BN ProSpec Research Articles

Diagnostic Performance of Serum IgG4 Levels in Patients With IgG4-Related Disease.

The aim of this study is to study the clinical features and diagnostic performance of IgG4 in Chinese populations with IgG4-related diseases (IgG4-RDs).The medical records of 2901 adult subjects who underwent serum IgG4 level tests conducted between December 2007 and May 2014 were reviewed.Serum concentrations of IgG4 were measured in 2901 cases, including 161 (5.6%) patients with IgG4-RD and 2740 (94.4%) patients without IgG4-RD (non-IgG4-RD group). The mean age of the IgG4-RD patients was 58.4 ± 16.1 years (range: 21–87), and 48 (29.8%) were women. The mean serum IgG4 level was significantly much higher in IgG4-RD patients than in non-IgG4-RD (1062.6 vs 104.3 mg/dL, P < 0.001) participants. For IgG4 >135 mg/dL, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR)+, and LR− were 86%, 77%, 18%, 99%, 3.70, and 0.19, respectively. When the upper limit of normal was doubled for an IgG4 >270 mg/dL, the corresponding data were 75%, 94%, 43%, 98%, 12.79, and 0.26, respectively. For IgG4 >405 mg/dL (tripling the upper limit of normal), the corresponding data were 62%, 98%, 68%, 98%, 37.00, and 0.39, respectively. When calculated according to the manufacturer's package insert cutoff (>201 mg/dL) for the diagnosis of IgG4-RD, the corresponding sensitivity, specificity, PPV, NPV, LR+, and LR− were 80%, 89%, 29%, 99%, 7.00, and 0.23, respectively. For IgG4 >402 mg/dL (>2× the upper limit of the normal range), the corresponding data were 62%, 98%, 68%, 98%, 36.21, and 0.39, respectively. For IgG4 >603 mg/dL (>3× the upper limit of the normal range), the corresponding data were 50%, 99%, 84%, 97%, 90.77 and 0.51, respectively. The optimal cutoff value of serum IgG4 (measured by nephelometry using a Siemens BN ProSpec instrument and Siemens reagent) for the diagnosis of IgG4-RD was 248 mg/dL, the sensitivity and specificity were 77.6% and 92.8%, respectively.The present study demonstrated that 2 or 3 times the upper limit of the manufacturer's reference range of the IgG4 level was a useful marker for the diagnosis of various types of IgG4-RD and the optimal cutoff level was 248 mg/dL.

Diagnosis of late presenting subarachnoid hemorrhage: Comparison of methods for cerebrospinal fluid ferritin

Background. The majority of subarachnoid hemorrhage (SAH) is diagnosed using imaging techniques. The sensitivity of computed tomography scans decreases with increasing time after the bleeding event which can lead to false negative CT scans. Spectrophotometry and microscopic investigations of the cerebrospinal fluid (Csf) can provide additional diagnostic support, but may not be available for emergency diagnoses. Csf-Ferritin has been suggested as an alternative additional marker for SAH that present late and has a potency to be measured in a routine laboratory. Methods. A routine Ferritin chemiluminescent assay (Dimension Vista) was compared with a branded and CE-marked Csf-Ferritin nephelometric assay (BN ProSpec) using surplus routine patient samples. We calculated imprecision at pertinent concentrations, compared patient samples, and established reference intervals. Results. The standard deviation was about a third for the Dimension Vista assay compared to that of the BN ProSpec assay at the three tested concentrations. The correlation showed a systematic difference between the methods but the correlation was high (r = 0.955). Accordingly, the reference intervals were higher for the BN ProSPec (2.7–16.8 μg/L) than for the Dimension Vista (2.0–12.6 μg/L). Conclusion. The precision of the Dimension Vista measurements was considerably better than that of the BN ProSpec. The Dimension Vista results correlated well with those of the comparative method, yielding slightly lower values. This is reflected in the reference intervals. These findings permit the use of the routinely available Ferritin assay of the Dimension Vista for measuring Csf-Ferritin and complementing the late diagnosis of SAH outside office hours of specialized Csf laboratories.

PKP-009 Markers of cardiovascular risk and age-related macular degeneration

BackgroundMany authors have hypothesised that cardiovascular disorders and age-related macular degeneration (AMD) share common antecedents and suggested that novel biomarkers associated with CVD be evaluated for their potential relationship with...

Correlative study of serum cystatin C levels with severity of acute ischemic stroke.

