Clinical Chemistry Research Articles

Analytical interference on measurement of immunoglobulins in monoclonal gammopathy.

Monoclonal gammopathy has been reported to interfere with several laboratory measurement results. We investigated potential interference in monoclonal gammopathy on immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations using three different routine chemistry instruments: Alinity (Abbott Laboratories), Cobas 8000 (Roche Diagnostics) and Optilite (Binding Site) at the Department of Clinical Biochemistry, Aalborg University Hospital, Denmark. Blood samples collected from 216 patients with known monoclonal gammopathy were analyzed on Alinity, Cobas and Optilite. Diagnoses were ascertained from clinical records. Scatter plots with Passing-Bablok regression were used to investigate associations between concentrations of IgA, IgG and IgM measured with each of the different instruments. Furthermore, comparison of IgG analyses on Alinity, Optilite and Cobas according to monoclonal IgM concentration was explored with Bland-Altman plots. A total of 81 patients were identified with IgM type monoclonal gammopathy and 8 of these patients (10%) had analytical interference as reflected by more than 25% decrease in the level of IgG measured on Alinity as compared to Optilite and Cobas. All blood samples with interference on IgG measurement using Alinity were from patients with lymphoplasmacytic lymphoma/Waldenströms macroglobulinemia and all of them had monoclonal IgM concentrations above 10 g/L. This study identified a source of interference from IgM monoclonal gammopathy on IgG measurement performed using Alinity. The interferences caused falsely low results of IgG which is important to recognize to ensure proper patient management.

Determining how the gestational changes, including low hemoglobin influence the hba1c and estimated average glucose relationship

ABSTRACT Background: Gestational Diabetes Mellitus (GDM) affects up to 14% of pregnancies globally, with accurate glycemic control critical for preventing adverse outcomes. While HbA1c is a standard marker for long-term glucose control, its reliability in pregnant women with anemia is debated. This study explores the association between anemia and glycemic indicators (Glycosylated hemoglobin HbA1c, Random plasma glucose (rPG), and Estimated average glucose (eAG) in pregnant women with GDM. Additionally, it examined the correlation between average glucose levels or eAG, measured by random plasma glucose rPG, and HbA1C. Methods: A prospective case-control study was carried out over eight months at the Departments of Chemical Pathology and Obstetrics and Gynecology, Dow University of Health Sciences (DUHS). Pregnant women in their second trimester after being diagnosed for GDM through oral glucose tolerance test were classified into anemic (hemoglobin < 10.5 g/dL) and non-anemic groups. Blood samples were collected and analyzed for HbA1c, hemoglobin, and random plasma glucose levels. Data were processed using SPSS (version-26) different variables compared by using independent t-test and correlation analyses at a significance level of p < 0.05. Results: Mean values for eAG, HbA1C, and rPG were 174.22 ± 24.489 mg/dl, 8.342 ± 1.6152%, and 166.21 ± 21.478 mg/dl, respectively. Anemia was associated with significantly higher HbA1C (p < 0.001), eAG (p < 0.001), and rPG (p = 0.004). A strong positive correlation was observed between eAG and rPG (r = 0.958, p < 0.01), while eAG showed a moderate correlation with HbA1C (r = 0.501, p < 0.01). In contrast, the correlation between HbA1C and rPG was weaker (r = 0.331, p < 0.01). Conclusion: eAG proved to be a good indicator for assessing glycemic control in pregnant non-anemic women with GDM. Anemia significantly affected glycemic metrics, leading to higher HbA1C and glucose levels.

The Need for Standardization of Continuous Glucose Monitoring Performance Evaluation: An Opinion by the International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Continuous Glucose Monitoring.

Metrics derived from continuous glucose monitoring (CGM) systems are often discordant between systems. A major cause is that CGM systems are not standardized; they use various algorithms and calibration methods, leading to discordant CGM readings across systems. This discordance can be addressed by standardizing CGM performance assessments: If manufacturers aim their CGM systems at the same target, then CGM readings will align across systems. This standardization should include the comparator device, sample origin, and study procedures. With better aligned CGM readings, CGM-derived metrics will subsequently also align better between systems.

