Aging profoundly alters the neuromotor and cognitive systems that support gait control, leading to increased variability and instability that predict functional decline and dementia risk. In this pilot study, conducted to inform the design of the Semmelweis Study gait assessment pipeline, we examined how aging and cognitive load influence the magnitude and temporal organization of gait fluctuations. The Semmelweis Study is a large, prospective workplace cohort at Semmelweis University designed to identify the determinants of unhealthy aging and the mechanisms that preserve functional resilience across the life course. One hundred three adults aged 23–87 years completed single- and dual-task walking trials on a 20-foot pressure-sensitive walkway. Gait variability was quantified using the median absolute deviation (MAD) and coefficient of variation (CoV) of key spatiotemporal parameters, while permutation entropy (PE) captured the complexity of stride-to-stride dynamics. Aging was associated with progressive increases in both the variability (MAD, CoV) and changes in orderliness (PE) of gait fluctuations, particularly under dual-task conditions, suggesting a dual contribution of neuromotor degradation and compensatory recruitment of higher-order control processes. The amplification of these effects during cognitive load highlights the vulnerability of cognitive–motor integration with advancing age. By integrating robust, relative, and nonlinear variability metrics within a unified analytical framework, this study provides a multidimensional characterization of gait control and establishes sensitive indicators for detecting early functional decline. Within the translational framework of the Semmelweis Study, these quantitative gait measures—together with vascular, metabolic, and cognitive assessments—are expected to serve as informative components of a comprehensive biomarker system aimed at identifying early determinants of unhealthy brain aging and guiding preventive strategies to promote healthy longevity.

Workplace stress is an increasingly recognized determinant of both workforce well-being and healthy aging. However, few longitudinal studies have systematically integrated stress assessment into large occupational cohorts with an explicit focus on aging processes. The Semmelweis Study, launched in 2024, addresses this gap by embedding validated stress assessment tools into a comprehensive, multidisciplinary framework designed to explore the biological, psychological, and social determinants of healthy and unhealthy aging in a university workforce. This paper presents the conceptual foundation, methodology, and early applications of workplace stress assessment within the Semmelweis Study. We outline research hypotheses linking stress to aging outcomes and describe a pilot investigation among a high-risk subgroup-conductors trained at the András Pető Faculty of Semmelweis University. Stress is assessed using validated psychometric tools, including the Perceived Stress Scale, Effort-Reward Imbalance Questionnaire, Maslach Burnout Inventory, resilience measures, and social support scales. These are integrated with biological aging markers, cognitive assessments, mental health indicators, lifestyle factors, and detailed occupational data. A pilot study applying this framework was conducted among conductors, a professional group known for high emotional demands and role strain. Preliminary findings indicate elevated stress levels and burnout symptoms among conductors, with workload, perfectionism, and emotional burden identified as key stressors. Participants expressed strong interest in workplace-based stress management resources, informing plans for targeted interventions within this group. The integration of workplace stress assessment into the Semmelweis Study offers a novel platform for advancing healthy aging research and informing real-world prevention strategies. By systematically linking stress measurement to aging outcomes, and by addressing occupational stress through targeted interventions, Semmelweis University exemplifies how academic institutions can act as both research leaders and models of healthy workplace practices. These efforts align with the Semmelweis-EUniWell Workplace Health Promotion Model Program and contribute to broader European efforts to promote resilience, well-being, and healthy longevity across the working life course.

AimsKnowledge on insulin treatment simplification with fixed ratio combinations (e.g. iGlarLixi, combination of insulin glargine and lixisenatide) is limited. Our aim was to examine long-term effectiveness and safety of treatment simplification with iGlarLixi in type 2 diabetes.Materials and methodsWe report a single-centre, observational study of n=51 type 2 diabetes patients with HbA1c ≤ 7.5% (58 mmol/mol) who switched from basal-bolus or premixed insulins to iGlarLixi in 01/JAN/2017-30/JUN/2023 with up to 61-month follow-up. Outcomes were trajectories of HbA1c, BMI, insulin need, and risk of incident hypoglycaemia based on mixed linear models.ResultsParticipants (53% women) were 69.4 years old, BMI was 30.6 kg/m2, diabetes duration 13 years, HbA1c 6.4% [46 mmol/mol]), and insulin dose 0.46 IU/kg at baseline. HbA1c remained stable over follow-up. BMI dropped to 29.4 kg/m2 (slope: 0.54, 95%CI: 0.34-0.73 kg/month) in the first 7 months, then remained stable. Insulin dose dropped by 0.20 IU/kg (95%CI: 0.17-0.24) at baseline, then remained stable. Risk of hypoglycaemia decreased from 50 to 21% (odds ratio [OR] 0.88, 95%CI: 0.82-0.95/months) during the first 10 months, then remained stable. Subgroup analyses showed increasing HbA1c within the non-diabetic range in patients with very low and improvement in those with higher values. Furthermore, the subgroup with large BMI and low insulin dose at baseline had stable BMI trajectory (vs a decrease in all other subgroups).ConclusionsSimplification of complex regimens with iGlarLixi in patients with good glycaemic control maintains glycaemic control with weight loss, reduced risk of hypoglycaemia, and lower insulin dose over 42 months.

