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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.

To search this web page for specific words type "Ctrl" + "F" on your keyboard (Command + "F" on a Mac). Then: type the word you are searching for in the window that pops up!

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



Therapeutic drug monitoring of piperacillin and tazobactam by RP-HPLC of residual blood specimens

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Sylvia M. Verhoven, Joseph J. Groszek, William H. Fissell, Adam Seegmiller, Jennifer Colby, Pratish Patel, Alain Verstraete, Matthew Shotwell
BackgroundSepsis is a common diagnosis in critical care with inpatient mortality rates up to 50%. Sepsis care is organized around source control, antibiotics, and supportive care. Drug disposition is deranged by changes in volume of distribution and regional blood flow, as well as multiple organ failure. Thus, assuring that each patient with sepsis attains pharmacokinetic targets is challenging. There is currently no commercially available FDA-approved assay to measure piperacillin-tazobactam, very commonly used as a beta-lactam/beta-lactamase inhibitor combination antibiotic in the intensive care unit (ICU).MethodsSamples were prepared by ultrafiltration of plasma collected in lithium heparin Vacutainers. Separation was achieved by gradient elution on a C-18 column followed by UV detection at 214 nm. The method is validated in residual blood samples allowing investigators to exploit a waste product to develop insight into beta-lactam pharmacokinetics in the ICU.ResultsAccuracy and precision were within the 25% CLIA error standard for other antibiotic assays. Free piperacillin concentrations were also in good agreement with total piperacillin concentrations measured in the same plasma by an assay in clinical use outside the United States.ConclusionWe describe a method for measuring piperacillin and tazobactam that meets clinical validation standards. Quick turnaround time and excellent accuracy on a low-cost platform make this method more than adequate for use as a routine therapeutic drug monitoring tool.


Datum: 26.04.2018


Induction of inosine triphosphatase activity during ribavirin treatment for chronic hepatitis C

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Yoichi Tanaka, Hiroaki Yokomori, Katsuya Otori
BackgroundRibavirin (RBV) is an antiviral agent and the primary component for chronic hepatitis C (CHC) therapy. Hemolytic anemia is limitation for RBV treatment. Inosine triphosphatase (ITPA) activity has been associated with severity of RBV-induced anemia. However, changes in ITPA activity during CHC therapy are unknown. The aim of this study was to measure the time-dependent change in ITPA activity over the RBV treatment.MethodsForty-two patients with CHC were evaluated for ITPA activity over the course of RBV treatment.ResultsThe median value of ITPA activity at start of RBV treatment was 134.2 μmol/h/g hemoglobin (Hb; range, 26.3–251.0 μmol/h/g Hb). The ITPA activity values at 4, 8, and 12 weeks during RBV treatment were 143.2, 202.2, and 225.7 μmol/h/g Hb, respectively, and these ITPA values were significantly elevated compared with the start of treatment (p < 0.001). In patients with ITPA variants, patients with anemia (Hb < 10 g/dL) had greater elevated ITPA activities compared with patients without anemia at 12 weeks.ConclusionOur findings indicate that ITPA activities are elevated with RBV therapy, and this elevation may be a risk of anemia in late therapeutic phase in patients that began with low ITPA activity.


Datum: 26.04.2018


A rapid screening of a recurrent CYP24A1 pathogenic variant opens the way to molecular testing for Idiopathic Infantile Hypercalcemia (IIH)

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Elisa De Paolis, Angelo Minucci, Maria De Bonis, Giovanni Luca Scaglione, Jacopo Gervasoni, Aniello Primiano, Pietro Manuel Ferraro, Daniele Cappellani, Claudio Marcocci, Giovanni Gambaro, Ettore Capoluongo
IntroductionLoss-of-function mutations in cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene are associated with Idiopathic Infantile Hypercalcemia (IIH) and adult kidney stone disease. The enzyme deficiency leads to an impaired vitamin D catabolism pathway, resulting in a syndrome characterized by recurrent hypercalcemia, hypercalciuria and suppressed parathyroid hormone (PTH) levels. In these patients, the genetic evaluation of CYP24A1 is an important diagnostic tool, allowing the definitive diagnosis of IIH.MethodsA rapid CYP24A1 gene testing based on High Resolution Melting Analysis (HRMA) was designed in order to detect the CYP24A1 c.428_430delAAG (p.Glu143del), a recurrent IIH-associated variant.ResultsHRMA method was able to identify c.428_430delAAG genotypes evaluating melting curve shape and melting temperature (Tm). Heterozygous samples exhibited a typical melting profile while homozygous samples showed a specific Tm shift.ConclusionsWe provide evidence about application of HRMA in unambiguous genotyping of the CYP24A1 c.428_430delAAG variant, making this method useful in clinical molecular diagnostics. This approach opens the way to a helpful molecular analysis of CYP24A1 gene in IIH diagnosis, to an improved pharmacological treatment strategy and to a reduced risk of recurrent stones and worsening nephrocalcinosis.


Datum: 26.04.2018


Association and prognostic value of serum Cystatin C, IL-18 and Uric acid in urological patients with acute kidney injury

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Arpan Choudhary, Supriya Basu, Sujit K. Dey, Jayanta K. Rout, Ranjit K. Das, Ranjan K. Dey
PurposeTo assess the role of serum Cystatin C, IL-18 and Uric acid in acute kidney injury (AKI) in urological patients, along with their prognostic significance.Materials and methodsProspective observational study included 61 cases, admitted in urology ward with baseline serum creatinine ≤1.5 mg/dL. All patients had at least one or more predisposing factors for AKI. Daily urine output and creatinine level were checked. Serum levels of biomarkers were measured at baseline and postoperatively after 24 h. Development of AKI and its outcome were analysed.ResultsThirty nine patients (63.9%) developed AKI in the study. Patients with AKI were found to have a greater percentage rise of Cystatin C (118.7% v/s 81.8%, p = 0.005), IL-18 (59.0% v/s 25.5%, p = 0.004) and Uric acid (34.3% v/s 19.2%, p = 0.008) after 24 h. Absolute Uric acid level at day 1 was also significantly associated with AKI (5.18 ± 0.91 v/s 4.45 ± 0.86, p = 0.003). Risk stratification of AKI was poor for all biomarkers. Area under curve for Cystatin C, IL-18 and Uric acid was 0.715, 0.696 and 0.734 respectively. Renal function after 3 months, had a positive correlation with baseline creatinine and baseline Cystatin C levels (r = 0.56 & 0.39).ConclusionsPostoperative serum Cystatin C, IL-18 and Uric acid after 24 h were significantly associated with AKI. Baseline Cystatin C had moderate capability to predict short term renal function.


Datum: 26.04.2018


Voxelotor (GBT440) produces interference in measurements of hemoglobin S

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Nicola J. Rutherford, Katie L. Thoren, Zahra Shajani-Yi, Jennifer M. Colby



Datum: 26.04.2018


Association of red blood cell distribution width with severity of hepatitis B virus-related liver diseases

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Xiude Fan, Huan Deng, Xiqiang Wang, Shiqi Fu, Zitong Liu, Jiao Sang, Xiaoge Zhang, Na Li, Qunying Han, Zhengwen Liu
BackgroundRed blood cell distribution width (RDW) has been indicated to be an inflammatory indicator in a variety of diseases. However, no consistent conclusions regarding it's relevance to hepatitis B virus (HBV) -related liver diseases have been made. This meta-analysis was conducted to assess the significance of RDW in HBV-related liver diseases.MethodsA comprehensive literature review was conducted using PubMed, Embase, and China National Knowledge Infrastructure (CNKI) through August 20, 2017 to identify studies that reported the association between RDW and HBV-related liver diseases. The standard mean difference (SMD) and corresponding 95% confidence interval (CI) were used to assess the associations.ResultsTwenty-four studies met the eligibility criteria were included in the meta-analysis. These studies included 3272 HBV-infected patients and 2209 healthy controls. Chronic hepatitis B (CHB) patients had significantly increased RDW levels compared with healthy controls (SMD =1.399, 95% CI 0.971–1.827, p < 0.001]. Moreover, acute on chronic liver failure (ACLF) patients (SMD = 1.309, 95% CI 0.775–1.843, p < 0.001) and cirrhotic patients (SMD = 0.948, 95% CI 0.715–1.180, p < 0.001) had significantly elevated RDW levels compared with CHB patients. However, no statistical significance was obtained in RDW levels between cirrhosis and ACLF (SMD = 0.167, 95% CI -0.382 –0.716, p = 0.051).ConclusionRDW values were elevated in HBV-related liver diseases and correlated with the disease severity, suggesting that RDW levels may differentiate CHB from healthy controls and ACLF and cirrhosis from CHB but they appear to have no distinguishing characteristic between ACLF and cirrhosis.


Datum: 26.04.2018


Novel univariate and multivariate regression methods for the simultaneous analysis of ternary mixture of 1, 4-benzodiazepines in dosage forms and human urine

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): F. Belal, F. Ibrahim, Z.A. Sheribah, H. Alaa
In this paper, novel univariate and multivariate regression model updating methods were developed and validated for the simultaneous determination of ternary mixture of bromazepam, diazepam and clonazepam. The univariate methods used are the mean centering of ratio spectrophotometric method and iso-absorptive point coupled with ratio-subtraction and ratio difference spectrophotometric method. Linearity, ranges, precision and accuracy of these methods were determined. The multivariate methods adopted are the principal component regression and partial least-squares. These models were estimated using nineteen mixtures as calibration set and six mixtures as validation set. The minimum root square error of predication were 0.1215 and 0.0568 for BMZ, 0.0598 and 0.0712 for DIZ and 0.0867 and 0.0753 for CNP by PLS and PCR respectively. PCR and PLS methods were successfully applied for the analysis of BMZ, DIZ and CNP in their dosage forms. Content uniformity testing of the studied pharmaceutical tablets by PLS and PCR was also determined. MCR, IPRSRD and PLS model updating enabled the determination of BMZ, DIZ and CNP in spiked human urine. Moreover, PLS model updating was applied to drug-dissolution rate testing of BMZ and DIZ in their commercial tablets. The obtained results were statistically compared with those obtained by reported methods giving a conclusion that there is no significant difference regarding accuracy and precision.

