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Patients with Graves' disease who remain hyperthyroid under the treatment of antithyroid drugs (ATD) or cannot tolerate ATD usually receive radioactive iodine (RAI) to control disease activity. This pilot study aimed to identify predictors of prolonged euthyroidism12 months after receiving RAI.Demographic, clinical, and laboratory data from 117 patients receiving RAI were retrospectively collected, including age, gender, body surface area, smoking status, free thyroxine, thyrotropin, thyrotropin binding inhibiting immunoglobulin (TBII), microsomal antibody (MA), thyroglobulin antibody (TA), medication history, and thyroid volume. Only 85 patients without missing values were included in statistical analysis. The calculated RAI dose was the estimated thyroid volume × 0.4. The difference and ratio between the actual and calculated RAI doses were examined. A stepwise logistic regression analysis was conducted to identify important predictors of prolonged euthyroidism12 months. The cut-off values for discretizing continuous covariates were estimated by fitting generalized additive models.Among the 85 patients on RAI, 18 (21.2%) achieved prolonged euthyroidism12 months, 38 (44.7%) remained hyperthyroid with decreased ATD doses, but 29 (34.1%) suffered permanent hypothyroidism and needed long-term levothyroxine. Logistic regression analysis revealed that patients with age66 years, 33age ≤66 years, quitting smoking vs. non-smoking or current smoking, 600MA ≤1729 IU/mL, 47%TBII ≤81%, 7TA ≤162 IU/mL, 0.63ratio between actual and calculated RAI doses ≤1.96, or taking hydroxychloroquine (HCQ) would have a higher chance of reaching prolonged euthyroidism12 months after receiving RAI. Its area under the Receiver Operating Characteristic curve was 0.932.Patients with Graves' disease who received an actual RAI dose close to the calculated RAI dose achieved prolonged euthyroidism12 months if they also took HCQ during RAI treatment.

The incidence of breast cancer among premenopausal women has been increasing rapidly in recent decades in East Asia. This case–control study investigated whether estrogen-DNA adducts were associated with breast cancer risk in Taiwan. The control group (n = 146) comprised healthy female volunteers and women with non-proliferative breast disease. The case group (n = 221) comprised women either with proliferative benign breast disease or breast cancer. The ratios of estrogen-DNA adducts to their respective metabolites and conjugates in plasma were analyzed using ultraperformance LC/MS-MS. The SNPs of CYP1A1, CYP1B1, and COMT were genotyped. Logistic regression model was used to compare the estrogen-DNA adduct ratios between the two groups. The estrogen-DNA adduct ratio in the case group was significantly higher than that in the control group (median ratio: 58.52 vs. 29.36, P = 0.004). A multiple logistic regression model demonstrated that a unit increase in the natural log of the estrogen-DNA adduct ratio in premenopausal women was a significant predictor of breast cancer risk, with an estimated hazard ratio of 1.718 (1.444−2.046, P < 0.001). However, the CYP1A1, CYP1B1, and COMT SNPs were not associated with the estrogen-DNA adduct ratios. In conclusion, plasma estrogen-DNA adduct ratio was associated with the presence of breast cancer or proliferating benign breast disease in premenopausal women in Taiwan.Prevention Relevance:This study provides evidence that endogenous estrogen-induced genotoxicity may contribute to the carcinogenesis of breast cancer in premenopausal Asian women. This work could have important preventive implication for the emerging disease in East Asia.

Multiple system atrophy (MSA) has no definitive genetic or environmental (G-E) risk factors, and the integrated effect of these factors on MSA etiology remains unknown. This study was undertaken to investigate the integrated effect of G-E factors associated with MSA and its subtypes, MSA-P and MSA-C.A consecutive case-control study was conducted at two medical centers, and the interactions between genotypes of five previously reported susceptible single nucleotide polymorphisms (SNPs; SNCA_rs3857059, SNCA_rs11931074, COQ2_rs148156462, EDN1_rs16872704, MAPT_rs9303521) and graded exposure (never, ever, current) of four environmental factors (smoking, alcohol, drinking well water, pesticide exposure) were analyzed by a stepwise logistic regression model.A total of 207 MSA patients and 136 healthy controls were enrolled. In addition to SNP COQ2_rs148156462 (TT), MSA risk was correlated with G-E interactions, including COQ2_rs148156462 (Tc) × pesticide nonexposure, COQ2_rs148156462 (TT) × current smokers, SNCA_rs11931074 (tt) × alcohol nonusers, and SNCA_rs11931074 (GG) × well water nondrinkers (all p lt; 0.01), with an area under the receiver operating characteristic curve (AUC) of 0.804 (95% confidence interval [CI] = 0.671-0.847). Modulated risk of MSA-C, with MSA-P as a control, correlated with COQ2_rs148156462 (TT) × alcohol nondrinkers, SNCA_rs11931074 (GG) × well water ever drinkers, SNCA_rs11931074 (Gt) × well water never drinkers, and SNCA_rs3857059 (gg) × pesticide nonexposure (all p lt; 0.05), with an AUC of 0.749 (95% CI = 0.683-0.815).Certain COQ2 and SNCA SNPs interact with common environmental factors to modulate MSA etiology and subtype disposition. The mechanisms underlying the observed correlation between G-E interactions and MSA etiopathogenesis warrant further investigation.