Background: The attractiveness of cystatin C as a biomarker for acute ischemic stroke is obvious, in the background of accumulating evidence indicating a link between vascular disease of the kidney and brain. We investigated the association of serum cystatin C levels with first onset acute ischemic stroke and the correlation of serum cystatin C levels with severity of acute ischemic stroke as assessed by NIH stroke scale. Methods: A total of 50 patients with first onset of acute ischemic stroke, aged more than 45 years, presenting within 72 hours after onset, by interview, history, clinical examination, neuroimaging and other investigations. Serum Cystatin C was measured by means of a particle-enhanced immunenephelometric assay (N Latex Cystatin C) with a nephelometer (Siemens BN Prospec). Results: Serum cystatin C levels were significantly raised in 62% (n=31) patients of acute ischemic stroke compared with controls 14% (n=7), with a p < 0.001. Compared with controls, the mean serum cystatin C level was significantly higher in stroke patients (1.33±0.71 versus 0.83±0.24 mg / L, p < 0.001). The diagnostic accuracy of serum cystatin C as a marker of acute ischemic stroke evaluated using Receiver Operating Characteristic (ROC) curve analysis, showed a sensitivity of 66.00 and specificity of 84.00 with an area under curve of 0.80 (and 95 % CI (0.71 - 0.87)). Conclusion: Serum cystatin C was a better marker for acute ischemic stroke and indicator of severe neurological impairment. Key words: Acute ischemic stroke, Cystatin C, NIH Stroke scale.

β-Trace Protein and Prognosis in Patients With Atrial Fibrillation Receiving Anticoagulation Treatment

Atrial fibrillation (AF) is associated with a high risk of mortality and morbidity and it commonly coexists with chronic kidney disease. A biomarker of renal function, β-trace protein (BTP), has been implicated in the progression of cardiovascular disease. The aim of our study was to evaluate the association of BTP with adverse cardiovascular events, bleeding, and mortality in patients with AF. In a consecutive cohort of patients with nonvalvular AF receiving anticoagulation treatment, plasma BTP was determined using an automated nephelometer BN ProSpec System (Siemens) and related to estimated glomerular filtration rate (eGFR). We recorded adverse cardiovascular events (stroke, acute coronary syndrome, and acute pulmonary edema), major bleeding, and mortality. We included 1,279 patients (48.6% men), aged 76 years (IQR, 71-81 years), who were followed up for 996 days (IQR, 802-1,254 days). During the follow-up, there were 150 cardiovascular events (annual rate, 3.99%), 57 embolisms (annual rate, 1.54%), and 114 major bleeding events (annual rate, 3.04%), and 161 patients died (annual rate, 4.32%). BTP levels were inversely associated with eGFR (P &lt; .001). High BTP concentrations were significantly associated with embolic events (hazard ratio [HR], 4.64 [1.98-10.86]; P &lt; .001), composite adverse cardiovascular events (HR, 1.93 [1.31-2.85]; P = .001), and mortality (HR, 2.08 [1.49-2.90]; P &lt; .001), even after adjusting for CHAD2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes mellitus, stroke [doubled], vascular disease, age 65 to 74 years, sex category) score and renal function. High BTP was associated with major bleeding events (HR, 1.88 [1.18-3.00]; P = .008), even after adjusting for the HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or redisposition, labile international normalized ratio, elderly [&gt; 65 years], drugs/alcohol concomitantly) score. We suggest that BTP, a proposed renal damage biomarker, may be a novel predictor of adverse cardiovascular events, major bleeding, and mortality in patients with AF. BTP may help refine clinical risk stratification in these patients.

Neuroprotein Dynamics in the Cerebrospinal Fluid: Intraindividual Concomitant Ventricular and Lumbar Measurements

Objective: The measurement of neuromarker/neuroproteins in the cerebrospinal fluid (CSF) is gaining increased popularity. However, insufficient information is available on the rostrocaudal distribution of neuroproteins in the CSF to guarantee an appropriate interpretation of ventricular versus lumbar concentrations. Methods: In 10 patients treated with both an external ventricular and a lumbar CSF drain, we collected concomitant CSF samples. We measured CSF concentrations of the glial S100B protein, the neuron-specific enolase (Cobas e411®; Roche Diagnostics), the leptomeningeal β-trace protein (BN Pro Spec®; Dade Behring/Siemens), and the blood-derived albumin (Immage; Beckman Coulter). Statistical analysis was performed with a paired Wilcoxon signed ranks test. Results: In patients with a free CSF circulation without any recent neurosurgical procedure, S100B and neuron-specific enolase concentrations did not differ between the ventricular and lumbar CSF while β-trace and albumin levels were significantly higher in the lumbar than in the ventricular CSF (p = 0.008 and p = 0.005). Following posterior fossa tumor surgery, all proteins accumulate in the lumbar CSF. Conclusion: For brain-derived proteins, we could not confirm a rostrocaudal CSF gradient while lepto-meningeal and blood-derived proteins accumulate in the lumbar CSF. We conclude that for the interpretation of protein CSF concentrations, the source of the sample is of crucial importance.

