Simplified Assessment of Radioiodine Biokinetics for Thyroid Cancer Patients: A Practical Approach Using Continuous External Radiation Monitoring.

INTRODUCTION: The biokinetics of radioiodine (RAI) in thyroid cancer patients are complex. This study aims to develop a practical approach for assessing RAI biokinetics to predict patient discharge time and estimate radiation exposure to caregivers. METHODS: We retrospectively reviewed data from patients with differentiated thyroid carcinoma undergoing RAI treatment. Serial radiation dose rates were dynamically collected during hospitalization and fitted to a biexponential model to assess the biokinetic features: RAI uptake fraction of thyroid tissue (Ft) and effective half-life of extra-thyroid tissue (Tet). Correlations with 99mTc thyroid uptake ratio (TcUR), radiation retention ratio (RR), renal function, and body mass index (BMI) were analyzed. RESULTS: Thirty-five patients were enrolled. The derived Ft was 0.08 ± 0.06 and Tet was 7.57 ± 1.45 h. Pearson's correlation analysis revealed a significant association between Ft and both TcUR and RR (p < 0.05), while Tet correlated with renal function and BMI (p < 0.05). CONCLUSION: This novel and practical method assessing RAI biokinetics demonstrates consistency with other parameters and related studies, enhancing the model reliability. It shows promise in predicting an appropriate discharge time and estimating radiation exposure to caregivers, allowing for modifications to radiation protection precautions to follow ALARA principle and minimize the potential risks from radiation exposure.

A case-control study coupling with meta-analysis elaborates decisive association between IGF-1 rs35767 and osteoporosis in Asian postmenopausal females.

BACKGROUND: Osteoporosis (OP) is prevalent in postmenopausal women. Several studies investigated the association between IGF-1 polymorphisms and OP among postmenopausal females with conflicting outcomes. OBJECTIVE: To investigate whether the IGF-1 (rs35767, rs2288377, rs5742612) were associated with OP in postmenopausal females. METHODS: In case-control study, 95 OP cases and 222 healthy controls were recruited between March 2015 and July 2019. OP was diagnosed based on WHO criteria for diagnosis of OP as T score of bone mineral density (BMD) ≤-2.5; normal, as T score of BMD ≥-1. IGF-1 SNPs were genotyped by iPLEX Gold SNP genotyping. To be solid, related studies from PubMed, Embase, Cochrane, Web of science, and previous meta-analysis up until November 2020, along with our case-control study, were incorporated into a meta-analysis with criteria of significance using odds ratios (ORs) with corresponding 95% confidence intervals (CI) to evaluate risk factor of SNPs on OP. TSA was used to estimate the sample sizes required to achieve a conclusion. RESULTS: In dominant model of our case-control study, we found nonsignificant association of rs35767 [Adj-OR: 0.95 (95% CI: 0.56-1.60)], rs2288377 [Adj-OR: 1.15 (95% CI: 0.67-1.97)], and rs5742612 [Adj-OR: 1.07 (95% CI: 0.62-1.83)] with OP in postmenopausal females. However, integration of our case-control study and 3 published studies, rs35767 [OR: 1.24 (95% CI: 1.05-1.47)] showed a conclusively risk association with OP in postmenopausal females judged by TSA with 2267 Asians. CONCLUSIONS: This study demonstrates a crucial sample to conclude that IGF-1 rs35767 is significantly associated with OP in postmenopausal women.

Gender difference in appendicular muscle strength: determinant of the quality of life in the older Taiwanese.

BACKGROUND: The loss of skeletal muscle mass by aging determines the health status and the quality of life (QoL). OBJECTIVE: To examine the relationships between appendicular muscle strength and the QoL of elderly adults in gender difference. METHODS: This was a cross-sectional study, in which 690 subjects who participated in older adults health examination in the health management center of Tri-Service General Hospital from 2018 to 2021. A structured questionnaire was used to collect basic demographic data. The 12-Item Short Form Survey (SF-12) was used to evaluate the QoL of subjects. Their grip strength and gait speed were measured, and Dual-energy X-ray absorptiometry was used to measure muscle mass and other body composition data. Multivariate regression analysis was used to examine the relationships between upper and lower limb muscle strength and the QoL of older adults. RESULTS: In men, legs muscle mass percentage (LegsMM%) (ß = 3.67; 95% CI: 0.64-6.69; p = 0.018) and gait speed (ß = 6.09; 95% CI: 3.88-8.30; p < 0.001) were positively associated with physical component summary (PCS) scores, and gait speed (ß = 4.63; 95% CI: 2.66-6.60; p < 0.001) was also related to an improvement mental component summary (MCS) scores. In women, arms muscle mass percentage (ArmsMM%) (ß = 6.50; 95% CI: 2.34-10.66; p = 0.002) and grip strength (ß = 10.54; 95% CI: 6.27-14.81; p < 0.001) had the greatest effect on improving PCS scores, whereas grip strength (ß = 7.58; 95% CI 4.00-11.17; p < 0.001) was also found to help improve MCS scores. CONCLUSIONS: Men should focus on lower limb training, whereas females should focus on upper limb training to effectively improve their QoL. Appropriate exercise interventions should be designed for different genders for the promotion of the healthy aging policy.