Supplementary Table S2: The ratios of estrogen-DNA adduct by participant subgroups

Supplementary Methods S1 describes the statistical analysis in detail.

The incidence of breast cancer among premenopausal women has been increasing rapidly in recent decades in East Asia. This case–control study investigated whether estrogen-DNA adducts were associated with breast cancer risk in Taiwan. The control group (n = 146) comprised healthy female volunteers and women with non-proliferative breast disease. The case group (n = 221) comprised women either with proliferative benign breast disease or breast cancer. The ratios of estrogen-DNA adducts to their respective metabolites and conjugates in plasma were analyzed using ultraperformance LC/MS-MS. The SNPs of CYP1A1, CYP1B1, and COMT were genotyped. Logistic regression model was used to compare the estrogen-DNA adduct ratios between the two groups. The estrogen-DNA adduct ratio in the case group was significantly higher than that in the control group (median ratio: 58.52 vs. 29.36, P = 0.004). A multiple logistic regression model demonstrated that a unit increase in the natural log of the estrogen-DNA adduct ratio in premenopausal women was a significant predictor of breast cancer risk, with an estimated hazard ratio of 1.718 (1.444−2.046, P < 0.001). However, the CYP1A1, CYP1B1, and COMT SNPs were not associated with the estrogen-DNA adduct ratios. In conclusion, plasma estrogen-DNA adduct ratio was associated with the presence of breast cancer or proliferating benign breast disease in premenopausal women in Taiwan.Prevention Relevance:This study provides evidence that endogenous estrogen-induced genotoxicity may contribute to the carcinogenesis of breast cancer in premenopausal Asian women. This work could have important preventive implication for the emerging disease in East Asia.

Purpose:Abnormal spindle-like microcephaly associated (ASPM) plays an important role in neurogenesis and cell proliferation. This study is to elucidate its role in hepatocelllular carcinoma (HCC), particularly early tumor recurrence (ETR) and prognosis.Experimental Design: We used reverse transcription-PCR assays to measure the ASPM mRNA levels in 247 HCC and correlated with clinicopathologic and molecular features.Results:ASPM mRNA levels were high in fetal tissues but very low in most adult tissues. ASPM mRNA was overexpressed in 162 HCC (66%) but not in benign liver tumors. ASPM overexpression correlated with high α-fetoprotein (P = 1 × 10-8), high-grade (grade II-IV) HCC (P = 2 × 10-6), high-stage (stage IIIA-IV) HCC (P = 1 × 10-8), and importantly ETR (P = 1 × 10-8). ETR is the most critical unfavorable clinical prognostic factor. Among the various independent histopathologic (tumor size, tumor grade and tumor stage) and molecular factors (p53 mutation, high α-fetoprotein, and ASPM overexpression), tumor stage was the most crucial histologic factor (odds ratio, 14.7; 95% confidence interval, 6.65-33.0; P = 1 × 10-8), whereas ASPM overexpression (odds ratio, 6.49; P = 1 × 10-8) is the most important molecular factor associated with ETR. ASPM overexpression was associated with vascular invasion and ETR in both p53-mutated (all P values = 1 × 10-8) and non-p53-mutated HCC (P = 1 × 10-8 and 0.00088, respectively). Hence, patients with APSM-overexpressing HCC had lower 5-year survival (P = 0.000001) in both p53-mutated (P = 0.00008) and non-p53-mutated HCC (P = 0.0027). In low-stage (stage II) HCC, ASPM overexpression also correlated with higher ETR (P = 0.008).Conclusion:ASPM overexpression is a molecular marker predicting enhanced invasive/metastatic potential of HCC, higher risk of ETR regardless of p53 mutation status and tumor stage, and hence poor prognosis.

Supplementary Data from ASPM Is a Novel Marker for Vascular Invasion, Early Recurrence, and Poor Prognosis of Hepatocellular Carcinoma

Background: Hyperlipidemia and serum oxysterol levels are known to be associated with breast cancer risk. In murine model, altered oxysterol levels in adipose tissue were identified in obese mice. However, the significance of oxysterol levels in human adipose tissue and their association with breast cancer risk were largely unknown. In this study, we aimed to quantify the levels of different oxysterols in adipose tissue and to establish their association with breast cancer risk. Methods: The breast adipose tissue was collected from patients who underwent surgery at a tertiary medical center for benign breast disease or breast cancer. We have profiled oxysterol levels by liquid chromatography-mass spectrometry. Multivariate analysis was used to analyze the relationship of adipose tissue oxysterol levels and breast cancer risk. Result: Breast adipose tissue from 279 subjects (benign low risk, n=58; benign high risk, n=33, and breast cancer, n=188) collected between March 2009 and November 2014 were included in this analysis. Parity is a protective factor both for breast cancer in premenopausal and postmenopausal groups. Brassicasterol ≤0.28 ng/mg (OR=6.739, 95% C.I.=2.092-21.707, p=0.001) and age >40.06 years old (OR=3.774, 95% C.I.=1.328-10.722, p=0.013) in premenopausal patients; high log (7α-. hydroxycholesterol) levels (OR=6.690, 95% C.I.=1.915-23.369, p=0.003) and 24-hydroxycholesterol >0.92ng/mg (OR=4.539, 95% C.I.=1.153-17.866, p=0.030) in postmenopausal patients were associated with increased BC risk. Sitosterol ≤3.03ng/mg (OR=0.057, 95% C.I.= 0.016-0.205, p Citation Format: I-Chun Chen, Wen-Hung Kuo, Fu-Chang Hu, Ming-Yang Wang, Yen-Shen Lu, Dieter Lütjohann, Ching-Hung Lin. Oxysterol profiling in breast adipose tissue identifies brassicasterol and 24-hydroxycholesterol as breast cancer risk predictors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-09.