Brain-Derived Protein Concentrations in the Cerebrospinal Fluid: Contribution of Trauma Resulting from Ventricular Drain Insertion

In recent years, the measurement of biomarkers following neurotrauma assisted in improving outcome prediction and guiding therapy. The use of neuroproteins as diagnostic parameters requires a detailed knowledge of their dynamics in biological fluids for an appropriate interpretation. S100B is the most widely studied neuromarker, and its concentration in serum and cerebrospinal fluid (CSF) reflects the extent of brain damage. Neuron-specific enolase (NSE) is considered reflecting neuronal damage, while Beta-Trace is a lepto-meningeal protein used to diagnose CSF leakage. In five patients treated with an external ventricular drain (EVD) because of aneurysmal subarachnoid hemorrhage (SAH, n=3) or postinfectious hydrocephalus (n=2), an EVD exchange was performed 8 to 12 days after initial insertion. S100B and NSE were measured with the Cobas e411(®) electrochemiluminescence assay (Roche Diagnostics, Mannheim, Germany) and Beta-Trace with the BN Pro Spec(®) nephelometer (Dade Behring/Siemens, Germany) 1 h before EVD exchange, upon the insertion of the new drain, and 1, 3, 6, 12, 18, 24 and 48 h after EVD exchange. Before EVD exchange, S100B CSF concentrations were within the normal range in all patients (1.48 ± 0.37 μg/L), while NSE CSF concentrations were normal in four of five patients (6.51 ± 2.98 μg/L). Following EVD exchange, S100B and NSE CSF levels peaked significantly at 3 h after insertion of the new drain (S100B 39.02 ± 9.17 μg/L; NSE 54.80 ± 43.34 μg/L). S100B serum levels were slightly increased 6 to 24 h after EVD exchange. Beta-Trace concentrations in the CSF were not altered by EVD insertion. Our data demonstrate that EVD insertion results in a distinct increase of S100B and NSE concentrations in the CSF. Thus, the tampering of brain-derived protein concentrations in the CSF by diagnostic or therapeutic procedures has to be considered in the interpretation of neuromarker levels.

AB0178 Elevated serum igg4 correlates with disease activity in patients with rheumatoid arthritis

BackgroundElevated serum IgG4 is one of the characteristics of IgG4-related diseases and it has also been reported in some patients with rheumatoid arthritis (RA). However, the significance of elevated serum...

Anti-C reactive protein antibodies in Indian patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by over production of autoantibodies. C-reactive protein (CRP) is a phylogenetically highly conserved plasma protein that participates in the systemic response to inflammation. Anti-CRP antibodies might have biological functions of pathogenetic interest in SLE. We evaluated anti-CRP antibodies in Indian SLE patients and their association with anti-dsDNA antibodies and complement levels (C3 and C4). One hundred SLE patients diagnosed according to the American College of Rheumatology criteria were included. Disease activity was assessed using SLE disease activity index (SLEDAI). Anti-CRP autoantibodies were detected by enzyme linked immunosorbent assay. Anti-dsDNA antibodies were detected by indirect immunofluroscence test (Euroimmun Lubeck, Germany). High sensitivity CRP and complement levels (C3, C4) were detected using a Nephelometer. (BN ProSpec, Dade Behring, Germany). Anti-CRP antibodies were detected in 26% of SLE patients. Mean age of disease onset among anti-CRP positives was 22.4 ± 7.5, and 26.6 ± 9.3 years among anti-CRP negatives (P > 0.05). Anti-dsDNA positivity was significantly higher among anti-CRP positives (32.7%) as compared to anti-CRP negatives (16%) (P = 0.00519). No statistically significant difference was observed in SLEDAI scores of anti-CRP positive group and anti-CRP negative group (P > 0.05). We observed a positive correlation between anti-CRP antibodies and anti-dsDNA antibodies.

