ABSTRACT Background Insoluble fibre (IF) may reduce the risk factors of type 2 diabetes development, but evidence on its short‐term effects is limited. The influence of IF on oxidative stress markers, including reduced glutathione (GSH) and antioxidant enzymes, as well as on leukocyte telomere length (LTL), remains poorly studied. Coronavirus disease (COVID‐19) occurring before or during IF interventions may influence study outcomes. Methods The study included 29 adults with impaired fasting glucose (IFG) who received 15 g/day of IF for 3 months. Seven participants had a recent history of COVID‐19, defined as PCR‐confirmed infection within 6 months before the intervention or COVID‐19‐like symptoms during the study. Fasting plasma glucose, 2‐h plasma glucose (2hPG) during a WHO oral glucose tolerance test, glycated haemoglobin (HbA1c) and GSH were assessed at baseline and after 3 months. Fat mass (FM), blood pressure (BP), LTL, superoxide dismutase and catalase (CAT) were also measured. Results In participants without COVID‐19 (n = 22), IF intake was associated with reductions in 2hPG, HbA1c, FM and GSH, along with an increase in systolic BP. In the COVID‐19 group (n = 7), HbA1c decreased, while both systolic and diastolic BP increased. No significant changes in LTL, superoxide dismutase or CAT levels were observed in either group. Conclusion Short‐term IF supplementation in individuals with IFG improved selected glycaemic parameters but was accompanied by unexpected reductions in GSH and increases in blood pressure. These findings indicate complex physiological responses to IF that warrant further investigation. Trial Registration ClinicalTrials.gov identifier: NCT04283201

Most previous studies aimed to establish etiological signatures of thyroid tumors compared sporadic papillary thyroid carcinomas (sPTC) and PTC that develop in individuals exposed to ionizing radiation during childhood. However, such approaches may lead to a biased signature combining exposure markers independent of the carcinogenic process and markers of radiation-induced carcinogenesis. We analyzed the miRNome (Affymetrix) and transcriptome (RNA sequencing) of a series of normal thyroid tissues and PTC from Ukrainian individuals contaminated with iodine-131 released by the Chornobyl Nuclear Power Plant in 1986 at high (> 0.5 Gy; N = 9) or low (< 50 mGy; N = 12) thyroid radiation doses, and from unexposed Ukrainian individuals (N = 28). First, the six sample groups were analyzed jointly using partial least squares discriminant analysis (sPLS-DA) to assess whether normal tissues and PTC shared common multi-omic signatures associated with exposure history, independent of carcinogenesis. Next, we applied a multiblock sPLS-DA (DIABLO) to isolate markers associated with exposure in the three normal tissue groups. Then, using the remaining miR and genes from the datasets not associated with exposure, we searched for a multi-omics signature associated with a difference in the carcinogenic process. sPLS-DA analysis of the six sample groups showed that normal tissues and PTC from exposed individuals shared a common multi-omics signature (58 miR/snoRNA, 50 genes) compared to unexposed samples. Our DIABLO analysis identified 44 miR/snoRNA and 45 genes exposure signatures distinguishing exposed from unexposed normal tissues. These signatures, when applied to PTC groups, supported that PTC developed after radiation exposure exibited exposure markers independent of any carcinogenic process. In addition to this exposure signature, we identified 39 miR/snoRNA and 64 genes signatures that identified the PTC developed after radiation exposure which deviated significantly from the sPTC profile. Normal tissues and PTC from exposed individuals exhibit a common molecular long-term memory of exposure history. Furthermore, PTC developed after radiation exposure display dose-dependent molecular specificities compared to sPTC. As PTC associated with low doses are mainly subclinical sPTC revealed by screening in the post-Chornobyl population, the proposed multi-omic signature could be attributable to sPTC developed in an exposed thyroid gland.

