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 From the 413 studies identified, 32 were eventually included, of which 10 were unpublished data studies.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.

The Oral Microbiome Profile of Water Polo Players Aged 16-20.

OBJECTIVES: Chlorine has a strong antibacterial property and is the disinfectant most frequently used in swimming pools. Therefore, the microbiota community in the oral cavity of those who practice water sports is assumed to be special due to their regular immersion in water. Adverse changes in the composition of oral cavity microbiota may have serious health consequences. We aimed to compare the oral microbiome between water polo players and non-athletes. We hypothesized that the oral cavity microbiota community differed between water polo players and non-athletes. MATERIALS AND METHODS: Altogether, 124 water polo players (62 males and 62 females, aged between 9 and 20 years) and 16 non-athlete youths (control group, eight males and eight females, aged between 16 and 20 years, mean age + SD = 17.1 + 1.4 years) who participated in body structure examinations voluntarily agreed to participate in the study. In a randomly selected subsample of water polo players (n: 29, aged between 16 and 20 years, mean age + SD = 17.3 + 1.0 years), saliva samples were also collected. Saliva samples were collected from all non-athlete youths (n: 16, aged between 16 and 20 years). The oral microbiome was determined from a saliva sample, and DNA was isolated using the QIAmp DNA Blood Mini Kit. The 16S rRNA gene amplicon sequencing method was used to analyze the microbiome community. PCR primers were trimmed from the sequence reads with Cutadapt. R library DADA2 was used to process reads in the abundance analysis. RESULTS: In general, Streptococcus, Veilonella, and Prevotella genera constituted more than 50% of the oral microbiome community in the two participant groups combined (n = 45). The oral microbial profile had significant sexual dimorphism and differed between water polo players and the non-athletes. Compared to females, males had a higher (p < 0.05) relative abundance of the Atopobium (medium effect size) and Pravotella_7 (very large effect size) genera and a lower (p < 0.05) relative abundance of the Fusobacterium (large effect size), Gemella (large effect size), and Streptococcus (large effect size) genera. Compared to non-athletes, water polo players had higher (p < 0.05, medium effect size) relative abundance of the genus Veillonella and lower (p < 0.05, large effect size) relative abundance of the genus Gemella. CONCLUSIONS: The results suggest that regular water training can unfavorably alter the composition of the oral microbial community.

[Coding of laboratory parameters using the LOINC system at the Clinical Center of the University of Debrecen]. / Laboratóriumi paraméterek kódolása a LOINC-rendszer szerint a Debreceni Egyetem Klinikai Központjában.

INTRODUCTION: The research utility of the bulk of the medical data generated at the Clinical Center of the University of Debrecen, which is constituted mainly by the clinical diagnostic laboratory results and medical images, is quite constrained in its present unstandardized form. The primary aim of the Big Data Research and Development project at the University of Debrecen is to facilitate data transformation and standardization to propagate its research utility for the potential end-users. Data generated in the in vitro diagnostic laboratory setting are an ideal candidate for the aforementioned goals. Data generated in Hungarian language in this particular setting are typically acronyms that do not particularly confirm to any standard norms and the transformation of these data using the globally acknowledged Logical Observation Identifiers Names and Codes (LOINC) was the primary goal of this research project. Globally the LOINC is used by healthcare providers, government agencies, insurance companies, software and device manufacturers, researchers and reference laboratories for identifying medical laboratory observations and promote unhindered fluency between various systems. OBJECTIVE: The aim of the project was to assure compliance of the various routine diagnostic laboratory parameters (n = 448) generated at the Department of Laboratory Medicine of the University of Debrecen to the LOINC system paying particular attention to and accommodating data sensitive to timeline and methodology. METHODS: Keywords allocated to individual parameters determined by the laboratory were provided by the IT service provider of the facility. The individual codes for the various parameters were manually identified using the search engine of the LOINC database available at http://www.loinc.org, only upon attainment of proficiency in use of the database and ample familiarity with the scientific literature on the topic. RESULTS: All routine diagnostic laboratory parameters were LOINC coded with no exception. The list of LOINCs' was made available on the https://labmed.unideb.hu/hu/loinc-tablazatok web link of the University of Debrecen. CONCLUSION: The transformation of diagnostic laboratory parameters to globally recognized LOINCs' improves and further facilitates the international integration of data generated at the University of Debrecen, furthermore propels communications between laboratories and parties of interest beyond international boundaries and borders. Orv Hetil. 2023; 164(27): 1043-1051.

