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Clinica Chimica Acta

Current research reports and chronological list of recent articles..




The international scientific journal Clinica Chimica Acta publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids, cells or tissues.

The publisher is Elsevier. The copyright and publishing rights of specialized products listed below are in this publishing house. This is also responsible for the content shown.

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Additional research articles see Current Chemistry Research Articles. Magazines with similar content (clinical chemistry):

 - Clinical Biochemistry.

 - Clinical Chemistry and Laboratory Medicine.

 - Clinical Chemistry Online.

 - Clinical Science.

 - Clinical Toxicology.

 - Journal of Medicinal Chemistry.

 - Journal of Laboratory Medicine.



Clinica Chimica Acta - Abstracts



Genetic spectrum of low density lipoprotein receptor gene variations in South Indian population

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): K.N. ArulJothi, B. Suruthi Abirami, Arikketh Devi

Background Low density lipoprotein receptor (LDLR) is a membrane bound receptor maintaining cholesterol homeostasis along with Apolipoprotein B (APOB), Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) and other genes of lipid metabolism. Any pathogenic variation in these genes alters the function of the receptor and leads to Familial Hypercholesterolemia (FH) and other cardiovascular diseases. Objective This study was aimed at screening the LDLR, APOB and PCSK9 genes in Hypercholesterolemic patients to define the genetic spectrum of FH in Indian population. Methods Familial Hypercholesterolemia patients (n=78) of South Indian Tamil population with LDL cholesterol and Total cholesterol levels above 4.9mmol/l and 7.5mmol/l with family history of Myocardial infarction were involved. DNA was isolated by organic extraction method from blood samples and LDLR, APOB and PCSK9 gene exons were amplified using primers that cover exon-intron boundaries. The amplicons were screened using High Resolution Melt (HRM) Analysis and the screened samples were sequenced after purification. Results This study reports 20 variations in South Indian population for the first time. In this set of variations 9 are novel variations which are reported for the first time, 11 were reported in other studies also. The in silico analysis for all the variations detected in this study were done to predict the probabilistic effect in pathogenicity of FH. Conclusion This study adds 9 novel variations and 11 recurrent variations to the spectrum of LDLR gene mutations in Indian population. All these variations are reported for the first time in Indian population. This spectrum of variations was different from the variations of previous Indian reports.






Datum: 22.01.2018


High specificity of spot urinary free metanephrines in diagnosis and prognosis of pheochromocytomas and paragangliomas by HPLC with electrochemical detection

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Ming Zuo, Qianna Zhen, Xiaoqing Zhang, Wenbi Zou, Xiangchun Yang, Gang Tian, Zhenghu Shi, Qifu Li, Min Ding

Background The metanephrines (MNs) in plasma and urine were proposed as biomarkers for the diagnosis of pheochromocytomas and paragangliomas (PPGLs). However, plasma free MNs and 24h urinary fractionated MNs were not satisfactory enough in specificity for the diagnosis of PPGLs. Moreover, the collection of 24h urine was inconvenient. This work examined the diagnostic and prognostic efficiency of free MNs in spot urine for PPGLs. Methods We measured free MNs concentration in spot urine and plasma of 28 PPGLs patients and 155 control subjects by HPLC with electrochemical detection. Postoperative free MNs levels in spot urine and plasma of 14 PPGLs patients were also determined. Creatinine (Cr) concentration was used for the correction of urine volume. Results The specificity of spot urinary free MNs/Cr in the diagnosis of PPGLs was significantly higher than that of plasma free MNs [normetanephrine (NMN), 98.7% (95.4%–99.8%) vs 93.0% (87.4%–96.6%); metanephrine (MN), 93.6% (88.5%–96.9%) vs 84.5% (77.5%–90.0%)]. Meanwhile, the positive likelihood ratios for spot urinary free NMN/Cr and MN/Cr were 69.21 and 13.29, compared with 12.68 and 5.30 for plasma free NMN and MN, respectively. For the PPGLs patients underwent surgery, the plasma free MNs level appeared an abnormal elevation and yielded false-positive results for some patients. Our findings were validated in an independent cohort, resulting in the specificity of 100% for both urinary free NMN/Cr and MN/Cr, and 97.3% and 83.8% for plasma free NMN and MN, respectively. Conclusions Spot urinary free MNs/Cr, superior to plasma free MNs, presented a promising biomarker for the diagnosis and prognosis of PPGLs.






Datum: 22.01.2018


Prognostic role of serum total cholesterol and high-density lipoprotein cholesterol in cancer survivors: A systematic review and meta-analysis

Publication date: February 2018
Source:Clinica Chimica Acta, Volume 477

Author(s): Pingting Zhou, Bo Li, Bin Liu, Tianrui Chen, Jianru Xiao

Background The alterations of lipid profile in cancer has been reported to be associated with cancer development. However, the prognostic value of serum lipid markers level in cancer is currently under debate. Here we performed a meta-analysis to investigate the prognostic significance of serum blood total cholesterol (TC), Triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) for cancer. Methods We systematically searched in PubMed and EMBASE for follow-up studies to evaluate the association between blood TC, TG, HDL-C, LDL-C and overall survival (OS) or disease-free survival (DFS) in patients with cancer. Pooled hazard ratio (HR) and 95% CIs were pooled using the random models. Subgroup and sensitivity analyses were also performed. Results Twenty-six studies including 24655 individuals were identified. For patients with higher TC before diagnosis, the summary HR were 0.82 (95% CI 0.75–0.90) for OS, 0.920 (95% CI, 0.849–0.997) for DFS. Patients with higher HDL-C had a 37% reduced risk of death compared with lower HDL-C (HR 0.63, 95%CI 0.47–0.86, P<0.001). As for DFS, patients with higher HDL-C level had the risk of disease relapse reduced by 35% (HR 0.65, 95% CI, 0.48–0.89, P<0.001) compared with patients with lower levels. Conclusions After pooled analysis, only TC and HDL-C were significantly associated with cancer survival. Our findings demonstrate for the first time that serum TC and HDL-C was identified as a protective factor for overall survival in cancer patients.






Datum: 22.01.2018


Effect of iron supplementation on HbA1c levels in pregnant women with and without anaemia

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Paula Breitenbach Renz, Mayana Kieling Hernandez, Joíza Lins Camargo

Background Iron deficiency anaemia has been associated with higher HbA1c levels. However, during and after iron supplementation there is a decrease in HbA1c results, causing a misinterpretation. Our aim was to analyse the effect of iron supplementation on HbA1c levels in nondiabetic pregnant women with and without anaemia. Methods Pregnant women in prenatal care, without gestational diabetes (GDM) or previous diabetes mellitus (DM) that performed an oral glucose tolerance test (OGTT) in the third trimester of pregnancy were invited to participate. Clinical and laboratorial analyses were performed, including standardized questionnaire, OGTT, full blood count and HbA1c. Results A total of 231 pregnant women without DM or GDM were included in the study. According to anaemia and/or iron supplementation, we divided women in: no iron and no anaemia - Group 1 (N=86); no iron and with anaemia - Group 2 (N=29); iron and no anaemia - Group 3 (N=87); iron and anaemia - Group 4 (N=29). There was statistically a significant, although no clinically relevant, difference between HbA1c values in pregnant women in Groups 1 and 4 [5.1±0.4% (32±4.4mmol/mol) and 4.8±0.3% (29±3.3mmol/mol), P<0.01; respectively]. HbA1c values in pregnant women in Groups 1, 2 and 3 were similar, independently of anaemia [5.1±0.4% (32±4.4mmol/mol); 5.0±0.4% (31±4.4mmol/mol) and 5.0±0.4% (31±4.4mmol/mol); p>0.05; respectively]. Conclusions Iron supplementation during pregnancy does not affect HbA1c levels and has no clinical impact in the final interpretation of results in the absence of anaemia or presence of mild anaemia. Interpreting HbA1c results in pregnant women during iron therapy and with moderate or severe anaemia still requires caution.






Datum: 22.01.2018


Prognostic and clinicopathological value of long noncoding RNA XIST in cancer

Publication date: April 2018
Source:Clinica Chimica Acta, Volume 479

Author(s): Jianwei Zhu, Fanyang Kong, Ling Xing, Zhendong Jin, Zhaoshen Li

Background It has been reported that lncRNA X-inactive specific transcript (XIST) is dysregulated in various cancers. We performed this meta-analysis to clarify its promising functions as a prognosis marker in malignant tumors. Methods Eligible studies were recruited by a systematic search in OVID, Embase, Web of Science and PubMed databases. The hazard ratio (HR) and 95% confidence interval (CI) were calculated to explore the relationship between lncRNA XIST expression and patient's survival, which were extracted from the eligible studies. The odds ratio (OR) was calculated to assess the association between lncRNA XIST expression and pathological parameters using stata12.0 software. Results Total 10 studies and 878 cancer patients were included in the study. The pooled HR suggested that high lncRNA XIST expression was significantly correlated with poor overall survival (OS) (HR=2.61, 95% CI=1.91–3.13, P<0.0001) and short disease-free survival (DFS) (HR=2.10, 95% CI=1.10–3.11, P<0.0001). It was demonstrated high level of lncRNA XIST was positively correlated with larger tumor size (OR=1.89, 95% CI 1.34–2.06, P<0.001), positive distant metastasis (OR=1.75, 95% CI 1.03–2.96, P=0.038) and high-grade cancer (OR=1.64, 95% CI 1.22–2.21, P<0.001). However, no correlation was observed between expression of lncRNA XIST and age (OR=0.86, 95% CI 0.62–1.19, P=0.352), gender (OR=0.98, 95% CI 0.73–1.33, P=0.769), lymphatic metastasis (OR=1.41, 95% CI 0.97–2.04, P=0.069) and differentiation (OR=1.16, 95% CI 0.76–1.77, P=0.497). Conclusions This meta-analysis demonstrated that elevated lncRNA XIST expression predicts poor OS, poor DFS, larger tumor size, increased distant metastasis and advanced tumor stage, suggesting that high lncRNA XIST expression may serve as a novel biomarker for poor prognosis and metastasis in cancers.






