Hyperpolarized [1-13C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer.

BACKGROUND: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. METHODS: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39-60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. RESULTS: The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. CONCLUSIONS: This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951921 , registered 7 July 2021. RELEVANCE STATEMENT: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. KEY POINTS: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.

Prescribing Patterns and Outcomes of Edoxaban in Atrial Fibrillation Patients From Asia　- One-Year Data From the Global ETNA-AF Program.

Background: This study reports prescribing patterns and the 1-year effectiveness and safety of edoxaban in an Asian cohort of Edoxaban Treatment in routiNe clinical prActice (ETNA)-Atrial Fibrillation (AF) patients. Methods and Results: The Global ETNA-AF program integrates prospective, observational, noninterventional regional studies, collecting data on characteristics and clinical outcomes of patients with AF receiving edoxaban for stroke prevention. Baseline characteristics, medical history, and 1-year clinical event rates were assessed in patients from South Korea, Taiwan, Hong Kong, and Thailand. Clinically relevant events assessed at 12 months included all-cause death, cardiovascular death, ischemic and hemorrhagic stroke, systemic embolic events (SEEs), bleeding, and net clinical outcome (NCO). Overall, 3,359 patients treated with edoxaban 60 or 30 mg once daily completed 1-year follow-up; 70.9% of patients received recommended dosing according to local labels. Baseline mean±standard deviation age was 71.7±9.6 years, CHA2DS2-VASc score was 3.1±1.5, and modified HAS-BLED score was 2.3±1.1. Mean age and sex were similar across countries/regions. The 1-year event rate for all-cause death was 1.8%; major bleeding, 1.3%; ischemic stroke, 1.1%; cardiovascular mortality, 0.7%; hemorrhagic stroke, 0.3%; SEEs, 0%; and NCO, 4.1%; with differences observed between countries/regions and dosing groups. Conclusions: Most Asian patients with AF were prescribed recommended edoxaban dosing in routine care settings. At 1-year follow-up, this analysis supports the effectiveness and safety of edoxaban in these patients.

Taiwan Society of Cardiology Heart Failure Registry 2020: Rationale and Design.

Background: Heart failure (HF) is a significant public health problem worldwide. Death and rehospitalization rates are similar across different HF phenotypes. However, the existing Taiwanese HF registries mainly enrolled inpatients with HF and reduced ejection fraction (HFrEF) before 2019, so their results may not apply to outpatients or patients with HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF) phenotypes. Methods: The Taiwan Society of Cardiology Heart Failure Registry 2020 is a prospective, multicenter, observational registry that will enroll patients with HF from 27 hospitals in Taiwan between 2020 and 2022 and will be followed for two years. Patients eligible for enrollment include those admitted due to acute decompensated heart failure or outpatients with a history of hospitalization for heart failure within the past six months. The registry will collect patient demographics, medical history, HF diagnosis, medication use, examination results, and comorbidities. The registry plans to enroll 3,370 patients, with the distribution of HFrEF/HFmrEF/HFpEF as 59%/13%/28%. Follow-up intervals will occur every six months for up to two years to monitor clinical outcomes and major cardiac interventions. The registry will conclude in December 2024. Conclusions: The Taiwan Society of Cardiology Heart Failure Registry 2020 is a comprehensive and meticulous effort to demonstrate the epidemiology, adherence to guidelines, clinical outcomes, and disease progression of Taiwanese patients with HF in contemporary clinical practice.

2024 Guidelines of the Taiwan Society of Cardiology for the Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a multi-organ systemic syndrome that involves cardiac and extra-cardiac pathophysiological abnormalities. Its growing prevalence causes a major public concern worldwide. HFpEF is usually associated with multiple comorbidities, and non-cardiovascular death is common in patients with HFpEF. In Asia, patients with HFpEF has a younger age, higher prevalence of diabetes and chronic kidney disease than Western countries. A 2-step diagnostic algorithm is recommended in this guideline. In the first step, the diagnosis of HFpEF can be made if patients have symptoms and/or signs of heart failure, left ventricular ejection fraction ≥ 50%, increased natriuretic peptide, and objective evidence of left atrial or left ventricular abnormalities or raised left ventricular filling pressure. If diagnosis is still uncertain, invasive or noninvasive stress test can be performed in the second step. Comorbidities need to be controlled in HFpEF. Weight reduction for obesity and supervised exercise training are recommended for HFpEF. For pharmacological therapy, diuretic is used to relieve congestion and sodium-glucose cotransporter 2 inhibitor, empagliflozin or dapagliflozin, is recommended to improve prognosis of HFpEF. The research on HFpEF is advancing at a rapid pace. It is expected that newer modalities for diagnosis and management of HFpEF could appear in the near future.