Four-Week GLP Immunotoxicity Assessment of Lactoferrin Alpha Produced by Komagataella phaffii in Sprague-Dawley Rats.

Oral toxicity and toxicokinetic properties of human lactoferrin (LF) alpha produced in Komagataella phaffii (effera™) were investigated in adult Sprague-Dawley rats over a 28-day period under good laboratory practice conditions. Main study dosing used groups of 10 rats/sex/dose, and a secondary study evaluating toxicokinetic parameters used 6 rats/sex/dose. The vehicle control group received sodium citrate buffer, test groups received daily doses of 200, 600, and 2000mg of effera™ per kg body weight, and the comparative control group received 2000mg bovine LF (bLF)/kg body weight per day. T-cell-dependent antibody response against keyhole limpet hemocyanin and immunophenotyping of the spleen were performed as measures of immunotoxicity. Clinical observations, body weight, hematology, coagulation, clinical chemistry, urinalysis, immunotoxicity, gross necropsy, and histopathology were assessed. Toxicokinetic parameters were analyzed as an indication of LF bioavailability, and anti-LF antibody assays were conducted to detect antibodies produced against LF to measure immunogenicity. No treatment related toxicologically significant changes were observed. Based on the absence of toxicologically relevant changes, effera™ is well tolerated in rats at doses up to 2000mg rhLF/kg/day, an amount ∼400 times that of the estimated daily intake at the 90th percentile proposed for human adult use.

Harmonized Tubular Maximum Phosphate Reabsorption per Glomerular Filtration Rate (TmP/GFR) reporting in adults and children in Australia and New Zealand

Abstract Tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) is a key diagnostic test for renal phosphate wasting. However, there is a lack of international consensus regarding the reporting of age-related reference intervals. The TmP/GFR Harmonization Working Group, formed by The Australasian Association for Clinical Biochemistry and Laboratory Medicine and The Australian and New Zealand Bone and Mineral Society, aimed to evaluate analytical differences amongst commercial creatinine and phosphate assays, harmonize age-specific cut-offs and compare the ANZBMS TmP/GFR online calculator with existing products. A total of 11 360 results from The Royal College of Pathologists of Australasia Quality Assurance Programs were analyzed to assess creatinine and phosphate assay performance amongst five In Vitro Diagnostic (IVD) companies. Ortho-Clinical Diagnostics analyzers had a positive bias of up to 32% for serum phosphate and up to 29% for TmP/GFR. The other IVD companies produced comparable results and are suitable for harmonized reference intervals. To date, the AACB-ANZBMS TmP/GFR online calculator is the only validated Isotope Dilution Mass Spectrometry-creatinine aligned tool which caters for both pediatric and adult individuals, providing automatic interpretive comments to aid clinicians managing patients with hypophosphatemia.

Appraisal of six sigma in pre-analytical phase of clinical biochemistry laboratory

Objectives: The aim of the study is to measure the performance of pre-analytical phase of a clinical biochemistry laboratory using sigma metrics and the six sigma scale. Materials and Methods: The study included documented data of blood sample rejection from March 2023 to February 2024 and follow-up data from March 2024 to August 2024. International Federation of Clinical Chemistry and Laboratory Medicine developed Quality Indicators (QIs) used are QI-9 Wrong tubes; QI-10 Hemolyzed samples; QI-11 Clotted samples; QI-12 Insufficient samples; QI-14 Damaged samples in transport; and QI-15 Mislabeled samples. Based on “Six Sigma Quality Design and Control” established by Dr. Westgard, the sigma metric was calculated for the above-mentioned QIs. Statistical analysis: Obtained data were entered and analyzed using Microsoft Excel 2021. Results: Out of 162,380 received samples, 547 samples were rejected as not satisfied with the sample acceptance criteria. The most common pre-analytical error in the observed QIs is hemolyzed samples (458), followed by insufficient sample volume (55). The Sigma score of QI-10 was determined to be 4.81, whereas QI-9, QI-11, QI-12, and QI-15 were well maintained and graded excellent. Following training sessions, the follow-up month revealed a sigma score of 4.98 for QI-10. Conclusions: Six sigma metrics are a competent means to measure the performance of pre-analytical QIs in a clinical biochemistry laboratory. The observed QIs were effectively managed (>4 σ).

