A causal relationship between bone mineral density and breast cancer risk: a mendelian randomization study based on east Asian population.

BACKGROUND: Breast cancer (BC) poses significant burdens on women globally. While past research suggests a potential link between bone mineral density (BMD) and BC risk, findings remain inconsistent. Our study aims to elucidate the causal relationship between BMD and BC in East Asians using bidirectional Mendelian randomization (MR). METHODS: Genetic association data for bone mineral density T-scores (BMD-T) and Z-scores (BMD-Z) (Sample size = 92,615) and BC from two different sources (Sample size1 = 98,283; Sample size2 = 79,550) were collected from publicly available genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with BMD-T and BMD-Z as phenotype-related instrumental variables (IVs) were used, with BC as the outcome. As the primary means of causal inference, the inverse variance weighted (IVW) approach was employed. Heterogeneity analysis was conducted using Cochran's Q test, while MR-Egger regression analysis was implemented to assess the pleiotropic effects of the IVs. Sensitivity analyses were performed using methods such as MR-Egger, weighted median, and weighted mode to analyze the robustness and reliability of the results. The MR-PRESSO method and the RadialMR were used to detect and remove outliers. The PhenoScanner V2 website was utilized to exclude confounding factors shared between BMD and BC. Besides, the Bonferroni correction was also used to adjust the significance threshold. Then, the meta-analysis method was applied to combine the MR analysis results from the two BC sources. Finally, a reverse MR analysis was conducted. RESULTS: The results of the IVW method were consolidated through meta-analysis, revealing a positive correlation between genetically predicted BMD-T ([Formula: see text], [Formula: see text], [Formula: see text]) and BMD-Z ([Formula: see text],[Formula: see text], [Formula: see text]) with increased BC risk. The Cochran's [Formula: see text] test and MR-Egger regression suggested that neither of these causal relationships was affected by heterogeneity or horizontal pleiotropy. The sensitivity analyses supported the IVW results, indicating the robustness of the findings. Reverse MR analysis showed no causal relationship between BC and BMD. CONCLUSION: Our MR study results provide evidence for the causal relationship between BMD and BC risk in East Asian populations, suggesting that BMD screening is of great significance in detecting and preventing BC.

Whole exome sequencing identifies genetic markers of enterovirus susceptibility in East Asians.

Introduction: Following acute enterovirus (EV) infection, outcomes vary based on factors like the immune response, viral cell entry receptor expression levels, tissue tropism, and genetic factors of both the host and virus. While most individuals exhibit mild, self-limited symptoms, others may suffer severe complications or prolonged infections that can lead to autoimmune disorders. Methods: To elucidate host responses to EV infection, we performed whole exome sequencing on blood samples from both infected and uninfected individuals. Our initial focus was on genes encoding EV entry receptors-PSGL-1, SCARB2, and ANAXA2 for EV-A71, and CD155 for poliovirus-and on host genes ACBD3 and PI4KΒ, crucial for EV replication. Results: Although no specific genetic variants directly associated with EV infection were identified, we discovered 118 variants across 116 genes enriched in East Asian populations through multi-layered variant filtering. These variants were further analyzed for their potential impacts on organs, biological processes, and molecular pathways. Phenome-wide association studies were conducted to refine our understanding of their contributions to EV infection susceptibility. Discussion: Our findings aim to develop a predictive panel based on these 118 variants, which could help susceptible individuals during EV outbreaks, guiding targeted clinical interventions and preventative strategies.

Mendelian randomization study of childhood asthma and chronic obstructive pulmonary disease in European and East Asian population.