Comparing Artificial Intelligence-Enabled Electrocardiogram Models in Identifying Left Atrium Enlargement and Long-term Cardiovascular Risk.

BACKGROUND: The role of P-wave in identifying left atrial enlargement (LAE) with the use of artificial intelligence (AI)-enabled electrocardiography (ECG) models is unclear. It is also unknown if AI-enabled single-lead ECG could be used as a diagnostic tool for LAE surveillance. We aimed to build AI-enabled P-wave and single-lead ECG models to identify LAE using sinus rhythm (SR) and non-SR ECGs, and compare the prognostic ability of severe LAE, defined as left atrial diameter ≥ 50 mm, assessed by AI-enabled ECG models vs echocardiography. METHODS: This retrospective study used data from 382,594 consecutive adults with paired 12-lead ECG and echocardiography performed within 2 weeks of each other at Chang Gung Memorial Hospital. UNet++ was used for P-wave segmentation. ResNet-18 was used to develop deep convolutional neural network-enabled ECG models for discriminating LAE. External validation was performed with the use of data from 11,753 patients from another hospital. RESULTS: The AI-enabled 12-lead ECG model outperformed other ECG models for classifying LAE, but the single-lead ECG models also showed excellent performance at a left atrial diameter cutoff of 50 mm. AI-enabled ECG models had excellent and fair discrimination on LAE using the SR and the non-SR data set, respectively. Severe LAE identified by AI-enabled ECG models was more predictive of future cardiovascular disease than echocardiography; however, the cumulative incidence of new-onset atrial fibrillation and heart failure was higher in patients with echocardiography-severe LAE than with AI-enabled ECG-severe LAE. CONCLUSIONS: P-Wave plays a crucial role in discriminating LAE in AI-enabled ECG models. AI-enabled ECG models outperform echocardiography in predicting new-onset cardiovascular diseases associated with severe LAE.

Clinical factor-based risk stratification for precision therapy in locally advanced squamous cell carcinoma of the uterine cervix.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard of care for locally advanced cervical cancer. In this study, we analyzed the pretreatment clinical and 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) characteristics of patients with locally advanced cervical squamous cell carcinoma (SCC) to develop a scoring prototype for risk stratification. METHODS: Two cohorts were constructed in this study. Cohort 1 comprised patients with cervical SCC with 2009 FIGO stage III-IVA or stage I-II with positive pelvic or para-aortic lymph node (PALN) on PET/CT from AGOG09-001 trial. Cohort 2 comprised patients with similar characteristics who had received adequate therapy in our hospital between 2016 and 2021. Pretreatment patient characteristics and PET/CT parameters including maximum standardized uptake value (SUVmax ) and metabolic tumor volume (MTV) of primary tumor and nodal SUVmax were assessed for cancer-specific survival (CSS) using multivariate Cox regression. RESULTS: Analysis of combined data from cohorts 1 (n = 55) and 2 (n = 128) indicated age ≥ 66 years, primary tumor MTV ≥87 mL, and positive PALN on PET/CT to be independently significant adverse predictors for CSS (p < 0.001, p = 0.014, and p = 0.026, respectively) with a median follow-up duration of 51 months. Assigning a score of 1 to each adverse predictor, patients with cumulative risk scores of 0, 1, 2, and 3 were discovered to have a 5-year CSS of 86.9%, 71.0%, 32.2%, and 0%, respectively (p < 0.001). CONCLUSION: Age, primary tumor MTV, and positive PALN on PET/CT may serve as independent predictors of poor survival in patients with locally advanced cervical SCC. Our findings indicate that patients without any adverse factors can receive standard CCRT, whereas those with at least one adverse factor can consider novel combination therapies or clinical trials.