Datum: 22.01.2018


Relationships of kidney injury molecule-1 with renal function and cardiovascular risk factors in the general population

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Peter Egli, Stefanie Aeschbacher, Matthias Bossard, Lucien Eggimann, Steffen Blum, Pascal Meyre, Laura Bargetzi, Joel Estis, John Todd, Martin Risch, Lorenz Risch, David Conen

Background Kidney injury molecule-1 (KIM-1) has been associated with kidney damage in patients with preexisting renal disease. However, little is known about the relationships of KIM-1 with renal function and cardiovascular risk factors in healthy individuals from the general population. Methods Healthy individuals aged 25–41years were enrolled in a population-based study. Main exclusion criteria were a BMI >35kg/m2, preexisting kidney disease or established cardiovascular disease. KIM-1 was measured from frozen plasma samples using a high-sensitivity assay. Multivariable linear regression models were constructed to assess the relationships of KIM-1 with renal function and various cardiovascular risk factors. Results We included 2060 individuals (47% men, median (interquartile range) age: 37 (31–40) years) in this analysis. Median KIM-1 levels were 82.5 (IQR 59.4–112.7) pg/ml. We found no significant relationship of KIM-1 with creatinine (adjusted β-coefficient (95% confidence interval) 0.0005 (−0.002; 0.003), p =0.61) and cystatin C (−0.02 (−0.21; 0.17), p =0.84). There were significant linear relationships of log-transformed KIM-1 with systolic blood pressure (adjusted β-coefficient (95% confidence interval) 0.07 (0.04; 0.09), p <0.0001), diastolic blood pressure (0.04 (0.02; 0.07), p =0.001), low-density lipoprotein cholesterol (0.09 (0.06; 0.11), p <0.0001), high-density lipoprotein cholesterol (0.07 (0.05; 0.1), p <0.0001), high-sensitivity C-reactive protein (0.05 (0.03; 0.07), p <0.0001), age (0.09 (0.07; 0.11), p <0.0001), BMI (0.04 (0.01; 0.06), p =0.005) and current smoking (0.12 (0.07; 0.17), p <0.0001). Conclusion Among healthy adults from the general population, plasma levels of KIM-1 were not associated with renal function but were independently related to multiple cardiovascular risk factors.






Datum: 22.01.2018


Plasma FGF23 is not elevated in prostate cancer

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Mariska C. Vlot, Irene Bijnsdorp, Martin den Heijer, Robert de Jonge, R. Jeroen A. van Moorselaar, Annemieke C. Heijboer








Datum: 22.01.2018


Comparison of Single Nucleotide Polymorphism genotyping of CYP2C19 by Loop-mediated isothermal amplification and real-time PCR melting curve analysis

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): K.M. Kwong, C.C. Tam, Raymond Chan, Stephen W.L. Lee, P. Ip, Janette Kwok

Background CYP2C19, a member of cytochrome P450 enzymes, is involved in various drug metabolisms, such as Clopidogrel. Common Single Nucleotide Polymorphisms (SNPs) of CYP2C19 gene, CYP2C19*2 and CYP2C19*3, are liable for the poor metabolism of Clopidogrel. It is crucial to identify poor metabolizers for alternative treatment as poor metabolism of Clopidogrel has been shown to correlate with worse clinical outcome in acute coronary syndrome (ACS) patients. Method A genotyping method, Loop-mediated isothermal amplification (LAMP) was employed in this study. CYP2C19*2 and CYP2C19*3 were adapted from Iwasaki M. et al. with modifications in the reaction mixtures and end-point detection method where simpler visual detection using SYBR® Safe was employed instead of a more technical and equipment demanding real-time PCR. Real-time PCR melting curve analysis is a common method for SNPs analysis and hence chosen as a reference for results obtained from the LAMP assay. Results The CYP2C19-LAMP assay successfully detected CYP2C19*2 and CYPC19*3 mutants. The typing results of CYP2C19-LAMP assay, performed in triplicates, were concordant with the real-time PCR melting curve analysis results. Conclusion CYP2C19-LAMP assay using SYBR® Safe dye for visual detection of end-point result is a simple, rapid and cost-effective method for CYP2C19 genotyping.






Datum: 22.01.2018


Heavy/light chain assay as a biomarker for diagnosis and follow-up of multiple myeloma

Publication date: April 2018
Source:Clinica Chimica Acta, Volume 479

Author(s): Hyojin Chae, Eunhee Han, Jaeeun Yoo, Jaewoong Lee, Jeong Joong Lee, Kyoungho Cha, Myungshin Kim, Yonggoo Kim, Sung-Eun Lee, Chang-Ki Min

Background The heavy-light chain (HLC) assay enables the accurate measurement of each isotype-specific heavy and light chain (i.e., IgGĸ, IgGλ, IgAĸ, and IgAλ) and the derivation of an HLC-pair ratio. However, to date, only limited data have validated the usefulness of serial HLC measurements in the routine follow-up of intact immunoglobulin multiple myeloma (MM) patients. Methods A total of 36 diagnostic and 671 post-treatment sera from 115 IgG and 61 IgA MM patients were assessed with capillary zone electrophoresis, immunosubtraction electrophoresis, total immunoglobulin measurement, free light chain, and HLC assay. The correlations between M-protein levels and the HLC and FLC assay-derived parameters were examined and the clinical significance of the biomarkers was evaluated according to patients' status. Results Involved HLC (iHLC) was the best biomarker correlating with M-protein concentration in both IgG and IgA MM, and could provide a surrogate marker substituting M-protein levels to follow the course of the disease, especially in β-migrating IgA M-proteins. The distribution of iHLC values as well as HLC-pair ratios (rHLC) yielded significantly different results among the various response categories in both IgG and IgA MM. In addition, we detected 2 cases in which an abnormal rHLC in a stringent complete remission (sCR) sample was a marker of early non-symptomatic relapse. Conclusion In this study of a cohort of 176 patients in a routine clinical setting, we have provided evidence of the clinical utility of real world HLC assays for the identification of M-proteins and to monitor M-proteins with an emphasis on IgA monoclonal gammopathies.






Datum: 22.01.2018


The association of uric acid with the risk of metabolic syndrome, arterial hypertension or diabetes in young subjects- An observational study

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Yuan-Yuei Chen, Tung-Wei Kao, Hui-Fang Yang, Cheng-Wai Chou, Chen-Jung Wu, Ching-Huang Lai, Yu-Shan Sun, Chung-Ching Wang, Wei-Liang Chen

Background A growing number of studies are available to shed some light on the association between uric acid (UA) and cardiovascular diseases. However, there have been few studies to support a causal link between UA, metabolic syndrome (MetS), diabetes mellitus (DM) and hypertension (HTN) in young subjects. Methods From the Health Examination Registration System of Taiwanese military service during the period 2013–2015, there were 46,561 eligible participants who were 20years old or older in our study. Different analytical steps of analysis were performed to examine the association between UA and cardiometabolic risk using logistic regression, receiver operating characteristic (ROC) curve analysis and Cox regression. Results For total population, serum UA had significant associations with the presence of MetS (OR=2.08, 95% CI=1.51–2.87), DM (OR=2.59, 95% CI=1.09–6.19) and HTN (OR=1.49, 95% CI=1.07–2.07) in the cross-sectional analysis. According to the cut-off values of UA calculating by the ROC curve analysis in each sex/age subgroup, the association between UA and incident adverse outcomes were analyzed in a longitudinal study. In male, higher UA significantly increased the risks for developing MetS in 30–40years (HR=1.12, 95% CI=1.01–1.25), DM in <30years (HR=2.75, 95% CI=1.38–5.45) and HTN in all subgroups (HR=1.17, 95% CI=1.01–1.37; HR=1.65, 95% CI=1.08–2.53; HR=1.72, 95% CI=1.22–2.43). In females, a higher UA was significantly associated with an increased risk of incident MetS in >40years (HR=2.99, 95% CI=1.34–6.64), HTN in >40years (HR=2.58, 95% CI=1.02–6.55), and no increased risk of DM. Conclusions Our study concluded that serum UA is an important predictor for the risk of incident MetS, DM, and HTN in adults, especially in male population.






Datum: 22.01.2018


Balance between angiogenic and anti-angiogenic isoforms of VEGF-A is associated with the complexity and severity of coronary artery disease

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Yohei Shibata, Ryosuke Kikuchi, Hideki Ishii, Susumu Suzuki, Kazuhiro Harada, Kenshi Hirayama, Atsuo Suzuki, Yosuke Tatami, Kazuhisa Kondo, Toyoaki Murohara

Introduction Assessing the complexity of coronary artery disease (CAD) is clinically important. Vascular endothelial growth factor A (VEGF-A) is a powerful and the most important regulator of angiogenesis. It has been reported that the anti-angiogenic isoform of VEGF-A (VEGF-A165b) inhibits angiogenesis. The purpose of this study was to evaluate the relationship between the complexities of CAD using the Syntax score (SS) and the levels of circulating total VEGF-A or VEGF-A165b. Methods A total of 268 patients who underwent percutaneous coronary intervention (PCI) were enrolled. Of these, 73 patients without acute coronary syndrome or previous revascularization were included in this study. These subjects were divided into two groups according to the SS. Circulating total VEGF-A and VEGF-A165b levels were measured using an enzyme-linked immunosorbent assay. Results Circulating levels of total VEGF-A were significantly higher in the SS>22 (high SS) group than in the SS22 (low SS) group (p =0.018). Moreover, the ratio of VEGF-A165b to total VEGF-A was significantly lower for the high SS group (p =0.004). The levels of total VEGF-A independently predicted high SS after adjusting for other significant variables among patients who underwent PCI (odds ratio, 1.004; 95% CI, 1.001 to 1.006; p =0.01). Conclusions These data indicated that high SS was associated with circulating levels of total VEGF-A and the ratio of VEGF-A165b to total VEGF-A in patients with complex CAD.






