Is Nuchal Translucency of 3.0-3.4 mm an Indication for cfDNA Testing or Microarray? - A Multicenter Retrospective Clinical Cohort Study.

INTRODUCTION: This study aimed to evaluate the occurrence of clinically relevant (sub)microscopic chromosomal aberrations in fetuses with the nuchal translucency (NT) range from 3.0 to 3.4 mm, which would be potentially missed by cfDNA testing. METHODS: A retrospective data analysis of 271 fetuses with NT between 3.0 and 3.4 mm and increased first trimester combined test (CT) risk in five cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed. RESULTS: A chromosomal aberration was identified in 18.8% fetuses (1:5; 51/271). In 15% (41/271) of cases, trisomy 21, 18, or 13 were found. In 0.7% (2/271) of cases, sex chromosome aneuploidy was found. In 1.1% (3/271) of cases, CNV >10 Mb was detected, which would potentially also be detected by genome-wide cfDNA testing. The residual risk for missing a submicroscopic chromosome aberration in the presented cohorts is 1.8% (1:54; 5/271). CONCLUSION: Our results indicate that a significant number of fetuses with increased CT risk and presenting NT of 3.0-3.4 mm carry a clinically relevant chromosomal abnormality other than common trisomy. Invasive testing should be offered, and counseling on NIPT should include the test limitations that may result in NIPT false-negative results in a substantial percentage of fetuses.

The relationship between atherosclerosis and dementia.

OBJECTIVE: The main objective is to confirm a hypothesis that atherosclerosis, through various mechanisms, considerably influences cognitive impairment and significantly increases the risk for developing dementia. Complete sample should be 920 individuals. The present study aimed to analyse epidemiological data from a questionnaire survey. METHODS: The work was carried out in the form of an epidemiological case control study. Subjects are enrolled in the study based on results of the following examinations carried out in neurology departments and outpatient centres during the project NU20-09-00119 from 2020 to 2023. Respondents were divided into four research groups according to the results of clinical examination for the presence of atherosclerosis and dementia. The survey was mainly concerned with risk factors for both atherosclerosis and dementia. It contained questions on lifestyle factors, cardiovascular risk factors, leisure activities, and hobbies. RESULTS: Analysis of the as yet incomplete sample of 877 subjects has yielded the following selected results: on average, 16% of subjects without dementia had primary education while the proportion was 45.2% in the group with both dementia and atherosclerosis. Subjects with dementia did mainly physical work. Low physical activity was more frequently noted in dementia groups (Group 2 - 54.4% and Group 3 - 47.2%) than in subjects without dementia (Group 1 - 19.6% and Group 4 - 25.8%). Coronary heart disease was more frequently reported by dementia patients (33.95%) than those without dementia (16.05%). CONCLUSION: Cognitively impaired individuals, in particular those with vascular cognitive impairment, have poorer quality of life and shorter survival. Risk factors contributing to such impairment are similar to those for ischaemic or haemorrhagic stroke. It may be concluded that most of the analysed risk factors play a role in the development of both atherosclerosis and dementia.

Contribution of methamphetamine and insulin to the death of a woman suffering from type I diabetes - which played the greater role?

This report presents a fatal case of a young female Type I diabetic patient who developed convulsions and loss of consciousness after taking methamphetamine and spending some time in a dance club. During the convulsions, she was given sugar and when no response occurred, her boyfriend who was not experienced in the use of insulin administered a dose of insulin to her. The woman lost consciousness and died despite the efforts of the emergency service. A biochemical analysis revealed a high level of insulin (196.67 mU/L) and low levels of glucose (2.96 mmol/L) and C-peptide (26 pmol/L). Toxicological analysis revealed a methamphetamine concentration of 389 ng/mL and an amphetamine concentration of 19 ng/mL. The forensic perspective of the difficult determination of the contribution of each of the factors to the death, i.e., the pre-existing medical condition (Type I diabetes), the use of methamphetamine, the physical exertion at the dance club, and, finally, the non-indicated administration of insulin, is discussed. The ruling of the court is also reported.

Correlation of toxoplasmosis with small­for­gestational­age newborns.

BACKGROUND: Toxoplasma gondii infection in pregnant women could lead to significant changes during the pregnancy, affect the outcomes of pregnancy and the timing of labour. Small­for­gestational­age (SGA) newborns are defined by birthweight below the 10th percentile for gestational age. We tested an association between latent toxoplasmosis in pregnant women and deliveries of SGA babies. MATERIAL AND METHODS: For testing, we included 1,647 women who gave birth to a singleton baby at ≥ 37 weeks of gestation. The complement-fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA) tests for IgG and IgM were used. The latent form of toxoplasmosis was defined as a CFT titre of 1:8 or higher, together with index positivity IgG ELISA > 1.1 and negative IgM. RESULTS: There were 406 (24.7 %) women positive, and 1,241 (75.3 %) women negative for latent toxoplasmosis. Of all deliveries. 190 were SGA­positive and 1,457 were SGA­negative. Our study found a statistically significant association between latent toxoplasmosis and SGA foetuses born at term. The Pearson chi-square model was statistically significant (χ2(1) = 7.365, p = .007). The odds ratio was 1.567. CONCLUSION: Pregnant women with latent toxoplasmosis giving birth at ≥ 37 weeks of gestation have a 1.567 times higher risk of delivering an SGA baby (Tab. 2, Fig. 1, Ref. 30).