Association of phenotypic age and accelerated aging with severity and disability in patients with acute ischemic stroke

ObjectiveBiological age may be more accurate than chronological age in determining chronic health outcomes. However, few studies have shown the association between biological age and acute ischemic stroke (AIS). In this study we showed the association between phenotypic age (PhenoAge) or accelerated aging and severity and disability in patients with AIS. DesignRetrospective study. Setting and subjects936 patients with AIS during January 2019 to July 2021 and 512 patients during June 2022 to July 2023 for a validation. MethodsStroke severity was evaluated based on the National Institute of Health stroke scale (NIHSS) questionnaire scale. Disability was evaluated by modified Rankin Scale. PhenoAge was calculated based on chronological age and 9 clinical chemistry biomarkers. Logistic regression analyses were applied to estimate the relationship between PhenoAge and the severity and disability. ResultsPhenoAge (odds ratio [OR] = 1.03, 95% confidence interval [CI]: 1.0–1.04, for NIHSS ≥ 5; OR = 1.05, 95%CI: 1.03−1.07, for NIHSS ≥ 10) was independently associated with stroke severity. The probability of NIHSS ≥ 5 or NIHSS ≥ 10 was significantly increased in individuals with accelerated ageing versus individuals with no accelerated aging (age gap: OR = 1.79, 95%CI: 1.18−2.72; OR = 3.53, 95%CI: 1.60−7.77; phenotypically older vs. phenotypically younger: OR = 2.01, 95%CI: 1.21−3.35; OR = 3.69, 95%CI: 1.36−10.0). Similar trends was observed when accelerated aging was defined by residual discrepancies between PhenoAge and chronological age (OR = 1.02, 95%CI: 1.01−1.04, for NIHSS ≥ 5; OR = 1.05, 95%CI: 1.02−1.08, for NIHSS ≥ 10). The area under the curve of PhenoAge was higher than that of chronological age in identifying patients with NIHSS ≥ 5 (0.66, 95%CI:0.62−0.70 vs. 0.61, 95%CI: 0.58−0.65, p < 0.01) and NIHSS ≥ 10 (0.69, 95%CI:0.60−0.77 vs. 0.63, 95%CI: 0.55−0.72, p = 0.05). The probability of severe disability was significantly increased in individuals with accelerated aging versus individuals with no accelerated aging (age gap: OR = 2.87, 95%CI: 1.09−7.53; phenotypically older vs. phenotypically younger: 4.88 (1.20−19.88). Similar results were observed in the validation population. ConclusionPhenoAge or accelerated aging is associated with stroke severity and disability even after adjusting for chronological age.

Oral Toxicity and Hypotensive Influence of Sericin-Derived Oligopeptides (SDOs) from Yellow Silk Cocoons of Bombyx mori in Rodent Studies.

Sericin-derived oligopeptides (SDOs) from yellow silk cocoons exhibit antihypertensive and hypoglycemic properties in both in vitro and in vivo studies. This study investigated the acute toxicity of SDOs as a novel food for human consumption using female ICR mice and Wistar rats, as well as the chronic toxicity test on both sexes of Wistar rats. Clinical chemistry, hematology, and histopathological studies revealed that SDOs were safe for a single dose of 2000 mg kg-1 body weight (BW) and daily oral administration of 50, 100, and 200 mg kg-1 BW for six months. The chronic toxicity study additionally measured the rats' systolic blood pressure (SBP) and blood sugar monthly as they slowly aged. In the 2nd month for male rats and the 4th month for both sexes, SDOs had a significant hypotensive effect on Wistar rats' blood pressure, lowering it from 130 mmHg to a plateau at 110-115 mmHg. In contrast, the blood pressure of the control rats exceeded 140 mmHg after five months. Nonetheless, the hypoglycemic effect was not observed. Measurements of SBP and blood glucose in aged rats during chronic toxicity tests yielded insights beyond ordinary toxicity, including the health and fitness of the lab rats, perhaps resulting in novel discoveries or areas of study that justify the sacrifice of the animals' lives.

