± 0.90 vs. 2.39 ± 1.01, p < 0.001) than non-LVH participants. Those with thick LVH (n = 123) were more obese, had higher blood pressure and increased high-sensitivity C-reactive protein (hs-CRP); with dilated/thick LVH (n = 26) group demonstrating highest pro-brain natriuretic peptide (NT-proBNP) and worse GLS compared to indeterminate-/non-LVH groups. There were independent associations among larger EDVi, higher NT-proBNP and decreased torsion, and among greater LV mass/EDV0.67, worse GLS, greater GCS/torsion and hs-CRP. Over a median of 2.3 years (IQR: 1.2-4.8), the dilated, thick, and dilated/thick LVH categorizations were associated with higher risk of composite all-cause death and heart failure (HF) compared to non-LVH (adjusted hazard ratio [HR]: 3.65, 3.72, 6.01, respectively, all p < 0.05). Per 1% GLS reduction was independently associated with higher risk (adjusted HR: 1.31, p < 0.001) and improved risk prediction (p ≤ 0.001 by integrated discrimination improvement [IDI]: 3.5%, 95% CI: 1.5%-5.6%, and continuous net reclassification improvement [NRI]: 42.3%, 95% CI: 24.0%-60.6%) over LVH., Conclusion: GLS improved risk stratification of four-tiered classification of LVH in asymptomatic ethnic Chinese., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Hypertension is the most important modifiable cause of cardiovascular (CV) disease and all-cause mortality worldwide. Despite the positive correlations between blood pressure (BP) levels and later CV events since BP levels as low as 100/60 mmHg have been reported in numerous epidemiological studies, the diagnostic criteria of hypertension and BP thresholds and targets of antihypertensive therapy have largely remained at the level of 140/90 mmHg in the past 30 years. The publication of both the SPRINT and STEP trials (comprising > 8,500 Caucasian/African and Chinese participants, respectively) provided evidence to shake this 140/90 mmHg dogma. Another dogma regarding hypertension management is the dependence on office (or clinic) BP measurements. Although standardized office BP measurements have been widely recommended and adopted in large-scale CV outcome trials, the practice of office BP measurements has never been ideal in real-world practice. Home BP monitoring (HBPM) is easy to perform, more likely to be free of environmental and/or emotional stress, feasible to document long-term BP variations, of good reproducibility and reliability, and more correlated with hypertension-mediated organ damage (HMOD) and CV events, compared to routine office BP measurements. In the 2022 Taiwan Hypertension Guidelines of the Taiwan Society of Cardiology (TSOC) and the Taiwan Hypertension Society (THS), we break these two dogmas by recommending the definition of hypertension as ≥ 130/80 mmHg and a universal BP target of < 130/80 mmHg, based on standardized HBPM obtained according to the 722 protocol. The 722 protocol refers to duplicate BP readings taken per occasion ("2"), twice daily ("2"), over seven consecutive days ("7"). To facilitate implementation of the guidelines, a series of flowcharts encompassing assessment, adjustment, and HBPM-guided hypertension management are provided. Other key messages include that: 1) lifestyle modification, summarized as the mnemonic S-ABCDE, should be applied to people with elevated BP and hypertensive patients to reduce life-time BP burden; 2) all 5 major antihypertensive drugs (angiotensin-converting enzyme inhibitors [A], angiotensin receptor blockers [A], β-blockers [B], calcium-channel blockers [C], and thiazide diuretics [D]) are recommended as first-line antihypertensive drugs; 3) initial combination therapy, preferably in a single-pill combination, is recommended for patients with BP ≥ 20/10 mmHg above targets; 4) a target hierarchy (HBPM-HMOD- ambulatory BP monitoring [ABPM]) should be considered to optimize hypertension management, which indicates reaching the HBPM target first and then keeping HMOD stable or regressed, otherwise ABPM can be arranged to guide treatment adjustment; and 5) renal denervation can be considered as an alternative BP-lowering strategy after careful clinical and imaging evaluation.

Background: Despite known sex differences in cardiac structure and function, little is known about how menopause and estrogen associate with atrioventricular mechanics and outcomes., Objective: To study how, sex differences, loss of estrogen in menopause and duration of menopause, relate to atrioventricular mechanics and outcomes., Methods: Among 4051 asymptomatic adults (49.8 ± 10.8 years, 35%women), left ventricular (LV) and left atrial (LA) mechanics were assessed using speckle-tracking., Results: Post-menopausal (vs. pre-menopausal) women had similar LV ejection fraction but reduced GLS, reduced PALS, increased LA stiffness, higher LV sphericity and LV torsion (all p < 0.001). Multivariable analysis showed menopause to be associated with greater LV sphericity (0.02, 95%CI 0.01, 0.03), higher indexed LV mass (LVMi), lower mitral e', lower LV GLS (0.37, 95%CI 0.04-0.70), higher LV torsion, larger LA volume, worse PALS (∼2.4-fold) and greater LA stiffness (0.028, 95%CI 0.01-0.05). Increasing years of menopause was associated with further reduction in GLS, markedly worse LA mechanics despite greater LV sphericity and higher torsion. Lower estradiol levels correlated with more impaired LV diastolic function, impaired LV GLS, greater LA stiffness, and increased LV sphericity and LV torsion (all p < 0.05). Approximately 5.5% (37/669) of post-menopausal women incident HF over 2.9 years of follow-up. Greater LV sphericity [adjusted hazard ratio (aHR) 1.04, 95%CI 1.00-1.07], impaired GLS (aHR 0.87, 95%CI 0.78-0.97), reduced peak left atrial longitudinal strain (PALS, aHR 0.94, 95%CI 0.90-0.99) and higher LA stiffness (aHR 10.5, 95%CI 1.69-64.6) were independently associated with the primary outcome of HF hospitalizations in post-menopause. Both PALS < 23% (aHR:1.32, 95%CI 1.01-3.49) and GLS < 16% (aHR:5.80, 95%CI 1.79-18.8) remained prognostic for the incidence of HF in post-menopausal women in dichotomous analyses, even after adjusting for confounders. Results were consistent with composite outcomes of HF hospitalizations and 1-year all-cause mortality as well., Conclusion: Menopause was associated with greater LV/LA remodeling and reduced LV longitudinal and LA function in women. The cardiac functional deficit with menopause and lower estradiol levels, along with their independent prognostic value post-menopause, may elucidate sex differences in heart failure further., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sung, Chandramouli, Lo, Tsai, Lai, Hsiao, Tsai, Yun, Hung, Kuo, Lin, Hou, Chen, Su, Hung, Bulwer, Yeh and Lam.)

