rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology

Thymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3′ gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97–1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03–1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 × 10−28), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small.

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Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis

Infection and Immunity ◽

10.1128/iai.00882-19 ◽

2020 ◽

Vol 88 (4) ◽

Cited By ~ 1

Author(s):

C. B. Lupiañez ◽

M. Martínez-Bueno ◽

J. M. Sánchez-Maldonado ◽

J. Badiola ◽

C. Cunha ◽

...

Keyword(s):

Invasive Aspergillosis ◽

Meta Analysis ◽

Additive Model ◽

Population Based ◽

Nucleotide Polymorphisms ◽

Hematological Patients ◽

Number Of Patients ◽

Increased Risk ◽

Life Threatening ◽

Trait Locus

ABSTRACT Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10−5, PMeta = 1.5 · 10−4, and PMeta =7.9 · 10−5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AGCGG with an increased risk of IA (P = 4.0 · 10−4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10−7) and primary monocytes (P = 4.31 · 10−7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.

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Comparative Efficacy and Safety of Duration of Dual Antiplatelet Therapy in Patients with CAD Undergoing Drug-eluting Stent Implantation: A Systematic Review and Network Meta-analysis

Current Pharmaceutical Design ◽

10.2174/1381612826666200625110349 ◽

2020 ◽

Vol 26 (44) ◽

pp. 5739-5745

Author(s):

Jieqiong Guan ◽

Wenjing Song ◽

Pan He ◽

Siyu Fan ◽

Hong Zhi ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Major Bleeding ◽

Dual Antiplatelet Therapy ◽

Meta Analysis ◽

Cochrane Library ◽

Drug Eluting Stent ◽

Efficacy And Safety ◽

Risk Of Bleeding ◽

Increased Risk ◽

Drug Eluting

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.

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The GSTM1 and GSTT1 Null Genotypes Increase the Risk for Type 2 Diabetes Mellitus and the Subsequent Development of Diabetic Complications: A Meta-analysis

Current Diabetes Reviews ◽

10.2174/1573399814666171215120228 ◽

2018 ◽

Vol 15 (1) ◽

pp. 31-43 ◽

Cited By ~ 6

Author(s):

Sayantan Nath ◽

Sambuddha Das ◽

Aditi Bhowmik ◽

Sankar Kumar Ghosh ◽

Yashmin Choudhury

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Meta Analysis ◽

Subsequent Development ◽

Asian Population ◽

Gstm1 Null Genotype ◽

Increased Risk

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.

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ctDNA as a prognostic factor in operable colon cancer patients: a systematic review and meta-analysis

Future Oncology ◽

10.2217/fon-2020-0671 ◽

2020 ◽

Author(s):

Emre Yekedüz ◽

Elif Berna Köksoy ◽

Hakan Akbulut ◽

Yüksel Ürün ◽

Güngör Utkan

Keyword(s):

Colon Cancer ◽

Prognostic Factor ◽

Cancer Patients ◽

Meta Analysis ◽

Circulating Tumor Dna ◽

Random Effects Model ◽

Inverse Variance ◽

Increased Risk ◽

Significant Step ◽

Tumor Dna

Aim: Using circulating tumor DNA (ctDNA) instead of historical clinicopathological factors to select patients for adjuvant chemotherapy (ACT) may reduce inappropriate therapy. Material & methods: MEDLINE was searched on March 31, 2020. Studies, including data related to the prognostic value of ctDNA in the colon cancer patients after surgery and after ACT, were included. The generic inverse-variance method with a random-effects model was used for meta-analysis. Results: Four studies were included for this meta-analysis. ctDNA-positive colon cancer patients after surgery and ACT had a significantly increased risk of recurrence compared with ctDNA-negative patients. Conclusions: ctDNA is an independent prognostic factor, and this meta-analysis is a significant step for using ctDNA instead of historical prognostic factors in the adjuvant setting.

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Psychological interventions as an alternative and add-on to antidepressant medication to prevent depressive relapse: systematic review and meta-analysis

The British Journal of Psychiatry ◽

10.1192/bjp.2020.198 ◽

2020 ◽

pp. 1-8

Author(s):

Josefien Johanna Froukje Breedvelt ◽

Maria Elisabeth Brouwer ◽

Mathias Harrer ◽

Maria Semkovska ◽

David Daniel Ebert ◽

...

