Scandinavian Journal of Clinical & Laboratory Investigation最新文献

Background: Systolic murmur suggestive of aortic valve origin is a common accidental finding, particularly in the elderly. Usually, it is due to aortic stenosis (AS) or aortic sclerosis (ASc). Currently, echocardiography is used to differentiate AS from ASc. Plasma N-terminal (NT)-prohormone BNP (NT-proBNP) is known to correlate with the severity of AS. We assessed whether NT-proBNP separates AS from ASc.

Methods: The study population consisted of three groups: AS (n = 87, age 77 ± 7 years), ASc (n = 76, age 72 ± 10 years), and healthy controls (n = 101, age 55 ± 10 years). All subjects underwent transthoracic echocardiography and measurement of plasma NT-proBNP. Patients with diseases known to increase NT-proBNP were excluded.

Results: The crude plasma NT-proBNP (median; IQR) in AS patients (413; 165-1055 ng/l) was significantly higher compared to ASc patients (96; 53-237 ng/l, p < 0.001) and healthy controls (50; 29-76 ng/l, p < 0.001). After adjusting for the confounding factors (age, coronary artery disease, renal function and diastolic blood pressure), plasma NT-proBNP remained significantly higher in AS patients as compared to ASc (p < 0.002) and controls (p < 0.0001). In the receiver-operating characteristic curve for NT-proBNP to identify AS from ASc and controls, the area under the curve was 0.878 with optimal cutoff of 115 ng/l. In addition, using 115 ng/l to separate AS from ASc yielded sensitivity of 0.885, and negative predictive value of 0.808.

Conclusions: NT-proBNP was sensitive to identify AS and useful to rule out AS in patients with systolic murmur in the left ventricular outflow tract provided the patient does not have coexisting disease known to impact NT-proBNP.

Objectives: There appears to be marked discrepancies between total IgE reference intervals (RIs) in use by many laboratories and those recommended by published studies. The aim of this study was therefore to review total IgE RIs currently reported by Scandinavian and British laboratories and to compare these to published RIs identified by a literature review.

Methods: Relevant laboratories were identified by test directories provided by the national accreditation bodies in Norway, Sweden, Denmark and the UK. Total IgE RIs and their sources were acquired by accessing laboratory user handbooks or by an electronic survey. In addition a literature review of published total IgE RI studies was performed.

Results: From 172 accredited laboratories providing total IgE analysis, data was acquired from 122 laboratories. An adult upper reference limit between 81 to 150 kU/L was reported by 89% of these. Denmark and Sweden reported the most harmonised RIs whilst Norway and the UK exhibited the least degree of harmonisation. Published adult (n = 6) and paediatric (n = 6) RI studies reported markedly higher upper limits than those currently in use by the laboratories included in this study. There were also large variations in the number of age strata in use for paediatric RIs.

Conclusion: This study demonstrates large variations in currently utilised IgE RIs by Scandinavian and British accredited laboratories and most report markedly lower RIs than those recommended by recent RI publications. Many laboratories likely utilise outdated RIs and should consider critically reviewing and updating their RIs.

Biological variation (BV) plays a crucial role in determining analytical performance specifications, assessing serial measurements of individuals, and establishing the use of population-based reference intervals. Our study aimed to calculate the BV and BV-based quality goals of 25-hydroxyvitamin D₃ (25-OH D₃), ferritin, folate and vitamin B12 tests. We included a total of 22 apparently healthy volunteers (9 women and 13 men) aged 18-55 years in the study that we conducted in Turkey. Blood samples were collected from the participants once a week for five weeks. Serum ferritin, folate and vitamin B12 levels were measured using immunochemical method, while plasma 25-OH D₃ levels were determined using the high-performance liquid chromatography method. Analysis of variance (ANOVA) was used to estimate analytical variation(CV_A), within-subject BV(CV_I) and between-subject BV(CV_G). The individuality index (II) and reference change value (RCV) were calculated based on these data. The CV_I of 25-OH D₃, ferritin, folate, and vitamin B12 were found to be 1.8% (0.6%-2.5%), 16.9% (14.4%-20.2%), 10.7% (9.2%-12.7%), and 8.6% (6.8%-10.5%), respectively. CV_G were 44.2% (34.3%-69.9%), 132% (87.7%-238%), 19.4% (14.4%-28.8%), and 39.6% (29.8%-59.0%) for the same biomarkers, while CV_A were 3.2% (2.81%-3.71%), 3.5% (3.1%-4.1%), 4.0% (3.5%-4.6%), and 7.5% (6.6%-8.6%), respectively. The II values for 25-OH D₃, ferritin, folate, and vitamin B12 were calculated as 0.04, 0.13, 0.55, and 0.22, respectively. The RCV were 10.2%, 47.8%, 31.7%, and 31.6%, respectively. Because the tests analyzed in this study exhibit high individuality, RCV should be preferred rather than population-based reference ranges in clinical interpretation of results.