Differential gene expression orchestrated by transcription factors in osteoporosis: bioinformatics analysis of associated polymorphism elaborating functional relationships.

BACKGROUND: Identification of candidate SNPs from transcription factors (TFs) is a novel concept, while systematic large-scale studies on these SNPs are scarce. PURPOSE: This study aimed to identify the SNPs of six TF binding sites (TFBSs) and examine the association between candidate SNPs and osteoporosis. METHODS: We used the Taiwan BioBank database; University of California, Santa Cruz, reference genome; and a chromatin immunoprecipitation sequencing database to detect 14 SNPs at the potential binding sites of six TFs. Moreover, we performed a case-control study and genotyped 109 patients with osteoporosis (T-score ≤ -2.5 evaluated by dual-energy X-ray absorptiometry) and 262 healthy individuals (T-score ≥ -1) at Tri-Service General Hospital from 2015 to 2019. Furthermore, we used the expression quantitative trait loci (eQTL) from the Genotype-Tissue Expression database to identify downstream gene expression as a criterion for the function of candidate SNPs. RESULTS: Bioinformatic analysis identified 14 SNPs of TFBSs influencing osteoporosis. Of these SNPs, the rs130347 CC + TC genotype had 0.57 times higher risk than the TT genotype (OR = 0.57, p = 0.031). Validation of eQTL analysis revealed that rs130347 T allele influences mRNA expression of downstream A4GALT in whole blood (p = 0.0041) and skeletal tissues (p = 0.011). CONCLUSIONS: We successfully identified the unique osteoporosis locus rs130347 in the Taiwanese and functionally validated this finding. In the future, this strategy can be expanded to other diseases to identify susceptible loci and achieve personalized precision medicine.

Decisive gene strategy on osteoporosis: a comprehensive whole-literature-based approach for conclusive candidate gene targets.

PURPOSE: Previous meta-analyses only examined the association between single gene polymorphisms and osteoporosis; there is no compilation of all gene loci that correlate with osteoporosis in the literature. In this study, we develop a new literature-based approach, a decisive gene strategy (DGS), to examine the sufficiency of the cumulative sample size for each gene locus and to assess whether a definite conclusion of the association between the gene locus and osteoporosis can be drawn. METHODS: The DGS was used to search PubMed, Embase, and Cochrane databases for all meta-analyses that correlated gene polymorphisms with osteoporosis. Trial sequential analysis was employed to examine the sufficiency of the cumulative sample size. Finally, we assessed the importance of gene loci in osteoporosis based on whether there were enough sample sizes and the heterogeneity of the literature with the I2 value. RESULTS: After excluding 169 irrelevant publications, 39 meta-analysis papers were obtained. Among Caucasians, in 17 gene loci, there were eight gene loci (e.g., vitamin D Receptor ApaI rs7975232) with sufficient cumulative sample size to confirm that they were unrelated to the disease. Among Asians, in 15 gene loci, four gene loci that had sufficient sample sizes were risk factors: VDR FokI rs2228570 (odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.22-1.70), TGF ß1 rs1800470 (OR = 1.35, 95% CI = 1.10-1.65), IGF1 rs2288377 (OR = 1.44, 95% CI = 1.28-1.62), and IGF1 rs35767 (OR = 1.20, 95% CI = 1.06-1.36), respectively, whereas one gene locus, ESR2 RsaI rs1256049 (OR = 0.69, 95% CI = 0.59-0.81), was a protective factor. CONCLUSIONS: The DGS successfully identified five gene loci in osteoporosis that will apply to other diseases to find causal genes, which may contribute to further genetic therapy.

A Simple Algorithm Using Ventilator Parameters to Predict Successfully Rapid Weaning Program in Cardiac Intensive Care Unit Patients.

