Developing technologies to assess vascular ageing: a roadmap from VascAgeNet.

Vascular ageing is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.

Medical device regulation in vascular ageing assessment: a VascAgeNet survey exploring knowledge and perception.

BACKGROUND: Regulation has a key role for medical devices throughout their lifecycle aiming to guarantee effectiveness and safety for users. Requirements of Regulation (EU) 2017/745 (MDR) have an impact on novel and previously approved systems. Identification of key stakeholders' needs can support effective implementation of MDR improving the translation to clinical practice of vascular ageing assessment. The aim of this work is to explore knowledge and perception of medical device regulatory framework in vascular ageing field. RESEARCH DESIGN AND METHODS: A survey was developed within VascAgeNet and distributed in the community by means of the EUSurvey platform. RESULTS: Results were derived from 94 participants (27% clinicians, 62% researchers, 11% companies) and evidenced mostly a fair knowledge of MDR (despite self-judged as poor by 51%). Safety (83%), validation (56%), risk management (50%) were considered relevant and associated with the regulatory process. Structured support and regulatory procedures connected with medical devices in daily practice at the institutional level are lacking (only 33% report availability of a regulatory department). CONCLUSIONS: Regulation was recognized relevant by the VascAgeNet community and specific support and training in medical device regulatory science was considered important. A direct link with the regulatory sector is not yet easily available.

Atrial Fibrillation and Early Vascular Aging: Clinical Implications, Methodology Issues and Open Questions-A Review from the VascAgeNet COST Action.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field.

Non-invasive pulse arrival time as a surrogate for oscillometric systolic blood pressure changes during non-pharmacological intervention.

Background.Non-invasive continuous blood pressure (BP) monitoring is of longstanding interest in various cardiovascular scenarios. In this context, pulse arrival time (PAT), i.e., a surrogate parameter for systolic BP (change), became very popular recently, especially in the context of cuffless BP measurement and dedicated lifestyle interventions. Nevertheless, there is also understandable doubt on its reliability in uncontrolled and mobile settings.Objective.The aim of this work is therefore the investigation whether PAT follows oscillometric systolic BP readings during moderate interventions by physical or mental activity using a medical grade handheld device for non-invasive PAT assessment.Approach.A study was conducted featuring an experimental group performing a physical and a mental task, and a control group. Oscillometric BP and PAT were assessed at baseline and after each intervention. Interventions were selected randomly but then performed sequentially in a counterbalanced order. Multivariate analyses of variance were used to test within-subject and between-subject effects for the dependent variables, followed by univariate analyses for post-hoc testing. Furthermore, correlation analysis was performed to assess the association of intervention effects between BP and PAT.Mainresults.The study included 51 subjects (31 females). Multivariate analysis of variances showed that effects in BP, heart rate, PAT and pulse wave parameters were consistent and significantly different between experimental and control groups. After physical activity, heart rate and systolic BP increased significantly whereas PAT decreased significantly. Mental activity leads to a decrease in systolic BP at stable heart rate. Pulse wave parameters follow accordingly by an increase of PAT and mainly unchanged pulse wave analysis features due to constant heart rate. Finally, also the control group behaviour was accurately registered by the PAT method compared to oscillometric cuff. Correlation analyses revealed significant negative associations between changes of systolic BP and changes of PAT from baseline to the physical task (-0.33 [-0.63, 0.01],p< 0.048), and from physical to mental task (-0.51 [-0.77, -0.14],p= 0.001), but not for baseline to mental task (-0.12 [-0,43,0,20],p= 0.50) in the experimental group.Significance.PAT and the used digital, handheld device proved to register changes in BP and heart rate reliably compared to oscillometric measurements during intervention. Therefore, it might add benefit to future mobile health solutions to support BP management by tracking relative, not absolute, BP changes during non-pharmacological interventions.

2024 Recommendations for Validation of Noninvasive Arterial Pulse Wave Velocity Measurement Devices.

BACKGROUND: Arterial stiffness, as measured by arterial pulse wave velocity (PWV), is an established biomarker for cardiovascular risk and target-organ damage in individuals with hypertension. With the emergence of new devices for assessing PWV, it has become evident that some of these devices yield results that display significant discrepancies compared with previous devices. This discrepancy underscores the importance of comprehensive validation procedures and the need for international recommendations. METHODS: A stepwise approach utilizing the modified Delphi technique, with the involvement of key scientific societies dedicated to arterial stiffness research worldwide, was adopted to formulate, through a multidisciplinary vision, a shared approach to the validation of noninvasive arterial PWV measurement devices. RESULTS: A set of recommendations has been developed, which aim to provide guidance to clinicians, researchers, and device manufacturers regarding the validation of new PWV measurement devices. The intention behind these recommendations is to ensure that the validation process can be conducted in a rigorous and consistent manner and to promote standardization and harmonization among PWV devices, thereby facilitating their widespread adoption in clinical practice. CONCLUSIONS: It is hoped that these recommendations will encourage both users and developers of PWV measurement devices to critically evaluate and validate their technologies, ultimately leading to improved consistency and comparability of results. This, in turn, will enhance the clinical utility of PWV as a valuable tool for assessing arterial stiffness and informing cardiovascular risk stratification and management in individuals with hypertension.

