Scandinavian Journal of Clinical & Laboratory Investigation最新文献

Background and aims: Ectopic pregnancy (EP) is a leading cause of maternal morbidity and mortality in the first trimester, accounting for nearly 9% of pregnancy-related deaths. An accurate biochemical marker for early detection is still unavailable. The kynurenine pathway, the primary route of tryptophan metabolism, is involved in immune tolerance, oxidative stress, and placental development. This study aimed to evaluate kynurenine metabolites as potential biomarkers for EP.

Methods: In this prospective single-center study, 106 pregnant women were recruited between January and June 2025, including 53 women with confirmed EP and 53 healthy first-trimester controls. Serum levels of tryptophan and its metabolites [3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), kynurenine, quinolinic acid, and kynurenic acid] were quantified using LC-MS/MS. Group comparisons, correlation analyses, and ROC curve evaluations were conducted.

Results: No significant differences were found in tryptophan, kynurenine, quinolinic acid, or kynurenic acid between groups (p > 0.05). However, 3-HK and 3-HAA were significantly elevated in the EP group (p < 0.001). ROC analysis demonstrated good diagnostic accuracy for 3-HAA (AUC = 0.80, 95% CI: 0.71-0.88) and 3-HK (AUC = 0.77, 95% CI: 0.67-0.86). Combined use improved discrimination (AUC = 0.86; sensitivity = 0.85; specificity = 0.75). Additionally, 3-HK correlated negatively with gestational age (ρ=-0.42, p < 0.001) and positively with monocyte and leukocyte counts.

Conclusion: These findings suggest that elevated 3-HK and 3-HAA levels are associated with EP and may reflect immunometabolic dysregulation underlying abnormal implantation, rather than implying a causal relationship. Therefore, these metabolites may offer complementary biomarker potential in selected research settings.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system. Recently, research has highlighted the significance of biochemical evaluation of metabolic pathways and circulating amino acids beyond their fundamental role as protein building blocks. They also function as key modulators of the immune system, neurotransmission, collagen synthesis, metabolic and regenerative pathways, which may influence disease progression. We hypothesized that a disturbed amino acid profile could be used as a biomarker for MS in pregnancy. Amino acid profiles of pregnant women diagnosed with MS and healthy pregnant women were evaluated. MS diagnosis is done according to the McDonald criteria. The Expanded Disability Status Scale (EDSS) was used to evaluate MS patients. The medications used by pregnant women with MS for their disease were recorded. During the pregnancy period, none of them used a drug regimen. Progressive MS forms and EDSS > 3,5 were excluded from the study. Amino acid levels of MS patients were found to be different from healthy pregnant women. Excitatory amino acid levels were found to increase in MS patients. Glutamine and threonine levels are found to be decreased in MS pregnant women. Also, amino acids that take part in collagen synthesis are found to be different. Glutamic acid, histidine, asparagine, aspartate, proline, serine, ornithine, threonine, and tryptophan levels and citrulline/ornithine ratios are found to be significantly different between groups. These findings suggest that amino acid profiles could be potential biomarkers for early detection and new therapeutic targets for MS.

Blood collection tubes significantly impact laboratory test accuracy, yet supply chain vulnerabilities of imported tubes necessitate evaluating domestic alternatives. This study compared the analytical performance of Ampulab and BD Vacutainer tubes. Paired blood samples were collected from 44 adult volunteers into Ampulab and BD Vacutainer tubes. Sixty-five analytes across clinical chemistry, immunology, hematology, and coagulation panels were analyzed using established platforms. Statistical comparisons included Passing-Bablok regression, Bland-Altman analysis, Wilcoxon signed-rank tests, and bias estimation against desirable biological variation thresholds. Most analytes showed acceptable agreement between the two tube types. Lactate dehydrogenase showed greater variability, exceeding the desirable bias (-4.37% vs. 3.1%), whereas chloride demonstrated a marginal deviation (-0.43% vs. 0.4%) with absolute differences remaining within 1-2 mmol/L. Prostate-specific antigen exhibited a bias above the desirable threshold at low concentrations but showed good regression agreement overall. Several hematology parameters, including white blood cells, mean corpuscular volume, and neutrophils, showed statistically significant differences; however, all remained within acceptable bias limits. Coagulation analytes demonstrated strong analytical agreement, but fibrin degradation product (FDP) showed greater variability without established performance criteria, indicating a need for further validation. Ampulab tubes demonstrated analytical performance comparable to BD Vacutainer tubes for most parameters tested. Serum separator and EDTA tubes are suitable for routine clinical use. Sodium citrate tubes require further validation for fibrinogen and FDP. These findings support the implementation of Ampulab tubes in clinical laboratories, with targeted verification recommended for selected analytes.