Six years' experience and trends of serum 25-hydroxy vitamin D concentration and the effect of vitamin D3 consumption on these trends.

Introduction: Vitamin D (vitD) deficiency may have importance in some diseases, but there is a lack of data in our country to clarify the current situation. Our aim was to examine the basic characteristics of patients' vitD status, and the ratio of vitD deficiency and its relation to certain diseases, assess seasonality and trends, and reveal the indirect impact of the COVID-19 pandemic on vitD3 supplementation at the patient population level. Methods: Anonymized data on 25(OH)D test results were obtained from the clinical data registry of a tertiary teaching hospital covering the period between 1 January 2015 and 30 June 2021. VitD consumption (pharmacy sale) data were retrieved from the database of the National Health Insurance Fund of Hungary in order to calculate the defined daily dose (DDD)/1,000 inhabitants/day. Descriptive statistics and odds ratios with their 95% confidence intervals were calculated. The two-sample t-test and F-test were used to analyze our patients' data. Significant differences were considered if p <0.05. Results: Altogether, 45,567 samples were investigated; the mean age was 49 ± 19.1 years and 68.4% of them were female subjects. Overall, 20% of all patients had hypovitaminosis D, and just over 7% of patients had vitD deficiency. Male subjects had higher odds for hypovitaminosis or vitD deficiency (65.4 ± 28.2 nmol/L vs. 68.4 ± 28.4 nmol/L; p <0.0001). The mean 25(OH)D concentration has changed during the year, reaching a peak in September and a minimum in February. Patients with diseases of the circulatory system, genitourinary system, certain conditions originating in the perinatal period, and "sine morbo" (i.e., without a disease; such as those aged over 45 years and female teenagers) had statistically higher odds for lower 25(OH)D concentrations (p <0.00001). VitD consumption showed seasonality, being higher in autumn and winter. A slight increase started in the season of 2017/18, and two huge peaks were detected at the beginning of 2020 and 2021 in association with the COVID-19 waves. Conclusion: Our data are the first to describe data concerning vitD in our region. It reinforces the notion of vitD3 supplementation for some risk groups and also in healthy individuals. To prevent the winter decline, vitD3 supplementation should be started in September. This and the results during the COVID-19 pandemic highlight the importance of health education encouraging vitamin D3 supplementation.

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.

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.

Practical Considerations for the Clinical Application of Bone Turnover Markers in Osteoporosis.

Bone turnover markers (BTMs) are released during the bone remodelling cycle and are measurable in blood or urine, reflecting bone remodelling rate. They have been useful in elucidating the pharmacodynamics and effectiveness of osteoporosis medication in clinical trials and are increasingly used in routine clinical management of osteoporosis, especially for monitoring therapy, in addition to their use in other metabolic bone disease such as Paget's disease of bone and osteomalacia. Serum ß isomerised C-terminal telopeptide of type I collagen and pro-collagen I N-terminal propeptide have been designated as reference BTMs for use in osteoporosis. In addition, bone-specific isoenzyme of alkaline phosphatase (B-ALP) secreted by osteoblasts and tartrate-resistant acid phosphatase 5b (TRACP-5b) secreted by osteoclasts are also found to be specific markers of bone formation and resorption, respectively. The concentrations of the latter enzymes in blood measured by immunoassay provide reliable measures of bone turnover even in the presence of renal failure. B-ALP is recommended for use in the assessment of renal bone disease of chronic kidney disease, and TRACP-5b shows promise as a marker of bone resorption in that condition. BTMs in blood do not suffer from biological variation to the same extent as the older BTMs that were measured in urine. Appropriate patient preparation and sample handling are important in obtaining accurate measures of BTMs for clinical use. Reference change values and treatment targets have been determined for the reference BTMs for their use in monitoring osteoporosis treatment. Further ongoing studies will enhance their clinical applications.