Association between adherence to posttreatment National Comprehensive Cancer Network (NCCN) surveillance guidelines and detection of recurrent uterine cancer.

OBJECTIVE: To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer. METHODS: Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded. RESULTS: Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence. CONCLUSION: Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence.

Analysis of Sociodemographic Factors Affecting Ambulatory Surgical Center Discharge Patterns for Endometrial Cancer Hysterectomies.

STUDY OBJECTIVE: Investigate outcomes for patients undergoing minimally invasive hysterectomies (MIHs) performed for endometrial cancer at ambulatory surgery centers (ASCs). DESIGN: Our study aimed to explore the feasibility and discharge outcomes for MIHs for endometrial cancer in an ASC setting by using same-day discharge data. SETTING: The prevalence of MIH for endometrial cancer between 2016 and 2019 was estimated from the Nationwide Ambulatory Surgery Sample. PATIENTS: Patients who underwent MIHs for endometrial cancer at an ASC were included. INTERVENTIONS: N/A MEASUREMENTS MAIN RESULTS: Weighted estimates of prevalence and association between discharge status and sociodemographic factors were explored. Same-day discharge was defined as discharge on the day of surgery, and delayed discharge was defined as discharge after the day of surgery. An estimated 95 041 MIHs for endometrial cancer were performed at ASCs between 2016 and 2019. Notably, 91.9% (n = 87 372) resulted in same-day discharge, 1.2% (n = 1121) had delayed discharge, and 6.9% (n = 6548) had missing discharge information; 78.7% procedures (n = 68 812) were performed at public hospitals. The proportion of delayed discharges were lower in private, not-for profit ASCs (0.8%, p = .03) than public hospitals. Patients who had delayed discharges on average were older (69.7 vs 62.4 years, p <.001), more likely to have comorbid conditions including diabetes (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 1.25-1.75) and overweight or obese body mass indices (aOR 1.18, 95% CI 1.01-1.39), and more likely to have public insurance (aOR 1.78, 95% CI 1.40-2.25). CONCLUSION: MIHs for endometrial cancer are feasible in an ASC. Optimal candidates for receipt of MIHs for endometrial cancer at an ASC are patients who are younger and have less comorbidities, lower body mass index, and private insurance.

Automatic ECG-based detection of left ventricular hypertrophy and its predictive value in haemodialysis patients.

Objective.Left ventricular hypertrophy (LVH) is one of the most severe risk factors in patients with end-stage kidney disease (ESKD) regarding all-cause and cardiovascular mortality. It contributes to the risk of sudden cardiac death which accounts for approximately 25% of deaths in ESKD patients. Electrocardiography (ECG) is the least expensive way to assess whether a patient has LVH, but manual annotation is cumbersome. Thus, an automated approach has been developed to derive ECG-based LVH parameters. The aim of the current study is to compare automatic to manual measurements and to investigate their predictive value for cardiovascular and all-cause mortality.Approach.From the 12-lead 24 h ECG measurements of 301 ESKD patients undergoing haemodialysis, three different LVH parameters were calculated. Peguero-Lo Presti voltage, Cornell voltage, and Sokolow-Lyon voltage were automatically derived and compared to the manual annotations. To determine the agreement between manual and automatic measurements and their predictive value, Bland-Altman plots were created and Cox regression analysis for cardiovascular and all-cause mortality was performed.Main results.The median values for the automatic assessment were: Peguero-Lo Presti voltage 1.76 mV (IQR 1.29-2.55), Cornell voltage 1.14 mV (IQR 0.721-1.66), and Sokolow-Lyon voltage 1.66 mV (IQR 1.08-2.23). The mean differences when compared to the manual measurements were -0.027 mV (0.21 SD), 0.027 mV (0.13 SD) and -0.025 mV (0.24 SD) for Peguero-Lo Presti, Cornell, and Sokolow-Lyon voltage, respectively. The categorial LVH detection based on pre-defined thresholds differed in only 13 cases for all indices between manual and automatic assessment. Proportional hazard ratios only differed slightly in categorial LVH detection between manually and automatically determined LVH parameters; no differences could be found for continuous parameters.Significance.This study provides evidence that automatic algorithms can be as reliable in LVH parameter assessment and risk prediction as manual measurements in ESKD patients undergoing haemodialysis.

Handheld Device Measures Cardiovascular Effects of Cognitive and Physical Stress.