Screening kolorektálního karcinomu v České republice – minulost, současnost a budoucnost

The National Colorectal Cancer Screening Program has been conducted in the Czech Republic since 2000 and serves as an example of interdisciplinary collaboration. Specialists from gastroenterology, general practice, gynecology, and clinical biochemistry are involved in the program. It is based on two primary methods: the screening fecal immunochemical test for occult bleeding (iFOBT, FIT) and preventive colonoscopy (FOBT-positive colonoscopy and screening colonoscopy). The program‘s effectiveness is evidenced by the high number of detected colorectal precancerous and malignant lesions. Between 2006 and 2023, a total of 531,362 preventive colonoscopies were performed, diagnosing 202,575 patients with adenomas (38.1%) and 14,473 patients with cancers (2.7%). Program quality is monitored by indicators focused on both organization (target population coverage) and screening methods. Coverage with screening tests in a 2-year interval has consistently ranged around 30%, except between 2020 and 2021 during the COVID-19 pandemic (27%), reaching 30.0% in 2023. Non-screening tests also affect epidemiological indicators, with total coverage by all relevant methods in a 2-year interval in 2023 amounting to 37.5%. Colonoscopies are evaluated using six parameters (number of examinations, bowel preparation quality, total colonoscopies, and adenoma detection rate in total, in both women and men). In 2023, 72% of screening colonoscopy centers met all of these indicators. FOBT analyzers now must have the regular external quality assessment (EQA), which should help stabilize test positivity, standing at 9.1% in 2023. Thanks to the National Colorectal Cancer Screening Program, favorable epidemiological trends have been observed, with a 32.3% decrease in incidence and a 47.8% decrease in mortality between 2000 and 2022. The future of the program lies in its further optimization, with a goal of both increasing coverage of the target population by examination and quality improvement, ensuring the program’s feasibility and efficiency. Key words: colorectal cancer – adenoma – screening – colonoscopy – fecal immunochemical test – quality indicators

Brief Overview on Pathology of Blood and Urine

Clinical pathology is recognized as an essential component of the preclinical safety evaluation of test articles (new chemical entities, exploratory novel medicines, and xenobiotics), particularly in short- and medium-term toxicity studies. Traditionally, this evaluation includes clinical chemistry, coagulation, hematology, and urinalysis assessments. The findings of these assessments include details on the general state of health of the animals as well as target organs and general metabolic, adaptive, or harmful processes linked to test material exposure. Consequently, in the preclinical safety assessment of a test article, clinical pathology evaluations aid in the establishment of toxicological dose-response correlations. These findings hold significance and relevance for dose selection in long-term research, as well as for risk assessment and management when applied to humans. Guidance on the fundamentals of clinical pathology testing and interpretation in the species utilized in toxicological investigations is the aim of this chapter. In order to increase testing capacity and enhance its ability to identify more sensitive, early signals of drug-induced target organ toxicity or pathophysiology, the application of clinical pathology testing in preclinical safety assessment as well as the areas of development for novel biomarker implementation within the laboratory are discussed. Lastly, the significance of interpreting clinical pathology and combining the results with data from other studies is emphasized when assessing overall safety or risk assessment

Serum Vitamin D Testing – A Necessity Or An Injudicious Expenditure

Objective: To evaluate the serum vitamin D levels and to determine the justification for vitamin D testing in patients. Study Design: Cross-Sectional study. Place and Duration of Study: Department of Chemical Pathology, Armed Forces Institute of Pathology Rawalpindi, Pakistan from Oct to Dec 2022. Methodology: Patients of either gender coming for vitamin D level estimation were included. Vitamin D levels were analyzed on Immunoassay auto-analyzer. Data was analyzed using SPSS version 26. Results: Out of 249 patients, 87(34.9%) were male while 162(65.1%) were female, with mean age 41.09±19.10 years and mean Vitamin D levels 73.08±45.86nmol/l. None of the patients (0%) had vitamin D deficiency, 174(69.9%) had vitamin D insufficiency, 72(28.9%) had vitamin D sufficiency, while 3(1.2%) had vitamin D excess. Major reasons for Vitamin D testing was bone pains, which were present in 72(28.9%) patients. A significant difference in vitamin D levels according to reason of testing (p&lt;0.05) was observed. Total expense on vitamin D testing for 249 patients was PKR 722100/- (249x2900), as compared to cost of supplementation PKR 199200/- (249x800) in clinical suspected cases. Conclusion: Majority of patients that tested for vitamin D were in lower risk group, and were not vitamin D deficient, with bone pains being the complaint due to which most patients were tested.

