Blood gas analyzers (BGAs) offer rapid results and operational convenience in emergency settings, whereas laboratory auto analyzers (LAAs) remain the reference standard despite slower processing. This study compared BGA and LAA measurements of sodium (Na), potassium (K), hemoglobin (Hb), and hematocrit (Hct). A secondary aim was to evaluate their agreement across acid-base subgroups and in cases of severe acidosis. This study included ≥18 years patients from January 1 to June 30, 2024. BGA and LAA results were compared overall and across acid-base subgroups. Patients with pH <7.20 were analyzed separately as the severe acidosis group. Bland-Altman analysis showed the following mean differences and 95% limits of agreement: Na, 1.36 ± 2.33 mmol/L (-3.21 to 5.92); K, 0.221 ± 0.197 mmol/L (-0.166 to 0.607); Hb, 0.531 ± 0.649 g/dL (-0.742 to 1.804); and Hct, 1.68% ± 2.60 (-3.42 to 6.78). At clinical decision thresholds, BGA demonstrated varying diagnostic performance with sensitivities and specificities of 56.9% and 95.8% for hyponatremia, 67.5% and 98.7% for hypernatremia, 95.4% and 95.6% for hypokalemia, 48.7% and 99.8% for hyperkalemia, and 73.4% and 99.9% for transfusion decisions, respectively. In patients with severe acidosis, correlations remained strong, though agreement limits were notably wider. BGA-derived K values showed acceptable agreement with LAA and may be used interchangeably. Hb and Hct did not meet agreement criteria, while Na may be acceptable with clinical correlation. In severe acidosis, none of the parameters achieved acceptable agreement, indicating that BGA results should be interpreted with caution in this subgroup.
The aim was to assess and compare the analytical performance of the FUS-200 and its new upgrade, the MUS-3600 urine autoanalyzers, and to compare performance with manual microscopy. First morning, void urine samples were randomly collected, and suitable samples were analyzed on both autoanalyzers. In addition, concurrent manual microscopic examinations were performed for all suitable urine samples. Carry-over, linearity and imprecision analysis were performed to assess analytical and diagnostic performance of both urine autoanalyzers according to Clinical and Laboratory Standards Institute (CLSI) EP15-A2, and the study was conducted in accordance with CLSI GP16-A3 Urinalysis; Approved Guideline. A total of 518 samples were collected, and of these, 494 (95.4%) were suitable for analysis and were included in the study. Sensitivity and positive likelihood ratio (LR+) values for WBC and squamous epithelium (SqEC) counts for both autoanalyzers were >90% and >10%, respectively. Specificity and LR+ values obtained from MUS-3600 were better compared to the FUS-200 (respectively 92.8 vs. 84.7; 5.5 vs. 10.1). One group agreement between the MUS-3600 and manual microscopy was >90%. Both analyzers displayed comparable performance for RBC and WBC counts, which were moderately correlated with each other. These results show the diagnostic performance of the MUS-3600 and FUS-200 was satisfactory for urine sediment analysis and was compatible with manual microscopy findings. However, random urine samples are sub-optimal for evaluating diagnostic performance, particularly for bacterial, cast, crystal and yeast analysis. Thus, we recommend using more appropriate urine samples for this comparison, such as from patients with suspected urinary tract infections.
This study was carried out to estimate sigma values of two HbA1c analysers and compare laboratory's quality control (QC) procedure with a patient risk based statistical quality control (SQC) strategy. Internal quality control (IQC) and External quality control (EQC) results are downloaded from the laboratory data for different six-months' period when each analyser was used in the laboratory. Mean percent coefficient of variation (CV) and bias values of study period were calculated. Sigma values for each system were calculated. QC constellation program was used for risk-based QC parameters calculation and severity of harm level for HbA1c was taken as 'serious'. Sigma values for Capillarys 3 Tera analyser (Captera) were 3.83 and for Premier Hb9210 analyser (Premier) were 2.95. Using ±2 standard deviation (SD) as control limits; on Captera with a run size of 110 samples, probability of false rejection rate (Pfr) was 8.89%, expected maximum unreliable patient results (Max E(Nuf)) was 0.78 and on Premier analyser with a run size of 800 samples Pfr was 8.89% and Max E(Nuf) was 40.73. Effective statistical quality control strategies for both systems with acceptable Pfr and affordable Max E(Nuf) are provided in the study. HbA1c is a key parameter in diabetes management and accurate methods are required for an efficient clinical use.