OBJECTIVE:To explore trends of gestational diabetes (GDM) prevalence, as well as fasting, 1 h and 2 h post-load glucose and its determinants in Hungary between 2010 and 2017. DESIGN:Cross-sectional universal screening programme for GDM (3-point 75 g OGTT at 24-28 weeks of gestation). SETTING:Tolna County (South-Western Hungary). POPULATION:All singleton pregnancies between 2010 and 2017. METHODS:Participants with available co-variables (including 3-point OGTT) and deliveries ≥ 24 weeks of gestation were included (n = 7071, 88.4% of those eligible). Exposures (known GDM risk factors) were collected after delivery including BMI at early-pregnancy and at OGTT. MAIN OUTCOME MEASURES:Time trends of GDM occurrence (WHO-2013 diagnostic criteria) and fasting, 1 h, and 2 h post-load glucose. Analyses were done with multiple logistic and linear regression. RESULTS:The prevalence of GDM increased by 5% (95% CI: 4%-6%) from 15% to 20% between 2010 and 2017. Fasting, 1 h, and 2 h post-load glucose increased by 0.1 (95% CI 0.08-0.12), 0.5 (95% CI 0.4-0.6) and 0.2 (95% CI 0.1-0.3) mmol/l, respectively. On the basis of fully adjusted models including both BMI measures, a significant proportion (25%-30%) of this increase for GDM diagnosis and for fasting glucose was explained by increasing calendar trend in BMI measured at the OGTT. Smaller proportions of 1 h (12%) and 2 h (NS) post-load glucose were explained by BMI changes. CONCLUSIONS:Our finding suggests that BMI-gain during the first two trimesters of pregnancy is a more important determinant of the GDM epidemic in Hungary than early-pregnancy BMI. To prevent the further increase in the prevalence of GDM, both factors should be targeted.

Abstract Alzheimer's disease (AD) is anticipated to emerge as a dominant contributor to global disease burden in the coming decades, coinciding with an unprecedented expansion of disease-modifying pharmacological development pipelines. This mini-review analyzes global, regional, and national trends in AD incidence and prevalence between 2010 and 2019 and discusses their implications for future pharmacological research and therapeutic implementation. In 2019, the global incidence and prevalence of AD were estimated at 93.52 (80.35–106.40) and 667.20 (572.24–762.80) per 100,000 individuals, respectively. The highest rates were observed in Japan, the European Union, and the United States, with Japan reporting an incidence of 421.62 and a prevalence of 3079.09 per 100,000, whereas the lowest rates were documented in Israel and China. Globally, annual increases in incidence and prevalence were 0.239 (0.215–0.261) and 0.256 (0.233–0.277) per 100,000, respectively, with the most pronounced changes observed in East Asian countries. Age-standardized analyses revealed broadly similar trends across regions, underscoring population aging as a dominant driver of AD occurrence, while additional contributors include improved diagnostic intensity, reduced disease-specific mortality, and shifts in lifestyle and cardiometabolic risk profiles. Importantly, these epidemiological patterns have direct relevance for pharmacology-driven AD research. The rapid expansion of disease-modifying pharmacological therapies, including anti-amyloid, anti-tau, and emerging vascular- and inflammation-targeted agents, necessitates large-scale, geographically diverse clinical trials and health-system preparedness for therapeutic deployment. Country-specific prevalence and incidence data are therefore critical for optimizing trial site selection, forecasting treatment demand, and enabling precision pharmacology approaches that account for demographic structure, comorbidity burden, and regional risk profiles.