Ecosystem structure determines material circulation, energy flow, and system function. Based on field investigation data in the Sanmen Bay, East China Sea from 2017 to 2018, ecological channel model was constructed by Ecopath, describing energy flow routes and functional characteristics of the Sanmen Bay ecosystem. Results showed that grazing food chain was the main energy circulation channel, and the trophic level of each functional group ranged from 1 to 3.80. Energy flow of the system was mainly concentrated in the first five levels, with an average energy conversion efficiency of 13.0%. Energy conversion efficiency was 12.8% and 14.5% from primary producers and debris, respectively. Connectance index (CI) and system omnivory index (SOI) were 0.40 and 0.24 respectively. Finn's cycling index (FIC) was 0.40, and Finn's mean path length (MPL) was 2.06. The ratio of total primary productivity to total respiration was 13.59. In conclusion, Sanmen Bay ecosystem was immature in material circulation and energy flow. This work is helpful to understand the structural and functional traits of coastal ecosystems in China.

Advances in cancer management have significantly improved survival in patients with cancers. Cardiovascular complications of cancer treatment are becoming significant competing causes of death in these patients. Radiotherapy is an indispensable component of cancer treatment, and irradiation of the heart and vasculature during cancer radiotherapy is now recognized as a new risk factor for cardiovascular diseases. It is important to involve multidisciplinary expertise and provide practical recommendations to promote awareness, recognize risks, and provide adequate interventions without jeopardizing cancer control. In this consensus paper, experts from the Taiwan Society for Therapeutic Radiology and Oncology and Taiwan Society of Cardiology provide a focused update on the clinical practice for risk stratification and management of radiation-induced cardiovascular disease (RICVD). We believe that implementing RICVD care under a collaborative cardio-oncology program will significantly improve cancer treatment outcomes and will facilitate high quality clinical investigations.

Background Visceral adipose tissue is assumed to be an important indicator for insulin resistance and diabetes beyond overweight/obesity. We hypothesized that region-specific visceral adipose tissue may regulate differential biological effects for new-onset diabetes regardless of overall obesity. Methods and Results We quantified various visceral adipose tissue measures, including epicardial adipose tissue, paracardial adipose tissue, interatrial fat, periaortic fat, and thoracic aortic adipose tissue in 1039 consecutive asymptomatic participants who underwent multidetector computed tomography. We explored the associations of visceral adipose tissue with baseline dysglycemic indices and new-onset diabetes. Epicardial adipose tissue, paracardial adipose tissue, interatrial fat, periaortic fat, and thoracic aortic adipose tissue were differentially and independently associated with dysglycemic indices (fasting glucose, postprandial glucose, HbA1c, and homeostasis model assessment of insulin resistance) beyond anthropometric measures. The superimposition of interatrial fat and thoracic aortic adipose tissue on age, sex, body mass index, and baseline homeostasis model assessment of insulin resistance expanded the likelihood of baseline diabetes (from 67.2 to 86.0 and 64.4 to 70.8, P for ∆ ꭕ 2 : <0.001 and 0.011, respectively). Compared with the first tertile, the highest interatrial fat tertile showed a nearly doubled risk for new-onset diabetes (hazard ratio, 2.09 [95% CI, 1.38-3.15], P <0.001) after adjusting for Chinese Visceral Adiposity Index. Conclusions Region-specific visceral adiposity may not perform equally in discriminating baseline dysglycemia or diabetes, and showed differential predictive performance in new-onset diabetes. Our data suggested that interatrial fat may serve as a potential marker for new-onset diabetes.

Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is a common genetic variant in Asians that is responsible for defective toxic aldehyde and lipid peroxidation metabolism after alcohol consumption. The extent to which low alcohol consumption may cause atrial substrates to trigger atrial fibrillation (AF) development in users with ALDH2 variants remains to be determined. We prospectively enrolled 249 ethnic Asians, including 56 non-drinkers and 193 habitual drinkers (135 (70%) as ALDH2 wild-type: GG, rs671; 58 (30%) as ALDH2 variants: G/A or A/A, rs671). Novel left atrial (LA) mechanical substrates with dynamic characteristics were assessed using a speckle-tracking algorithm and correlated to daily alcohol consumption and ALDH2 genotypes. Despite modest and comparable alcohol consumption by the habitual alcohol users (14.3 [8.3~28.6] and 12.3 [6.3~30.7] g/day for those without and with ALDH2 polymorphism, p = 0.31), there was a substantial and graded increase in the 4-HNE adduct and prolonged PR, and a reduction in novel LA mechanical parameters (including peak atrial longitudinal strain (PALS) and phasic strain rates (reservoir, conduit, and booster pump functions), p < 0.05), rather than an LA emptying fraction (LAEF) or LA volume index across non-drinkers, and in habitual drinkers without and with ALDH2 polymorphism (all p < 0.05). The presence of ALDH2 polymorphism worsened the association between increasing daily alcohol dose and LAEF, PALS, and phasic reservoir and booster functions (all P interaction : <0.05). Binge drinking superimposed on regular alcohol use exclusively further worsened LA booster pump function compared to regular drinking without binge use (1.66 ± 0.57 vs. 1.97 ± 0.56 1/s, p = 0.001). Impaired LA booster function further independently helped to predict AF after consideration of the CHARGE-AF score (adjusted 1.68 (95% CI: 1.06-2.67), p = 0.028, per 1 z-score increment). Habitual modest alcohol consumption led to mechanical LA substrate formation in an ethnic Asian population, which was more pronounced in subjects harboring ALDH2 variants. Impaired LA booster functions may serve as a useful predictor of AF in such populations.