BACKGROUND: Ventilator weaning is one of the most significant challenges in the intensive care unit (ICU). Approximately 30% of patients fail to wean, resulting in prolonged use of ventilators and increased mortality. There are numerous high-performance prediction models available today, but they require a large number of parameters to predict and are thus impractical in clinical practice. OBJECTIVES: This study aims to create an artificial intelligence (AI) model for predicting weaning time and to identify the most simplified key predictors that will allow the model to achieve adequate accuracy with as few parameters as possible. METHODS: This is a retrospective study of to-be-weaned patients (n = 1439) hospitalized in the cardiac ICU of Cheng Hsin General Hospital's Department of Cardiac Surgery from November 2018 to August 2020. The patients were divided into two groups based on whether they could be weaned within 24 h (i.e., "patients weaned within 24 h" (n = 1042) and "patients not weaned within 24 h" (n = 397)). Twenty-eight variables were collected including demographic characteristics, arterial blood gas readings, and ventilation set parameters. We created a prediction model using logistic regression and compared it to other machine learning techniques such as decision tree, random forest, support vector machine (SVM), extreme gradient boosting, and artificial neural network. Forward, backward, and stepwise selection methods were used to identify significant variables, and the receiver operating characteristic curve was used to assess the accuracy of each AI model. RESULTS: The SVM [receiver operating characteristic curve (ROC-AUC) = 88%], logistic regression (ROC-AUC = 86%), and XGBoost (ROC-AUC = 85%) models outperformed the other five machine learning models in predicting weaning time. The accuracies in predicting patient weaning within 24 h using seven variables (i.e., expiratory minute ventilation, expiratory tidal volume, ventilation rate set, heart rate, peak pressure, pH, and age) were close to those using 28 variables. CONCLUSIONS: The model developed in this research successfully predicted the weaning success of ICU patients using a few and easily accessible parameters such as age. Therefore, it can be used in clinical practice to identify difficult-to-wean patients to improve their treatment.

The Effect of PPARγ rs1801282 Variant on Mortality Risk Among Asians With Chronic Kidney Disease: A Cohort Study and Meta-Analysis.

Background: Chronic kidney disease (CKD) is a public health issue, and an independent risk factor for cardiovascular disease. The peroxisome proliferator-activated receptor gamma (PPARG) plays an important role in the cardiovascular system. Previous studies have examined one important exon polymorphism, Pro12Ala, in PPARG with respect to mortality of CKD patients, but the results were inconsistent and current evidence is insufficient to support a strong conclusion. This study aimed to examine the correlation between Pro12Ala gene polymorphism and mortality among Asians with CKD by trial sequential analysis (TSA). Methods: The research was divided into observational research and meta-analysis. For the cohort study, 767 subjects from dialysis centers in Taipei were selected as samples, and tracked from December 2015 to February 2017. For the meta-analysis, relevant literature from "PubMed" and "Embase" databases (until December 2016), was searched and TSA was used to verify the results. In order to achieve the best evidence hierarchies, our retrospective cohort study was added to the meta-analysis and the TSA. Results: The combined sample size for Asian was 1,685 after adding our cohort study, and there was no significant correlation between PPARG Pro12Ala and mortality by the allele model (RR: 0.85, 95% CI: 0.39-1.83, I2 = 79.3%). Under the parameter setting with the RR value of 1.5, TSA estimation presented that the cumulative sample size entered into the futility area, and it confirmed the conclusion in this study. Conclusion: We found that PPARG Pro12Ala gene polymorphism was not related to mortality in CKD Asians patients, and validated our conclusion using TSA after adding our sample.

Novel and Efficient Quantitative Posterior-Circulation-Structure-Based Scale via Noncontrast CT to Predict Ischemic Stroke Prognosis: A Retrospective Study.

