A Knitted and MXenzyme-Integrated Dressing for Geriatrics Diagnosis and Ulcer Healing.

Integrated diagnostic and therapeutic dressings are desirable to relieve diabetic patients who often suffer from diabetic foot ulcers (DFUs) and peripheral vascular diseases (PVDs). However, it is highly difficult to monitor the pulse waves with fidelity under wet environments and connect the waveforms to diseases through a small strain sensor. Additionally, immobilizing MXenzyme to regulate spatially heterogeneous levels of reactive oxygen species (ROS) and applying active intervention to enhance ulcer healing on a single structure remain a complex task. To address these issues, we designed a multiscale wearable dressing comprising a knitted all-textile sensing array for quantitatively investigating the pulse wave toward PVD diagnosis. MXenzyme was loaded onto the dressing to provide multiple enzyme mimics for anti-inflammatory activities and deliver electrical stimulation to promote wound growth. In mice, we demonstrate that high and uniform expression of the vascular endothelial growth factor (VEGF) is observed only in the group undergoing dual mediation with electrical stimulation and MXenzyme. This observation indicates that the engineered wound dressing has the capability to accelerate healing in DFU. In human patient evaluations, the engineered dressing distinguishes vascular compliance and pulse period, enabling the diagnosis of arteriosclerosis and return blockage, two typical PVDs. The designed and engineered multiscale dressing achieves the purpose of integrating diagnostic peripheral vessel health monitoring and ulcer healing therapeutics for satisfying the practical clinical requirements of geriatric patients.

Part II: Cutaneous manifestations of peripheral vascular disease.

In this Part 2 of a 2-part continuing medical education series, we review the epidemiology of peripheral vascular disease, its association with cutaneous symptoms, and the diagnosis and evaluation of cutaneous features of vascular disorders. As peripheral vascular disease becomes more prevalent globally, it is essential for dermatologists to become competent at accurately recognizing and diagnosing cutaneous manifestations and directing individuals to receive appropriate care and treatment.

Modern approaches and innovations in the diagnosis and treatment of peripheral vascular diseases.

Amongst the three major vascular beds (coronary, cerebrovascular, and peripheral), peripheral vascular disease (PVD) has traditionally received the least attention, despite its growing global burden. The aging population has led to the increased prevalence of PVD, thereby increasing visibility to its various diagnostic and treatment modalities. In the past decade, research and development of innovations in the management of PVD has exploded. Modern advances in imaging, molecular technology, medical devices, and surgical techniques have reduced the morbidity and mortality of PVD. However, many challenges still remain due to the debilitating and progressive nature of this disease. In this article, we will introduce some common vascular diseases, the state of art in diagnosis and treatment, the limitations of modern technology, and our vision for this field over the next decade.

Direct aortic transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is a safe and effective alternative to surgical valve replacement in intermediate and even in low-risk patient cohorts. Direct aortic (DAo) route may be used in patients with severe peripheral vascular disease. Here, we present an 88-year old patient hospitalized with cardiogenic shock. Echocardiography revealed severe aortic valve stenosis with aortic valve area 0.5 cm², mean gradient of 55 mmHg, and peak gradient 92 mmHg. TAVI was considered by the Institutional Heart Team. Multislice computed tomography (MSCT) revealed severe peripheral vascular disease, decreased calibration of abdominal aorta, and multiple large vulnerable atherosclerotic plaques. The patient was scheduled for a DAo TAVI. A 26-mm Medtronic CoreValve Evolut R valve was implanted after predilatation with median sternotomy. The patient was discharged after 96 hours. Although transfemoral (TF) access is used as the default approach for TAVI, it was contraindicated in our patient owing to severe peripheral vascular disease and decreased calibration of the abdominal aorta at its narrowest point (4.5 mm) with multiple large vulnerable atherosclerotic plaques. Careful preprocedural MSCT evaluation is essential and directly affects the success of the procedure. MSCT is also mandatory to confirm the best cannulation zone that must be met for a successful DAo TAVI.

Current status of patient-reported outcome measures in vascular surgery.