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Datum: 26.04.2018


Serum Toll-like receptor 4: A novel and promising biomarker for identification of aortic aneurysmal diseases

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Tan Li, Jing-Jing Jing, Li-ping Sun, Yue-hua Gong, Nan-nan Dong, Jun Yang, Yuan Yuan
BackgroundImmune inflammation appears to play a role in aortic aneurysm (AA) pathology. Toll-like receptor 4 (TLR4) has been proved to involve in immune inflammatory diseases. However, the relationship between serum TLR4 and AA is still unclear.MethodsThe study included 282 AA patients and 287 controls. The clinical test related information was collected in medical records. The levels of serum TLR4 were measured by enzyme-linked immunosorbent assay.ResultsSerum TLR4 levels were significantly higher in case groups and could be influenced by age, smoking, hypertension, diabetes and hyperlipidemia. Serum TLR4 was positively correlated with circulating CRP, Hcy, D-dimer, Fg and Cys-c in AA patients, even after adjusting the possible influencing factors. The optimal cut-off value of TLR4 was 13.64 ng/ml for discriminating AA, and the screening accuracy was higher for those who were males (sensitivity of 63.5% and specificity of 68.6%), smokers (sensitivity of 63.5% and specificity of 82.7%) and hyperlipidemia (sensitivity of 59.1% and specificity of 81.2%). Multiple logistic analyses showed that serum TLR4 was significantly correlated with AA risk (OR = 1.119, 95% CI = 1.077–1.162, p < 0.001) and subjects with high TLR4 levels (>13.64 ng/ml) were more likely to have AA (OR = 4.225, 95% CI = 2.477–7.206, p < 0.001).ConclusionsSerum TLR4 was closely related to AA and associated with some AA-related circulating markers. Serum TLR4 could be a novel and promising biomarker with important diagnostic and predictive value in the identification of aortic aneurysmal diseases.


Datum: 26.04.2018


ZAP-70 in chronic lymphocytic leukemia: A meta-analysis

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Yini Liu, Yangfeng Wang, Jule Yang, Yongyi Bi, Hong Wang
BackgroundRecent studies have reported that zeta-chain-associated protein kinase 70 (ZAP-70) expression plays a prognostic role in chronic lymphocytic leukemia (CLL). However, these results remain controversial. Thus, we performed a meta-analysis to clarify the prognostic value of ZAP-70 expression in CLL.Materials and methodsRelevant studies were searched in PubMed, Embase, Cochrane library, and Web of Science up to January 2018. Clinicopathological features and prognostic data were extracted from the studies. We pooled estimates and 95% confidence intervals (CIs) and estimated the heterogeneity of studies using Mantel–Haenszel or DerSimonian and Laird method.ResultsTwelve studies that included 1956 patients with CLL were eligible for inclusion. The pooled results revealed that increased ZAP-70 expression was significantly associated with poor overall survival (hazard ratio [HR] = 2.48, 95% CI: 1.72–3.59, P = 0.019, I2 = 53.0%) and event-free survival (HR = 4.17, 95% CI: 2.17–8.01, P = 0.014, I2 = 68.2%) in a random-effects model with significant heterogeneity. Clinicopathological analysis demonstrated that ZAP-70 expression was significantly associated with unmutated immunoglobulin heavy-chain genes, CD38 expression, serum β-2 microglobulin, and lymphocyte doubling time.ConclusionsOur findings indicated that ZAP-70 was a strong prognostic biomarker for patients with CLL.


Datum: 26.04.2018


Aquaporin 1 gene deletion affects the amniotic fluid volume and composition as well as the expression of other aquaporin water channels in placenta and fetal membranes

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Hui Luo, Ailan Xie, Ying Hua, Jing Wang, Yanyun Liu, Xueqiong Zhu
ObjectiveTo explore the role of aquaporin 1 (AQP1) in regulation of amniotic fluid volume and composition. To investigate the effects of AQP1 gene knockout on expression of other aquaporin water channels (AQP3, AQP8 and AQP9) in placentas and fetal membranes.MethodsMice were sacrificed at 9.5, 13.5 and 16.5 gestational day (GD). Amniotic fluid volume, osmolality and composition, fetal membranes, placental and fetal weights as well as placenta areas were recorded in Aqp1 homozygote conceptus group, heterozygote conceptus group and wild-type group, respectively. The expression of AQP1, AQP3, AQP8 and AQP9 mRNA and protein in placenta and fetal membranes were examined by quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting.ResultsAqp1 homozygote conceptus had a greater volume of amniotic fluid, lower osmolality and calcium concentration than their wild-type counterparts at 16.5 GD. There was no significant difference in expression of AQP1, AQP3, AQP8 and AQP9 in placentas among three groups. While expression of AQP8 was increased at 13.5 and 16.5 GD in fetal membranes, the expression of AQP9 was significantly decreased in fetal membranes in Aqp1 homozygote group compared with Aqp1 heterozygote and wild-type groups.ConclusionAQP1 may play an important role in the homeostasis of maternal-fetal fluid at late gestation days. The mechanism of mutual compensation among AQPs gene needs further investigation.


Datum: 26.04.2018


Prognostic significance of pre-resection albumin/fibrinogen ratio in patients with non-small cell lung cancer: A propensity score matching analysis

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Shuaishuai Chen, Haixi Yan, Juping Du, Jun Li, Bo Shen, Haijian Ying, Ying Zhang, Shiyong Chen
BackgroundNutrition and coagulation play important roles in cancer progression. This study was aimed to investigate the value of the albumin/fibrinogen ratio (AFR) in non-small cell lung cancer (NSCLC) patients, through a propensity score matching (PSM) method.MethodsWe retrospectively analyzed 529 NSCLC patients underwent surgical resection from 2010 to 2015. PSM was used to eliminate possible biases. A Cox proportional hazards regression model was performed to evaluate the prognostic value of AFR in NSCLC.ResultsThe optimal value was 9.67 for the AFR by ROC (receiver operating characteristic) curve. The AFR was statistically significantly associated with age, sex, smoking history, histological subtype, tumor size, pathological stage and adjuvant therapy (p < 0.05). Multivariate analysis indicated that the pathological stage and pre-resection AFR were independent prognostic factors for patients with NSCLC. Additionally, elevated AFR indicated a better outcome, and patients with higher AFR had lower risk for overall death (OS) (HR 0.512, 95% CI 0.316–0.829, p = 0.006) as well as disease-free death (DFS) (HR 0.561, 95% CI 0.399–0.787, p = 0.001). The propensity score model identified 120 patients from each group that were balanced for age, sex, smoking history, histological subtype, tumor size, stage distribution and adjuvant therapy. In multivariable regression analysis of PSM groups, the result indicated that the AFR was predictive for OS (HR 0.392, 95% CI 0.225–0.683, p < 0.001) and DFS (HR 0.526, 95% CI 0.344–0.805, p = 0.003).ConclusionsPre-resection AFR can be considered as an independent prognostic factor in NSCLC patients, and higher AFR may enhance OS and DFS of NSCLC patients.


Datum: 26.04.2018


Comment on “Copeptin in heart failure: Review and meta-analysis” by Zhong Y et al.

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Luca Molinari, Marco Baldrighi, Luigi Mario Castello



Datum: 26.04.2018


Remnant-like particles and coronary artery disease in familial hypercholesterolemia

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Hayato Tada, Masa-aki Kawashiri, Atsushi Nohara, Kenji Sakata, Akihiro Inazu, Hiroshi Mabuchi, Masakazu Yamagishi, Kenshi Hayashi
BackgroundAlthough remnant-like particle cholesterol (RLP-C) has been associated with coronary artery disease (CAD) in the general population, few data exist regarding this issue in patients with familial hypercholesterolemia (FH). The aim of our study was to investigate the association between RLP-C and the presence of CAD in patients with FH.MethodsWe examined 282 patients with FH (144 males, mean age, 41 ± 17 years) whose RLP-C levels were measured. We assessed the baseline characteristics, including lipid levels, other conventional risk factors for cardiovascular events, the presence of CAD, and the serum RLP-C levels.ResultsSerum RLP-C levels significantly correlated with serum triglyceride (TG) levels (Pearson's r = 0.631, p < 0.001). We observed that a larger proportion of individuals in the higher tertiles of serum RLP-C had a larger number of diseased coronary arteries (p < 0.001 for the trend of multi-vessel disease). Logistic regression analysis, after adjusting for age, sex, hypertension, diabetes, smoking, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and lipoprotein (a) [Lp(a)], revealed that RLP-C was significantly associated with CAD [odds ratio (OR): 1.08, 95% confidence interval (CI): 1.00–1.16, p = 0.046]; however, adding serum TG levels into the logistic regression model nullified this association (OR: 1.07, 95% CI: 0.98–1.17, p = 0.141), whereas Lp(a) was independently associated with CAD (OR: 1.02, 95% CI: 1.00–1.03, p = 0.015).ConclusionsSerum RLP-C levels were significantly associated with the presence and severity of CAD in patients with FH. However, the clinical usefulness of measuring RLP-C levels beyond that of measuring TG levels should be further assessed.


