Showing papers in "Journal of Clinical Laboratory Analysis in 2017"

The ACE2 G8790A Polymorphism: Involvement in Type 2 Diabetes Mellitus Combined with Cerebral Stroke.

Abstract: Background We aimed to investigate the correlations between ACE2 polymorphisms and type 2 diabetes mellitus (T2DM) combined with cerebral stroke (CS). Methods A total of 346 patients treated or hospitalized in our hospital were enrolled, including 181 cases without cerebrovascular complications (T2DM group) and 165 cases combined with CS (T2DM + CS group); 284 healthy individuals were selected as the control group. PCR-RFLP and ELISA were used to analyze ACE2 G8790A polymorphisms and serum ACE2 levels, respectively. Results Significant differences were observed in the genotype/allele frequency of ACE2 G8790A between the T2DM + CS and control groups, and the T2DM and T2DM + CS groups, and in the genotype frequency of ACE2 G8790A between the T2DM and the control groups. The A allele may increase the risk of T2DM combined with CS. The AA genotype may also increase the risk of T2DM combined with CS (OR = 3.733, 95%CI = 2.069-6.738; OR = 3.597, 95%CI = 1.884-6.867). Serum ACE2 levels showed statistically significant differences among the groups. Systolic pressure and diastolic pressure were protective factors of T2DM combined with CS. Conclusion The ACE2 G8790A polymorphism in T2DM patients was correlated with CS, and the A allele might be a risk factor of T2DM combined with CS.

Association of hematocrit with blood pressure and hypertension.

Abstract: Background Hypertension (HTN) is a risk factor for stroke, renal failure, and cardiovascular disease. The association between biochemical and hematological parameters with high blood pressure may provide a more precise approach to risk prediction conferred by HTN in these patients. Objective The aim of current study was to explore whether biochemical and hematological parameters are associated with HTN in a cohort study with a 7-year follow-up. Materials and Methods A total of 9808 individuals were enrolled and recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study, and biochemical and hematological factors were measured in all subjects. Univariate and multivariate logistic regression analysis were performed to determine the association of biochemical and hematological parameters with HTN. Results Several biochemical parameters including fasting plasma glucose (FBG), serum high-sensitivity C-reactive protein (hs-CRP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and uric acid were increased in hypertensive participants. In contrast, serum high-density lipoprotein cholesterol (HDL-C) was lower in hypertensive individuals. Furthermore, we demonstrated that hematological parameters including white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (HGB), hematocrit (HCT), and mean corpuscular hemoglobin (MCH) were higher in the hypertensive group compared to the control group. But mean corpuscular volume (MCV), and red cell distribution width (RDW), were decreased in the hypertensive group. Furthermore, our results strongly suggested that among these parameters, hematocrit was the independent risk factor for hypertension in the population. Conclusion We demonstrated the association of altered biochemical and hematological factors with hypertension supporting the value of emerging markers for early prediction of high blood pressure in prone individuals.

Combination of preoperative NLR, PLR and CEA could increase the diagnostic efficacy for I-III stage CRC.

Abstract: BACKGROUND Inflammation plays an important role in the development and progression of CRC. The members of inflammatory biomarkers, preoperative NLR and PLR, have been proved by numerous studies to be promising prognostic biomarkers for CRC. However, the diagnostic value of the two biomarkers in CRC remains unknown, and no study reported the combined diagnostic efficacy of NLR, PLR and CEA. METHODS Five hundred and fifty-nine patients with I-III stage CRC undergoing surgical resection and 559 gender- and age-matched healthy controls were enrolled in this retrospective study. NLR and PLR were calculated from preoperative peripheral blood cell count detected using white blood cell five classification by Sysmex XT-1800i Automated Hematology System and serum CEA were measured by electrochemiluminescence by ELECSYS 2010. The diagnostic performance of NLR, PLR and CEA for CRC was evaluated by ROC curve. RESULTS Levels of NLR and PLR in the cases were significantly higher than them in the healthy controls. ROC curves comparison analyses showed that the diagnostic efficacy of NLR (AUC=.755, 95%CI=.728-.780) alone for CRC was significantly higher than PLR (AUC=.723, 95%CI=.696-.749, P=.037) and CEA (AUC=.690, 95%CI=.662-.717, P=.002) alone. In addition, the diagnostic efficacy of the combination of NLR, PLR and CEA(AUC=.831, 95%CI=.807-.852)for CRC was not only significantly higher than NLR alone but also higher than any combinations of the two of these three biomarkers (P<.05). Moreover, the NLR and PLR in the patients with TNM stage I/II was higher than that in the healthy controls, and patients with stage III had a higher NLR and PLR than those with stage I/II, but no significant difference was observed. CONCLUSION Our study indicated that preoperative NLR could be a CRC diagnostic biomarker, even for early stage CRC, and the combination of NLR, PLR and CEA could significantly improve the diagnostic efficacy.

Association between malnutrition and hyperhomocysteine in Alzheimer's disease patients and diet intervention of betaine.