Stress is an increasing burden for our society and related to cardiovascular (CV) parameters and diseases. Effects of mental or physical stress were observed in CV parameters during task completion and recovery. These effects were measured using a novel handheld device, which can be incorporated in mHealth solutions.

Arterial pulse wave modeling and analysis for vascular-age studies: a review from VascAgeNet.

Arterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propagation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life.

Vascular ageing: moving from bench towards bedside.

Prevention of cardiovascular disease (CVD) remains one of the largest public health challenges of our time. Identifying individuals at increased cardiovascular risk at an asymptomatic, sub-clinical stage is of paramount importance for minimizing disease progression as well as the substantial health and economic burden associated with overt CVD. Vascular ageing (VA) involves the deterioration in vascular structure and function over time and ultimately leads to damage in the heart, brain, kidney, and other organs. Vascular ageing encompasses the cumulative effect of all cardiovascular risk factors on the arterial wall over the life course and thus may help identify those at elevated cardiovascular risk, early in disease development. Although the concept of VA is gaining interest clinically, it is seldom measured in routine clinical practice due to lack of consensus on how to characterize VA as physiological vs. pathological and various practical issues. In this state-of-the-art review and as a network of scientists, clinicians, engineers, and industry partners with expertise in VA, we address six questions related to VA in an attempt to increase knowledge among the broader medical community and move the routine measurement of VA a little closer from bench towards bedside.

Developing a Questionnaire on Knowledge, Perceptions and Application of Vascular-Aging Measurements.

BACKGROUND: Vascular age (VA) is independent and chronological age for assessing cardiovascular disease (CVD) risk. However, tools for the implementation of VA are currently lacking. We aimed to develop a questionnaire to assess the current knowledge gaps related to VA and barriers to its implementation in routine practice. METHODS: Using a stepwise mixed-method approach, a quantitative questionnaire was constructed in four phases: (1) basic item generation and the development of a semi-qualitative questionnaire (SQQ); (2) dissemination to the VascAgeNet extended network and an analysis of the semi-qualitative questionnaire responses; (3) the development of a quantitative questionnaire (QQ); and (4) an assessment of the content and face validity and internal reliability in an additional sample. RESULTS: Based on six main topics initially identified through an expert panel, a SQQ was developed and disseminated. Finally, a 22-item QQ was developed, with questions grouped around three main themes: knowledge of VA and its risk factors; perceptions and beliefs regarding the importance and contribution of VA to risk classification; and the application of VA measurements in clinical and research practice and its potential limitations (Cronbach's alpha between 0.920 and 0.982 for all three categories). CONCLUSION: We report the development of a QQ on VA addressed to both clinicians and non-clinicians aiming to assess their knowledge, perceptions and application of VA measurements.

[The potential of complementary music interventions in patients with head and neck cancer]. / Das Potenzial komplementärer Musikinterventionen bei Patienten mit malignen Kopf-Hals-Tumoren.

PURPOSE: The established treatment regimen for patients suffering from cancer in the head and neck region often leads to physical and mental health problems and therefore can significantly reduce the quality of life (QoL) in these patients. The available data indicate that additional complementary treatments, such as music interventions, may improve patients' QoL and compliance and reduce symptoms during therapy. METHODS: Anonymous data collection using a self-designed questionnaire was conducted in patients suffering from cancer in the head and neck area in our outpatient department. The questionnaire particularly asked the patients about their need and interest in music interventions during therapy. RESULTS: In total, 138 patients were consecutively enrolled in the study. The mean age was 64.9 years, including 68.1% men and 31.9% women. Only 11.5% listened to music regularly during their therapy at the time of data collection, yet 52.2% stated that they would be interested in music interventions. Patients especially conceived the relaxing and encouraging effects from listening to music. Most patients would prefer group therapies (56%) or listening to their own music (36.6%). CONCLUSION: Our data suggest that there is a need for music interventions in patients suffering from cancer in the head and neck, as they anticipate they would experience positive effects, including reduced somatic and non-somatic symptoms and improved QoL. The lack of homogenous data emphasizes the need for further trials in the field of complementary music interventions to establish science-based concepts in the future.

Ultrafiltration-induced decrease in relative blood volume is larger in hemodialysis patients with low specific blood volume: Results from a dialysate bolus administration study.