A New Phenotype of TUBB4A Mutation in a Family With Adult-Onset Progressive Spastic Paraplegia and Isolated Hypomyelination Leukodystrophy: A Case Report and Literature Review.

Tubulin beta 4A class IVa (TUBB4A) spectrum disorders include autosomal dominant dystonia type 4 or hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). However, in rare cases, only mild hypomyelination in the cortex with no basal ganglia atrophy may be observed. We report a case of a family with TUBB4A mutation and complicated hereditary spasticity paraplegia (HSP). We performed quadro whole-exome sequencing (WES) on the family to identify the causative gene of progressive spastic paraparesis with isolated hypomyelination leukodystrophy. We identified a novel TUBB4A p.F341L mutation, which was present in all three affected patients but absent in the unaffected father. The affected patients presented with adult-onset TUBB4A disorder, predominant spastic paraparesis with/without ataxia, and brain hypomyelination with no cognitive impairment or extrapyramidal symptoms. In the literature, HSP is considered a TUBB4A spectrum disorder.

Machine learning-based prediction of acute mortality in emergency department patients using twelve-lead electrocardiogram.

Background: The risk of mortality is relatively high among patients who visit the emergency department (ED), and stratifying patients at high risk can help improve medical care. This study aimed to create a machine-learning model that utilizes the standard 12-lead ECG to forecast acute mortality risk in ED patients. Methods: The database included patients who visited the EDs and underwent standard 12-lead ECG between October 2007 and December 2017. A convolutional neural network (CNN) ECG model was developed to classify survival and mortality using 12-lead ECG tracings acquired from 345,593 ED patients. For machine learning model development, the patients were randomly divided into training, validation and testing datasets. The performance of the mortality risk prediction in this model was evaluated for various causes of death. Results: Patients who visited the ED and underwent one or more ECG examinations experienced a high incidence of 30-day mortality [18,734 (5.42%)]. The developed CNN model demonstrated high accuracy in predicting acute mortality (hazard ratio 8.50, 95% confidence interval 8.20-8.80) with areas under the receiver operating characteristic (ROC) curve of 0.84 for the 30-day mortality risk prediction models. This CNN model also demonstrated good performance in predicting one-year mortality (hazard ratio 3.34, 95% confidence interval 3.30-3.39). This model exhibited good predictive performance for 30-day mortality not only for cardiovascular diseases but also across various diseases. Conclusions: The machine learning-based ECG model utilizing CNN screens the risks for 30-day mortality. This model can complement traditional early warning scoring indexes as a useful screening tool for mortality prediction.

Early experiences with edoxaban for stroke prevention in atrial fibrillation in the Southeast Asia region.

Edoxaban, a once-daily, direct-acting oral anticoagulant, is approved to prevent stroke or systemic embolism in non-valvular atrial fibrillation (NVAF) and treat venous thromboembolism. The clinical benefit of edoxaban for stroke prevention in Asian patients with NVAF has been demonstrated in clinical and real-world studies. We share early clinical experiences with once-daily edoxaban and discuss its evidence-based use in patients with NVAF in Southeast Asia through several cases of patients at high risk, including frail patients, elderly patients with multiple comorbidities and patients with increased bleeding risk. These cases demonstrate the effectiveness and safety of once-daily edoxaban in patients with NVAF in Southeast Asia.

Clinical outcome analysis of non-small cell lung cancer patients with brain metastasis receiving metastatic brain tumor resection surgery: a multicenter observational study.