Rapid and accurate bacteria identification through deep-learning-based two-dimensional Raman spectroscopy

Surface-enhanced Raman spectroscopy (SERS) offers a distinctive vibrational fingerprint of the molecules and has led to widespread applications in medical diagnosis, biochemistry, and virology. With the rapid development of artificial intelligence (AI) technology, AI-enabled Raman spectroscopic techniques, as a promising avenue for biosensing applications, have significantly boosted bacteria identification. By converting spectra into images, the dataset is enriched with more detailed information, allowing AI to identify bacterial isolates with enhanced precision. However, previous studies usually suffer from a trade-off between high-resolution spectrograms for high-accuracy identification and short training time for data processing. Here, we present an efficient bacteria identification strategy that combines deep learning models with a spectrogram encoding algorithm based on wavelet packet transform and Gramian angular field techniques. In contrast to the direct analysis of raw Raman spectra, our approach utilizes wavelet packet transform techniques to compress the spectra by a factor of 1/15, while concurrently maintaining state-of-the-art accuracy by amplifying the subtle differences via Gramian angular field techniques. The results demonstrate that our approach can achieve a 99.64 % and a 90.55 % identification accuracy for two types of bacterial isolates and thirty types of bacterial isolates, respectively, while a 90 % reduction in training time compared to the conventional methods. To verify the model's stability, Gaussian noises were superimposed on the testing dataset, showing a specific generalization ability and superior performance. This algorithm has the potential for integration into on-site testing protocols and is readily updatable with new bacterial isolates. This study provides profound insights and contributes to the current understanding of spectroscopy, paving the way for accurate and rapid bacteria identification in diverse applications of environment monitoring, food safety, microbiology, and public health.

Perturbation Patterns of Bone Metabolism Secondary to COVID-19 Among Nigerian Healthcare Workers

&amp;lt;i&amp;gt;Background&amp;lt;/i&amp;gt;: Severe acute respiratory coronavirus-2 (SARS-CoV-2), the etiologic agent of coronavirus disease of 2019 (COVID-19) is known to affect several organ systems. However, the disease’s influence on bone metabolism is poorly characterized especially among native Nigerians. Consequently, the current study explored the effect of the disease on bone metabolism among Nigerian healthcare workers (HCWs). &amp;lt;i&amp;gt;Methods:&amp;lt;/i&amp;gt; This was a prospective longitudinal study conducted in the Department of Chemical Pathology of the Rivers State University Teaching Hospital among unvaccinated HCWs in Rivers State, Southern Nigeria. Eligible HCWs (n=96) were followed up from when they unwittingly had contact with SARS-CoV-2 infected/COVID-19 patients until they developed symptomatic RT-PCR-confirmed COVID-19. Demographic, anthropometric, clinical, and laboratory data were obtained before and at diagnosis/confirmation of COVID-19 among the eligible HCWs. Statistical analysis was done using descriptive/inferential statistics at a p-value of &amp;lt;0.05. &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt;: At COVID-19 diagnosis, the HCWs had increased levels of inflammatory markers (procalcitonin, C-reactive protein, and D-dimer), raised bone resorption marker (s-CTX), but reduced bone formation marker (s-PINP) compared to the pre-COVID-19 parameters (p&amp;lt;0.001). These cardinal biochemical findings were more prominent among those with severe disease variant than those with non-severe disease variant (p&amp;lt;0.001). In addition, a negative correlation pattern was observed between these inflammatory markers and the bone formation marker, however, a positive correlation was observed between the inflammatory markers and the bone resorption marker (p&amp;lt;0.001). &amp;lt;i&amp;gt;Conclusion: &amp;lt;/i&amp;gt;The current finding indicates perturbation of bone metabolism, associated with increased bone resorption pattern, secondary to COVID-19 among the studied population. Hence, it is highly recommended that the evaluation of bone metabolism status be incorporated into the management protocols for COVID-19.