(1) Background: Posterior circulation ischemic stroke has high mortality and disability rates and requires an early prediction prognosis to provide the basis for an interventional approach. Current quantitative measures are only able to accurately assess the prognosis of patients using magnetic resonance imaging (MRI). However, it is difficult to obtain MRI images in critically urgent cases. Therefore, the development of a noncontrast CT-based rapid-assist tool is needed to enhance the value of the clinical application. (2) Objective: This study aimed to develop an auxiliary-annotating noncontrast CT-efficient tool, which is based on a deep learning model, to provide a quantitative scale and the prognosis of posterior circulation ischemic stroke patients. (3) Methods: A total of 31 patients with posterior circulation ischemic stroke, diagnosed in the stroke registry at the Tri-Service General Hospital from November 2019 to July 2020, were included in the study, with a total of 578 CT images collected from noncontrast CT and MRI that were ≤ 3 days apart. A 5-fold cross validation was used to develop an image segmentation model to identify nine posterior circulation structures, and intersection over union (IoU) was used to assess the ability of the model to identify each structure. A quantitative score was integrated to assess the importance of the proportion of ischemic lesions in each posterior circulation structure, and the ROC curve was compared with the semiquantitative score for prognostic power. The prognoses of the patients were defined into two groups of 18 patients. An mRS score of 0-2 at discharge was defined as a good prognosis, while an mRS score of 3-6 was deemed to be a poor prognosis. (4) Results: The performance of the image segmentation model for identifying the nine posterior circulation structures in noncontrast CT images was evaluated. The IoU of the left cerebellum was 0.78, the IoU of the right cerebellum was 0.79, the IoU of the left occipital lobe was 0.74, the IoU of the right occipital lobe was 0.68, the IoU of the left thalamus was 0.73, the IoU of the right thalamus was 0.75, the IoU of the medulla oblongata was 0.82, and the IoU of the midbrain was 0.83. The prognostic AUC of posterior circulation patients predicted using a quantitative integrated score was 0.74, which was significantly higher than that of the pc-ASPECTS (AUC = 0.63, p = 0.035), with a sensitivity of 0.67 and a specificity of 0.72. (5) Conclusions: In this study, a deep learning model was used to develop a noncontrast CT-based quantitative integrated score tool, which is an effective tool for clinicians to assess the prognosis of posterior circulation ischemic stroke.

The Polymorphism at PLCB4 Promoter (rs6086746) Changes the Binding Affinity of RUNX2 and Affects Osteoporosis Susceptibility: An Analysis of Bioinformatics-Based Case-Control Study and Functional Validation.

Purpose: Genome-wide association studies have identified numerous genetic variants that are associated with osteoporosis risk; however, most of them are present in the non-coding regions of the genome and the functional mechanisms are unknown. In this study, we aimed to investigate the potential variation in runt domain transcription factor 2 (RUNX2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding variants within RUNX2 binding sites and risk of osteoporosis in postmenopausal osteoporosis (PMOP). Methods: We performed bioinformatics-based prediction by combining whole genome sequencing and chromatin immunoprecipitation sequencing to screen functional SNPs in the RUNX2 binding site using data from the database of Taiwan Biobank; Case-control studies with 651 postmenopausal women comprising 107 osteoporosis patients, 290 osteopenia patients, and 254 controls at Tri-Service General Hospital between 2015 and 2019 were included. The subjects were examined for bone mass density and classified into normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Furthermore, mRNA expression and luciferase reporter assay were used to provide additional evidence regarding the associations identified in the association analyses. Chi-square tests and logistic regression were mainly used for statistical assessment. Results: Through candidate gene approaches, 3 SNPs in the RUNX2 binding site were selected. A novel SNP rs6086746 in the PLCB4 promoter was identified to be associated with osteoporosis in Chinese populations. Patients with AA allele had higher risk of osteoporosis than those with GG+AG (adjusted OR = 6.89; 95% confidence intervals: 2.23-21.31, p = 0.001). Moreover, the AA genotype exhibited lower bone mass density (p < 0.05). Regarding mRNA expression, there were large differences in the correlation between PLCB4 and different RUNX2 alleles (Cohen's q = 0.91). Functionally, the rs6086746 A allele reduces the RUNX2 binding affinity, thus enhancing the suppression of PLCB4 expression (p < 0.05). Conclusions: Our results provide further evidence to support the important role of the SNP rs6086746 in the etiology of osteopenia/osteoporosis, thereby enhancing the current understanding of the susceptibility to osteoporosis. We further studied the mechanism underlying osteoporosis regulation by PLCB4.

The Decisive Case-Control Study Elaborates the Null Association between ADAMTS5 rs226794 and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis.

