Clinical biochemistry最新文献

Objectives and aim

This study aimed to identify precise biomarkers and develop targeted therapeutic strategies for preventing premature atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia (FH) by investigating the quantitative and qualitative abnormalities in the metabolic network of lipids in these patients using an advanced lipidomics platform.

Design & Methods

The study population comprised 18 homozygous (HoFH), 18 heterozygous (HeFH) FH patients, and 20 healthy controls. Cholesterol oxidation products (oxysterol, COPs) and main lipid classes were determined using gas chromatography–mass spectrometry. Results were expressed as percentages of total fat matter for lipid classes and percentages of total COPs for oxysterols. The principal component analysis (PCA) was also carried out, to highlight the correlation between studied parameters and groups investigated.

Results

Patients (both HoFH and HeFH) showed lower content of free fatty acids (FFAs) and greater values of triacylglycerols (TAGs) in comparison to controls. HoFH showed lower monoacylglycerols (P<0.01) and higher free cholesterol (FC) (P<0.05) when compared to HeFH and controls. The total content of COPs ranged from 1.96 to 4.25 mg/dL, from 2.27 to 4.05 mg/dL, and from 0.79 to 4.12 mg/dL in healthy controls, HoFH and HeFH groups, respectively, with no significant differences between patients and controls. In general, the 7α-hydroxycholesterol (7α-HC) was greater than other COPs. However, no significant differences were found between the three studied groups. Moreover, an opposite trend was observed between 7α-HC and 7-ketocholesterol (7-KC). Additionally, when PCA was carried out, the first two PCs explained 92.13 % of the total variance, of which the PC1 describes 53.94 % of variance mainly correlated to TAGs, diacylglycerols (DAGs), and 7-KC. On the other hand, the PC2 was correlated primarily for FFAs, FC and esterified sterols (E-STE).

Conclusions

In conclusion, abnormal levels of TAGs, DAGs and 7-KC were associated with HeFH while HoFH was associated with the abnormal amount of E-STE.

Introduction

Identifying controllable risk factors for large-artery atherosclerosis (LAA) stroke is crucial due to its significant role as a leading cause of ischemic stroke. We aimed to validate the correlation of serum vitamin B₁₂ with LAA stroke.

Methods

Inpatients with LAA stroke and healthy controls were retrospectively collected for a case-control study from January 2020 to May 2022. Serum vitamin B₁₂ concentration and other blood indicators, demographic, lifestyle factors and comorbidities were investigated. Logistic regression analysis was used to identify the correlation of serum vitamin B₁₂ concentrations with LAA stroke, meanwhile adjusted for confounding factors.

Results

Patients with LAA stroke had significantly lower serum vitamin B₁₂ concentrations in comparison to those of controls. In the fully adjusted model, vitamin B₁₂ (per 1 interquartile range increase, odds ratio [OR] = 0.84, 95 % confidence interval [CI]: 0.77–0.91), vitamin B₁₂ < 200 pg/mL (OR=7.70, 95 %CI: 2.19–27.03) and vitamin B₁₂ < 300 pg/mL (OR=4.19, 95 %CI: 1.82–9.66) were independently factors for LAA stroke. Furthermore, the optimal cut-off values for vitamin B₁₂ to predict LAA stroke were 305.25 pg/mL (area under the curve [AUC] = 0.71) when unadjusted and 308.25 pg/mL when adjusted for age and sex (AUC=0.68). Lower vitamin B₁₂ concentrations were significantly associated with male sex, smoking, older age, higher neutrophil count, higher creatinine, lower folate and higher total homocysteine.

Conclusion

Results indicate that low concentration of serum vitamin B₁₂ may be a strong predictor for the risk of LAA stroke.

Exocrine pancreatic insufficiency (EPI) is a condition caused by a deficiency of exocrine pancreatic enzymes, resulting in malabsorption of nutrients. Clinical manifestations of EPI may include steatorrhea, weight loss, diarrhea, and abdominal pain. Although direct testing is the most sensitive and specific for EPI, these tests are invasive, time consuming, expensive, and not well standardized. Fecal elastase (FE-1) has been shown to be an indirect marker of the exocrine secretory capacity of the pancreas and has become the most commonly employed indirect test for diagnosis of EPI. Measurement of fecal elastase consists of two main phases, a preanalytical phase and analytical phase. The preanalytical phase involves stool collection, storage and handling. The second phase is the analytical phase, which includes the actual assay processes and products used to produce a result. For FE-1 this includes sample extraction and measurement on an immunoassay. Each step in the process can influence the result and contribute to heterogeneity in FE-1 measurement, potentially impacting clinical diagnosis and management. Thus, this paper provides an overview of the preanalytical and analytical factors that can affect measurement and interpretation of FE-1 results.