The Triglyceride/HDL-Cholesterol (TG/HDL-C) ratio is a recognized biomarker for cardiovascular risk, linked to atherogenic dyslipidemia and insulin resistance. Recent evidence also implicates molecules like trimethylamine N-oxide (TMAO), CD36, and CD38 in metabolic inflammation and atherosclerosis. This study investigated the relationship between TMAO, CD36, and CD38 in individuals with a high TG/HDL-C ratio. A total of 82 volunteer individuals with no known cardiac disease were enrolled in the study (41 dyslipidemic individuals and 41 healthy controls). Serum TMAO levels from participants were quantitatively measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The surface expression levels of CD36 and CD38 on the monocyte population were assessed by flow cytometry. The plasma atherogenic index (PAI) was calculated using the log(TG/HDL-C) formula to assess the atherogenic risk status. The TG/HDL-C ratio, TMAO level, and CD38 expressions were significantly higher in the dyslipidemia group compared to the control group (p < 0.05). Additionally, low-density lipoprotein cholesterol levels and HOMA-IR scores were higher in dyslipidemic individuals. According to the PAI assessment, the entire dyslipidemia group was in the high cardiovascular risk category. The TG/HDL-C ratio showed a positive correlation with TMAO and CD38 levels. The positive relationship between the TG/HDL-C ratio and TMAO and CD38 levels suggests that these parameters could be evaluated together to reflect cardiovascular risk. However, given the cross-sectional design of the study, these findings indicate associations rather than causal relationships, and metabolic and inflammatory markers may reflect early stages of subclinical atherosclerosis in individuals without known cardiovascular disease.
This study evaluted the Sysmex XR-9000 hematology analyzer in a clinical setting, comparing it with the XN-9100 system using patient samples from routine laboratory. The evaluation followed CLSI H26-A2 and ICSH guidelines, incorporating state-of-the-art (SOTA) and EFLM biological variation criteria. The XR-9000 met LLoQ criteria for leukocyte and platelet counts using the White cell Differential channel by Fluorescence (WDF) and platelet fluorescence (PLT-F) channels, with CV% below 7% for WBC at 0.1 x109/L and platelets at 1.5 x109/L. Linearity was excellent across all parameters (r2 > 0.99) and imprecision reported by the manufacturer was verified. For Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and Mean Corpuscular Hemoglobin Concentration (MCHC), CV% values reached 0.7%, 1.3%, and 1.7%, respectively, exceeding EFLM criteria of 0.4%, 0.3%, and 0.5%. The low concentration controls for neutrophils counts (NEUT) and platelets exceeded SOTA limits of 2.5% and 3%, respectively, with CV% up to 3.6% and 4.1%. Clinically relevant levels for platelets, hemoglobin, and NEUT showed acceptable imprecision with CV% <5, ≤1.3, and <9, respectively. Accuracy testing confirmed agreement with manufacturer's controls and an EQA program, with immature granulocytes as the only exception due to its level falling below LLoQ. Method comparison between the XR-9000 and XN-9100 systems demonstrated strong agreement, with minor discrepancies in MCHC, basophils count (BASO), and platelets. In conclusion, the XR-9000 demonstrated reliable performance across key metrics, meeting clinical requirements for accurate diagnosis and monitoring in hematology.