Aim: To investigate the effect of latanoprost eye drops on the conjunctival lymphatics., Methods: Twenty-four healthy New Zealand White rabbits weighing 1.5 to 2.0 kg were randomly divided into three groups: latanoprost group ( n =8) administered with latanoprost eye drops once a day for 2mo, carteolol group ( n =8) administered with carteolol eye drops once a day for 2mo, and control group ( n =8) without any treatment. The conjunctival tissues in the three groups were extracted to investigate the expression levels of 5'-nucleotidase (5'-Nase) by Western blot, reverse transcription-polymerase chain reaction (RT-PCR), and immunofluorescence staining, respectively., Results: The protein expression level of 5'-Nase was significantly higher in latanoprost group than carteolol group ( F =231.175, P <0.001) and control group ( P <0.001), while there was no significant difference between the carteolol group and the control group ( P >0.05). The mRNA expression level of 5'-Nase in the latanoprost group was also significantly higher than carteolol group ( F =71.169 P <0.005) and control group ( P <0.005). The conjunctival lymphatics were positive immunofluorescence stained with the 5'-Nase antibodies in the latanoprost group and not stained in the control group., Conclusion: Latanoprost eye drops can induce conjunctival lymphangiogenesis which may be concerned in clinical implications., (International Journal of Ophthalmology Press.)

Advances in cancer treatments have led to an increasing number of cancer survivors, but also high rates of short- and long-term cardiovascular (CV) toxicities. The number of new cancer drugs is constantly increasing, and the uncertain CV toxicities of these drugs make long-term care and monitoring difficult. Moreover, traditional type I and type II cardiotoxicities may not be applicable to all of these agents. Multidisciplinary care with expertise in oncology, cardiology and other related specialties is required to mitigate cancer therapeutics-related cardiovascular dysfunction (CTRCD). The aim of this review is to provide an overview of the main CTRCD, risk assessment, early diagnosis, and strategies for the prevention and management of patients receiving cancer therapies. There are still unmet needs for cardio- oncology researchers with regards to early detection measures, better treatment strategies, better follow-up protocols, and better management of CTRCD. Experts in cardiology, oncology, hematology, and radio-oncology should thus work closely in an attempt to foster patient awareness and research in this field, as well as call for support from public and industrial sources to initiate pivotal clinical trials to solve these unmet needs.

Type 2 diabetes is a major threat to human health in the 21st century. More than half a billion people may suffer from this pandemic disease in 2030, leading to a huge burden of cardiovascular complications. Recently, 2 novel antidiabetic agents, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, reduced cardiovascular complications in a number of randomized control trials. To integrate new information and to achieve a streamlined process for better patient care, a working group was appointed by the Taiwan Society of Cardiology to formulate a stepwise consensus pathway for these therapies to reduce cardiovascular events in patients with type 2 diabetes. This consensus pathway is complementary to clinical guidelines, acting as a reference to improve patient care., Competing Interests: This work was supported, in part, by grants from the Ministry of Health and Welfare (MOHW110-TDU-B-211-124001) and intramural grants from the Taipei Veterans General Hospital (V110C-181). D. C.-E.Chiang has received honoraria from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Merck Sharpe & Dohme, Novartis, Pfizer, and Sanofi. Dr T.-H. Chao has received honoraria from AstraZeneca, Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and Orient EuroPharma. Dr T.-H. Lin has received honoraria from AstraZeneca, Boehringer Ingelheim, Tanabe, Merck Sharpe & Dohme, Novartis, Pfizer, Takeda, Sanofi, Novo Nordisk, and Lilly. Dr Y.-J. Wu has received honoraria from Johnson & Johnson, Pfizer, GlaxoSmithKline, AstraZeneca, and Boehringer Ingelheim. Dr K.-L. Wang has received honoraria from Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, and Pfizer. Dr H.-I. Yeh has received honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Lilly, Mitsubishi Tanabe, Novartis, Merck Sharpe & Dohme, Orient EuroPharma, Pfizer, and Sanofi. Dr Y.-H. Li has received honoraria from Pfizer, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Sanofi, Bayer, and Orient EuroPharma. Dr P.-Y. Liu has received honoraria from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Merck Sharpe & Dohme, Novartis, Pfizer, and Sanofi. Dr K.-C. Chang has received honoraria from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Bayer, Tanabe, Novartis, Pfizer, and Sanofi. Dr K.-G. Shyu has received honoraria from Pfizer, Daiichi-Sankyo, Bayer, AstraZeneca, Boehringer Ingelheim, Orient EuroPharma, and Eli Lilly. Dr J.-L. Huang has received honoraria from Abbott, Bayer, Biotronik, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Novartis, and Pfizer. Dr C-D. Tsai has received honoraria from Pfizer, Daiichi-Sankyo, and Novartis. Dr M.-E. Liu has received honoraria from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Merck Sharpe & Dohme, Novartis, and Pfizer. Dr T.-F. Chao has received honoraria from Abbott, Bayer, Biotronik, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Novartis, and Pfizer. Dr H.-M. Cheng has received honoraria from AstraZeneca, Pfizer, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Servier, Eli Lilly, Sanofi, and Takeda; and has received grants for clinical research from Microlife and Intelligent Vision Technology. Dr P.-H. Chu has received honoraria from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, and Pfizer. Dr Y.-W. Wu has received honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Menarini, Mitsubishi Tanabe, Novartis, Merck Sharp & Dohme, Pfizer, and Sanofi. Dr W.-T. Lai has received honoraria from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Pfizer, and Sanofi. Dr S.-J. Yeh has received honoraria from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and Tanabe. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

