Analytical performance specifications for the measurement uncertainty of 24,25-dihydroxyvitamin D examinations.

OBJECTIVES: The exploration of the metabolites in the degradation pathways of vitamin D (VTD) has gained importance in recent years and simultaneous quantitation of twenty-five-hydroxy vitamin D (25(OH)D) mass concentration together with 24,25-dihydroxyvitamin D (24,25(OH)2D) has been proposed as a newer approach to define VTD deficiency. Yet, no data are available on 24,25(OH)2D biological variation (BV). In this study, we evaluated 24,25(OH)2D's BV on the European Biological Variation Study (EuBIVAS) cohort samples to determine if analytical performance specifications (APS) for 24,25(OH)2D could be generated. METHODS: Six European laboratories recruited 91 healthy participants. 25(OH)D and 24,25(OH)2D concentrations in K3-EDTA plasma were examined weekly for up to 10 weeks in duplicate with a validated LC-MS/MS method. The Vitamin D Metabolite Ratio (24,25(OH)2D divided by 25(OH)D × 100) was also calculated at each time point. RESULTS: Linear regression of the mean 24,25(OH)2D concentrations at each blood collection showed participants were not in steady state. Variations of 24,25(OH)2D over time were significantly positively associated with the slopes of 25(OH)D concentrations over time and the concentration of 25(OH)D of the participant at inclusion, and negatively associated with body mass index (BMI), but not with age, gender, or location of the participant. The variation of the 24,25(OH)2D concentration in participants over a 10 weeks period was 34.6%. Methods that would detect a significant change linked to the natural production of 24,25(OH)2D over this period at p<0.05 would need a relative measurement uncertainty (u%)<14.9% while at p<0.01, relative measurement uncertainty should be <10.5%. CONCLUSIONS: We have defined for the first time APS for 24,25(OH)2D examinations. According to the growing interest in this metabolite, several laboratories and manufacturers might aim to develop specific methods for its determination. The results presented in this paper are thus necessary prerequisites for the validation of such methods.

ISO 15189 is a sufficient instrument to guarantee high-quality manufacture of laboratory developed tests for in-house-use conform requirements of the European In-Vitro-Diagnostics Regulation.

The EU In-Vitro Diagnostic Device Regulation (IVDR) aims for transparent risk-and purpose-based validation of diagnostic devices, traceability of results to uniquely identified devices, and post-market surveillance. The IVDR regulates design, manufacture and putting into use of devices, but not medical services using these devices. In the absence of suitable commercial devices, the laboratory can resort to laboratory-developed tests (LDT) for in-house use. Documentary obligations (IVDR Art 5.5), the performance and safety specifications of ANNEX I, and development and manufacture under an ISO 15189-equivalent quality system apply. LDTs serve specific clinical needs, often for low volume niche applications, or correspond to the translational phase of new tests and treatments, often extremely relevant for patient care. As some commercial tests may disappear with the IVDR roll-out, many will require urgent LDT replacement. The workload will also depend on which modifications to commercial tests turns them into an LDT, and on how national legislators and competent authorities (CA) will handle new competences and responsibilities. We discuss appropriate interpretation of ISO 15189 to cover IVDR requirements. Selected cases illustrate LDT implementation covering medical needs with commensurate management of risk emanating from intended use and/or design of devices. Unintended collateral damage of the IVDR comprises loss of non-profitable niche applications, increases of costs and wasted resources, and migration of innovative research to more cost-efficient environments. Taking into account local specifics, the legislative framework should reduce the burden on and associated opportunity costs for the health care system, by making diligent use of existing frameworks.

Evaluation of the sarcopenia quality of life (SarQoL) questionnaire in community dwelling outpatient postmenopausal hungarian women.