Abstract: Background Alzheimer's disease (AD) is a neurodegenerative disease, which is associated with malnutrition and hyperhomocysteine. The current study aimed to analyze the relationship between malnutrition and hyperhomocysteine in AD patients, and effects of diet intervention with betaine on the disease. Methods The nutritional statuses of the AD patients were assessed by short form mini nutritional assessment (MNA-SF). The levels of Hcy, tau hyperphosphorylation, synaptic proteins, blood inflammatory factors were measured by enzymatic cycling assay, Western blot and ELISA. The cognitive function was measured by AD assessment scale (ADAS-cog). Results There was a significant difference in mental status between normal people and AD patients (P<.05). Overall, malnutrition was reported in a larger proportion of AD patients and high level of Hcy was closely associated with malnutrition. Betaine decreased the levels of phosphorylated tau, elevated PP2Ac activity and inhibited Aβ accumulation (P<.05). The levels of IL-lβ and TNF-α were significantly higher in the untreatment group while much lower in the intervention group (P<.05). After intervention of betaine treatment, the expression level of Hcy can be restored and betaine can effectively suppress inflammation as well as trigger an increase in memory-related proteins. ADAS-Cog suggested that significant improvement was found after the intervention of betaine. Conclusions AD was associated with both malnutrition and higher levels of Hcy. Betaine could restore Hcy expression to normal level in AD patient, which might ameliorate memory deficits.

Feature Analysis and Automatic Identification of Leukemic Lineage Blast Cells and Reactive Lymphoid Cells from Peripheral Blood Cell Images.

Abstract: Background Automated peripheral blood (PB) image analyzers usually underestimate the total number of blast cells, mixing them up with reactive or normal lymphocytes. Therefore, they are not able to discriminate between myeloid or lymphoid blast cell lineages. The objective of the proposed work is to achieve automatic discrimination of reactive lymphoid cells (RLC), lymphoid and myeloid blast cells and to obtain their morphologic patterns through feature analysis. Methods In the training stage, a set of 696 blood cell images was selected in 32 patients (myeloid acute leukemia, lymphoid precursor neoplasms and viral or other infections). For classification, we used support vector machines, testing different combinations of feature categories and feature selection techniques. Further, a validation was implemented using the selected features over 220 images from 15 new patients (five corresponding to each category). Results Best discrimination accuracy in the training was obtained with feature selection from the whole feature set (90.1%). We selected 60 features, showing significant differences (P < 0.001) in the mean values of the different cell groups. Nucleus-cytoplasm ratio was the most important feature for the cell classification, and color-texture features from the cytoplasm were also important. In the validation stage, the overall classification accuracy and the true-positive rates for RLC, myeloid and lymphoid blast cells were 80%, 85%, 82% and 74%, respectively. Conclusion The methodology appears to be able to recognize reactive lymphocytes well, especially between reactive lymphocytes and lymphoblasts.

Urinary exosomes as a novel biomarker for evaluation of α-lipoic acid's protective effect in early diabetic nephropathy

Abstract: Background Long-term administration of α-lipoic acid (α-LA) is proved to ameliorate renal impairment. Herein we assessed serum, urinary biomarkers and vascular endothelium function to evaluate its short-period therapeutic effect and identify novel biomarkers for diabetic nephropathy (DN). Methods Sixty-two microalbuminuria-stage DN patients were randomly divided into two groups and received the following treatment for 8 weeks: (1) routine treatment(DM group); (2) routine treatment with 600 mg/d α-lipoic acid intravenously (α-LA group). Another total of 21 patients were recruited for the second-stage study and randomly divided into two groups: normoalbuminuria (UAER <30 mg/24 h) and microalbuminuria (UAER from 30-300 mg/24 h). Results With α-LA treatment, urinary albumin excretion rates (UAER), serum creatinine (SCr) and malonaldehyde (MDA) declined significantly, whereas plasma superoxide dismutase (SOD)activity increased and endothelium-dependent flow mediated vasodilation (FMD) flexibility improved dramatically. Furthermore, the improvement of FMD showed positive correlation with the variation in MDA and SOD as well (r values are .516 and .435, P<.01 and P<.05, respectively). In contrast, these markers have no significant difference in the DM group with routine treatment. Notably, the CD63 expressing of exosomes in urine was found higher in the normoalbuminuria patients compared with those in microalbuminuria, parallelly only declined markedly after α-LA administration in normoalbuminuria patients. Conclusion In summary, we emphasize short-term α-LA could protect the kidney in the early DN against general oxidative stress, particularly the urinary CD63-positive exosome could be a potential sensitive and therapeutic indicator.

Establishment of reference intervals for complete blood count parameters during normal pregnancy in Beijing

Abstract: Objective To observe the changes of complete blood count (CBC) parameters during pregnancy and establish appropriate reference intervals for healthy pregnant women. Methods Healthy pregnant women took the blood tests at all trimesters. All blood samples were processed on Sysmex XE-2100. The following CBC parameters were analyzed: red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), white blood cell count (WBC), and leukocyte differential count. Reference intervals were established using the 2.5th and 97.5th percentile of the distribution. Results Complete blood count parameters showed dynamic changes during trimesters. RBC, Hb, Hct declined at trimester 1, reaching their lowest point at trimester 2, and began to rise again at trimester 3. WBC, neutrophil count (Neut), monocyte count (MONO), RDW, and PDW went up from trimester 1 to trimester 3. On the contrary, MCHC, lymphocyte count (LYMPH), PLT, and MPV gradually descended during pregnancy. There were statistical significances in all CBC parameters between pregnant women and normal women, regardless of the trimesters (P<.001). The median obtained were (normal vs pregnancy) as follows: RBC 4.50 vs 3.94×1012/L, Hb 137 vs 120 g/L, WBC 5.71 vs 9.06×109/L, LYMPH% 32.2 vs 18.0, Neut% 58.7 vs 75.0, and PLT 251 vs 202×109/L. Conclusion The changes of CBC parameters during pregnancy are described, and reference intervals for Beijing pregnant women are demonstrated in this study.