Impact of Endocrine Disorders on IVF Outcomes: Results from a Large, Single-Centre, Prospective Study.

Endocrine disorders negatively influence the ovarian function, and increasing incidence of endocrine diseases with age may have further negative effects on pregnancy rate. Prospective cohort study of 231 consecutively enrolled patients underwent IVF treatment. In patients with known endocrine disorders, the laboratory parameters were corrected before IVF treatment. One hundred sixty one patients (69.7%) had at least one known and treated endocrine disorder (study group), and 70 patients were endocrine negative (control group). Endocrine disorders diagnosed were thyroid disorders (32.5%), diminished ovarian reserve (23.8%), insulin resistance (22.5%), PCOS (15.2%), hyperprolactinaemia (13.4%), obesity (12.1%), hypogonadotropic hypogonadism (0.8%) and congenital adrenal hyperplasia (0.2%). Before the IVF treatment, systematic endocrine laboratory examinations were performed in all patients. Higher age, BMI and FSH were found in the study group, while AMH level was lower. There were no differences in LH, E2, prolactin, TSH, FT3, FT4, TT, DHEAS, androstendione, 17-OHP and SHBG level between the study and control groups. The study group had higher baseline glucose, baseline insulin, 120-min glucose and 120-min insulin level after oral glucose tolerance test. With no difference in the IVF cycles performed, pregnancy rate was lower in the study group (61.43% vs. 34.16%; p = 0.003), and this difference (p = 0.0151) remained in age-corrected rates, as well. The analyses were also performed in individual endocrinology groups. The prevalence of endocrine disorders is high in females participating in IVF programs, and they are often accompanying each other. Even after proper correction, the presence of the endocrine disorder negatively influences the pregnancy rate in IVF treatment.

Alcohol consumption affects the late endocrine consequences of mild traumatic brain injury.

BACKGROUND: Currently there are no widely applied methods which could identify, at the time of head trauma, those mild traumatic brain injury (mTBI) patients who later develop pituitary dysfunction. The effect of alcohol consumption on post-TBI endocrine dysfunction is unclear. METHODS: Five hundred and eight TBI patients, 406 of them with mTBI, were studied. Sixty-one patients (46 males, 15 females) were available for follow-up. Admission serum samples were evaluated for S100B protein and markers of alcohol consumption: ethanol level for day-of-injury intake and carbohydrate deficient transferrin (CDT) level for regular alcohol consumption. Regular alcohol consumption was defined as CDT > 1.5%, including both social and heavy drinkers. Admission and one-year follow-up samples were evaluated for pituitary dysfunction. RESULTS: Newly developed pituitary hormone deficiency was found in 16% of mTBI patients. When cohorts developing and not developing late pituitary dysfunction were compared, 30% and 69% of patients were regular alcohol consumers, respectively (p = 0.02). Neither S100B level nor day-of-injury alcohol consumption was predictive of late pituitary dysfunction. CONCLUSION: The findings of this preliminary study suggest that regular alcohol consumption may protect against the late endocrine consequences of mTBI. Alcohol intake during the weeks preceding mTBI may identify patients at higher risk for late pituitary dysfunction.

Prevalence and association of endocrine disorders in women participating in an in vitro fertilization program / Endokrin kórképek elofordulása és társulása in vitro fertilizációs programban részt vevo nok körében