With the aging population in Europe, particularly Hungary, unhealthy aging is emerging as a growing public health challenge. Physical inactivity is a modifiable risk factor for age-related diseases and remains highly prevalent. Increasing daily physical activity is a key strategy for extending health span. Step-count-based interventions, including motivational interviewing and email-based feedback, have been shown to promote physical activity, but direct comparisons of these approaches in workplace settings are limited. Conducted within the framework of the Semmelweis-EUniWell Workplace Health Promotion Model Program, this study aimed to evaluate the effect of two scalable workplace interventions compared with a control group on increasing daily step count and total weekly physical activity, and to examine the sustainability of intervention effects over six months. In this three-armed randomized controlled trial, Semmelweis university employees were assigned to one of three groups: combined program of face-to-face motivational interviewing and email-based motivation, email-based motivation program alone or a control group with no intervention. Daily step counts were self-reported using participants' personal smart devices and recorded at baseline, every two weeks during an eight-week intervention, and at 1-, 3-, and 6-month follow-up. Total weekly physical activity was assessed using the International Physical Activity Questionnaire. Changes were modeled and compared with mixed model regression. A total of 155 employees participated (49 in the face-to-face motivational interviewing group, 53 in the email-based motivation group, and 53 controls). Both interventions were associated with increased step counts during the intervention period compared with control, with an average increase of 1,624 steps per day. Initial improvements were comparable between the two intervention groups, but the decline in step count during follow-up was slower in the face-to-face group. Additionally, at one-month post-intervention, the face-to-face group also showed a significantly higher total MET-minutes per week (997 MET/week) compared with controls. Both face-to-face and email-based interventions were effective in increasing physical activity during the intervention period. The slower decline in the face-to-face group suggests differences in sustainability between approaches. The results suggest a potential short-term benefit of workplace health promotion programs on physical activity, and that motivational interviewing may support longer-term maintenance of gains. Embedding such hybrid interventions into broader healthy aging strategies, such as those promoted by the Semmelweis-EUniWell Workplace Health Promotion Model Program, offers a promising pathway to address the aging challenge in Hungary and across Europe. Looking ahead, artificial intelligence-driven tools could enhance these programs by delivering personalized feedback, adaptive goal setting, and real-time engagement at scale, complementing human-delivered motivational support and further extending their reach and impact.