BACKGROUND: Sarcopenia is defined as an age-related progressive and systemic loss of muscle mass and function. World Health Organization (WHO) definition of health-related quality of life (QoL) states that health is considered "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity", and a decline in QoL is anticipated in individuals with sarcopenia. Beaudart et al. framed the concept of defining QoL in patients suffering from sarcopenia (SarQoL) based on fundamental procedures of QoL questionnaire development, expert recommendations and studies. The aim of the present study is to evaluate the discriminative power, internal consistency and floor and ceiling effects using data available from a sarcopenia study published recently, where the Hungarian version of the SarQoL questionnaire was also administered. METHODS: In this cross-sectional study, data from SarQoL questionnaire administered to a postmenopausal sarcopenia study cohort (n = 100) was scrutinized for evaluation of psychometric properties of the questionnaire. Our verification of the psychometric properties consisted of discriminative power analysis, assessment of internal consistency, and floor and ceiling effects. The homogeneity of the SarQoL questionnaire, i.e., its internal consistency was measured using Cronbach's alpha coefficient. Correlation between the overall and domain SarQoL questionnaire scores and appendicular skeletal muscle mass in sarcopenic individuals was assessed. Furthermore, the difference of SarQoL overall and domain scores between sarcopenic and non-sarcopenic patients was also evaluated. RESULTS: The median (interquartile range (IQR)) overall SarQoL questionnaire score was 81.5 (67.1-91.5). There was a statistically significant lower overall SarQoL score comparing sarcopenic and non-sarcopenic subjects median (IQR): 75.3 (62.1-86.3) vs. 83.7 (71.4-92.1); p = 0.041). The sarcopenic subjects showed a statistically significant (p = 0.021) correlation between the overall SarQoL score and appendicular skeletal muscle mass (Spearman's ϱ = 0.412). The overall Cronbach's alpha of 0.937 indicated a high internal consistency of the Hungarian version of the SarQoL questionnaire. No floor or ceiling effects were noted in the overall SarQoL questionnaire score. CONCLUSION: In our study on community dwelling outpatient postmenopausal Hungarian women, the overall score of the Hungarian version of the SarQoL questionnaire had significant discriminative power to distinguish between sarcopenic and non-sarcopenic patients, had high internal consistency and no floor or ceiling effects.

Prevalence of sarcopenia in community dwelling outpatient postmenopausal Hungarian women.

BACKGROUND: Ageing is an inherent feature of life and as per the United Nations, in the year 2020, 985 million women were ≥ 50 years of age worldwide, and the figure is expected to rise to 1.65 billion by 2050. Preservation of health and well-being in the elderly are challenging, and on the same note generalized changes in the musculoskeletal system contribute to this scenario. Musculoskeletal changes with ageing are referred to as sarcopenia. Reduced muscle mass and physical performance are hallmarks of sarcopenia, exclaimed with difficulty in independent activity and poor quality of life. Knowing that there is a hiatus in our knowledge as regards to the prevalence of sarcopenia in Hungary, the aim of this study was to determine the prevalence of sarcopenia in a community dwelling outpatient postmenopausal Hungarian cohort using the EWGSOP2 consensus recommendation. METHODS: In this cross-sectional study, women arriving for routine bone densitometry examination at the Regional Osteoporosis Center, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen were invited to participate in the study. A total of a 100 community-dwelling women were recruited who confirmed to the inclusion criteria of self-reported postmenopausal status, ≥ 50 years of age and gave written informed consent. The study procedures included the self-administered SARC-F questionnaire, followed by assessment of muscle strength, muscle quantity and physical preformance. Muscle strength was determined with the hand grip strength (HGS), appendicular skeletal muscle mass was assessed using dual energy X-ray absorptiometry and physical performance was determined by the gait speed (GS) test. RESULTS: As per the EWGSOP2 definition, the percentage of study participants with probable sarcopenia (low muscle strength), sarcopenia (low muscle strength and low muscle quantity) and severe sarcopenia (low muscle strength, muscle quantity and low physical performance) was 36, 31 and 8%, respectively. Multiple linear regression analysis revealed that height, weight, HGS and GS were all independent predictors of appendicular skeletal muscle mass. CONCLUSION: The 31% prevalence of sarcopenia in the studied post-menopausal women highlights the need for adequate assessment of the condition in the elderly. Our findings most probably bear public health implications and may accelerate formulation of policies promoting healthy ageing.

Implementation of the new EU IVD regulation - urgent initiatives are needed to avert impending crisis.