BACKGROUND: Osteoarthritis is an important health issue for the elderly. Many studies indicate that genetics is an important risk factor for osteoarthritis, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is one gene that is most frequently implicated. Many recent studies have examined the relationship between a polymorphism in the ADAMTS5 gene (rs226794) and the risk for developing osteoarthritis without definitive results. OBJECTIVE: In this case-control study, we examined the correlation between the ADAMTS5 gene polymorphism, rs226794, and knee osteoarthritis. We used a meta-analysis and trial sequential analysis to determine whether ADAMTS5 rs226794 expression increases susceptibility to osteoarthritis. METHODS: This study consisted of two parts: a case-control study and a meta-analysis. The case-control study included subjects who underwent knee radiography at the Health Examination Center of the Tri Service General Hospital from 2015 to 2019. The Kellgren-Lawrence (KL) grading system was used as diagnostic criteria. Patients with unsuccessful gene sequencing were excluded. There were 606 subjects in the knee osteoarthritis group (KL ≥ 2) and 564 in the control group (KL < 2). Gene sequencing was performed using iPLEX Gold to determine the association between the gene polymorphism of ADAMTS5 rs226794 and knee osteoarthritis. For the meta-analysis, databases such as PubMed, Embase, and Cochrane were queried to identify studies that examined the relationship between ADAMTS5 rs226794 and osteoarthritis. Next, the findings of the meta-analysis were incorporated with the results of the case-control study and samples from the published studies to estimate the association between the genetic polymorphism and osteoarthritis using an odds ratio and a 95% confidence interval. RESULTS: We found a non-significant association between the G allele and knee OA (crude-OR: 0.93 (95% CI: 0.79-1.10) and adjusted-OR: 1.02 (95% CI: 0.76-1.36) in the allele model) in the present study, and the analysis of other genetic models revealed a similar trend. After including five published studies and our case-control study, the results with 2866 Asians indicated a conclusively null association between ADAMTS5 rs226794 and knee OA) OR: 1.09 (95% CI: 0.93-1.26). The results for Caucasians also revealed a null association (OR: 1.21 (95% CI: 0.81-1.82)). CONCLUSIONS: This study indicates that the gene polymorphism, ADAMTS5 rs226794, is not significantly associated with knee osteoarthritis. Additionally, assuming that the cumulative sample size in the allele model is sufficient, we confirmed that the G allele is not a risk factor for osteoarthritis. This study integrated all available evidence to arrive at this conclusion, and it suggests that no additional studies are necessary.

Genetic association between TNF-α G-308A and osteoarthritis in Asians: A case-control study and meta-analysis.

BACKGROUND: Osteoarthritis (OA) is an important health issue in elderly people. Many studies have suggested that genetic factors are important risk factors for OA, of which tumor necrosis factor-α (TNF-α) is one of the most examined genes. Moreover, several studies have investigated the relationship between TNF-α G-308A polymorphisms and OA risk, but consistent results have not been obtained. OBJECTIVE: This study examines the association between TNF-α G-308A polymorphisms and knee OA. Moreover, meta-analysis and trial sequential analysis (TSA) was used to determine whether this is a susceptibility gene for knee OA. METHODS: Between 2015 and 2019, 591 knee OA cases and 536 healthy controls were recruited. The Kellgren-Lawrence grading system was used to identify the knee OA cases. A meta-analysis was conducted including related studies published until 2020 from PubMed, Embase, and previous meta-analysis to improve the evidence level of the current study. The results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) to evaluate the effect of this polymorphism on knee OA risk. The TSA was used to estimate the sample sizes required in this issue. RESULTS: A nonsignificant association was found between the AA genotype and knee OA [adjusted OR, 0.84; 95% CI, 0.62-1.15) in the recessive model] in the present case-control study, and analysis of other genetic models showed a similar trend. After adding the critical case-control samples for Asians, the TNF-α G-308A, AA genotype exhibited 2.57 times more risk of developing arthritis when compared with the GG + GA genotype (95% CI, 1.56-4.23), and the cumulative samples for TSA (n = 2182) were sufficient to obtain a definite conclusion. CONCLUSIONS: The results of this meta-analysis revealed that the TNF-α G-308A, AA genotype is a susceptible genotype for OA in the Asian population. This study integrated all current evidence to arrive at this conclusion, suggesting that future studies on Asians are not required.

Prognostic Analysis of Patients with Acute Myocardial Infarction Undergoing Implantation of Different Stents for the First Time.