Datum: 22.01.2018


Presepsin as a novel diagnostic biomarker for differentiating active pulmonary tuberculosis from bacterial community acquired pneumonia

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Zhi-jiang Qi, Han Yu, Jing Zhang, Chun-sheng Li

Background The expression of presepsin in active pulmonary tuberculosis (APTB) is unknown. We observed the expression of presepsin in APTB, and to evaluate the value for discriminating between APTB and bacterial community acquired pneumonia (BCAP). Methods Consecutive APTB patients who were accurately diagnosed by sputum culture and BCAP patients were enrolled from August 2013 to July 2015. Clinical data were collected, and plasma presepsin concentrations were tested. Receiver operating characteristic (ROC) curves were performed for diagnostic analysis. Results In all, 133 healthy individuals, 103 APTB and 202 BCAP patients were enrolled. Presepsin concentrations in APTB group (218.0 [146.0, 368.0] pg/ml) were higher than those in the healthy control group (128.0 [101.5, 176.5] pg/ml, P <0.001), and lower than the concentrations measured in the BCAP group (532.0 [364.0, 852.3] pg/ml, P <0.001). Simple APTB and miliary tuberculosis patients showed no significant differences in presepsin concentrations. Compared with both Gram-positive and negative bacteria, Mycobacterium tuberculosis caused a limited increase of presepsin. With the cut-off value set at 401pg/ml, presepsin demonstrated high positive predictive value, allowing initial discriminating between APTB and BCAP. Presepsin combined with CURB-65 score could significantly improve the discrimination ability. Conclusions Presepsin concentrations in APTB patients were slightly increased, and may be helpful for initial discrimination between APTB and BCAP.






Datum: 22.01.2018


The value of fluorimetry (Qubit) and spectrophotometry (NanoDrop) in the quantification of cell-free DNA (cfDNA) in malignant melanoma and prostate cancer patients

Publication date: April 2018
Source:Clinica Chimica Acta, Volume 479

Author(s): Giovanni Ponti, Monia Maccaferri, Marco Manfredini, Shaniko Kaleci, Mauro Mandrioli, Giovanni Pellacani, Tomris Ozben, Roberta Depenni, Giampaolo Bianchi, Giacomo Maria Pirola, Aldo Tomasi

Background Circulating cell-free tumor DNA (cfDNA) is of crucial interest in oncology. cfDNA constitutes a potential prognostic and therapeutic marker for different solid tumors and can be used in the diagnostic and therapeutic management of cancer patients for which nowadays there are no valid laboratory markers. In the present study, the quality and quantity of the cfDNA were assessed by different quantification procedures, in order to identify the potential applications of these techniques in the preliminary cfDNA quantification. Methods Qubit with single (ss) and double strand (ds) DNA assay kits, NanoDrop and quantitative Real Time PCR (qPCR), were adopted to assess the cfDNA in the blood samples of 18 melanoma patients, 67 prostate cancer patients and 15 healthy controls. Results The quantification by NanoDrop (average value 8.48ng/μl, 95% confidence limit (CL)=7.23–9.73), Qubit ssDNA (average value 23.08ng/μl, CL=19.88–26.28), dsDNA (average value 4.32ng/μl, CL=3.52–5.12) assay kits and qPCR (average value 0.39ng/μl, CL=0.31–0.47) revealed differences among the four procedures. Qubit 2.0 ss-DNA kit gave higher cfDNA concentration values for all the samples analyzed. In detail, Qubit ssDNA assay revealed higher sensitivity in the quantification of small amounts of pure ss-DNA and ds-DNA, while NanoDrop allowed the assessment of the purity of cfDNA samples. Conclusions The NanoDrop and Qubit 2.0 measurements were analyzed in order to define their correlation with qPCR cfDNA assessment, showing good correlation values with the qPCR that should be considered the “gold standard”. In our proposal, the sequential combination of NanoDrop and Qubit ssDNA methods should be adopted for a cost-effective preliminary assessment of total circulating cfDNA in melanoma and prostate cancer patients, and only discordant values should undergo qPCR assessment.






Datum: 22.01.2018


Angiopoietin-2 (Ang-2) is a useful serum tumor marker for liver cancer in the Chinese population

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Yuxin Chen, Yanping Wu, Xiao Zhang, Hong Zeng, Ya Liu, Qi Wu, Yan Chen, GuoQing Zhu, Qiuhui Pan, Lei Jin, Lin Guo, Fenyong Sun

Background We estimated the diagnostic and prognostic value of serum angiopoietin-2 (Ang-2) in liver cancer patients. Methods Tissue Ang-2 was measured using immunohistochemistry (IHC). Cell localization of Ang-2 was tested using immunofluorescence (IF). Cell viability and apoptosis were evaluated using MTT and caspase3/7 assays, respectively. Colony-formation was measured using a soft agar assay. Serum Ang-2 was examined using enzyme-linked immunosorbent assay (ELISA) and Western blotting. Results Ang-2 was up-regulated in liver cancer compared to the levels in normal tissues. Serum Ang-2 concentrations were much higher in liver cancer patients than in healthy individuals and those with chronic liver disease (CLD). Inhibitions of Ang-2 using specific shRNA decreased cell proliferation. Serum Ang-2 decreased significantly after surgery. Serum Ang-2 was positively correlated with serum alpha-fetoprotein (AFP; R=0.375, P =0.005). Receiver operating characteristic (ROC) curves suggested that serum Ang-2 could be used with relatively high sensitivity and specificity in differentiating liver cancer patients from CLD patients or healthy controls, with corresponding AUC values of 0.742 and 0.924, respectively. Serum Ang-2 was negatively correlated with overall survival. Subgroup analysis also showed that Ang-2 retained its prognostic value in overall survival prediction in different risk subgroups. Conclusion Serum Ang-2 may be a useful tumor marker in predicting liver cancer prognosis.






Datum: 22.01.2018


Perturbation of muscle metabolism in patients with muscular dystrophy in early or acute phase of disease: In vitro, high resolution NMR spectroscopy based analysis

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Niraj Kumar Srivastava, Ramakant Yadav, Somnath Mukherjee, Neeraj Sinha

Background Muscular dystrophy is an inherited muscle disease, characterized by progressive muscle wasting and weakness of variable distribution and severity. Methods In vitro, high-resolution proton nuclear magnetic resonance (NMR) spectroscopy based analysis was performed on perchloric acid (PCA) extract of muscle specimens of patients suffering from various types of muscular dystrophies to identify alteration in hydrophilic low-molecular weight substances (aqueous metabolites) as compared to muscle of control subjects as well as in between the types of muscular dystrophy. Muscle tissue specimens were obtained from Duchenne muscular dystrophy (DMD) [n=11], Becker muscular dystrophy (BMD) [n=12], facioscapulohumeral dystrophy (FSHD) [n=9] and limb girdle muscular dystrophy (LGMD)-2B [n=22]. Control muscle specimens [n=40] were also taken. Results Concentration of branched chain amino acids (BCA), glutamine/glutamate (Gln/Glu), acetate (Ace) and fumarate (Fum) was decreased and His was increased in muscle tissue of DMD, BMD, FSHD and LGMD-2B patients as compared to control subjects. Alanine (Ala) was significantly reduced in BMD, FSHD and LGMD-2B patients as compared to control subjects. Tyrosine (Tyr) was present only in the muscle tissue of control subjects. Propionate (Prop) was present in muscle tissue of DMD, BMD, FSHD and LGMD-2B patients and was absent in muscle tissue of control subjects. Concentration of BCA and Prop is significantly reduced in patients with DMD as compared to BMD, but Glucose is significantly higher in patients with DMD as compared to BMD. Quantity of Glucose, His and Gln/glu are significantly higher in patients with DMD as compared to FSHD, but Prop is significantly reduced in patients with DMD as compared to FSHD. Concentration of Ala and His is significantly higher in patients with DMD as compared to LGMD-2B, but BCA, Glucose and Prop are significantly reduced in patients with DMD as compared to LGMD-2B. Concentration of His is significantly higher in patients with BMD as compared to FSHD. Concentration of His is significantly reduced and Glucose is higher in patients with LGMD-2B as compared to BMD. Glucose concentration is significantly reduced in patients with FSHD as compared to LGMD-2B. ROC curves supported the noticeable discrimination in between the patients with DMD and FSHD for the quantity of Gln/Glu, and patients with LGMD-2B and DMD for the quantity of Ala. Collectively, these findings showed the perturbation of muscle metabolism in muscular dystrophy. Conclusions The data of presented study may be used as supporting information for existing methods of the diagnosis for patients with muscular dystrophy.






Datum: 22.01.2018


Stabilizing specimens for routine ammonia testing in the clinical laboratory

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Jessica L. Gifford, William N.T. Nguyen, Lawrence de Koning, Isolde Seiden-Long

Background In vitro deamination generates ammonia in freshly collected blood specimens. To prevent this, samples for ammonia testing are usually collected on ice and run rapidly (e.g., within 1h). We developed a method to stabilize specimens for ammonia analysis. Methods Following plasma separation, 500μmol/l cycloserine or a combination of 2mmol/l sodium borate with 5mmol/l l-serine were added to sample pools with normal or increased concentrations of ALT and/or GGT to inhibit deamination; and/or residual platelets were removed via centrifugation. Sample pools were then incubated at room temperature or 4°C. Untreated sample pools were also incubated at −80°C. Ammonia was measured at 0, 1, 2, 4, 8, 16, and 24h. Results When incubated at 4°C without treatment, sample pools with enzymes within their reference limit had an increase of 0.5μmol/l/h, whereas sample pools with ALT and/or GGT activity above their upper reference limit had an increase of 3.6μmol/l/h (p <0.001). When sample pools were incubated at 4°C with sodium borate/l-serine, the rate of ammonia increase was significantly reduced in samples with normal (0.3μmol/l/h, p <0.001 vs. untreated controls) or high enzyme activity (0.1μmol/l/h, p <0.001 vs. untreated controls). Independent of the ALT and/or GGT concentrations, storing the sample at −80°C also preserved the specimens for ammonia analysis (0.2μmol/l/h, p <0.001 vs. untreated controls). Conclusions By combining sodium borate/l-serine with refrigeration, plasma ammonia specimens can be stabilized for >12h.