Plasma Leptin in Patients at Intermediate to High Cardiovascular Risk With and Without Type 2 Diabetes Mellitus.

Abstract: BACKGROUND A number of clinical studies have demonstrated that leptin concentrations are related to the metabolic disturbances that constitute the metabolic syndrome (MetS) and to diabetes mellitus (DM). AIM To investigate possible determinants of leptin concentrations in a sample of patients at high cardiovascular (CV) risk carrying two or more features of the MetS and to investigate if any difference exist between at risk patients with or without DM. METHODS Serum leptin concentrations were measured in 60 consecutive male patients affected by at least two CV risk factors which belong to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) definition of MetS: 30 patients affected by type 2 DM (T2DM) and 30 nondiabetic patients (non-T2DM). Nineteen healthy subjects were included in the study as a control group (HC). RESULTS Leptin was significantly higher in patients carrying two or more features of the MetS compared with HC (P = 0.02). Stratifying MetS patients for DM, we found that leptin level was higher in non-T2DM patients (7.8 ng/ml), intermediate in T2DM (6.2 ng/ml), and lower in HC (4.6 ng/ml). In MetS patients, a positive correlation was found between leptin and waist, triglycerides, and number of MetS criteria. After stratification for T2DM, the correlations were still significant in the non-T2DM but not in the T2DM group. CONCLUSIONS In our sample of moderate-to-high-risk patients, leptin level is positively associated with waist circumference and triglycerides but only in non-T2DM patients. Our data suggest that diabetic subjects could modulate leptin production in a different way compared with patients carrying other MetS-related anomalies.

Reliability of parameters of complete blood count with different storage conditions

Abstract: Introduction The complete blood count (CBC) is a frequently performed laboratory test today. This study evaluated the effects of temperature and sample storage time on parameters of CBC which could produce misleading results of clinical significance. Methods In a cross-sectional study, CBC was checked in 102 randomly selected healthy individuals and baseline measurements were analyzed using the Sysmex XS 500i fully automated hematology analyzer. CBC was done on samples up to 48 hr of storage at temperatures of 4 ± 2°C, 23 ± 2°C, and 31 ± 2°C. Values were checked at time intervals of 6, 24, and 48 hr. Results Among CBC parameters, white blood cell, red blood cell, hemoglobin, mean cell hemoglobin (MCH), neutrophils and lymphocytes were stable at all three temperatures up to 48 hr. Monocytes, eosinophils, MCH concentration, hematocrit (Htc), and red cell distribution width-coefficient of variation showed statistically significant changes at 23 ± 2°C and 31 ± 2°C. A significant decline in platelet count (PLT) and increment in mean platelet volume and basophil count were seen at all study temperatures up to 48 hr. Conclusion This study shows that most parameters of the CBC are unaffected with the studied storage temperature up to 48 hr except for the PLT which should be performed within 6 hr of the post-collection time. To avoid changes in a few parameters such as Htc, it is best to store the sample at 4 ± 2°C if any delay is anticipated.

The Relationship between the Methylated Septin-9 DNA Blood Test and Stool Occult Blood Test for Diagnosing Colorectal Cancer in Taiwanese People.

Abstract: Background Colorectal cancer (CRC) is a common and lethal disease in the world. There is an increasing number of cases in Taiwan and a higher rate at advanced stages. The immune fecal occult blood test (iFOBT) has been used as a screening method in Taiwan for years. A new novel diagnostic tool, the Methylated Septin-9 (MS-9) DNA blood test, had been reported to have high sensitivity and specificity for CRC detection. There are no available data in Taiwan, so we conducted this prospective randomized trial to investigate the relationship among the MS-9 DNA blood test, iFOBT, and a combination of the two tests for diagnosing CRC in Taiwanese people. Methods From July 1, 2012 to December 31, 2013, we prospectively selected 60 plasma samples from patients who were diagnosed with CRC and otherwise, the healthy group by colonoscopy in our hospital. Patients were divided into the CRC group and healthy group. CRC stages 0, I, II and stages III and IV were separately analyzed. We calculated the sensitivity and specificity of each group to determine the relationship among the MS-9 DNA blood test, iFOBT, and a combination of the two tests for diagnosing CRC in Taiwanese people. Results The results of the MS-9 DNA blood test for the 60 samples were divided into three groups, and the sensitivity as well as the specificity of the MS-9 DNA blood test to detect CRC were 47% and 89%, respectively. The results of iFOBT were also divided into three groups, and had higher sensitivity (84%) but lower specificity (55%) using iFOBT to detect CRC. Higher rates could be predicted to detect CRC if both the tests were positive. Conclusions A combined MS-9 DNA blood test and iFOBT may help in a higher detection rate of CRC. It could be offered to individuals who are unwilling or unable to undergo colonoscopy. Further large prospective, randomized studies are needed in the future.

Association of ADIPOQ, leptin, LEPR, and resistin polymorphisms with obesity parameters in Hammam Sousse Sahloul Heart Study.

Abstract: BACKGROUND Adipose tissue is an important endocrine organ that secretes a number of adipokines, such as adiponectin (ADIPOQ), leptin (LEP), leptin receptor (LEPR), and resistin (RETN) which may be implicated in obesity. Some adipokines' polymorphisms of genes might influence their concentrations and/or activities. Our aim was to study the relationship between seven SNPs in ADIPOQ (+45T

Alterations of the hematologic cells in synthetic cannabinoid users.