Background This meta-analysis aimed to test the hypothesis that the HER2-positive metastatic breast cancer (mBC) patients treated with anti-HER2 antibodies in trial intervention arms have a greater prolongation of overall survival (OS) than of progression-free survival (PFS) and this extra-prolongation of median survival time in OS relates specifically to the anti-HER2 antibody. Methods The NCBI/Pubmed and Cochrane databases were searched systematically for HER2-positive or mBC trials published in English during January 1999–November 2017. Treatment arms with shorter PFS were considered as the “control” arm, whereas those with longer PFS as the “test” arm. The between-treatment drug differences were grouped into nine categories. Groups with or without anti-HER2 antibodies were pooled respectively for comparisons. The interrelationships between PFS and OS hazard ratios (HRs) and median survival time differences were investigated by conducting fixed-effects and mixed-effects linear meta-regression analyses. Results Twenty-eight trials (10,928 patients) from 438 articles were collected, and four with missing data were excluded in meta-regression analysis. Overall median PFS (HR = 0.73, 95% CI: 0.68–0.78) and median OS (HR = 0.82, 95% CI: 0.77–0.87) weakly favored the longer PFS arm with a weak correlation between the PFS and OS HRs. However, the between-treatment drug difference was anti-HER2 antibody, the absolute increment in median OS time was double that of median PFS time (p, Highlights • Our study dissected the overall survival benefit over progression-free survival in HER-2 positive metastatic breast cancer treated with anti-HER2 antibody by meta-analysis. • Use of anti-HER2 antibodies, but not other anticancer drugs, to treat HER2-positive metastatic breast cancer independently predicted the OS compared with PFS. • The design of future clinical trials should consider anti-HER2 antibodies carefully in the treatment armamentarium for HER2-positive metastatic breast cancer.

Several laboratory data have been identified as predictors of disease severity or mortality in COVID-19 patients. However, the relative strength of laboratory data for the prediction of health outcomes in COVID-19 patients has not been fully explored. This meta-analytical study aimed to evaluate the prediction capabilities of laboratory data on the prognosis of COVID-19 patients during 2020 while mass vaccination has not started yet.Two electronic databases, MEDLINE and EMBASE, from inception to October 10, 2020 were searched. Observational studies of laboratory-confirmed COVID-19 patients with well-defined severity or survival status, and with the desired laboratory data at initial hospital administrations, were selected. Meta-regression analysis with the generalized estimating equations (GEE) method for clustered data was performed sequentially. Primary outcome measures were to compare the level of laboratory data and their impact on different health outcomes (severe vs non-severe, critically severe vs non-critically severe, and dead vs alive).Meta-data of 13 clinical laboratory items at initial hospital presentations were extracted from 76 selected studies with a total of 26 627 COVID-19 patients in 16 countries. After adjusting for the effect of age, 1.03lymphocyte count mean or median ( × 10Lymphocyte count was the most powerful predictor among the 13 common laboratory variables explored from COVID-19 patients to differentiate disease severity and to predict mortality. Lymphocyte count should be monitored for the prognoses of COVID-19 patients in clinical settings in particular for patients not fully vaccinated.

Background The incidence of breast cancer among East Asian women has been increasing rapidly in recent decades, but the etiology remains unclear. This case–control study investigated whether estrogen-DNA adducts ratio is a predictor of breast cancer risk in East Asian women. Methods The control group (n = 146) comprised healthy female volunteers and women with benign breast disease without atypia. The case group (n = 221) comprised women either with benign breast disease with atypia and breast cancer. The ratios of estrogen-DNA adducts to their respective metabolites and conjugates in plasma were analyzed using ultraperformance liquid chromatography and tandem mass spectrometry. The single nucleotide polymorphisms (SNPs) of CYP1A1, CYP1B1, and COMT were genotyped, and a logistic regression model was used to compare the estrogen-DNA adduct ratios between the two groups. Results The estrogen-DNA adduct ratio in the case group was significantly higher than that in the control group (median ratio: 58.52 vs. 29.36, P = 0.004). A multiple logistic regression model demonstrated that a unit increase in the natural log of the estrogen-DNA adduct ratio in premenopausal women was a significant predictor of breast cancer risk, with an estimated hazard ratio of 1.718 (1.444 − 2.046, P CYP1A1, CYP1B1, and COMT SNPs were not associated with the estrogen-DNA adduct ratios. Conclusion Plasma estrogen-DNA adduct ratio predicts breast cancer risk in premenopausal women in East Asia, and the genotoxic effects may contribute to the carcinogenesis of this emerging disease.