Background. Survivin is a member of Inhibitors of Apoptosis proteins (IAP) family. It is expressed in actively proliferating cells, and is upregulated in most cancers; consequently, it has received significant attention as a potential oncotherapeutic target. Akt is a central signalling molecule of the phosphoinositide 3-kinase (PI3K)/Akt signalling pathway. It is a serine/threonine-specific protein kinase and involved in apoptosis, proliferation, transcription and migration. Aberrant activation of this pathway has been identified in a wide range of cancers and thyroid as well. The aim of the study was to compare the expression of survivin and activation of protein kinase Akt in the tissues of patients with goiter, multinodular goiter (MNG), papillary thyroid carcinoma (PTC) with and without metastasis (Mts) to the lymph nodes.Materials and methods. Postoperative specimens of tumor tissue, metastasis (Mts), benign neoplasms (goiters) and conditionally normal tissue were used for the studies. The expression of survivin mRNA was determined using real-time polymerase chain reaction (qPCR). The expression of Akt was determined using Western-blotting.Results. The obtained data indicate that the expression of the survivin mRNA in PTC tissue and Mts significantly exceeds the level of its expression in conditionally normal (more than 4.5 times) and goiter tissues. The expression of survivin in PTC without metastasis more than three times lower compared to PTC with metastasis. In metastasis the level of IAP mRNA expression is lower than in the primary tumor. The expression of the phosphorylated (activated) form of Akt in PTC tissue and Mts significantly higher than level of its expression in conditionally normal tissue. The level of Akt in Mts is almost 4 times higher than in the primary tumor and almost 8 times higher than in the conditionally normal tissue.Сonclusions. Thus, an increased survivin mRNA expression in papillary thyroid carcinoma may be marker of metastasis formation. It can also be used to differentiate between benign and malignant thyroid lesions. The level of the phosphorylated (activated) form of Akt is especially high in metastasis.

Background:The ongoing war in Ukraine have exposed the population to unprecedented stressors the long-term metabolic consequences of which remain insufficiently characterised. This study evaluated changes in glycaemic control and related biomarkers in the Ukrainian population during ongoing war between 2021 and 2024. Methods:This large-scale, single centre repeated cross-sectional study analysed routine laboratory data across Ukraine from January 2021 to December 2024. We included a convenience sample of adults aged 18-90 years with complete demographic data who underwent on fasting plasma glucose (FPG) (108,346 individuals), of whom 86,077 also had glycated haemoglobin (HbA1c) results. Additional data was available for 2502 insulin and 9000 cortisol measurements. Biomarker trends were assessed annually and quarterly, stratified by sex, age, and geographic region, and categorised as corresponding to normoglycemia, prediabetes, and diabetes. Findings:In 2021, median HbA1c was 5.71% (interquartile range; IQR 5.34-6.34), with 28.7% of individuals in the prediabetic and 22.3% in the diabetic range. By 2024, median HbA1c rose to 5.91%, with prediabetes increasing from 28.7% to 37.7%, and diabetic levels rate growing from 22.3% to 26.4%. As a result, 64% of all individuals tested in 2024 had HbA1c above the normoglycaemic threshold. Women and working-age adults showed the greatest glycaemic deterioration, despite men having higher absolute levels. Interpretation:The Ukrainian population experienced significant metabolic deterioration during the war. Rising HbA1c and the growing prevalence of prediabetes and diabetes, particularly among women and younger adults, indicate escalating cardiometabolic risks. Future prospective longitudinal studies are needed to evaluate the long-term effectiveness of integrated metabolic and psychosocial interventions in conflict-affected populations. Funding:National Research Foundation of Ukraine.

Deletion of the long q arm of chromosome 22 (22qDEL) is the most frequently identified recurrent somatic copy number alteration observed in papillary thyroid carcinoma (PTC). Since its role in PTC is not fully understood, we conducted a pooled analysis of genomic characteristics and clinical correlates in 1094 primary tumors from four published PTC genomic studies. The majority of PTC cases with 22qDEL exhibited arm-level loss of heterozygosity (86%); nearly all PTC cases with 22qDEL had losses in 22q12 and 13, which together constitute 70% of the q arm. Our analysis confirmed that 22qDEL occurs more frequently with RAS point mutations (50.4%), particularly HRAS (70.3%), compared with other PTC drivers (9.3%), supporting the conclusion that 22qDEL is unlikely to be a solitary driver of PTC but possibly an important co-factor in carcinogenesis, particularly in PTCs with RAS driver mutations. Differential RNA expression analyses revealed downregulation of most genes located on chromosome 22 in cases with 22qDEL compared to those without 22qDEL. Many differentially expressed genes are drawn from immune response and regulation pathways. These findings highlight the value of further investigations into the contributions of 22qDEL events to PTC, perhaps mediated through immune perturbations.