Abstract: Background Functions, morphology, distributions, and index of the circulating cells are the most useful parameters that indicate various inflammatory and toxic conditions. The aim of this study was to investigate the clinical significance of these parameters in patients diagnosed with (synthetic) cannabis use disorder. Methods This study included a total of 40 patients in the study group (SG) with synthetic cannabis use; and 40 healthy individuals as the control group (CG). Participants, who had hematological disorders and other chronic diseases, were excluded from the study. All hematological parameters of SG were compared with CG. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) values were calculated and compared between groups. Results There were statistically significant differences between the groups in terms of WBC, MCH, RDW, MCV, MPV, and NEU, LYM%, MONO% parameters (P<.05). MPW and LYM% were significantly lower in SG compared to CG. WBC, MCH, RDW, MCV, MPV, MONO, and NEU parameters were significantly higher in SG compared to CG (P<.05). UIBC and TIBC levels were significantly higher in SG compared to CG (P<.001). Although there was statistically significant difference between groups in terms of NLR, there was no significant difference for PLR values. Conclusion Our data suggested that chronic use of cannabinoids can lead to deterioration of hematopoietic cells. Chronic use of cannabinoids was consistent with subthreshold/subclinical megaloblastic anemia with iron deficiency. Inflammatory cells, especially neutrophil and monocyte counts were higher in SG compared to CG. Thus, recovery of subclinical hematological parameters should be considered in cannabis use disorder patients.

Establishment of reference intervals for serum thyroid‐stimulating hormone, free and total thyroxine, and free and total triiodothyronine for the Beckman Coulter DxI‐800 analyzers by indirect method using data obtained from Chinese population in Zhejiang Province, China

Abstract: Background In order to establish suitable reference intervals of thyroid-stimulating hormone (TSH), free (unbound) T4 (FT4), free triiodothyronine (FT3), total thyroxine (T4), and total triiodothyronine (T3) for the patients collected in Zhejiang, China, an indirect method was developed using the data from the people presented for routine health check-up. Methods Fifteen thousand nine hundred and fifty-six person's results were reviewed. Box-Cox or Case Rank was used to transform the data to normal distribution. Tukey and Box-Plot methods were used to exclude the outliers. Nonparametric method was used to establish the reference intervals following the EP28-A3c guideline. Pearson correlation was used to evaluate the correlation between hormone levels and age, while Mann-Whitney U test was employed for quantification of concentration differences on the people who are younger and older than 50 years old. Results Reference intervals were 0.66–4.95 mIU/L (TSH), 8.97–14.71 pmol/L (FT4), 3.75–5.81 pmol/L (FT3), 73.45–138.93 nmol/L (total T4), and 1.24–2.18 nmol/L (total T3) in male; conversely, reference intervals for female were 0.72–5.84 mIU/L (TSH), 8.62–14.35 pmol/L (FT4), 3.59–5.56 pmol/L (FT3), 73.45–138.93 nmol/L (total T4), and 1.20–2.10 nmol/L (total T3). FT4, FT3, and total T3 levels in male and FT4 level in female had an inverse correlation with age. Total T4 and TSH levels in female were directly correlated. Significant differences in these hormones were also found between younger and older than 50 years old except FT3 in female. Conclusions Indirect method can be applied for establishment of reference intervals for TSH, FT4, FT3, total T4, and total T3. The reference intervals are narrower than those previously established. Age factor should also be considered.

Serum endocan levels in endometrial and ovarian cancers.

Abstract: Background Ovarian and endometrial carcinomas are the two most common malignancies of the female reproductive system. Endocan is a proteoglycan that is specific to vascular endothelial cells. Increased serum levels have been reported in some tumors. The aim of this study was to investigate serum endocan levels in cases of endometrial and ovarian cancer. Methods Levels of serum endocan were assessed in 27 patients with endometrial cancer and 20 with ovarian cancer, and in 38 control subjects with benign ovarian or endometrial disorders. Thirty-five healthy subjects were also included. Serum endocan levels were measured using a specific enzyme-linked immunosorbent assay. Serum CA-125 levels were also measured in the patient and control groups. Results All patients had detectable serum endocan levels among endometrial and ovarian cancer groups except six cases. However, in the benign and healthy control groups, all endocan levels were undetectable except for two cases in the benign group and three in the healthy control group. Serum endocan levels were significantly higher in the entire patient group than in the controls (P<.0001 for both). Serum endocan levels in cases of endometrial cancer and ovarian cancer were higher than in both the control groups (P<.0001 for both). Evaluation of all groups revealed a positive correlation between serum CA-125 and endocan levels (r=.43, P<.0001). Conclusion Although benign ovarian or endometrial disorders do not lead to expression of endocan, malignant cases can result in measurable endocan levels. This may be useful in differentiating benign and malign diseases of the endometrium or ovary.