56th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC- Laboratory Medicine).

56th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC- Laboratory Medicine).

Biomarker identification and risk assessment of cardiovascular disease based on untargeted metabolomics and machine learning

Cardiovascular disease (CVD) is the leading cause of mortality, disability, and healthcare costs, with a significant impact on the elderly and contributing to premature deaths across various age groups, including those below age 70. Despite decades of transformative discoveries and clinical efforts, the challenges of diagnosis, prevention, and treatment of CVD persist on a massive scale. This study aimed to unravel potential CVD-associated biomarkers and establish a machine learning model for the risk assessment of CVD. Untargeted metabolic assay with ultra-high performance liquid chromatography-tandem mass spectrometry and routine clinical biochemistry test were undertaken on the fasting venous blood specimens from 57 subjects. Four relevant clinical traits and 164 CVD-associated metabolites were identified, especially those related to glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids. The machine learning model achieved from an integrated biomarker panel of palmitic amide, oleic acid, 138-pos (the 138th detected metabolomic feature in positive ion mode), phosphatidylcholine, linoleic acid, age, direct bilirubin, and inorganic phosphate, was able to improve the accuracy of CVD risk assessment up to a high satisfactory value of 0.91. The findings indicate that disorders in the metabolic processes of biological membranes and energy are significantly associated with increased risk of vascular damage in CVD patients. With machine learning methods, the pivotal metabolites and clinical biomarkers offer a promising potential for the efficient risk assessment and diagnosis of CVD.

Strategies to verify equimolar peptide release in mass spectrometry-based protein quantification exemplified for apolipoprotein(a).

Quantitative protein mass spectrometry (MS) is ideally suited for precision diagnostics and for reference standardization of protein analytes. At the Leiden Apolipoprotein Reference Laboratory we apply MS strategies to obtain detailed insight into the protein-to-peptide conversion in order to verify that quantifier peptides are not partly concealed in miscleaved protein backbone. Apolipoprotein(a) (apo(a)) was digested in a non-optimal manner to enhance the number of miscleaved peptides that were identified by high resolution liquid chromatography tandem-MS measurements. The protein-to-peptide conversion was carefully mapped with specific attention for miscleaved peptides that contain an apo(a) quantifier peptide. Four different isotopologues of each apo(a)-quantifier peptide were applied to evaluate linearity of internal peptide standards during measurement of specific real-life samples. Two apo(a) quantifier peptides that were concealed in two different miscleaved peptides were included into a multiple reaction monitoring list in our targeted MS-based apo(a) quantifications to alert for potential protein digestion discrepancies. The presence of miscleaved peptides could be ruled out when applying our candidate reference measurement procedure (RMP) for apo(a) quantification. These data further corroborate the validity of our apo(a) candidate RMP as higher order method for certification of commercial Lp(a) tests that is endorsed by theInternational Federation of Clinical Chemistry and Laboratory Medicine. MS-based molecular detection and quantification of heterogeneous apo(a) proteoforms will allow manufacturers' transitioning from confounded lipoprotein(a) [Lp(a)] mass levels into accurate molar apo(a) levels.

Lipoprotein(a) levels in acute myocardial infarction patients and their associations with prior events and coronary artery disease severity: a real-world cohort study