C-reactive protein (CRP)/Albumin ratio (CAR) seems to mirror disease severity and prognosis in several acute disorders particularly in elderly patients, which we aimed to study. As method we use a prospective study design; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 912, women 50%; mean age 70 years, baseline 2001 and 2004, median follow-up 15.0 years, end of follow-up 2019) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 924 mean age 71 years, baseline 1991-1995, median follow-up 15.6 years, end of follow-up 2016). Serum samples were used for analyses of CRP and Albumin. Cox regression analyses were performed for cardiovascular and all-cause mortality in models adjusting for several factors (age; physical activity; Interleukin-6; cardiovascular (CVD) risk factors: smoking, BMI level, systolic blood pressure, LDL-cholesterol, and diabetes), with 95% confidence interval (CI). When adjusting for age and CVD risk factors, CAR was significantly associated with cardiovascular mortality for meta-analyzed results from PIVUS and ULSAM, HR 1.09 (95% 1.01-1.18), but neither in PIVUS (HR 1.14, 95% CI 0.99-1.31) nor in ULSAM (1.07, 95% CI 0.98-1.17). Additionally, CAR was significantly associated with all-cause mortality in ULSAM 1.31 (95% CI 1.12-1.54) but not in PIVUS HRs 1.01 (95% 0.089-1.15). The predictive value of CAR was similar to CRP alone in PIVUS and ULSAM and slightly better than albumin for the prediction of CVD-mortality in ULSAM. In conclusion, CAR was not consistently associated with cardiovascular and all-cause mortality in the two cohorts. The prognostic value of CAR for long-term CVD-mortality was similar to CRP.

IgE sensitization profiles to single birch allergens in birch-sensitized patients differ among European countries. The aim of this study was to determine the distribution of specific IgE antibodies to major and minor birch pollen allergens in a population of allergic Norwegian individuals by using a birch allergic blood donor population as a surrogate sample. Sixty blood donors were recruited and sampled based on birch allergy symptoms such as rhinitis, rhinoconjunctivitis and/or mild asthma in previous seasons. All sera were collected before start of the pollen season and tested using a line blot assay (Euroimmun AG, Lübeck, Germany) for IgE to birch and timothy pollen. Both extracts, single allergens, and cross-reacting carbohydrate determinants (CCD) were analysed. Only donors with specific IgE to birch and/or timothy grass were further evaluated. Specific IgE to birch pollen extract was found in 52 sera, and sensitization to timothy grass in 40 sera. Specific IgE to Bet v 1 was predominant in contrast to Bet v 4 which was absent. However, sensitization to the minor allergens Bet v 2 and 6 was always found together with high levels of IgE to Bet v 1. Subjects sensitized to the profilin Bet v 2 from birch were also sensitized to Phl p 12 from timothy grass. In conclusion, there was predominantly Bet v 1 sensitization in this cohort and low sensitization to minor allergens and cross-reactive allergens (Bet v 2, Bet v 4, Phl p 7 and Phl p 12).