A previously published review focused on generic and disease-specific patient-reported outcome measures (PROMs) relevant to vascular surgery but limited to arterial conditions. The objective of this project was to identify all available PROMs relevant to diseases treated by vascular surgeons and to evaluate vascular surgeon perceptions, barriers to widespread implementation, and concerns regarding PROMs. We provide an overview of what a PROM is and how they are developed, and summarize currently available PROMs specific to vascular surgeons. We also report results from a survey of 78 Society for Vascular Surgery members serving on committees within the Policy and Advocacy Council addressing the barriers and facilitators to using PROMs in clinical practice. Finally, we report the qualitative results of two focus groups conducted to assess granular perceptions of PROMS and preparedness of vascular surgeons for widespread implementation of PROMs. These focus groups identified a lack of awareness of existing PROMs, knowledge of how PROMs are developed and validated, and clarity around how PROMs should be used by the clinician as main subthemes for barriers to PROM implementation in clinical practice.

Mosaic RASopathy due to KRAS variant G12D with segmental overgrowth and associated peripheral vascular malformations.

Oncogenic RAS variants lead to constitutive overactivation and increased signal transduction into downstream pathways. They are found as somatic driver events in various types of human cancer. In a somatic mosaic status, the same RAS variants have been associated with a wide spectrum of focal or segmental tissue dysplasia and overgrowth including various types of congenital nevi, vascular malformations, and other changes (mosaic RASopathies). We present a 3-year-old male patient with segmental overgrowth of the subcutaneous fatty tissue of the right lower extremity with colocalized arteriovenous and capillary malformations and dysplastic draining veins in combination with talipes equinovarus of the right foot. In tissue biopsies of the affected extremity, we identified a mosaic KRAS variant, c.35G>A (p.Gly12Asp), while this variant was absent in the DNA extracted from a biopsy of the normal extremity. This report provides further evidence for the wide clinical and phenotypic variability associated with mosaic KRAS variants. The described pattern confirms that the combination of segmental overgrowth and vascular anomalies in the form of arteriovenous and capillary malformations is a possible manifestation of a mosaic RASopathy. The accurate genetic diagnosis is crucial for molecular-targeted therapy, which might be a future therapeutic target for mosaic RASopathies.

A 19-Year-Old-Woman With Backache, Hemoptysis, and Hypereosinophilia.

CASE PRESENTATION: A 19-year-old woman presented to our ED with complaints of backache and massive hemoptysis. Her medical history included acute dyspnea that developed within hours caused by angioneurotic edema 6 months earlier. Two days later, she was given thrombolytic treatment because of massive pulmonary thromboembolism. She had been given methylprednisolone 4 mg and tinzaparin sodium 0.7 mL subcutaneously and was still under treatment on the current admission. She had no history of smoking, alcohol, or oral contraceptive use, surgery, trauma, recent travel, clotting disorders, or familial diseases.

Case Report: Novel SAVI-Causing Variants in STING1 Expand the Clinical Disease Spectrum and Suggest a Refined Model of STING Activation.

Gain-of-function mutations in STING1 cause the monogenic interferonopathy, SAVI, which presents with early-onset systemic inflammation, cold-induced vasculopathy and/or interstitial lung disease. We identified 5 patients (3 kindreds) with predominantly peripheral vascular disease who harbor 3 novel STING1 variants, p.H72N, p.F153V, and p.G158A. The latter two were predicted by a previous cryo-EM structure model to cause STING autoactivation. The p.H72N variant in exon 3, however, is the first SAVI-causing variant in the transmembrane linker region. Mutations of p.H72 into either charged residues or hydrophobic residues all led to dramatic loss of cGAMP response, while amino acid changes to residues with polar side chains were able to maintain the wild type status. Structural modeling of these novel mutations suggests a reconciled model of STING activation, which indicates that STING dimers can oligomerize in both open and closed states which would obliviate a high-energy 180° rotation of the ligand-binding head for STING activation, thus refining existing models of STING activation. Quantitative comparison showed that an overall lower autoactivating potential of the disease-causing mutations was associated with less severe lung disease, more severe peripheral vascular disease and the absence of a robust interferon signature in whole blood. Our findings are important in understanding genotype-phenotype correlation, designing targeted STING inhibitors and in dissecting differentially activated pathways downstream of different STING mutations.