Objective: The present study aimed to explore the potential causal relationship between childhood asthma and chronic obstructive pulmonary disease (COPD) in European and East Asian populations with Mendelian randomization (MR) analysis. Methods: Based on summary data from genome-wide association studies, single nucleotide polymorphisms (SNPs) associated with childhood asthma were used as instrumental variables. The MR analysis employed the inverse variance weighting, MR-Egger regression and weighted median method to estimate the causal effect between childhood asthma and COPD in European and East Asian populations. Cochran's Q test, MR-PRESSO method and MR-Egger intercept were used to detect heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis applied to assess the effect of removing individual SNP on the estimate of causal association. Results: The MR analysis showed no genetic causal relationship between childhood asthma and COPD. The results of Cochran's Q test, MR-PRESSO and MR-Egger regression indicated the absence of heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis showed no significant difference in the statistical results after exclusion of single SNPs. Conclusions: The MR analysis revealed that there is no causal relationship between childhood asthma and COPD at the genetic level in both European and East Asian populations. Additionally, due to the presence of shared confounding factors and pathogenic genes, further research is needed to comprehensively assess the relationship between childhood asthma and COPD.

A causal association between esophageal cancer and the oral microbiome: a Mendelian randomization study based on an Asian population.

Background: Previous studies have suggested a crosstalk between the oral microbiome and esophageal cancer (EC), but the exact relationship is unclear. This study aimed to investigate the causal relationship between changes in the oral microbiome and EC by Mendelian randomization (MR). Materials and methods: In the study, bidirectional MR analyses were conducted using genome-wide association study data from the oral microbiomes from the 4D-SZ cohort and EC data from the BioBank Japan cohort. Multiple sensitivity tests, including Cochrane's Q statistic, MR-Egger intercept, and MR-PRESSO, were used to assess and validate the relative stability of the resulting data at various levels. Results: Among the 3,117 samples studied, 73 oral microbiomes were found to be statistically causally associated with EC, 38 of which were considered protective factors. According to species analyses, positive results were concentrated in three phyla: Firmicutes (29 species), Patescibacteria (18 species), and Actinobacteria (9 species). It was also determined that Parvimonas micra, Aggregatibacter, and Clostridia had a negative causal relationship, implying that EC caused a decrease in the counts. Following p-value correction, periodonticum_C, unclassified_mgs_3234, and unclassified_mgs_45 were identified as having a strong evidence-grade causal relationship with EC. There was no strong evidence in the results of the inverse MR analyses of EC to the oral microbiome. The sensitivity analysis confirmed the robustness of the findings. Conclusion: This study discovered a bidirectional causal relationship between the oral microbiome and EC, which may provide new insights into the future use of the microbiome for early screening and probiotic therapy.

Obstructive Sleep Apnea and Medical Comorbidities in the Asian Population: Evidence From a Nationwide Healthcare System Data in South Korea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a breathing disorder characterized by recurrent airway obstruction during sleep. Previous western studies have investigated the link between medical disorders and the pathophysiology of OSA. The prevalence and comorbidity rates of OSA; however, vary across different countries and racial groups. This study aimed to delve into medical comorbidities in patients with OSA using a large nationwide healthcare database in Korea. METHODS: This nationwide study used the Korean National Health Insurance claims database (2010-2019). The effect of OSA on the incidence of medical disorders was estimated using the Cox proportional hazard ratio (HR) model. The results were reported as crude and adjusted HRs with 95% confidence intervals (CI). Subgroup analysis was conducted by sex and age. RESULTS: In total, 103,785 patients with OSA and 207,570 patients without OSA were included. OSA group had significantly higher HRs for ischemic heart disease and stroke even after adjusting for hypertension, dyslipidemia, and diabetes. The OSA group also showed an increased risk of metabolic syndrome-related diseases, chronic kidney disease, and gastroesophageal reflux disease. Female patients with OSA exhibited notably higher rates of comorbid liver cirrhosis, chronic obstructive pulmonary disease, and asthma. The cardiovascular burden of patients increased in accordance with the patients' age. CONCLUSION: Korean patients with OSA have a significantly increased risk of cardio-cerebrovascular diseases, which aligns with the previous studies conducted in the western countries. This result holds particular significance as it represents the first nationwide, population-based study conducted in Asia.