Harmonization of serum 25‐hydroxycalciferol assay results from high‐performance liquid chromatography, enzyme immunoassay, radioimmunoassay, and immunochemiluminescence systems: A multicenter study

Abstract: BACKGROUND Remarkable disagreement among different systems of 25-hydroxy vitamin D 25(OH)D assay makes decision making for both clinical and community interventions very difficult. This study aimed to harmonize the results obtained from different 25(OH)D assay systems. METHODS A total of 275 serum samples were analyzed for 25(OH)D using DIAsource-enzyme immunoassay (EIA), DIAsource-radioimmunoassay (RIA), Roche-electrochemiluminescence (ECL), Diasorin-chemiluminescent immunoassay (CLIA), and high-performance liquid chromatography (HPLC), as the reference method. Serum intact parathyroid hormone (iPTH) was also measured in all samples. Between-system agreement and harmonization were evaluated using Bland-Altman analysis, receiver operating characteristic (ROC), and regression analysis. RESULTS Mean serum 25(OH)D concentrations and frequency distribution of vitamin D status showed a significant difference among the studied systems (P<.001 for both). Serum 25(OH)D assay results from all systems correlated with those from HPLC. As compared with HPLC, ECL showed a positive bias (+3.8 nmol/L), whereas CLIA had a negative bias (-11.9 nmol/L). Both EIA and RIA showed a more or less similar positive bias (8.0 and 8.1 nmol/L, respectively). Using serum iPTH-based 25(OH)D cutoff points, only ECL results became comparable to and without significant difference with HPLC. However, when system-specific cutoffs were defined based on HPLC results using regression equations, mean 25(OH)D and frequency distribution of vitamin D status were more harmonized compared with the other methods. CONCLUSION Our findings showed that with adjustment of circulating 25(OH)D based on HPLC, frequency distribution of vitamin D status, as judged by different methods, can be well harmonized with no statistically significant inter-system difference.

Detection of Circulating Auto-Antibodies Against Ribosylated-LDL in Diabetes Patients.

Abstract: Background This study analyzes effect of glycation on ApoB-100 residues by D-ribose as D-ribosylated-glycated LDL might be responsible for the cause of diabetes mellitus because of its far higher antigenic ability. The binding characteristics of circulating auto-antibodies in type 1 and type 2 diabetes patients against native and modified LDL were assessed. Methods T1 Diabetes (n = 43), T2 diabetes patients (n = 100) were examined by direct binding ELISA as well as inhibition ELISA, were compared with healthy age-matched controls (n = 50). Results High degree of specific binding was observed by 74.42% of T1 diabetes and 45.0% of T2 diabetes patient's sera toward glycated LDL, in comparison to its native analog. Competitive inhibition ELISA reiterates the direct binding results. Furthermore, ketoamine content, Hydroxymethylfurfural (HMF) content and carbonyl content were also estimated in patient's sera healthy subjects. The increase in total serum protein carbonyl levels in the diabetes patients was largely due to an increase in oxidative stress. The increase in ketoamine as well as HMF content inpatients sera than healthy subjects is an agreement of induced glycation reaction in patients than healthy subjects. Conclusion D-ribosylated-LDL has resulted in structural perturbation causing generation of neo-antigenic epitopes that are better antigens for antibodies in T1 and T2 diabetes patients.

Diagnostic performance of procalcitonin, presepsin, and C-reactive protein in patients with hematological malignancies.

Abstract: Introduction Infections represent a major complication of hematological malignancies. C-reactive protein (CRP) and procalcitonin (PCT) have been used as diagnostic biomarkers of infections, but do not produce definitive findings. Recently, a new biomarker, presepsin, has been used as a diagnostic tool for detecting infections in the fields of emergency and neonatal medicine. However, the usefulness of presepsin for identifying infections in patients with hematological malignancies, including those who develop febrile neutropenia, remains unclear. Methods In this study, we retrospectively analyzed the utility of PCT, presepsin, and CRP as biomarkers of infections during 49 febrile episodes that occurred in 28 patients with hematological malignancies. Results The levels of PCT, but not those of CRP or presepsin, were significantly higher in the infection group than in the uninfected group (P<.03), indicating that PCT might be a more sensitive biomarker of infections. No differences in presepsin levels were detected between the patients with and without neutropenia, or between the infected and uninfected patients with neutropenia, indicating that presepsin might have less diagnostic value in patients with neutropenia. Conclusions We conclude that PCT might provide additional information and could be used in combination with other biomarkers to detect infections in patients with hematological malignancies.

The association of NLRP3 and TNFRSF1A polymorphisms with risk of ankylosing spondylitis and treatment efficacy of etanercept

Abstract: Background To discover how NLRP3 and TNFRSF1A polymorphisms affect the efficacy of traditional medicine and etanercept for ankylosing spondylitis (AS) patients. Methods Single nucleotide polymorphism (SNP) and haplotype analyses were conducted based on determined NLRP3 and TNFRSF1A among AS patients. We subsequently analyzed the relationship between relevant clinical indexes and polymorphisms of NLRP3 and TNFRSF1A. Results The 4 SNP loci on NLRP3 and 3 SNP loci on TNFRSF1A showed significant linkage disequilibrium, respectively. The T allele of NLRP3 rs4612666 and the T allele of TFRSF1A rs4149570 are both associated with AS (P<.05). The T-A-C-T haplotype of NLRP3 as well as the G-C-C, T-C-C, T-C-T, and T-T-T haplotypes of TFRSF1A are associated with AS (P<.05). The morning stiffness time, BASDAI scoring, and ESR of patients receiving etanercept were significantly higher than those receiving traditional medicine. T allele of NLRP3 rs4612666 had a significantly greater negative impact on the ASAS20 improvement than C allele. Whereas the A allele of NLRP3 rs3806268 had a significantly greater positive impact on the ASAS20 improvement than G allele. There is no significant association between SNP and efficacy of traditional medicine in the treatment of AS. Conclusion NLRP3 and TFRSF1A (rs4149570) are associated with AS susceptibility. There is a significant association between NLRP3 polymorphisms and treatment of etanercept.

