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.

Shop-to-stop hypertension: A multicenter cluster-randomized controlled trial protocol to improve screening and text message follow-up of adults with high blood pressure at health kiosks in hardware retail stores.

High blood pressure (BP) is the leading preventable risk factor for death, but only one in three patients achieve target BP control. A key contributor to this problem is poor population awareness of high BP, as the majority of patients are asymptomatic. The Shop-To-Stop Hypertension study is a multicenter, cluster-randomized controlled trial to identify, refer and follow adults in need of hypertension care, whilst raising population-wide awareness. In participants with high BP measured by SiSU Health Stations located in major hardware chain stores across New South Wales, Australia, we will determine whether text message-based nudges will encourage repeat BP checks and visits to their doctor. Based on pilot data, we anticipate 65,340 participants will be screened over 12 months, of which 18% will have high BP. Thirty hardware stores will be randomized (1:1) to: (i) Intervention: participants detected with high BP (≥140/≥90 mmHg) will receive text message-based nudges to return for a repeat SiSU Health Station BP check and to visit their general practitioner (GP) to check and manage their BP; (ii) Control: participants with high BP will not receive text messages. The primary outcome is the difference in the proportion of participants with high BP having a repeat BP check at hardware Health Stations in the intervention vs. control group at 12 months. This novel setting for screening utilises a novel 'citizen science' approach inviting the general public to perform their own BP screening at health kiosks and foster behavioral change. This will allow screening in a low-stress environment.

Skin Manifestations of VEXAS Syndrome and Associated Genotypes.

Importance: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined genetic disease with an estimated prevalence of 1 in 4269 men older than 50 years and is marked by systemic inflammation, progressive bone marrow failure, and inflammatory cutaneous manifestations. Objective: To define the spectrum of cutaneous manifestations in VEXAS syndrome and the association of these findings with clinical, genetic, and histological features. Design, Setting, and Participants: This observational cohort study included data from 112 patients who were diagnosed with VEXAS-defining genetic variants in UBA1 between 2019 and 2023. Data were collected from medical record review or from patients with VEXAS directly evaluated at the National Institutes of Health in Bethesda, Maryland. Main Outcomes and Measures: To define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histological, and other clinical findings. A secondary outcome was cutaneous response to treatment in VEXAS. Results: Among the 112 patients (median [range] age, 69 [39-79] years; 111 [99%] male), skin involvement was common (93 [83%]), and the most frequent presenting feature of disease (68 [61%]). Of 64 histopathologic reports available from 60 patients, predominant skin histopathologic findings were leukocytoclastic vasculitis (23 [36%]), neutrophilic dermatosis (22 [34%]), and perivascular dermatitis (19 [30%]). Distinct pathogenic genetic variants were associated with specific cutaneous manifestations. The p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates (14 of 17 patients [82%]), often resembling histiocytoid Sweet syndrome. In contrast, the p.Met41Val variant was associated with vasculitic lesions (11 of 20 patients [55%]) with a mixed leukocytic infiltrate (17 of 20 patients [85%]). Oral prednisone improved skin manifestations in 67 of 73 patients (92%). Patients with VEXAS treated with anakinra frequently developed severe injection-site reactions (12 of 16 [75%]), including ulceration (2 of 12 [17%]) and abscess formation (1 of 12 [8%]). Conclusions and Relevance: Results of this cohort study show that skin manifestations are a common and early manifestation of VEXAS syndrome. Genetic evaluation for VEXAS should be considered in older male patients with cutaneous vasculitis, neutrophilic dermatoses, or chondritis. Awareness of VEXAS among dermatologists is critical to facilitate early diagnosis.

The Pathophysiology, Prognosis and Treatment of Hypertension in Females from Pregnancy to Post-menopause: A Review.

PURPOSE OF REVIEW: We summarise the physiological changes and risk factors for hypertension in females, potential sex-specific management approaches, and long-term prognosis. KEY FINDINGS: Pregnancy and menopause are two key phases of the life cycle where females undergo significant biological and physical changes, making them more prone to developing hypertension. Gestational hypertension occurs from changes in maternal cardiac output, kidney function, metabolism, or placental vasculature, with one in ten experiencing pregnancy complications such as intrauterine growth restriction and delivery complications such as premature birth. Post-menopausal hypertension occurs as the protective effects of oestrogen are reduced and the sympathetic nervous system becomes over-activated with ageing. Increasing evidence suggests that post-menopausal females with high blood pressure (BP) experience greater risk of cardiovascular events at lower BP thresholds, and greater vulnerability to treatment-related adverse effects. Hypertension is a key risk factor for cardiovascular disease in females. Current BP treatment guidelines and recommendations are similar for both sexes, without addressing sex-specific factors. Future investigations into ideal diagnostic thresholds, BP control targets and treatment regimens in females are needed.