Abstract Introduction Circulating lipoprotein(a) [Lp(a)] has been associated with the risk of atherosclerotic coronary artery disease (CAD) and is an emergent therapeutic target. The objective of this study is to explore the association between serum levels of Lp(a) and previous myocardial infarction (MI) and/or coronary revascularization and the extension of obstructive CAD in patients with acute MI undergoing coronary angiography. Methods All consecutive patients with MI who underwent coronary angiography and Lp(a) measurement between May and November 2023 were included. Patient data were either registered prospectively or completed retrospectively using electronic health records. Lp(a) was measured using the Immunoturbidimetric Assay method with reaction intensification by particles, employing the World Health Organization/International Federation of Clinical Chemistry and Laboratory Medicine (WHO/IFCC) International Reference Reagent (SRM2B), on the "Roche Cobas C702" chemistry analyzer. The number of major coronary arteries (left main, left anterior descending, left circumflex and right coronary arteries) with stenosis &amp;gt;50% on the coronary angiography were registered. In the primary analysis we explored the association between Lp(a) levels using tertiles and previous occurrence of MI/revascularization, as well as the extension of obstructive CAD. In the secondary analysis we compared Lp(a) levels in patients with and without previous MI/revascularization and patients with 3-4 major vessels CAD vs. 0-2 vessels. Results A total of 116 patients were enrolled, with a mean age of 62±13 years, 79% males, 29% with known coronary artery disease, 71% with dyslipidemia, 24% with diabetes, 65% with hypertension, and 58% were either active or former smokers. The median Lp(a) level was 72 (20-183) nmol/L. In the primary analysis (table 1), the number of previous MI/revascularizations was significantly higher in the third tertile of Lp(a) (T3) versus T1 (p=0.044). No significant differences were found for the remaining analyses. In the secondary analysis (figure 1) the level of Lp(a) was significantly higher in patients with 3-4 vessel CAD vs. 0-2 vessel (158.4±145.2 nmol/L vs. 103.16±104.6 p=0.044). Conclusion In this small real-world cohort population with acute MI, the number of previous MI or coronary revascularization was higher in patients with increased levels of Lp(a) and this marker of atherosclerotic disease was greater in patients with more extensive CAD.

Relationship between lipoprotein(a) and endogenous fibrinolytic status in patients with STEMI

Abstract Background The risk of myocardial infarction is at least doubled in individuals with lipoprotein(a) (Lp[a]) levels &amp;gt;90th percentile.[1] Lp(a) may exert pro-thrombotic effects by impairing fibrinolysis. Lp(a) has a high degree of homology to plasminogen and can competitively inhibit tissue plasminogen activator (tPA)-mediated plasminogen activation and tPA-mediated clot lysis.[2] Furthermore, Lp(a) stimulates the activity of plasminogen activator inhibitor-1, the major inhibitor of the fibrinolytic system. In patients with ST-segment elevation myocardial infarction (STEMI), impaired endogenous fibrinolysis is a strong, independent risk factor for recurrent cardiovascular events,[3] but the drivers of this are not fully understood. Whether impaired endogenous fibrinolysis is related to increased Lp(a) levels in patients with STEMI, is not known. Purpose We aimed to assess the relationship between Lp(a) and endogenous fibrinolysis in patients with STEMI. Methods In a prospective, observational study, venous blood samples were drawn from patients presenting with STEMI immediately before revascularisation, after dual antiplatelet therapy but before heparin administration. Endogenous fibrinolysis was measured immediately in non-anticoagulated whole blood using the point-of-care Global Thrombosis Test, which measures the time for occlusive thrombus formation under high shear (occlusion time) and the time for spontaneous lysis of the thrombus (lysis time).[3] Assessment of Lp(a) levels, measured by particle enhanced immunoturbidimetric assay, was performed with paired plasma samples, standardized against the International Federation of Clinical Chemistry reference material SRM2B for nmol/L. Lp(a) &amp;gt;32 nmol/L is associated with increased risk of ischaemic heart disease. Results A total of 80 patients were included (age 64±14y, 25% females and 86% Caucasian). There was a positive correlation between Lp(a) level and lysis time (r = 0.330, P = 0.003) (Figure 1). Lysis time was significantly longer in patients with Lp(a) &amp;gt;32 nmol/L (2782 [1626-3683] vs. 1725 [1259-2955] s, P = 0.044). Using a cut-point of lysis time ≥2500 s previously associated with a significantly increased cardiovascular risk in patients with STEMI, we showed that Lp(a) was significantly higher in patients with lysis time ≥2500 s (40 (22-111) vs. 18 (7-73) nmol/L, P = 0.045). Table 1 shows the relationship between clinical characteristics and Lp(a) and lysis time. Lp(a) level was higher in non-Caucasian patients. There was no correlation between Lp(a) and occlusion time (r = 0.156, P = 0.168). Conclusion In patients with STEMI, longer endogenous fibrinolysis time is related to higher Lp(a) level. Raised Lp(a) levels may, in part, contribute to impaired endogenous fibrinolysis. Future studies are required to assess whether reduction in Lp(a) with novel therapies currently in phase 3 trials can favourably modulate fibrinolysis and improve clinical outcomes.Figure 1