Datum: 22.01.2018


The value of serum visfatin in predicting in-stent restenosis of drug-eluting stents

Publication date: April 2018
Source:Clinica Chimica Acta, Volume 479

Author(s): Xing-An Wu, Gang Xie, Xiu-Qi Li, Hui-Ting Wu, Xiang Wang

Objective This study aims to determine the association between serum visfatin level and in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) using drug-eluting stents (DES). Methods A total of 460 patients with stable coronary heart disease who underwent DES placement were included. According to the results of coronary angiography 1year after PCI, 62 patients diagnosed as ISR were enrolled into the ISR group and 398 patients without ISR were recruited into the control group. Baseline clinical data were collected, and serum visfatin level was measured using ELISA method. Results The serum visfatin levels before PCI were not different between ISR and control groups (P =0.41). However, visfatin level after PCI in the ISR group was significantly higher than in the control group [(30.2±8.6) ng/ml vs. (22.6±7.9) ng/ml, P <0.01]. In multivariate logistic regression, the independent predictors for ISR included post-procedural visfatin level (odds ratio [OR]: 2.08, 95% confidence interval [CI]: 1.19–3.65), type 2 diabetes (OR: 2.30, 95% CI: 1.10–4.79), reference vessel diameter (OR: 0.79, 95% CI: 0.63–0.98), stent length (OR: 1.52, 95% CI: 1.05–2.21) and stent diameter (OR: 0.67, 95% CI: 0.51–0.88). ROC curve analysis indicated that the area under the curve for post-procedural visfatin in predicting ISR was 0.82 (95% CI: 0.77–0.86), with the optimal cut-off value of 25.9ng/ml showing a sensitivity of 84.0% and a specificity of 69.3%. Conclusion Increased serum visfatin level after DES placement is independently associated with ISR. Serum visfatin may be useful in the prediction of ISR.






Datum: 22.01.2018


HDL acceptor capacities for cholesterol efflux from macrophages and lipid transfer are both acutely reduced after myocardial infarction

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Alexandre A.S. Soares, Thauany M. Tavoni, Eliane C. de Faria, Alan T. Remalay, Raul C. Maranhão, Andrei C. Sposito

Background The transport of lipids from the artery wall is one of the most essential anti-atherogenic functions of high-density lipoprotein (HDL). Recent reports of changes in the HDL composition, during myocardial infarction (MI), suggest that this function may be altered. Methods Forty-one consecutive patients with ST-segment elevation MI enrolled at the Brasilia Heart Study were selected. The following HDL-related measures were determined upon admission (D1) and on the fifth day (D5) after MI: C-reactive protein, CETP and PLTP activity, HDL composition, efflux of cholesterol from J774 macrophages to HDL, and transfer of unesterified and esterified cholesterol, triglycerides and phospholipids from a donor nanoemulsion to HDL. Results From D1 to D5, the activity of CETP decreased by 25%, but PLTP activity remained unchanged. Esterified cholesterol (−23%) and phospholipid (−9.5%) contents of HDL decreased. Transfer of triglycerides (−36.5%) and esterified cholesterol (−14.7%) to HDL from nanoemulsions was reduced, but other lipids transfers were unchanged. Cholesterol efflux to HDL was also diminished by 8.5% (p =0.04) on D5 compared to D1. It was more pronounced in patients above the 75th percentile of C-reactive protein. Conclusions After an MI, a simultaneous decrease in lipid transfer to HDL and in the capacity of HDL to efflux cholesterol from cells occurs. Thus, HDL with inferior atheroprotective properties may be generated in the acute post-MI period.






Datum: 22.01.2018


Clinical proteomics: Insights from IGF-I

Publication date: February 2018
Source:Clinica Chimica Acta, Volume 477

Author(s): Jakob Albrethsen, Hanne Frederiksen, Trine Holm Johannsen, Anna-Maria Andersson, Anders Juul

Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS)-platforms already implemented in many clinical laboratories for routine quantitation of small molecules (i.e. uHPLC coupled to triple-quadrupole MS). Progress in targeted proteomics of circulating insulin-like growth factor 1 (IGF-I) have provided valuable insights about tryptic peptides, transitions, internal standards and calibrants. The present challenge is to examine if targeted proteomics of IGF-I can truly measure up to the routine performance that must be expected from a clinical testing platform.






Datum: 22.01.2018


Investigation of correlation of urinary globotriaosylceramide (Gb3) levels with markers of renal function in patients with Fabry disease

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Alana Pimentel Moura, Tatiane Hammerschmidt, Marion Deon, Roberto Giugliani, Carmen Regla Vargas

Fabry disease (FD) is a disorder that results from mutations of hydrolase α-galactosidase A. The enzymatic defect leads to accumulation of globotriaosylceramide (Gb3) in the kidney. Substrate deposition is related to tissue damage in FD, but the relation of urinary Gb3 levels in patients and the renal function markers remain not completely understood. Once nephropathy is one of the main features of FD and is marked by an insidious development, we investigated a possible correlation of Gb3 with biochemical markers of nephropathy including albuminuria, estimated glomerular filtration rate (eGFR), serum creatinine and urea, and proteinuria in male and female patients under or not enzyme replacement therapy (ERT).Gb3, proteinuria and albuminuria were increased in male and female FD patients. We found no correlation between urinary Gb3 levels and all renal function parameters evaluated in Fabry patients (in both sexes and using or not ERT). On the other hand, albuminuria showed negative correlation with eGFR only in male under or not ERT, demonstrating that albuminuria seems to be an early marker of renal function alteration. In conclusion, the results suggest that urinary Gb3 level does not reflect the renal function and that albuminuria is an important biomarker in male FD patients.






Datum: 22.01.2018


Gene mutation patterns of Chinese acute myeloid leukemia patients by targeted next-generation sequencing and bioinformatic analysis

Publication date: April 2018
Source:Clinica Chimica Acta, Volume 479

Author(s): Xiaoyu Han, Wei Li, Na He, Panpan Feng, Yihua Pang, Chunyan Ji, Daoxin Ma

Purposes The conventional risk stratification of acute myeloid leukemia (AML), based on cytogenetics, cannot meet the demand for accurate prognostic evaluations. In recent years, gene mutations are found to be potential markers for more accurate risk stratification, but reports on mutation screening of Chinese AML are limited. We aim to display the mutation patterns of Chinese AML patients, reveal the genotype-phenotype correlations and make a comparison with Caucasians patients. Methods Genome DNA from 78 patients' bone marrow were extracted for targeted gene mutation panel by next-generation sequencing (NGS) technology. Statistics and bioinformatics were used to analyze the correlations between gene mutations and clinical features, as well as the comparison of our results with the Cancer Genome Atlas Research Network (TCGA) public AML dataset. Results We found patients with mutations of FLT3 and TET2 had higher bone marrow blasts, peripheral blasts and white blood cell (WBC) count, mutations of SRSF2 were related with age, and mutations of FLT3-ITD, DNMT3A, IDH1, TET2 and SRSF2 were risk factors for overall survival. What's more, we discovered 15 novel mutations and difference of mutational incidence in 6 genes between Chinese and Caucasians AML. Bioinformatic analysis revealed some relationship between gene mutations and expressions as well as drug sensitivities. Conclusions We made an investigation on the mutation patterns of Chinese AML patients by NGS technique and revealed correlations between gene mutations and clinical features. Thus we recommend routine testing of suspected genes for better prognostic prediction and individualized treatment.






Datum: 22.01.2018


Preanalytical and analytical challenges in gas chromatographic determination of cholesterol synthesis and absorption markers

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Tamara Gojkovic, Sandra Vladimirov, Vesna Spasojevic-Kalimanovska, Aleksandra Zeljkovic, Jelena Vekic, Jelena Arsenijevic, Ivana Djuricic, Sladjana Sobajic, Zorana Jelic-Ivanovic

Introduction Cholesterol homeostasis disruption contributes to the development of different pathologies. Non-cholesterol sterols (NCSs) serve as cholesterol synthesis markers (desmosterol and lathosterol), and cholesterol absorption surrogate markers (campesterol, stigmasterol and β-sitosterol). The study aimed to resolve certain new pre-analytical and analytical problems and ensure a reliable and validated method. Materials and methods Method optimization, validation and stability studies were executed in human serum and plasma. Freeze-thaw cycles were done with and without antioxidant. Gas chromatography-mass spectrometer (GC-MS) was used for NCSs confirmation and plasticizer identification, while GC-flame ionization detector (GC-FID) was used for NCSs quantitation. Results Intra- and inter-assay variabilities for all NCSs were 2.75–9.55% and 5.80–7.75% for plasma and 3.10–5.72% and 3.05–10.92% for serum, respectively. Recovery studies showed satisfactory percentage errors for all NCSs: 93.4–105.7% in plasma and 87.5–106.9 in serum. Derivatized samples were stable up to 7days at −20°C and derivatization yield was affected by presence of plasticizers. Fatty acid amids were identified as interfering plastic leachates. Statistically different NCSs concentrations were observed after the 1st freeze-thaw cycle, in antioxidant-free samples, and after the 4th cycle in antioxidant-enriched samples. Conclusions All of the in-house procedures proved to be useful for minimizing the preanalytical and analytical variations, as proven by the validation results.