For patients with acute myocardial infarction scheduled to undergo percutaneous coronary stent implantation, in most cases a drug-eluting stent is recommended as the first choice for treatment. However, there is a lack of research on the effectiveness of bare-metal stents and drug-eluting stents on patients with different types of myocardial infarction. Our objective was to explore the effects of bare-metal stents and drug-eluting stents on patients with different types of myocardial infarction in terms of major cardiovascular incidents. This retrospective cohort study included 934 patients with myocardial infarction undergoing coronary artery stent implantation for the first time at the cardiac catheter room of the Tri-Service General Hospital in the Neihu District between 2014 and 2018. Patients' information, including demographic data, laboratory data, cardiac echocardiography results, and angiocardiography results, was collected by reviewing medical records. Cox proportional hazards regression was used to adjust the potential confounding factors, and the adjusted data were then used to compare the correlation between different types of stents and major cardiovascular incidents in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction. After the confounding factors were adjusted, in patients with ST-elevation myocardial infarction receiving a drug-eluting stent compared with those receiving a bare-metal stent, it was found that the mortality risk was lower in terms of all causes of death (Adj-HR = 0.26, 95% CI = 0.14-0.48, p < 0.001) and cardiogenic death (Adj-HR = 0.20, 95% CI = 0.08-0.55, p = 0.002), the risk of non-fatal myocardial infarction was lower (Adj-HR = 0.17, 95% CI = 0.04-0.73, p = 0.017), and there was no difference in the risk of revascularization at the lesion site (Adj-HR = 0.59, 95% CI = 0.24-1.43, p = 0.243). It terms of the findings in patients with non-ST-elevation myocardial infarction, those receiving a drug-eluting stent had a lower risk of revascularization at the lesion site (Adj-HR = 0.48, 95% CI = 0.24-0.97, p = 0.04); however, there was no difference in the mortality risk in terms of all causes of death (Adj-HR = 0.71, 95% CI = 0.37-1.35, p = 0.296) or cardiogenic death (Adj-HR = 0.59, 95% CI = 0.18-1.90, p = 0.379),or in the risk of non-fatal myocardial infarction (Adj-HR = 0.27, 95% CI = 0.06-1.25, p = 0.093). Compared with bare-metal stents, drug-eluting stents provide better protection against death to receivers with ST-elevation myocardial infarction; however, this protection is decreased in receivers with non-ST-elevation myocardial infarction. It is recommended that for patients with non-ST-elevation myocardial infarction who are indicated to receive a drug-eluting stent, the clinical effectiveness of the treatment must be considered.

Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis.

BACKGROUND: Several meta-analyses of the relationship between endothelial nitric oxide synthase (eNOS) T-786C gene polymorphism and chronic kidney disease (CKD) have been published. However, the results of these studies were inconsistent, and it is undetermined whether sample sizes are sufficient to reach a definite conclusion. OBJECTIVE: To elucidate the relationship between T-786C and CKD by combining previous studies with our case-control sample and incorporate trial sequential analysis (TSA) to verify whether the sample size is adequate to draw a definite conclusion. METHODS: PubMed and Embase databases were searched for relevant articles on eNOS T-786C and CKD before February 28, 2021. TSA was also incorporated to ascertain a conclusion. A total of 558 hemodialysis cases in the case-control study was recruited from nine dialysis centers in the northern area of Taiwan in 2020. Additionally, 640 healthy subjects of the control group, with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2, were selected from participants of the annual elderly health examination program at the Tri-Service General Hospital. The functional analysis was based on eQTL data from GTExPortal. RESULTS: After screening with eligibility criteria, 15 papers were included and eventually combined in a meta-analysis. The result of the TSA showed that the sample size for Caucasians was adequate to ascertain the correlation between eNOS T-786C and CKD but was insufficient for Asians. Therefore, we added our case-control samples (n = 1198), though not associated with CKD (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.69-1.46), into a meta-analysis, which supported that eNOS T-786C was significantly associated with CKD in Asians (OR = 1.39, 95% CI = 1.04-1.85) by using an adequate cumulative sample size (n = 4572) analyzed by TSA. Data of eQTL from GTEx showed that T-786C with the C minor allele exhibited relatively lower eNOS mRNA expression in whole blood, indicating the hazardous role of eNOS T-786C in CKD. CONCLUSIONS: eNOS T-786C genetic polymorphism was of conclusive significance in the association with CKD among Asians in our meta-analysis. Our case-control samples play a decisive role in changing conclusions from indefinite to definite.

The Decisive Case-Control Study Elaborates the Null Association between ESR1 XbaI and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis.