Association of 24-h central hemodynamics and stiffness with cardiovascular events and all-cause mortality. The VASOTENS Registry.

OBJECTIVES: In hemodialysis patients, central hemodynamics, stiffness, and wave reflections assessed through ambulatory blood pressure monitoring (ABPM) showed superior prognostic value for cardiovascular (CV) events than peripheral blood pressures (BPs). No such evidence is available for lower-risk hypertensive patients. METHODS: In 591 hypertensive patients (mean age 58 ±â€Š14 years, 49% males), ambulatory brachial and central BP, pulse wave velocity (PWV), and augmentation index (AIx) were obtained with a validated upper arm cuff-based pulse wave analysis technology. Information on treatment for hypertension (73% of patients), dyslipidemia (27%), diabetes (8%), CV disease history (25%), was collected. Patients were censored for CV events or all-cause death over 4.2 years. RESULTS: One hundred and four events (24 fatal) were recorded. Advanced age [hazard ratio and 95% confidence interval: 1.03 (1.01, 1.05), P = 0.0001], female sex [1.57 (1.05, 2.33), P = 0.027], CV disease [2.22 (1.50, 3.29), P = 0.0001], increased 24-h central pulse pressure (PP) [1.56 (1.05, 2.31), P = 0.027], PWV [1.59 (1.07, 2.36), P = 0.022], or AIx [1.59 (1.08, 2.36), P = 0.020] were significantly associated with a worse prognosis (univariate Cox regression analysis). The prognostic power of peripheral and central BPs was lower. However, PWV [1.02 (0.64, 1.63), P = 0.924], AIx [1.06 (0.66, 1.69), P = 0.823], and central PP [1.18 (0.76, 1.82), P = 0.471], were not significant predictors in multivariate analyses. CONCLUSIONS: In hypertensive patients, ambulatory central PP, PWV, and AIx are associated with an increased risk of CV morbidity and all-cause mortality. However, this association is not independent of other patient characteristics.

Precision Dermatology: A Review of Molecular Biomarkers and Personalized Therapies.

The evolution of personalized medicine in dermatology signifies a transformative shift towards individualized treatments, driven by the integration of biomarkers. These molecular indicators serve beyond diagnostics, offering insights into disease staging, prognosis, and therapeutic monitoring. Specific criteria guide biomarker selection, ensuring attributes like specificity, sensitivity, cost feasibility, stability, rapid detection, and reproducibility. This literature review, based on data from PubMed, SCOPUS, and Web of Science, explores biomarkers in Hidradenitis Suppurativa (HS), Psoriasis, Atopic Dermatitis (AD), Alopecia Areata (AA), Vitiligo, and Chronic Spontaneous Urticaria (CSU). In HS, TNF-α, IL-1ß, and MMPs serve as biomarkers, influencing targeted therapies like adalimumab and anakinra. Psoriasis involves biomarkers such as TNF-α, IL-23, and HLA genes, shaping treatments like IL23 and IL17 inhibitors. AD biomarkers include ECP, IL-4, IL-13, guiding therapies like dupilumab and tralokinumab. For AA, lipocalin-2, cytokines, and genetic polymorphisms inform JAK inhibitors' use. Vitiligo biomarkers range from cytokines to genetic markers like TYR, TYRP1, guiding treatments like JAK inhibitors. CSU biomarkers encompass IgE, cytokines, and autologous serum tests, influencing therapies like omalizumab and cyclosporine. Comparing conditions, common proinflammatory markers reveal limited specificity. While some biomarkers aid diagnosis and standard treatments, others hold more scientific than clinical value. Precision medicine, driven by biomarkers, has shown success in skin malignancies. Future directions involve AI-powered algorithms, nanotechnology, and multi-omics integration for personalized dermatological care.