Datum: 22.01.2018


Validation and evaluation of two porphobilinogen deaminase activity assays for diagnosis of acute intermittent porphyria

Publication date: April 2018
Source:Clinica Chimica Acta, Volume 479

Author(s): Chia-Ni Lin, Ya-Ching Huang, Long-Sun Ro, Ming-Feng Liao, Hsiao-Chen Ning, Hung-Chou Kuo

Background Acute intermittent porphyria (AIP) is caused by diminished activity of porphobilinogen deaminase (PBGD). The purpose of this study was to validate and compare two assays for PBGD activity. The clinical sensitivity of the PBGD activity assays in AIP diagnosis was also evaluated. Methods This study included 74 subjects from 18 Taiwanese families including symptomatic patients with AIP, asymptomatic carriers, and healthy family members. The specific mutations in AIP patients were identified by DNA sequencing. PBGD activity was measured in erythrocytes by quantifying formation of coproporphyrin or uroporphyrin by the enzyme using porphobilinogen (PBG) as a substrate and fluorimetry for detection. Results The calibration curves obtained with pure coproporphyrin or uroporphyrin were linear with correlation coefficients >0.99 in the range of 0–200nM for coproporphyrin and 0–150nM for uroporphyrin. The coefficients of variation for within-run and between-day imprecision were <9.8% for both assays. The three groups of subjects were used to establish the best cut-off of PBGD activity for identifying symptomatic AIP patients by using area under receiver operating characteristic curve analysis. The symptomatic AIP patients and asymptomatic carriers had significantly lower PBGD activity compared with the healthy family members (all p <.001). Conclusion Two different PBGD activity assays were validated. The best cut-off for coproporphyrin was derived as 46.4nmol/h/mL RBC with corresponding sensitivity of 100% and specificity of 100% and the best cut-off for uroporphyrin was derived as 43.7nkat/L RBC with corresponding sensitivity of 100% and specificity of 97.4%.






Datum: 22.01.2018


Performance characteristics of the Beckman Coulter UniCel DxI 800 TSH (3rd IS) assay

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Gabrielle N. Winston-McPherson, Annie N. Samraj, Kristina Poster, Diane Yamaguchi, Jane A. Dickerson, Julia C. Drees, Daniel T. Holmes, Dina N. Greene

Introduction Beckman Coulter recently reformulated their commercial TSH assay with primary calibration to the World Health Organization 3rd TSH international standard. An extensive evaluation of the performance characteristics for this assay was completed. Methods Intra-day and inter-day precision was evaluated using 3 concentrations of commercial quality control material. Linearity, reportable range, stability, sensitivity and susceptibility to common inferences were determined using pooled patient specimens. Inter-assay variability was assessed across 5 different platforms (n=47 patient specimens). Results Intra-day and inter-day CVs were <10% at all concentrations evaluated. The LOQ, LOD and LOB were 0.0047 μIU/ml (10% CV), 0.0012 μIU/ml and 0.0005 μIU/ml, respectively. Variable bias was observed for the TSH3 assay when evaluated against the previous generation assay and other platforms, but overall TSH3 gave comparable results. Conclusions The TSH3 assay for UniCel DxI 800, is precise, highly sensitive and comparable to the previous generation assay. The assay is acceptable for clinical testing.






Datum: 22.01.2018


Study of measurement of the alcohol biomarker phosphatidylethanol (PEth) in dried blood spot (DBS) samples and application of a volumetric DBS device

Publication date: April 2018
Source:Clinica Chimica Acta, Volume 479

Author(s): Olof Beck, Naama Kenan Modén, Sabina Seferaj, Gabriel Lenk, Anders Helander

Phosphatidylethanol (PEth) is a group of phospholipids formed in cell membranes following alcohol consumption. PEth measurement in whole blood samples is established as a specific alcohol biomarker with clinical and medico-legal applications. This study further evaluated the usefulness of dried blood spot (DBS) samples collected on filter paper for PEth measurement. Specimens used were surplus volumes of venous whole blood sent for routine LC–MS/MS quantification of PEth 16:0/18:1, the major PEth homolog. DBS samples were prepared by pipetting blood on Whatman 903 Protein Saver Cards and onto a volumetric DBS device (Capitainer). The imprecision (CV) of the DBS sample amount based on area and weight measurements of spot punches were 23–28%. Investigation of the relationship between blood hematocrit and PEth concentration yielded a linear, positive correlation, and at around 1.0–1.5μmol/L PEth 16:0/18:1, the PEth concentration increased by ~0.1μmol/L for every 5% increase in hematocrit. There was a close agreement between the PEth concentrations obtained with whole blood samples and the corresponding results using Whatman 903 (PEthDBS =1.026 PEthWB +0.013) and volumetric device (PEthDBS =1.045 PEthWB +0.016) DBS samples. The CV of PEth quantification in DBS samples at concentrations0.05μmol/L were ≤15%. The present results further confirmed the usefulness of DBS samples for PEth measurement.






Datum: 22.01.2018


Point-of-care creatinine testing in patients receiving contrast-enhanced computed tomography scan

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Anne-Sophie Bargnoux, Olivier Beaufils, Maryse Oguike, Aurélie Lopasso, Anne-Marie Dupuy, Mustapha Sebbane, Stéphanie Badiou, Pierre Fesler, Jean-Paul Cristol

Background The aim of this study was to evaluate the creatinine assay on the ABL800 FLEX© blood gas analyzer for the screening of pre-existing renal impairment before radiographic contrast administration in the emergency department (ED), by comparing it with standard practice using central laboratory blood testing. Methods The evaluation comprised two elements. The first, conducted in the central laboratory, focused on the analytical performance of the ABL800 creatinine assay. This included assessment of imprecision and accuracy by comparison with central laboratory standard creatinine assay. We also compared ABL 800 estimated glomerular filtration rate (eGFR) and 99mTc-DTPA measured GFR (mGFR). The second part, conducted in ED sought to determine the impact that implementation of the creatinine at the point-of-care (POC) has on the timeframe in which ED patients are submitted for computed tomography scan (CT). Results The ABL800 enzymatic creatinine assay met the National Kidney Disease Education Program acceptance criteria for imprecision and showed good agreement with the isotope dilution mass spectrometry-traceable Roche enzymatic assay used in the central laboratory. Furthermore, ABL800 eGFR was in total agreement with mGFR by a reference method. The implementation of POC testing creatinine in the ED significantly reduced patient waiting times for contrast enhanced CT (1.73[0.75–3.01] vs 2.57 [1.53–3.48] hours, for period with and without ABL800 respectively, p =0.04). Conclusion The ABL800 assay is comparable with central laboratory reference method in terms of analytical performance and superior in terms of turnaround time. Implementation of creatinine at POC reduces delay results, potentially allowing ED clinical staff to make more rapid clinical decisions and reduce patient waiting time.






Datum: 22.01.2018


Rapid amino acid quantitation with pre-column derivatization; ultra-performance reverse phase liquid chromatography and single quadrupole mass spectrometry

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Carel J. Pretorius, Brett C. McWhinney, Bilyana Sipinkoski, Alice Wilce, David Cox, Avis McWhinney, Jacobus P.J. Ungerer

Background We optimized a quantitative amino acid method with pre-column derivatization, norvaline (nva) internal standard and reverse phase ultra-performance liquid chromatography by replacing the ultraviolet detector with a single quadrupole mass spectrometer (MSnva). Method We used 13C15N isotopically labeled amino acid internal standards and a C18 column with 1.6μm particles to optimize the chromatography and to confirm separation of isobaric compounds (MSlis). We compared the analytical performance of MSnva with MSlis and the original method (UVnva) with clinical samples. Results The chromatography time per sample of MSnva was 8min, detection capabilities were <1μmol/L for most components, intermediate imprecisions at low concentrations were <10% and there was negligible carryover. MSnva was linear up to a total amino acid concentration in a sample of approximately 9500μmol/L. The agreements between most individual amino acids were satisfactory compared to UVnva with the latter prone to outliers and suboptimal quantitation of urinary arginine, aspartate, glutamate and methionine. MSnva reliably detected argnininosuccinate, β-alanine, citrulline and cysteine-s-sulfate. Conclusion MSnva resulted in a more than fivefold increase in operational efficiency with accurate detection of amino acids and metabolic intermediates in clinical samples.






Datum: 22.01.2018


A new enzyme immunoassay for the determination of highly sialylated and fucosylated human α1-acid glycoprotein as a biomarker of tumorigenesis

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Shin Yazawa, Takehiko Yokobori, Kyoichi Kaira, Hiroyuki Kuwano, Takayuki Asao

Background Upon initiation and progression of cancer, α1-acid glycoprotein (AGP) possessing highly sialylated and fucosylated glycans appears in the serum, and recently has attracted a great deal of attention, as a potential biomarker of tumorigenesis in humans. Methods To establish a rapid and precise method for the quantitative assay of fucosylated AGP in serum samples, we developed an enzyme immunoassay (EIA) bearing an anti-AGP antibody and a fucose-binding lectin, Aleuria aurantia (AAL) with additional endeavor to improved sample handling, and antibody preparations. Results The amounts of fucosylated AGP could be determined by the present method with a good performance feature in all tested samples from both cancer patients and healthy controls. From cancer patients under chemotherapy we show that fucosylated AGP could be a clinically relevant biomarker for cancer progression or prognosis as well as for an early assessment of clinical response and treatment outcomes. Furthermore, in a different setting, fucosylated AGP also showed relevance in patients who received immunotherapy with an anti-programmed cell death-1 (PD-1) antibody. Conclusions α1,3fucosylated AGP is a potential biomarker of cancer initiation, progression and response to treatment in cancer patients.






