Scandinavian Journal of Clinical & Laboratory Investigation最新文献

We investigated serum concentrations of specific inflammatory parameters in patients with significant carotid artery stenosis (CAS) of 50-99%, with an additional focus on patients with moderate stenosis (50-69%), in terms of both symptomatic status and plaque morphology, to determine whether there are certain parameters that can be associated with plaque instability before the progression of CAS to a high degree. The study included 119 CAS patients, 29 of whom had moderate stenosis, and 46 controls. Ultrasonography of the carotid arteries was performed using color flow Doppler and B-mode duplex ultrasound, and serum inflammatory parameters were measured using commercially available enzyme immunoassays. When comparing patients with 50-99% stenosis, only serum amyloid A (SAA) was higher in symptomatic patients, while in the group of patients with 50-69% stenosis, myeloperoxidase (MPO) was higher and pentraxin-3 (PTX-3) was lower in symptomatic compared to asymptomatic patients, and soluble urokinase plasminogen activator receptor (suPAR) was higher in patients with carotid plaque of unstable compared to stable morphology. Our results suggest that the importance of different inflammatory parameters in patients with moderate CAS is not the same as in CAS patients in general, and therefore their separate investigation in patients with high and moderate stenosis may be beneficial. SAA has the potential to be further considered in research to predict CAS symptom risk. There is a possibility that MPO and PTX-3 play a role in the development of CAS symptoms originating from less stenotic plaques and that suPAR is involved in the destabilisation of such plaques.

Measuring plasma albumin is a common and important laboratory test. We compared the results obtained with the bromocresol green (BCG) colorimetric, immunoturbidimetric (IT), and capillary electrophoresis (CE) methods and evaluated the clinical reliability of the colorimetric test. Samples from 320 patients including 227 patients with hypoalbuminemia (albumin levels <35 g/L) were analyzed. Results were compared between different patient groups. The BCG method indicated significantly higher plasma albumin levels than the CE and IT methods, especially in patients with elevated C-reactive protein, alpha-1 globulin (a1G), and alpha-2 globulin (a2G) values. A significant proportion of patients with mild hypoalbuminemia tested using the BCG method (alb_BCG) and were classified as severely hypoalbuminemic (albumin <20 g/L) when switching to the CE or IT method (alb_CE and alb_IT). These patients had elevated a1G and/or a2G levels. This change of result implied an additional indication for albumin replacement therapy. The BCG method significantly overestimates albumin levels in patients with inflammation and hypoalbuminemia, which may lead to inappropriate therapeutic decisions.

Hemoglobin Tacoma is known to potentially interfere HbA1c assays. The variant is common in Finland with prevalence of up to 2% regionally and cases are also reported in areas that have attracted Finnish immigrants, especially in Sweden and North America. Here, we investigated the effect of Hb Tacoma on seven HbA1c methods. 20 non-variant and 20 Hb Tacoma samples were measured with Tina-quant Gen. 3 (immunoassay, considered as reference) and the following point of care instruments: Afinion 2, HbA1c 501 (both utilizing boronate affinity), QuikRead go, cobas b 101, DCA Atellica, and Standard F (all immunoassays). Repeatability was also assessed by measuring both non-variant and Hb Tacoma samples five times each at two different levels. For non-variant samples, the mean relative bias with all methods was < ±4%, whereas for Hb Tacoma samples Standard F had 38% mean relative bias. In absolute bias, the difference was 17 mmol/mol on average and constant through the measured range. For other methods the mean relative bias for Hb Tacoma samples was < ±6%. The repeatability with all methods was similar for non-variant and Hb Tacoma samples and at highest 4.1% (mean CV% of two levels). The observed interference by Standard F is likely due to two-antibody assay design as Hb Tacoma has been shown to result in conformational change. This interference is clinically significant and highlight the need for better controlling and better understanding hemoglobin variants in HbA1c testing.