Upper blepharoplasty in Asian population: A novel technique based on functional zoning and dynamic reconstruction with anatomical structure.

BACKGROUND: Double eyelid blepharoplasty is the most popular cosmetic operation in Asian population. Various surgical techniques have been developed in order to create dynamic eyelid folds with natural-looking in recent years, but postoperative complications like so-called sausage-like appearance have not been resolved completely. AIMS: To create natural-looking dynamic folds, we propose a new method imitating the original anatomical structure of congenital double-eyelid. PATIENTS AND METHODS: Eighty-six patients who underwent the double-eyelid surgery from June 1st, 2018 to October 31st, 2020 were included in this retrospective study, including 10 males and 76 females, aged 18-39 years (mean 27.4 ± 5.6 years). All the included patients received double eyelid surgery performed by the same senior doctor, using the pretarsal orbicularis oculi muscle-releasing technique. Patient Reported Outcome Measures questionnaires were administrated to assess the severity of scarring, pain, and asymmetry, as well as functional and appearance issues. Surgical outcome was assessed through objective and subjective evaluation forms (PROM and patient satisfaction rate). RESULTS: Among the 86 patients, 5 were lost during the follow-up period. The absolute number of enrolled patients is 81. 91.36% of the enrolled patients reported minimal or non-visible scarring at the double eyelid incision. As to functional and appearance issues, the main problem were asymmetry (12.35%) and the narrowing of the supratarsal crease width (8.64%). No supratarsal depression and "sausage-like" appearance occurred in this study. 95.1% of patients reported either good or excellent outcome (mean score: 108 of 120) based on analysis of PROM results, and 96.3% of patients reported either high or very high satisfaction (mean score: 96 of 120) for the patient satisfaction assessment. CONCLUSIONS: This new surgical method of double-eyelid blepharoplasty provides comparatively safe and effective results.

Etiologic factors for Barrett's esophagus: toward countermeasures in Asia.

INTRODUCTION: Over the past several decades, Europe and the United States have experienced a rapid increase in esophageal adenocarcinoma. Research and countermeasures against Barrett's esophagus, its precancerous lesion, are progressing. Because esophageal adenocarcinoma has an extremely poor prognosis when diagnosed in an advanced stage, recommendations for early cancer detection have been made based on the various proven etiological factors of Barrett's esophagus and the actual cancer risk of Barrett's esophagus. In recent years, there have been indications of an increase in esophageal adenocarcinoma in Japan, and a similar trend of cancer will occur shortly in other Asian countries. Consequently, Asian countries must implement similar countermeasures against Barrett's esophagus and esophageal adenocarcinoma, referencing the knowledge gained thus far in Europe and the United States. AREAS COVERED: This review summarizes the latest findings on the etiologic factors of Barrett's esophagus and discusses the differences between Westerners and Asians. The current status of Barrett's esophagus in Japan and other Asian countries is also summarized. EXPERT OPINION: The etiological factors and cancer incidence of Barrett's esophagus in Asia diverge somewhat from those observed in Europe and America. Therefore, it is imperative to implement measures that are tailored to the actual circumstances of Asian people.

New look at the power of zero coronary artery calcium (CAC) in Asian population: a systemic review and meta-analysis.