Biologics for Treatment of Pityriasis Rubra Pilaris: A Literature Review.

OBJECTIVE: To describe the published efficacy and adverse event rates associated with existing biologics for the treatment of pityriasis rubra pilaris (PRP). DATA SOURCES: A literature review using the PubMed database (January 1990-July 2023) was conducted. Multiple search combinations were conducted using "pityriasis rubra pilaris" and various biologics as keywords to identify relevant articles. STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria included all study types that were published within the past 30 years in English and mentioned at least one biologic and PRP. A preliminary search yielded a total of 499 results. After screening using inclusion and exclusion criteria, 77 relevant articles (69 case reports, 5 case series, 2 clinical trials, and 1 retrospective analysis) were analyzed. DATA SYNTHESIS: TNF-α inhibitors have been evaluated and are effective in treating PRP. However, recent treatment with anti-interleukin (IL)-17 and anti-IL-23 therapies such as ustekinumab, secukinumab, and ixekizumab are emerging as new treatment options with a mean improvement in PRP Area and Severity Index scores, change in severity of erythema, scaling, and thickness of PRP lesions. From initial clinical trials, secukinumab and ixekizumab are promising treatment options for achieving remission. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review compares the efficacy for numerous biologics and a discussion to guide clinicians on benefits and risks in choosing a biologic for PRP patients. CONCLUSIONS: Biologics may be a favourable treatment option leading to greater patient adherence due to reduced dosing frequencies, improvement in quality of life, and reduction in frequency and severity of flares.

Artificial intelligence in dermatology: advancements and challenges in skin of color.

Artificial intelligence (AI) uses algorithms and large language models in computers to simulate human-like problem-solving and decision-making. AI programs have recently acquired widespread popularity in the field of dermatology through the application of online tools in the assessment, diagnosis, and treatment of skin conditions. A literature review was conducted using PubMed and Google Scholar analyzing recent literature (from the last 10 years through October 2023) to evaluate current AI programs in use for dermatologic purposes, identifying challenges in this technology when applied to skin of color (SOC), and proposing future steps to enhance the role of AI in dermatologic practice. Challenges surrounding AI and its application to SOC stem from the underrepresentation of SOC in datasets and issues with image quality and standardization. With these existing issues, current AI programs inevitably do worse at identifying lesions in SOC. Additionally, only 30% of the programs identified in this review had data reported on their use in dermatology, specifically in SOC. Significant development of these applications is required for the accurate depiction of darker skin tone images in datasets. More research is warranted in the future to better understand the efficacy of AI in aiding diagnosis and treatment options for SOC patients.

From Tugs to Treatments: A Systematic Review on Pharmacological Interventions for Trichotillomania.

Trichotillomania (TTM) is a psychiatric disorder with dermatologic consequences, characterized by recurrent hair-pulling. It affects 1-3% of the population, and often coexists with other psychiatric disorders, leading to emotional distress. Effective management of TTM can be challenging due to underdiagnosis, symptom heterogeneity, and stigma. Pharmacological interventions, including SSRIs and NAC are commonly utilized. The objective of this review is to assess the existing literature on pharmacotherapy for trichotillomania and identify potential avenues for future research and treatment advancements. A systematic review of the literature was performed using PubMed and Scopus databases within the last 10 years. Included studies assessed pharmacotherapy for trichotillomania and provided insights into current evidence and potential directions for future research and treatment advancements. In total, 23 articles were identified that met inclusion criteria. The most successful interventions were NAC, aripiprazole, and monoamine oxidase inhibitors. NAC was identified as the most impressive adjunctive therapy in treatment through its mechanism of decreased glutamate-induced excitatory neuronal damage, with adjunctive antioxidant properties. Most of the other therapeutics that were identified require further research and controlled trials to validate their findings. Even if successful therapeutic outcomes are achieved, it is important to consider the patient's comorbidities and to combine pharmacologic interventions with behavioral therapy interventions to comprehensively manage TTM.

Evaluating the clinical efficacy of pulsed dye laser with sirolimus for treatment of capillary malformations: A systematic review.