Comparative analysis of immunoglobulin free light chains quantification by Freelite™ (The Binding Site) and N Latex FLC (Siemens) methods

Serum immunoglobulin free light chain assay has proved to be an invaluable biological tool for diagnosis and monitoring of monoclonal gammopathies including multiple myeloma, primary amyloidosis, solitary plasmocytoma or monoclonal gammopathy of undetermined significance. Free light chain quantification, although essential, cannot be achieved by serum protein electrophoresis either because there is no monoclonal peak or because the peak is hidden in beta or alpha-globulin fraction. As for serum protein immunofixation, this major test allows the typing of the paraprotein but does not provide any quantitative evaluation. Hence, the development of free light chain assays constitutes a significant improvement in the management of these patients. In this context, we compared the results of serum free light chains quantification and of calculation of the ratio kappa/lambda, indicator of monoclonality, in forty samples performed on BN ProSpec(®) analyzer, with the two methods available on the European market. This comparative analysis provided evidence of a good correlation of results between the two methods. However, we noticed clinically significant differences in four samples. In addition, this evaluation highlighted the fact that all free light chain results must be biologically validated on the light of different criteria such as serum protein electrophoresis, serum protein immunofixation, presence of proteinuria, presence of renal failure, and additional clinical data, in order to ascertain the best interpretation for clinical use.

Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure

To investigate serum cystatin C level as an early biomarker for predicting acute kidney injury (AKI) in patients with acute-on-chronic liver failure (ACLF). Fifty-six consecutive patients with hepatitis B virus-related ACLF who had normal serum creatinine (Cr) level (< 1.2 mg/dL in men, or < 1.1 mg/dL in women) were enrolled in the Liver Failure Treatment and Research Center of Beijing 302 Hospital between August 2011 and October 2012. Thirty patients with chronic hepatitis B (CHB) and 30 healthy controls in the same study period were also included. Measurement of serum cystatin C (CysC) was performed by a particle-enhanced immunonephelometry assay using the BN Prospec nephelometer system. The ACLF patients were followed during their hospitalization period. In the ACLF group, serum level of CysC was 1.1 ± 0.4 mg/L, which was significantly higher (P < 0.01) than those in the healthy controls (0.6 ± 0.3 mg/L) and CHB patients (0.7 ± 0.2 mg/L). During the hospitalization period, eight ACLF patients developed AKI. Logistic regression analysis indicated that CysC level was an independent risk factor for AKI development (odds ratio = 1.8; 95%CI: 1.4-2.3, P = 0.021). The cutoff value of serum CysC for prediction of AKI in ACLF patients was 1.21 mg/L. The baseline CysC-based estimated glomerular filtration rate (eGFR(CysC)) was significantly lower than the creatinine-based eGFR (eGFR(CG) and eGFR(MDRD)) in ACLF patients with AKI, suggesting that baseline eGFR(CysC) represented early renal function in ACLF patients while the Cr levels were still within the normal ranges. Serum CysC provides early prediction of renal dysfunction in ACLF patients with a normal serum Cr level.

The Chronic Kidney Disease-Epidemiology Collaboration-Cystatin C (CKD-EPI-CysC) Equation Has an Independent Prognostic Value for Overall Survival in Newly-Diagnosed Patients with Symptomatic Multiple Myeloma: Comparison with 3 Other Equations for GFR Estimation