ABTRACTThis study retrospectively reviews individuals diagnosed with biotinidase deficiency in Eastern Anatolia to analyze the genetic variants and their relationship with biotinidase activity levels. The research focuses on determining the percentage impact of different variants on enzyme activity. The study included 357 patients who presented to Erzurum City Hospital with symptoms of biotinidase deficiency between 2018 and 2023 and were referred to the medical genetics department. Biotinidase enzyme levels were determined using spectrophotometric and colorimetric techniques, while Sanger sequencing analyzed the four exons and intron boundaries of the BTD gene. In the analysis of 357 patients (181 boys, 176 girls), the most frequent variant was c.1270G > C | p.Asp424His. Biotinidase enzyme activity was above 30% in 97.3% of patients with a homozygous p.D424His mutation. The mutations that caused the most significant decrease in enzyme activity were c.410G > A p.Arg137His, c.38_delinsTCC p.Cys13phefs*36, and c.1535C > T p.Thr512Met. Hearing loss (4 patients) and optic atrophy (1 patient) were mainly observed in patients with the c.38_delinsTCC mutation (homozygous or heterozygous). Most patients were asymptomatic, and mild symptoms were effectively prevented with biotin treatment. This study provides a detailed analysis of genetic diversity and clinical presentation in biotinidase deficiency cases in Eastern Anatolia, demonstrating the efficacy of biotin treatment. It highlights the significant role of genetic variants in phenotypic diversity and the need for personalized treatment, calling for further genetic research to enhance understanding of variant diversity and its impact on enzyme activity.

A low eGFR_{cystatin C}/eGFR_creatinine-ratio is characteristic of a group of serious kidney disorders called 'Selective Glomerular Hypofiltration Syndromes'. This study examines if such a low ratio can also be used to evaluate the risk for women with hypertensive disorders in pregnancy to develop severe maternal morbidity. All women discharged from the perinatal ward at the Skåne University Hospital in Lund during the period of 1-9-2016 to 31-8-2017 under one of the diagnoses within hypertensive disorders in pregnancy were considered for inclusion in the study. After delivery and discharge from the hospital, records from included patients were reviewed and all registered measures of renal function were analysed. An eGFR_{cystatin C}/eGFR_creatinine-ratio ≤0.60 in a sample drawn not earlier than three days before delivery was considered as defining a high risk for severe maternal morbidity. A strong association (p-value: 0.035) between severe maternal morbidity and an eGFR_{cystatin C}/eGFR_creatinine-ratio ≤0.60 was found in a subgroup of 32 women diagnosed with 'preeclampsia with severe features'. A total of 69 women were included in the study. Fifty were defined as high-risk and seventeen of them (34%) developed severe maternal morbidity. Among the nineteen women defined as low-risk only two (10.5%) developed severe maternal morbidity (p-value: 0.051). A low eGFR_{cystatin C}/eGFR_creatinine-ratio seems promising as a predictive marker for maternal morbidity in hypertension in pregnancy. Its performance as a tool in the monitoring of progressing disease should be evaluated further in larger cohorts. Delivery before the eGFR_{cystatin C}/eGFR_creatinine-ratio decreases to, or below, 0.60 might help avoid maternal complications.

Background: Cobalamin C is the most common inborn error of intracellular cobalamin metabolism caused by biallelic pathogenic variants in the MMACHC gene, leading to impaired conversion of dietary vitamin B12 into its two metabolically active forms, methylcobalamin and adenosylcobalamin. Biochemical hallmarks are elevated plasma total homocysteine (HCYs) and low methionine accompanied by methylmalonic aciduria. This study aimed to evaluate the clinical, biochemical, and molecular analysis of Pakistani patients with CblC defect.

Methods: Medical charts, urine organic acid (UOA) chromatograms, plasma amino acid levels, plasma tHcy and MMACHC gene results of patients presenting at the Biochemical Genetics Clinic, AKUH from 2013-2021 were reviewed. Details were collected on a pre-structured questionnaire. SPSS 22 was used for data analysis.

Results: CblC was found in 33 cases (Male:Female 19:14). The median age of symptoms onset and diagnosis were 300 (IQR:135-1800) and 1380 (IQR: 240-2730) days. The most common clinical features were cognitive impairment (n = 29), seizures (n = 23), motor developmental delay (n = 20), hypotonia (n = 17), and sparse/hypopigmented scalp hair (n = 16). The MMACHC gene sequencing revealed homozygous pathogenic variant c.394C > T, (p.Arg132*) in 32 patients, whereas c.609G > A, (p.TRP203*) in one patient whose ancestors had settled in Pakistan from China decades ago. The median age of treatment initiation was 1530 (IQR: 240-2790). The median pre-treatment HCYs levels were 134 (IQR:87.2-155.5) compared to post-treatment levels of 33.3 (IQR: 27.3-44.95) umol/L.