Laboratory medicine in the European Union is at the dawn of a regulatory revolution as it reaches the end of the transition from IVDD 98/79/EC (https://eur-lex.eur-opa.eu/legal-content/EN/TXT/?uri=CELEX%3A31998L0079&qid=1628781352814) to IVDR 2017/746 https://eur-lex.europa.eu/eli/reg/2017/746. Without amendments and contingency plans, implementation of the IVDR in May 2022 will lead the healthcare sector into uncharted waters due to unpreparedness of the EU regulatory infrastructure. Prospective risk analyses were not made by the European Commission, and if nothing happens it can be anticipated that the consequences will impact all stakeholders of the medical test pipeline, may seriously harm patients and may prevent caregivers from making appropriate clinical decisions due to non-availability of medical tests. Finally, it also may discourage manufacturers and academia from developing specialty tests, thereby hampering innovation in medical diagnostic care. We hereby inform laboratory professionals about the imminent diagnostic collapse using testimonies from representative stakeholders of the diagnostic supply chain and from academia developing innovative in-house tests in domains of unmet clinical needs. Steps taken by the EFLM Task Force on European Regulatory Affairs, under the umbrella of the Biomedical Alliance in Europe, will be highlighted, as well as the search for solutions through dialogue with the European Commission. Although we recognize that the IVDR promotes positive goals such as increased clinical evidence, surveillance, and transparency, we need to ensure that the capabilities of the diagnostic sector are not damaged by infrastructural unpreparedness, while at the same time being forced to submit to a growing bureaucratic and unsupportive structure that will not support its "droit d'exister".

Characterization of bone metabolism in hungarian psoriatic arthritis patients: a case-control study.

BACKGROUND: Skeletal manifestations are predominant in psoriatic arthritis (PsA). The aim of this cross-sectional, case-control study is the complex assessment of areal and volumetric bone mineral density (BMD), fracture risk, vitamin D status and bone turnover markers, and its association with disease-related variables. METHODS: Lumbar spine (L1-L4) and femoral neck (FN) areal, and distal radius (DR) volumetric BMD, 10-year probability of major and hip osteoporotic fracture as assessed by the fracture risk assessment (FRAX) tool, markers of bone metabolism and disease activity were assessed. RESULTS: Upon comparison of the disease and age- and sex-matched control groups, there was a statistically significant difference in FN areal (0.952 (0.607-1.292) g/cm2 vs. 1.016 (0.760-1.550) g/cm2; p = 0.001) and DR total volumetric (284.3 (138.9-470.3) mg/cm3 vs. 367.0 (287.0-412.0) mg/cm3; p < 0.001) BMD, 10 year probability for major osteoporotic (3.7% (0.7-32%) vs. 2.6% (0-17.5%); p = 0.003) and hip (0.4% (0-16%) vs. 0.05% (0-6.1%); p = 0.002) fracture and 25-hydroxyvitamin D status (47.5 (10-120) nmol/L vs. 64 (10-137; p < 0.001) nmol/L). As compared to areal assessment, volumetric BMD measurements identified a significantly higher number of patients with low bone mineral density (T-Score ≤ - 1.00) (34% vs. 88%, p < 0.001). Upon multiple linear regression analysis, disease activity score, as determined by DAS28 assessment, was an independent predictor of 10-year probability for major osteoporotic fracture (B (95%CI) = 1.351 (0.379-2.323); p = 0.007). CONCLUSION: In the studied PsA cohort, disease activity was an independent predictor of 10-year probability for a major osteoporotic fracture, and complemented assessment of volumetric and areal BMD assured better efficacy at identifying those with low bone mineral density.

Peripheral quantitative computed tomography in the assessment of bone mineral density in anti-TNF-treated rheumatoid arthritis and ankylosing spondylitis patients.

INTRODUCTION: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with osteoporosis. There have not been many peripheral quantitative computed tomography (QCT) studies in patients receiving biologics. We assessed volumetric and areal bone mineral density (BMD) by forearm QCT and dual-energy X-ray absorptiometry (DXA), respectively in addition to laboratory biomarkers in these arthritides. METHODS: Forty RA and AS patients treated with either etanercept (ETN) or certolizumab pegol (CZP) were undergoing follow-ups for one year. Volumetric and areal BMD, as well as parathyroid hormone (PTH), osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin (SOST), Dickkopf 1 (DKK-1) and cathepsin K (CATHK) were determined. RESULTS: We did not observe any further bone loss during the 12-month treatment period. Volumetric and areal BMD showed significant correlations with each other (p<0.017 after Bonferroni's correction). Trabecular QCT BMD at baseline (p=0.015) and cortical QCT BMD after 12 months (p=0.005) were inversely determined by disease activity at baseline in the full cohort. Trabecular QCT BMD at baseline also correlated with CTX (p=0.011). In RA, CRP negatively (p=0.014), while SOST positively (p=0.013) correlated with different QCT parameters. In AS, RANKL at baseline (p=0.014) and after 12 months (p=0.007) correlated with cortical QCT BMD. In the full cohort, 12-month change in QTRABBMD was related to TNF inhibition together with elevated VITD-0 levels (p=0.031). Treatment and lower CATHK correlated with QCORTBMD changes (p=0.006). In RA, TNF inhibition together with VITD-0 (p<0.01) or CATHK-0 (p=0.002), while in AS, treatment and RANKL-0 (p<0.05) determined one-year changes in QCT BMD. CONCLUSIONS: BMD as determined by QCT did not change over one year of anti-TNF treatment. Disease activity, CATHK, RANKL and VITD may be associated with the effects of anti-TNF treatment on QCT BMD changes. RA and AS may differ in this respect.