Datum: 22.01.2018


Circulating microparticles levels are increased in patients with diabetic kidney disease: A case-control research

Publication date: April 2018
Source:Clinica Chimica Acta, Volume 479

Author(s): Kathryna Fontana Rodrigues, Nathalia Teixeira Pietrani, Ana Paula Fernandes, Adriana Aparecida Bosco, Maira Cândida Rodrigues de Sousa, Ieda de Fátima Oliveira Silva, Josianne Nicácio Silveira, Fernanda Magalhães Freire Campos, Karina Braga Gomes

Background Type 2 diabetes mellitus (T2DM) is associated with chronic lowgrade inflammation. Microparticles (MPs) are extracellular microvesicles released during apoptosis and cellular activation. The MP's pro-coagulant and pro-inflammatory activities are involved in endothelial dysfunction observed in T2DM patients. This study aimed to evaluate the circulating MPs profile in T2DM patients with diabetic kidney disease (DKD) and correlate it with clinical and laboratorial parameters. Methods MPs derived from platelets (PMPs), leukocytes (LMPs), endothelial cells (EMPs), and expressing tissue factor (TFMPs) were measured by flow cytometry, in plasma of 39 DKD patients and 30 non-diabetic controls. Results We observed higher PMPs, LMPs, EMPs, and TFMPs (all p<0.0001) levels in case group as compared to controls. For patients with DKD, circulating MPs levels were influenced by gender, but not by obesity status nor by T2DM onset. Fasting glucose and 25-hydroxyvitamin D levels showed correlation with circulating MPs levels in both groups. Conclusions These results suggest that type 2 diabetes mellitus patients with DKD presented higher circulating MPs levels - PMPs, LMPs, EMPs, and TFMPs - which correlated with metabolic alterations.






Datum: 22.01.2018


High-dose of vitamin D supplement is associated with reduced susceptibility of monocyte-derived macrophages to dengue virus infection and pro-inflammatory cytokine production: An exploratory study

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Diana Marcela Giraldo, Andrés Cardona, Silvio Urcuqui-Inchima

Background Dengue, one the most important public health problems in tropical and subtropical areas, is the most important mosquito-borne viral infection in humans. In the absence of effective treatment and vaccine against dengue, the active form of vitamin D could play a central role in protection against dengue virus (DENV), the causal agent of dengue. Recently we reported that monocyte-derived macrophages (MDMs) differentiated in the presence of vitamin D, in addition to expressing lower levels of mannose receptor, are less susceptible to DENV infection and produce low levels of pro-inflammatory cytokines, compared to MDMs differentiated in the absence of vitamin D. Objective The aim of this study was to determine that oral vitamin D supplementation exerts an effect on DENV susceptibility and pro-inflammatory cytokine production in MDMs. Methods Healthy individuals were supplemented with 1000 or 4000 international units (IU)/day of vitamin D during 10days. Before and after vitamin D supplementation, a peripheral blood (PB) sample was taken and the monocytes recovered were used to obtain MDMs and were challenged with DENV-2. Furthermore, the expression of genes encoding vitamin D receptor (VDR), CYP24A1 and CAMP were analyzed using real-time quantitative PCR. Results The data indicate that macrophages differentiated from monocytes obtained from healthy donors who received higher doses of vitamin D (4000IU/day), exhibited higher resistance to DENV-2 infection and produced a significant decrease of pro-inflammatory cytokines and high production of interleukin-10 (IL-10). Furthermore, a significant decrease in intracellular toll-like receptor (TLR) and CAMP mRNA was observed. Conclusion A supplement of 4000IU/day of vitamin D may represent an adequate dose to control dengue progression and DENV replication. Although the results of our study suggest that the vitamin D status can influence the immune response, further studies are needed to determine the feasibility of vitamin D as anti-DENV agent and immune modulator.






Datum: 22.01.2018


Screening of ZnT8 autoantibodies in the diagnosis of autoimmune diabetes in a large French cohort

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Lorna Garnier, Lucien Marchand, Marine Benoit, Marc Nicolino, Nathalie Bendelac, Catherine Wright, Philippe Moulin, Christine Lombard, Charles Thivolet, Nicole Fabien

Aim of the study Evaluate the added value of screening anti-ZnT8 antibodies (ZnT8A) in addition to the classical anti-GAD (GADA) and anti-IA-2 (IA-2A) antibodies for the diagnosis of type-1 diabetes (T1D) within a large cohort of both children and adults. Materials and methods Retrospective 2-year study including 516 patients (215 children, 301 adults) who had blood tests at diabetes onset and/or for diabetes classification. ZnT8A, GADA, and IA-2A were analyzed in all samples. Results Among those individuals included, 142 (28%) were ZnT8A-positive. A total of 228/516 suffered from T1D, of whom 110 (48%) were ZnT8A-positive and 166 (73%) GADA and/or IA-2A positive. When adding ZnT8A to GADA/IA-2A, 184 (81%) patients were positive for ≥1 Ab. Regarding the 122 patients at T1D onset, 75 (61%) were positive for ZnT8A and the proportion of patients with T1D with ≥1 Ab reached 89%. The highest prevalence of ZnT8A was observed in children aged 6–10years. Fourteen of the 124 patients positive for ZnT8A with a known clinical diagnosis suffered from a disease other than T1D. Conclusions ZnT8A should be included in routine evaluation at diabetes onset and is a valuable biological marker to classify newly-diagnosed diabetics. The predictive value in our high-risk subjects has to be confirmed.






Datum: 22.01.2018


Serum levels of endocan and endoglin are associated with large-artery atherosclerotic stroke

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Xin-Wei He, Shao-Fa Ke, Yu-Yan Bao, Wei-Jun Hong, Yu-Guang Shen, Cai Li, Feng Zhu, En Wang, Xiao-Ping Jin

Background Accumulating evidence has suggested that endocan and endoglin may play important roles in cardiovascular disease. However, no previous study has focused on these circulating levels in patients with large-artery atherosclerotic (LAA) stroke. Methods Serum levels of endocan and endoglin in 114 patients with LAA stroke and 114 age- and sex-matched controls were measured by ELISA. Serum samples from patients were available on day 1, day 6 and in the 4th week after ischaemic stroke(IS). Stroke severity was determined based on the NIHSS score and the stroke volume. An unfavourable outcome was defined as a mRS score>2 on day 90 after IS. Results The endocan levels were significantly higher in patients with LAA stroke compared with the controls (p =0.001), and after adjustment for other factors (p =0.001). In addition, higher endocan levels were independently associated with unfavourable outcomes on both day 1 and day 6 after IS (p =0.018 and p =0.011). Endoglin levels were decreased on day 6 (p =0.002) and then recovered in the 4th week after IS. No correlation was found between endocan or endoglin and stroke severity. Conclusions Endocan levels are higher in patients with LAA stroke and can help in predicting the short-term unfavourable outcome. Endoglin levels are changed after stroke.






Datum: 22.01.2018


Determination of dolutegravir's unbound fraction in human plasma using validated equilibrium dialysis and LC-MS/MS methods

Publication date: April 2018
Source:Clinica Chimica Acta, Volume 479

Author(s): David Metsu, Thomas Lanot, François Fraissinet, Mélanie Picot, Didier Concordet, Marion Cabrol, Frédérique Dubois-Galopin, Etienne Chatelut, Pierre Delobel, Peggy Gandia

Assessment of the unbound pharmacologically active fraction (fu; as the ratio of unbound to total concentration) of dolutegravir could improve therapeutic drug monitoring (TDM) in patients that experience virological failure or toxicity, despite receiving adequate total concentrations. This study evaluated (i) dolutegravir's fu through equilibrium dialysis (ED), (ii) the pre-analytical parameters that influence fu, and (iii) fu's inter-individual variability in HIV patients. Validation of the LC-MS/MS method followed FDA guidelines. The results, based on coefficients of variation (results from nominal concentrations <15%), allowed accurate measurement of unbound and total dolutegravir concentrations. Equilibrium during ED was obtained in 4h. Sparse non-specific binding (9%) was observed, allowing results interpretation without interference. Steps before analysis (e.g., conservation at +4°C, freeze/thaw cycles) did not influence fu, allowing easy integration of fu analysis within laboratory routines. Anticoagulants from samples (citrated versus heparinized; p <0.001) and hemolysis (p =0.007) influenced fu and could lead to misinterpretation. Developed was then performed to the HIV-patients' plasma (n =54). Results, expressed as median InterQuartile Range [25%;75%] were 0.45% IQR [0.38; 0.55] for fu, 9.26μg/L IQR [4.62; 15.14] for unbound, and 2035μg/L IQR [878.5; 2640] for total concentration. The high inter-individual variability observed in the unbound form from HIV patients was a first step towards integrating dolutegravir TDM.

Graphical abstract

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Datum: 22.01.2018


Galectin-3 in patients with coronary heart disease and atrial fibrillation

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Qi Kang, XiaoLong Li, Mengyun Yang, Taniya Fernando, Zheng Wan

Objective To observe the change of the inflammatory factor Galectin-3 in patients with coronary heart disease, and the correlation between Galectin-3 and the severity of the disease. To observe changes of Galectin-3 in patients with atrial fibrillation (AF) before and after radiofrequency ablation, and the changes of Galectin-3 before and after an interim treatment with a high dose of atorvastatin on patients with acute myocardial infarction(AMI). Methods Patients with coronary heart disease and atrial fibrillation having normal heart function were selected, among them, the patients with AMI were given a short term treatment of 80mg atorvastatin before PCI, and patients with atrial fibrillation underwent radiofrequency catheter ablation. ELISA technique was equipped to observe the Galectin-3 changes in patients with coronary heart disease and that of patients with AF before and after radiofrequency ablation. Results Galectin-3 level of the AMI group was higher than that of the unstable angina pectoris (UAP) group, and its levels were higher than that of the stable angina pectoris (SAP) group, the differences were statistically significant among both groups (P<0.05); Galectin-3 level of multivessel coronary disease group was higher than that of single vessel group, in which a statistically significant difference was noted (P<0.05); There was no statistically significant difference associated in the drop of Galectin-3 levels in patients with AMI after PCI (P>0.05); Galectin-3 of patients with AF decreased after RFCA, but no statistical significance noted (P>0.05); Galectin-3 was negatively correlated with the LVEF value(r=0.405, P<0.05). Conclusion Galectin-3 belongs to a class of inflammatory mediators that is associated with the degree of myocardial inflammation and fibrosis. It is related to the severity of myocardial ischemia and is negatively correlated with the cardiac ejection fraction.