Background: Numerous studies have validated a 5-year warranty period for heart health in Western populations with a coronary artery calcium (CAC) score of zero. While the calcium score is a crucial cardiovascular risk indicator, its interpretation in Asian populations remains unclear. This meta-analysis aimed to clarify the uncertainty surrounding the prevalence, warranty period, and prognostic implications of zero CAC scores in Asian populations. It also examined the impact of sex on subclinical CAC progression. While the calcium score is a crucial cardiovascular risk indicator, its interpretation in Asian populations remains unclear. The study aimed to shed light on these issues by exploring the specificities of subclinical CAC progression in the Asian context. Methods: Our systematic literature search, from the study's inception to October 2023, targeted studies on subclinical CAC progression in the Asian population with a zero CAC score. We searched the Cochrane Library, and PubMed. The search terms included "zero score", "coronary calcification", "zero CAC score", and "CAC scan". Results: We evaluated seven published studies through a meta-analysis and assessed the risk of bias using the Newcastle-Ottawa Scale (NOS). In this meta-analysis of three observational studies addressing zero CAC prevalence (n=7,661), the pooled prevalence of zero CAC scores in the Asian population was 18.2% [95% confidence interval (CI): 12.5-25.9%]. A significant difference in follow-up warranty period was observed between the CAC zero group and subclinical CAC progression group (mean difference, 1.26 years; 95% CI: 0.94-1.58; P<0.001). Furthermore, the conversion rate of subclinical CAC progression differed significantly between males and females (risk ratio, 2.37; 95% CI: 1.98-2.84; P<0.001). Analysis of four studies revealed a notable discrepancy in the major adverse cardiovascular event (MACE) rate between the CAC (-) and CAC (+) groups (risk ratio, 4.78; 95% CI: 2.21-10.36; P<0.001). Conclusions: The meta-analysis of zero CAC scores in Asian populations suggested an 18.2% prevalence. A 5-year warranty period was noted, with heightened subclinical CAC progression likelihood after this duration. Additionally, sex-based differences were observed in subclinical CAC progression rates. These findings will provide clinical cardiovascular risk stratification for guiding gender-specific clinical decision-making in asymptomatic in Asian individuals.

Investigation of the causal relationship between breast cancer and thyroid cancer: a set of two-sample bidirectional Mendelian randomization study.

PURPOSE: A potential association between breast (BC) and thyroid cancer (TC) has been observed. We investigated if the relationship between BC and TC is causal using bidirectional Mendelian randomization (MR) in Asian and European populations. METHODS: BC-linked single nucleotide polymorphisms (SNPs) were acquired from a genome-wide association study (GWAS) conducted by the Breast Cancer Association Consortium and Biobank Japan. The most recent TC GWAS data were obtained from the FinnGen Project and National Biobank of Korea. We assessed the potential causal relationship between BC and TC using various MR methods, including inverse-variance-weighting (IVW). Sensitivity, heterogeneity, and pleiotropic tests were performed to assess reliability. RESULTS: We found a bidirectional causal association between BC and TC within Europeans (IVW, TC on BC: odds ratio [OR] 1.090, 95% confidence interval [CI]: 1.012-1.173, P = 0.023; BC on TC: OR 1.265, 95% CI: 1.158-1.381, P < 0.001). A one-way causal relationship between BC susceptibility and TC risk was found in Asians (IVW BC on TC: OR 2.274, 95% CI: 2.089-2.475, P < 0.001). Subsequently, we identified a noteworthy bidirectional causal relationship between estrogen receptor (ER)-positive BC and TC (IVW, TC on ER-positive BC: OR 1.104, 95% CI: 1.001-1.212, P = 0.038; ER-positive BC on TC: OR 1.223, 95%CI: 1.072-1.395, P = 0.003), but not ER-negative BC and TC in Europeans. CONCLUSION: We revealed a reciprocal causal association between ER-positive BC and TC. These findings establish a theoretical framework for the simultaneous surveillance and treatment of BC and TC.

T2DM may exert a protective effect against digestive system tumors in East Asian populations: a Mendelian randomization analysis.