Laser-induced plasma spectroscopy (LIPS): use of a geological tool in assessing bone mineral content.

Bone may be similar to geological formulations in many ways. Therefore, it may be logical to apply laser-based geological techniques in bone research. The mineral and element oxide composition of bioapatite can be estimated by mathematical models. Laser-induced plasma spectrometry (LIPS) has long been used in geology. This method may provide a possibility to determine the composition and concentration of element oxides forming the inorganic part of bones. In this study, we wished to standardize the LIPS technique and use mathematical calculations and models in order to determine CaO distribution and bone homogeneity using bovine shin bone samples. We used polished slices of five bovine shin bones. A portable LIPS instrument using high-power Nd++YAG laser pulses has been developed (OpLab, Budapest). Analysis of CaO distribution was carried out in a 10 × 10 sampling matrix applying 300-µm sampling intervals. We assessed both cortical and trabecular bone areas. Regions of interest (ROI) were determined under microscope. CaO peaks were identified in the 200-500 nm wavelength range. A mathematical formula was used to calculate the element oxide composition (wt%) of inorganic bone. We also applied two accepted mathematical approaches, the Bartlett's test and frequency distribution curve-based analysis, to determine the homogeneity of CaO distribution in bones. We were able to standardize the LIPS technique for bone research. CaO concentrations in the cortical and trabecular regions of B1-5 bones were 33.11 ± 3.99% (range 24.02-40.43%) and 27.60 ± 7.44% (range 3.58-39.51%), respectively. CaO concentrations highly corresponded to those routinely determined by ICP-OES. We were able to graphically demonstrate CaO distribution in both 2D and 3D. We also determined possible interrelations between laser-induced craters and bone structure units, which may reflect the bone structure and may influence the heterogeneity of CaO distributions. By using two different statistical methods, we could confirm if bone samples were homogeneous or not with respect to CaO concentration distribution. LIPS, a technique previously used in geology, may be included in bone research. Assessment of element oxide concentrations in the inorganic part of bone, as well as mathematical calculations may be useful to determine the content of CaO and other element oxides in bone, further analyze bone structure and homogeneity and possibly apply this research to normal, as well as diseased bones.

Thyroglobulin level at week 16 of pregnancy is superior to urinary iodine concentration in revealing preconceptual and first trimester iodine supply.

Pregnant women are prone to iodine deficiency due to the increased need for iodine during gestation. Progress has recently occurred in establishing serum thyroglobulin (Tg) as an iodine status biomarker, but there is no accepted reference range for iodine sufficiency during pregnancy. An observational study was conducted in 164 pregnant women. At week 16 of gestation urinary iodine concentration (UIC), serum Tg, and thyroid functions were measured, and information on the type of iodine supplementation and smoking were recorded. The parameters of those who started iodine supplementation (≥150 µg/day) at least 4 weeks before pregnancy (n = 27), who started at the detection of pregnancy (n = 51), and who had no iodine supplementation (n = 74) were compared. Sufficient iodine supply was found in the studied population based on median UIC (162 µg/L). Iodine supplementation ≥150 µg/day resulted in higher median UIC regardless of its duration (nonusers: 130 µg/L vs. prepregnancy iodine starters: 240 µg/L, and pregnancy iodine starters: 205 µg/L, p < .001, and p = .023, respectively). Median Tg value of pregnancy starters was identical to that of nonusers (14.5 vs. 14.6 µg/L), whereas prepregnancy starters had lower median Tg (9.1 µg/L, p = .018). Serum Tg concentration at week 16 of pregnancy showed negative relationship (p = .010) with duration of iodine supplementation and positive relationship (p = .008) with smoking, a known interfering factor of iodine metabolism, by multiple regression analysis. Serum Tg at week 16 of pregnancy may be a promising biomarker of preconceptual and first trimester maternal iodine status, the critical early phase of foetal brain development.

Vitamin D: Musculoskeletal health.