Datum: 22.01.2018


Association between metabolic syndrome and chronic kidney disease

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Tomoyuki Kawada








Datum: 22.01.2018


Vitamin D C3 epimer in a mid-Swedish region—Analytical measurement and epidemiology

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Christos Karefylakis, Paul Pettersson-Pablo, Stefan Särnblad, Eva Rask, Manar Bitar, Anders Magnuson, Clas-Göran Eriksson








Datum: 22.01.2018


Decreased cytoplasmic X-box binding protein-1 expression is associated with poor prognosis and overall survival in patients with oral squamous cell carcinoma

Publication date: April 2018
Source:Clinica Chimica Acta, Volume 479

Author(s): Hui-Ting Hsu, Ming-Tai Hsing, Chung-Min Yeh, Chih-Jung Chen, Jia-Sin Yang, Kun-Tu Yeh

Introduction Squamous cell carcinoma is the most common cancer of the oral cavity. In spite of advancements in surgical, chemoradiological and targeted therapies, these therapeutic strategies still have had little impact on survival rates. X-box binding protein-1 (XBP-1) is a potent transcription factor that is involved in the unfolded protein response (UPR) pathway, which itself is activated in response to endoplasmic reticulum stress as a method to restore cellular homeostasis. The role XBP-1 plays in oral squamous cell carcinoma (OSCC) has yet to be determined. In this study, we used molecular and immunohistochemical analyses to investigate the role of XBP-1 protein playing in the OSCC carcinogenesis. Materials and methods We used immunohistochemical analyses to investigate XBP-1 expression in 255 OSCC tissue specimens, as well as migration and invasion assays with XBP-1 siRNA transfection of oral cancer cell lines to confirm its role in OSCC. Results The XBP-1 immunostaining was dichotomized as low-level expression and high-level expression. We found that low-level cytoplasmic XBP-1expression was significantly correlated with larger tumor size (p =0.047), more advanced clinical stage (p <0.0001), lymph node metastasis (p =0.002), and shorter overall survival (p =0.011). Kaplan-Meier survival curves showed that low-level cytoplasmic XBP-1 expression was significantly correlated with shorter overall survival (p =0.031). The univariate Cox regression analysis revealed that cytoplasmic XBP-1 expression was a prognostic factor for overall survival of patients with OSCC. We also found that inhibition of XBP-1 promoted OSCC cell migration and invasion. Conclusion Our results suggest that XBP-1 expression may play an essential role in the pathogenesis of OSCC and that targeting XBP-1 may be a sound therapeutic strategy.






Datum: 22.01.2018


A pilot study of the metabolomic profiles of saliva from female orthodontic patients with external apical root resorption

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Jinglin Zhou, Huimin Hu, Renhuan Huang

Background Orthodontically induced external apical root resorption (OIEARR) is one of the most severe complications of orthodontic treatment, which is hard to diagnose at early stage by merely radiographic examination. This study aimed to identify salivary metabolic products using unbiased metabolic profiling in order to discover biomarkers that may indicate OIEARR. Materials and methods Unstimulated saliva samples were analyzed from 19 healthy orthodontic patients with EARR (n=8) and non-EARR (n=11). Metabolite profiling was performed using 1H Nuclear Magnetic Resonance (NMR) spectroscopy. Results A total of 187 metabolites were found in saliva samples. With supervised partial least squares discriminant analysis and regression analysis, samples from 2 groups were well separated, attributed by a series of metabolites of interest, including butyrate, propane-1,2-diol, α-linolenic acid (Ala), α-glucose, urea, fumarate, formate, guanosine, purine, etc. Indicating the increased inflammatory responses in the periodontal tissues possibly associated with energy metabolism and oxidative stress. Conclusions The effective separation capacity of 1H NMR based metabolomics suggested potential feasibility of clinical application in monitoring periodontal and apical condition in orthodontic patients during treatment and make early diagnosis of OIEARR. Metabolites detected in this study need further validation to identify exact biomarkers of OIEARR. Saliva biomarkers may assist in diagnosis and monitoring of this disease.






Datum: 22.01.2018


Editorial board member, Aims and Scope, Publication Info.

Publication date: February 2018
Source:Clinica Chimica Acta, Volume 477










Datum: 22.01.2018


Progesterone rise on hCG day is negatively correlated with IVF-ET outcomes in natural cycles

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Xiadi Wu, Yundong Mao, Yan Gao, Xiaoqiao Qian, Wei Wang, Wei Ding, Shi-Wen Jiang, Jiayin Liu

Objective To investigate the effect of progesterone rise on hCG day on the laboratory and clinical outcomes in natural cycles and to explore the possible factors related to the occurrence of progesterone elevation. Patients and study methods Retrospective analysis was performed in 1157 infertile women with decreased ovarian reserve. Eligible infertile women undergoing IVF in natural cycles were assigned to four groups according to serum progesterone levels on the day of hCG administration: group 1, P<2nmol/L; group 2, 2<P<2.9nmol/L; group 3, 3<P<3.9nmol/L; group 4, P4.0nmol/L. Data on clinical outcomes and LH level were collected and analyzed. Results Number of retrieved oocytes, pronucleus cells, fertilized cells, and good embryos significantly decreased (p<0.05). A significant elevation of cancelled cycle rate, early follicle elimination rate and LH level on hCG day occurred when the serum progesterone levels were higher than 4.0nmol/L on the day of hCG administration (p<0.05). Conclusion In natural cycles, progesterone rise on the day of hCG administration (in this study, P4.0nmol/L) may negatively correlated with the quality of oocytes and embryos.






Datum: 22.01.2018


Single nucleotide polymorphisms of microRNA in cardiovascular diseases

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Kamna Srivastava, Kirti Tyagi

Despite the advances in medicine and in science of diagnosis, cardiovascular diseases (CVD) remain the number one cause of morbidity and mortality worldwide. Apart from the modifiable risk factors, genetic factors are believed to also influence the outcome of this umbrella of diseases. Under the genetic factors, miRNA polymorphisms, namely miR-146a (rs2910164), miR-196 (rs11614913) and miR-499 (rs3746444), have become an important tool to study the mechanism that underlie the pathogenesis of this disease. In this review, we analyze the advances made through various research studies and the evidence provided by them in the area of miRNA polymorphisms by comparing the allelic frequencies and genotyping patterns. Interestingly, these studies have contradicting results even those conducted in same set of population. We also highlight the gap in literature search as majority of these studies have been conducted in Chinese population and data gaps are evident in Caucasian population, along with developing countries like, India, where no such data is available. This makes the daunting task of presenting a global picture and of the extent these polymorphisms play a role in CVD progression, even more difficult. Therefore, we suggest that more work needs to be done by taking various geographical domains in to consideration. Also, larger sample size calculated through statistical tools is the key to progress in establishing the genetic co-relation of miRNA polymorphisms and CVDs.






Datum: 22.01.2018


Prognostic significance of neutrophil to lymphocyte ratio in patients with gastrointestinal stromal tumors: A meta-analysis

Publication date: February 2018
Source:Clinica Chimica Acta, Volume 477

Author(s): Xiao-feng Luo, Lin-hua Zhou

Background The neutrophil to lymphocyte ratio (NLR) is reported to be a prognostic factor in multiple malignancies. However, its prognostic value in patients with gastrointestinal stromal tumors (GISTs) remains controversial. This study aims to evaluate the prognostic value of preoperative NLR in GISTs. Methods MEDLINE, EMBASE, and, Cochrane databases were searched until February 2017. Eligible articles were defined as studies assessing the prognostic role of preoperative NLR in GISTs. The end points were overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and clinicopathological parameters. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects/random-effects models. Results A total of eight studies comprising 1676 patients with GISTs were included. Elevated NLR had an association with decreased DFS/RFS (HR: 2.18, 95% CI: 1.30–3.67, P=0.003), but not OS (HR: 1.74, 95% CI: 0.63–4.84, P=0.29). The findings from most subgroup analyses were consistent with those from the overall analysis. Moreover, high NLR was significantly correlated with male, stomach lesion, tumor size (>5cm), tumor rupture (+), tumor recurrence (+), mitotic index (>5/50HPF), and NIH risk category (high/intermediate). Conclusions Elevated preoperative NLR may be an unfavorable prognostic biomarker in patients with GISTs.






Datum: 22.01.2018


Cardiac troponin and adverse outcomes in atrial fibrillation: A meta-analysis

Publication date: February 2018
Source:Clinica Chimica Acta, Volume 477

Author(s): Yichuan Fan, Xingzhi Zhao, Xiaodong Li, Nan Li, Xinhua Hu

Background The prognostic value of cardiac troponin elevation in atrial fibrillation (AF) is unclear. Objective To investigate the association of cardiac troponin elevation with adverse outcomes in AF by conducting a meta-analysis. Methods We systematically searched the PubMed and Embase databases until April 2017 for studies assessing the association of cardiac troponin-T (cTnT) or troponin-I (cTnI) elevation with adverse outcomes in AF. The outcome measures were all-cause mortality and major adverse cardiac events (MACEs: death, stroke, myocardial infarction, pulmonary embolism, major bleeding, or revascularization). Results Six studies involving 22,697 AF patients were identified. Meta-analysis showed that AF with elevated cardiac troponin was independently associated with increased risk of all-cause mortality (HR 2.04; 95% CI 1.56–2.67) and MACEs (HR 1.93; 95% CI 1.61–2.30). Furthermore, the prognostic value of cardiac troponin elevation was consistently found irrespective of method determination, type of troponin measured, sample size, and study quality subgroup. Conclusions AF with cardiac troponin elevation was independently associated with increased risk of all-cause mortality and MACEs. Therefore, determination of troponin should be considered for risk stratification in AF.