To explore cutoffs of gestational hypertriglyceridemia based on the risk of adverse pregnancy outcomes.Pregnant women who visited National Taiwan University Hospital for prenatal care were included. Fasting plasma TG in the first and second trimesters were measured. Adverse pregnancy outcomes, including gestational diabetes and large for gestational age, were recorded and used in simple and multiple generalized additive models (GAM) to identify cutoffs for gestational hypertriglyceridemia.We recruited 807 pregnant woman-newborn pairs. Using GAM analyses, we identified plasma TG at 95 or 140 mg/dL (1.07 or 1.58 mmol/L) in the first trimester, and 173 or 220 mg/dl (1.95 or 2.48 mmol/L) in the second trimester as potential cutoffs. Gestational hypertriglyceridemia defined by the higher cutoffs in both trimesters were associated with adverse pregnancy outcomes and had a more reasonable prevalence and better specificity than the lower cutoffs (First trimester plasma TG ≥ 140 mg/dL, adjusted OR 2.56, 95% CI 1.17-5.69, p = 0.019, prevalence 19%, specificity 83%; Second trimester plasma TG ≥ 220 mg/dL, adjusted OR 1.70, 95% CI 1.00-2.87, p = 0.049, prevalence 19%, specificity 81%).Fasting plasma TG ≥ 140 mg/dL in the first trimester and ≥ 220 mg/dL in the second trimester can be used as cutoffs of gestational hypertriglyceridemia.

SummaryBackgroundThis study aimed to evaluate the prediction capabilities of clinical laboratory biomarkers to the prognosis of COVID-19 patients.MethodsObservational studies reporting at least 30 cases of COVID-19 describing disease severity or mortality were included. Meta-data of demographics, clinical symptoms, vital signs, comorbidities, and 14 clinical laboratory biomarkers on initial hospital presentation were extracted. Taking the outcome group as the analysis unit, meta-regression analysis with the generalized estimating equations (GEE) method for clustered data was performed sequentially. The unadjusted effect of each potential predictor of the three binary outcome variables (i.e., severe vs. non-severe, critically severe vs. non-critically severe, and dead vs. alive) was examined one by one by fitting three series of simple GEE logistic regression models due to missing data. The worst one was dropped one at a time. Then, a final multiple GEE logistic regression model for each of the three outcome variables was obtained.FindingsMeta-data was extracted from 76 articles, reporting a total of 26,627 cases of COVID-19. Patients were recruited across 16 countries. The number of studies (patients) included in the final models of the analysis for severity, critical severity, and mortality was 38 studies (9,764 patients), 21 studies (4,792 patients), and 24 studies (14,825 patients), respectively. After adjusting for the effect of age, lymphocyte count mean or median ≤ 1.03 (estimated hazard ratio [HR] = 46.2594, p < 0.0001), smaller lymphocyte count mean or median (HR < 0.0001, p = 0.0028), and lymphocyte count mean or median ≤ 0.8714 (HR = 17.3756, p = 0.0079) were the strongest predictor of severity, critical severity, and mortality, respectively.InterpretationLymphocyte count should be closely watched for COVID-19 patients in clinical practice.

The 36-item Dispositional Flow Scale-2 (DFS-2) and Flow State Scale-2 (FSS-2) were developed to assess flow experience in daily and specific activities. Although their validity and reliability had been examined in general populations and different cultures, little is known for schizophrenic subjects. Thus, this study aimed to validate Traditional-Chinese DFS-2 (TCDFS-2) and FSS-2 (TCFSS-2) in Taiwanese subjects with schizophrenia or schizoaffective disorder.We recruited 229 adult participants from outpatient clinics, day care centers, and psychiatric rehabilitation centers in Taipei. They filled out 36-item TCDFS-2 and TCFSS-2 under guidance. The LISREL 9.30 software was used to conduct exploratory factor analysis for exploring measurement structures, and then confirmatory factor analysis for identifying factor models.The six first-order factor and one second-order factor measurement models were obtained for both 36-item TCDFS-2 (Chi-square statistic = 999.1, df = 545, p 0.0001, Root Mean Square Error of Approximation [RMSEA] = 0.0603, and Comparative Fit Index [CFI] = 0.9213) and TCFSS-2 (Chi-square statistic = 987.9, df = 539, p 0.0001, RMSEA = 0.0603, and CFI = 0.9213).Our factor models differed remarkably from those of 36-item DFS-2 and FSS-2. Yet, they were barely acceptable to be used to measure flow experiences in schizophrenic subjects in clinical applications. Since the factor scores, measurement structures, or even definitions of flow experiences could differ substantially between healthy people and patients with mental illness, disease-specific instruments of flow experiences should be considered in the future.