Abstract 1849Renal impairment (RI) is a frequent complication in multiple myeloma (MM). The estimation of glomerular filtration rate (GFR) is based on equations that use serum creatinine (sCr) as a marker of RI (i.e. MDRD or CKD-EPI). The IMWG has recommended the use of the MDRD formula for the estimation of GFR in MM patients with stabilized sCr, while the classification of RI is based on the 5 stages of the KDIGO classification (Dimopoulos et al, JCO 2010;28:4976–84). However, the equations based on sCr are imprecise and thus novel markers of renal injury have been used in patients with renal damage, including cystatin-C (CysC). CysC is considered as a more sensitive marker of GFR than sCr. Recently, the CKD-EPI investigators have reported that a combined sCr-CysC (CKD-EPI-sCr-CysC) equation correlated better with GFR than equations based on either of these markers alone (CKD-EPI or CKD-EPI-CysC; Inker et al, NEJM 2012;367:20–9). Although cysC has been reported by our group to be elevated in MM patients, the CKD-EPI equations and their value on MM patients’ survival have never been evaluated.Therefore, we studied 220 newly-diagnosed, previously untreated, symptomatic MM patients. The median age was 69 years (range: 36–94 years) and 16% had sCr ≥2 mg/dl. Serum CysC was measured on the BN ProSpec analyser using a latex particle-enhanced nephelometric immunoassay (Dade Behring-Siemens Healthcare Diagnostics, Liederbach, Germany). Serum CysC was increased in MM patients compared to 52 age- and gender-matched controls [median: 1.07 mg/l vs. 0.72 mg/l, p<0.0001]. The median values for eGFR calculated by the MDRD, CKD-EPI, CKD-EPI-CysC and CKD-EPI-sCr-CysC equations were 63.45 ml/min/1.73m2, 68.13 ml/min/1.73m2, 68.11 ml/min/1.73 m2, and 64.87 ml/min/1.73 m2, respectively (p<0.01).Patients were divided in the 5 CKD stages of KDIGO classification, according to eGFR (stage 1: eGFR >90 ml/min/1.73 m2; stage 2: 60–89 ml/min/1.73m2; stage 3: 30–59 ml/min/1.73 m2; stage 4: 15–29 ml/min/1.73 m2; stage 5: <15 ml/min/1.73 m2 or on dialysis). For each studied equation, the number of patients with RI stage 3–5 (i.e. eGFR <60 ml/min/1.732) was 39.5% for MDRD vs. 42.2% for CKD-EPI vs. 43.1% for CKD-EPI-CysC vs. 45% for CKD-EPI-sCr-CysC (p<0.01; see also the table). Concordance for CKD stage allocation for the 4 equations of estimating eGFR was 97% for MDRD vs. CKD-EPI, 60% for MDRD vs. CKD-EPI-CysC and 84% for MDRD vs. CKD-EPI-sCr-CysC. A significant correlation was found between ISS stage and all studied equations (p<0.01 for all).The median overall survival (OS) for all patients was 52 months. In the univariate analysis per CKD stage, the 4 equations could predict for OS (the higher CKD stage had poorer survival) with the following significance: MDRD (p=0.057), CKD-EPI (p=0.01), CKD-EPI-CysC (p<0.0001), and CKD-EPI-sCr-CysC (p=0.006). When we tested the 4 equations as continuous variables, all had prognostic value for OS but the CKD-EPI-CysC had the strongest prognostic value (p<0.0001 and Wald=24.0 vs. p<0.0001 and Wald=19.7 for CKD-EPI-sCr-CysC, p=0.003 and Wald=8.9 for CKD-EPI and p=0.005 and Wald=7.7 for MDRD). In the multivariate analysis, that included ISS stage, LDH ≥300 U/l and eGFR for each different equation (as a continuous variable) only eGFR that included CysC but not sCr (CKD-EPI-CysC and not CKD-EPI-sCr-CysC) had independent significance (p=0.013) along with high LDH (p=0.029).Our data suggest that the CKD-EPI-sCr-CysC equation for the estimation of GFR detects more MM patients with stage 3–5 RI than the MDRD, CKD-EPI or CKD-EPI-CysC equations. However, CKD-EPI-CysC was the only equation that could predict for OS, possibly due to the very strong correlation of CysC with ISS (as myeloma cells produce CysC also). The confirmation of these data will lead to the broader use of equations based on CysC (CKD-EPI-CysC with or without sCr) for the evaluation of RI in patients with MM, as it has been suggested for patients with several other renal disorders.TableEvaluation of Renal Function Stage by Different EquationsCKD stageMDRD equationCKD-EPI equationCKD-EPI-CysC equationCKD-EPI-sCr-CysC equationp-value160 (27%)57 (26%)67 (30%)44 (20%)273 (33%)70 (32%)58 (26%)77 (35%Friedman-test353 (24%)55 (25%)57 (26%)62 (28%)p<0.01421 (9.5%)25 (11%)27 (12%)24 (11%)513 (6%)13 (6%)11 (5%)13 (6%) Disclosures:No relevant conflicts of interest to declare.

Tubular Damage Is Ubiquitous in Newly-Diagnosed Patients with Multiple Myeloma: Comparison of Three Urinary and Two Serum Markers of Kidney Injury.