Conclusions: Thirty-three cases of CblC defect from a single center underscores a significant number of the disorder within Pakistan. Late diagnosis emphasizes the need for increased clinical awareness and adequate diagnostic facilities.

To establish age- and sex-specific reference intervals (RIs) for serum tumor markers (AFP, CEA, CA125, CA199, CA153, HE4, CA724, CYFRA21-1, PSA, and NSE) among a cohort of healthy individuals in South China, a retrospective analysis was conducted on 51,353 samples collected from 2015 to 2020, during health assessments at Guangdong Provincial People's Hospital. The influence of age and gender on serum tumor markers was investigated. New RIs were determined using non-parametric rank-based methods per CLSI EP28-A3C guidelines. Significant differences were detected across age groups for AFP, CEA, CA125, CA199, HE4, CYFRA21-1, PSA, and NSE (p < 0.05). The upper reference limits (URLs) for CA153 and HE4 are significantly lower compared to our current laboratory standards. The URL for CA125 exceeds these limits in individuals under 50 but decreases in those aged 50 and above. For CA199, CEA, and PSA, the URLs are below current standards in individuals younger than 60 but exceed them in those aged 60 and older. Noteworthy elevations were observed in CA724, CYFRA21-1, and NSE levels. Our study establishes age- and sex-specific RIs for ten serum tumor markers among healthy individuals from South China, providing a fundamental resource for the prevention, early detection, and management of tumor-related disorders.

Preeclampsia (PE) pathogenesis is strongly related to diminished nitric oxide (NO) bioavailability and enhanced oxidative stress. Emerging evidence suggests that red blood cells (RBCs) eNOS enzyme contributes to systemic NO bioavailability by its ability of both NO and ROS generation. We aimed to investigate RBC eNOS enzyme activity, NO and ROS generation capacity, eryptosis index and aggregation levels in preeclamptic and uncomplicated pregnant women. Fifty-eight PE patients and 36 healthy pregnant women were included to the investigation. RBC eNOS enzyme activity, intracellular NO, calcium and ROS concentrations and eryptosis levels were determined via flow cytometric methods. RBC deformability and aggregation were measured via LORRCA. Intracellular NO and phosphorylated RBC eNOS levels decreased in PE group compared to healthy pregnant group (p < 0.05, p < 0.001 respectively). Intracellular ROS and calcium levels, eryptosis values and aggregation indexes in the PE group were significantly higher than healthy pregnant group (p < 0.05, p < 0.01, p < 0.05, p < 0.05 respectively). Our results demonstrate for the first time that RBC produce lower NO and higher ROS under PE conditions. Further, RBC of PE patients were more prone to eryptosis and aggregation compared to control group. Our results suggest that, in addition to endothelial cells, RBC also contribute to decreased plasma NO bioavailability via producing less NO and high ROS in PE. Considering increased tendency to eryptosis and aggregation, RBC seem to play role in haemodynamic changes of PE pathogenesis.

The association between the MCM6-13910-C/T polymorphism and lactose intolerance in individuals of European descent is well known. However, the notion that having a single versus a double allelic mutation might influence one's phenotype has been hypothesized. This study investigated whether patients with the three genotypes C/C, C/T, T/T differed in response to a lactose tolerance test (LTT) in a Danish setting. Anonymized data on 603 individuals with results for both genetic test and LTT were investigated. Mean delta glucose values were plotted for the time points of the LTT (0, 15, 30, 45 and 60 min) for the C/C, C/T and T/T genotype, respectively. Further, the agreement between the three genotypes and the diagnostic interpretation of the LTT were examined using a cut-off of > 1.4 mmol/L rise in glucose. In subjects with the C/C genotype, mean glucose delta levels were markedly lower compared to both the C/T and T/T genotypes at all time points. Overall, a difference between mean glucose delta values among the C/T and T/T genotype could not be shown. Using a LTT cut-off of > 1.4 mmol/L, the proportions of lactose intolerant LTT results for each genotype were as follows: 58% among C/C, 5% among C/T, and 7% among T/T. In a Danish healthcare setting, the C/C genotype was on average associated with a smaller glucose response during a LTT when compared to the C/T and T/T genotypes. A marked difference in the LTT response among the C/T and T/T genotype was not observed.