Introduction: Type 2 diabetes mellitus (T2DM) was associated with digestive system tumors. We analyzed publicly available data from GWAS studies using Mendelian randomization methods to clarify its causal relationship and mechanisms. Five common digestive system tumors and four diabetes-related phenotypes were included. Methods: Inverse variance weighted method was the main analytical method. Meta-analysis was used to summarize results of multiple data sources. Horizontal pleiotropy was tested using Egger-intercept method and validated by MRPRESSO method. Heterogeneity and sensitivity analysis were conducted by Cochran's Q test and leave-one-out method, respectively. Results: T2DM is associated with a reduced risk of esophageal (OR: 0.77, 95% CI: 0.71 to 0.83, P< 0.001), gastric (OR: 0.87, 95% CI: 0.84 to 0.90, P< 0.001) and colorectal cancer (OR: 0.88, 95% CI: 0.85 to 0.91, P< 0.001) and hepatocellular carcinoma (OR: 0.92, 95% CI: 0.86 to 0.97, P = 0.005) and an increased risk of pancreatic cancer (OR: 1.92, 95% CI: 1.47 to 2.50, P< 0.001) in East Asian population. T2DM causes decreased fasting insulin levels (OR = 0.966, 95% CI: 0.95 to 0.98, P< 0.001) and increased glycated hemoglobin levels (OR=1.41, 95% CI: 1.39 to 1.44, P<0.001). Elevated fasting insulin levels increase the risk of esophageal cancer (OR = 10.35, 95% CI: 1.10 to 97.25, P = 0.041), while increased glycated hemoglobin levels increase pancreatic cancer risk (OR=2.33, 95% CI: 1.37 to 3.97, P=0.002) but decrease gastric cancer risk (OR=0.801, 95% CI: 0.65 to 0.99, P=0.044). Conclusion: T2DM is associated with a reduced risk of esophageal, gastric and colorectal cancer and hepatocellular carcinoma in East Asian populations. The causal relationships between T2DM with esophageal and gastric cancer are partially mediated by decreased fasting insulin and increased glycated hemoglobin levels, respectively. T2DM indirectly increases the risk of pancreatic cancer by increasing glycated hemoglobin levels.

Fructosamine and HbA1c: A Correlational Study in a Southeast Asian Population.

Objectives: Fructosamine correlates well with glycated haemoglobin (HbA1c) in Caucasians. This study investigates this correlation and whether fructosamine can reliably estimate glycated haemoglobin in Southeast Asians. Methods: We recruited 193 participants based on 4 HbA1c bands (<6.0%; 6.0 - 7.9%; 8.0- 9.9%; ≥10%) from a secondary hospital in Singapore between August 2017 and December 2021. Blood samples for fructosamine, glycated haemoglobin, albumin, haemoglobin, thyroid stimulating hormone and creatinine were drawn in a single setting for all participants. Scatter plot was used to explore correlation between fructosamine and glycated haemoglobin. Strength of linear correlation was reported using Pearson's correlation coefficient. Simple linear regression was used to examine the relationship between fructosamine and glycated haemoglobin. Results: We performed simple linear regression to study the relationship between fructosamine and HbA1c in the research participants (R2 = 0.756, p<0.01). Further analysis with natural logarithmic transformation of fructosamine demonstrated a stronger correlation between HbA1c and fructosamine (R2 = 0.792, p<0.01). Conclusions: Fructosamine is reliably correlated with HbA1c for the monitoring of glycaemic control in Southeast Asians.

Longitudinal analysis of epigenome-wide DNA methylation reveals novel loci associated with BMI change in East Asians.

BACKGROUND: Obesity is a global public health concern linked to chronic diseases such as cardiovascular disease and type 2 diabetes (T2D). Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may contribute to obesity. However, the molecular mechanism underlying the longitudinal change of BMI has not been well-explored, especially in East Asian populations. METHODS: This study performed a longitudinal epigenome-wide association analysis of DNA methylation to uncover novel loci associated with BMI change in 533 individuals across two Chinese cohorts with repeated DNA methylation and BMI measurements over four years. RESULTS: We identified three novel CpG sites (cg14671384, cg25540824, and cg10848724) significantly associated with BMI change. Two of the identified CpG sites were located in regions previously associated with body shape and basal metabolic rate. Annotation of the top 20 BMI change-associated CpGs revealed strong connections to obesity and T2D. Notably, these CpGs exhibited active regulatory roles and located in genes with high expression in the liver and digestive tract, suggesting a potential regulatory pathway from genome to phenotypes of energy metabolism and absorption via DNA methylation. Cross-sectional and longitudinal EWAS comparisons indicated different mechanisms between CpGs related to BMI and BMI change. CONCLUSION: This study enhances our understanding of the epigenetic dynamics underlying BMI change and emphasizes the value of longitudinal analyses in deciphering the complex interplay between epigenetics and obesity.