Thyroid nodules are common, and the majority are of benign nature, however the main clinical aim remains to discriminate malignant ones. Despite that, the actual routine workup for thyroid nodules including hormonal testing, ultrasound scan, scintigraphy, and Fine needle aspiration cytology (FNAC) is still deficient, often necessitating surgical intervention for a conclusive histopathological examination and diagnosis. Therefore, searching for molecular tools that help in differentiating benign and malignant thyroid nodules gains an increasing interest. This case-control study was conducted on 46 adults, categorized into two groups (23 patients each) one with benign and another with malignant thyroid nodules, based on post- operative histopathology. Prior to surgery patients have undergone clinical examination and ultrasonography (US) neck and only patients with US - TIRADs 3, 4 and 5 thyroid lesions were referred for FNAC and included in this study. Surgery decisions were made according to FNAC Bethesda classification. Total RNA was extracted from plasma samples prior to surgery. The reverse transcription of miRNA to cDNA was followed by Real Time PCR Amplification in triplet to analyze miRNA-222, miRNA-146b and reference miRNA-16. Plasma from 40 healthy subjects was used as control for the calculations of the relative expression of miRNA using RT-qPCR. The results showed a statistically significant increased expression of plasma miRNA-222 and miRNA-146b in the malignant nodules group than benign group (p = 0.001 and p= <0.001, respectively). Also, there is a statistically significant difference between benign and malignant groups regarding the presence of plasma miRNA-222 or plasma miRNA-146b with higher levels than Youden Index cutoffs (p= <0.001). MiRNA-222 showed increased plasma expression with vascular invasion of malignant nodules. Adding the estimation of plasma miRNA-222 and 146b levels to the actual ultrasound features and to FNAC Bethesda classification, raised AUC of ROC of the mentioned tools for the diagnosis of malignant thyroid nodules. These findings suggest a potential role for miRNA-222 and miRNA-146b in differentiating benign and malignant thyroid nodules and may provide a valuable diagnostic addition to the current routine workup.
Diabetes is a growing global health concern affecting millions worldwide. Glucose measurement remains a cornerstone in the diagnosis, monitoring, and management of this disease. Considering that numerous point-of-care (POC) devices for glucose measurements are available, systematic evaluation of their analytical performance and user-friendliness is essential. This study presents the findings of an independent evaluation of the cobas pulse glucose meter (Roche Diagnostics GmbH) conducted by the Scandinavian evaluation of laboratory equipment for point of care testing (SKUP). The study, which assessed both the analytical performance and user-friendliness, included 217 participants with diabetes and was conducted in both a hospital laboratory and primary healthcare settings. Capillary whole blood measurements were compared to a plasma glucose hexokinase method at Vejle hospital, Denmark. Certified reference materials from the National Institute of Standards and Technology (NIST) were used to correct all sample results. Repeatability and accuracy were assessed against predefined analytical performance specifications, and user-friendliness was evaluated using a structured questionnaire developed by SKUP. The cobas pulse demonstrated good repeatability (CV: 1.8-4.0%) and fulfilled the specification for accuracy, with minimal bias (maximum +0.16 mmol/L in the 7-10 mmol/L range). Haematocrit had no significant effect within the tested range (5-70%). User-friendliness was rated satisfactory, attributed to intuitive operation, rapid analysis times, and effective quality control features. In conclusion, the cobas pulse glucose meter met the performance criteria for professional use in clinical and primary care settings, supporting its suitability in near-patient glucose monitoring.
Understanding biological variation (BV) is crucial for accurate clinical decision-making and for establishing analytical quality standards. This study established the BV of low-density lipoprotein cholesterol (LDL-C), assessed using both direct measurement and calculated values obtained from the Friedewald and Martin-Hopkins formulas in healthy individuals. A total of twenty-six healthy Turkish subjects (15 females and 11 males) underwent fasting LDL-C measurement, along with calculated LDL-C derived from serum cholesterol, triglycerides, and high-density lipoprotein cholesterol, using samples collected concurrently on 10 weekly occasions. All measurements were conducted in duplicate by the enzymatic colorimetric method. Within-subject (CVI) and between-subject (CVG) BV estimates, with 95% confidence intervals (CI), were determined by CV-ANOVA following evaluation of trends, homogeneity of variance, and outlier removal. No significant gender-related differences were observed in the BV components for either direct or calculated LDL-C. According to direct LDL-C, Friedewald LDL-C, and Martin Hopkins LDL-C, CVI values were 8.7%, 9.3% and 9.0%, and the CVG values were 14.7% for direct LDL-C, 18.5% for Friedewald LDL-C, 18.6% for Martin Hopkins LDL-C. These values supported the use of updated analytical performance specifications and reference change values (RCV). All LDL-C exhibited marked individuality (II < 0.6). By applying a rigorously standardized experimental protocol, the inter-individual variability observed supports the preferred use of RCVs over conventional population-based reference intervals for serial monitoring. These results have important implications for enhancing the clinical utility of LDL-C measurements, regarding cardiovascular risk assessment and individualized therapeutic decision-making.