There is an established link between cardiometabolic abnormality, central arterial stiffness, and preserved ejection fraction heart failure (HFpEF). Adipocyte free fatty acid binding protein (a-FABP) has been shown to signal endothelial dysfunction through fatty acid toxicity, though its role in mediating ventricular-arterial dysfunction remains unclear. We prospectively examined the associations of a-FABP with central arterial pressure using non-invasive applanation tonometry (SphygmoCor) and cardiac structure/function (i.e., tissue Doppler imaging [TDI] and global longitudinal myocardial strain [GLS]) in patients with cardiometabolic (CM) risk (n = 150) and HFpEF (n = 50), with healthy volunteers (n = 49) serving as a control. We observed a graded increase of a-FABP across the healthy controls, CM individuals, and HFpEF groups (all paired p < 0.05). Higher a-FABP was independently associated with higher central systolic and diastolic blood pressures (CSP/CPP), increased arterial augmentation index (Aix), lower early myocardial relaxation velocity (TDI-e'), higher left ventricle (LV) filling (E/TDI-e') and worsened GLS (all p < 0.05). During a median of 3.85 years (interquartile range: 3.68-4.62 years) follow-up, higher a-FABP (cutoff: 24 ng/mL, adjusted hazard ratio: 1.01, 95% confidence interval: 1.001-1.02, p = 0.04) but not brain natriuretic peptide, and higher central hemodynamic indices were related to the incidence of heart failure (HF) in fully adjusted Cox models. Furthermore, a-FABP improved the HF risk classification over central hemodynamic information. We found a mechanistic pathophysiological link between a-FABP, central arterial stiffness, and myocardial dysfunction. In a population with a high metabolic risk, higher a-FABP accompanied by worsened ventricular-arterial coupling may confer more unfavorable outcomes in HFpEF., (© 2021. The Author(s).)

Fabry disease (FD) is an X-linked, rare inherited lysosomal storage disease caused by α-galactosidase A gene variants resulting in deficient or undetectable α-galactosidase A enzyme activity. Progressive accumulation of pathogenic globotriaosylceramide and its deacylated form globotriaosylsphingosine in multiple cell types and organs is proposed as main pathophysiology of FD, with elicited pro-inflammatory cascade as alternative key pathological process. The clinical manifestations may present with either early onset and multisystemic involvement (cutaneous, neurological, nephrological and the cardiovascular system) with a progressive disease nature in classic phenotype, or present with a later-onset course with predominant cardiac involvement (non-classical or cardiac variant; e.g. IVS4+919G>A in Taiwan) from missense variants. In either form, cardiac involvement is featured by progressive cardiac hypertrophy, myocardial fibrosis, various arrhythmias, and heart failure known as Fabry cardiomyopathy with potential risk of sudden cardiac death. Several plasma biomarkers and advances in imaging modalities along with novel parameters, cardiac magnetic resonance (CMR: native T1/T2 mapping) for myocardial tissue characterization or echocardiographic deformations, have shown promising performance in differentiating from other etiologies of cardiomyopathy and are presumed to be helpful in assessing the extent of cardiac involvement of FD and in guiding or monitoring subsequent treatment. Early recognition from extra-cardiac red flag signs either in classic form or red flags from cardiac manifestations in cardiac variants, and awareness from multispecialty team work remains the cornerstone for timely managements and beneficial responses from therapeutic interventions (e.g. oral chaperone therapy or enzyme replacement therapy) prior to irreversible organ damage. We aim to summarize contemporary knowledge based on literature review and the gap or future perspectives in clinical practice of FD-related cardiomyopathy in an attempt to form a current expert consensus in Taiwan.

In response to the COVID-19 pandemic, several vaccines were developed and rolled out at unprecedented speed, and notwithstanding this rapid pace of development, the results from initial clinical trials involving tens of thousands of adult subjects generally indicated that most vaccines were remarkably effective and safe, with no major safety warnings noted. However, with more than 2 billion vaccination doses administered to date, reports of rare adverse events following immunization (AEFI) are beginning to emerge. In late February 2021, atypical thrombotic events following immunization with the adenoviral vector-based ChAdOx1 nCov-19 vaccine were first reported, and similar events have also been observed in recipients of the adenoviral vector-based Ad26.COV2.S vaccine and the mRNA-based BNT162b2 and mRNA-1273 vaccines. These manifestations of atypical thrombosis and thrombocytopenia following COVID-19 vaccine immunization are now collectively referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Although the reported incidence remains very low and does not affect the overall benefit of immunization, it is also true that if left untreated, VITT can be debilitating or even fatal. Therefore, this review seeks to provide a comprehensive overview regarding the incidence, pathogenesis, presentation, diagnosis, and treatment of VITT, as well as considerations for special populations, based on the currently available evidence in the literature. It is hoped that this will enhance awareness of this vaccine side effect, so that cases of VITT may be identified and treated in a timely and appropriate manner.