Datum: 26.04.2018


Analytical validation of an ultra low-cost mobile phone microplate reader for infectious disease testing

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Li-Ju Wang, Nicole Naudé, Misganaw Demissie, Anne Crivaro, Malek Kamoun, Ping Wang, Lei Li
Most mobile health (mHealth) diagnostic devices for laboratory tests only analyze one sample at a time, which is not suitable for large volume serology testing, especially in low-resource settings with shortage of health professionals. In this study, we developed an ultra-low-cost clinically-accurate mobile phone microplate reader (mReader), and clinically validated this optical device for 12 infectious disease tests. The mReader optically reads 96 samples on a microplate at one time. 771 de-identified patient samples were tested for 12 serology assays for bacterial/viral infections. The mReader and the clinical instrument blindly read and analyzed all tests in parallel. The analytical accuracy and the diagnostic performance of the mReader were evaluated across the clinical reportable categories by comparison with clinical laboratorial testing results. The mReader exhibited 97.59–99.90% analytical accuracy and <5% coefficient of variation (CV). The positive percent agreement (PPA) in all 12 tests achieved 100%, negative percent agreement (NPA) was higher than 83% except for one test (42.86%), and overall percent agreement (OPA) ranged 89.33–100%. We envision the mReader can benefit underserved areas/populations and low-resource settings in rural clinics/hospitals at a low cost (~$50 USD) with clinical-level analytical quality. It has the potential to improve health access, speed up healthcare delivery, and reduce health disparities and education disparities by providing access to a low-cost spectrophotometer.


Datum: 26.04.2018


Lactase persistence genotyping on whole blood by loop-mediated isothermal amplification and melting curve analysis

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Anders Abildgaard, Sara K. Tovbjerg, Axel Giltay, Liselot Detemmerman, Peter H. Nissen
BackgroundThe lactase persistence phenotype is controlled by a regulatory enhancer region upstream of the Lactase (LCT) gene. In northern Europe, specifically the −13910C > T variant has been associated with lactase persistence whereas other persistence variants, e.g. −13907C > G and −13915 T > G, have been identified in Africa and the Middle East. The aim of the present study was to compare a previously developed high resolution melting assay (HRM) with a novel method based on loop-mediated isothermal amplification and melting curve analysis (LAMP-MC) with both whole blood and DNA as input material.MethodsTo evaluate the LAMP-MC method, we used 100 whole blood samples and 93 DNA samples in a two tiered study. First, we studied the ability of the LAMP-MC method to produce specific melting curves for several variants of the LCT enhancer region. Next, we performed a blinded comparison between the LAMP-MC method and our existing HRM method with clinical samples of unknown genotype.ResultsThe LAMP-MC method produced specific melting curves for the variants at position −13909, −13910, −13913 whereas the −13907C > G and −13915 T > G variants produced indistinguishable melting profiles.ConclusionThe LAMP-MC assay is a simple method for lactase persistence genotyping and compares well with our existing HRM method.


Datum: 26.04.2018


Prognostic role of haematological indices in sudden sensorineural hearing loss: Review and meta-analysis

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Zaizai Cao, Ziyue Li, Haijie Xiang, Saiyu Huang, Jinjian Gao, Xiang Zhan, Xiuxiu Zheng, Bangliang Li, JianBin Wu, Bobei Chen
BackgroundComplete blood count (CBC) is an important blood test in clinical practice, and it has been recently used to predict the prognosis of patients with sudden sensorineural hearing loss (SSNHL). Some haematological indices of the CBC test have been reported to be associated with the clinical outcome of SSNHL. However, the prognostic value of these haematological indices in SSNHL is currently under debate. Here, we performed a meta-analysis to investigate the association between haematological indices of the CBC test and clinical outcomes in patients with SSNHL.MethodsWe conducted a meta-analysis of studies that evaluated the association between haematological indices and prognoses in patients with sudden hearing loss. Subgroup and sensitivity analyses were also performed to explore potential sources of heterogeneity.ResultsTen studies that included 972 individuals were identified. Pooled analysis showed neutrophil-to-lymphocyte ratio (NLR) (weighted mean difference [WMD] = −1.69 and p < 0.001), platelet-to-lymphocyte ratio (PLR) (WMD = −38.45 and p < 0.001), neutrophil count (WMD = −1.57 × 109/L and p < 0.001) and lymphocyte count (WMD = 0.41 × 109/L and p < 0.001) to be the factors associated with the prognosis of SSNHL.ConclusionsOur findings indicated that NLR, PLR, neutrophil count and lymphocyte count are strongly associated with the prognosis of SSNHL. These four indices could be recommended as inexpensive markers to report treatment outcomes.


Datum: 26.04.2018


Practical laboratory-based clinical decision tools and associations with short-term bleeding and mortality outcomes

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Kevin G. Graves, Joseph B. Muhlestein, Donald L. Lappé, Raymond O. McCubrey, Heidi T. May, Stacey Knight, Viet T. Le, Tami L. Bair, Jeffrey L. Anderson, Benjamin D. Horne
BackgroundThe red cell distribution width (RDW) predicts mortality in numerous populations. The Intermountain Risk Scores (IMRS) predict patient outcomes using laboratory measurements including RDW. Whether the RDW or IMRS predicts in-hospital outcomes is unknown.MethodsThe predictive abilities of RDW and two IMRS formulations (the complete blood count [CBC] risk score [CBC-RS] or full IMRS using CBC plus the basic metabolic profile) were studied among percutaneous coronary intervention patients at Intermountain (males: N = 6007, females: N = 2165). Primary endpoints were a composite bleeding outcome and in-hospital mortality.ResultsIMRS predicted the composite bleeding endpoint (females: χ2 = 47.1, odds ratio [OR] = 1.13 per +1 score, p < 0.001; males: χ2 = 108.7, OR = 1.13 per +1 score, p < 0.001) more strongly than RDW (females: χ2 = 1.6, OR = 1.04 per +1%, p = 0.20; males: χ2 = 11.2, OR = 1.09 per +1%, p < 0.001). For in-hospital mortality, RDW was predictive in females (χ2 = 4.3, OR = 1.13 per +1%, p = 0.037) and males (χ2 = 4.4, OR = 1.11 per +1%, p = 0.037), but IMRS was profoundly more predictive (females: χ2 = 35.5, OR = 1.36 per +1 score, p < 0.001; males: χ2 = 72.9, OR = 1.40 per+1 score, p < 0.001). CBC-RS was more predictive than RDW but not as powerful as IMRS.ConclusionsThe IMRS, the CBC-RS, and RDW predict in-hospital outcomes. Risk score-directed personalization of in-hospital clinical care should be studied.

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Datum: 26.04.2018


Reticulocyte hemoglobin content in a large sample of the general Dutch population and its relation to conventional iron status parameters

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): A.Mireille Baart, Michiel G.J. Balvers, Maria T.E. Hopman, Thijs M.H. Eijsvogels, Jacqueline M.T. Klein Gunnewiek, Corine A. van Kampen
BackgroundNo full consensus exists on which iron status parameters to use for iron status assessment. In this study, we assessed the usefulness of measurement of the hemoglobin content of reticulocytes (CHr) in the general population.MethodsThe following iron status parameters were assessed in 1024 adults: CHr, reticulocytes, hemoglobin (Hb), ferritin, serum iron, transferrin, transferrin saturation and mean corpuscular volume (MCV). Mean parameter values and correlation coefficients for CHr and other parameters were calculated. In addition, mean CHr levels in subgroups based on low and normal values of other iron status parameters were compared.ResultsMean CHr values in men were 31.81 (SD = 1.50) pg and in women 31.32 (SD = 1.51) pg. A positive correlation was observed between CHr and Hb, ferritin, serum iron, transferrin saturation and MCV; a negative correlation was observed between CHr and transferrin. CHr levels were lower in subjects with low values of Hb, ferritin, serum iron and MCV compared to subjects with normal values for these parameters.ConclusionMean CHr values in this population were comparable to values reported in small healthy control groups. Associations with other parameters were in agreement with associations reported in literature. CHr measurement might have additional value in iron status assessment.


Datum: 26.04.2018


Serum secretory phospholipase A2 group IB correlates with the severity of membranous nephropathy

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Weihao Li, Mingming Zhang, Yaping Guo, Xiaomei Liu, Xin Ji, Junhua Su, Zhiping Zhang, Feifei Zhang
BackgroundSerum secretory phospholipase A2 group IB (sPLA2-IB) is involved in the pathological processes of membranous nephropathy (MN). To date, there is no large-scale study validating the usefulness of circulating sPLA2-IB in the follow-up of patients with MN. This study investigated the role of circulating sPLA2-IB in the evaluation of severity of MN.MethodsA total of 158 patients with primary membranous nephropathy (pMN), 34 with secondary membranous nephropathy (sMN) and 53 healthy controls were enrolled. Histological staging was made for all MN patients. 36 of the pMN patients accepted immunosuppressive therapy and 11 sMN patients who received treatment of primary disease were followed up for 6 months. Serum group IB secretory phospholipase A2 (sPLA2-IB), M-type phospholipase A2 receptor antibody (PLA2R-Ab), blood urea nitrogen, creatinine, total protein, albumin, cholesterol, triglyceride and 24-hour urine protein were measured at the time of diagnosis. SPLA2-IB and 24-hour urine protein were measured at the end of follow-up.ResultsCirculating sPLA2-IB levels were significantly higher in pMN and sMN patients compared to controls and negatively correlated with TP and albumin, whereas positively correlated with 24-hour urine protein. PLA2-IB was found increased with the severity of proteinuria when divided MN patiens into three groups according to degree of proteinuria. Through the 6-month follow-up, sPLA2-IB and 24 h-urine protein levels were found significantly decreased when patients with pMN or sMN reached remission. By ROC analysis, PLA2R-Ab was demonstrated to be most significant in the differential diagnosis of pMN and sMN compared with 24-hour urinary protein and serum sPLA2-IB.ConclusionDespite the limited significance to differentiate pMN from sMN, sPLA2-IB was correlated with the level of proteinuria in MN patients suggesting to be a potential biomarker for monitoring disease severity and therapeutic effects of both pMN and sMN.