Metastases are the leading cause of death from malignant tumors. Hypoxia is a hallmark of all solid tumors and their metastases, including papillary thyroid carcinoma (PTC). This leads to activation of the hypoxia-inducible factor (HIF) family of transcription factors, which modulate gene expression within both tumor cells and immune cells within the tumor microenvironment, influencing tumor progression and treatment response. The aim of the study was to compare the levels of HIF-1α in blood and tissue samples of follicular adenoma, goiter, papillary thyroid carcinoma, metastases, and conditionally normal tissue. Materials and methods. Postoperative samples of tissue and blood plasma, obtained from the surgical department of the Institute's clinic, were used for research. Patients with РТС, PTC + metastases, follicular adenoma and goiters (88 samples in total) participated in the study. Plasma from 5 individuals without thyroid disease and other chronic diseases, representative for age, was used as a control. The amount of HIF-1α was determined using enzyme immunoassay kits. Student's t-test was used to compare data groups. Values of P < 0.05 were considered significant. Results. The level of HIF-1α in the tissue of nodular goiter exceeded the levels in conditionally normal tissue by 2 times. A more then 2.5 ratio was observed in РТС tissues without metastases. The concentration of HIF-1α in the tumor tissue of the РТС with metastases was higher than in the conditionally normal tissue by more then 3.5 times. The level of HIF-1α in metastases was much lower comparing tumor tissue. In blood plasma of patients with PTC and metastases the concentration of the HIF-1α was more then 3 times higher than in control (healthy people) and more then 2 times higher than in tumor tissue of РТС without metastases. Conclusions. Our data indicate significant differences in the concentration of HIF-1α between tumor tissues of papillary thyroid carcinoma with and without metastasis. It should be emphasized the fact that in the blood plasma the level of HIF-1α was also significantly higher in papillary thyroid carcinoma patients with metastasis than in healthy people and papillary thyroid carcinoma patients without metastases. The latter circumstance can become the basis for the preoperative prognosis of the development of metastases in papillary thyroid carcinoma.

OBJECTIVE:A relationship among hypothyroidism and lipid disorders is well established. However, current evidence and guidelines do not support the use of thyroid hormones (TH) in euthyroid patients with hyperlipidaemia as potential harms are considerable. This European survey investigated the use of TH in euthyroid patients with severe hypercholesterolemia as a complementary treatment. DESIGN:Data were derived from the THESIS (Treatment of Hypothyroidism in Europe by Specialists) project that surveyed TH use. Univariable and multivariable analyses were used to explore associations. RESULTS:Out of 17,232 invitations, 5695 (33.0%) valid responses were received, and of these, 328 (5.8%) stated that TH are indicated in euthyroid patients with severe hypercholesterolemia. Univariable analyses disclosed significant differences and associations: (a) more non-endocrinologists (8.9%) than endocrinologist (5.4%) used TH (p < 0.001), (b) the number of hypothyroid patients treated per year was inversely related to use of TH (p = 0.024), (c) members of international endocrine/thyroid societies were more likely to use TH than non-members (p < 0.001), (d) significant variations by country and geographical region (p < 0.001), and (e) inverse relationship between gross national income per capita (GNIPC) and TH use (p < 0.001). Multivariable analyses yielded significant associations between use of TH, and male gender, specialty and GNIPC (p < 0.001). CONCLUSIONS:This study suggests that a small but noteworthy minority of European thyroid specialists may be using TH to treat of severe hypercholesterolemia in euthyroid patients. If confirmed, this finding highlights the importance of raising awareness among thyroid specialists, professional societies, and healthcare providers to ensure adherence to evidence-based practices.

Diabetes mellitus (DM) and cardiovascular disease (CVD) are factors that complicate the course of COVID-19, and the last one provokes further complications of these diseases. Oxidized low-density lipoproteins (oxLDL) play a crucial role in the occurrence of atherosclerosis. Interleukin-17 (IL-17) regulates NF-κB activity and stimulates the expression of IL-6, which are the key factors that cause a cytokine storm in COVID-19. Lipoprotein(a) (Lp(a)) is a genetically determined risk factor for atherosclerosis and other CVDs. The objective: to study the effect of sodium-dependent glucose cotransporter type 2 inhibitors (SDG-2i) on the levels of oxLDL, IL-17A and Lp(a) in the blood of patients with DM who had COVID-19 in 2020–2023. Materials and methods. The levels of oxLDL, IL-17A and Lp(a) were determined using enzyme-linked immunosorbent assay kits (Elabscience, USA). Results. SGLT-2i drugs effectively reduce the amount of oxLDL in the blood of patients who have recovered from COVID-19. The data obtained indicate a high level of IL-17A in the blood plasma of diabetic patients who have recovered from COVID-19 2–4 years ago. In the absence of treatment of patients with DM with glucose-lowering drugs after COVID-19 the level of IL-17A reaches high values. Patients who recovered from COVID-19 in 2020–2023 had high level of Lp(a). SGLT-2i significantly reduced the concentration of IL-17A, Lp(a) in the blood plasma of patients in the post-COVID-19 period. Conclusions. SGLT2 inhibitors were found to markedly reduce plasma concentrations of oxLDL, IL-17A, and Lp(a) in patients with DM during the post-COVID-19 period. In the absence of glucose-lowering therapy in patients with DM during acute COVID-19, plasma levels of oxLDL, IL-17A, and Lp(a) tend to reach markedly elevated values. Thus, treatment with SGLT2 inhibitors may represent a promising therapeutic strategy for mitigating elevations in oxLDL, IL-17A, and Lp(a) among individuals recovering from COVID-19, thereby potentially improving clinical outcomes in patients with DM in the post-COVID-19 phase.