Brain metastasis is most common in primary non-small cell lung cancer (NSCLC), and some patients require neurosurgical resection for intracranial disease control. Because advances in systemic therapies for metastatic NSCLC have been developed in the past decade, we aimed to analyze and determine clinical factors associated with the postresection survival of NSCLC patients with brain metastasis who underwent neurosurgery followed by systemic therapy. Between January 2017 and December 2021, data for 93 NSCLC patients with brain metastasis treated with neurosurgery followed by systemic therapy at Linkou, Kaohsiung and Chiayi Chang Gung Memorial Hospitals were retrospectively retrieved for analysis. For all study patients, median postresection survival was 34.36 months (95% confidence interval (CI), 28.97-39.76), median brain metastasis (BM)-free survival was 26.90 months (95% CI, 22.71-31.09), and overall survival (OS) was 41.13 months (95% CI, 34.47-47.52). In multivariate analysis, poor performance status (Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2) and concurrent liver metastasis were identified as independent unfavorable factors associated with significantly shortened postresection survival (P<0.001). The histological type adenocarcinoma was associated with significantly longer postresection survival (P = 0.001). The median postresection survival for adenocarcinoma and nonadenocarcinoma patients was 36.23 and 10.30 months, respectively (hazard ratio (HR) = 0.122; 95% CI, 0.035-0.418; P<0.001); that for patients with and without concurrent liver metastasis was 11.43 and 36.23 months, respectively (HR = 22.18; 95% CI, 5.827-84.459; P<0.001). Patients with preserved ECOG PS, adenocarcinoma histology type and no concurrent liver metastasis appeared to have better postresection survival than nonadenocarcinoma patients. Our results provide counseling and decision-making references for neurosurgery feasibility in NSCLC patients with brain metastasis.

Treatment and mortality risk of older adults with non-small cell cancer in Taiwan: A population-based cohort study.

BACKGROUND: Older patients tend to have decreased physical functions and more comorbidities than younger patients. At present, the best management for very elderly patients with lung cancer is not known. In this study, we aimed to investigate treatment and mortality risk of older adults with non-small cell cancer (NSCLC) in Taiwan. METHODS: This study analyzed data from the Taiwan Cancer Registry database. Patients aged ≥80 years with newly diagnosed NSCLC between 2010 and 2017 were included. Treatment options were categorized as curative, palliative, and no treatment. Patients were followed up until death or December 31, 2020. Univariable and multivariable Cox proportional hazards models were used to estimate mortality risk, and Kaplan-Meier survival curves were drawn. RESULTS: A total of 11 941 patients, aged ≥80 years, with newly diagnosed NSCLC between 2010 and 2017 were identified from the Taiwan Cancer Registry and followed up until 2020. The mean age was 84.4 ± 3.7 years old, and 7468 (62.54%) were men. The Kaplan-Meier survival curves showed significant differences across the three treatment options (log-rank p < 0.001). Results from multivariate Cox regression demonstrated that patients on palliative treatment (adjusted HR: 0.52, 95% CI: 0.48-0.56, p < 0.001) and curative treatment (adjusted HR: 0.45, 95% CI: 0.42-0.48, p < 0.001) had a significantly lower mortality risk than those with no treatment. The subgroup analyses stratified by cancer stages also showed consistent findings. CONCLUSION: Elderly patients with NSCLC had significantly decreased mortality risk when receiving curative or palliative treatment compared with those without treatment. In the future, further studies are warranted to investigate complications and quality of life of elderly patients with NSCLC during palliative or curative treatment.

First principal observation documenting the three-dimensional uptake of cadmium and spatial distribution of cadmium hydroxyapatite mineral in bone char.

The 3-D matrix scale ion-exchange mechanism was explored for high-capacity cadmium (Cd) removal using bone chars (BC) chunks (1-2 mm) made at 500 °C (500BC) and 700 °C (700BC) in aqueous solutions. The Cd incorporation into the carbonated hydroxyapatite (CHAp) mineral of BC was examined using a set of synchrotron-based techniques. The Cd removal from solution and incorporation into mineral lattice were higher in 500BC than 700BC, and the diffusion depth was modulated by the initial Cd concentration and charring temperature. A higher carbonate level of BC, more pre-leached Ca sites, and external phosphorus input enhanced Cd removal. The 500BC showed a higher CO32-/PO43- ratio and specific surface area (SSA) than the 700BC, providing more vacant sites by dissolution of Ca2+. In situ observations revealed the refilling of sub-micron pore space in the mineral matrix because of Cd incorporation.The X-ray nanodiffraction (XND) analyses revealed that Cd was mainly removed from water by incorporation into the mineral lattice of 500BC via ion exchange, rather than surface sorption and precipitation, and the mineral phase was transformed from hydroxyapatite (HAp) to cadmium hydroxyapatite (Cd-HAp). The Rietveld's refinement of X-ray diffraction (XRD) data resolved up to 91% of the crystal displacement of Ca2+ by Cd2+. The specific phase and stoichiometry of the new Cd-HAp mineral was dependent on the level of ion exchange. This mechanistic study confirmed that 3-D ion exchange was the most important path for heavy metal removal from aqueous solution and immobilization in BC mineral matrix, and put forward a novel and sustainable remediation strategy for Cd removal in wastewater and soil clean-up.