INTRODUCTION: Prescribing the ultrafiltration in hemodialysis patients remains challenging and might benefit from the information on absolute blood volume, estimated by intradialytic dialysate bolus administration. Here, we aimed at determining the relationship between absolute blood volume, normalized for body mass (specific blood volume, Vs), and ultrafiltration-induced decrease in relative blood volume (∆RBV) as well as clinical parameters including body mass index (BMI). METHODS: This retrospective analysis comprised 77 patients who had their dialysate bolus-based absolute blood volume extracted routinely with an automated method. Patient-specific characteristics and ∆RBV were analyzed as a function of Vs, dichotomizing the data above or below a previously proposed threshold of 65 ml/kg for Vs. Statistical methodology comprised descriptive analyses, two-group comparisons, and correlation analyses. FINDINGS: Median Vs was 68.6 ml/kg (54.9 ml/kg [Quartile 1], 83.4 ml/kg [Quartile 3]). Relative blood volume decreased by 6.3% (2.6%, 12.2%) over the entire hemodialysis session. Vs correlated inversely with BMI (rs  = -0.688, p < 0.001). ∆RBV was 9.8% in the group of patients with Vs <65 ml/kg versus 6.0% in the group of patients with Vs ≥65 ml/kg (p = 0.024). The two groups did not differ significantly regarding their specific ultrafiltration volume, normalized for body mass, which amounted to 34.1 ml/kg and 36.0 ml/kg in both groups, respectively (p = 0.630). ∆RBV correlated inversely with Vs (rs  = -0.299, p = 0.008). DISCUSSION: The present study suggests that patients with higher BMI and lower Vs experience larger blood volume changes, despite similar ultrafiltration requirements. These results underline the clinical plausibility and importance of dialysate bolus-based absolute blood volume determination in the assessment of target weight, especially in view of a previous study where intradialytic morbid events could be decreased when the target weight was adjusted, based on Vs.

Usability testing of the first prototype of the Memento system: a technological device to promote an independent living in people with dementia.

PURPOSE: Assistive technologies have the potential for supporting people with memory complaints in their daily life. User-centered interaction design research helps developers to create systems that are suitable for users. The aim of this work is to describe the methodology and the results of the usability test for the first Memento prototype involving users. MATERIALS AND METHODS: In each country, 5 subjects with different levels of cognitive reserve and technical proficiency were enrolled in Italy, Austria and Spain, respectively (15 subjects; 6 M; 9 F, age 72.8 ± 10.8 years, MMSE score 25.6 ± 1.6). Observation methods, performance metrics and the System Usability Scale were used to collect data. RESULTS: The results are presented in terms of design, technical problems, target-group-related challenges and usability perception from the participant perspective. Suggestions for improvement were pointed out by the users. Considering the usability scores interpretation, the first prototype was classified as "OK" and "Good" by users. CONCLUSIONS: The results of the Lab Trials provide important information on usability and the users' needs in order to improve the Memento prototype and to create a final system to be evaluated during the Field Trials phase of the project.Implication for rehabilitationThe MEMENTO project mission is to improve the quality of life of people in the early and middle stages of dementia, by supporting the management of daily activities that are usually affected by the loss of memory and cognition. The Lab Trial phase is essential to have feedback on the usability of the Memento prototype to allow a better understanding of users' needs and expectations.

Sex differences in pressure and flow waveform physiology across the life course.

Cardiovascular disease (CVD) has long been deemed a disease of old men. However, in 2019 CVD accounted for 35% of all deaths in women and, therefore, remains the leading cause of death in both men and women. There is increasing evidence to show that risk factors, pathophysiology and health outcomes related to CVD differ in women compared with men, yet CVD in women remains understudied, underdiagnosed and undertreated. Differences exist between the sexes in relation to the structure of the heart and vasculature, which translate into differences in blood pressure and flow waveform physiology. These physiological differences between women and men may represent an important explanatory factor contributing to the sex disparity in CVD presentation and outcomes but remain understudied. In this review we aim to describe sex differences in arterial pressure and flow waveform physiology and explore how they may contribute to differences in CVD in women compared to men. Given that unfavourable alterations in the cardiovascular structure and function can start as early as in utero, we report sex differences in waveform physiology across the entire life course.

The TAM receptor tyrosine kinases Axl and Mer drive the maintenance of highly phagocytic macrophages.

Many apoptotic thymocytes are generated during the course of T cell selection in the thymus, yet the machinery through which these dead cells are recognized and phagocytically cleared is incompletely understood. We found that the TAM receptor tyrosine kinases Axl and Mer, which are co-expressed by a specialized set of phagocytic thymic macrophages, are essential components of this machinery. Mutant mice lacking Axl and Mer exhibited a marked accumulation of apoptotic cells during the time that autoreactive and nonreactive thymocytes normally die. Unexpectedly, these double mutants also displayed a profound deficit in the total number of highly phagocytic macrophages in the thymus, and concomitantly exhibited diminished expression of TIM-4, CD163, and other non-TAM phagocytic engulfment systems in the macrophages that remained. Importantly, these previously unrecognized deficits were not confined to the thymus, as they were also evident in the spleen and bone marrow. They had pleiotropic consequences for the double mutants, also previously unrecognized, which included dysregulation of hemoglobin turnover and iron metabolism leading to anemia.