Port-wine stains (PWS) are capillary vascular anomalies that are often treated with pulsed-dye laser (PDL). Revascularization limits persistent clearance; however, the anti-angiogenic effects of sirolimus (SIRO) may inhibit revascularization. This review aims to determine differences in PWS outcomes when treated with PDL monotherapy or in combination with SIRO. A systematic review was conducted using PubMed, Cochrane, and Embase databases. The following search terms were used: 'port wine stain PDL SIRO', 'port wine stain PDL', and 'port wine stain PDL and topical treatment' with (MeSH) and (Title/Abstract) limits. The search was limited to the English language and human-subject studies conducted between 1 January 2000 and 1 June 2023. Inclusion criteria included studies evaluating SIRO as an adjunct to PDL in patients with PWS. Data extraction and quality assessment were performed by two independent reviewers. A total of nine studies met the inclusion criteria, which included randomized controlled trials (3), case series (2), case reports (3), and a prospective intrapatient study (1), which represented a total of 58 patients. Five studies showed improvement of a measured post-treatment PDL parameter including shortening treatment time and less frequent dosing. A subset of studies (4/9) which did not demonstrate significant clinical improvements exhibited significant photographic evidence of improvement. Heterogeneity among the studies highlights the need for further research and standardization. While adjunctive SIRO shows promise, larger studies and comprehensive evaluation methods are required to establish conclusive safety and efficacy guidelines to shape clinical decision-making.

Unraveling the mirage of fairness cream commercials: A cross-sectional analysis of commercials from South Asia.

BACKGROUND: Fairness products are an essential component of daily beauty routines for many individuals in subcontinental Asia. However, it is important to be aware that these products often contain ingredients that can be detrimental to the skin and are banned in several developed countries. OBJECTIVE: Our study aims to analyze the content of fairness cream commercials in order to gain a deeper understanding of the information used to persuade and influence consumers to use these products. METHODS: Fairness cream commercials originating from countries in subcontinental Asia, including India, Pakistan, Bangladesh, Sri Lanka, and Nepal, were specifically searched and analyzed on the YouTube platform. RESULTS: An analysis of 152 fairness cream commercials on YouTube identified 84.21% of commercials targeted female consumers, while only 15.79% targeted male consumers. 77.63% of commercials used celebrities in their commercials and 47.37% of commercials mentioned specific ingredients. CONCLUSIONS: Based on our findings, it is crucial for dermatologists to take an active role in educating patients and consumers about the potential risks associated with certain ingredients found in fairness creams. Dermatologists should emphasize the importance of prioritizing overall skin health rather than solely focusing on skin lightening.

Myocardial oxygen supply and demand imbalance predicts mortality in older nursing home residents: The PARTAGE study.

BACKGROUND: A mismatch between myocardial oxygen supply and demand is the most common cause of ischemic myocardial injury in older persons. The subendocardial viability ratio (SEVR) can usefully estimate the degree of myocardial perfusion relative to left-ventricular workload. The aim of the present study was to evaluate the ability of SEVR to predict long-term mortality in the older population. Additionally, we aimed to identify the SEVR cutoff value best predicting total mortality. METHODS: This is a multicenter, longitudinal study involving a large population of individuals older than 80 years living in nursing homes. Patients with cancer, severe dementia, and very low level of autonomy were excluded from the study. Participants were monitored for 10 years. Adverse outcomes were recorded every 3 months from inclusion to the end of the study. SEVR reflects the balance between subendocardial oxygen supply and demand, and was estimated non-invasively by analyzing the carotid pressure waveform recorded by applanation arterial tonometry. RESULTS: A total of 828 people were enrolled (mean age: 87.7 ± 4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow-up. SEVR was inversely associated with mortality at univariate Cox-regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502-0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini-Mental State Examination score (risk ratio, 0.647; 95% CI [0.472-0.930]). The lowest tertile of SEVR was associated with higher 10-years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality. CONCLUSIONS: SEVR may be considered as a marker of "cardiovascular frailty." An accurate non-invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults. TRIAL REGISTRATION: NCT00901355, registered on ClinicalTrials.gov website.

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.

Interaction of large artery stiffness and baroreceptor function explored through multiple measurement techniques - a pilot study.