BACKGROUND:Preexisting diabetes (PDM) increases the risk of maternal and perinatal mortality and morbidity. Reduction of maternal hyperglycemia prior to and during pregnancy can reduce these risks. Despite compelling evidence that preconception care (PCC), which includes achieving strict glycemic goals, reduces the risk of congenital malformations and other adverse pregnancy outcomes, only a minority of individuals receive PCC. Suboptimal pregnancy outcomes demonstrated in real-world data highlight the need to further optimize prenatal glycemia. New evolving technology shows promise in helping to achieve that goal. Dysglycemia is not the only driver of poor pregnancy outcomes in PDM. The increasing impact of obesity on pregnancy outcomes underscores the importance of optimal nutrition and management of insulin sensitizing medications during prenatal care for PDM. OBJECTIVE:To provide recommendations for the care of individuals with PDM that lead to a reduction in maternal and neonatal adverse outcomes. METHODS:The Guideline Development Panel (GDP) composed of a multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 10 clinically relevant questions related to the care of individuals with diabetes before, during and after pregnancy. The GDP prioritized randomized controlled trials (RCTs) evaluating the effects of different interventions (eg, PCC, nutrition, treatment options, delivery) during the reproductive life cycle of individuals with diabetes, including type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Systematic reviews queried electronic databases for publications related to these 10 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and develop recommendations. The approach incorporated perspectives from 2 patient representatives and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. RESULTS:In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest asking a screening question about pregnancy intention at every reproductive, diabetes, and primary care visit. Screening for pregnancy intent is also suggested at urgent care/emergency room visits when clinically appropriate (2 | ⊕OOO). This was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced glycated hemoglobin (HbA1c) at the first prenatal visit and congenital malformations.In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest use of contraception when pregnancy is not desired (2 | ⊕⊕OO). This was suggested based on indirect evidence in women with diabetes, where PCC-including contraception as a key component-showed a clinically significant association with improvements in first-trimester HbA1c and the rate of congenital malformations, together with indirect evidence from the general population regarding the reduction of unplanned pregnancies and pregnancy terminations with the use of contraception.In individuals with T2DM, we suggest discontinuation of glucagon-like peptide-1 receptor agonist (GLP-1RA) before conception rather than discontinuation between the start of pregnancy and the end of the first trimester (2 | ⊕OOO). This was suggested based on limited data on risk of exposure to GLP-1RA receptor agonists during pregnancy.In pregnant individuals with T2DM already on insulin, we suggest against routine addition of metformin (2 | ⊕OOO). This was suggested based on the GDP judgment that the benefit of adding metformin to insulin to achieve decrease in rates of large for gestational age infants did not outweigh the potential harm of increasing the risk of small for gestational age infants or adverse childhood outcomes related to changes in body composition.In individuals with PDM, we suggest either a carbohydrate-restricted diet (<175 g/day) or usual diet (>175 g/day) during pregnancy (2 | ⊕OOO). This was suggested based on the GDP judgment that the available evidence was limited and very indirect, resulting in significant uncertainty about the net benefits or harms. As such, the evidence was insufficient to support a recommendation either for or against a carbohydrate intake cutoff of 175 g/day.In pregnant individuals with T2DM, we suggest either the use of a continuous glucose monitor (CGM) or self-monitoring of blood glucose (SMBG) (2 | ⊕OOO). There is lack of direct evidence supporting superiority of CGM use over SMBG for T2DM during pregnancy. There is indirect evidence supporting improved glucometrics with the use of CGM for individuals with T2DM outside of pregnancy, substantial improvements in neonatal outcomes for individuals with T1DM using CGM during pregnancy and the potential for decreasing adverse pregnancy outcomes with improved glucometrics in individuals with T2DM.In individuals with PDM using a CGM, we suggest against the use of a single 24-hour CGM target <140 mg/dL (7.8 mmol/L) in place of standard-of-care pregnancy glucose targets of fasting <95 mg/dL (5.3 mmol/L), 1-hour postprandial <140 mg/dL (7.8 mmol/L), and 2-hour postprandial < 120 mg/dL (6.7 mmol/L) (2 | ⊕OOO). This was suggested based on indirect evidence that associated adverse pregnancy outcomes with a fasting glucose > 126 mg/dL (7 mmol/L).In individuals with T1DM who are pregnant, we suggest the use of a hybrid closed-loop pump (pump adjusting automatically based on CGM) rather than an insulin pump with CGM (without an algorithm) or multiple daily insulin injections with CGM (2 | ⊕OOO). This was suggested based on a meta-analysis of RCTs which demonstrated improvement in glucometrics with increased time in range (MD +3.81%; CI -4.24 to 11.86) and reduced time below range (MD -0.85%; CI -1.98 to 0.28) with the use of hybrid closed-loop pump technology.In individuals with PDM, we suggest early delivery based on risk assessment rather than expectant management (2 | ⊕OOO). This was suggested based on indirect evidence that risks may outweigh benefits of expectant management beyond 38 weeks gestation and that risk assessment criteria may be useful to inform ideal delivery timing.In individuals with PDM (including those with pregnancy loss or termination), we suggest postpartum endocrine care (diabetes management), in addition to usual obstetric care (2 | ⊕OOO). As the postpartum period frequently overlaps with preconception, this was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced HbA1c at the first prenatal visit and congenital malformations. CONCLUSION:The data supporting these recommendations were of very low to low certainty, highlighting the urgent need for research designed to provide high certainty evidence to support the care of individuals with diabetes before, during, and after pregnancy. Investment in implementation science for PCC is crucial to prevent significant mortality and morbidity for individuals with PDM and their children. RCTs to further define glycemic targets in pregnancy and refinement of emerging technology to achieve those targets can lead to significant reduction of harm and in the burden of diabetes care. Data on optimal nutrition and obesity management in pregnancy are lacking. More research on timing of delivery in women with PDM is also needed.

Gait alterations are recognized as early markers of age-related decline and cognitive impairment. Dual-task assessments, which impose cognitive load while walking, provide valuable insights into gait control limitations and cognitive-motor interactions in aging populations. This study evaluates age-related and cognitive load-induced changes in gait parameters, with a particular focus on asymmetry, and aims to optimize the gait assessment protocol for the Semmelweis Study framework. The Semmelweis Study is a large-scale workplace cohort investigating the determinants of unhealthy aging and promoting healthy brain aging by identifying risk factors and protective mechanisms influencing vascular, metabolic, and neurocognitive decline. As part of this initiative, gait analysis is emerging as a critical tool for assessing functional aging, detecting early signs of mobility and cognitive impairment, and contributing to biological age assessment. A cross-sectional analysis was conducted on adults aged 23 to 87 years using a pressure-sensitive walkway system. Participants were evaluated under single-task conditions (normal walking) and dual-task conditions (walking while performing a concurrent cognitive task). Spatiotemporal gait parameters, asymmetry indices, and dual-task costs were analyzed to assess age-related changes in gait performance and cognitive-motor interactions. Aging was associated with significant reductions in gait speed, step length, and stride length, along with a corresponding increase in gait asymmetry. Dual-task conditions exacerbated these alterations, indicating age-related impairments in cognitive-motor integration. Asymmetry indices were sensitive to aging effects, suggesting their potential as biomarkers for functional decline. The dual-task cost on gait was significantly greater in older adults, reinforcing the interplay between cognitive and motor systems in aging. Age-related gait alterations, particularly under cognitive load, underscore the importance of comprehensive gait assessments in aging research. Our findings contribute to the optimization of the Semmelweis Study gait assessment protocol by identifying key gait parameters that capture functional decline and biological aging. Integrating dual-task gait analysis into large-scale epidemiological studies has the potential to enhance early detection of brain health decline, refine biological age estimation, and guide targeted interventions to support healthy aging and neuromotor resilience.