Perhaps the role of Vitamin D supplementation has been most exhaustively studied in calcium absorption, skeletal wellbeing, muscular potency, balance and risk of falling. Nonetheless, new data has emerged and the recent research on sarcopenia makes the topic increasingly interesting. Given the socioeconomic burden of the musculoskeletal consequences of hypovitaminosis D it is vital to keep abreast with the latest literature in the field. The recommended Vitamin D supplementation dose should suffice to increase the serum 25 hydroxyvitamin D level to 30 ng/mL (75 nmol/L) and this level should be optimally maintained with a maintenance dose, particularly for those diagnosed with osteoporosis.

The role of hyperinsulinemia as a cardiometabolic risk factor independent of obesity in polycystic ovary syndrome.

The aim of this study was to utilize various insulin resistance measuring methods to determine whether insulin resistance and other parameters impact the serum lipid levels of polycystic ovary syndrome (PCOS) patients and how the serum lipid levels in these patients are affected by the body mass index (BMI). Our dataset included patients between the ages of 16 and 42 (N = 228) from the outpatient endocrinology clinic of the Department of Obstetrics and Gynecology, who demonstrated increased hair growth and bleeding disorders and came for a routine oral glucose tolerance test (OGTT). Differences in the serum lipid levels were evaluated by t-test and linear regression analysis after adjusting for BMI. A stepwise regression model was constructed to evaluate the influence of each variable on the lipid levels. In PCOS patients, we found that dyslipidemia is more prevalent among hyperinsulinemic women compared with normoinsulinemic women, even after normalizing for BMI. PCOS patients with insulin resistance, determined by the insulin sensitivity index (ISI) method, showed more significant lipid abnormalities such as low high-density lipoprotein (HDL) and apo-A levels and high total cholesterol, low-density lipoprotein (LDL) and apo-B levels than if insulin resistance (IR) determination was based on insulin level or homeostatic model assessment (HOMA).

Haemodiafiltration elicits less platelet activation compared to haemodialysis.

BACKGROUND: Mortality in patients with end-stage renal disorders is often a consequence of cardiovascular complications. Renal replacement therapies may contribute to this morbidity by promoting cellular activation. In renal failure patients peripheral blood samples were investigated for platelet and endothelial cell activation markers to compare the effects of haemodiafiltration (HDF) and haemodialysis (HD). METHODS: Overall 28 patients were included in the study. Platelet P-selectin and leukocyte - platelet heterotypic aggregates were studied by flow cytometry. Soluble P- and E-selectin values were determined by ELISA, while von Willebrand factor (vWF) antigen levels were measured by immunoturbidimetry. Statistical analysis was done by the SPSS v22 software. RESULTS: Platelet surface P-selectin was below 3.0 % in healthy controls, but it was higher during the dialysis after 4 h, 8 % and 14.3 % in HDF and HD, respectively. Monocyte-platelet heterotypic aggregates were significantly elevated after 4 h in both treatments, up to 69.2 % in HDF and to 82.9 % in HD. Soluble P-selectin levels were also significantly elevated by the end of both treatment procedures (p < 0.001), vWF antigen values, however, showed elevation only during HD treatment. CONCLUSIONS: The attenuated platelet activating effects of HDF compared to HD may contribute to a less unfavourable vascular effect in this treatment modality.

Anti-Atherogenic Properties of Allium ursinum Liophylisate: Impact on Lipoprotein Homeostasis and Cardiac Biomarkers in Hypercholesterolemic Rabbits.

The present investigation evaluates the capacity of Allium ursinum (wild garlic) leaf lyophilisate (WGLL; alliin content: 0.261%) to mitigate cardiovascular damage in hypercholesterolemic rabbits. New Zealand rabbits were divided into three groups: (i) cholesterol-free rabbit chow (control); (ii) rabbit chow containing 2% cholesterol (hypercholesterolemic, HC); (iii) rabbit chow containing 2% cholesterol + 2% WGLL (hypercholesterolemic treated, HCT); for eight weeks. At the zero- and eight-week time points, echocardiographic measurements were made, along with the determination of basic serum parameters. Following the treatment period, after ischemia-reperfusion injury, hemodynamic parameters were measured using an isolated working heart model. Western blot analyses of heart tissue followed for evaluating protein expression and histochemical study for the atheroma status determination. WGLL treatment mediated increases in fractional shortening; right ventricular function; peak systolic velocity; tricuspidal annular systolic velocity in live animals; along with improved aortic and coronary flow. Western blot analysis revealed WGLL-associated increases in HO-1 protein and decreases in SOD-1 protein production. WGLL-associated decreases were observed in aortic atherosclerotic plaque coverage, plasma ApoB and the activity of LDH and CK (creatine kinase) in plasma. Plasma LDL was also significantly reduced. The results clearly demonstrate that WGLL has complex cardioprotective effects, suggesting future strategies for its use in prevention and therapy for atherosclerotic disorders.