Background: Although childhood exposure to radioactive iodine-131 (I-131) is an established risk factor for thyroid cancer, evidence for an association with thyroid nodules is less clear. The objective of this study is to evaluate the association between childhood I-131 exposure and prevalence of ultrasound-detected thyroid nodules overall and by nodule histology/cytology (neoplastic/suspicious/non-neoplastic), size (<10 mm/>= 10 mm), and number (single/multiple). Methods: This is a cross-sectional study of radiation dose (mean = 0.53 gray, range: 0.0003-31 gray) and screen-detected thyroid nodules conducted in 1998-2000 (median population age 21.5 years) in a cohort of 13,243 residents of Ukraine who were under 18 years at the time of the Chornobyl accident on April 26, 1986. Excess odds ratios per gray (excess odds ratio [EOR]/Gy) and confidence intervals (CIs) were estimated using logistic regression. Results: Among 13,078 eligible individuals, we identified 358 (2.7%) with at least one thyroid nodule. Significantly increased dose-response associations were found for all nodules and nodule groups with doses <5 Gy except individuals with non-neoplastic nodules. Among individuals with doses <5 Gy, the EOR/Gy for neoplastic nodules (5.35; CI: 2.19-15.5) was significantly higher than for non-neoplastic nodules (0.24; CI: 0.07-0.74), but the EOR/Gy did not vary by nodule size or number. Conclusions: Childhood exposure to I-131 is associated with an increased risk of thyroid nodules detected 12-14 years following exposure, and the risk for neoplastic nodules is higher than for non-neoplastic nodules. Analyses of incident thyroid nodules may help clarify dose-response patterns by nodule characteristics and provide insights into thyroid nodule etiology.

Abstract Deletion in the long arm of chromosome 22 (22qDEL) is the most prevalent somatic copy number alteration (SCNA) observed in papillary thyroid carcinoma (PTC). Despite its recurrence, the specific characteristics and role of 22qDEL in PTC have not been fully studied. We conducted a pooled analysis of 22qDEL by integrating patient and clinical information and molecular profiles from 1,094 primary PTC tumors across four major published PTC genomic studies: The Cancer Genome Atlas (TCGA) PTC profile study, the National Cancer Institute (NCI) post-Chornobyl PTC study, the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets (MSKCC-IMPACT) PTC cases, and the Seoul National University (SNU) thyroid cancer profile study. The majority of PTC with 22qDEL demonstrated arm-level loss of heterozygosity (86%). Even in PTC cases with partial 22qDEL, we observed a loss across 70% of chromosome 22, encompassing regions 22q12 and 22q13, which harbors known cancer genes (NF2 and CHEK2). More than 90% of 22qDEL co-occurred with established oncogenic drivers of PTC, though a full assessment of PTC drivers was not available for all cases. 22qDEL occurred more frequently with RAS point mutations (50.4%) than other drivers (9.3%). A higher fraction of 22qDEL was clonal in RAS-driven PTCs (78.3%), suggesting 22qDEL occurs early in RAS-driven tumor development. We did not observe any association between 22qDEL and established PTC risk factors such as age, sex, and radiation, nor with clinical features including tumor size, multifocality, and metastasis (p-values>0.22). RNA sequencing gene expression analysis based on 22qDEL status revealed downregulation of most genes residing on chromosome 22q and significant differential expression activity of immune-related genes, further implicating a role of immune dysregulation in PTC. Our study suggests that 22qDEL may not act as a primary driver of PTC but plays an important role as a co-factor of RAS point mutations, which could further drive PTC development. Citation Format: Olivia W. Lee, Danielle Karyadi, Stephen Hartley, Weyin Zhou, Mitchell Machiela, Mykola Tronko, Tetiana Bogdanova, Liudmyla Zurnadzhy, Lindsay Morton, Stephen Chanock. Characterization of somatic copy number deletion of chromosome 22q in papillary thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1762.