Progress in aorta and peripheral cardiovascular disease research.

Although coronavirus disease 2019 seems to be the leading topic in research number of outstanding studies have been published in the field of aorta and peripheral vascular diseases likely affecting our clinical practice in the near future. This review article highlights key research on vascular diseases published in 2020. Some studies have shed light in the pathophysiology of aortic aneurysm and dissection suggesting a potential role for kinase inhibitors as new therapeutic options. A first proteogenomic study on fibromuscular dysplasia (FMD) revealed a promising novel disease gene and provided proof-of-concept for a protein/lipid-based FMD blood test. The role of NADPH oxidases in vascular physiology, and particularly endothelial cell differentiation, is highlighted with potential for cell therapy development. Imaging of vulnerable plaque has been an intense field of research. Features of plaque vulnerability on magnetic resonance imaging as an under-recognized cause of stroke are discussed. Major clinical trials on lower extremity peripheral artery disease have shown added benefit of dual antithrombotic (aspirin plus rivaroxaban) treatment.

Repeatability, and Intra-Observer and Interobserver Agreement of Two Dimensional Perfusion Angiography in Patients with Chronic Limb Threatening Ischaemia.

OBJECTIVE: Two dimensional (2D) perfusion angiography is a method that provides quantitative foot perfusion information from standard digital subtraction angiography acquisitions. The aim of this study was to test the reliability of this method in patients with chronic limb threatening ischaemia (CLTI) by investigating repeatability, and intra-observer and interobserver agreement. METHODS: Twenty patients with CLTI and a below the knee endovascular revascularisation were included in a prospective clinical study. Prior to treatment two perfusion angiography runs were acquired with a five minute interval without performing an intervention. In these recordings, regions of interest were selected and time density curves and perfusion parameters were determined. To investigate intra-observer agreement one observer performed five measurements on the same acquisition for each patient. To investigate interobserver agreement three observers performed measurements on the same acquisition for each patient. Results were presented in Bland-Altman plots and as the intraclass correlation coefficient per parameter. RESULTS: Two patients were excluded from repeatability analyses because of major motion artefacts. Repeatability analyses of the 18 remaining patients showed excellent correlation for every parameter (> .96). Intra-observer and interobserver agreement for all 20 patients were excellent for all parameters (1.00). CONCLUSION: Repeatability and intra-observer and interobserver agreement of 2D perfusion angiography in patients with CLTI were found to be excellent. It is therefore a reliable tool when used according to the standardised methods described in this study.

The oral health status of patients with peripheral vascular disorders: A systematic review.

OBJECTIVES: Periodontal disease and tooth loss were found to be associated with several peripheral vascular disorders. Nonetheless, an evaluation of the literature on the broader domains of oral health in individuals with peripheral vascular disorders is lacking. This systematic review aims to collate the current evidence on the oral health status of individuals with peripheral vascular disorders. METHODS: Five electronic databases were searched for studies assessing oral health parameters in individuals with peripheral vascular disorders. Outcome measures considered were periodontal health, dentition status, caries indices, oral prostheses, oral pathologies and oral hygiene behaviours. The Newcastle-Ottawa scale was used to appraise the quality of the studies. RESULTS: From 3025 records identified, 24 studies involving 1232 participants with peripheral vascular disorders were included in this review. In nine studies, periodontitis was significantly more prevalent in peripheral vascular disorders compared to non-peripheral vascular disorders participants. A further six studies reported individuals with peripheral vascular disorders also had significantly fewer teeth and increased rates of edentulism. Only one study reported a higher incidence of dental caries in peripheral vascular disorders participants. Other aspects of oral health such as oral prosthesis, oral pathology and oral hygiene behaviours were seldom assessed. CONCLUSIONS: The scarcity of studies reporting on broader domains limited our ability to arrive at a conclusion regarding the oral health status of individuals with peripheral vascular disorders. Future studies ought to assess these domains in individuals with peripheral vascular disorders and controls to gain a more complete understanding of oral health and its potential association with peripheral vascular disorders.

Peripheral Vascular Disease and Kidney Transplant Outcomes: Rethinking an Important Ongoing Complication.