The recently revised 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension (HTN) guidelines employ a lower blood pressure threshold to define HTN, aiming for earlier prevention of HTN-related cardiovascular diseases (CVD). Thoracic aortic calcification (TAC), a new surrogate marker of aging and aortic medial layer degeneration, and different stages of HTN, according to the 2017 ACC/AHA HTN guidelines, remain unknown. We classified 3022 consecutive asymptomatic individuals enrolled into four HTN categories using the revised 2017 ACC/AHA guidelines: normal blood pressure (NBP), elevated blood pressure (EBP), and stage 1 (S1) and stage 2 (S2) HTN. The coronary artery calcification score and TAC metrics (total Agaston TAC score, total plaque volume (mm 3 ), and mean density (Hounsfield units, HU)) were measured using multi-detector computed tomography. Compared to NBP, a graded and significant increase in the TAC metrics was observed starting from EBP and S1 and S2 HTN, using the new 2017 ACC/AHA guidelines (NBP as reference; all trends: p < 0.001). These differences remained consistent after being fully adjusted. Older age (>50 years), S1 and S2 HTN, prevalent diabetes, and chronic kidney disease (<60 mL/min/1.73 m 2 ) are all independently contributing factors to higher TAC risk using multivariate stepwise logistic regressions (all p ≤ 0.001). The optimal cutoff values of systolic blood pressure, diastolic blood pressure, and pulse pressure were 121, 74, and 45 mmHg, respectively, for the presence of TAC after excluding subjects with known CVD and ongoing HTN medication treatment. Our data showed that the presence of TAC starts at a stage of elevated blood pressure not categorized as HTN from the updated 2017 ACC/AHA hypertension guidelines.

Transthyretin cardiac amyloidosis (ATTR-CM) is an increasingly recognized cause of heart failure with preserved ejection fraction. Favorable prognosis depends on early diagnosis and correct treatment strategy. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis, 99m Tc-labeled bone avid scintigraphy including 99m Tc-pyrophosphate (PYP) scintigraphy may be of diagnostic and prognostic importance. Various international guidelines support the non-biopsy diagnosis of ATTR-CM using 99m Tc-PYP scintigraphy, yet emphasize the gap in standardization of acquisition and imaging analysis protocols, as well as the appropriateness of its clinical use. Therefore, a joint expert consensus has been reached by the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China, to advocate for the application of 99m Tc-PYP scintigraphy in the diagnosis of ATTR-CM. This article aims to highlight the recommendations on image acquisition, qualitative and quantitative assessments of cardiac 99m Tc-PYP uptake, and diagnostic algorithms. We hope the implementation of these recommendations in Taiwan will facilitate the process and enhance the diagnostic rate of ATTR-CM.

Alterations in miRNAs are associated with many metabolic disorders, such as type 2 diabetes (T2DM). The miR-23b/27b/24-1 cluster contains miR-23b, miR-27b, and miR-24-1, which are located within 881 bp on chromosome 9. Studies examining the roles of miR-23b, miR-27b, and miR-24-1 have demonstrated their multifaceted functions in variable metabolic disorders. However, their joint roles in metabolism in vivo remain elusive. To investigate this subject, we constructed miR-23b/27b/24-1 cluster knockout (KO) mice. Compared with wild-type (WT) mice, the KO mice exhibited impaired glucose tolerance, which was accompanied by a reduction in the respiratory exchange rate (RER). These alterations were more noticeable after a high-fat diet (HFD) induction. Hepatic metabolomic results showed decreased expression of reduced nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide (NAD), phosphoenolpyruvic acid (PEP), and phosphoric acid, which are involved in the glycolysis pathway. The transcriptomic results indicated that genes involved in glycolysis showed a downregulation trend. qPCR and Western blot revealed that pyruvate kinase (PKLR), the key rate-limiting enzyme in glycolysis, was significantly reduced after the deletion of the miR-23b/27b/24-1 cluster. Together, these observations suggest that the miR-23b/27b/24-1 cluster is involved in the regulation of glucose homeostasis via the glycolysis pathway.

The debate regarding the actual cardiovascular burden in metabolically healthy obese or metabolically unhealthy non-obesity individuals is ongoing. Accumulating data have suggested a unique pathophysiological role of pro-inflammatory cytokines in mediating metabolic and cardiovascular disorders by dysregulated visceral adiposity. To compare the burden of visceral adiposity, the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and the prevalent atherosclerotic burden in metabolically healthy obese (MHO) or metabolically unhealthy (MU) populations, were compared to those of metabolically healthy non-obesity subjects (MHNO). Coronary artery calcification score (CACS) and visceral fat, including pericardial fat (PCF)/thoracic peri-aortic fat (TAT), were quantified in 2846 asymptomatic subjects using a CT dataset. A cross-sectional analysis comparing CACS, inflammatory marker hs-CRP, and visceral fat burden among four obesity phenotypes (MHNO, metabolically unhealthy non-obesity (MUNO), MHO, and metabolically unhealthy obese (MUO)) was performed. Both MUNO and MUO demonstrated significantly higher hs-CRP and greater CACS than MHNO/MHO (adjusted coefficient: 25.46, 95% confidence interval (CI): 5.29-45.63; 43.55, 95% CI: 23.38-63.73 for MUNO and MUO (MHNO as reference); both p < 0.05). Visceral fat (PCF/TAT) was an independent determinant of MU and was similarly higher in the MUNO/MHO groups than in the MHNO group, with the MUO group having the largest amount. PCF/TAT, obesity, and MU remained significantly associated with higher CACS even after adjustment, with larger PCF/TAT modified effects for MU and diabetes in CACS (both p interaction < 0.05). MU tightly linked to excessive visceral adiposity was a strong and independent risk factor for coronary atherosclerosis even in lean individuals, which could be partially explained by its coalignment with pathological pro-inflammatory signaling.