Abstract 2919Renal impairment is a common complication of multiple myeloma (MM). The CRAB criteria define the serum creatinine (sCr) level of >2 mg/dl as the cut-off value for starting therapy in MM patients. However, the measurement of sCr for the evaluation of renal impairment has several limitations. Furthermore, the estimation of glomerular filtration rate (GFR) by the MDRD equation has greater value in patients with stabilized sCr, while the majority of MM patients have acute renal damage, which may be irreversible. Thus, identification of individuals at higher risk of early kidney dysfunction is critical to the timely initiation of treatment to prevent permanent renal damage. For this reason, several markers of renal dysfunction have been used in renal disorders. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein overproduced by proximal tubular cells in response to kidney injury, while kidney injury molecule-1 (KIM-1) is a type 1 transmembrane glycoprotein that is overexpressed in dedifferentiated proximal tubule epithelial cells after ischemic or toxic injury. Urinary NGAL and KIM-1 have never been evaluated in MM patients.To assess the value of these molecules in MM, we measured urinary and serum NGAL, urinary KIM-1, urinary and serum cystatin-C (cys-C; a sensitive marker of GFR which is not secreted in the urine) in 48 newly diagnosed symptomatic MM patients (27M/21F, median age 65 years). The estimated GFR (eGFR) was calculated using the CKD-EPI equation (proposed by the CKD Epidemiology Collaboration and is widely accepted in renal impairment). Serum and urinary NGAL was evaluated using an ELISA method (BioPorto Diagnostics A/S, Gentofte, Denmark) with a protocol applied in the Siemens Advia 1800 clinical chemistry system. Serum and urinary cys-C was measured on the BN ProSpec analyser using a latex particle-enhanced nephelometric immunoassay (Dade Behring-Siemens Healthcare Diagnostics, Liederbach, Germany), while urinary KIM-1 was also measured using an ELISA (R&D Systems, Minneapolis, MN, USA). For the urinary measurements, a 24h urine collection was used.Nine (19%) patients had sCr >2mg/dl, while 60% had eGFR ≥60 ml/min (CKD stages 1 & 2), 18.5% had eGFR 30–59 ml/min (CKD stage 3) and 21.5% eGFR <30 ml/min (CKD stages 4 & 5). The median values (range) for the studied markers in MM patients and in 120 healthy controls were: for urinary NGAL 36 ng/ml (0.5–2512 ng/ml) vs. 5.3 ng/ml (0.7–9.8 ng/ml), p<0.0001; for serum NGAL 162 ng/ml (53–576 ng/ml) vs. 63 ng/ml (37–106 ng/ml), p<0.0001; for urinary KIM-1 1.1 ng/ml (0.13–4.87 ng/ml) vs. 1.3 (0.1–5.3 ng/ml), p=0.345; for urinary Cys-C 0.05 mg/l (ND-13.9) vs. non-detectable, p<0.01; and for serum cys-C 1.0 mg/l (0.4–3.2 mg/l) vs. 0.7 (0.3–0.9 mg/l), p<0.01. Almost all patients (93%) had higher levels of urinary NGAL than the higher value of the controls; the respective frequency for the other markers was: 68% for serum NGAL and serum cys-C, 50% for urinary cys-C and only 10% for urinary KIM-1.All studied markers correlated with eGFR: serum cys-C (r=−0.758, p<0.001), serum NGAL (r=−0.627, p<0.001), urinary cys-C (r=−0.498, p=0.008), urinary NGAL (r=−0.430, p=0.01) and urinary KIM-1 (r=−0.369, p=0.021). Only serum cys-C strongly correlated with the involved serum free light chain (r=0.806, p<0.001). Urinary NGAL correlated also with urinary cys-C (r=0.880, p<0.001), serum NGAL (r=0.503, p=0.002), 24-h proteinuria (r=0.431, p=0.01) and ISS stage (mean±SD values for ISS-1, ISS-2 and ISS-3 were: 31±29 ng/mL, 47±52 ng/mL and 408±695 ng/mL, respectively; p=0.03). Serum cys-C correlated also with ISS stage (the values for ISS-1, ISS-2 and ISS-3 were: 0.85±0.19 mg/L, 0.94±0.24 mg/L and 2.15±0.98 mg/L, respectively; p=0.01), while urinary cys-C correlated with 24-h proteinuria (r=0.564, p<0.001).Our data suggest that almost all newly diagnosed symptomatic MM patients have tubular damage as assessed by elevated urinary NGAL suggesting that renal impairment is present very early in the disease course. Measurement of urinary NGAL and serum cys-C offers valuable information for the kidney function of MM patients and their measurement may help in the identification of patients with high risk for the development of acute renal function. The value of KIM-1 seems to be very low in myeloma reflecting the differences in the pathogenesis of myeloma-related renal dysfunction than toxic acute renal injury of other etiology. Disclosures:No relevant conflicts of interest to declare.