Cystatin C as a potential predictor of osteoprotegerin levels in healthy men, a cross-sectional, observational study.

BACKGROUND: The aim of the present study is to evaluate serum osteoprotegerin (OPG) and soluble receptor activator of nuclear factor κB ligand (sRANKL) levels in a randomly selected male cohort over 50 years of age and its association with cystatin C, a cysteine proteinase inhibitor that decreases formation of osteoclasts by interfering at a late stage of pre-osteoclast differentiation, apart from being a marker of renal function independent of gender, muscle mass and age; in addition to known predictors such as age, sex hormones, vitamin D, bone mineral density (BMD) and biochemical markers of bone turnover. METHODS: We determined serum OPG and sRANKL levels and examined its relationship with cystatin C, age, osteocalcin, C-terminal telopeptides of type-I collagen, procollagen type 1 amino-terminal propeptide, 25-hydroxyvitamin D, parathyroid hormone, total 17ß-estradiol (E2), total testosterone and L1-L4 (LS) and femur neck (FN) BMD data available from 194 (age, range: 51-81 years) randomly selected ambulatory men belonging to the HunMen cohort. RESULTS: OPG correlated significantly with age (Spearman's rho (r) = 0.359, p < 0.001), cystatin C (r = 0.298, p < 0.001), E2 (r = 0.160, p = 0.028) and free testosterone index (FTI) (r = -0.230, p = 0.001). Compared to the middle-aged (age: ≤ 59 years, n = 98), older men (age > 59 years, n = 96) had significantly higher serum OPG (4.6 pmol/L vs. 5.4 pmol/L; p < 0.001), and lower sRANKL (0.226 pmol/L vs. 0.167 pmol/L; p = 0.048) levels. The older men showed a significant correlation between serum OPG levels and cystatin C (Spearman's rho = 0.322, p = 0.002), and E2 (Spearman's rho = 0.211, p = 0.043). Including cystatin C and E2 in a regression model showed that cystatin C (standard regression coefficient (ß) = 0.345; p = 0.002) was the only significant predictor of serum OPG levels in the older men. CONCLUSIONS: The results of this study demonstrated that in addition to age (which was the stronger predictor), other modifiable factors such as cystatin C, FTI and E2 were also significant predictors of OPG, and that the association between cystatin C and OPG was more evident with increased age (older age group). As such, cystatin C is a significant predictor of OPG independently of age, FTI and E2.

Serum human epididymis protein 4 (HE4) as a tumor marker in men with lung cancer.

BACKGROUND: Human epididymis protein 4 (HE4) is a reliable tumor marker for ovarian cancer, but only limited data are available on HE4 levels in lung malignancies. METHODS: HE4 levels were measured at diagnosis in 98 men with lung cancer at different stages of the disease, and these results were compared to an age-matched healthy male cohort (n=98). The concentrations of classical tumor markers were also determined, and their efficacy was compared to that of HE4. RESULTS: Compared to healthy controls, patients with lung neoplasm showed significantly higher HE4 levels [118.2 (80.6-150.1) pmol/L vs. 62.2 (47.2-76.1) pmol/L; p<0.001]. Although age and smoking modulated HE4 levels in the healthy cohort, no such effect was observed in the patient population. The area under the receiver operating characteristic curve (ROC-AUC) for HE4 was 0.848 (95% CI 0.792-0.904) for differentiating lung cancer patients from healthy controls, with a cut-off value of 97.6 pmol/L (sensitivity: 64.3%, specificity: 95.9%). HE4 levels were significantly elevated in all stages of lung cancer, and even in patients without clinical symptoms (p<0.05), but no difference was found between the different histological subgroups. A significant correlation was found between HE4 values and the tumor size determined by CT/MRI (Spearman's ρ=0.227, p=0.030). The combination of HE4 with CEA and CA 125 considerably enhanced the diagnostic efficacy [ROC-AUC: 0.963 (95% CI 0.937-0.990), sensitivity: 91.8%, specificity: 92.8%]. CONCLUSIONS: Our data suggest that serum HE4, especially in combination with CEA and CA 125, qualifies as a surrogate diagnostic marker in men with lung cancer.