Background: This study aimed to evaluate the prediction capabilities of clinical laboratory biomarkers to the prognosis of COVID-19 patients. Methods: Observational studies reporting at least 30 cases of COVID-19 describing disease severity or mortality were included. Meta-data of demographics, clinical symptoms, vital signs, comorbidities, and 14 clinical laboratory biomarkers on initial hospital presentation were extracted. Taking the outcome group as the analysis unit, meta-regression analysis with the generalized estimating equations (GEE) method for clustered data was performed sequentially. The unadjusted effect of each potential predictor of the three binary outcome variables (i.e., severe vs. non-severe, critically severe vs. non-critically severe, and dead vs. alive) was examined one by one by fitting three series of simple GEE logistic regression models due to missing data. The worst one was dropped one at a time. Then, a final multiple GEE logistic regression model for each of the three outcome variables was obtained. Findings: Meta-data was extracted from 76 articles, reporting a total of 26,627 cases of COVID-19. Patients were recruited across 16 countries. The number of studies (patients) included in the final models of the analysis for severity, critical severity, and mortality was 38 studies (9,764 patients), 21 studies (4,792 patients), and 24 studies (14,825 patients), respectively. After adjusting for the effect of age, lymphocyte count mean or median ≤ 1.03 (estimated hazard ratio [HR] = 46.2594, p < 0.0001), smaller lymphocyte count mean or median (HR < 0.0001, p = 0.0028), and lymphocyte count mean or median ≤ 0.8714 (HR = 17.3756, p = 0.0079) were the strongest predictor of severity, critical severity, and mortality, respectively. Interpretation: Lymphocyte count should be closely watched for COVID-19 patients in clinical practice. Funding: None to declare. Declaration of Interest: None to declare.

The aim of this study was to update the information on internationally acceptable standards and clinical practice recommendations for the management of patients with primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force acknowledged the novel issues of PA and reached a group consensus on PA in Taiwan by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. Unilateral adrenalectomy is the preferred treatment for patients with aldosterone-producing adenoma (APA). For medical treatment with mineralocorticoid receptor antagonists (MRAs), spironolactone is the first-line treatment, and eplerenone is a reasonable alternative in PA patients intolerant or contraindicated to spironolactone. The dose of MRAs can be titrated according to plasma renin activity (PRA). For screening PA-related comorbidities, we suggest albuminuria to predict a post-treatment decline in renal function, echocardiography as cardiac evaluation, bone mineral density scan for osteoporosis, and obstructive sleep apnea. In tissue and genetic surveys, we suggest immunohistochemical staining and somatic mutation screening for post-operative adrenal specimens in APA patients. With this consensus, we hope to update the information on PA for clinical physicians to facilitate better identification, management and treatment of patients with PA.

Background Patients with childhood cancer are at increased risk for the development of second cancers. Methods A national multicenter survey of second cancers conducted by the Taiwan Pediatric Oncology Group retrieved retrospective data from the database at the Children Cancer Foundation in Taiwan beginning in 1995. The characteristics of second cancers and associations of patient demographic and clinical characteristics with time to death due to a second cancer were analyzed. Results We examined the records of 8782 patients with a primary cancer diagnosed between January 1, 1995 and December 31, 2013, and a total of 99 patients with a second cancer were identified. The most common type of second cancer was acute myeloid leukemia (n = 35), followed by acute lymphoblastic leukemia (n = 15), central nervous system (CNS) tumors (n = 15), and sarcomas (n = 10). Secondary hematological malignancies occurred earlier than other secondary cancers. The frequencies of second CNS tumors and second bone cancers and sarcomas were notably increased when prior radiation doses increased from zero, low dose to high dose. The overall 5-year survival of patients with a second cancer was poor (33.7%). Multivariate survival analysis revealed that the year of primary diagnosis ≤2002, secondary hematological malignancies, and age at second cancer diagnosis ≤9.3 years or >26.8 years increased the risk of death following second cancer. Conclusion Children who develop a second cancer have an unfavorable outcome. Early detection and improved treatment for second cancers are needed.

BackgroundHow could we anticipate the progression of the ongoing epidemic of the coronavirus disease 2019 (COVID-19) in China? As a measure of transmissibility, we aimed to estimate concurrently the time-varying reproduction number over time during the COVID-19 epidemic in China.MethodsWe extracted the epidemic data from the “Tracking the Epidemic” website of the Chinese Center for Disease Control and Prevention for the duration of January 19, 2020 and March 14, 2020. Then, we specified two plausible distributions of serial interval to apply the novel estimation method implemented in the incidence and EpiEstim packages to the data of daily new confirmed cases for robustly estimating the time-varying reproduction number in the R software.ResultsThe epidemic curve of daily new confirmed cases in China peaked around February 4–6, 2020, and then declined gradually, except the very high peak on February 12, 2020 owing to the added clinically diagnosed cases of the Hubei Province. Under two specified plausible scenarios for the distribution of serial interval, both curves of the estimated time-varying reproduction numbers fell below 1.0 around February 17–18, 2020. Finally, the COVID-19 epidemic in China abated around March 7–8, 2020, indicating that the prompt and aggressive control measures of China were effective.ConclusionSeeing the estimated time-varying reproduction number going downhill speedily was more informative than looking for the drops in the daily number of new confirmed cases during an ongoing epidemic of infectious disease. We urged public health authorities and scientists to estimate time-varying reproduction numbers routinely during an epidemic of infectious diseases and to report them daily to the public until the end of the epidemic.