Assessment of genetic diversity in IL-6 and RANTES promoters and their level in Saudi coronary artery disease patients.

Abstract: Background The present study consisted of a total of 200 subjects (100 confirmed coronary artery disease (CAD) patients), both men and women, and 100 healthy control individuals. Methods Serum concentration of IL-6 and RANTES were measured by enzyme-linked immunosorbent assay kit. For SNPs analysis, sanger method of DNA sequencing was followed. Results We observed variable numbers of SNP sites at -174 G/C, -572 G/C, and -597 G/A in IL-6 and -28 C/G and -109 C/T in RANTES promoters in CAD patients compared with control individuals. However, the observed changes in the number of SNPs were found to be non-significant compared with control individuals. The IL-6 level was found to be significantly (P<.001) elevated in CAD patients compared with control. Moreover, RANTES serum level did not show any significant change in CAD patients. Conclusion Based on our result, it is quite clear that inflammation has a role in the pathogenesis of CAD but does not lead to significant changes at the genetic level in our population. As far as our knowledge goes, this is the first report that shows the genetic diversity in IL-6 and RANTES promoters and their respective levels in Saudi CAD patients.

Associations among Serum Beta 2 Microglobulin, Malnutrition, Inflammation, and Advanced Cardiovascular Event in Patients with Chronic Kidney Disease

Abstract: Objectives: This study examines the associations among serum β2 microglobulin (B2M), malnutrition, inflammation, and atherosclerosis (MIA) in those with chronic kidney disease (CKD). Methods: CKD patients who were followed in Taoyuan General Hospital from 2009 to 2015 were enrolled. Demographic and biochemical data, including B2M and C-reactive protein (CRP) were reviewed. The participants were stratified according to B2M tertiles. Adjusted hazard ratios (AHRs) and cumulative survival curves for death and MIA syndrome were evaluated by Cox hazard model and Kaplan–Meier method. We also calculated the area under the curve for the receiver operating characteristic curve (AUROC). Results: From a total of 312 CKD patients, mean follow-up time was 39.7 months. Compared to those with lowest tertile of B2M, the highest tertile group had lower serum albumin, hemoglobin, and estimated glomerular filtration rate. After multivariate adjustment, the associations among tertiles of B2M, death or dialysis, cardiovascular events (CVEs), and MIA syndrome remained significant. The AHRs for the highest tertile group in death or dialysis, CVEs, and MIA syndrome were 25.91 and 65.84 and 152.50(all Ps <0.05).The AUROC for B2M in death or dialysis, CVEs, and MIA syndrome were greater than that for creatinine. The best cut-off value of B2M for predicting death or dialysis, CVEs, and MIA syndrome were 5.39 mg/dL(sensitivity: 67.1%, specificity 62.5%), 4.21 mg/dL(sensitivity: 85.1%, specificity 52.1%), and 5.40 mg/dL(sensitivity: 79.7%, specificity 64.1%). Conclusions: In those with CKD, serum B2M was more sensitive than creatinine in predicting CVEs and MIA syndrome.

Calculation of LDL-Cholesterol vs. Direct Homogenous Assay.

Abstract: Background Low-density lipoprotein cholesterol (LDLc) can be calculated or measured directly and their accordance is the subject of controversy. Objectives The aim of this study was to identify the independent predictors of LDLc, to formulate the best equation for calculating LDLc and to evaluate the validity of it and the published formulas, including the new method with adjustable coefficient. Methods The profile of serum lipids and (apo)lipoproteins of 310 subjects was used to determine the most accurate formula for calculating serum LDLc. Serum lipids, lipoproteins and apolipoproteins were measured by enzymatic, new homogenous and immunoturbidometric methods, respectively. Results Multiple linear regression analysis indicates that total cholesterol, apoB, HDLc and triglyceride are independent predictors of LDLc. We proposed four new formulas to calculate LDLc. As total cholesterol (TC) is the major determinant of LDLc, it can be estimated simply as 0.545 of total cholesterol. Inclusion of HDLc, triglyceride, apoB and a constant value improved the equation slightly. The equation of: LDLc (mg/dl) = 0.75 TC − 0.5 HDLc − 0.1 TG had the lowest mean and SD of difference among all the methods examined here. LDLc was also calculated by the new modified Friedewald's equation using adjustable factor from Martin's table, but it did not improve the results significantly. LDLc gap was correlated significantly and positively with triglyceride and negatively with cholesterol or its subfractions. Conclusions Our data suggest the simplest formula: LDLc = 0.545 TC or a more detailed: LDLc = 0.75 TC − 0.5 HDLc − 0.1 TG be used for calculating serum LDLc.