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.

Cancer survivorship and risk of pregnancy complications, adverse obstetric outcomes, and maternal morbidities in female adolescents and young adults: a nationwide population-based study from Taiwan.

BACKGROUND: Cancer treatment in female adolescent and young adult (AYA) cancer survivors (i.e., those diagnosed between 15 and 39 years of age) may adversely affect multiple bodily functions, including the reproductive system. METHODS: We initially assembled a retrospective, nationwide population-based cohort study by linking data from two nationwide Taiwanese data sets. We subsequently identified first pregnancies and singleton births to AYA cancer survivors (2004-2018) and select AYA without a previous cancer diagnosis matched to AYA cancer survivors for maternal age and infant birth year. RESULTS: The study cohort consisted of 5151 and 51,503 births to AYA cancer survivors and matched AYA without a previous cancer diagnosis, respectively. The odds for overall pregnancy complications (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.01-1.18) and overall adverse obstetric outcomes (OR, 1.07; 95% CI, 1.01-1.13) were significantly increased in survivors compared with matched AYA without a previous cancer diagnosis. Specifically, cancer survivorship was associated with an increased risk of preterm labour, labour induction, and threatened abortion or threatened labour requiring hospitalisation. CONCLUSIONS: AYA cancer survivors are at increased risk for pregnancy complications and adverse obstetric outcomes. Efforts to integrate individualised care into clinical guidelines for preconception and prenatal care should be thoroughly explored.

Injectable Hydrogel Guides Neurons Growth with Specific Directionality.

Visual disabilities affect more than 250 million people, with 43 million suffering from irreversible blindness. The eyes are an extension of the central nervous system which cannot regenerate. Neural tissue engineering is a potential method to cure the disease. Injectability is a desirable property for tissue engineering scaffolds which can eliminate some surgical procedures and reduce possible complications and health risks. We report the development of the anisotropic structured hydrogel scaffold created by a co-injection of cellulose nanofiber (CNF) solution and co-polypeptide solution. The positively charged poly (L-lysine)-r-poly(L-glutamic acid) with 20 mol% of glutamic acid (PLLGA) is crosslinked with negatively charged CNF while promoting cellular activity from the acid nerve stimulate. We found that CNF easily aligns under shear forces from injection and is able to form hydrogel with an ordered structure. Hydrogel is mechanically strong and able to support, guide, and stimulate neurite growth. The anisotropy of our hydrogel was quantitatively determined in situ by 2D optical microscopy and 3D X-ray tomography. The effects of PLLGA:CNF blend ratios on cell viability, neurite growth, and neuronal signaling are systematically investigated in this study. We determined the optimal blend composition for stimulating directional neurite growth yielded a 16% increase in length compared with control, reaching anisotropy of 30.30% at 10°/57.58% at 30°. Using measurements of calcium signaling in vitro, we found a 2.45-fold increase vs. control. Based on our results, we conclude this novel material and unique injection method has a high potential for application in neural tissue engineering.

Comparative microstructural study on the teeth of Mesozoic birds and non-avian dinosaurs.