Transferrin saturation in plasma (P-TSAT) is 100 × P-iron/P-total iron binding capacity (P-TIBC). It is still used to diagnose iron deficiency, although P-ferritin is considered to be a better test. Both tests are sensitive to inflammation: P-TSAT decreases and P-ferritin increases. Unbound iron binding capacity in plasma (P-UIBC), which is P-TIBC minus P-iron, has a better diagnostic accuracy for iron deficiency than P-TSAT. However, how P-UIBC reacts in inflammation is less well known. We used cross-sectional data from 21681 patients to study how P-UIBC, P-TSAT, and P-ferritin varied with P-CRP. In a subpopulation of 8928 patients without inflammation (P-CRP ≤ 1 mg/L), we compared the diagnostic accuracy of P-TSAT and P-UIBC, using P-ferritin less than 15, 20, and 30 µg/L as reference standards for iron deficiency. We also estimated which values of P-UIBC and P-TSAT corresponded to a P-ferritin of 15, 20, and 30 µg/L. P-UIBC varied much less with P-CRP than did P-TSAT and P-ferritin. P-UIBC had better diagnostic accuracy than P-TSAT. Using P-ferritin < 20 µg/L as a reference standard, the areas under the ROC curves were 0.894 (95% confidence interval 0.883-0.905) for P-UIBC and 0.850 (0.836-0.864) for P-TSAT. At various ages, the values corresponding to a P-ferritin of 20 µg/L varied around 60 µmol/L for P-UIBC and around 20% for P-TSAT. In conclusion, when diagnosing iron deficiency, calculating P-UIBC is a better way of using P-iron and P-TIBC than calculating P-TSAT.

Often a measurement of an analyte is repeated in the same patient. Then the physician must interpret a pair of test results of the same analyte (x1, x2), measured in specimens collected hours to weeks apart. Physicians compare both test results against the univariate reference limits (RLs) and perhaps the difference x2 - x1 against reference change values (RCVs). We believe that it would be rational to compare a specific pair of (x1, x2) values against percentiles in the bivariate distribution of (x1, x2) from reference individuals. That has never been done, so we simulated (x1, x2) reference values using data on RLs, intraindividual biological variation in healthy individuals, and analytical variation. The bivariate percentiles corresponding to (x1, x2) observations were estimated from the Mahalanobis distances (MDs) in the bivariate distribution of (x1, x2) reference values. With a very few exceptions, the combination of 95% RLs and 95% RCVs did not enclose any (x1, x2) reference value with a bivariate percentile above 95. However, the combination enclosed only 92-93% of the (x1, x2) reference values below the bivariate 95 percentile. In conclusion, bivariate percentiles in the distribution of (x1, x2) reference values from a healthy reference population can be derived from available data, and used for reporting and interpreting the finding of a specific (x1, x2) observation in a patient.

Previous research suggests that the use of snus, a smokeless tobacco product, is associated with increased all-cause and cardiovascular mortality, but the underlying mechanisms are unknown. We aimed to evaluate the associations of snus use with biomarkers of cardiometabolic importance: high-sensitivity C-reactive protein (hs-CRP), 25-hydroxyvitamin D (25(OH)D) and calculated free testosterone (cfT). We performed cross-sectional analyses within the population-based Northern Sweden MONICA-study. The study sample consisted of 6 158 never-smoking men and women (of whom 21 and 3.3% were current snus users, respectively), examined between 1990 and 2014. Harmonized analyses on biomarkers were conducted 2016 to 2018. We evaluated the relationships between snus use and biomarker concentrations using linear and logistic regression. Snus use, compared to never-use, was associated with lower hs-CRP (exp(β_ln) 0.88, 95% CI 0.81; 0.96) and 25(OH)D-concentrations (β - 1.01, 95% CI -1.70; -0.33) in mixed-sex analyses. Among men, snus use was also associated with higher cfT-concentrations (exp(β_ln) 1.04, 95% CI 1.01; 1.07). Former snus users had no significant differences in biomarker concentrations. Snus users have lower concentrations of 25(OH)D and hs-CRP, irrespective of sex, while male users have higher cfT-concentrations. These findings may in part contribute to the previously observed increased mortality among snus users.