The Association between Bone Mineral Density and Risk of Mortality: A Prospective Cohort Study of 233,397 Taiwanese.

PURPOSE: Osteoporosis is an important public health challenge given its high prevalence in western populations and the prevalence has shown an upward trend in recent decades in Asia. However, epidemiological evidence on the association between bone mineral density (BMD) and mortality risk in the Asian population is sparse. METHODS: The Cox proportional hazards model and cause-specific hazard models were used to investigate the association of BMD with the risk of all-cause mortality and cause-specific mortality. RESULTS: The present study comprised of 3,332,207 person-years with a median follow-up of 14.6 years. 27,508 participants (15,967 men and 11,541 women) died among 233,397 participants (112,348 men and 121,049 women) during the follow-up period. Compared to those with normal BMD level, both men and women with low BMD had a significantly higher risk of all-cause, cardiovascular disease (CVD), and cancer mortality after adjusting for the covariates. [For men with osteoporosis: all-cause: 1.37 (1.27-1.49); CVD: 1.28 (1.08-1.52); cancer: 1.29 (1.12-1.49); For women with osteoporosis: all-cause: 1.72 (1.63-1.82); CVD: 1.85 (1.64-2.08); cancer: 1.47 (1.35-1.61)]. The P for interactions for BMD with sex were significant for all-cause and CVD mortality. The adverse effects of BMD on the risk of all-cause and CVD were higher in women than in men [men vs. women: all-cause: 1.37 (1.27-1.49) vs. 1.72 (1.63-1.82); CVD: 1.28 (1.08-1.52) vs. 1.85 (1.64-2.08)]. In the nonlinear dose-response analyses, the association between BMD increments and all-cause mortality risk shows an L-shaped pattern in men and a similar U-shaped trend in women (P for non-linear association: <0.001). Likewise, a similar L-shaped association was observed between BMD levels and cancer mortality risk in men. CONCLUSIONS: Low BMD had an increased risk of all-cause, CVD, and cancer mortality in both men and women. Women had a stronger positive association between low BMD and an increased risk of all-cause and CVD mortality compared to men.

SCORE and SCORE2 in East Asian Population: A Performance Comparison.

Background: Systematic COronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons (OP) models have been proposed as new cardiovascular risk evaluation tools. Objectives: This study evaluated the performance of SCORE/SCORE-OP and SCORE2/SCORE2-OP in the East Asian population by using population-based cohort data from the National Health Insurance Service (NHIS) Health Screening Cohort of Korea. Methods: A total of 324,384 NHIS examinees from 2004 to 2005 were divided into 5 age groups: 40-49 years, 50-59 years, 60-69 years,70-79 years, and more than 80 years. The examinees had their predicted cardiovascular disease risks calculated by using SCORE, SCORE2, SCORE-OP, and SCORE2-OP models. The low-risk model was applied on the basis of the cohort's observed event rates. The observed and predicted cardiovascular risks were compared. Results: A total of 324,384 subjects were included (mean age 51.4 ± 7.3 years; women, 37.9% for the SCORE/SCORE2 group and mean age 73.0 ± 2.8 years; women, 47.5% for the SCORE/SCORE2-OP group). Over a median follow-up of 9 years, cardiovascular events occurred in 15.0% and 28.9% in SCORE/SCORE2 and SCORE/SCORE2-OP groups, respectively. The SCORE/SCORE-OP model underestimated cardiovascular disease risk in young men (aged 40-49 years) and women (aged 40-59 years) and overestimated it in older age groups. In contrast, SCORE2/SCORE2-OP invariably overestimated the risk in all age groups and sexes. SCORE2/SCORE2-OP showed no improvement in Harrell's concordance index (C-index) compared with SCORE/SCORE-OP. Calibration plots favored SCORE2 over SCORE but not SCORE2-OP over SCORE-OP. Conclusions: Both SCORE2/SCORE2-OP and SCORE/SCORE-OP overestimated cardiovascular disease risk with low performance. SCORE2/SCORE2-OP showed slight improvement over older versions, but modifications are necessary for the East Asian population.