Pseudonormokalemia case report - What does it mean to have normal blood potassium?

This case report describes a case of pseudonormokalemia, true hypokalemia. Often, only laboratory values outside the normal range gain attention and false normal results are at risk of not being noticed. However, a disease state may be masked by another pathological process. Here, a 50-year old male was admitted to the Department of Internal Medicine due to sepsis from a dental infection. Initially, serum potassium measurement revealed a normal value of 4 mmol/L (reference interval 3.8-5.1 mmol/L). Thrombocyte number was above 500x109/L. Due to our policy to recommend a repeated measurement of potassium in whole blood or heparin plasma if a patient has thrombocytosis, pseudonormokalemia was identified because the heparin plasma potassium value was only 2.9 mmol/L (reference interval 3.5-4.8 mmol/L). The physiological difference between serum and plasma concentration is no more than 0.3 mmol/L. In this case, potassium concentration were falsely elevated in the serum sample, probably caused by the high number of platelets releasing potassium during clotting. Interpretative comments in patients with thrombocytosis over 500x109/L recommending plasma potassium measurement are helpful. The best way to eliminate pseudohyperkalemia and pseudonormokalemia phenomena caused by thrombocytosis is to completely change towards heparin plasma as the standard material.

Fast and Easy Simultaneous Determination of Riboflavin, Folic Acid, All-Trans-Retinol and α-Tocopherol in Human Serum by LC/MS/MS for Bariatric Patients.

The aim of this study was to develop and validate methods for the determination of vitamins B2, B9, E and A in serum using liquid chromatography with mass spectrometry (MS) detection. Vitamin analysis was performed using an ultra performance liquid chromatography combined with tandem MS. The compounds were separated on a BEH C18 RP column (2.1 × 100 mm, 1.7 µm) using a gradient elution with an analysis time of 10 min. Sample preparation included protein precipitation with ethanol. The concentration range in human serum was as follows: riboflavin 5-1000 nmol/L, folic acid 2.5-250 nmol/L, α-tocopherol 0.5-100 µmol/L and all-trans-retinol 25-2500 nmol/L. Accuracy and precision were validated according to Food and Drug Administration guidelines, with coefficients of variation ranging from 3.1-11.7% and recoveries from 94.4-107.5%. Routine monitoring of the complex range of vitamins in bariatric medicine is still not common. This is despite the fact that patients are at risk for glitch deficits, especially of a neurological nature. An analytical method that allows for the complex measurement of both water-soluble and fat-soluble vitamins is important and necessary for the clinical monitoring of bariatric patients. The method we have described could benefit both clinical practice and nutritional research.

Corrigendum: Secretoneurin levels are higher in dilated cardiomyopathy than in ischaemic cardiomyopathy: preliminary results.

[This corrects the article DOI: 10.3389/fcvm.2023.1297900.].

Serum neurofilament light chain levels in patients with cognitive deficits and movement disorders: comparison of cerebrospinal and serum neurofilament light chain levels with other biomarkers.

Background: Serum neurofilament light chain (S NfL) is a non-specific marker of neuronal damage, including Alzheimer's disease (AD). We aimed to verify the reference interval (RI) of serum NfL using a highly sensitive ELISA, and to estimate the optimal cut-off value for neuronal damage. Our second objective was to compare NfL in cerebrospinal fluid (CSF) and serum (S) with the routine neurodegeneration biomarkers used in AD, and to assess their concentrations relative to the degree of cognitive deficit. Methods: Samples from 124 healthy volunteers were used to estimate the S NfL RI. For the comparison study, we used CSF and S samples from 112 patients with cognitive disorders. Cognitive functions were assessed using the mini-mental state examination. ELISA assays were used to determine the CSF and S NfL levels, CSF ß-amyloid peptide42 (Aß42), CSF ß-amyloid peptide40 (Aß40), CSF total tau protein (tTau), CSF phosphorylated tau protein (pTau), and CSF alpha-synuclein (αS). Results: The estimated RI of S NfL were 2.25-9.19 ng.L-1. The cut-off value of S NfL for assessing the degree of neuronal impairment was 10.5 ng.L-1. We found a moderate statistically significant correlation between S NfL and CSF Aß42 in the group with movement disorders, without dementia (rs = 0.631; p = 0.016); between S NfL and CSF Aß40 in the group with movement disorder plus dementia (rs = -0.750; p = 0.052); between S NfL and CSF tTau in the control group (rs = 0.689; p = 0.009); and between S NfL and CSF pTau in the control group (rs = 0.749; p = 0.003). The non-parametric Kruskal-Wallis test revealed statistically significant differences between S NfL, CSF NfL, CSF Aß42, CSF tTau, and CSF pTau and diagnosis within groups. The highest kappa coefficients were found between the concentrations of S NfL and CSF NfL (κ = 0.480) and between CSF NfL and CSF tTau (κ = 0.351). Conclusion: Our results suggested that NfL and tTau in CSF of patients with cognitive decline could be replaced by the less-invasive determination of S NfL using a highly sensitive ELISA method. S NfL reflected the severity of cognitive deficits assessed by mini-mental state examination (MMSE). However, S NfL is not specific to AD and does not appear to be a suitable biomarker for early diagnosis of AD.