Cardiotoxic, anthracycline-based therapies have high value in selected patients with breast cancer. We aimed to describe the effect of anthracycline plus taxane and single taxane chemotherapies on echocardiographic parameters in women with breast cancer. We retrospectively analysed data of 68 women (> 18 years old) treated for breast cancer in 2018–2021 in the Cardiology Outpatient Clinic of Semmelweis University, Department of Internal Medicine and Oncology. Cardiovascular medical history was collected at baseline and transthoracic echocardiography was completed at each visit. Also, we reviewed electronic medical records for other relevant medical information. Measured echocardiography parameters were assigned to five periods (0–14 days, then every half year and beyond day 545) based on the time since the first treatment. Trajectories of ejection fraction and diastolic function associated markers over the follow-up periods were analysed by linear mixed models. Mean age of the anthracycline plus taxane group was 52.7 ± 14.1 years, of the single taxane group 55.2 ± 13.1 years. The mean anthracycline dose was equivalent to 240 mg/m2 of doxorubicin. Overall pre-existing cardiovascular burden was low. Statistically significant changes were found only in the anthracycline plus taxane group: ejection fraction decreased mildly from 65.5 ± 3.1

AIM:Glucose management indicator (GMI) may not perform equally well for different continuous glucose monitoring (CGM) systems. Thus, we aimed to develop device-specific GMI for the Guardian 3 and 4 sensors, compare them to the original GMI, and investigate the association between the glycaemic gap (=HbA1c-GMI) and HbA1c. METHODS:In a single-centre, observational study of adult type 1 diabetes patients using Guardian Sensor 3 (G3) and 4 (G4) CGM devices, we estimated HbA1c using CGM-derived mean glucose for both CGMs using linear mixed models. We compared the estimates and their residuals (G3-gap and G4-gap) to the original GMI and its residuals (Bergenstal-gap) using regression and Bland-Altman plots. RESULTS:We included 120 adult type 1 diabetes patients (90 with G3 and 30 with G4) and 194 measurement points. We found that for G3 and G4 sensors, GMI significantly underestimated glycaemia in high HbA1c ranges, reaching the clinically significant 0.5 %[4.4 mmol/mol] difference at 7.6 % [60 mmol/mol] for G3 and 8.3 % [67 mmol/mol] for G4 sensors. For G4, GMI significantly overestimated glycaemia in the lower HbA1c range. We found a strong relationship between all 3 gaps and HbA1c, and the slope was steeper for the Bergenstal-gap versus the sensor-specific G3 and G4 gaps. The G3-gap was approximately half as large as the Bergenstal-gap for HbA1c > 7 % [53 mmol/mol], and the G4-gap is approximately half of the Bergenstal-gap for the whole HbA1c range. CONCLUSION:Device-specific GMI equations could reduce the risk of clinically significant under- and overestimation of HbA1c, improving clinical decision-making.

Abstract Background The trajectories of anthropometric and body composition measures (important predictors of diabetes) are rarely explored before diabetes diagnosis. Our study aimed to compare trajectories of fat mass (FM), fat-free mass (FFM), body mass index (BMI), and waist circumference (WC) preceding type 2 diabetes mellitus (T2DM) to aging trajectories of individuals without diabetes during follow-up. Methods We used data from the Whitehall II study, a prospective cohort of British civil servants. 5-yearly BMI and WC were available for up to 20 years, while 5-yearly FM and FFM measures were available for up to 10 years. Linear mixed models with a backward timescale (from diabetes diagnosis or end of follow-up) were performed stratified by sex and adjusted for age, occupational grade, ethnicity, and lifestyle factors. Results A total of 1674/990 (anthropometric/body composition analysis) women (233/81 incident diabetes) and 3917/2710 men (479/217 incident diabetes) 49.81 [0.08]/60.91 [0.9] (mean [SE]) years of age at baseline were included. All outcomes were higher in cases compared to controls. Women’s FM, BMI, and WC followed a quadratic increase in both groups with a faster increase among incident diabetes cases (dBMI 0.04 [0.01] kg/m2/year, dFM 0.19 [0.09] kg/year, dWC 0.2 cm/year [0.05]). FFM decreased linearly with similar slopes in cases and controls. Men’s FM, BMI, and WC also showed a quadratic increase with faster increase in incident cases compared to controls (dBMI 0.03 [0.01] kg/m2/year, dFM 0.23 [0.04] kg/year, dWC 0.08 [0.02] cm/year). FFM followed a quadratic decrease in both groups with a slower rate (0.06 [0.03] kg/year) in incident cases. Conclusions Incident diabetes cases have higher anthropometric and body composition measures 10-20 years before diabetes diagnosis compared to controls. Furthermore, incident cases showed faster increases in these measures except for FFM that decreased during follow-up with similar or lower speeds in cases than controls. Key messages • Traditional anthropometric measures do not capture the underlying changes in body composition. • The inclusion of body composition in risk calculators may result in more precise diabetes prediction.