[Applicability of laser-based geological techniques in bone research: analysis of calcium oxide distribution in thin-cut animal bones]. / Lézeralapú geológiai technikák felhasználhatósága a csontkutatásban: kalcium-oxid-eloszlás vizsgálata állati csont vékonycsiszolatain.

The structural similarities between the inorganic component of bone tissue and geological formations make it possible that mathematic models may be used to determine weight percentage composition of different mineral element oxides constituting the inorganic component of bone tissue. The determined weight percentage composition can be verified with the determination of element oxide concentration values by laser induced plasma spectroscopy and inductively coupled plasma optical emission spectrometry. It can be concluded from calculated weight percentage composition of the inorganic component of bone tissue and laboratory analyses that the properties of bone tissue are determined primarily by hydroxylapatite. The inorganic bone structure can be studied well by determining the calcium oxide concentration distribution using the laser induced plasma spectroscopy technique. In the present study, thin polished bone slides prepared from male bovine tibia were examined with laser induced plasma spectroscopy in a regular network and combined sampling system to derive the calculated calcium oxide concentration distribution. The superficial calcium oxide concentration distribution, as supported by "frequency distribution" curves, can be categorized into a number of groups. This, as such, helps in clearly demarcating the cortical and trabecular bone structures. Following analyses of bovine tibial bone, the authors found a positive association between the attenuation value, as determined by quantitative computer tomography and the "ρ" density, as used in geology. Furthermore, the calculated "ρ" density and the measured average calcium oxide concentration values showed inverse correlation.

[131I]6ß-Iodomethyl-19-norcholesterol SPECT/CT for the Lateralization of Mineralocorticoid Overproduction in Primary Aldosteronism.

Primary: aldosteronism is a frequent cause of secondary hypertension. With access to specialized care, an increasing number of patients with aldosteronism are being identified. Primary aldosteronism is treatable by adrenal surgery if aldosterone excess originates from one of the two, and not from both, adrenals. Bilateral hyperplasia requires lifelong mineralocorticoid receptor antagonist treatment. Up till now, adrenal venous sampling (AVS) has been widely used to distinguish between one-sided and two-sided aldosterone overproduction and patient selection for surgery. AVS is an invasive technique, and the unsuccessful sampling of the right adrenal vein during AVS often prevents side comparison, making the AVS procedure useless. Molecular imaging using [131I]6ß-iodomethyl-19-norcholesterol with SPECT CT imaging (SPECT/CT) may be a potential alternative. METHODS: In 42 consecutive patients with confirmed primary aldosteronism, molecular imaging has been performed. After dexamethasone suppression of the non-affected adrenal tissue, 37 MBq [131I]6ß-iodomethyl-19-norcholesterol was injected i.v., and SPECT/CT images were taken 7 days later. Based on the visual evaluation of the images by two nuclear medicine specialists, patients with one-sided tracer accumulation underwent adrenalectomy. To identify a SPECT/CT parameter that best characterizes the side difference, the maximum counts and the mean counts of spherical VOIs were analyzed. RESULTS: Of the 42 patients, 24 had one-sided aldosterone overproduction by SPECT/CT. After surgical removal of the involved adrenal, all 24 patients with SPECT/CT-identified unilateral aldosteronism achieved biochemical cure, defined as a normalized potassium level combined with an aldosterone-to-renin ratio ≤ 30. To identify the best measurable parameter of SPECT/CT side difference, the mean counts and maximum counts of a series of spherical VOIs of different diameters were analyzed. The ratio of the mean counts of 3 cm spherical VOIs of the right and left adrenal regions (lateralization index) was the best discriminator; a ratio of ≥1.29 was characteristic of one-sided disease, without overlap between the one-sided and two-sided patient groups. CONCLUSIONS: [131I]6ß-iodomethyl-19-norcholesterol SPECT/CT with a count-based image interpretation and side-ratio calculation may be an equipollent non-invasive substitute for adrenal venous sampling in the lateralization of mineralocorticoid overproduction. It reliably identifies unilateral disease and facilitates patients' selection for surgical intervention. If confirmed by others, this functional imaging may replace AVS when lateralization is required for management decisions in primary aldosteronism.

Low Serum Fibroblast Growth Factor 21 Level and Its Altered Regulation by Thyroid Hormones in Patients with Hashimoto's Thyroiditis on Levothyroxine Substitution.