To investigate the combined predictive value of plasma trimethylamine N-oxide (TMAO) and white matter lesions (WMLs) burden for 90-day prognosis after endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) with large vessel occlusion (AIS-LVO). This retrospective study included 202 AIS-LVO patients from six centers who achieved successful recanalization after EVT between February 2023 and October 2024. Patients were categorized into good (mRS ≤ 3, n = 89) and poor prognosis (mRS > 3, n = 113) groups based on 90-day modified Rankin Scale (mRS). Univariate and multivariable logistic regression analyses were performed to identify independent predictors of poor prognosis. Receiver operating characteristic (ROC) curves evaluated the predictive performance of combined TMAO and WML scores. DeLong's test confirmed that combining TMAO with the Aharon Peretz score improves the predictive value for poor outcomes over traditional risk factors (NIHSS score and age). The poor prognosis group exhibited significantly higher age, TMAO levels, creatinine, Aharon Peretz scores and NIHSS compared to the good prognosis group (p < 0.05). Multivariable analysis identified TMAO (OR = 2.854, 95%CI: 1.693-4.812), and Aharon Peretz score (OR = 1.881, 95%CI: 1.384-2.558) as new independent predictors (p < 0.05). The combination of TMAO and Aharon Peretz scores predicted poor prognosis with an AUC of 0.786 (95%CI: 0.723-0.848). TMAO and Aharon Peretz scores are independent risk factors for poor short-term prognosis after EVT in patients with AIS. The combination of TMAO and Aharon Peretz scores more accurately predicts the occurrence of short-term poor prognosis after EVT in patients with AIS.

Our study aimed to compare the quality of patient self-collected capillary samples with venous blood samples. Additionally, we assessed whether patients with rheumatic disease are both capable of and willing to perform capillary self-sampling through subjective and objective assessments. This research explores the future potential of at-home self-sampling. Patients with rheumatic diseases were asked to perform up to four supervised self-collected capillary blood samples, followed by a standard venous sample performed by study personnel. Anti-rheumatic drug treatment monitoring parameters, including biochemistry and hematology, were analyzed using Cobas 8000 and Sysmex XN-9000, respectively. The agreement was evaluated by Bland-Altman plots and compared to critical difference limits. Study personnel and patients answered a survey questionnaire after every visit to evaluate feasibility. In total, 21 patients completed 53 paired capillary and venous samples from November 2019 to December 2020. We found a strong correlation (r > 0.87) and good agreement for most parameters; platelets showed the poorest agreement. Patients experienced little pain, found self-sampling easy and reported no serious complications. Hemolysis affected 12/53 capillary biochemistry samples, and 5/53 capillary hematology samples coagulated. The good agreement for most parameters and excellent feasibility encourages the potential for capillary self-sampling of DMARD monitoring parameters, relevant limitations were hemolysis and aggregating platelets.

Large language models (LLMs) have demonstrated high performance across various fields due to their ability to understand, generate, and manipulate human language. However, their potential in specialized medical domains, such as clinical chemistry and laboratory management, remains underexplored. This study evaluated the performance of nine LLMs using zero-shot prompting on 109 clinical problem-based quizzes from peer-reviewed journal articles in the Laboratory Medicine Online (LMO) database. These quizzes covered topics in clinical chemistry, toxicology, and laboratory management. The models, including GPT-4o, Claude 3 Opus, and Gemini 1.5 Pro, along with their earlier or smaller versions, were assigned roles as clinical chemists or laboratory managers to simulate real-world decision-making scenarios. Among the evaluated models, GPT-4o achieved the highest overall accuracy, correctly answering 81.7% of the quizzes, followed by GPT-4 Turbo (76.1%), Claude 3 Opus (74.3%), and Gemini 1.5 Pro (69.7%), while the lowest performance was observed with Gemini 1.0 Pro (51.4%). GPT-4o performed exceptionally well across all quiz types, including single-select, open-ended, and multiple-select questions, and demonstrated particular strength in quizzes involving figures, tables, or calculations. These findings highlight the ability of LLMs to effectively apply their pre-existing knowledge base to specialized clinical chemistry inquiries without additional fine-tuning. Among the evaluated models, GPT-4o exhibited superior performance across different quiz types, underscoring its potential utility in assisting healthcare professionals in clinical decision-making.

Vitamin B12 (B12) is essential for DNA synthesis in all cells and for the development and maintenance of a healthy nervous system. B12 is transported in the circulation bound to two carrier proteins, haptocorrin and transcobalamin, measured as the biomarkers total B12 and holotranscobalamin (holoTC). The latter measures the fraction of cobalamin available for tissue uptake and is considered to have a better sensitivity and specificity for diagnosing vitamin deficiency. The concentration of both carrier proteins depends on age, but data on paediatric reference values for holoTC are still sparse. Blood samples were obtained from 1320 healthy school children, mainly Caucasians (age 6-12 years old) in three different municipalities in Norway. The holoTC and total B12 levels were determined by chemiluminescent microparticle immunoassay on the Architect 2000 analyser. Age specific paediatric reference intervals (RIs) were estimated by calculating the 2.5 and 97.5 percentiles by the nonparametric method with corresponding 90% confidence intervals, according to the Clinical and Laboratory Standards Institute C28-A3C guidelines. The 95% RIs for total B12 were 295-1066 pmol/L for children 6-8 years old, and 249-879 pmol/L for children 9-12 years old. Reference intervals for holoTC were ≥56 pmol/L for children 6-8 years old, and ≥37 pmol/L for children 9-12 years old. Age specific RIs will aid clinicians in interpretation of cobalamin results in children aged 6-12 years old.