Secretoneurin levels are higher in dilated cardiomyopathy than in ischaemic cardiomyopathy: preliminary results.

Background: Secretoneurin (SN) is a neuropeptide with potential utility as a biomarker of cardiovascular episodes. The main effect of SN is mediated through its inhibition of calmodulin-dependent kinase II (CaMKII), which influences calcium handling. We aimed to associate the levels of SN in plasma with different causes of heart failure. Methods: We prospectively enrolled consecutive patients with ischaemic (ICM) and dilated (DCM) cardiomyopathy from the outpatient heart failure clinic and healthy individuals. SN was analysed from venous blood by use of the ELISA method. SN plasma levels were compared in DCM, ICM and healthy individuals with non-parametric tests. Results: A total of 53 patients (81.1% male, 18.9% female; mean age 67.9 ± 12.6 years) and 34 healthy individuals (38% male, 62% female) were included in the analysis. Plasma SN levels were significantly higher in the dilated cardiomyopathy (38.8 ± 27 pmol/L) as compared with the ischaemic cardiomyopathy (19.7 ± 22.6 pmol/L) group (P = 0.006). There was no significant difference between females vs. males (27.1 ± 23 vs. 25.5 ± 26.2 pmol/L, P = NS). Plasma SN levels allowed DCM and ICM to be differentiated with 88% sensitivity and 61% specificity (P = 0.007), the cut of value is 13.3 pmol/L. Plasma SN levels differed significantly between healthy volunteers and both ICM (P < 0.0001) and DCM (P = 0.049). Plasma SN levels did not differ according to age and were not associated with comorbidities, left ventricular ejection fraction, heart failure medication, troponin, creatinine, or natriuretic peptide plasma levels. Conclusion: Plasma secretoneurin levels differed significantly in DCM vs. ICM, being higher in the former. Based on plasma SN levels, discrimination between DCM and ICM might be possible. Healthy individuals produce higher SN plasma levels than stable HFrEF patients.

Patient Stratification for Antibiotic Prescriptions Based on the Bound-Free Phase Detection Immunoassay of C-Reactive Protein in Serum Samples.

C-reactive protein is a well-studied host response biomarker, whose diagnostic performance depends on its accurate classification into concentration zones defined by clinical scenario-specific cutoff values. We validated a newly developed, bead-based, bound-free phase detection immunoassay (BFPD-IA) versus a commercial CE-IVD enzyme-linked immunosorbent assay (ELISA) kit and a commercial CE-IVD immunoturbidimetric assay (ITA) kit. The latter was performed on a fully automated DPC Konelab 60i clinical analyzer used in routine diagnosis. We classified 53 samples into concentration zones derived from four different sets of cutoff values that are related to antibiotic prescription scenarios in the case of respiratory tract infections. The agreements between the methods were ELISA/ITA at 87.7%, ELISA/BFPD-IA at 87.3%, and ITA/-BFPD-IA at 93.9%, reaching 98-99% in all cases when considering the calculated relative combined uncertainty of the single measurement of each sample. In a subgroup of 37 samples, which were analyzed for absolute concentration quantification, the scatter plot slopes' correlations were as follows: ELISA/ITA 1.15, R2 = 0.97; BFPD-IA/ELISA 1.12, R2 = 0.95; BFPD-IA/ITA 0.95, R2 = 0.93. These very good performances and the agreement between BFPD-IA and ITA (routine diagnostic), combined with BFPD-IA's functional advantages over ITA (and ELISA)-such as quick time to result (~20 min), reduced consumed reagents (only one assay buffer and no washing), few and easy steps, and compatibility with nucleic-acid-amplification instruments-render it a potential approach for a reliable, cost-efficient, evidence-based point-of-care diagnostic test for guiding antibiotic prescriptions.