Type 2 diabetes is a frequent chronic disease. Given its strong positive association with older age, it is a significant public health issue in elderly populations. Furthermore, the aging of the population, driven by increasing life expectancy in high and middle -income countries leads to an increasing prevalence of diabetes. Although the same diagnostic criteria apply to the elderly and to younger people, there are unique aspects to the care for elderly type 2 diabetes patients. Both treatment goals and preferred medications, as well as non -pharmacological approaches should be adjusted in the elderly. For example, increasing the amount of physical activity may encounter difficulties, while introducing an appropriate diet may be more challenging. The patients' therapeutic adherence requires special attention due to cognitive and physical limitations. The most important treatment goal is to avoid hypoglycemia. Frailty, social and economic issues, comorbidities and the consequent polypharmacy frequently causing drug -drug interactions, as well as the increased danger of drug toxicity due to renal failure are only some of the problems that make the health care for old diabetes patients extremely difficult. Adequate care requires cooperation from a multidisciplinary team of health care professionals. Acute diabetes complications have a higher mortality in the elderly, thus close attention must be paid to avoid them. Family members should be involved in the care of elderly diabetes patients, and it is recommended to educate them on clinical signs of complications. Regular care for the patients including feedback on quality of life and early signs of health issues are essential.

PURPOSE Medullary thyroid carcinoma (MTC) in MEN2B syndrome is associated with germline RET mutation. Patients harboring de novo mutations are usually diagnosed at more advanced disease stages. We present a young woman with Met918Th mutation diagnosed with stage IV MTC at age 10 years. METHODS The disease progressed despite total thyroidectomy and multiple surgical interventions for cervical lymph node recurrences, leading to distant metastases in the fifth year after the initial diagnosis. Subsequently, she underwent five different types of tyrosine kinase inhibitor (TKI) treatments. The 17-year disease course was divided into periods defined by four surgical interventions and sequential treatment intervals with four multikinase (sunitinib, vandetanib, cabozantinib, and lenvatinib) and one RET-selective TKI (selpercatinib). Tumor growth for different phases of spontaneous development and drug treatment intervals was characterized by changes in serial log-transformed calcitonin measurements (n = 114). RESULTS Three operations (one for calcitonin-producing adrenal pheochromocytoma) were associated with drops in calcitonin levels. All of the nonselective TKIs were stopped due to adverse effects. As reflected by the negative calcitonin doubling rate, the best treatment response was observed with selpercatinib, which was associated with an initial large drop followed by a decreasing calcitonin trajectory over 514 days without any major side effects. CONCLUSION This case of MEN2B medullary thyroid cancer with long-term survival presents how the effectiveness of different treatment modalities can be estimated using log-transformed calcitonin levels. Furthermore, our experience supports the view that serial calcitonin measurements may be more sensitive than radiological follow-up in advanced MTC. Our patient also represents a new case of rarely reported calcitonin-producing pheochromocytomas.

With a growing elderly population in the European Union, age-related diseases associated with unhealthy aging pose increasing public health challenges, including a loss of independence and heightened societal burdens. The Semmelweis Study, a prospective occupational cohort study in Hungary, seeks to identify determinants of unhealthy aging, focusing on the complex relationship between lifestyle, environmental, occupational factors, and the development of chronic age-associated diseases, including age-related vascular cognitive impairment (VCI). The primary objective of this pilot study was to establish a robust, high-throughput assessment methodology to comprehensively evaluate both peripheral and cerebrovascular health to provide a solid foundation for the forthcoming Semmelweis Study framework. The study involved 49 participants aged 23 to 87 years, and it assessed multi-domain cognitive performance through an automated battery of tests (CANTAB). Vascular health was comprehensively evaluated using laser speckle contrast imaging (LSCI), flow-mediated dilation (FMD), static and dynamic retinal vessel analysis (SVA, DVA), and measurements of vascular stiffness. The retinal microvasculature, which closely mirrors the cerebral circulation in anatomy, physiology, and pathophysiology, provided a unique window for examination. Optical imaging through SVA and DVA enables the identification of structural and functional changes in the central nervous system’s microcirculation, which are highly relevant to the pathogenesis of VCI. Subsequently, the collected measures were integrated into vascular health indices using principal component analysis (PCA) and the relationship to the age and cognitive status of study participants was explored. These comprehensive vascular health indices demonstrated a correlation not only with age but also with cognitive performance. This methodology holds promise for providing novel insights into the intricate interplay between vascular and cognitive health within the context of the Semmelweis Study.