Introduction: Ovulatory dysfunction associated with endocrine diseases is a common leading or associated cause of female infertility, but at optimal reproductive age, causal or ovulation-induction treatment can usually settle fertility. The leading indications for in vitro fertilization (IVF) treatments are currently andrological and originated from age related ovarian infertility, but other accompanying endocrine dysfunctions affect treatment outcomes. Objective: To investigate the incidence of endocrine diseases in female members of couples participating in IVF program. Method: During aptitude tests prior to the IVF program, from the leading indication independently, a detailed endocrinological examination was performed in 231 women (mean age: 34 years). The studies of hypothalamic and ovarian function, thyroid function and thyroid autoimmunity, adrenal function, carbohydrate metabolism and insulin resistance were covered. In addition to the incidence of each endocrine disease, the frequency of their association was analyzed. Results: The distribution of IVF lead indications was in line with the international trends, it was endocrine nature in 87 cases (37.6%; decreased ovarian reserve in 55 cases and chronic anovulation in 32 cases). Associated endocrine abnormalities were found in 141 cases, and a total of 161 women was affected by endocrine dysfunction (69.7%; mean age: 35 years). Endocrine dysfunction incidences in order of frequency were thyroid dysfunction (32.5%), diminished ovarian reserve (23.8%), thyroid autoimmunity (22.5%), polycystic ovarian syndrome (15.6%), insulin resistance (22.5%), obesity (23.8%), hyperprolactinemia (13.4%). The endocrine disease associations were found in all of the cases above. Hypogonadotropic hypogonadism occurred in 2 cases, congenital adrenal hyperplasia occurred in 1 case. No endocrine abnormalities were found in 70 cases (30.3%). Conclusion: Our study confirms the cumulative appearance of endocrine dysfunctions and frequent association in IVF participants with any lead indication. The detailed endocrine examination and proficiency/skill in reproductive endocrinology of IVF practitioners may contribute to IVF treatment success.

Effects of targeted therapies on bone in rheumatic and musculoskeletal diseases.

Generalized bone loss (osteoporosis) and fragility fractures can occur in rheumatic and musculoskeletal diseases including rheumatoid arthritis and spondyloarthritis (SpA; including ankylosing spondylitis and psoriatic arthritis). In addition, rheumatoid arthritis can involve localized, periarticular bone erosion and, in SpA, local (pathological) bone formation can occur. The RANK-RANKL-osteoprotegerin axis and the Wnt-ß-catenin signalling pathway (along with its inhibitors sclerostin and Dickkopf 1) have been implicated in inflammatory bone loss and formation, respectively. Targeted therapies including biologic DMARDs and Janus kinase (JAK) inhibitors can stabilize bone turnover and inhibit radiographic joint damage, and potentially also prevent generalized bone loss. Targeted therapies interfere at various points in the mechanisms of local and generalized bone changes in systemic rheumatic diseases, and they effect biomarkers of bone resorption and formation, bone mass and risk of fragility fractures. Studies on the effects of targeted therapies on rates of fragility fracture are scarce. The efficacy of biologic DMARDs for arresting bone formation in axial SpA is debated. Improved understanding of the most relevant therapeutic targets and identification of important targeted therapies could lead to the preservation of bone in inflammatory rheumatic and musculoskeletal diseases.

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.

EDTA-Induced Pseudothrombocytopenia up to 9 Months after Initial COVID-19 Infection Associated with Persistent Anti-SARS-CoV-2 IgM/IgG Seropositivity.

Platelets have a role in vascular complications of COVID-19-related viral coagulopathy. Although immune-induced thrombocytopenia has been described mostly in moderate-to-severe COVID-19, the prognostic role of platelet count in COVID-19 is still controversial. Pseudothrombocytopenia has been reported to represent COVID-19-associated coagulopathy in critical illness, and transient EDTA-dependent pseudothrombocytopenia lasting less than 3 weeks was described in a patient with severe acute COVID-19 pneumonia. In our case study, EDTA-induced pseudothrombocytopenia was still present at 9 months after an initial SARS-CoV-2 virus infection in an apparently recovered 60 year old man. The persistence of antinucleocapside and antispike antibodies 9 months after the initial infection suggests that EDTA-induced pseudothrombocytopenia may be related to anti-SARS-CoV-2 IgG or IgM antibodies. We should acknowledge the possibility that pseudothrombocytopenia may also appear in some patients after seroconversion after the launch of large-scale vaccination programs.

Associations of vascular and bone status in arthritis patients.