Genetic diversity among the present Japanese population: evidence from genotyping of human cell lines established in Japan.

Japan is often assumed to have a highly homogeneous ethnic population, because it is an island country. This is evident in human cell lines collected from cell banks; however, these genotypes have not been thoroughly characterized. To examine the population genotypes of human cell lines established in Japan, we conducted SNP genotyping on 57 noncancerous cell lines and 43 lung cancer cell lines. Analysis of biogeographic ancestry revealed that 58 cell lines had non-admixed Japanese genotypes, 21 cell lines had an admixture of Japanese and East Asian genotypes, and the remaining 21 cell lines had East Asian genotypes. The proportion of non-admixed Japanese genotypes was similar between lung cancer and noncancerous cell lines, suggesting that patients in Japan may not exclusively have Japanese genotypes. This could influence the incidence of inherited diseases and should be taken into account in personalized medicine tailored to genetic background. The genetic makeup of the present-day Japanese population cannot be fully explained by the ancestral Jomon and Yayoi lineages. Instead, it is necessary to consider a certain level of genetic admixture between Japanese and neighboring Asian populations. Our study revealed genetic variation among human cell lines derived from Japanese individuals, reflecting the diversity present within the Japanese population.

Postural orthostatic tachycardia syndrome and other autonomic dysfunctions following COVID-19: Incidence, characteristics, and associated factors.

Background: Long-COVID syndrome has become a new health concern. Many major clinical centers have experienced more patients with symptoms suggestive of autonomic dysfunction, especially postural orthostatic tachycardia syndrome (POTS) following COVID-19. However, there is a lack of information regarding the incidence and associated factors in Asian population. Methods: A retro-prospective study was conducted to evaluate patients with symptoms suggestive of POTS or other autonomic dysfunctions. These symptoms last at least 3 months after PCR-proven COVID-19. Exclusion criteria were age under 18 years old, pregnancy, and pre-COVID-19 autonomic dysfunction symptoms. Patients with a symptom severity score greater than two were assessed with blood tests, 24-h Holter, 24-h ambulatory blood pressure, echocardiogram, and head-up tilt table (HUTT). Results: Seven hundred ninety-three patients were interviewed at 146 ± 37 days after COVID-19. The majority of patients were middle-aged females (53%). Of those, 15 patients had the symptom severity score greater than 2. Out of those 15 patients, 12 had positive HUTT (1 demonstrating POTS, 10 neurocardiogenic syncope, and 1 orthostatic hypotension). Among those with positive HUTT patients, C-reactive protein (CRP) was significantly higher (OR 1.01; p-value 0.041). Fatigue and dyspnea on exertion were the two most complaint symptoms. Conclusions: This study shows the incidence of autonomic dysfunction and POTS is 1.5% (12/793) and 0.1% POTS (1/793), respectively, in a primary care setting (among general post-COVID-19 patients). The most common symptoms for these patients were fatigue and dyspnea.

Low-dose prasugrel versus standard-dose ticagrelor in east Asian patients with acute coronary syndrome.