Aims: Excessive visceral adiposity (VAT) plays an essential role in metabolic derangements with those close to heart further mediates myocardial homeostasis. The disparate biological links between region-specific VAT and cardiometabolic profiles as mediators influencing atrial kinetics remain unexplored., Methods and Results: Among 1326 asymptomatic individuals, region-specific VAT including peri-aortic root fat (PARF) and total pericardial fat (PCF) of cardiac region, together with thoracic peri-aortic adipose tissue (TAT), was assessed using multiple-detector computed tomography. VAT measures were related to functional left atrial (LA) metrics assessed by speckle-tracking algorithm and clinical outcomes of atrial fibrillation (AF) and heart failure (HF). Multivariate linear regression models incorporating body fat, metabolic syndrome, and E/TDI-e' consistently demonstrated independent associations of larger PARF/PCF with peak atrial longitudinal systolic strain (PALS) reduction, higher LA stiffness, and worsened strain rate components; instead, TAT was independently associated with cardiometabolic profiles. PARF rather than PCF or TAT conferred independent prognostic values for incident AF/HF by multivariate Cox regression (adjusted hazard ratio: 1.56, 95% confidence interval: 1.17-2.08, P = 0.002) during a median of 1790 days (interquartile range: 25th to 75th: 1440-1927 days) of follow-up, with subjects categorized into worst PALS and largest VAT tertiles demonstrating highest events (all log-rank P < 0.001). Mediation analysis showed that higher triglyceride and lower high-density lipoproteins may serve as intermediary factors for effects between VAT and LA functional metrics, with lesser role by glucose level., Conclusions: Visceral adiposity surrounding atrial region was tightly associated with subclinical atrial dysfunction and incident AF or HF beyond metabolic factors. Instead, peri-aortic adiposity may mediate their toxic effects mainly through circulating cardiometabolic profiles., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Hyperuricemia (HU) is a marker for heart failure. There are relatively few data in the Asian population regarding the effects of hyperuricemia and gouty disorders on cardiac remodeling and diastolic dysfunction (DD), an intermediate stage in the development of heart failure. We consecutively recruited asymptomatic Asian individuals to undergo cardiovascular surveys. We categorized them into Non-HU, HU, and Gout groups. We measured cardiac structure and indices for diastolic function, including tissue Doppler (TDI)-derived LV e' and E/e'. Among 5525 participants, 1568 had HU and 347 had gout. The presence of gout and higher uric acid levels (SUA) (<4, 4-6, 6-8, 8-10, > = 10 mg/dL) were associated with greater LV wall thickness, greater LV mass/volumes, larger LA volume, lower LV e' and higher E/e'. Higher SUA was associated with greater LV mass index (adjusted coefficient: 0.37), greater mass/volume ratio (adjusted coefficient: 0.01) and larger LA volume index (adjusted coefficient: 0.39, all p<0.05). Both HU and Gout groups were associated with lower LV e' (coefficient: -0.086, -0.05), higher E/e' (coefficient: 0.075, 0.35, all p <0.05), larger LA volume, and higher DD risk (adjusted ORs: 1.21 and 1.91 using Non-HU as reference, respectively, both p <0.05). SUA set at 7.0 mg/dL provided the optimal cut-off for identifying DD, with markedly lower e' (HU: 8.94 vs 8.07, Gout: 7.94 vs 7.26 cm/sec) and higher LV E/e' in HU/Gout women than in men (HU: 7.84 vs 9.79 cm/sec for men and women, respectively, all p <0.05). Hyperuricemia, even at a relatively low clinical cut-off, was associated with unfavorable remodeling and was tightly linked to diastolic dysfunction. The presence of gout likely aggravated these conditions. Women with hyperuricemia or gout had worse diastolic indices than men despite similar degrees of LV remodeling., Competing Interests: The authors have declared that no competing interests exist.

We evaluated the adaptability of Granier's empirical formula in the measurement of trunk sap flow in Populus tomentosa. The thermal diffusion probe method (TDP) was used to mea-sure sap flow rate, and the whole tree weighing was simultaneously measured for each tree. We compared results from the Granier empirical formula with that from the whole tree weighing to find out whether Granier formula had any error in measuring the trunk sap flow of P. tomentosa. The transpiration rate by the whole tree weighing method and the temperature difference coefficient K by the thermal diffusion method were fitted with power exponential regression to establish a corrected Granier formula. Compared with the transpiration rate measured by the whole tree weighing method, sap flow rate calculated by the Granier empirical formula was underestimated by 67.7%. Therefore, a calibrated Granier correction formula of P. tomentosa was established: F d =0.0135K 0.6952 (R 2 =0.77). The calculated result from this calibrated formula was only 3.4% lower than the transpiration rate estimated with the whole tree weighing method, which showed good consistency. Thus, the calculation of the P. tomentosa sap flow rate should be corrected when using the Granier empirical formula.