Baroreceptors, sensors that play a role in controlling arterial blood pressure (BP), are mechanical stretch receptors located in the aortic arch and carotid sinuses. Factors affecting the degree of stretch in the vessel wall with BP, such as increased arterial stiffness, may compromise baroreceptor sensitivity (BRS) to BP changes. Yet, evidence of this is scattered, as both baroreceptor sensitivity (BRS) and arterial stiffness are calculated variables with multiple methodological approaches. This pilot study (n=10) investigates the correlation of arterial stiffness and BRS using multiple BRS calculation techniques (spectral and sequence methodologies at aortic and finger sites) and arterial stiffness measurement [carotid-femoral pulse wave velocity (cfPWV), carotid compliance and distensibility]. BRS was assessed under resting BP conditions and during BP altered by maneuvers (0.1 Hz controlled breathing and leg ischemia). Magnitude of arterial stiffness - BRS correlation was positive for carotid distensibility and compliance, and negative for cfPWV, supporting the theory. A sample size of 100 participants (not rounded - exact figure by power calculation) would be required to confirm or reject all permutations of correlation between BRS by multiple calculation methods and large artery stiffness by PWV and compliance/distensibility measures.

From peripheral finger-derived pulse waveforms to aortic pressure waveform features: an application of a generalized transfer function.

OBJECTIVE: Aortic (central) pressure features are associated with cardiovascular complications and can be algorithmically derived from non-invasive peripheral arterial waveforms. This has conventionally been performed with a pressure waveform (i.e., tonometry or oscillometry) rather than with the optical-based sensor (photoplethysmography (PPG)) that is predominantly used in wearable health devices. Extraction of aortic features from a peripheral PPG waveform has yet to be investigated. This study aims to compare aortic features extracted from peripheral arterial waveforms acquired with different sensor modalities using the same transfer function. DESIGN AND METHOD: Radial tonometry (reference), finger volume-clamped PPG (Penáz) and fingertip PPG waveforms were measured in participants (n=29, 36±16 years, 15 female) under baseline conditions. Waveforms were converted into an aortic pressure waveform using the transfer function. Waveform features were extracted from the converted waveform. Extracted features were compared with correlation plots and a Bland-Altman analysis. RESULTS: Aortic pressure features extracted from a finger using the Penáz technique were comparable to radial tonometry derived features. Aortic features extracted from a fingertip waveform were more variable in comparison to radial tonometry-derived features. CONCLUSIONS: Aortic (central) pressure waveform features contain valuable haemodynamic information and have the capacity to be easily and conveniently implemented in wearable health devices. Future use of these features in wearable health devices incorporating PPG requires the development, and/or, optimization of a unique transfer function to more accurately represent the aortic pressure waveform for cardiovascular assessment.Clinical Relevance- Aortic pressure features might be used in wearable health devices following the development of a unique transfer function for optical-transduced peripheral vascular signals.

Comparison of effects of peripheral vasculature on tonometric radial pulse and cuff-based brachial pulse waveform as used in estimation of central aortic pressures.

OBJECTIVE: Aortic pressure estimation requires reliable peripheral pulse waveform acquisition. The peripheral waveform can change with local vascular effects that can be independent of aortic pressure. This study quantifies the effects of peripheral vasculature changes on radial and brachial waveforms. DESIGN AND METHOD: In 20 subjects (37± 15 years, 7 female), brachial volumetric displacement (cuff-based) and radial tonometry waveforms were simultaneously measured whilst a cuff around the hand on the same arm was inflated to induce transmural pressures of -60, -30, -15, 0, 15 and 30 mmHg, altering local peripheral resistance and compliance by graded arterial wall unloading. Aortic blood pressure (BP), augmentation index (AIx) and ejection duration were calculated from the measurements using a generalized transfer function. The parameters under unloaded conditions were compared to baseline measurements. RESULTS: Brachial systolic and diastolic BP did not change throughout the experiment. Altering peripheral resistance and compliance did not significantly change calculated aortic BP values, although changes were nominally greater for radial (maximum +8±1 mmHg) compared to brachial (maximum +2±1 mmHg) waveforms. AIx at 0 mmHg transmural pressure (maximum arterial wall unloading) was higher when derived from radial waveforms (+24±3%, p<0.001) but not when derived from brachial waveforms. CONCLUSIONS: Localized changes in peripheral resistance and compliance affect tonometer acquired radial waveforms but not volumetric displacement acquired brachial pressure waveforms, as judged by computed central aortic augmentation pressure parameters. This suggests aortic pressure estimation from the brachial cuff waveform is less sensitive to peripheral vasculature disturbances that alter the peripheral arterial pulse morphology.