Datum: 26.04.2018


Prognostic role of microRNA-155 in patients with leukemia: A meta-analysis

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Xiaoyu Zhang, Yong Wang, Qiang Guo, Yutao Diao, Hongyan Liu, Guanhua Song, Wei Wang, Zhiyong Zhang, Haipeng Yin, Lianlian Li
BackgroundRecent studies have shown that microRNA-155 (miR-155) is correlated with clinical outcomes of leukemia. This meta-analysis explores to evaluate the prognostic value of miR-155 for survival in patients with leukemia.MethodsEligible studies were searched from PubMed and EMBASE databases. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS), disease-free survival, event-free survival, progression-free survival and treatment-free survival were extracted, if available. Pooled HRs and 95% CIs were used to study any correlation between miR-155 and survival.Results11 studies from 10 articles containing 1718 leukemia patients were included. Data showed that the pooled HR for OS was 1.67 (95% CI: 1.44–1.95, P < 0.01). Subgroup analyses for OS showed that the pooled HRs and their 95% CIs were 1.68, 1.41–2.00 (P < 0.01) and 1.73, 1.25–2.41 (P < 0.01) for acute myeloid leukemia and chronic lymphoblastic leukemia, respectively. Furthermore, there was no significant heterogeneity or publication bias among the enrolled datasets.ConclusionWe conclude that high miR-155 expression was associated with shorter OS for leukemia patients, and that miR-155 might be a promising prognostic biomarker for this patient population.


Datum: 26.04.2018


The prognostic role of programmed cell death-ligand 1 expression in non-small cell lung cancer patients: An updated meta-analysis

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Guangzhi Ma, Yunfu Deng, Hai Jiang, Wen Li, Qiang Wu, Qinghua Zhou
BackgroundProgrammed cell death-ligand 1 (PD-L1) seemed to be associated with the outcomes of non-small cell lung cancer. However the prognostic role of PD-L1 expression among NSCLC remained unclear and inconsistent. The aim of the study set out to evaluate the correlation between PD-L1 expression and the prognosis of patients that developed NSCLC.MethodsIdentified literatures were extracted of various electronic databases and a meta-analysis was performed to evaluate the prognostic role of PD-L1 among NSCLC patients.ResultsTotally 25 studies from 11 countries containing 5861 patients were included in the meta-analysis. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were 1.176 (95% CI: 1.016–1.361, P = 0.029) and 1.170 (95% CI: 0.984–1.392, P = 0.076), respectively. High PD-L1 expression on NSCLC tissue was also related with worse OS among Asian patients (HR = 1.381, 95% CI: 1.127–1.629, P = 0.002), adenocarcinomas (HR = 1.899, 95% CI: 1.306–2.762, P = 0.001) and poor PFS in non-Asian patients (HR = 1.695, 95% CI: 1.158–2.480, P = 0.002). Sensitivity analysis indicated that removal of any particular included literature won't affect the pooled results. Publication bias among the studies was not significant neither.ConclusionsPD-L1 expression is a prognostic factor related with poor survival among patients that developed NSCLC.


Datum: 26.04.2018


The prognostic value of HOXA13 in solid tumors: A meta-analysis

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Yaoan Wen, Fangpeng Shu, Yeda Chen, Yiwen Chen, Yu Lan, Xiaolu Duan, Shan-Chao Zhao, Guohua Zeng
PurposeThe prognostic value of homeobox (HOX) A13 (HOXA13) in cancer remains uncertain due to limitations of sample size and discrete outcome in previous studies. We performed this meta-analysis to explore the prognostic effect of HOXA13 in patients with solid tumors.MethodsPubMed, Embase, and Web of Science were searched to identify eligible studies. Hazard ratios (HR) with 95% confidence interval (95%CI) and clinicopathological factors were extracted. Subgroup analysis according to cancer type, sample size and analysis method were also performed.ResultsA total of 844 patients with solid tumor from 9 eligible studies were incorporated in the meta-analysis. We found that high HOXA13 expression level was significantly associated with poor overall survival (OS) in human cancer (HR = 2.23; 95%CI: 1.74–2.85), and significantly related to poorer histological grade (odds ratio (OR) = 2.03, 95%CI: 1.40–2.96), positive lymph node metastasis (OR = 1.96, 95%CI: 1.26–3.02) and more advanced tumor–node–metastasis (TNM) stage (OR = 3.92, 95%CI: 2.46–6.22).ConclusionOur meta-analysis suggests that HOXA13 might be a valuable biomarker of poor prognosis and a potential therapeutic target for human solid tumors.


Datum: 26.04.2018


Biochemical and molecular analyses of infantile sialic acid storage disease in a patient with nonimmune hydrops fetalis

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Eungu Kang, Yoon-Myung Kim, Sun Hee Heo, Euiseok Jung, Ki-Soo Kim, Hyun Ju Yoo, Eun Na Kim, Chong Jai Kim, Gu-Hwan Kim, Beom Hee Lee
Nonimmune hydrops fetalis is the most severe clinical manifestation of lysosomal storage diseases (LSDs). Around 14 different LSDs have been accounted for as 1–15% of the cause of nonimmune hydrops fetalis. We report a Korean infant affected by an extremely rare but severe form of sialic acid storage disease. The patient presented with nonimmune hydrops fetalis, dysmorphic facial features, hepatosplenomegaly, and dysostosis multiplex and died at 39 days of age due to persistent pulmonary hypertension. LSD was suspected based on the presence of diffuse vacuolation of syncytiotrophoblast, villous stromal cells, and intermediate trophoblast in placental biopsy. Increased excretion of urinary free sialic acid was detected by liquid chromatography-tandem mass spectrometry. The patient was compound heterozygous of the c.908G>A (p.Trp303Ter) and the splicing mutation c.1259+5G>T (IVS9+5 G>T) in the SLC17A5 gene.


Datum: 26.04.2018


Mass spectrometry-based metabolomics for tuberculosis meningitis

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Peixu Zhang, Weiguanliu Zhang, Yue Lang, Yan Qu, Fengna Chu, Jiafeng Chen, Li Cui
Tuberculosis meningitis (TBM) is a prevalent form of extra-pulmonary tuberculosis that causes substantial morbidity and mortality. Diagnosis of TBM is difficult because of the limited sensitivity of existing laboratory techniques. A metabolomics approach can be used to investigate the sets of metabolites of both bacteria and host, and has been used to clarify the mechanisms underlying disease development, and identify metabolic changes, leadings to improved methods for diagnosis, treatment, and prognostication. Mass spectrometry (MS) is a major analysis platform used in metabolomics, and MS-based metabolomics provides wide metabolite coverage, because of its high sensitivity, and is useful for the investigation of Mycobacterium tuberculosis (Mtb) and related diseases. It has been used to investigate TBM diagnosis; however, the processes involved in the MS-based metabolomics approach are complex and flexible, and often consist of several steps, and small changes in the methods used can have a huge impact on the final results. Here, the process of MS-based metabolomics is summarized and its applications in Mtb and Mtb-related diseases discussed. Moreover, the current status of TBM metabolomics is described.


Datum: 26.04.2018


Analytical interference of HBOC-201 (Hemopure, a synthetic hemoglobin-based oxygen carrier) on four common clinical chemistry platforms

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Erik A. Korte, Nicole Pozzi, Nina Wardrip, M.Tayyeb Ayyoubi, Saeed A. Jortani
BackgroundThere are 13 million blood transfusions each year in the US. Limitations in the donor pool, storage capabilities, mass casualties, access in remote locations and reactivity of donors all limit the availability of transfusable blood products to patients. HBOC-201 (Hemopure®) is a second-generation glutaraldehyde-polymer of bovine hemoglobin, which can serve as an “oxygen bridge” to maintain oxygen carrying capacity while transfusion products are unavailable. Hemopure presents the advantages of extended shelf life, ambient storage, and limited reactive potential, but its extracellular location can also cause significant interference in modern laboratory analyzers similar to severe hemolysis.MethodsObserved error in 26 commonly measured analytes was determined on 4 different analytical platforms in plasma from a patient therapeutically transfused Hemopure as well as donor blood spiked with Hemopure at a level equivalent to the therapeutic loading dose (10% v/v).ResultsSignificant negative error ratios >50% of the total allowable error (>0.5tAE) were reported in 23/104 assays (22.1%), positive bias of >0.5tAE in 26/104 assays (25.0%), and acceptable bias between −0.5tAE and 0.5tAE error ratio was reported in 44/104 (42.3%). Analysis failed in the presence of Hemopure in 11/104 (10.6%). Observed error is further subdivided by platform, wavelength, dilution and reaction method.ConclusionAdministration of Hemopure (or other hemoglobin-based oxygen carriers) presents a challenge to laboratorians tasked with analyzing patient specimens. We provide laboratorians with a reference to evaluate patient samples, select optimal analytical platforms for specific analytes, and predict possible bias beyond the 4 analytical platforms included in this study.