External Evaluation of the Dimension Vista 1500® Intelligent Lab System

Dimension Vista® analyzer combines four technologies (photometry, nephelometry, V-LYTE® integrated multisensor potentiometry, and LOCI® chemiluminescence) into one high-throughput system. We assessed analytical performance of assays routinely performed in our emergency laboratory according to the VALTEC protocol, and practicability. Precision was good for most parameters. Analytical domain was large and suitable for undiluted analysis in most clinical settings encountered in our hospital. Data were comparable and correlated to our routine analyzers (Roche Modular DP®, Abbott AXSYM®, Siemens Dimension® RxL, and BN ProSpec®). Performance of nephelometric and LOCI modules was excellent. Functional sensitivity of high-sensitivity C-reactive protein and cardiac troponin I were 0.165 mg/l and 0.03 ng/ml, respectively (coefficient of variation; CV < 10%). The influence of interfering substances (i.e., hemoglobin, bilirubin, or lipids) was moderate, and Dimension Vista® specifically alerted for interference according to HIL (hemolysis, icterus, lipemia) indices. Good instrument performance and full functionality (no reagent or sample carryover in the conditions evaluated, effective sample-volume detection, and clot detection) were confirmed. Simulated routine testing demonstrated excellent practicability, throughput, ease of use of software and security. Performance and practicability of Dimension Vista® are highly suitable for both routine and emergency use. Since no volume detection and thus no warning is available on limited sample racks, pediatric samples require special caution to the Siemens protocol to be analyzed in secured conditions. Our experience in routine practice is also discussed, i.e., the impact of daily workload, "manual" steps resulting from dilutions and pediatric samples, maintenances, flex hydration on instrument's performance on throughput and turnaround time.

PP031. The prevalence of microalbuminuria following preeclampsia

About 7years after preeclampsia, the prevalence of microalbuminuria is reported to be around 30% [1]. As proteinuria resolves in most cases within two years of post partum, [2] this raises the question of whether microalbuminuria first regresses after preeclampsia or persists. This cross-sectional study describes the prevalence of microalbuminuria in the years following preeclampsia. Women with a history of preeclampsia (n=823) were evaluated 4-180months after delivery. Women with pre-existing hypertension, renal disease or diabetes mellitus were excluded (n=65). In a 24h urine collection we determined total protein (pyrogallol red), microalbuminuria (turbidometry, Cobas Bio and since 2007 nephelometry, BN ProSpec) and creatinine (Jaffe method). Microalbuminuria was considered to be present when there was ⩾3.5mg/mmol of creatinine. Proteinuria was defined as a total protein level of ⩾300mg/24h. Microalbuminuria was present in 12.0%, CI 9.7-14.6 and proteinuria in 2.7%, CI 1.7-4.1 of all cases. Microalbuminuria decreased up to 40months postpartum, but increased after that period of time (p=0.01 compared with 24-40months). This study suggests a U-shaped microalbuminuria pattern over time. Longitudinal research is necessary to confirm this.

Dilatation of the ascending aorta and serum alpha 1-antitrypsin level in patients with bicuspid aortic valve

Predictors of aortic dilatation are not well described in patients with bicuspid aortic valves (BAV). This study sought to examine the relationship between proximal aortic dilatation and matrix metalloproteinase-9 (MMP-9) and alpha 1-antitrypsin (α1AT) levels in patients with BAV. All patients underwent echocardiography using a standard protocol, and aortic measurements were taken in end-diastole. We studied 82 patients with BAV and categorized them into two groups according to aortic dimensions corrected for body surface area and age. The plasma level of α1AT was routinely determined using a BN ProSpec analyzer (Siemens Healthcare Diagnostics, Marburg, Germany), and that of MMP-9 were determined by ELISA (RayBiotech Inc. Norcross, GA, USA). Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS; SPSS Inc., Chicago, IL, USA) software for Windows version 12. This study included patients with BAV with no or mild valvular impairment. There were no significant differences between groups in terms of gender, body surface area, associated hypertension, diabetes mellitus, hyperlipidemia, or smoking. The mean ascending aortic diameter was 4.38±0.5mm in group 1 and 3.34±0.35mm in group 2 (p<0.001). Plasma concentration of α1AT in patients with ascending aortic dilatation was significantly lower than that in the non-dilated group (1.32±0.27 and 1.49±0.25g/l, respectively; p=0.005). However, no significant difference was found in the MMP-9 level between the two groups (336.49±233.11 and 336.39±268.072pg/ml, respectively; p=0.96). We observed a significantly negative correlation between ascending aortic diameter and α1AT level (r=-0.300, p=0.006) and a positive correlation between ascending aortic diameter and age (r=0.413, p<0.001). No significant correlation was found between plasma MMP-9 concentration and ascending aortic diameter (r=-0.008, p=0.94). A multiple linear regression analysis was performed, including age, α1AT level, MMP-9 level, and left ventricular diastolic diameter. In this analysis, α1AT level and age were the independent predictors of aortic dilatation (p=0.03 and p=0.02, respectively).