Keyword(s):

Psychological Intervention ◽

Meta Analysis ◽

Antidepressant Medication ◽

Cochrane Library ◽

Psychological Interventions ◽

Relapse Risk ◽

Increased Risk ◽

Antidepressant Use ◽

Randomised Controlled ◽

Risk Of Relapse

Background After remission, antidepressants are often taken long term to prevent depressive relapse or recurrence. Whether psychological interventions can be a viable alternative or addition to antidepressants remains unclear. Aims To compare the effectiveness of psychological interventions as an alternative (including delivered when tapering antidepressants) or addition to antidepressants alone for preventing depressive relapse. Method Embase, PubMed, the Cochrane Library and PsycINFO were searched from inception until 13 October 2019. Randomised controlled trials (RCTs) with previously depressed patients in (partial) remission where preventive psychological interventions with or without antidepressants (including tapering) were compared with antidepressant control were included. Data were extracted independently from published trials. A random-effects meta-analysis on time to relapse (hazard ratio, HR) and risk of relapse (risk ratio, RR) at the last point of follow-up was conducted. PROSPERO ID: CRD42017055301. Results Among 11 included trials (n = 1559), we did not observe an increased risk of relapse for participants receiving a psychological intervention while tapering antidepressants versus antidepressants alone (RR = 1.02, 95% CI 0.84–1.25; P = 0.85). Psychological interventions added to antidepressants significantly reduced the risk of relapse (RR = 0.85, 95% CI 0.74–0.97; P = 0.01) compared with antidepressants alone. Conclusions This study found no evidence to suggest that adding a psychological intervention to tapering increases the risk of relapse when compared with antidepressants alone. Adding a psychological intervention to antidepressant use reduces relapse risk significantly versus antidepressants alone. As neither strategy is routinely implemented these findings are relevant for patients, clinicians and guideline developers.

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Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome

Clinical Epigenetics ◽

10.1186/s13148-021-01004-w ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Pinpin Long ◽

Qiuhong Wang ◽

Yizhi Zhang ◽

Xiaoyan Zhu ◽

Kuai Yu ◽

...

Keyword(s):

Dna Methylation ◽

Acute Coronary Syndrome ◽

Methylation Level ◽

Meta Analysis ◽

Regulation Of Gene Expression ◽

Density Lipoprotein ◽

Blood Leukocytes ◽

Coronary Syndrome ◽

A Genome ◽

Increased Risk

Abstract Background Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. Methods We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. Results We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02–1.48; P = 0.03). Conclusions We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

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EXPRESS: Stroke risk following traumatic brain injury: systematic review and meta-analysis

International Journal of Stroke ◽

10.1177/17474930211004277 ◽

2021 ◽

pp. 174749302110042

Author(s):

Grace Mary Turner ◽

Christel McMullan ◽

Olalekan Lee Aiyegbusi ◽

Danai Bem ◽

Tom Marshall ◽

...

Keyword(s):

Systematic Review ◽

Stroke Risk ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Cochrane Library ◽

Control Group ◽

Large Sample Size ◽

Hazard Ratios ◽

Increased Risk ◽

The Cochrane Library

Aims To investigate the association between TBI and stroke risk. Summary of review We undertook a systematic review of MEDLINE, EMBASE, CINAHL, and The Cochrane Library from inception to 4th December 2020. We used random-effects meta-analysis to pool hazard ratios (HR) for studies which reported stroke risk post-TBI compared to controls. Searches identified 10,501 records; 58 full texts were assessed for eligibility and 18 met the inclusion criteria. The review included a large sample size of 2,606,379 participants from four countries. Six studies included a non-TBI control group, all found TBI patients had significantly increased risk of stroke compared to controls (pooled HR 1.86; 95% CI 1.46-2.37). Findings suggest stroke risk may be highest in the first four months post-TBI, but remains significant up to five years post-TBI. TBI appears to be associated with increased stroke risk regardless of severity or subtype of TBI. There was some evidence to suggest an association between reduced stroke risk post-TBI and Vitamin K antagonists and statins, but increased stroke risk with certain classes of antidepressants. Conclusion TBI is an independent risk factor for stroke, regardless of TBI severity or type. Post-TBI review and management of risk factors for stroke may be warranted.

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Exploring the Relationship between Biologics and Postoperative Surgical Morbidity in Ulcerative Colitis: A Review

Journal of Clinical Medicine ◽

10.3390/jcm10040710 ◽

2021 ◽

Vol 10 (4) ◽

pp. 710

Author(s):

Abel Botelho Quaresma ◽

Fernanda da Silva Barbosa Baraúna ◽

Fábio Vieira Teixeira ◽

Rogério Saad-Hossne ◽

Paulo Gustavo Kotze

Keyword(s):