Diagnostic validity of hematologic parameters in evaluation of massive pulmonary embolism

Abstract: Background The aim of this study was to determine the hematologic parameter with the highest diagnostic differentiation in the identification of massive acute pulmonary embolism (APE). Methods A retrospective study was performed on patients diagnosing with APE between June 2014 and June 2016. All radiological and laboratory parameters of patients were scanned through the electronic information management system of the hospital. PLR was obtained from the ratio of platelet count to lymphocyte count, NLR was obtained from the ratio of neutrophil count to lymphocyte count, WMR was obtained from white blood cell in mean platelet volume ratio, MPR was obtained from the ratio of mean platelet volume to platelet count, and RPR was obtained from the ratio of red distribution width to platelet count. Results Six hundred and thirty-nine patients consisting of 292 males (45.7%) and 347 females (54.3%) were included in the research. Independent predictors of massive risk as compared to sub-massive group were; pulmonary arterial systolic pressure (PASP) (OR=1.40; P=.001), PLR (OR=1.59; P<.001), NLR (OR=2.22; P<.001), WMR (OR=1.22; P<.001), MPR (OR=0.33; P<.001), and RPR (OR=0.68; P<.001). Upon evaluation of the diagnostic differentiation of these risk factors for massive APE by employing receiver operating characteristic curve analysis, it was determined that PLR (AUC±SE=0.877±0.015; P<.001), and NLR (AUC±SE=0.893±0.013; P<.001) have similar diagnostic differentiation in diagnosing massive APE and these two parameters are superior over PASP, MPR, WMR, and RPR. Conclusion We determined that the levels of NLR and PLR are superior to other parameters in the determination of clinical severity in APE cases.

Comparison of different enzyme-linked immunosorbent assay methods for avidity determination of antiphospholipid antibodies.

Abstract: Background Avidity of antiphospholipid antibodies may be clinically useful as a valuable additional characteristic. The aim of this study was to compare several ELISA modifications with different chaotropic agents and calculation of avidity indices for the determination of anticardiolipin antibody (aCL) avidity. Methods We examined 28 serum samples with positive IgG aCL by adapted ELISA using various concentrations of urea and sodium chloride as chaotropic agents and different dilution of sera. We tested these conditions of ELISA—a single diluted serum sample with fixed concentration of a chaotrope and a serially diluted serum in the constant concentration of a chaotropic agent. Results We demonstrated that ELISA method for avidity determination based on a single dilution of serum in the presence of fixed concentration of chaotrope is convenient for determination of IgG aCL antibody avidity. Concentrations 6 and 8 mol/L of urea or 1 and 2 mol/L of NaCl were suitable for sufficient dissociation of immune complexes during ELISA procedure. Conclusion This way was in good agreement with more demanding procedures. Both urea and sodium chloride may be used as chaotropic agents. Reference values of avidity indices essential for interpretation of patients’ results must be established individually for distinct assay conditions.

Comparing calculated free testosterone with total testosterone for screening and diagnosing late-onset hypogonadism in aged males: A cross-sectional study.

Abstract: Objective The aim of this study is to compare calculated free testosterone (cFT) and total testosterone (T) in predicting late-onset hypogonadism (LOH) in middle-aged and elderly males. Methods We surveyed a random sample of 608 males between the ages of 45 and 87 years from Shanghai, China. The Aging Male Symptoms (AMS) questionnaire and the Androgen Deficiency in Aging Male (ADAM) questionnaire were completed by the subjects. Testosterone (T), sex hormone-binding globulin (SHBG), albumin, and other blood biochemical indexes were measured in 332 males. The corresponding cFT was obtained using the Vermeulen formula and the correlations between T and cFT were analyzed by SPSS statistical software. Results Among the 332 males who underwent biochemical evaluation, 289 males (87.0%) was positively screened by the ADAM questionnaire and 232 males (69.9%) by the AMS questionnaire. As suggested by linear regression, cFT exhibited a negative correlation with age in both ADAM+ and AMS+ group, whereas T did not appear to have significant correlation with age. Besides, there were statistically significant differences in cFT (P<.001) in the AMS questionnaire. Conclusions Calculated free testosterone levels are more reliable than T levels for diagnosing LOH in middle-aged and elderly males.

The establishment of biological reference intervals of nontraditional glycemic markers in a Chinese population

Abstract: Background We established the reference intervals for glycated albumin (GA), fructosamine (FA), and 1,5-anhydroglucitol (1,5-AG) in a Chinese healthy population. Methods This study enrolled a total of 458 eligible reference individuals, consisted of 226 men and 232 women, aged from 20~79 years (median age 43 years), who attending routine healthy checks. We stratified the subjects according to gender (males and females) and age (20-39, 40-59, and 60-79 years), and combined statistical methods with Lahti algorithm, as well as appropriate clinical consideration, to judge whether partitioning for data was needed. Results Glycated albumin levels between males and females were statistically different (P .05). The reference interval for FA was 220-298 μmol/L. Conclusion New reference intervals for nontraditional glycemic markers were established based on a Chinese population.

A novel turbidimetric immunoassay for fecal calprotectin optimized for routine chemistry analyzers

Abstract: BACKGROUND: Fecal calprotectin assays are widely used to exclude inflammatory bowel disease (IBD) in patients with suspected IBD. A problem with the fecal calprotectin assays is the rather long tes ...

The importance of serum biglycan levels as a fibrosis marker in patients with chronic hepatitis B.