BACKGROUND/OBJECTIVES: Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism exerting protection against atherosclerosis by multiple actions on the blood vessels, liver, and adipose tissues. We aimed to investigate serum FGF21 level and its relation to thyroid hormones and metabolic parameters among patients with Hashimoto's thyroiditis (HT). METHODS: Eighty patients with HT on levothyroxine treatment and eighty-two age- and BMI-matched adults without thyroid disease serving as controls were enrolled. Serum FGF21 concentrations were determined with an enzyme-linked immunosorbent assay. RESULTS: Median serum FGF21 level was significantly lower in HT patients compared with controls (74.2 (33.4-148.3) pg/mL vs. 131.9 (44.8-236.3) pg/mL; p = 0.03). We found a positive correlation between FGF21 and age, triglyceride, total cholesterol, and low-density lipoprotein cholesterol in both groups, while thyroid stimulating hormone and C-reactive protein showed a positive correlation, and thyroxine had an inverse correlation with FGF21 only in control subjects. According to multiple regression analyses, thyroid status is the main predictor of FGF21 in healthy controls, while it is not a significant predictor of FGF21 among HT patients on levothyroxine supplementation therapy. CONCLUSIONS: Our results indicate that the physiological role of thyroid function in the regulation of FGF21 synthesis is impaired in HT patients, which may contribute to the metabolic alterations characteristic of HT patients.

Quality of life in sarcopenia measured with the SarQoL questionnaire: A meta-analysis of individual patient data.

Age-related sarcopenia, resulting from a gradual loss in skeletal muscle mass and strength, is pivotal to the increased prevalence of functional limitation among the older adult community. The purpose of this meta-analysis of individual patient data is to investigate the difference in health-related quality of life between sarcopenic individuals and those without the condition using the Sarcopenia Quality of Life (SarQoL) questionnaire. A protocol was published on PROSPERO. Multiple databases and the grey literature were searched until March 2023 for studies reporting quality of life assessed with the SarQoL for patients with and without sarcopenia. Two researchers conducted the systematic review independently. A two-stage meta-analysis was performed. First, crude (mean difference) and adjusted (beta coefficient) effect sizes were calculated within each database; then, a random effect meta-analysis was applied to pool them. Heterogeneity was measured using the Q-test and I2 value. Subgroup analyses were performed to investigate the source of potential heterogeneity. The strength of evidence of this association was assessed using GRADE. From the 413 studies identified, 32 were eventually included, of which 10 were unpublished data studies. Sarcopenic participants displayed significantly reduced health-related quality of life compared with non-sarcopenic individuals (mean difference = -12.32; 95 % CI = [-15.27; -9.37]). The model revealed significant heterogeneity. Subgroup analyses revealed a substantial impact of regions, clinical settings, and diagnostic criteria on the difference in health-related quality of life between sarcopenic and non-sarcopenic individuals. The level of evidence was moderate. This meta-analysis of individual patient data suggested that sarcopenia is associated with lower health-related quality of life measured with SarQoL.

Serum sclerostin levels in healthy men over 50 years of age.

The aim of this study is to evaluate the relationship of serum sclerostin levels with age, cystatin C, bone mineral density (BMD) and biochemical markers of bone turnover in healthy Hungarian men >50 years of age. We determined serum levels of sclerostin and examined its relationship to age, cystatin C, osteocalcin, C-terminal telopeptides of type-I collagen, procollagen type 1 amino-terminal propeptide, 25-hydroxyvitamin D, parathyroid hormone, and L1-L4 (LS) and femur neck (FN) BMD data available from 194 randomly selected ambulatory men belonging to the HunMen cohort. In the study population as a whole [n = 194; age (median, range) 59 (51-81) years], statistically significant correlation was found between sclerostin and age (r = 0.211; p = 0.003), cystatin C (r = 0.246; p = 0.001), FN BMD (r = 0.147; p = 0.041) and LS BMD (r = 0.169; p = 0.019). Compared to middle-aged men (age ≤59 years, n = 98), elderly men (age >59 years, n = 96) had significantly higher serum sclerostin levels (67.8 ± 15.9 vs 63.5 ± 14 pmol/L; p = 0.047). Among men with normal (T score >-1.0) FN BMD, the elderly had significantly higher serum sclerostin levels compared to the middle-aged men (70.4 ± 17 vs 63.9 ± 11.5 pmol/L; p = 0.019). Furthermore, among the elderly men cystatin C was the only significant predictor of serum sclerostin levels (standardized regression coefficient (ß) = 0.487; p < 0.001). In the studied healthy elderly cohort, this study reports a significant increase in sclerostin levels with increasing age and deteriorating kidney function as determined by plasma cystatin C levels.