Aim

In various experimental animal studies, it has been proven that solanine, a subtype of glycoalkaloids, is responsible for neural tube defects. However, there have not been any human studies yet in this area. Our aim is to investigate whether there are any connections between blood glycoalkaloid levels and anencephaly in humans.

Methods

Blood and amniotic fluid samples were taken from patients diagnosed with fetal anencephaly during pregnancy. The samples from patients with normal pregnancies were taken as well and was compared to the patients with fetal anencephaly during pregnancy. We searched the levels of three glycoalkaloids: solanine, chaconine and solamargine in the collected samples.

Results

Solanine, which is one of the glycoalkaloids, could not be detected in both serum and amniotic fluid in the anencephaly as well as the control groups. However, alpha-solamargine levels were observed to be significantly higher in the blood and amniotic fluid samples of the control group than in the study group (p = 0.04). Alpha-chaconine levels were also significantly higher in the control group (p < 0.001) as well.

Conclusion

Based on our tests, we can conclude that no connections were found between blood solanine levels and anencephaly during pregnancy. Alpha-chaconine and alpha-solamargine levels were observed to be higher in blood and amniotic fluid in pregnancies without anencephaly. The relationship between glycoalkaloids and congenital anomalies needs to be further investigated in tissues other than blood.

Introduction

Serum is the International Federation of Clinical Chemistry (IFCC)-recommended matrix for the measurement of lactate dehydrogenase (LD); however, many laboratories opt for lithium heparin plasma to achieve quicker turnaround times and minimize tube usage.

When introducing the new Sigma-Strong IFCC-recommended LDH2 assay from Abbott Laboratories on lithium-heparin collected samples, we observed a rise in the patient median LD activity as well as several samples exhibiting falsely elevated values.

Materials and methods

120 + serum and plasma samples from consenting patients were collected and evaluated for complete blood count and lactate dehydrogenase using two different assays. Aggregated patient results before and after introduction of the LDH2 assay were compared.

Results

Mean LD was 14% higher in plasma than in serum when using the LDH2 assay but only 5% higher when using the previous LDH legacy assay from Abbott Laboratories. Similarly, platelets and leukocytes were 10–30 times higher in plasma than in serum. Aggregated lactate dehydrogenase patient results demonstrated a dramatic increase in patient median following introduction of the LDH2 assay. Various experiments were tried to reduce cellular interference, but the only viable solution we found, apart from reverting to the LDH legacy assay, was to utilize serum tubes.

Conclusion

We conclude that lithium-heparin plasma leads to falsely elevated lactate dehydrogenase activity when using the LDH2 assay. These errors can be prevented by using serum collected in gel separator tubes.

Introduction

Current diagnostic approaches for bladder cancer (BLCA) are often invasive or lack the required sensitivity and specificity. This underscores the need for an early non-invasive diagnostic test for BLCA. This work aimed to explore the potential of molecular markers in urine-exfoliated cells for the diagnosis of non-muscle-invasive bladder cancer (NMIBC).

Materials and methods

Urine specimens (n = 140) were collected from NMIBC patients (n = 68) and control subjects (31 healthy volunteers and 41 non-cancer patients with common urological diseases [CUD]. Total RNA was extracted from the cells isolated from urine specimens. mRNA expression of selected genes: CDC20, KRT15, FOXM1, CXCR2, UPK1B, MDK, KRT20, and KRT17 was determined using RT-qPCR. The receiver operating characteristic (ROC) curve was then plotted to obtain the area under the curve (AUC), specificity, and sensitivity of the urinary mRNA markers.

Results

The expression of CDC20, MDK, UPK1B, FOXM1, KRT17, and KRT20 was up-regulated in samples obtained from low- and high-grade pathological grades of NMIBC compared to that measured in healthy subjects. Notably, MDK and KRT17 mRNA levels in the low- and high-grade cases were substantially higher than in normal and CUD groups. The AUC of the KRT17 and MDK combination in diagnosing NMIBC was 0.92, surpassing that of single genes. The sensitivity and specificity of the KRT17 and MDK combination were 74% and 94%, respectively. In diagnosing low-grade from healthy and CUD groups, analysis of the KRT17 and MDK combination yielded AUCs of 0.94 and 0.95, respectively, with sensitivities of 85% and 97%, and specificities of 93% and 85%.