In intensive care units (ICU), malnutrition is very common and closely related to severe inflam-matory states. The aim of this study was to develop and validate a nutritional inflammatory prognostic score (NIPS) predictive of short-term mortality, and to verify the validity of existing scores. A total of 606 ICU patients were included in a longitudinal study. The population was randomly divided into two groups: development (383) and validation (223). The NIPS score was developed from nutritional and inflammatory parameters using multi-adjusted Cox proportional regression. Validation of NIPS as a prognostic score was tested using the area under the ROC curve (AUC), Cox proportional regression, and the Kaplan-Meier curve. The validity of five selected scores was also assessed. The NIPS score was developed from C-reactive protein to prealbumin ratio, total cholesterol, procalcitonin and neutrophil to lymphocyte ratio. With an AUC of 0.89 and a cutoff of 5.0, NIPS predicted short-term mortality with a sensitivity of 80.5% and a specificity of 93.8%. The risk of mortality was fivefold higher in the high nutritional risk group (RR= 5.0, [3.1-7.9], p < 0.0001). The crude cumulative incidence of mortality was significantly higher in the high-risk group (pLog-Rank < 0.0001). The five selected scores had a significant, but, lower prognostic value, compared with the developed score (AUC between 0.59 and 0.70). This study provides a new nutritional risk score, based on widely available biological parameters, with proven efficiency in predicting ICU mortality risk. Nutritional risk screening should be routinely performed at the earliest admission stages.
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.
Haematologists are often consulted on the need for additional diagnostic workup in patients with blast cells in peripheral blood. However, cancer risk (including solid tumors) after detection of blast cells in peripheral blood is lacking. Therefore we evaluated the 1-year cancer risk following detection of blast cells in peripheral blood. We used population-based retrospective data from the Region of Southern Denmark (2014-2021), including 2,187 individuals aged ≥20 years with blast cells in blood samples, excluding those with prior cancer. Results from haematological parameters derived from the laboratory information system, while diagnoses and vital status were from administrative registers. Natural language processing assisted review of clinical notes for individuals without cancer codes. We estimated age-standardised cancer incidence rates and compared observed versus expected cancers using standardised incidence ratios (SIR). We found that the overall 1-year cancer risk was 23% [95% CI: 21-24], with 19% [95% CI: 18-21] for haematological cancers and 3% [95% CI: 2-3] for solid cancers, compared to 0.87% in the background population. The age-adjusted SIR was 22 [95% CI: 21-24] and was highest for haematological cancers at 199 [95% CI: 184-214]. Although 78% of individuals had no blast cells upon repeated testing, 27% still developed cancer within a year. In conclusion the presence of blast cells in peripheral blood may warrant consideration of further diagnostic evaluation, particularly in the presence of other haematological abnormalities. We aim to elucidate the 1-year risk of cancer for persons with blast cells in peripheral blood.Even the presence of small amounts of blast cells in peripheral blood are associated with highly increased 1-year cancer risk of mainly haematological cancers, and therefore a threshold for blast cells in peripheral blood could not be detected in this study.Presence of blast cells in peripheral blood may warrant consideration of further diagnostic evaluation, particularly in the presence of other haematological abnormalities.
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. 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. 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. 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.
The digestion of food is known to have significant hemodynamic and metabolic effects where many have not been fully investigated. The potential effect of food intake could be interesting both from a physiological point of view and from a methodological point of view, as it could affect when blood samples are collected. The objective of this study was to investigate the effect of food intake on 143 different predominantly inflammatory but also some organ damage biomarkers. Twenty-two healthy subjects (11 male and 11 female aged 25.9 ± 4.2 years) were investigated. A total of 143 biomarkers were measured before a standardized meal as well as 30 and 120 min afterwards with the Proseek Multiplex Inflammation I, and Multiplex Organ Damage panels, both using the Olink's Proximity Extension Assay. The levels for 23 biomarkers were significantly (p < 0.001) changed due to food intake. A total of 14 biomarkers decreased 30 min and 120 min after food intake. Four biomarkers were increased only at 120 min after food intake. The changes for the biomarkers were between 2% and 105%. This study shows that food intake has some effect on 143 different biomarkers. The timing of blood sampling in relation to food intake could be a concern when investigating Interleukin-6, Anterior gradient protein 2 homolog, BH3-interacting domain death agonist, Tyrosine-protein kinase Fes/Fps, Syntaxin-8, Probetacellulin, Peptidyl-prolyl cis-trans isomerase FKBP1B, Ribonucleoside-diphosphate reductase subunit M2 B, and Enteropeptidase, which all changed more than 30%.