Datum: 26.04.2018


LC-MS/MS reveals the formation of reactive ortho-quinone and iminium intermediates in saracatinib metabolism: Phase I metabolic profiling

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Mohamed W. Attwa, Adnan A. Kadi, Hany W. Darwish, Haitham Alrabiah
Saracatinib (AZD-0530) is a drug under clinical trials that developed by AstraZeneca. It is considered a dual kinase inhibitor, with selective actions as a Src inhibitor and a Bcr-Abl tyrosine-kinase inhibitor. Saracatinib chemical structure contains N-methyl piperazine group and 1,3 benzodioxole group. N-methyl piperazine group that can be bioactivated to form iminium intermediates which can be captured by KCN. 1,3-Benzodioxole group can be bioactivated to form ortho-quinone intermediate that can be conjugated with GSH. The formed conjugates are stable and can be identified using LC-MS/MS. In our current work, we are trying to give insight into the reasons that may be responsible for saracatinib side effects. Using LC-MS/MS, in vitro metabolic pathways were investigated for saracatinib in rat liver microsomes. Ten saracatinib phase I metabolites were characterized and the metabolic pathways were found to be hydroxylation, oxidation, reduction, dealkylation, N-oxidation and ether cleavage. Also, four potential reactive intermediates (three cyanide adducts and one GSH conjugate) were identified and the bioactivation mechanisms were explained. The existence of these four reactive metabolites may be the main reason for observed saracatinib side effects in clinical trials. Literature review showed no previous articles have been proposed the detailed structural identification of the formed reactive metabolites.

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Datum: 26.04.2018


A metabolomics study on the immunosuppressive effect of Tripterygium hypoglaucum (Levl.) Hutch in mice: The discovery of pathway differences in serum metabolites

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Yanlei Guo, Yongde Wang, Xuan Shi, Weihan Qin, Xiaomei Zhang, Jiahong Xu, Xiaoling Liu, Dajian Yang, Yong Yang
Tripterygium hypoglaucum (Levl.) Hutch (THH), a typical traditional Chinese medicine, is widely used in clinical practice for the treatment of rheumatoid arthritis, systemic lupus erythematous, and other connective tissue and autoimmune diseases. However, most related researches focused on the pharmacological effects of THH, while less attention has been paid to the immunosuppressive mechanism. The present study aims to determine the metabolic profiles, based on UPLC-Q-TOF-MS, identify differential metabolites, and find related metabolic pathways among the sensitization red blood cell (SRBC) model mice, THH treated mice, and cyclophosphamide treated group. Totally, 24 and 19 changed metabolites were found in the THH and cyclophosphamide treated groups respectively. Among them, we found that urocanate metabolic pathway change could be considered as the most relevant pathway associated with immunosuppression. This is the first study that comprehensively assessed the differences in metabolome between the model and THH treated groups. The results provide insights into the difference between the immunosuppressive mechanisms of THH and cyclophosphamide and also demonstrated that metabolomics is a valuable tool for investigating the efficacy of drugs in the treatment of diseases and the associated mechanism involved.


Datum: 26.04.2018


Calcium dobesilate: A drug treatment for diabetic retinopathy can negatively interfere with the measurement of glycated albumin using the enzymatic method

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Xiuzhi Guo, Fang Zhao, Yicong Yin, Danchen Wang, Li'an Hou, Jie Wu, Dandan Li, Xinqi Cheng, Liangyu Xia, Ermu Xu, Ling Qiu
BackgroundWe reported that calcium dobesilate, a vasoprotective agent mainly used for diabetic retinopathy (DR), negatively interferes with glycated albumin (GA) assays involving enzymatic methods.MethodsA calcium dobesilate standard was added to 3serum pools in vitro to prepare concentration-response series according to Clinical and Laboratory Standards Institute EP7-A2 guidelines. Percentage deviation between each drug concentration and the drug-free sample was calculated for 6 commercially available GA assays. The acceptable limit of deviation for GA was ±5.61%. For in vivo analyses, changes in serum concentrations of GA and calcium dobesilate were monitored in eight healthy participants before and after oral calcium dobesilate administration.ResultsAt 16 μg/ml calcium dobesilate, within the therapeutic range, the percentage deviations for Asahi Kasei, Maccura, Leadman, Homa, and Medicalsystem assays were −8.7% to −49.7%, −2.0% to −47.7%, and −10.1% to −35.7% for low-, medium- and high-GA level interference pools, respectively, exhibiting dose-dependent negative interference. In vivo, calcium dobesilate ingestion was associated with statistically significant, falsely decreased measurements in 5 GA assays, 2 h after daily 500 mg administration.ConclusionsCalcium dobesilate ingestion was associated with erroneously low measurements in 5 GA assays. The degree of interference varied greatly among the assays examined.


Datum: 26.04.2018


Long non coding RNA XIST as a prognostic cancer marker – A meta-analysis

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Qun Zhou, Wei Hu, Wei Zhu, Feng Zhang, Li Lin-lin, Cong Liu, Yi-yan Songyang, Cheng-cao Sun, Dejia Li
BackgroundThe X inactivate-specific transcript (XIST), derived from XIST gene, is aberrantly expressed in various cancers. High-expression of XIST is related to poor clinical outcome. This meta-analysis evaluated the potential role of XIST as novel predictor of prognosis in human cancer.Materials and methodsThis meta-analysis collected eligible studies about XIST and tumor prognosis through retrieving keywords in Web of Science, PubMed, Embase and the CNKI database, from 1993 to August 21, 2017. The quantitative meta-analysis was carried out with Stata SE12.0 and RevMan3.23 software. The aim was to determine whether XIST expression is associated with cancer prognosis and clinicopathology.ResultsA total of 858 patients from 10 eligible studies were included in the final meta-analysis. Overall, a significant negative association between XIST and overall survival (OS) time (HR = 2.62, 95% CI: 2.18–3.14) was observed. Statistical significance was also showed in subgroup meta-analysis stratified by the country, sample size, follow-up and publication year. It was reported that increased XIST was positively related to advanced clinical TNM stage (OR = 4.03, 95% CI: 2.22–7.30), lymph node metastasis (LNM) (OR = 2.70, 95% CI: 1.73–4.21), distant metastasis (DM) (OR = 2.61, 95% CI: 1.57–4.33) and tumor size (OR = 3.10, 95% CI: 2.24–4.30).ConclusionsLncRNA XIST may serve as a potential biomarker to predict solid tumor prognosis. This molecule can be effectively used to predict the clinical and pathological features of cancers.


Datum: 26.04.2018


Lectin-induced renal local complement activation is involved in tubular interstitial injury in diabetic nephropathy

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Jing-Min Zheng, Xian-Guo Ren, Zuan-Hong Jiang, De-Jun Chen, Wen-Jin Zhao, Li-Juan Li
BackgroundComplement has been suggested to be involved in diabetic nephropathy (DN), but the exact significance and underlying mechanisms remain unclear. Data about renal local complement activation in DN patients is scarce. The purpose of the study was to clarify the significance and mechanism of renal local complement activation in DN.MethodsSixty-two biopsy-proven DN patients were recruited. Renal expression of C1Q, factor B, C5b-9, MBL and MBL-associated serine protease 1 (MASP1) were detected and associated with the kidney damage.ResultsC5b-9, MBL and MASP1 was found to increase with the progression of DN. Especially, the level of C5b-9, MBL and MASP1 in tubular interstitium was closely associated with the damage degree of tubular interstitium. In addition, MBL and MASP1 co-localized and their levels in tubular interstitium correlated with the levels of C5b-9 in tubules and tubular interstitium.ConclusionIncreased renal local complement activation was present in DN patients and might contribute to the kidney damage, especially tubular interstitial damage. MBL pathway might play an important role in renal tubular interstitial complement activation. Methods against complement activation or MBL pathway might be effective in reducing renal tubular interstitial damage in DN patients.


Datum: 26.04.2018


Circulating parathyroid hormone and risk of hypertension: A meta-analysis

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Yi Zhang, Dian-zhong Zhang
ObjectivesTo examine the relationship between circulating parathyroid hormone (PTH) level and risk of hypertension (HTN).MethodsThe electronic databases of PubMed, Web of Science and Embase were searched up to December 2017, for prospective cohort studies on the relationship between circulating PTH level and risk of HTN. The pooled relative risk (RR) of HTN for the highest versus lowest category of circulating PTH level as well as their corresponding 95% confidence interval (CI) were calculated.ResultsA total of six prospective cohort studies, which involved 18,994 participants and 5040 HTN cases, were included in this meta-analysis. The overall multi-variable adjusted RR showed a positive relationship between circulating PTH level and risk of HTN (RR = 1.35, 95%CI: 1.09 to 1.67; P = 0.006). A substantial level of heterogeneity was observed among the studies (P < 0.001, I2 = 77.6%). No evidence of publication bias was observed among the studies according to Begg's rank-correlation test (P = 0.452).ConclusionsThe existing evidence suggests that an increase in circulating PTH level may be associated with a higher risk of HTN. However, due to the limited number of included studies, more well-designed prospective cohort studies are needed to further elaborate the issues examined in this study.