Chronic hypertension is one of the major risk factors for preeclampsia. Pregnancy-specific beta-1-glycoprotein (PSG-1) is a protein that plays a critical role in fetomaternal immune modulation and has been shown to be closely associated with pregnancy adverse events such as preeclampsia. It is also known that PSG-1 and its source placenta are associated with many molecular pathways associated with blood pressure regulation. In addition, the nondipping pattern (NDP) of chronic hypertension has been shown to be an independent risk factor for preeclampsia. Dipper individuals experience a notable nighttime drop in blood pressure, typically around 10% or more compared to daytime levels, while nondipper individuals show a smaller nighttime blood pressure decrease, indicating potential circadian blood pressure regulation disruption. In this context, we aimed to reveal the relationship between PSG-1, NDP and preeclampsia in this study. A total of 304 pregnant women who were newly diagnosed in the first trimester and started on antihypertensive medication were included in this study. All subjects performed 24-h ambulatory blood pressure monitoring twice throughout pregnancy, the first in the 1. trimester to confirm the diagnosis of hypertension and the second between 20⁺⁰ and 21⁺¹ gestational weeks to determine the dipper-nondipper status of hypertension. Subjects were grouped as dipper and nondipper according to blood pressure, and groups were compared in terms of PSG-1 levels. In this study, low PSG-1 levels and NDP were independently associated with preeclampsia. Findings from this study suggest that PSG-1 may play an important role in the causal relationship between NDP and preeclampsia.

Objectives: Data were collected to establish a reference interval for glycated albumin (GA), as well as to calculate a cutoff value for diagnosing diabetes mellitus and the GA level corresponding to a 75-g oral glucose tolerance test (OGTT) 2 h plasma glucose (2h-PG) level of 200 mg/dL.Methods: This study involved 1,843 subjects who were undergoing medical check-ups at several medical institutions and whose HbA1c and GA levels had been measured by OGTT.Results: The GA reference interval that was calculated based on the data obtained from study subjects with normal glucose tolerance was 12.1-17.1%. Using standardized major axis regression, the levels that corresponded to an OGTT 2h-PG level of 11.1 mmol/L were a GA level of 17.5% and an HbA1c level of 47.5 mmol/mol. A receiver-operating characteristic curve analysis was used to calculate the points at which sensitivity and specificity matched as the cutoff values, and the results yielded a GA level of 15.0% (sensitivity 69.3%).Conclusions: The GA reference interval was calculated to be 12.1-17.1%. We propose a GA level of 17.4% as a cutoff value to diagnose diabetes mellitus and a GA level of 15.0% as a screening cutoff value for diabetes mellitus, taking previous reports into account.

To assess the impact of high levels of hemolysis on the laboratory results for free β-hCG, PAPP-A, and TRAb performed on the B·R·A·H·M·S KRYPTOR Compact PLUS. Adapted from the CLSI guidelines EP07-A2, paired difference testing was performed on serum samples from the routine laboratory workflow. Three sample pools for each assessed analyte was prepared and subjected to increased levels of added hemolysate. For β-hCG and PAPP-A, the relative difference in the measured analyte concentration between the sample with 0 g/L added Hb and the samples with increasing free Hb concentrations (up to 6 g/L), was well below the pre-set acceptance criterion of 10% at all levels. The TRAb results showed greater variation than the other analytes, likely a consequence of imprecision rather than hemolysis. Hemolysis has a negligible effect on the analysis results of free beta-hCG, PAPP-A and TRAb measured on the B·R·A·H·M·S KRYPTOR Compact PLUS.

This study investigates the impact of sample type on the measurement of 25-OH-vitamin D using the Liaison XL (Diasorin) and Cobas e801 (Roche). This investigation was motivated by the need to optimize sample volume usage, which led us to adopt the use of heparin plasma, an alternative proposed by Diasorin in their specification. Discordant and unexplainable results were observed, prompting us to evaluate the effect of sample type on the accuracy of the 25-OH-vitamin D measurements. We collected 34 different paired samples from a randomly selected patients who had two types of tubes taken simultaneously: serum-gel and lithium-heparin plasma tubes. The 25-OH-vitamin D levels were measured using Cobas e801 and Liaison. Statistical analysis was performed using the Mann-Whitney test to calculate the p-value. Biases were also calculated. When comparing the heparin matrix with the serum matrix on the Liaison XL analyzer, a higher proportion (p < .0001; 79% versus 64%) of patients were classified in the 'normal group', while fewer were classified in the 'insufficiency' or 'deficiency group'. The heparin tubes on the Liaison XL analyzer showed a mean bias of 57.5%) (p-value < .001; 95%CI: 37.6-77.4) compared to the serum tubes. On the other hand, the heparin tubes on the Cobas e801 analyzer showed a mean bias of -0.2% (95%CI: -4.8 to 4.5) compared to the serum tubes. It is imperative for laboratory professionals to be aware of this interference for an accurate measurement of 25-OH-vitamin D levels on the Liaison XL. Further research is needed to understand the mechanism of this interference.