Although it is commonly considered that, in birds, there is a trend towards reduced dentition, teeth persisted in birds for 90 Ma and numerous macroscopic morphologies are observed. However, the extent to which the microstructure of bird teeth differs from other lineages is poorly understood. To explore the microstructural differences of the teeth of birds in comparison with closely related non-avialan dinosaurs, the enamel and dentine-related features were evaluated in four Mesozoic paravian species from the Yanliao and Jehol biotas. Different patterns of dentinal tubular tissues with mineralized extensions of the odontoblast processes were revealed through the examination of histological sectioning under electron microscopy. Secondary modification of the tubular structures, forming reactive sclerotic dentin of Longipteryx, and the mineralization of peritubular dentin of Sapeornis were observed in the mantle dentin region. The new observed features combined with other dentinal-associated ultrastructure suggest that the developmental mechanisms controlling dentin formation are quite plastic, permitting the evolution of unique morphologies associated with specialized feeding behaviours in the toothed birds. Proportionally greater functional stress placed on the stem bird teeth may have induced reactive dentin mineralization, which was observed more often within tubules of these taxa. This suggests modifications to the dentin to counteract potential failure.

2023 Consensus of Taiwan Society of Cardiology on the Pharmacological Treatment of Chronic Heart Failure.

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.

Novel Compound Heterozygous Mutations in the SYNE1 Gene in a Taiwanese Family: A Case Report and Literature Review.

Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene are associated with substantial clinical heterogeneity. Here, we report the first case of SYNE1 ataxia in Taiwan due to two novel truncating mutations. Our patient, a 53-year-old female, exhibited pure cerebellar ataxia with c.1922del in exon 18 and c. C3883T mutations in exon 31. Previous studies have indicated that the prevalence of SYNE1 ataxia among East Asian populations is low. In this study, we identified 27 cases of SYNE1 ataxia from 22 families in East Asia. Of the 28 patients recruited in this study (including our patient), 10 exhibited pure cerebellar ataxia, and 18 exhibited ataxia plus syndromes. We could not find an exact correlation between genotypes and phenotypes. Additionally, we established a precise molecular diagnosis in our patient's family and extended the findings on the ethnic, phenotypic, and genotypic diversity of the SYNE1 mutational spectrum.

Association of smoking and ALK tyrosine-kinase inhibitors on overall survival in treatment-naïve ALK-positive advanced lung adenocarcinoma.

Introduction: Anaplastic lymphoma kinase (ALK) fusion mutation is more common in younger and never-smoking lung cancer patients. The association of smoking and ALK-tyrosine kinase inhibitors (TKIs) on overall survival (OS) of treatment-naïve ALK-positive advanced lung adenocarcinoma remains unclear in real-world. Methods: This retrospective study evaluated all 33170 lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2019, of whom 9575 advanced stage patients had ALK mutation data. Results: Among the 9575 patients, 650 (6.8%) patients had ALK mutation with the median follow-up survival time 30.97 months (median age, 62 years; 125 [19.2%] were aged ≥75 years; 357 (54.9%) females; 179 (27.5) smokers, 461 (70.9%) never-smokers, 10 (1.5%) with unknown smoking status; and 544 (83.7%) with first-line ALK-TKI treatment). Overall, of 535 patients with known smoking status who received first-line ALK-TKI treatment, never-smokers and smokers had a median OS of 40.7 months (95% confidence interval (CI), 33.1-47.2 months) and 23.5 months (95% CI, 11.5-35.5 months) (P=0.015), respectively. Among never-smokers, those who received first-line ALK-TKI treatment had a median OS of 40.7 months (95% CI, 22.7-57.8 months), while those ALK-TKI not as first-line treatment had a median OS of 31.7 months (95% CI, 15.2-42.8 months) (P=0.23). In smokers, the median OS for these patients was 23.5 months (95% CI, 11.5-35.5 months) and 15.6 months (95% CI, 10.2-21.1 months) (P=0.026), respectively. Conclusions and relevance: For patients with treatment-naïve advanced lung adenocarcinoma, the ALK test should be performed irrespective of smoking status and age. Smokers had shorter median OS than never-smokers among treatment-naïve-ALK-positive patients with first-line ALK-TKI treatment. Furthermore, smokers not receiving first-line ALK-TKI treatment had inferior OS. Further investigations for the first-line treatment of ALK-positive smoking advanced lung adenocarcinoma patients are needed.