Background Primary aldosteronism ( PA ) is associated with higher atrial fibrillation prevalence and other cardiovascular complications. However, the effect of target treatment to prevent new‐onset atrial fibrillation ( NOAF ) remains unclear. This study investigated incidence of NOAF under different treatment strategies in patients with PA. Methods and Results We analyzed longitudinal data for patients with PA without atrial fibrillation history from 1997 to 2009 within the National Health Insurance Research Database in Taiwan. Patients with essential hypertension matched by propensity score were enrolled as controls. The primary outcome measurement was NOAF , and secondary outcome measurements were mortality, major cardiac and cardiac/cerebrovascular events, and a combined end point of NOAF and mortality. We identified 2202 patients with PA (534 adrenalectomy, 1668 mineralocorticoid receptor antagonist [MRA] therapy) and 8808 essential hypertension controls with mean follow‐up of 4.4 years. In primary outcome measurement, patients with PA who underwent adrenalectomy had a lower incidence of NOAF (adjusted hazard ratio; 0.28, P =0.011) than controls. In contrast, the patients with PA who received MRA therapy had comparable risk of NOAF (adjusted hazard ratio, 1.20; P =0.224). In secondary outcome measurement, patients with PA who underwent adrenalectomy had a lower rate of mortality and combined end point of NOAF and mortality than controls. Patients with PA who received MRA therapy had a higher risk of mortality, major cardiac and cardiac/cerebrovascular events, and combined NOAF with mortality than the essential hypertension controls. Conclusions Compared with patients with essential hypertension, patients with PA who underwent adrenalectomy had a lower incidence of NOAF . However, this finding was not observed in patients with PA who received MRA therapy with a lower dose. Differences between the 2 strategies may reduce with a higher dose of MRA therapy.

Background Primary aldosteronism is the most common cause of secondary hypertension and is associated with left ventricular hypertrophy. However, whether aldosterone excess is responsible for left ventricular (LV) diastolic dysfunction is unknown. Methods and Results We prospectively enrolled 129 patients with aldosterone‐producing adenoma and 120 patients with essential hypertension, and analyzed their clinical, biochemical, and echocardiographic data, including tissue Doppler images. The patients with aldosterone‐producing adenoma were reevaluated 1 year after adrenalectomy. After propensity score matching, there were 105 patients in each group. The patients with aldosterone‐producing adenoma had worse diastolic function than the patients with essential hypertension, as reflected by lower e′ ( P P =0.003). Multivariate analysis showed that LV diastolic function was significantly correlated with age ( P P P =0.002), systolic blood pressure ( P =0.004), creatinine ( P =0.008), and log‐transformed aldosterone‐renin ratio ( P =0.003). After adrenalectomy, the patients with aldosterone‐producing adenoma had significant improvements in LV diastolic function as reflected by an increase in e′ ( P =0.003) and decrease in E/e′ ( P =0.002). The change in E/e′ was independently correlated with baseline E/e′ ( P P =0.006). Conclusions The patients with primary aldosteronism had worse LV diastolic function than the patients with essential hypertension after propensity score matching, and this could be reversed after adrenalectomy, suggesting that aldosterone excess may induce LV diastolic dysfunction.

AIM Increased oxidative stress significantly modifies the outcome of patients with diabetes mellitus (DM) and end-stage renal disease (ESRD), and is counteracted by antioxidative capacity. We aimed to investigate whether antioxidant single nucleotide polymorphisms (SNPs) influence the outcome of ESRD individuals and the influences exerted by DM, which has not been tested before. METHODS We prospectively enrolled multi-centre ESRD patients of Han Chinese origin between 2002 and 2003, recording their antioxidant (superoxide dismutase [SOD2], glutathione peroxidase [GPX1]) and peroxisome proliferator activated receptor-γ (PPAR-γ) genotyping results, and stratified based on DM. They were followed up until 2008, with risk factors for mortality analyzed by Cox proportional hazard regression. RESULTS We discovered that diabetic ESRD carriers of CC genotype of SOD2 exon 2 had an increased risk of mortality compared to non-diabetic ones with other genotypes (hazard ratio [HR] 4.04, P = 0.04), while GPX1 SNPs had no influence. Interactions between SOD2 and PPAR-γ SNPs regarding the mortality influence were also detected (for SOD2 CC genotype x PPAR-γ exon 6 CT genotype, HR 3.19, P = 0.008), suggesting the importance of considering a combination panel of SNPs on patient survival. CONCLUSION This might be the largest study focusing on the relationship between antioxidant SNPs and the outcomes of diabetic ESRD patients of Han Chinese origin. More studies are needed to validate our findings.

Current guidelines recommend harvesting ≥3 sentinel nodes if sentinel lymph node biopsy (SLNB) alone is considered after neoadjuvant therapy (NAT) for initially node-positive (cN+) breast cancer. We attempted to investigate factors predicting one or two sentinel lymph nodes harvested to be accepted for SLNB alone after NAT in initially cN + patients.Overall, 157 patients who received NAT (clinically T1-3/N1-2/M0) and underwent SLNB were identified from a prospectively maintained database. Significant factors were identified using a multiple logistic regression model.The overall SLN identification rate was 83.4%. Failed SLN identification was associated with a 2-day protocol using a single tracer (odds ratio: 0.331 [95% confidence interval {CI}: 0.132-0.830], p = 0.018), age52 years (0.345 [0.131-0.913], p = 0.032), and lobular histology (0.156 [0.026-0.944], p = 0.043). The overall false-negative SLNB rate was 14.7%. Its increased risk was associated with radioactivity count530 for any SLN during SLNB (96.4 [4.00-2320], p = 0.005), age ≥57 years (34.2 [1.92-610], p = 0.016), and taxane use (105 [1.02-10700], p = 0.049); its decreased risk was associated with more harvested SLNs (0.191 [0.054-0.669], p = 0.01) and dual tracers (0.101 [0.012-0.843], p = 0.034). A predictive model using these factors achieved an area under the curve of 0.935 (95% CI: 0.878-0.991).When taxane was administered during NAT, the false-negative rate was predicted at5% for patients aged57 years, if 1-2 SLNs were harvested using dual tracers, and when the count of every SLN was lower than 530 after NAT in cN + breast cancer.