Datum: 22.01.2018


Prognostic and clinicopathological value of Nanog in hepatocellular carcinoma: A meta-analysis

Publication date: February 2018
Source:Clinica Chimica Acta, Volume 477

Author(s): Chaojie Liang, Kaitong Zhang, Hua Ge, Wei Li, Guangming Li, Jixiang Wu

Background and aims Recently, studies indicate that Nanog is over-expressed in hepatocellular carcinoma (HCC); however, the relationship between Nanog expression and clinicopathological and prognostic value remains controversial. Therefore, we conducted a meta-analysis to explore the role of Nanog in HCC. Methods Articles were included from PubMed, Cochrane Library, Web of Science, EMBASE database, Chinese CNKI, and the Chinese WanFang database. The relationships between Nanog expression, clinicopathological features, and survival rate were calculated. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with STATA14.2. Results A total of 845 patients from 9 articles were enrolled. Positive Nanog expression was correlated with HBsAg, differentiation, and TNM stage, although it was not related to gender, age, alpha-fetoprotein (AFP), tumor size, tumor number, liver cirrhosis, and vascular invasion. Positive Nanog expression indicates a poor 3-year and 5-year overall survival and disease-free survival rate. Conclusion The results show that Nanog expression was related to HBsAg, differentiation, and TNM stage in HCC. Nanog may be an unfavorable prognostic biomarker for HCC.






Datum: 22.01.2018


Quantification of CSF cystatin C using liquid chromatography tandem mass spectrometry

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Chikashi Matsuda, Yuri Shiota, Abdullah Md Sheikh, Ryota Okazaki, Kazuo Yamada, Shozo Yano, Toshikazu Minohata, Ken-ichi Matsumoto, Shuhei Yamaguchi, Atsushi Nagai

Background Cystatin C (CST3), a ubiquitously expressed cysteine protease inhibitor, is implicated in several neurological diseases. Here, we have developed an accurate CST3 measurement system based on liquid chromatography tandem mass spectrometry (LC-MS/MS). Methods LC-MS/MS based measurement for CSF CST3 was validated by determination of assay precision, accuracy and recovery. The values were compared with those measured by immunoassay. Glycosylation of CST3 in CSF was analyzed by Western blotting and lectin blotting. Results Measuring standard CST3 by LC-MS/MS produced a linear standard curve that correlated with assigned values (r2 =0.99). Both intra- and inter-assay variation was <10%. Although showed a correlation, the average CST3 concentration measured by LC-MS/MS was significantly higher than that of immunoassay. Western blotting showed the presence of a 25KDa species along with CST3 monomer (14KDa) in CSF. The volume of 25KDa species was decreased by deglycosylation. Lectin blotting revealed a 25KDa glycosylated protein in sialidase-treated CSF, which was decreased by deglycosylation. However, deglycosylation did not alter CST3 concentration measured by immunoassay. Conclusions Our results suggest that LC-MS/MS-based CST3 measurement is a robust method with higher detection ability. Such method could be useful for the diagnosis and monitoring of neurological diseases.






Datum: 22.01.2018


Interleukin-23 receptor polymorphism (rs10889677 A/C) in ankylosing spondylitis: Meta-analysis in Caucasian and Asian populations

Publication date: February 2018
Source:Clinica Chimica Acta, Volume 477

Author(s): Renfang Han, Qing Xia, Shengqian Xu, Dazhi Fan, Faming Pan

Background The association between interleukin-23 receptor (IL23R) gene rs10889677 polymorphism and ankylosing spondylitis (AS) susceptibility was inconsistent in the recent literatures. A systematic review and meta-analysis was therefore performed. Methods Online electronic databases were searched for relevant studies published up to November 2017. Meta-analyses were performed for the comparisons of allele (A versus C) and multiple genetic models, including dominant, recessive, heterozygous, and homozygous models using fixed or random effects models. Odds ratios (OR) with 95% confidence intervals (95%CI) were utilized to assess the potential relationship. Results Sixteen studies containing 19 separate comparisons, totaling 6450 cases and 8009 controls were included. A significant association between rs10889677 A allele and AS susceptibility was detected (OR=1.136, 95%CI=1.043–1.236, P =0.003). Stratified analysis by ethnicity indicated that rs10889677 A allele was significantly associated with AS in Europeans (OR=1.192, 95%CI=1.080–1.315, P <0.001), but not Asians (OR=1.045, 95%CI=0.913–1.197, P =0.523). In addition, there were no significant associations between rs10889677 polymorphism and AS susceptibility in any of dominant, recessive, homozygous and heterozygous models. Conclusion This meta-analysis demonstrates that IL23R gene rs10889677 A allele confers increased risk of AS in Europeans, but its role in Asian populations needs further exploration.






Datum: 22.01.2018


mRNA, microRNA and lncRNA as novel bladder tumor markers

Publication date: February 2018
Source:Clinica Chimica Acta, Volume 477

Author(s): Edyta Wieczorek, Edyta Reszka

Early detection of bladder cancer (BC) is essential for improvement of the patient's prognosis and general survival rates. Current diagnostic methods are still limited, so new specific and cost-effective biomarkers are emerging as the noninvasive tools in treatment decisions in recurrent BC. Gene expression and epigenetic profile can be analysed using quantitative real-time-PCR (qRT-PCR) method in urine, blood and tissue. This review provides an update of recent findings on BC molecular profile as novel markers in diagnosis and prognosis of bladder tumors. We describe mRNA-, microRNA- and lncRNA-based biomarkers involved in the BC detection, diagnosis, prediction of recurrence and monitoring after treatment.






Datum: 22.01.2018


Oxidative stress in urea cycle disorders: Findings from clinical and basic research

Publication date: February 2018
Source:Clinica Chimica Acta, Volume 477

Author(s): Belisa Parmeggiani, Carmen Regla Vargas

Inborn errors of metabolism (IEM) comprise a group of over 600 disorders, each with a specific metabolic impairment due to a genetic defect. Urea cycle disorders (UCD) are IEM that affect the nitrogen disposal system, leading to hyperammonemia and the accumulation of other toxic metabolites in tissues of affected patients. UCD arise from mutations in the genes coding any of the enzymes participating in the urea cycle, either directly or as regulators of this pathway, causing severe respiratory alkalosis. Considering that the exact mechanisms underlying the damage found in UCD, the purpose of this minireview is to obtain data and search for links between UCD and oxidative stress, a phenomenon common to several IEM. In vitro studies and animal models of UCD suggest that, not only the accumulation of ammonia, but also of the other metabolites involved in each UCD may impair redox status. Nitric oxide metabolism also seems to play an interesting role in the maintenance of redox balance in these conditions. Clinical research provides little information on the subject, but, studies appear to support the role of oxidative stress in pathologic mechanisms of UCD.






Datum: 22.01.2018


A nomogram for predicting prognostic value of inflammatory biomarkers in patients with acute-on-chronic liver failure

Publication date: March 2018
Source:Clinica Chimica Acta, Volume 478

Author(s): Jiao Gong, Wenying Zhou, Cuicui Xiao, Yusheng Jie, Shuguang Zhu, Jun Zheng, Yutian Chong, Bo Hu

Background Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) in china is a critical clinical syndrome with a high short-term mortality. This study aimed to construct and validate a model for neutrophil to lymphocyte ratio (NLR)-based nomogram for 3-month mortality estimation for patients with ACLF. Methods The nomogram was based on a retrospectively study of 96 patients with ACLF. The predictive accuracy and discriminative ability of nomogram were evaluated by a concordance index (C-index), and calibration curve, comparing with model for end-stage liver disease (MELD) score. The results were validated using bootstrap resampling and an external cohort of 88 patients. Results A total of 184 patients with ACLF were enrolled, with 3-month mortality of 40.76%. The cut-off value for NLR was 5.7 using X-tile program. Patients with NLR>5.7 had significantly higher mortality (p <0.001). On multivariate analysis of the training cohort, independent factors for survival were age, NLR and total bilirubin, which were all selected into the nomogram. The calibration curve for probability of survival showed optimal agreement between prediction by nomogram and actual observation. The C-index of nomogram was higher than that of MELD score for predicting survival (0.72 vs 0.56). The results were confirmed in validation cohort. Conclusions The proposed nomogram with NLR resulted in more accurate prognostic prediction for patients with HBV-related ACLF.






Datum: 22.01.2018


Serum S100A12 and 30-day mortality after acute intracerebral hemorrhage

Publication date: February 2018
Source:Clinica Chimica Acta, Volume 477

Author(s): Song-Quan Qian, Su-Rong He, Bei-Bei Li, Jing Qian, Xu-Dong Zheng

Background S100A12 is implicated in inflammatory reactions. The purpose of this study was to determine the association between serum S100A12 concentrations and 30-day mortality in patients with acute intracerebral hemorrhage (ICH). Methods We prospectively included 182 healthy controls and 182 ICH patients within 24h after stroke onset. Serum samples were collected for the measurement of S100A12 concentrations. Multivariable analysis was used to evaluate the relationship between serum S100A12 concentrations and mortality of ICH patients within 30days. Results Serum S100A12 concentrations were significantly increased compared to control subjects. S100A12 concentrations were positively correlated with National Institutes of Health Stroke Scale (NIHSS) score, ICH volume, blood glucose concentrations, blood white blood cell count and plasma C-reactive protein concentrations. 36 (19.8%) patients were deceased within 30days after stroke onset. Non-survivors had significantly higher concentrations of serum S100A12 than survivors. Additionally, Serum S100A12 concentrations significantly discriminated patients at risk of 30-day mortality and its predictive value was equivalent to those of NIHSS score and hematoma volume. Moreover, higher serum S100A12 concentrations showed a significantly higher risk for 30-day mortality and overall survival. Conclusions Higher S100A12 concentrations are positively associated with inflammation, hemorrhagic severity and short-term mortality among ICH patients, indicating S100A12 may represent a biomarker for predicting poor outcome after hemorrhagic stroke.






Datum: 22.01.2018


 


Category: Current Chemistry Research

Last update: 04.01.2018.






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