Comparison of the clinical chemistry score to other biomarker algorithms for rapid rule-out of acute myocardial infarction and risk stratification

Abstract Background The clinical chemistry score (CCS) comprising high-sensitivity (hs) cardiac troponins (cTn), glucose and estimated glomerular filtration rate has been previously validated with superior accuracy for detection and risk stratification of acute myocardial infarction (AMI) compared to hs-cTn alone. Methods The CCS was directly compared to other biomarker-based algorithms for rapid rule-out and prognostication of AMI including the hs-cTnT limit-of-blank (LOB, &amp;lt;3 ng/L) or limit-of-detection (LOD, &amp;lt;5 ng/L) and the dual marker strategy (DMS) (copeptin &amp;lt;10 pmol/L and hs-cTnT ≤14 ng/L) in 1506 patients presenting to the emergency department (ED) with symptoms suggestive of acute coronary syndrome. Negative predictive values (NPV) and sensitivities for rule-out of AMI were assessed and outcomes included rates of the combined end-point of all-cause mortality, myocardial re-infarction and stroke within 12 months. Results NPVs of 100% (98.3-100%) could be found for a CCS=0, hs-cTnT LoB and hs-cTnT LoD with rule-out efficacies of 11.1%, 7.6% and 18.3% as well as specificities of 13.0% (9.9-16.6%), 8.8% (7.3-10.5%) and 21.4% (19.2-23.8%), respectively. A CCS≤ 1 achieved a rule-out in 32.2% of all patients with a NPV of 99.6% (98.4-99.9%) and specificity of 37.4% (34.2-40.5%) compared to a rule-out efficacy of 51.2%, NPV of 99.0 (98.0-99.5) and specificity of 59.7% (57.0-62.4%) for the DMS. Rates of the combined end-point of death/AMI within 30 days ranged between 0.0% and 0.5% for all fast-rule-out protocols. Conclusions The CCS enables a reliable rule-out of AMI with low outcome rates in short and long-term follow-up for a specific population of ED patients. However, compared to a single or dual biomarker strategy, the CCS rule-out is attenuated by a loss of specificity and lower efficacy. Thus, the clinical benefit of the CCS in clinical practice seems to be negligible.

Prospective and External Validation of Machine Learning Models for Short- and Long-Term Mortality in Acutely Admitted Patients Using Blood Tests.

Background: Predicting mortality in emergency departments (EDs) using machine learning models presents challenges, particularly in balancing simplicity with performance. This study aims to develop models that are both simple and effective for predicting short- and long-term mortality in ED patients. Our approach uses a minimal set of variables derived from one single blood sample obtained at admission. Methods: Data from three cohorts at two large Danish university hospitals were analyzed, including one retrospective and two prospective cohorts where prognostic models were applied to predict individual mortality risk, spanning the years 2013-2022. Routine biochemistry analyzed in blood samples collected at admission was the primary data source for the prediction models. The outcomes were mortality at 10, 30, 90, and 365 days after admission to the ED. The models were developed using Light Gradient Boosting Machines. The evaluation of mortality predictions involved metrics such as Area Under the Receiver Operating Characteristic Curve (AUC), sensitivity, specificity, negative predictive values, positive predictive values, and Matthews correlation coefficient (MCC). Results: A total of 43,648 unique patients with 65,484 admissions were analyzed. The models showed high accuracy, with very good to excellent AUC values between 0.87 and 0.93 across different time intervals. Conclusions: This study demonstrates that a single assessment of routine clinical biochemistry upon admission can serve as a powerful predictor for both short-term and long-term mortality in ED admissions.