Datum: 26.04.2018


Association between SCN1A and SCN2A mutations and clinical/EEG features in Chinese patients from epilepsy or severe seizures

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Yanting Kong, Kai Yan, Liyuan Hu, Mingbang Wang, Xinran Dong, Yulan Lu, Bingbing Wu, Huijun Wang, Lin Yang, Wenhao Zhou
BackgroundWe investigated the association between SCN1A and SCN2A mutations and clinical phenotype and electroencephalography (EEG) features.MethodsIn this study, 48 patients suffered from epilepsy or severe seizures with SCN1A and SCN2A mutations were recruited. Medical data and molecular diagnosis were analyzed.ResultsA total of 47 mutations were identified, including 33 novel mutations. The onset of most epilepsy caused by SCN1A mutations (1-6 m) was later than that of SCN2A mutations (neonatal). SCN1A mutations included truncating mutations and missense mutations occurred in the crucial region were associated with more severe phenotypes and developmental delay (85.7%, P = 0.020). De novo mutations or truncating mutations of SCN2A mutations are mainly associated with severe phenotypes. The proportion of initial abnormal EEG of SCN2A mutation was higher than that of SCN1A mutation (54.2%, 100%). Patients with SCN1A mutations showed more focal epileptiform discharges (69.2%), while patients with SCN2A mutations had more multifocal epileptiform discharges (53.8%). Sodium channel blockers were less effective for patients with SCN1A mutations and SCN2A mutations with early seizures onset.ConclusionsOur study expanded the mutation spectrum of the SCN1A and SCN2A, and led to a better understanding of the similarities and difference in the genetic and clinical features between the two genes.


Datum: 26.04.2018


Human epididymis protein 4 in endometrial cancer: A meta-analysis

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Li-man Li, Yu-xuan Zhu, Yi Zhong, Tao Su, Xiao-ming Fan, Qian Xi, Ming-yong Li, Jun Fu, Hong Tan, Shan Liu
BackgroundSerum human epididymis protein 4 (HE4) is a potential marker for endometrial cancer (EC), however, the diagnostic value of HE4 for EC remains controversial. In this study, we performed a meta-analysis to estimate the diagnostic accuracy of serum HE4 for EC.MethodsLiterature reports of the diagnostic accuracy of serum HE4 for EC were systematically identified using online data-bases. The meta-analysis was performed using STATA 12.0, Meta-Disc 1.4, and Review Manager 5.2.ResultsA total of 4182 participants and 23 studies were included in our meta-analysis. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.65 (95% CI: 0.56–0.73), 0.91 (95% CI: 0.84–0.95), (95% CI: 4.38–12.64), 0.38 (95% CI: 0.31–0.47), 19.46 (95% CI: 11.61–32.62) and 0.84 (95% CI: 0.81 to 0.87), respectively. Our overall analysis suggested that HE4 is a useful diagnostic marker for EC. Subgroup analysis indicated that studies with benign disease controls showed higher diagnostic accuracies than those with healthy controls.ConclusionSerum HE4 may serve as a potential biomarker for EC diagnosis. Due to certain limitations, this conclusion should to be cautiously interpreted.


Datum: 26.04.2018


Prognostic value of pretreatment plasma D-dimer levels in patients with diffuse large B cell lymphoma (DLBCL)

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Bin Liu, Bo Li, Pingting Zhou, Wenqin Yue, Tao Wang, Jianmin Wang, Xiaoxia Hu, Weiping Zhang, Jie Chen, Li Chen, Lei Gao, Miaoxia He, Jianmin Yang
BackgroundWe assessed the prognostic significance of D-dimer in patients of diffuse large B cell lymphoma (DLBCL).MethodsWe performed a retrospective study including 254 patients who were newly diagnosed DLBCL. X-tile was used to generate a cutoff value for D-dimer. Both univariate screen by Cox proportional hazard model and multivariable analysis by Cox regression model were used to assess the impact of pretreatment D-dimer levels on the overall survival (OS).ResultAccording to X-tile, the optimal cut-off value of D-dimer for prediction of survival was set as 1.6 μg/mL, and a D-dimer level ≥ 1.6 μg/mL was significantly associated with poor overall survival (OS) (OS: 31.7 vs. 79.1%, P < 0.001). In multivariable analysis, it was found that a higher D-dimer level was an independent predictor for worse OS (Hazard ratio (HR): 3.594 95% Confidence interval (CI): 2.296–5.267, P < 0.001). In subgroup analysis of International Prognostic Index (IPI), survival of low-risk and intermediate-risk group with a D-dimer level ≥ 1.6 μg/mL were both similar to that of the high-risk group (OS: 31.6 vs. 36.5%, P = 0.957; OS: 38.0 vs. 36.5%, P = 0.758). In addition, among patients treated with surgery, those with higher D-dimer had substantially worse survival than that with lower D-dimer (OS: 27.0 vs. 84.5%, P < 0.001).ConclusionPretreatment D-dimer is a simple but effective predictor of survival among patients with DLBCL.


Datum: 26.04.2018


Advances in biomarkers for dermatomyositis

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Wei-ming Yang, Juan-juan Chen
Dermatomyositis (DM) and polymyositis (PM) are heterogeneous complex autoimmune diseases involving muscle damage. Patients with DM and PM display a wide spectrum of clinical manifestations and serological biomarkers, which may mislead and delay the proper diagnosis. Therefore, specific biomarkers or indicators for diagnosing DM and PM and monitoring disease activity are essential. Significant progress has been made through identifying novel serological biomarkers for DM and PM in recent years. Our aim is to focus on novel biomarkers for diagnosing and monitoring disease activity in DM and PM to highlight their predictive value and applicability in clinical practice.


Datum: 26.04.2018


Novel artificial stool material for external quality assurance (EQA) on a fecal immunochemical test for hemoglobin (FIT): The confirmed utility of stable hemoglobin and an internal standard material

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Ryota Yasui, Miyu Yamada, Shizuka Takehara, Ikunosuke Sakurabayashi, Katsunori Watanabe
The fecal immunochemical test for hemoglobin (FIT), which detects lower gastrointestinal bleeding, is widely accepted for population-based colorectal cancer (CRC) screening programs. However, the FIT screening process has not been standardized yet, and standardizing the pre-analytical phase and establishing an external quality assurance (EQA) program compliant with ISO requirements is urgently needed. Although there have been various attempts to establish EQA materials suitable for FIT, no materials have yet been reported to have sufficient uniformity and acceptable immunochemical stability of hemoglobin (Hb). The Health Care Technology Foundation (HECTEF; Tokyo Japan) is now developing a ready-to-use artificial stool containing Hb and an internal standard, glycerol. Accordingly, we verified the adaptability and efficacy of this material for the evaluation of the specimen collection phase of FIT. This material uniformly contained both Hb and glycerol. The glycerol allowed us to estimate the weight of the collected artificial stool and to correct the Hb concentration with the estimated weight. Furthermore, the stability of both Hb and glycerol were confirmed to be sufficient for an EQA material under appropriate storage, in-use, repeated freeze-thaw, and heated conditions. These in-house performance characteristics suggest that HECTEF artificial stool is acceptable as an EQA material for FIT.


Datum: 26.04.2018


Potential role of “omics” technique in prenatal diagnosis of congenital heart defects

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Lizhu Chen, Johnny Guan, Qiuju Wei, Zhengwei Yuan, Mo Zhang
Congenital heart defect (CHD) is one of the most common birth defects and is the leading cause of neonatal death. Currently, there are no biomarkers available for prenatal diagnosis of CHD. Clinical strategies to diagnose CHD mostly depend on fetal echocardiography. Recent advances in “omics” techniques have opened up new possibilities for biomarker discoveries. In this review, we discuss recent advances in prenatal detection of CHD using biomarkers obtained by “omics” approaches, including genomics, proteomics, metabolomics, and others. There is great potential in obtaining various kinds of parameters using “omics” studies to facilitate early and accurate diagnosis of CHD.


Datum: 26.04.2018


Dynamic reference intervals for coagulation parameters from infancy to adolescence

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Christina Weidhofer, Elias Meyer, Robin Ristl, Helmut Wiedemann, Janne Cadamuro, Ulrike Kipman, Jakob Zierk, Christoph Male, Peter Quehenberger, Elisabeth Haschke-Becher, Elisa Einwallner
IntroductionPractical and ethical challenges as well as time and costs have restricted the generation of pediatric reference intervals. Therefore, pediatric reference intervals on coagulation parameters based on solid evidence are still scarce. Furthermore, reference intervals by age-group cannot reflect the dynamics of age and sex specific coagulation values during childhood. This study is the first to close this gap and provide continuous age and sex dependent reference intervals during childhood in hemostasis.MethodsWe used an innovative indirect method for providing continuous reference intervals for five common coagulation parameters: Activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin clotting time (TT), fibrinogen (FIB) and antithrombin (AT). Calculations were performed using retrospective laboratory data from pediatric patients between 2005 and 2015 of two major Austrian hospitals, resulting in a total of 195.360 measurements (aPTT: 55,100; PT: 35,492; TT: 35,295; FIB: 49,789; AT: 19,684).ResultsThis multicenter study provides calculations of continuous reference intervals for five common coagulation parameters in a large pediatric cohort, accounting for age and gender.ConclusionTo the best of our knowledge, this is the first multicenter study, determining continuous pediatric coagulation reference intervals based on a large retrospective dataset.