Abstract: BACKGROUND Liver biopsy is recommended in the majority of patients with chronic viral hepatitis for fibrosis evaluation. Because of the potential risks of liver biopsy, many studies related to non-invasive biomarkers of hepatic fibrosis have been performed. We aimed to assess the diagnostic value of serum biglycan as a non-invasive fibrosis marker in chronic hepatitis B patients. METHODS This study included 120 patients with biopsy-proven hepatitis B patients and 60 healthy controls. Fibrosis stage and necroinflammatory activity were assessed in liver biopsy specimens. Biglycan level was measured using an ELISA assay. RESULTS Serum biglycan levels of chronic hepatitis B patients were found to be significantly higher than those of healthy controls (337.3±363.0 pg/mL vs 189.1±61.9 pg/mL, respectively, P<.001). There was a statistically significant positive correlation between serum biglycan level and fibrosis stage (P=.004; r=.213). Besides, a statistically significant positive correlation was found between serum biglycan level and necroinflammatory activity (P<.001; r=.271). The AUROC of BGN levels was 0.702 for fibrosis stage, differentiating patients from healthy controls with statistical significance (P<.001). The AUROC of BGN levels was 0.632 for necroinflammatory activity score, differentiating patients from healthy controls with statistical significance (P=.004). CONCLUSIONS Serum biglycan might be used as a non-invasive marker of liver fibrosis. Further studies are needed to evaluate the usefulness of this marker.

Laboratory diagnosis of Clostridium difficile infection: Comparison of Techlab C. diff Quik Chek Complete, Xpert C. difficile, and multistep algorithmic approach

Abstract: Background Clostridium difficile is a major pathogen responsible for nosocomial infectious diarrhea. We explored optimal laboratory strategies for diagnosis of C. difficile infection (CDI) in our clinical settings, a 1400-bed tertiary care hospital. Methods Using 191 fresh stool samples from adult patients, we evaluated the performance of Xpert C. difficile (Xpert CD), C. diff Quik Chek Complete (which simultaneously detects glutamate dehydrogenase [GDH] and C. difficile toxins [CDT]), toxigenic culture, and a two-step algorithm composed of GDH/CDT as a screening test and Xpert CD as a confirmatory test. Results Clostridium difficile was detected in 35 samples (18.3%), and all isolates were toxigenic strains. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of each assay for detecting CDI were as follows: Quik Chek Complete CDT (45.7%, 100%, 100%, 89.1%), Quik Chek Complete GDH (97.1%, 99.4%, 97.1%, 99.4%), Xpert CD (94.3%, 100%, 100%, 98.7%), and toxigenic culture (91.4%, 100%, 100%, 98.1%). A two-step algorithm performed identically with Xpert CD assay. Conclusion Our data showed that most C. difficile isolates from adult patients were toxigenic. We demonstrated that a two-step algorithm based on GDH/CDT assay followed by Xpert CD assay as a confirmatory test was rapid, reliable, and cost effective for diagnosis of CDI in an adult patient setting with high prevalence of toxigenic C. difficile.

The Predictive Role of the Neutrophil/Lymphocyte Ratio in Survival with Multiple Myeloma: A Single Center Experience

Abstract: Background Recent studies have shown a positive correlation between tumor-related immune response markers and the poor outcome in solid tumors. In this study, we aimed to investigate the neutrophil/lymphocyte ratio (NLR) in multiple myeloma. To the best of our knowledge, this would be the second report concerning this topic. Methods We retrospectively reviewed the data for 52 multiple myeloma patients. The patients were grouped using the baseline NLR as NLR ≤ 1.72 and NLR > 1.72 using receiver operating characteristic analysis to determine a cut off. We compared the two groups in terms of both the known prognostic factors of the myeloma and the overall survival (OS). Results Our study showed that NLR is associated with C-reactive protein and β2 microglobulin (P = 0.02 and P = 0.001, respectively). The patients with NLR > 1.72 had significantly worse stages, performance status, and kidney functions. The whole group's OS was estimated as 35.1 months while the patients with lower NLR had better OS when compared with those with NLR > 1.72 (42.75 and 26.14 months, respectively, P: 0.04). Conclusion Neutrophil/lymphocyte ratio, which is associated with stage, performance status, and kidney functions, can be used in daily practice as a predictor for survival in multiple myeloma. Simply adding NLR to the routine charts may enrich our data for larger studies.

The Glycated Albumin (GA) to HbA1c Ratio Reflects Shorter-Term Glycemic Control than GA: Analysis of Patients with Fulminant Type 1 Diabetes.

Abstract: Background Glycated albumin (GA) reflects shorter-term glycemic control than HbA1c. We have reported that HbA1c is paradoxically increased in diabetic patients whose glycemic control deteriorated before ameliorating. In this study, we analyzed paradoxical increases of glycemic control indicators after treatment in patients with fulminant type 1 diabetes (FT1D). We also investigated whether the GA/HbA1c ratio may reflect shorter-term glycemic control than GA. Methods Five FT1D patients whose post-treatment HbA1c and GA levels were measured were enrolled. We also used a formula to estimate HbA1c and GA from the fictitious models of changes in plasma glucose in FT1D patients. In this model, the periods during which HbA1c, GA, and the GA/HbA1c ratio were higher than at the first visit were compared. In addition, the half-life for the GA/HbA1c ratio was calculated in accordance with the half-lives for HbA1c and GA (36 and 14 days, respectively). Results In all FT1D patients, HbA1c levels 2–4 weeks after treatment were increased, with three patients (60%) experiencing an increase of GA levels. In contrast, an increase of the GA/HbA1c ratio was observed in only one patient. In all of the different models of changes in plasma glucose in FT1D patients, the length of time during which the values were higher than at the first visit was in the order of HbA1c > GA > GA/HbA1c ratio. The half-life for the GA/HbA1c ratio was 9 days, shorter than GA. Conclusions These findings suggest that the GA/HbA1c ratio reflects shorter-term glycemic control than GA.