Conclusion

The findings of this study revealed that KRT17 and MDK together are potential urine-based biomarkers for early diagnosis of NMIBC.

Objectives

Serum lactate and creatinine levels upon admission in cardiac arrest (CA) patients significantly correlate with acute kidney injury (AKI) post-restoration of autonomic circulation. However, the association between serum lactate/creatinine ratio (LCR) and AKI in this population remains unclear. This study aimed to explore the relationship between LCR at admission and cardiac arrest-associated acute kidney injury (CA-AKI).

Design and methods

We conducted a secondary analysis of previously published data on CA patient resuscitation, categorizing them into tertiles based on LCR levels. Univariate and multivariate logistic regression models and subgroup analyses were employed to investigate the association between LCR and CA-AKI. Non-linear correlations were explored using restricted cubic splines, and a two-piece wise logistic proportional hazards model for both sides of the inflection point was constructed.

Results

A total of 374 patients (72.19 % male) were included, with intensive care unit mortality, in-hospital mortality, and neurologic dysfunction rates of 51.87 %, 56.95 %, and 39.57 %, respectively. The overall CA-AKI incidence was 59.09 %. Multivariate logistic proportional hazards analysis revealed a negative association between LCR and CA-AKI incidence (adjusted odds ratio [OR] 0.85, 95 % confidence intervals [CI] = 0.78–0.93, P=0.001). Triple spline restriction analysis depicted an L-shaped correlation between baseline LCR and CA-AKI incidence. Particularly, a baseline LCR<0.051 was negatively associated with CA-AKI incidence (OR 0.494, 95 % CI=0.319–0.764, P=0.002). Beyond the LCR turning point, estimated dose–response curves remained consistent with a horizontal line.

Conclusions

Baseline LCR in CA patients exhibits an L-shaped correlation with AKI incidence following restoration of autonomic circulation. The threshold for CA-AKI is 0.051. This finding suggests that LCR may aid in identifying CA patients at high risk of AKI.

Elevated troponin levels are often indicative of various cardiac diseases; however, analytical interference can lead to false positive troponin concentrations. We present the case of a 48-year-old female patient with persistently falsely elevated high sensitivity troponin I (hsTnI) probably caused by the presence of macrotroponin. Laboratory testing included determination of hsTnI using various analytical methods, serial dilutions and determination of heterophilic antibodies and other autoimmune antibodies. Only precipitation with polyethylene glycol (PEG) indicated the presence of an interference by causing a significant decrease in hsTnI concentration.

Our results suggest that the falsely elevated hsTnI concentration could be due to interference with the macrotroponin complex.

Background

Fractional excretion of magnesium (FE_Mg) is commonly used to diagnose of renal magnesium (Mg) wasting, but it can be affected by serum Mg (SMg) and serum creatinine concentration (SCr). We investigated the sensitivity and specificity of FE_Mg to diagnose Mg wasting in subgroups with different SMg and eGFR (estimated glomerular filtration rate) in pediatric nephrology practice.

Methods

One hundred and nineteen patients (59 males and 60 females, median 15 years) seen in our pediatric clinic were investigated for FE_Mg, SMg, eGFR, and urine Mg-to-creatinine ratio (Mg/Cr). Normal eGFR was defined as ≥ 90 ml/min/1.73 m² or for infants SCr < chronic kidney disease stage 2. Urine Mg/Cr was compared with age-specific reference values.

Results

Sixteen of all patients (13 %) had hypomagnesemia. All had FE_Mg greater than the cut-off value of 2 %. Only 4 patients had elevated urine Mg/Cr. Of 65 patients with normal SMg and eGFR, 19 had FE_Mg above the cut-off value of 4 %. Of these, 13 patients had elevated urine Mg/Cr i.e. Mg wasting (sensitivity and specificity of FE_Mg, 93 % and 88 %, respectively). Among 38 patients with normal SMg and low eGFR, 30 had FE_Mg > 4 %, but only 6 had elevated urine Mg/Cr (sensitivity 100 % and specificity 25 %). Overall, hypomagnesemic patients and normomagnesemic patients with elevated urine Mg/Cr were diagnosed with Mg wasting (36/119, 30 %).

Conclusions

FE_Mg has variable sensitivity and specificity depending on SMg and eGFR in the diagnosis of Mg wasting. Mg wasting is not uncommon in pediatric nephrology practice.