(1) Background: The prevalence of knee osteoarthritis (OA) in women is significantly higher than in men. The estrogen receptor α (ERα) has been considered to play a key role due to a large gender difference in its expression. ERα is encoded by the gene estrogen receptor 1 (ESR1), which is widely studied to explore the gender difference in knee OA. Several polymorphisms in ESR1 [PvuII (rs2234693) and BtgI (rs2228480)] were confirmed as the risk factors of OA. However, the evidence of the last widely investigated polymorphism, ESR1 Xbal (rs9340799), is still insufficient for concluding its effect on knee OA. (2) Objective: This study proposed a case-control study to investigate the association between ESR1 Xbal and knee OA. Moreover, a meta-analysis and trial sequential analysis (TSA) were conducted to enlarge the sample size for obtaining a conclusive evidence. (3) Methods: In total, 497 knee OA cases and 473 healthy controls were recruited between March 2015 and July 2018. The Kellgren-Lawrence grading system was used to identify the knee OA cases. To improve the evidence level of our study, we conducted a meta-analysis including the related studies published up until December 2018 from PubMed, Embase, and previous meta-analysis. The results are expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for evaluating the effect of this polymorphism on knee OA risk. TSA was used to estimate the sample sizes required in this issue. (4) Results: We found non-significant association between the G allele and knee OA [Crude-OR: 0.97 (95% CI: 0.78-1.20) and adjusted-OR: 0.90 (95% CI: 0.71-1.15) in allele model] in the present case-control study, and the analysis of other genetic models showed a similar trend. After including six published studies and our case-control studies, the current evidence with 3174 Asians showed the conclusively null association between ESR1 XbaI and knee OA [OR: 0.78 (95% CI: 0.59-1.04)] with a high heterogeneity (I2: 78%). The result of Caucasians also concluded the null association [OR: 1.05 (95% CI: 0.56-1.95), I2: 87%]. (5) Conclusions: The association between ESR1 XbaI and knee OA was not similar with other polymorphisms in ESR1, which is not a causal relationship. This study integrated all current evidence to elaborate this conclusion for suggesting no necessity of future studies.

Polymorphism of rs6426749 at 1p36.12 is associated with the risk of osteoarthritis in Taiwanese female population.

BACKGROUND: Osteoarthritis (OA) is a multifactorial disease that is associated with several genetic factors. TFAP2A with a motif of C allele at rs6426749 demonstrates a higher binding ability, thereby increasing CDC42 expression, potentially affecting OA occurrence. In this study, we evaluated the role of rs6426749 polymorphisms on knee OA in a female Taiwanese population. METHODS: We performed a case-control study of 368 OA cases and 379 controls between March 2017 and October 2018. Knee OA was defined using the Kellgren-Lawrence grading system, and genotypes were determined using the Sequenom MassArray iPLEX Gold assay. Stratified sex and body mass index (BMI) analyses were performed using logistic regression to explore interactions between genes and the environment. We also used expression quantitative trait loci data from the genotype-tissue expression project to conduct functional analyses. RESULTS: The C allele of rs6426749 was associated with the risk of knee OA (odds ratio [OR] = 1.31, 95% confidence interval [CI], 1.01-1.71; p = 0.042), after adjusting for gender, age, and BMI. In addition, subgroup analyses indicated that females expressing C alleles showed an increased risk for knee OA (OR = 1.56; 95% CI, 1.12-2.18; p = 0.009). Females with a normal BMI and the C allele had the highest OA risk (OR = 1.73; 95% CI, 1.08-2.76; p = 0.022). CONCLUSION: Our findings indicated that rs6426749 may be related to OA susceptibility in the Taiwanese population. This was particularly true for women with normal BMI.

Decisive evidence corroborates a null relationship between MTHFR C677T and chronic kidney disease: A case-control study and a meta-analysis.