Background: Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic disorders that can damage various organs, including the heart. Cardiac abnormalities have been observed in patients with all MPS types, with the most documented abnormalities being cardiac valvular regurgitation and stenosis, valvular thickening, and hypertrophic cardiomyopathy., Methods: Cardiac features of 53 Taiwanese patients with MPS (31 men and 22 women; age range 1.1-34.9 years; seven with MPS I, 16 with MPS II, nine with MPS III, 14 with MPS IVA, and seven with MPS VI) were evaluated using two-dimensional speckle-tracking echocardiography and conventional echocardiography., Results: The mean z scores of the global longitudinal strain (GLS), left ventricular mass index (LVMI), interventricular septum diameter in diastole (IVSd), left ventricular posterior wall diameter in diastole (LVPWd), and aortic diameter of the 53 patients with MPS were 1.71, 0.35, 1.66, 1.03, and 3.15, respectively. Furthermore, z scores >2 were identified in 45%, 13%, 40%, 13%, and 70% of the GLS, LVMI, IVSd, LVPWd, and aortic diameter, respectively. The most severe GLS was observed in those with MPS VI, followed by in those with MPS II and MPS I. The GLS z score was positively correlated with the LVMI z score (p < 0.01). Moreover, diastolic dysfunction (reversed ratio between early and late (atrial) ventricular filling velocity (E/A ratio < 1)) was identified in 12 patients (23%). Ejection and shortening fractions were abnormal in four (8%) and seven (13%) patients, respectively. Mitral regurgitation (MR) (92%) was the most common valvular heart disease, followed by aortic regurgitation (AR) (57%), mitral stenosis (MS) (21%), and aortic stenosis (AS) (15%). The z scores of the GLS and LVMI and severity scores of the MS, MR, AS, and AR were all positively correlated with increasing age (p < 0.05). Twenty patients (38%) had a left ventricular remodeling pattern., Conclusions: The most significant left ventricular myocardial deformation, hypertrophy and valvular heart disease were observed in the patients with MPS VI, II, and I, followed by those with MPS IV; in contrast, patients with MPS III had the mildest manifestations. Cardiac abnormalities in patients with MPS worsened with increasing age in accordance with the progressive nature of this disease., Competing Interests: The authors declare no conflict of interest. The authors confirm independence from the sponsors. The contents of the article, including the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, have not been influenced by the sponsors

Smoking is known as a powerful predictor of pathological coronary atherosclerosis. Thoracic aortic calcification (TAC), an alternative marker for pathological atherosclerosis, has also been shown to be associated unfavorable cardiovascular outcomes. We aimed to investigate the dose-response relationship between cigarette use and calcification burden in subjects free from clinical symptoms. Among 3109 patients enrolled in this analysis, we categorized study participants according to smoking exposure pattern as: non-smokers, ex-smokers and current smokers. Smoking dose (cigarette/day), duration (years) and pack-years were semi-quantified as smoking dose exposure variables. Thoracic aortic calcification burden (including TAC score, plaque volume and plaque density) were determined and related to smoking dose and pattern information. TAC burdens (including TAC score, plaque volume and density) were highest in current smoker compared to non-smoker group, with ex-smoker showing TAC burdens in-between (all ANOVA p<0.05). Linear regression models consistently demonstrated that TAC burdens as continuous variables were independently higher in a dose-dependent manner with smoking exposure, particularly in high-dose (> 10 cigarettes/day) and the long-duration (> 3 years) smokers, even after adjusting for baseline demographic differences (all p<0.05). By logistic regression, subjects who never smoke consistently demonstrated reduced risk of TAC existence (adjusted OR: 0.65 [95% CI: 0.48-0.86], P = 0.003) in contrary to those current smokers (adjusted OR: 1.47 [95% CI: 1.10-1.89], P = 0.009). A dose-response relationship between active cigarette use and TAC burden was observed, with those who never exposed to smoking or quitted demonstrating partial protective effects. Our data provided imaging-based evidence about the potential deleterious biological hazards of long-term and high-dose cigarette consumption., Competing Interests: The authors have declared that no competing interests exist.

Objective: Corneal allograft rejection is an immunological hypersensitive reaction caused by the antigenicity of the donor cornea. This study aimed to explore the effects of RMT1-10 on the prevention of corneal graft rejection by modifying immunological characteristics of dendritic cells (DCs)., Materials and Methods: DCs and CD4+T cells were sorted using flow cytometry and used for in vitro mixed lymphocyte culture. The cultured cells were prepared for the characterization of the DC cell phenotypes using the markers CD11c, CD80, MHC II, CD54, and TIM-4. Cytokine concentrations of IL-4, IL-12, and IL-10 of supernatants were measured by the enzyme-linked immunosorbent assay. CD4+T cells were examined by flow cytometry for apoptosis and proliferation. We also investigated the effect of RMT1-10 in the prevention and treatment of high-risk corneal graft rejection using a mouse model of corneal transplantation., Results: DCs were identified as the CD11c+MHC-II-expressing subset. RMT1-10 suppressed the expression of CD11c, CD80, MHC II, CD54, and TIM-4 of DCs using the blockade of TIM-1 signaling. Moreover, TIM-1 blockade inhibited the production of IL-12 and IL-10 in a mixed lymphocyte culture system. However, a TIM-1 blockade had no effect on the apoptosis of CD4+T cells. RMT1-10 suppressed DC maturation, inhibiting the proliferation of CD4+T cells., Conclusions: RMT1-10 significantly improved the survival rate of the corneal allografts in mice compared with saline-injected controls. This clinical improvement from RMT1-10 occurred through the inhibition of CD4+T cell proliferation. Moreover, RMT1-10 induced antigen-specific detection of receptor immune tolerance. The cross-linking of TIM-1 on CD4+T cells with the agonist mAb provided a costimulatory inhibition signal for T cell activation or proliferation.

The new style spectacle frame for eye moxibustion is designed, which is characterized by adjustable direction, constant temperature and smoke absorption. Combined with mechanical structure design and physical and chemical technology, a new style of moxibustion spectacle frame is designed by means of spring mechanism, damping bearing, filter cotton, etc. The moxibustion spectacle frame includes the right and left eye frames, spectacle legs, nose mask, eye mask, slide rod, screw rod, spring structure, damping bearing, support rod and pin. The eye mask can prevent from the risks induced by the burning moxa stick. A ventilate hole is designed in the lower part of the nose mask to keep breathing unobstructed. In the upper end of the ventilate hole, a filter cotton is placed to prevent from moxa smoke penetrating to the nasal cavity. The spring structure can keep relatively the fixed distance between the combustion area and the acupoints. Such device ensures the safety of eye moxibustion, reduces the complexity of operation and is suitable for moxibustion treatment for all kinds of eye diseases.