The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether “Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions”. Of 17,232 invitations 5695 responses were received (33

Vitamin D deficiency (VDD) is a global problem, however, there were no Ukrainian guidelines devoted to its screening, prevention, and treatment, which became the reason for the Consensus creation. This article aimed to present the Consensus of Ukrainian experts devoted to VDD management. Following the creation of the multidisciplinary Consensus group, consent on the formation process, drafting and fine-tuning of key recommendations, and two rounds of voting, 14 final recommendations were successfully voted upon. Despite a recent decrease in VDD prevalence in Ukraine, we recommend raising awareness regarding VDD’s importance and improving the strategies for its decline. We recommend screening the serum 25-hydroxyvitamin D (25(OH)D) level in risk groups while maintaining a target concentration of 75–125 nmol/L (30–50 ng/mL). We recommend prophylactic cholecalciferol supplementation (800–2000 IU/d for youthful healthy subjects, and 3000–5000 IU/d for subjects from the risk groups). For a VDD treatment, we recommend a short-term administration of increased doses of cholecalciferol (4000–10,000 IU/d) with 25(OH)D levels monitored after 4–12 weeks of treatment, followed by the use of maintenance doses. Additionally, we recommend assessing serum 25(OH)D levels before antiosteoporotic treatment and providing vitamin D and calcium supplementation throughout the full course of the antiosteoporotic therapy.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices.Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses.Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita.Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

BACKGROUND:Treatment of simple goiter (SG) growing over time with thyroid hormone (TH) therapy is discouraged by international guidelines. PURPOSE:To ascertain views of European thyroid specialists about TH treatment for euthyroid patients with growing SG and explore associations with management choice. METHODS:Online survey on the use of TH for growing SG among thyroid experts from 28 European countries. RESULTS:The response rate was 31.5% (5430/17,247). Most respondents were endocrinologists. Twenty-eight percent asserted that TH therapy may be indicated in euthyroid patients with a growing SG. National and regional differences were noted, from 7% of positive responses in The Netherlands to 78% in Czech Republic (p < 0.0001). TH was more frequently prescribed by respondents over 40 years old (OR 1.77, 2.13, 2.41 if 41-50, 51-60, >60, respectively), and working in areas of former iodine insufficiency (OR 1.24, 95% CI 1.03-1.50). TH was less frequently prescribed by endocrinologists (OR 0.77, 95% CI 0.62-0.94) and respondents working in Southern Europe (OR 0.40, 95% CI 0.33-0.48), Northern Europe (OR 0.28, 95% CI 0.22-0.36) and Western Asia (OR 0.16, 95% CI 0.11-0.24) compared to Western Europe. Associations with respondents' sex, country, availability of national thyroid guidelines, and gross national income per capita were absent or weak. CONCLUSIONS:Almost a third of European thyroid specialists support treating SG with TH, contrary to current guidelines and recommendations. This calls for urgent attention.

Increased thyroid cancer incidence has been one of the principal adverse health effects of the Chornobyl (Chernobyl) nuclear power plant accident. Accurate dose estimation is critical for assessing the radiation dose-response relationship. Current dosimetry estimates for individuals from the Chornobyl Tissue Bank (CTB) are based only on the limited information on their places of residence at the time of the accident and/or at the time of surgery for thyroid cancer. The present study aimed to assess whether additional residential and dietary history data collected during personal interviews would substantially impact dose estimates. This paper presents an assessment of thyroid doses from 131I intake for the 197 exposed individuals from the CTB with pathologically confirmed papillary thyroid cancer. Thyroid doses, which had been calculated for these individuals in 2010, were revised in this study using the recently substantially revised ‘Thyroid Dosimetry 2020 system for Ukraine’ (TDU20). In addition, residence and diet history data were collected during personal interviews with individuals for whom dosimetry-related data were scarce. The arithmetic mean of thyroid doses estimated in this study was 510 mGy (previously 700 mGy), while the median was 81 mGy (previously 120 mGy). A rather wide range of thyroid doses from zero to 11.9 Gy (previously up to 15.0 Gy) was observed among study participants. The uncertainties in doses were characterized by the geometric standard deviation of 1,000 individual stochastic doses. As a result, the geometric standard deviation varied from 1.3 to 5.3 with an overall arithmetic mean of 2.7 and a median of 2.9. This study clearly showed that the use of individual questionnaire data in dose assessment of individuals who completed personal dosimetry interviews had a noticeable impact on the thyroid dose values: the thyroid doses changed by more than 100 mGy in 31 out of 104 (29.8