Aim Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction. Methods The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge. Conclusion The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.

Objective International institutes have developed their own clinical performance indicators for ambulance services. It is unknown whether these process measures are related to survival of patients after out-of-hospital cardiac arrest (OHCA). We aimed to determine whether Emergency Medical Service (EMS)-related ambulance team process measures correlate with patient survival. Methods Four years of observational data were collected from an urban EMS OHCA registry. The two process measures were achieving an EMS response time ≤4 min and prehospital ROSC (return of spontaneous circulation). The outcome measure was survival to discharge. We used the GLMM (generalised linear mixed model) with stepwise selection to examine this process-outcome link at the patient and EMS team levels, respectively. Results We analyzed 3856 OHCA patients distributed across forty-three EMS ambulance teams. Survival to discharge was observed in 193 (5%) patients. The two EMS team process measures were positively associated with an improvement in survival at the patient level after case-mix adjustment. However, they were not associated with improvement in the risk-adjusted survival rate. Conclusions The EMS team-level process measures proposed by international institutes may not predict the risk-adjusted survival rate. Using these measures to motivate EMS teams to improve their quality performance would be questionable. Increased efforts should be devoted to constructing more pivotal EMS team-level process measures that are tightly linked to survival.

Date Presented 03/26/20 The Traditional Chinese version of the Revised Self-Efficacy Scale showed adequate goodness of fit when applied to schizophrenic patients in Taiwan. That means this scale can measure the subjective feelings of self-efficacy in schizophrenic people, specifically relating to their positive and negative symptoms and interpersonal deficits. Future studies would be suggested to apply the same validation method for this disease-specific self-efficacy scale in other cultures. Primary Author and Speaker: Lin-Jye Huang Additional Authors and Speakers: Fu-Chang Hu, Chien-Te Wu, Yi-Hong Yang, Shu-Chun Lee, Powen Lin, Shih-Jui Hu

BACKGROUND AND AIMS Fibroblast growth factor 19 (FGF19) and fibroblast growth factor receptor 4 (FGFR4) signalling play critical roles in hepatocarcinogenesis. This study explored the potential of FGF19- and FGFR4-related biomarkers in predicting early tumour recurrence (ETR) and survival in patients with resectable hepatocellular carcinoma (HCC). METHODS We examined the mRNA expressions of FGF19, FGFR4, klotho-beta (KLB), cyclin D1 (CCND1) and FGF4 in 151 surgically resected, primary unifocal HCCs through quantitative real-time polymerase chain reaction. Generalized additive models were fitted to detect nonlinear effects of continuous covariates and define thresholds of biomarker expressions. Univariate and multivariate analyses were performed to evaluate prognostic values of these biomarkers for tumour recurrence and patient survival. RESULTS Overexpression of FGF19, FGFR4, KLB, CCND1 and FGF4 mRNA was detected in 40%, 32%, 26%, 15% and 35% of 151 tumours respectively. ETR was the strongest prognostic factor predicting worse overall survival (hazard ratio [HR], 5.678; 95% confidence interval, 3.7-8.713; P

BackgroundThe incidence of breast cancer among younger East Asian women has been increasing rapidly over recent decades. This international collaborative study systemically compared the differences in age-specific incidences and pathological characteristics of breast cancer in East Asian women and women of predominantly European ancestry.MethodsWe excerpted analytic data from six national cancer registries (979 675 cases) and eight hospitals (18 008 cases) in East Asian countries and/or regions and, for comparisons, from the US Surveillance, Epidemiology, and End Results program database. Linear regression analyses of age-specific incidences of female breast cancer and logistic regression analyses of age-specific pathological characteristics of breast cancer were performed. All statistical tests were two-sided.ResultsUnlike female colorectal cancer, the age-specific incidences of breast cancer among East Asian women aged 59 years and younger increased disproportionally over recent decades relative to rates in US contemporaries. For years 2010–2014, the estimated age-specific probability of estrogen receptor positivity increased with age in American patients, whereas that of triple-negative breast cancer (TNBC) declined with age. No similar trends were evident in East Asian patients; their probability of estrogen receptor positivity at age 40–49 years was statistically significantly higher (odd ratio [OR] = 1.50, 95% confidence interval [CI] = 1.36 to 1.67, P < .001) and of TNBC was statistically significantly lower (OR = 0.79, 95% CI = 0.71 to 0.88, P < .001), whereas the probability of ER positivity at age 50–59 years was statistically significantly lower (OR = 0.88, 95% CI = 0.828 to 0.95, P < .001). Subgroup analyses of US Surveillance, Epidemiology, and End Results data showed similarly distinct patterns between East Asian American and white American patients.ConclusionsContrasting age-specific incidences and pathological characteristics of breast cancer between East Asian and American women, as well as between East Asian Americans and white Americans, suggests racial differences in the biology.