Cardiovascular (CV) disease and osteoporosis (OP) have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Bone and vascular biomarkers and parameters along with the effect of 1-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS. Thirty-six patients treated with etanercept or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were previously assessed by ELISA. Bone density was measured by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) were assessed by ultrasound. Multiple correlation analyses indicated associations between bone and vascular markers. Osteoprotegerin, sclerostin and cathepsin K were significantly associated with FMD, IMT and PWV, respectively (p < 0.05). Moreover, total and trabecular BMD determined by QCT inversely correlated with IMT (p < 0.05). On the other hand, among vascular parameters, platelet-derived growth factor BB and IMT correlated with DXA femoral and QCT total BMD, respectively (p < 0.05). In the RM-ANOVA analysis, anti-TNF treatment together with baseline osteocalcin, procollagen 1 N-terminal propeptide (P1NP) or vitamin D3 levels determined one-year changes in IMT (p < 0.05). In the MANOVA analysis, baseline disease activity indices (DAS28, BASDAI), the one-year changes in these indices, as well as CRP exerted effects on multiple correlations between bone and vascular markers (p < 0.05). As the pattern of interactions between bone and vascular biomarkers differed between baseline and after 12 months, anti-TNF therapy influenced these associations. We found a great number of correlations in our RA and AS patients undergoing anti-TNF therapy. Some of the bone markers have been associated with vascular pathophysiology, while some vascular markers correlated with bone status. In arthritis, systemic inflammation and disease activity may drive both vascular and bone disease.

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.

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".

Lower educational status interferes with maternal iodine intake during both pregnancy and lactation.

OBJECTIVE: To investigate factors affecting conscious iodine intake among pregnant and lactating women in a rural area in Hungary. METHODS: Pregnant women were studied and followed during lactation. Urinary and breast milk iodine concentration (UIC and MIC) were measured by inductively coupled plasma mass spectrometry. Potential interfering factors, including age, educational status and smoking were assessed. RESULTS: During pregnancy and lactation, mild iodine deficiency was observed; median UIC were 66 and 49 µg/L, respectively. Educational status was found to be a strong determinant of both iodine nutrition and smoking status during pregnancy (P < 0.01 and P < 0.001) and lactation (P < 0.001 and P < 0.01). While smoking and non-smoking lactating mothers had similar concentrations of urinary iodine (median UIC: 47 and 51 µg/L, P = 0.95), the breast milk of smoking mothers contained less iodine (median MIC: 150 and 203 µg/L, P = 0.03). CONCLUSIONS: Both low iodine intake and smoking contribute to the higher risk of iodine deficiency in women with lower educational status. In smokers, MIC is often low in spite of normal UIC, presumably due to the iodine transport blocking effect of the cigarette smoke towards breast milk; normal UIC may be misinterpreted as sufficient iodine supply towards the child. Antenatal health promotion strategies should focus on young women with lower educational status, even in regions where sufficient iodine intake has been achieved in non-pregnant adults.

The 4G/5G Polymorphism of Plasminogen Activator Inhibitor Type 1 is a Predictor of Moderate-to-Severe Thyroid Eye Disease.

INTRODUCTION: Thyroid eye disease (TED) is an autoimmune disease of the orbits. Once developed, complete cure is rare. Plasminogen activator inhibitor type 1 (PAI-1) contributes to remodeling of connective tissue and has a central role in the pathogenesis of TED. We aimed to test if the 4G/5G polymorphism of PAI-1 is a predictor of the development of moderate-to-severe TED. METHODS: A total of 185 patients with Graves' disease, 87 of them with TED, 98 without TED, as well as 201 healthy controls, were studied. Genomic DNA was isolated from peripheral blood samples. The 4G/5G polymorphism of the PAI-1 gene was analyzed by allele-specific PCR, and the distribution of genotypes was calculated in each group. Plasma PAI-1 and thyroid hormone levels were measured by ELISA and ECLIA, respectively. RESULTS: The 4G/4G genotype was associated with the development of moderate-to-severe TED (OR = 2.54; 95% CI: 1.26-5.14; p < 0.01). The 4G/5G polymorphism of PAI-1 was not a predictor of plasma PAI-1 levels. CONCLUSION: The 4G/4G genotype of PAI-1 is a risk factor for the development of moderate-to-severe TED. Patients with Graves' disease who harbor this genotype may be candidates for special attention towards the development of TED.