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.
Elevated triglyceride (TG) levels, common in hypertriglyceridemia, can significantly interfere with electrolyte analysis, particularly by the indirect ion-selective electrode (ISE) method. However, comprehensive data on the concentration-dependent measurement differences for potassium, sodium and chloride, along with validated corrective algorithms, are lacking. This study assessed the discrepancies in these electrolytes between direct and indirect ISE methods in serum samples with high TGs, while developing correction formulas for the indirect ISE. A total of 154 serum samples with high TGs and 50 control serum samples were analyzed in this retrospective cross-sectional study. Triglycerides were measured using colorimetric methods on the Roche Cobas 8000 analyzer (Roche Laboratories, Basel, Switzerland). Sodium, potassium and chloride were measured with direct ISE (Vitros 5600 Integrated System; Ortho-Clinical Diagnostics, Inc., Raritan, NJ) and indirect ISE (Roche Cobas 8000 analyzer). Our results revealed significant negative biases in the indirect ISE, particularly in samples with TG >20.00 mmol/L. For TG levels between 20.01 and 30.00 mmol/L, the negative biases for sodium, potassium and chloride were -2.31%, -3.86% and -4.58%, respectively. Notably, in the subgroup with TG >60.00 mmol/L, the negative biases reached their maximum values: -12.05% for potassium, -6.88% for sodium, and -10.59% for chloride. Additionally, linear correction formulas that aligned indirect results with direct measurements were developed and validated. Post-correction, differences fell within clinical thresholds (Diff_Na of |4| mmol/L, Diff_Cl of |4| mmol/L, Diff_K of |0.5| mmol/L). Collectively, high TGs impact electrolyte measurements by indirect ISE, but the correction formulas might mitigate the discrepancies. These correction formulas were platform-specific, and their generalizability to other analytical systems requires further investigation.
Early kidney function decline may be associated with reduced filtration of middle-sized molecules, currently defined as selective glomerular hypofiltration syndrome (SGHS), and driven by the accumulation of atherosclerosis-promoting proteins. We aimed to investigate whether SGHS and other markers of kidney function are associated with subclinical atherosclerosis as evaluated by intima-media thickness (IMT) in the carotid arteries, and whether these associations differ by sex. Data from 2,902 individuals in the 'Malmö Diet Cancer Study', with a mean age of 56 years ± 6, none of whom had a prior diagnosis of cardiovascular disease or diabetes, were followed for 17 years (IQR 2). Kidney function was estimated using glomerular filtration equations based on cystatin C and creatinine (eGFRcys and eGFRcr). The ratio eGFRcys/eGFRcr was used to assess glomerular filtration capacity and eGFR slopes were calculated. Two indices of atherosclerosis were utilized: (1) IMT of a. carotis communis (IMTCCA), (2) IMT of the far wall of the carotid bulb, both at baseline and follow-up (IMTBULB). In women, the eGFRcys/eGFRcr ratio was associated with the annual progression of IMTBULB. Additionally, the eGFRcys/eGFRcys ratio was associated with IMTBULB values greater than 1.5 mm at follow-up. In men, only eGFRcys slope was predictive of being in the sex-specific 75th percentile of IMTCCA at follow-up; no such association was found in women. Overall, SGHS was associated with the progression of IMTBULB, plaque presence, and greater IMT thickness at follow-up in women. In men, only a faster decline in eGFRcys was associated with plaque presence (IMTBULB above 1.5 mm), independent of traditional cardiovascular risk factors.
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(βln) 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(βln) 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.