Datum: 26.04.2018


Meta-analysis of mitochondrial T16189C polymorphism for cancer and Type 2 diabetes risk

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Taruna Kumari, Meenakshi Vachher, Savita Bansal, Rameshwar N.K. Bamezai, Bhupender Kumar
AimWhereas many previous studies have revealed that mitochondrial DNA (mtDNA) polymorphism T16189C is associated with the risk of cancer and Type 2 diabetes mellitus (T2DM), there are others that have disputed the same. As a result, clarity on the role of mitochondrial T16189C in these disorders is missing. The aim of this study is to evaluate the association of T16189C polymorphism with the risk of cancer and T2DM development by pooling all case-control studies available.MethodsPublished studies till November 2017 were searched from PubMed, Google scholar, Google and EMBASE and isolated a total of 36 studies having 44,203 subjects (20,439 cases and 23,764 controls) based on strict inclusion and exclusion criteria. We used the statistical software “R” to calculate the Pooled Odds Ratios and 95% confidence intervals to evaluate the association of T16189C polymorphism with a possible risk towards cancer and T2DM development.ResultFrom the meta-analysis, we obtained Pooled Odds Ratios using Random effect model for cancer (OR: 1.20, 95% CI: 0.96–1.49, P = 0.104) and for T2DM (OR: 1.22, 95% CI: 1.09–1.36, P = 0.0004). In the subgroup analysis with Random effect model, we found that both Asians and Caucasians were at a statistically significant risk (OR: 1.25, P < 0.0001 and OR: 1.20, P < 0.0001, respectively) for the development of T2DM, whereas, a statistically non-significant risk (OR: 1.28 P = 0.1965 and OR: 1.16, P = 0.1148) emerged for the development of cancer. There was no evidence of a significant publication bias (Egger's and Begg's test) in this meta-analysis. Further sensitivity analysis also demonstrated that our meta-analysis was relatively stable and credible.ConclusionIndividuals with ‘C’ allele at position 16,189 within the mitochondrial D-loop are seemingly at a higher risk of developing T2DM and cancer. However, before arriving at generalizations, it would be pertinent to conduct similar studies in different populations with larger numbers to corroborate these results, especially in cancer.


Datum: 26.04.2018


Analysis of human blood plasma cell-free DNA fragment size distribution using EvaGreen chemistry based droplet digital PCR assays

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): M. Rohan Fernando, Chao Jiang, Gary D. Krzyzanowski, Wayne L. Ryan
BackgroundPlasma cell-free DNA (cfDNA) fragment size distribution provides important information required for diagnostic assay development. We have developed and optimized droplet digital PCR (ddPCR) assays that quantify short and long DNA fragments. These assays were used to analyze plasma cfDNA fragment size distribution in human blood.MethodsAssays were designed to amplify 76,135, 490 and 905 base pair fragments of human β-actin gene. These assays were used for fragment size analysis of plasma cell-free, exosome and apoptotic body DNA obtained from normal and pregnant donors.ResultsThe relative percentages for 76, 135, 490 and 905 bp fragments from non-pregnant plasma and exosome DNA were 100%, 39%, 18%, 5.6% and 100%, 40%, 18%,3.3%, respectively. The relative percentages for pregnant plasma and exosome DNA were 100%, 34%, 14%, 23%, and 100%, 30%, 12%, 18%, respectively. The relative percentages for non-pregnant plasma pellet (obtained after 2nd centrifugation step) were 100%, 100%, 87% and 83%, respectively.ConclusionNon-pregnant Plasma cell-free and exosome DNA share a unique fragment distribution pattern which is different from pregnant donor plasma and exosome DNA fragment distribution indicating the effect of physiological status on cfDNA fragment size distribution. Fragment distribution pattern for plasma pellet that includes apoptotic bodies and nuclear DNA was greatly different from plasma cell-free and exosome DNA.


Datum: 26.04.2018


Cell death after traumatic brain injury: Detrimental role of anoikis in healing

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Alexandre P. Sater, Leonard T. Rael, Allen H. Tanner, Mark J. Lieser, David L. Acuna, Charles W. Mains, David Bar-Or
Within the first few hours of a traumatic brain injury, the activity of extracellular matrix degradative enzymes increases. As a result, the blood brain barrier becomes disrupted as secondary white matter injury increases. Anoikis, a form of apoptosis, results from cells detaching from the extracellular matrix leading to cell death. This “homelessness” (anoikis) of cells hinders recovery progression, exacerbating brain injury while disrupting synaptic plasticity and other central nervous system functions. Here, we discuss the current knowledge of molecular pathways and proteins involved in both the activation and inhibition of anoikis.


Datum: 26.04.2018


Blue-green discoloration of urine and false nephrotic range proteinuria at dipstick urinalysis

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): José Antonio Tesser Poloni, Marina Gomes de Moraes Sassi, Tiago Franco de Oliveira, Liane Nanci Rotta, Mark Anthony Perazella
A 32 year-old woman presented to the emergency department with symptoms of urinary tract infection. Over the past 2 days, she reported the use of a medication whose active compounds were methenamine (120 mg) + methylthioninium chloride (20 mg). A collected urine sample had a strong blue-green discoloration. Uroculture was negative and dipstick urinalysis revealed the following results: SG 1.015, pH  7, Albumin 3+, Bilirubin 2+ and Haemoglobin 2+. Urine microscopic analysis revealed 5–6 squamous epithelial cells/high power field (HPF), 5–6 leukocytes/HPF and 7–8 erythrocytes/HPF. No bacteria, cellular casts, or renal tubular epithelial cells were present in the urine sample. The most remarkable feature of the urine sediment was that some cells (squamous epithelial cells, macrophages, leukocytes and erythrocytes) were strongly stained in blue. The albuminuria measured by dipstick shows 3+ (300 mg/dL), but in turbidimetric method the urine protein concentration was 18 mg/dL, showing an important interference of methylene blue on the dipstick albumin area.


Datum: 26.04.2018


Relationship between plasma angiogenic growth factors and diabetic foot ulcers

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Zongcun Chen, Shasha Fu, Zurong Wu, Jinyi Chen, Yalian Huang, Yi Wang, Maoxiong Fu
BackgroundAngiogenic growth factors play an important role in wound healing. However, their associations with diabetic foot ulcers (DFUs) in humans have rarely been investigated. We examined the relationships between circulating concentrations of vascular endothelial growth factor (VEGF)-A and placenta growth factor (PlGF), and DFU risk.MethodsWe recruited 447 participants, including 169 DFU patients, 182 diabetes patients without DFUs, and 96 diabetes-free individuals. Plasma VEGF-A and PlGF concentrations were measured using commercial enzyme immunoassay kits.ResultsConcentrations of VEGF-A and PlGF in DFU patients were higher than those in diabetes-free controls (P < 0.05), but lower than those in the diabetic controls (P < 0.05). Increased concentrations of VEGF-A and PlGF were associated with a reduced risk of DFUs. The odds ratios (95% confidence intervals) were 0.93 (0.88, 0.97) for every 10 pg/ml increase in VEGF-A concentrations, and 0.96 (0.94, 0.99) for every 5 pg/ml increase in PlGF concentrations. VEGF-A concentrations were positively related to BMI, glycated hemoglobin (HbA1c), hypertension, and neuropathy, and PlGF was positively correlated to age, HbA1c, and hypertension, among DFU patients.ConclusionVEGF-A and PlGF play important roles in the development of DFU but need to be confirmed in prospective studies.


Datum: 26.04.2018


In silico prediction of the pathogenic effect of a novel variant of BCKDHA leading to classical maple syrup urine disease identified using clinical exome sequencing

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Cynthia Fernández-Lainez, Carmen Aláez-Verson, Isabel Ibarra-González, Sergio Enríquez-Flores, Karol Carrillo-Sanchez, Leonardo Flores-Lagunes, Sara Guillén-López, Leticia Belmont-Martínez, Marcela Vela-Amieva
Maple syrup urine disease (MSUD) is a metabolic disorder caused by mutations in three of the branched-chain α-keto acid dehydrogenase complex (BCKDC) genes. Classical MSUD symptom can be observed immediately after birth and include ketoacidosis, irritability, lethargy, and coma, which can lead to death or irreversible neurodevelopmental delay in survivors. The molecular diagnosis of MSUD can be time-consuming and difficult to establish using conventional Sanger sequencing because it could be due to pathogenic variants of any of the BCKDC genes. Next-generation sequencing-based methodologies have revolutionized the molecular diagnosis of inborn errors in metabolism and offer a superior approach for genotyping these patients. Here, we report an MSUD case whose molecular diagnosis was performed by clinical exome sequencing (CES), and the possible structural pathogenic effect of a novel E1α subunit pathogenic variant was analyzed using in silico analysis of α and β subunit crystallographic structure. Molecular analysis revealed a new homozygous non-sense c.1267C>T or p.Gln423Ter variant of BCKDHA. The novel BCKDHA variant is considered pathogenic because it caused a premature stop codon that probably led to the loss of the last 22 amino acid residues of the E1α subunit C-terminal end. In silico analysis of this region showed that it is in contact with several residues of the E1β subunit mainly through polar contacts, hydrogen bonds, and hydrophobic interactions. CES strategy could benefit the patients and families by offering precise and prompt diagnosis and better genetic counseling.