Aims: This study aimed to evaluate the prognostic significance of nutritional status in post-discharge Asians with heart failure with preserved ejection fraction (HFpEF)., Methods and Results: We examined the prognostic implications of body mass index (BMI) and nutritional markers among consecutive patients hospitalized for HFpEF. Nutritional metrics were estimated by serum albumin (SA), prognostic nutritional index (PNI), Controlling Nutritional Status (CONUT) score, and geriatric nutritional risk index. Among 1120 patients (mean age: 77.2 ± 12.6 years, 39.4% men), mean SA levels, PNI, CONUT scores, and geriatric nutritional risk index were 3.3 ± 0.6 g/dL, 40.2 ± 8.7, 5.5 ± 2.1, and 95.9 ± 14.5, respectively. Lean body size, higher white blood cell counts and C-reactive protein levels, anaemia, and lack of angiotensin blocker use were independently associated with malnutrition (defined by SA < 3.5 g/dL). Higher SA levels [hazard ratio (HR): 0.67 (95% confidence interval, CI: 0.53-0.85)], higher PNI [HR: 0.97 (95% CI: 0.95-0.99)], and higher geriatric nutritional risk index [HR: 0.98 (95% CI: 0.97-0.99)] (all P < 0.05) were all associated with longer survival, with higher CONUT score [HR: 1.08 (95% CI: 1.02-1.13)] exhibited higher mortality in Cox regression models and with higher SA levels/PNI but not BMI further contributing to the reduced rate of re-hospitalization (both P < 0.05). Categorizing BMI (25 kg/m 2 as cut-off) and nutritional status showed significantly higher mortality rates among patients with lower BMI/malnutrition than among those with BMI/better nutrition (SA level, PNI, and CONUT score, all P < 0.01). Restricted cubic spline regression revealed a marked survival benefit of better nutrition with increasing BMI (adjusted P interaction for both SA level and PNI: <0.001; adjusted P interaction for CONUT score: 0.046)., Conclusions: Malnutrition was frequently and strongly associated with systemic inflammation in Asian patients hospitalized for acute HFpEF. Our findings also indicate that nutrition may play a pivotal role in metabolic protection in this population., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Aims: Left atrial (LA) remodelling is an important predictor of cardiovascular events of heart failure (HF) and atrial fibrillation. Data regarding diagnostic value of LA remodelling on diastolic dysfunction (DD) and preclinical HF remain largely unexplored., Methods and Results: We assessed LA dimension (LAD) in 8368 consecutive asymptomatic Asians (mean age: 49.7, 38.9% women) and related such measure to updated American Society of Echocardiography (ASE) DD criteria and newly revised N-terminal pro-brain natriuretic peptide (NT-proBNP) cut-off (≥125 pg/mL) and HF with preserved ejection fraction criteria incorporating NT-proBNP and echocardiography parameters by the European Society of Cardiology (ESC). LAD and indexed LAD (LADi) were both inversely correlated with myocardial relaxation e' and positively associated with indexed LA volume, left ventricular E/e', and tricuspid regurgitation velocity (all P < 0.001) and showed significantly graded increase across ASE-defined 'normal', 'inconclusive', and 'DD' categories (30.9, 34.4, and 36.5 mm; 16.7, 19.1, and 20.6 mm/m 2 , for LAD/LADi, both P for trend: <0.001, respectively). Substantial differences of LAD/LADi (31.3 vs. 33.6 mm/16.7 vs. 19.2 mm/m 2 , both P < 0.001) between ESC low and high HF probability using NT-proBNP cut-off were also observed. Multivariate linear and logistic models demonstrated that LAD set at 34 mm was independently associated with ASE-defined diastolic indices, DD existence, and elevated NT-proBNP (all P < 0.05). The use of LAD further yielded high diagnostic accuracy in DD (area under receiving operative characteristic curve: 0.77, 95% confidence interval [0.73, 0.80]; negative predictive value: 97.9%) and in ESC-recommended HF with preserved ejection fraction criteria (area under receiving operative characteristic curve: 0.70, 95% confidence interval [0.65, 0.75]; negative predictive value: 98.7%) with high predictive value in LA remodelling (>34 mL/m 2 ; positive predictive value: 96%) and well-discriminated ESC-recommended NT-proBNP (≥125 pg/mL, LAD: 37 mm) for HF., Conclusions: Single utilization of atrial remodelling is highly useful for ruling out presence of DD and provides practical threshold for identifying preclinical HF based on most updated guidelines., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Kilometer-scale evapotranspiration is usually estimated by remote sensing images, combined with empirical or semi-empirical models, with results being verified with empirical data. However, it is usually difficult to obtain real-time measurements which can match the pixel scale of remote sensing. We analyzed kilometer-scale evapotranspiration by the combination of near-infrared and microwave technique in the Ecosystem Research Station of the Yellow River in Xiaolangdi, during period of plantation growth (1st July to 19th October 2016). Results showed that the combination of near-infrared and microwave technique could obtain well diurnal cycles in different weather conditions, with the overall energy balance reaching 0.87. The technique was sensitive to the variation of relative humidity of air, but not sensitive to that of soil moisture. The error of estimation was resulted from Bowen ratios and atmospheric stability. Compared with the eddy covariance method, the error was within a reasonable range. As estimated by the two-wavelength method, the maximum daily and total evapotranspiration of the study area was 3.5 mm and 162.4 mm, respectively.