Objectives Peripheral blood parameters implicating the irreversible damages of cardiogenic shock under extracorporeal membrane oxygenation (ECMO) support patients were investigated. Methods The blood was collected from 23 cardiogenic shock cases at the time of ECMO installation, and 2, 6, 12, and 24h after oxygenation. Plasma levels of IL-2, IL-6, IL-7, IL-8, IL-10, IFN-γ, MCP-1, and carbonic anhydrase IX (CA IX) were determined by ELISA. Reactive oxygen species were measured by luminol and lucigenin and leukocyte subpopulations were analyzed by flow cytometry. Generalized additive models (GAMs) were performed to identify the death ranges of every variable and the variables were further discretized at each time point. The combination of predictors was selected from both original and discretized covariates by the generalized linear model (GLM) at each time point. Results Plasma IL-10 level was the most distinct biomarker between survivors and non-survivors after oxygenation. IL-10 sequentially partnered with IL-6, IL-7, and lymphocyte percentage at 2h, with CD3 + CD4 + T cells at 6h, with CA IX at 12h, and CD3 + T lymphocytes at 24h predicted death with AUCs 1.000, 0.975, 0.992, and 0.992, respectively. Conclusions Combination of the GAM plots and GLM models overcame the complexity of different disease categories. The systemic irreversible damages from cardiogenic shock ECMO cases might be detected from several peripheral blood parameters.

Date Presented 04/04/19 The study implicated that when helping schizophrenic people obtain flow experience through daily activities, OTs should not only provide activities that correspond to their abilities and interests but also facilitate their self-determined behaviors and self-efficacy. This theory-based study may serve as a piece of evidence in practice to establish the foundations for further inquiring OT intervention outcomes and cross-cultural differences. Primary Author and Speaker: LIN-JYE HUANG Additional Authors and Speakers: Fu-Chang Hu, Chinyu Wu, Yi-Hong Yang, Shu-Chun Lee, Powen Lin, Shih-Jui Hu

Date Presented 4/21/2018 The study results did not support the measurement equivalence of the adapted Chinese Leisure Satisfaction Scale between schizophrenia and general populations. Developing a measure of leisure satisfaction for the schizophrenia population should be considered. Primary Author and Speaker: Lin-Jye Huang Additional Authors and Speakers: Fu-Chang Hu, Chinyu Wu, Yi-Hong Yang, Shu-Chun Lee, Hsu-Chang Huang, Chun-Yi Yu, Kuan-Yu Lai

Date Presented 4/19/2018 The results in this study did not support the measurement equivalence of the Chinese Dispositional Flow Scale–2 between schizophrenia and general populations. Developing a measuring of dispositional flow tendency for the schizophrenia population should be considered. Primary Author and Speaker: Lin-Jye Huang Additional Authors and Speakers: Fu-Chang Hu, Chinyu Wu, Yi-Hong Yang, Shu-Chun Lee, Hsu-Chang Huang, Chun-Yi Yu, Kuan-Yu Lai

Date Presented 4/19/2018 The study results did not support the measurement equivalence of the Chinese Flow State Scale–2 between schizophrenia and general populations. Developing a measure of flow state during activity for the schizophrenia population should be considered. Primary Author and Speaker: Lin-Jye Huang Additional Authors and Speakers: Fu-Chang Hu, Chinyu Wu, Yi-Hong Yang, Shu-Chun Lee, Hsu-Chang Huang, Chun-Yi Yu

Increased oxidative stress significantly modifies the outcome of patients with diabetes mellitus (DM) and end-stage renal disease (ESRD), and is counteracted by antioxidative capacity. We aimed to investigate whether antioxidant single nucleotide polymorphisms (SNPs) influence the outcome of ESRD individuals and the influences exerted by DM, which has not been tested before.We prospectively enrolled multi-centre ESRD patients of Han Chinese origin between 2002 and 2003, recording their antioxidant (superoxide dismutase [SOD2], glutathione peroxidase [GPX1]) and peroxisome proliferator activated receptor-γ (PPAR-γ) genotyping results, and stratified based on DM. They were followed up until 2008, with risk factors for mortality analyzed by Cox proportional hazard regression.We discovered that diabetic ESRD carriers of CC genotype of SOD2 exon 2 had an increased risk of mortality compared to non-diabetic ones with other genotypes (hazard ratio [HR] 4.04, P = 0.04), while GPX1 SNPs had no influence. Interactions between SOD2 and PPAR-γ SNPs regarding the mortality influence were also detected (for SOD2 CC genotype x PPAR-γ exon 6 CT genotype, HR 3.19, P = 0.008), suggesting the importance of considering a combination panel of SNPs on patient survival.This might be the largest study focusing on the relationship between antioxidant SNPs and the outcomes of diabetic ESRD patients of Han Chinese origin. More studies are needed to validate our findings.