The Semmelweis Study is a prospective occupational cohort study that seeks to enroll all employees of Semmelweis University (Budapest, Hungary) aged 25 years and older, with a population of 8866 people, 70.5% of whom are women. The study builds on the successful experiences of the Whitehall II study and aims to investigate the complex relationships between lifestyle, environmental, and occupational risk factors, and the development and progression of chronic age-associated diseases. An important goal of the Semmelweis Study is to identify groups of people who are aging unsuccessfully and therefore have an increased risk of developing age-associated diseases. To achieve this, the study takes a multidisciplinary approach, collecting economic, social, psychological, cognitive, health, and biological data. The Semmelweis Study comprises a baseline data collection with open healthcare data linkage, followed by repeated data collection waves every 5 years. Data are collected through computer-assisted self-completed questionnaires, followed by a physical health examination, physiological measurements, and the assessment of biomarkers. This article provides a comprehensive overview of the Semmelweis Study, including its origin, context, objectives, design, relevance, and expected contributions.

Despite the availability of various antihyperglycaemic therapies and comprehensive guidelines, glycaemic control in diabetes management has not improved significantly during the last decade in the real-world clinical setting. Treatment inertia arising from a complex interplay among patient-, clinician- and healthcare-system-related factors is the prime reason for this suboptimal glycaemic control. Also, the key factor leading to inadequate glycaemic levels remains limited communication between healthcare professionals (HCPs) and people with type 2 diabetes (PwT2D). Early insulin administration has several advantages including reduced glucotoxicity, high efficacy and preserved β-cell mass/function, leading to lowering the risk of diabetes complications. The current publication is based on consensus of experts from the South-Eastern European region and Israel who reviewed the existing evidence and guidelines for the treatment of PwT2D. Herein, the experts emphasised the timely use of insulin, preferably second-generation basal insulin (BI) analogues and intensification using basal-plus therapy, as the most-potent glucose-lowering treatment choice in the real-world clinical setting. Despite an increase in the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), the experts urged timely insulin initiation for inadequate glycaemic control in PwT2D. Furthermore, the combination of BI and GLP-1 RA addressing both fasting plasma glucose and post-prandial excursions as a free- or fixed-ratio combination was identified to reduce treatment complexity and burden. To minimise discontinuation and improve adherence, the experts reiterated quality, regular interactions and discussions between HCPs and PwT2D/carers for their involvement in the diabetes management decision-making process. Clinicians and HCPs should consider the opinions of the experts in accordance with the most recent recommendations for diabetes management.

IntroductionLow socioeconomic status affects not only diagnosis rates and therapy of patients with diabetes mellitus but also their health behavior. Our primary goal was to examine diagnosis rates and therapy of individuals with diabetes living in Ormánság, one of the most deprived areas in Hungary and Europe. Our secondary goal was to examine the differences in lifestyle factors and cancer screening participation of patients with diagnosed and undiagnosed diabetes compared to healthy participants.MethodsOur study is a cross-sectional analysis using data from the “Ormánság Health Program”. The “Ormánság Health Program” was launched to improve the health of individuals in a deprived region of Hungary. Participants in the program were coded as diagnosed diabetes based on diagnosis by a physician as a part of the program, self-reported diabetes status, and self-reported prescription of antidiabetic medication. Undiagnosed diabetes was defined as elevated blood glucose levels without self-reported diabetes and antidiabetic prescription. Diagnosis and therapeutic characteristics were presented descriptively. To examine lifestyle factors and screening participation, patients with diagnosed and undiagnosed diabetes were compared to healthy participants using linear regression or multinomial logistic regression models adjusted for sex and age.ResultsOur study population consisted of 246 individuals, and 17.9% had either diagnosed (n=33) or undiagnosed (n=11) diabetes. Metformin was prescribed in 75.8% (n=25) of diagnosed cases and sodium-glucose cotransporter-2 inhibitors (SGLT-2) in 12.1% (n=4) of diagnosed patients. After adjustment, participants with diagnosed diabetes had more comorbidities (adjusted [aOR]: 3.50, 95% confidence interval [95% CI]: 1.34–9.18, p<0.05), consumed vegetables more often (aOR: 2.49, 95% CI: 1.07–5.78, p<0.05), but desserts less often (aOR: 0.33, 95% CI: 0.15–0.75, p<0.01) than healthy individuals. Patients with undiagnosed diabetes were not different in this regard from healthy participants. No significant differences were observed for cancer screening participation between groups.ConclusionsTo increase recognition of diabetes, targeted screening tests should be implemented in deprived regions, even among individuals without any comorbidities. Our study also indicates that diagnosis of diabetes is not only important for the timely initiation of therapy, but it can also motivate individuals in deprived areas to lead a healthier lifestyle.