Hypertriglyceridemia as an independent and potentially modifiable risk factor. Prevention and treatment strategy Maria S. Cherska, Mykola D. Tronko, Valeriia L. Orlenko, Liubov K. Sokolova, Olena V. Bolshova, Olesia V. Zinych, Nataliia A. Sprynchuk, Olena V. Dobrovynska, Nataliia M. Kushnarova, Olena I. Pavlenko State Institution «V. P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine», 69 Vyshgorodska St., Kyiv 04114, Ukraine Resume. The review highlights the disorder of triglyceride metabolism, which is an independent and potentially modifiable risk factor, important for both individual and population prevention and treatment strategies. Hypertriglyceridemia has a high prevalence worldwide against the background of the increasing prevalence of diabetes mellitus and associated metabolic disorders. Epidemiological studies indicate that from 10% to almost 25% of the adult population have elevated triglyceride levels. The prevalence of the disease varies and depends on race, ethnicity, and genetic heredity. Triglyceride levels inversely correlated with high-density lipoprotein (HDL-C) levels. The risk of cardiovascular disease (CVD) associated with hypertriglyceridemia has traditionally been explained by a reduction in the supposed protective effect of HDL-C, since elevated triglycerides are usually accompanied by a decrease in HDL-C. In previous studies evaluating the association between CVD and elevated triglycerides, adjustment for HDL-C often attenuated or even eliminated this association. However, recent data indicate a key role for triglyceride-rich lipoproteins (TGRLs) in the causative development of CVD, confirming that patients with hypertriglyceridemia do indeed have an increased CVD risk. Despite this, hypertriglyceridemia remains underdiagnosed and undertreated. In addition to CVD, hypertriglyceridemia can also lead to non-cardiac complications, such as hepatic steatosis (fatty liver disease) and acute pancreatitis. Keywords: treatment, hypertriglyceridemia, diabetes mellitus, pancreatitis, chylomicrons, genetics, complications

IntroductionThe radioiodine-refractory (RAI-R) recurrent papillary thyroid carcinomas (PTCs) are more frequent in elderly patients and have an unfavorable prognosis. Data on the prevalence and characteristics of RAI-R recurrent PTCs in patients of young and middle age with or without a history of radiation exposure in childhood are poorly described. The aim of the current study was: i) to determine the frequency of RAI-R recurrent PTCs among donors of the Chornobyl Tissue Bank (CTB) and analyze the clinicopathological features of primary tumors (PTs), primary metastases (PMTSs), recurrent metastases (RMTSs) and risk factors for RMTS, and ii) to determine the immune checkpoint status (ICS) of the RAI-R recurrent PTCs and to assess the factors associated with ICS positivity.MethodsSixty RAI-R recurrent PTCs (46 exposed to radiation and 14 non-exposed, 2.5% of all cases registered with the CTB) from the Ukrainian patients aged up to 48 years were identified.ResultsThe clinicopathological characteristics of the PTs moderately to weakly resembled those of the PMTS and RMTS from the same patients while the metastatic tissues were highly similar. The multivariate model of RMTS included the dominant solid-trabecular growth pattern of the PT, cystic changes, N1b metastases, and the probability of a causation (POC) of PTC by radiation as risk factors. Among these factors, the lateral PMTS (N1b) had the strongest effect. The longer period of latency (a POC component) was the second statistically significant characteristic. ICS percent agreement between the PT and RAI-R RMTS was 91.5%; 23.7% of PTs and 28.8% of RMTSs had positive ICS (positive PD-L1 tumor epithelial cells (TECs) and positive PD-L1/PD1 tumor-associated immune cells). ICS positivity of PTs was associated with pronounced oncocytic changes and high density of the p16INK4A-positive TECs in the invasive areas of PTs. In RMTSs, ICS positivity was associated with pronounced oncocytic changes and Ki-67 labeling index ≥ 4.5% of PTs, and the dominant solid-trabecular growth pattern, Ki-67 labeling index ≥ 7.6% and p16INK4A-positivity of RMTS.DiscussionThe findings are of clinical relevance and may be useful for developing individual treatment approaches for patients with RAI-R recurrent PTCs possibly involving immunotherapy.

OBJECTIVES:The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN:The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS:A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS:A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.