Datum: 26.04.2018


Reference limits of the urinary gamma-glutamyltransferase in a healthy population and effects of short-term storage on the enzyme activity

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Yãnaí S. Bollick, José Antonio M. de Carvalho, Etiane Tatsch, Bruna S. Hausen, Rafael N. Moresco
BackgroundGamma-glutamyltransferase (GGT) is present mainly in proximal renal tubule, and urinary GGT is an indicator of tubular damage since it may show renal changes before they are identified by using conventional measurements. Therefore, it is of interest to establish the reference limits of urinary GGT for a healthy population, as well as to investigate the stability of GGT in urine samples stored at 4 °C and −20 °C.MethodsGGT was assessed in urine samples from 127 healthy patients by use of a reference method based on the 5-Amino-2-Nitrobenzoate formation. Stability of GGT was evaluated in 10 urine samples stored at temperatures of 4 °C and −20 °C for a period up to 4 weeks.ResultsUrinary GGT values for healthy volunteers were 14 U/g creatinine for the lower reference limit and 79 U/g creatinine for the upper reference limit. Urinary GGT values were approximately 56% lower in samples stored at −20 °C than fresh samples, while samples stored at 4 °C presented a decrease of 11% in GGT values compared to fresh samples.ConclusionsReference limits for urinary GGT in healthy subjects were 14 to 79 U/g creatinine, and it is recommended to measure urinary GGT in fresh specimens.


Datum: 26.04.2018


Platelet-to-lymphocyte ratio in advanced Cancer: Review and meta-analysis

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Bo Li, Pingting Zhou, Yujie Liu, Haifeng Wei, Xinghai Yang, Tianrui Chen, Jianru Xiao
BackgroundInflammation biomarkers have been introduced into clinical practice for risk-rating in treatment of patients with cancer. We aimed to confirm the prognostic role of platelet-to-lymphocyte ratio (PLR) as a powerful biomarker for patients with advanced cancer.MethodA systematic literature search was conducted through PubMed, Embase and Web of Science databases for studies on advanced tumors. Research articles that analyzed the PLR and hazard ratios (HR) in patients with overall survival (OS) or progression-free survival (PFS) data were involved. Two authors assessed the eligibility of trials and extracted data independently. Meta-analyses were performed with random-effect models. Data heterogeneity was calculated with the I2 method.ResultsThirty-three eligible cohort studies including 8215 patients were further analyzed. Elevated PLR was associated with reduced OS (HR = 1.45, 95% CI, 1.31–1.61, p < 0.001) and PFS (HR = 1.73, 95% CI, 1.31–2.29, p < 0.001) in patients with advanced cancer. A extreme result was observed in a subgroup analysis in metastatic renal cancer with the worst OS (HR = 2.47, 95% CI, 1.32–4.62, p = .005) and PFS (HR = 3.89, 95% CI, 1.23–12.28, p = 0.021).ConclusionsPatients with high pretreatment blood PLR level have poor OS and PFS. Further investigations are needed to explore the underlying mechanisms.


Datum: 26.04.2018


Biomarker potential of IL-6 and VEGF-A in ascitic fluid of epithelial ovarian cancer patients

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Venus Dalal, Raman Kumar, Sunesh Kumar, Alpana Sharma, Lalit Kumar, Jai Bhagwan Sharma, Kallol Kumar Roy, Neeta Singh, Perumal Vanamail
BackgroundOvarian cancer is represented with significantly higher mortality rate predominately due to asymptomatic behaviour during initial disease course and at diagnosis majority patients already progressed to advanced stage. Acellular fraction of ascites in epithelial ovarian cancer (EOC) has been suggested to promote growth of tumor cells by providing ambient micro-environment for their proliferation. This acellular fraction contains multiple growth factors including IL-6 and VEGF-A, which were exploited to establish their bio-marker significance in EOC patients.MethodsIL-6 and VEGF-A levels in ascitic fluid of 30 EOC patients and 15 controls were measured using high sensitivity sandwich enzyme linked immune sorbent (ELISA) assay. Their levels were correlated with clinico-pathological characteristics and bio-marker potential was assessed.Results and conclusionEOC patients showed significantly higher levels for IL-6 (median-5636 pg/ml) and VEGF-A (median-4556 pg/ml) in ascitic fluid compared to controls. Levels of IL-6 and VEGF-A significantly correlated with clinico-pathological parameters. ROC curves of IL-6 and VEGF-A showed absolute combination of sensitivity and specificity. Kaplan Meier analysis demonstrated that higher levels of IL-6 and VEGF-A were significantly associated with shorter progression free survival. Thus, this study revealed that IL-6 and VEGF-A have great potential to be used as superior bio-markers for progression free survival in future after validation in larger patients' cohort.


Datum: 26.04.2018


Sustained or higher levels of growth factors in platelet-rich plasma during 7-day storage

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Ying-Hao Wen, Wan-Ying Lin, Chi-Jui Lin, Yu-Chen Sun, Pi-Yueh Chang, Hsin-Yao Wang, Jang-Jih Lu, Wen-Lin Yeh, Tzong-Shi Chiueh
BackgroundThe effectiveness of platelet-rich plasma (PRP) for treating soft tissue injuries is still controversial. Most of PRPs were prepared simply by concentrating in volume and were injected right after preparation in physician offices. Neither platelet count nor growth factors were quantitated in advance. We prepared and stored leukocyte and platelet-rich plasma (L-PRP) by regular separation protocols for blood components in the blood bank. And we investigated the dynamic change of growth factors in the L-PRPs over the period of storage.MethodsThe L-PRPs were prepared by 2-step centrifugation and stored agitatedly at22 °C for 7 days in the platelet incubator of blood bank. Levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-basic, hepatocyte growth factor (HGF), insulin-like growth factor (IGF)-1, platelet derived growth factor (PDGF)-AB, endothelial growth factor (EGF), and transforming growth factor (TGF) over the period of storage were evaluated daily after freeze-thawing to release growth factors from platelet.ResultsCompared to original whole blood, platelet concentration, VEGF, FGF-basic, PDGF-AB, EGF, and TGF-beta1 levels of L-PRPs significantly increased after PRP preparation. Both HGF and IGF-1 in L-PRPs remained the original plasma level. Platelet, FGF, and TGF-beta1 concentrations sustained during storage, and concentrations of VEGF, HGF, IGF-1, PDGF-AB, and EGF in L-PRPs increased over the period of storage.ConclusionsDuring the storage in blood bank, platelet counts and 7 growth factors sustained or reached higher level than L-PRP obtained on first day. Multiple injections of stored PRPs could become applicable by our protocol.


Datum: 26.04.2018


Long noncoding RNA LINC00152 as a novel predictor of lymph node metastasis and survival in human cancer: a systematic review and meta-analysis

Publication date: August 2018
Source:Clinica Chimica Acta, Volume 483
Author(s): Jiaming Zhang, Minuo Yin, Junming Huang, Zhengtao Lv, Shuang Liang, Xiaoao Miao, Fang Huang, Yingchao Zhao
BackgroundLINC00152, a novel long noncoding RNA (lncRNA), was identified as an oncogene involved various cancers. This study was designed to explore the clinical significance and prognosis role of LINC00152.MethodsEligible studies were recruited by a systematic search in PubMed, Web of Science, and Embase up to August 23, 2017. Odds ratios (ORs), hazard ratios (HRs) and 95% confidence interval (95% CI) were pooled using Review Manager 5.3 and STATA 12.0.ResultA total of 10 studies with 913 patients were included to evaluate the association between LINC00152 expression and clinicopathological factors, overall survival (OS) and disease-free survivals (DFS). The results indicated that the expression level of LINC00152 was positively correlated with tumor size (OR = 5.19, 95% CI: 2.33–11.52, p < .0001), TNM stage (OR = 3.12, 95% CI: 1.77–5.51, p < .0001) and lymph node metastasis (OR = 3.41, 95% CI: 2.13–5.48, p < .00001). Moreover, elevated LINC00152 could predict unfavorable OS with pooled HR of 1.66 (95% CI: 1.29–2.13, p < .0001) and poor DFS (HR = 2.13, 95% CI: 1.39–3.25, p = .0005) in cancer patients.ConclusionLINC00152 was correlated with advanced clinicopathological features and poor prognosis as a novel predictive biomarker in various cancers.


Datum: 26.04.2018


Comparison of serum serotonin and serum 5-HIAA LC-MS/MS assays in the diagnosis of serotonin producing neuroendocrine neoplasms: A pilot study

Publication date: July 2018
Source:Clinica Chimica Acta, Volume 482
Author(s): Mikael Lindström, Niina Tohmola, Risto Renkonen, Esa Hämäläinen, Camilla Schalin-Jäntti, Outi Itkonen
BackgroundSerotonin (5-hydroxytyramine) is a mediator of gastrointestinal smooth muscle contraction, and is secreted by neuroendocrine neoplasms (NENs). We developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for serum serotonin to be used in NEN diagnostics and follow-up.MethodsWe used serum samples from healthy volunteers (n = 31) and patients suspected or monitored for NEN (n = 98). Serotonin-D4 internal standard was added to samples before solid phase extraction (SPE) and quantification by LC-MS/MS. The effects of sample handling and preparation on serotonin stability were studied. Finally, we established a provisional reference range for serum serotonin and compared our assay with serum 5-hydroxyindoleacetic acid (5-HIAA) for detection of NENs.ResultsOur assay is sensitive and has a wide linear range (10–10,000 nmol/l). Serum serotonin is stable for 7 days at room temperature and for 3 months at −20 °C. Sampling temperature is not critical. Normal range for serum serotonin was 270–1490 nmol/l. We found that serum serotonin and 5-HIAA performed equally well as diagnostic tests for NENs.ConclusionsOur LC-MS/MS assay for serum serotonin is well suited for clinical research and patient diagnostics. Our results confirm that it can complement 5-HIAA in diagnosis of NENs.


Datum: 26.04.2018


 


Category: Current Chemistry Research

Last update: 28.03.2018.






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