IntroductionPatients with systemic lupus erythematosus are prone to develop cardiovascular disease (CVD), and have increased morbidity and mortality.MethodsWe conducted a retrospective analysis on lupus nephritis patients to assess the occurrence and predictors of major adverse cardiovascular events (MACE). Data were collected from patients who underwent kidney biopsy between 2005 and 2020. Statistical analysis was performed to unveil correlations.Results91 patients were analyzed in this period, with a mean age of 37.3 ± 12.3 years and 86% being female. The mean follow-up time was 62 ± 48 months. 15.38% of the patients underwent at least one MACE. Two patients deceased of CVD. Increased age (35.81 ± 11.14 vs 45.5 ± 15.11 years, p=0.012) entailed a higher occurrence of MACEs. Neutrophil count (5.15 ± 2.83 vs 7.3 ± 2.99 Giga/L, p=0.001) was higher, whereas diastolic blood pressure (DBP) was lower (89.51 ± 10.96 vs 78.43 ± 6.9 mmHg, p<0.001) at the time of the biopsy in patients with MACE. Age, neutrophil count, and DBP proved to be independent predictors of MACEs. We propose a new model (CANDE – Cardiovascular risk based on Age, Neutrophil count, and Diastolic blood pressure Estimation score) calculated from these variables, which predicts the probability of MACE occurrence.ConclusionThis study underscores the importance of actively screening for cardiovascular risks in this vulnerable patient population. Age, neutrophil count, and diastolic blood pressure have been established as independent risk factors for MACE in lupus nephritis. The CANDE score derived from these parameters may serve as a prompt, cost-effective, and easily accessible estimation tool for assessing the likelihood of major adverse cardiovascular risk. These findings emphasize the necessity for comprehensive management strategies addressing both immune dysregulation and cardiovascular risk factors in systemic lupus erythematosus to mitigate adverse outcomes.

There is abundant evidence that bone mineral content is highly heritable, while the heritability of bone quality (i.e. trabecular bone score [TBS] and quantitative ultrasound index [QUI]) is rarely investigated. We aimed to disentangle the role of genetic, shared and unique environmental factors on TBS and QUI among Hungarian twins. Our study includes 82 twin (48 monozygotic, 33 same-sex dizygotic) pairs from the Hungarian Twin Registry. TBS was determined by DXA, QUI by calcaneal bone ultrasound. To estimate the genetic and environmental effects, we utilized ACE-variance decomposition. For the unadjusted model of TBS, an AE model provided the best fit with > 80

Abstract Background The increasing birthweight trend stopped and even reversed in several high income countries in the last 20 years, however the reason for these changes is not well characterized. We aimed to describe birthweight trends of term deliveries in Hungary between 1999 and 2018 and to investigate potential maternal and foetal variables that could drive these changes. Methods We analysed data from the Hungarian Tauffer registry, a compulsory anonymized data collection of each delivery. We included all singleton term deliveries in 1999–2018 (n = 1,591,932). We modelled birthweight trends separately in 1999–2008 and 2008–2018 in hierarchical multiple linear regression models adjusted for calendar year, newborn sex, maternal age, gestational age at delivery, and other important determinants. Results Median birthweights increased from 3250/3400 g (girl/boy) to 3300/3440 g from 1999 to 2008 and decreased to 3260/3400 g in 2018. When we adjusted for gestational age at delivery the increase in the first period became more pronounced (5.4 g/year). During the second period, similar adjustment substantially decreased the rate of decline from 2.5 to 1.4 g/year. Further adjustment for maternal age halved the rate of increase to 2.4 g/year in the first period. During the second period, adjustment for maternal age had little effect on the estimate. Conclusions Our findings of an increasing birthweight trend (mostly related to the aging of the mothers) in 1999–2008 may forecast an increased risk of cardiometabolic diseases in offsprings born in this period. In contrast, the decreasing birthweight trends after 2008 may reflect some beneficial effects on perinatal morbidity. However, the long-term effect cannot be predicted, as the trend is mostly explained by the shorter pregnancies.