Low-dose prasugrel demonstrated a similar effectiveness profile to clopidogrel in East Asian ACS patients, but its comparison with another new-generation potent P2Y12 inhibitor, ticagrelor, remains unclear. To compare the effectiveness and safety of low-dose prasugrel against those of standard-dose ticagrelor in East Asian patients with ACS. This retrospective cohort study used Taiwan's National Health and Welfare Database. This study included ACS patients who underwent percutaneous coronary intervention and, at discharge between January 1, 2018 and December 31, 2020, were prescribed with low-dose prasugrel plus aspirin or standard-dose ticagrelor plus aspirin. Stabilized inverse probability of treatment weighting was used to balance the covariates across these two groups. The primary effectiveness outcome was a composite of acute myocardial infarction, ischemic stroke, and cardiovascular death; the secondary effectiveness outcome was each of the individual components of the primary outcome, transient ischemic attack, and repeat revascularization. The primary safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding, and the two secondary safety outcomes were intracranial hemorrhage and gastrointestinal bleeding. A total of 24,807 patients were included in this study. Among them, 1,493 were low-dose prasugrel users and 23,314 were standard-dose ticagrelor users. No significant differences were found in primary effectiveness [HR: 0.97 (0.74-1.28)] or primary safety outcomes [HR: 1.22 (0.73-2.01)] between the two study groups. For East Asian patients with ACS, low-dose prasugrel provides comparable effectiveness without increasing bleeding risk compared to standard-dose ticagrelor. Low-dose prasugrel may be an appropriate alternative for East Asian populations.

Apical Hypertrophic Cardiomyopathy Presenting With Syncope in a Hispanic Woman: A Report of a Rare Case.

Yamaguchi syndrome or apical hypertrophic cardiomyopathy is a rare subtype of non-obstructive hypertrophic cardiomyopathy that is defined as the focused hypertrophy of the left ventricular apex. It is typically seen in Asian populations. Herein, we present a rare case of Yamaguchi syndrome seen in a Hispanic female.

Identification of TNF-α as Major Susceptible Risk Locus for Vitiligo: A Systematic Review and Meta-Analysis Study in the Asian Population.

INTRODUCTION: Vitiligo is a common depigmentation disorder characterized by defined white patches on the skin and affecting around 0.5% to 2% of the general population. Genetic association studies have identified several pre-disposing genes and single nucleotide polymorphisms (SNPs) for vitiligo pathogenesis; nonetheless, the reports are often conflicting and rarely conclusive. This comprehensive meta-analysis study was designed to evaluate the effect of the risk variants on vitiligo aetiology and covariate stratified vitiligo risk in the Asian population, considering all the studies published so far. METHODS: We followed a systematic and comprehensive search to identify the relevant vitiligo-related candidate gene association studies in PubMed using specific keywords. After data extraction, we calculated, for the variants involved, the study-level unadjusted odds ratio, standard errors, and 95% confidence intervals by using logistic regression with additive, dominant effect, and recessive models using R software package (R, 3.4.2) "metafor." Subgroup analysis was performed using logistic regression (generalized linear model; "glm") of disease status on subgroup-specific genotype counts. For a better understanding of the likely biological function of vitiligo-associated variant obtained through the meta-analysis, in silico functional analyses, through standard publicly available web tools, were also conducted. RESULTS: Thirty-one vitiligo-associated case-control studies on eleven SNPs were analysed in our study. In the fixed-effect meta-analysis, one variant upstream of TNF-α gene: rs1800629 was found to be associated with vitiligo risk in the additive (p = 4.26E-06), dominant (p = 1.65E-7), and recessive (p = 0.000453) models. After Benjamini-Hochberg false discovery rate (FDR) correction, rs1800629/TNF-α was found to be significant at 5% FDR in the dominant (padj = 1.82E-6) and recessive models (padj = 0.0049). In silico characterization revealed the prioritized variant to be regulatory in nature and thus having potential to contribute towards vitiligo pathogenesis. CONCLUSION: Our study constitutes the first comprehensive meta-analysis of candidate gene-based association studies reported in the whole of the Asian population, followed by an in silico analysis of the vitiligo-associated variant. According to the findings of our study, TNF-α single nucleotide variant rs1800629G>A has a risk association, potentially contributing to vitiligo pathogenesis in the Asian population.