RHEUMATOID FACTOR AND ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES IN PATIENTS WITH PSORIATIC ARTHRITIS

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Relationship between increased systemic inflammation and impaired aortic elasticity in young patients with prehypertension

This study was designed to evaluate the possible relationship between vascular inflammatory status [namely, high-sensitivity C-reactive protein (hs-CRP) and white blood cell (WBC)] and aortic elasticity parameters in patients with prehypertension. The study population consisted of 25 newly diagnosed prehypertensive individuals (18 men, mean age=34±6 years) and 25 healthy controls (16 men, mean age=33±6 years) eligible for this study. Aortic elasticity parameters were calculated from aortic diameters measured by echocardiography and blood pressures, simultaneously measured by sphygmomanometry. hs-CRP measurements were taken with latex-enhanced reagent using a Behring BN ProSpec analyzer. Baseline characteristics of patients with prehypertension and controls were homogeneous. Inflammatory markers were significantly higher in patients with prehypertension compared with those of controls [for WBC (×10(9)/l): 11.46±0.77 (11.50) vs. 8.94±0.91 (9.20), P<0.001; for hs-CRP (μg/dl): 137.84±50.71 (130.00) vs. 78.30±35.20 (65.27), P<0.001]. There was a strong positive correlation between the mean aortic stiffness index and markers of inflammation (for WBC, r=0.857, P<0.001; for hs-CRP, r=0.858, P<0.001), whereas strong negative correlations were observed between aortic elasticity parameters and markers of inflammation (for aortic distensibility of WBC and hs-CRP, r=-0.862, P<0.001; r=-0.869, P<0.001, respectively, and for aortic strain of WBC and hs-CRP, r=-0.890, P<0.001; r=-0.906, P<0.001, respectively). Young prehypertensives have increased markers of inflammation, namely, hs-CRP and WBC, compared with controls. More importantly, impaired arterial stiffness is significantly associated with the markers of inflammation in patients with prehypertension.

Plasma soluble transferrin receptor assay when screening for iron‐deficiency in an unselected population of elderly anaemic patients

Plasma soluble transferrin receptor assay when screening for iron-deficiency in an unselected population of elderly anaemic patients

Mobile and cordless telephones, serum transthyretin and the blood-cerebrospinal fluid barrier: a cross-sectional study

BackgroundWhether low-intensity radiofrequency radiation damages the blood-brain barrier has long been debated, but little or no consideration has been given to the blood-cerebrospinal fluid barrier. In this cross-sectional study we tested whether long-term and/or short-term use of wireless telephones was associated with changes in the serum transthyretin level, indicating altered transthyretin concentration in the cerebrospinal fluid, possibly reflecting an effect of radiation.MethodsOne thousand subjects, 500 of each sex aged 18–65 years, were randomly recruited using the population registry. Data on wireless telephone use were assessed by a postal questionnaire and blood samples were analyzed for serum transthyretin concentrations determined by standard immunonephelometric techniques on a BN Prospec® instrument.ResultsThe response rate was 31.4%. Logistic regression of dichotomized TTR serum levels with a cut-point of 0.31 g/l on wireless telephone use yielded increased odds ratios that were statistically not significant. Linear regression of time since first use overall and on the day that blood was withdrawn gave different results for males and females: for men significantly higher serum concentrations of TTR were seen the longer an analogue telephone or a mobile and cordless desktop telephone combined had been used, and in contrast, significantly lower serum levels were seen the longer an UMTS telephone had been used. Adjustment for fractions of use of the different telephone types did not modify the effect for cumulative use or years since first use for mobile telephone and DECT, combined. For women, linear regression gave a significant association for short-term use of mobile and cordless telephones combined, indicating that the sooner blood was withdrawn after the most recent telephone call, the higher the expected transthyretin concentration.ConclusionIn this hypothesis-generating descriptive study time since first use of mobile telephones and DECT combined was significantly associated with higher TTR levels regardless of how much each telephone type had been used. Regarding short-term use, significantly higher TTR concentrations were seen in women the sooner blood was withdrawn after the most recent telephone call on that day.