Ulcerative Colitis ◽

Postoperative Complications ◽

Meta Analysis ◽

Qualitative Evaluation ◽

Complication Rates ◽

Surgical Morbidity ◽

Randomized Studies ◽

Pubmed Database ◽

Increased Risk ◽

The Impact

Background: With the paradigm shift related to the overspread use of biological agents in the treatment of inflammatory bowel diseases (IBD), several questions emerged from the surgical perspective. Whether the use of biologicals would be associated with higher rates of postoperative complications in ulcerative colitis (UC) patients still remains controversial. Aims: We aimed to analyze the literature, searching for studies that correlated postoperative complications and preoperative exposure to biologics in UC patients, and synthesize these data qualitatively in order to check the possible impact of biologics on postoperative surgical morbidity in this population. Methods: Included studies were identified by electronic search in the PUBMED database according to the PRISMA (Preferred Items of Reports for Systematic Reviews and Meta-Analysis) guidelines. The quality and bias assessments were performed by MINORS (methodological index for non-randomized studies) criteria for non-randomized studies. Results: 608 studies were initially identified, 22 of which were selected for qualitative evaluation. From those, 19 studies (17 retrospective and two prospective) included preoperative anti-TNF. Seven described an increased risk of postoperative complications, and 12 showed no significant increase postoperative morbidity. Only three studies included surgical UC patients with previous use of vedolizumab, two retrospective and one prospective, all with no significant correlation between the drug and an increase in postoperative complication rates. Conclusions: Despite conflicting results, most studies have not shown increased complication rates after abdominal surgical procedures in patients with UC with preoperative exposure to biologics. Further prospective studies are needed to better establish the impact of preoperative biologics and surgical complications in UC.

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Endometriosis and Risk of Adverse Pregnancy Outcome: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10040667 ◽

2021 ◽

Vol 10 (4) ◽

pp. 667

Author(s):

Kjerstine Breintoft ◽

Regitze Pinnerup ◽

Tine Brink Henriksen ◽

Dorte Rytter ◽

Niels Uldbjerg ◽

...

Keyword(s):

Preterm Birth ◽

Cesarean Section ◽

Placental Abruption ◽

Gestational Hypertension ◽

Adverse Pregnancy Outcome ◽

Placenta Previa ◽

Meta Analysis ◽

Increased Risk ◽

Spontaneous Hemoperitoneum ◽

In Pregnancy

Background: This systematic review and meta-analysis summarizes the evidence for the association between endometriosis and adverse pregnancy outcome, including gestational hypertension, pre-eclampsia, low birth weight, and small for gestational age, preterm birth, placenta previa, placental abruption, cesarean section, stillbirth, postpartum hemorrhage, spontaneous hemoperitoneum in pregnancy, and spontaneous bowel perforation in pregnancy. Methods: We performed the literature review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), by searches in PubMed and EMBASE, until 1 November 2020 (PROSPERO ID CRD42020213999). We included peer-reviewed observational cohort studies and case-control studies and scored them according to the Newcastle–Ottawa Scale, to assess the risk of bias and confounding. Results: 39 studies were included. Women with endometriosis had an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth, compared to women without endometriosis. These results remained unchanged in sub-analyses, including studies on spontaneous pregnancies only. Spontaneous hemoperitoneum in pregnancy and bowel perforation seemed to be associated with endometriosis; however, the studies were few and did not meet the inclusion criteria. Conclusions: The literature shows that endometriosis is associated with an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth.

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Prognostic role of Krebs von den Lungen-6 (KL-6) measurement in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0199 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Elena Aloisio ◽

Federica Braga ◽

Chiara Puricelli ◽

Mauro Panteghini

Keyword(s):

Systematic Review ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Binary Data ◽

Meta Analysis ◽

Mortality Prediction ◽

Asian Populations ◽

Increased Risk ◽

Using Data ◽

Patient Prognosis

Abstract Objectives Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease with limited therapeutic options. The measurement of Krebs von den Lungen-6 (KL-6) glycoprotein has been proposed for evaluating the risk of IPF progression and predicting patient prognosis, but the robustness of available evidence is unclear. Methods We searched Medline and Embase databases for peer-reviewed literature from inception to April 2020. Original articles investigating KL-6 as prognostic marker for IPF were retrieved. Considered outcomes were the risk of developing acute exacerbation (AE) and patient survival. Meta-analysis of selected studies was conducted, and quantitative data were uniformed as odds ratio (OR) or hazard ratio (HR) estimates, with corresponding 95% confidence intervals (CI). Results Twenty-six studies were included in the systematic review and 14 were finally meta-analysed. For AE development, the pooled OR (seven studies) for KL-6 was 2.72 (CI 1.22–6.06; p=0.015). However, a high degree of heterogeneity (I2=85.6%) was found among selected studies. Using data from three studies reporting binary data, a pooled sensitivity of 72% (CI 60–82%) and a specificity of 60% (CI 52–68%) were found for KL-6 measurement in detecting insurgence of AE in IPF patients. Pooled HR (seven studies) for mortality prediction was 1.009 (CI 0.983–1.036; p=0.505). Conclusions Although our meta-analysis suggested that IPF patients with increased KL-6 concentrations had a significant increased risk of developing AE, the detection power of the evaluated biomarker is limited. Furthermore, no relationship between biomarker concentrations and mortality was found. Caution is also needed when extending obtained results to non-Asian populations.

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