Kidney dysfunction is a significant complication of allogeneic hematopoietic cell transplantation (alloHCT). Standard serum creatinine (sCr) testing is imperfect due to latency from the event causing damage to sCr increase. The purpose of this study was to evaluate the role of kidney damage biomarkers in the field of alloHCT. Seventy adult alloHCT candidates from 2 centers were recruited. 34 patients constituted pilot cohort and 36 - validation cohort. In pilot cohort serum and urine samples obtained at baseline and 7 timepoints were tested using ELISA assays for LFABP-1, KIM-1, NAG, uromodulin, TIMP-2 and IGFBP-7. Urine concentrations were corrected to urine creatinine concentration (uCr). Results were analyzed as predictors of acute kidney injury (AKI) within 100 days from alloHCT using receiver operating curve (ROC). LFABP-1, KIM-1, uromodulin, NAG and TIMP-2 performed significant predictive value for AKI. The best results were obtained for LFABP-1 and NAG and these biomarkers were tested in validation cohort where the results were borderline significant. Given the heterogeneity of the studied population, calculations for the whole group were performed: ROC for day +7/baseline ratio of urinary LFABP-1 and NAG in predicting AKI within 100 days from alloHCT was 0.673 and 0.678 respectively (p < 0.05). ROC for baseline urinary LFABP-1 in predicting early AKI was 0.721 (p < 0.05). Findings from our study confirm that patients undergoing alloHCT frequently experience subclinical kidney damage. However, due to the multifactorial nature of renal insults and preexisting kidney impairment, the predictive value of studied biomarkers in this population is limited.
Neuron-specific enolase (NSE) is an acknowledged biomarker for prognosticating neurological outcome after cardiac arrest, with elevated concentrations associated with poor outcome. This study assesses and compares the prognostic performance of NSE measured in serum and plasma for 1-year all-cause mortality among patients resuscitated from out-of-hospital cardiac arrest (OHCA). This investigation is based on post hoc analyses of the Blood Pressure and Oxygenation Targets After Out-of-Hospital Cardiac Arrest (BOX) trial, performed in patients remaining comatose after resuscitation. NSE was measured 48 h after admission using three distinct methods; 1) Serum-NSE measured in fresh serum samples, 2) frozen-plasma-NSE, measured in freeze-thaw EDTA-plasma from stored biobank samples, and 3) in a subset of the samples also as frozen-serum-NSE, measured in freeze-thaw serum from stored biobank samples. A total of 381 comatose OHCA patients were included, with an overall one-year mortality of 33.1%. Serum-NSE concentrations were significantly higher than frozen-plasma-NSE, with median concentrations of 21.2 µg/L (IQR: 15.7-45.5) versus 19.1 µg/L (IQR: 11.2-39.6), p < 0.001, respectively. Notably, the difference between serum-NSE and frozen-plasma-NSE increased with higher NSE concentrations. The mean difference was 65.8 µg/L with 95% limits of agreement of +/- 125.75 µg/L among patients with NSE > 60 µg/L. For predicting 1-year all-cause mortality, the AUROC for serum-NSE was 0.93 and 0.83 for frozen-plasma-NSE with a significant difference in AUROC of 0.10 (CI: 0.06; 0.14), p < 0.001. In a sub-group analysis (n = 67), there was no significant difference when comparing AUROC between serum-NSE and frozen-serum-NSE (difference of 0.03 [CI: -0.04; 0.09], p = 0.44). However, within this sub-group, frozen-serum-NSE performed better than frozen-plasma-NSE with an AUROC difference of 0.08 (CI: -0.15; -0.01), p = 0.02. Serum-NSE had greater accuracy in predicting 1-year mortality than frozen-plasma-NSE.
Measurement of plasma melatonin is important in studies of sleep disorders and neurodegenerative diseases and is also increasingly associated with cardiometabolic diseases and cancer. There is currently an increase in the usage of melatonin in the population. However, commercially available and reliable melatonin assays are lacking. Here we present a rapid and simple LC-MS/MS-based method for plasma melatonin in a clinical laboratory. The method demonstrates a limit of detection of 5 ng/L and inter-assay imprecision < 16%. This newly developed LC-MS/MS method was applied to 216 plasma samples collected from 24 men as part of The Bispebjerg study of diurnal variation. The results showed increased melatonin concentrations during the nighttime and fitted well to a diurnal rhythm curve (p < 0.0001). The LC-MS/MS assay correlated significantly with commercial RIA (p < 0.03) but demonstrated a substantial bias. We conclude that our simple LC-MS/MS method can detect biologically relevant changes in plasma melatonin and may enable insight into circadian biology in humans. We propose that the observed differences between melatonin assays could be clarified by the distribution of reference plasma melatonin material and that additional studies are needed to fully understand the minimum circulating levels of melatonin in the daytime.