BACKGROUND: Previous meta-analyses have explored the association between the C677T polymorphism of methyltetrahydrofolate reductase (MTHFR) and chronic kidney disease (CKD) but there were no studies with a decisive conclusion. Furthermore, the high heterogeneity among different populations is not yet interpreted. OBJECTIVES: This study used trial sequential analysis (TSA) to evaluate whether the nowadays conclusion supported by current cumulative samples. We also applied case-weighted meta-regression to explore the potential gene-environment interactions. METHODS: For the first stage of this study we conducted a case-control study involving 847 dialysis patients from 7 hemodialysis centers in Taipei during 2015 to 2018 and 755 normal controls from a health center in the Tri-Service General Hospital. The second stage combined the results from the first stage with previous studies. The previous studies were collected from PubMed, EMBASE, and Web of Science databases before January 2018. RESULTS: From the case-control study, the T allele of MTHFR C677T appeared to have a protective effect on end-stage renal disease compared with the C allele [odds ratio (OR): 0.80, 95% CI (confidence interval) = 0.69-0.93]. However, the meta-analysis contradicted the results in Asian (OR = 1.12, 95% CI = 0.96-1.30). The same analysis was also applied in Caucasian and presented similar results from Asian (OR = 1.18, 95% CI = 0.98-1.42). The TSA showed our case-control study to be the decisive sample leading to a null association among Asian population. The high heterogeneity (I = 75%) could explain the contradictory results between the case-control study and the meta-analysis. However, further case-weighted meta-regression did not find any significant interaction between measured factors and MTHFR C677T on CKD. CONCLUSIONS: High heterogeneities were found in both Caucasian and Asian, which caused the null relationship in meta-analysis while there were significant effects in individual studies. Future studies should further explore the high heterogeneity that might be hidden in unmeasured gene-environment interactions, to explain the diverse findings among different populations.

PPARG Pro12Ala Polymorphism with CKD in Asians: A Meta-Analysis Combined with a Case-Control Study-A Key for Reaching Null Association.

BACKGROUND: So far, numerous meta-analyses have been published regarding the correlation between peroxisome proliferator-activated receptor gamma (PPARG) proline 12 alanine (Pro12Ala) gene polymorphism and chronic kidney disease (CKD); however, the results appear to be contradictory. Hence, this study is formulated with the objective of using existing meta-analysis data together with our research population to study the correlation between PPARG Pro12Ala gene polymorphism and CKD and evaluate whether an accurate result can be obtained. METHODS: First, literature related to CKD and PPARG Pro12Ala available on the PubMed and EMBASE databases up to December 2016 was gathered from 20 publications. Then, the gathered results were combined with our case-control study of 1693 enrolled subjects and a trial sequential analysis (TSA) was performed to verify existing evidence and determine whether a firm conclusion can be drawn. RESULTS: The TSA results showed that the cumulative sample size for the Asian sample was 6078 and was sufficient to support a definite result. The results of this study confirmed that there is no obvious correlation between PPARG Pro12Ala and CKD for Asians (OR = 0.82 (95% CI = 0.66-1.02), I2 = 63.1%), but this was not confirmed for Caucasians. Furthermore, the case-control sample in our study was shown to be the key for reaching this conclusion. CONCLUSIONS: The meta-analysis results of this study suggest no significant correlation between PPARG Pro12Ala gene polymorphism and CKD for Asians after adding our samples, but not for Caucasian.

Author Correction: Angiotensin-converting enzyme inhibitors or angiotensin receptor blocker monotherapy retard deterioration of renal function in Taiwanese chronic kidney disease population.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: Relationship between body mass index and renal function deterioration among the Taiwanese chronic kidney disease population.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Accuracy augmentation of body composition measurement by bioelectrical impedance analyzer in elderly population.

Bioelectrical impedance analysis (BIA) is currently the most commonly used method in clinical practice to measure body composition. However, the bioelectrical impedance analyzer is not designed according to different countries, races, and elderly populations. Because different races may have different body compositions, a prediction model for the elderly population in Taiwan should be developed to avoid population bias, thereby improving the accuracy of community evaluation surveys.Dual energy X-ray absorptiometry (DXA) was used as a standard method for comparison, and impedance analysis was used for the development of a highly accurate predictive model that is suitable for assessing the body composition of elderly people.This study employed a cross-sectional design and recruited 438 elderly people who were undergoing health examinations at the health management center in the Tri-Service General Hospital as study subjects. Basic demographic variables and impedance analysis values were used in four predictive models, namely, linear regression, random forest, support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost) models, to predict DXA body composition. The data from 354 study subjects were used to develop the predictive model, while the data from 84 study subjects were used to validate the accuracy of the predictive model.The body composition of elderly people as estimated by InBody 720 was highly correlated with that estimated by DXA. The correlation coefficient between InBody 720 and DXA for muscle mass was 0.969, and that for fat mass was 0.935. Consistency analysis results showed that InBody 720 tends to underestimate muscle mass and fat mass. A comparison of the accuracy of the linear regression, random forest, SVM, and XGBoost models showed that the linear regression has the highest accuracy. The correlation coefficient between the new model and DXA for muscle mass and fat mass were 0.977 and 0.978, respectively.The new predictive model can be used to monitor the nutrition status of elderly people and identify people with sarcopenia in the community.