Peripheral vascular disease (PVD) is highly prevalent in patients on the waiting list for kidney transplantation (KT) and after transplantation and is associated with impaired transplant outcomes. Multiple traditional and nontraditional risk factors, as well as uremia- and transplant-related factors, affect 2 processes that can coexist, atherosclerosis and arteriosclerosis, leading to PVD. Some pathogenic mechanisms, such as inflammation-related endothelial dysfunction, mineral metabolism disorders, lipid alterations, or diabetic status, may contribute to the development and progression of PVD. Early detection of PVD before and after KT, better understanding of the mechanisms of vascular damage, and application of suitable therapeutic approaches could all minimize the impact of PVD on transplant outcomes. This review focuses on the following issues: (1) definition, epidemiological data, diagnosis, risk factors, and pathogenic mechanisms in KT candidates and recipients; (2) adverse clinical consequences and outcomes; and (3) classical and new therapeutic approaches.

A visually striking case of primary acrocyanosis: A rare cause of the blue digit.

Cold environments can trigger a variety of conditions, which, in their acute phase often present to the Emergency Department. Primary acrocyanosis is a distinct, rare condition which may be missed resulting in misdiagnosis and mismanagement. Primary acrocyanosis is a peripheral vascular disorder defined by painless, symmetrical discoloration of the distal appendages and uniquely characterized by persistence of the skin color changes after cold exposure. We present a case of a 24-year-old female who presented to the Emergency Department with peripheral cyanosis after cold exposure and was eventually diagnosed with primary acrocyanosis by Rheumatology. The prognosis for primary acrocyanosis is quite good in comparison to other acrosyndromes and once secondary causes of acrocyanosis have been ruled, out can be managed conservatively with lifestyle modifications and potential follow-up with Rheumatology.

Hemodynamic and Clinical Implications of Impaired Pulmonary Vascular Reserve in the Fontan Circulation.

BACKGROUND: Pulmonary vascular disease, pulmonary endothelial dysfunction, liver fibrosis, renal disease, and exercise intolerance are common in adults with Fontan physiology. Although the pathophysiologic mechanisms linking these phenomena have been studied, certain aspects are not well understood. OBJECTIVES: This study hypothesized that impaired pulmonary vascular reserve (VR) plays a central role linking these abnormalities, and that patients with abnormal pulmonary VR with exercise, compared with patients with normal VR, would display poorer pulmonary endothelial function, greater liver stiffness, more renal dysfunction, and poorer exercise capacity. METHODS: Symptomatic adults with the Fontan palliation (n = 29) underwent invasive cardiopulmonary exercise testing, echocardiography, and assessment of microvascular function. Abnormal pulmonary VR was defined by the slope of increase in pulmonary pressure relative to cardiac output with exercise >3 mm Hg/l/min. Pulmonary endothelial function was assessed using reactive hyperemia index. End-organ function was assessed using magnetic resonance elastography-derived liver stiffness, glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, and peak oxygen consumption (Vo2). RESULTS: Compared with individuals with normal VR (n = 8), those with abnormal VR (n = 21) displayed higher central and pulmonary venous pressures, and more severely impaired cardiac output and stroke volume responses to exertion, but similar pulmonary vascular resistance at rest. Patients with abnormal VR displayed more severely impaired reactive hyperemia index, increased liver stiffness, lower glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide, and lower peak Vo2. As compared to pulmonary vascular resistance at rest, slope of increase in pulmonary pressure relative to cardiac output displayed stronger correlations with reactive hyperemia index (r = -0.63 vs. r = -0.31; Meng test p = 0.009), magnetic resonance elastography-derived liver stiffness (r = 0.47 vs. r = 0.29; Meng test p = 0.07), glomerular filtration rate (r = -0.52 vs. r = -0.24; Meng test p = 0.03), N-terminal pro-B-type natriuretic peptide (r = 0.56 vs. r = 0.17; Meng test p = 0.02), and peak Vo2 (r = -0.63 vs. r = -0.26; Meng test p = 0.02). CONCLUSIONS: Pulmonary vascular limitations in Fontan physiology are related to pulmonary endothelial and end-organ dysfunction, suggesting a mechanistic link between these commonly observed findings, and these abnormalities are more apparent during exercise testing, with little relationship at rest.