Therapy of Pseudoxanthoma Elasticum: Current Knowledge and Future Perspectives

Pseudoxanthoma elasticum (PXE) is a rare, genetic, metabolic disease with an estimated prevalence of between 1 per 25,000 and 56,000. Its main hallmarks are characteristic skin lesions, development of choroidal neovascularization, and early-onset arterial calcification accompanied by a severe reduction in quality-of-life. Underlying the pathology are recessively transmitted pathogenic variants of the ABCC6 gene, which results in a deficiency of ABCC6 protein. This results in reduced levels of peripheral pyrophosphate, a strong inhibitor of peripheral calcification, but also dysregulation of blood lipids. Although various treatment options have emerged during the last 20 years, many are either already outdated or not yet ready to be applied generally. Clinical physicians often are left stranded while patients suffer from the consequences of outdated therapies, or feel unrecognized by their attending doctors who may feel uncertain about using new therapeutic approaches or not even know about them. In this review, we summarize the broad spectrum of treatment options for PXE, focusing on currently available clinical options, the latest research and development, and future perspectives

Endovascular management of femoral access-site and access-related vascular complications following percutaneous coronary interventions (PCI).

BACKGROUND:Major vascular complications (VCs) of ilio-femoral arterial access after percutaneous coronary interventions are infrequent, but are associated with increased mortality and morbidity. Routine endovascular repair of VCs is becoming the treatment of choice, especially for patients who cannot tolerate vascular surgery due to advanced cardiovascular disease or are in a bailout situation. Here, we review the different types of vascular access site complications associated with percutaneous coronary interventions (PCIs) and assess the safety and efficacy of endovascular treatment. METHODS:Data were retrospectively analysed from patients who experienced VCs after transfemoral PCIs, from December 2014 to May 2018. During this period, out of 2833 patients who underwent femoral coronary interventions, 53 (1.9%) experienced major VCs. RESULTS:In total, 40/53 (75.5%) cases with major VCs led to unplanned endovascular repair and 13/53 (24.5%) cases required surgical repair. VCs included 17 (32.1%) retroperitoneal bleeding events (BARC-2, 3a,b), 20 (37.7%) intimal dissections, and 16 (30.2%) femoral pseudoaneurysms. Overall, 32 (60.4%) patients received a covered stent, two (3.8%) received a nitinol stent, five (9.4%) patients with dissections were treated with prolonged balloon angioplasty alone, and one patient with femoral pseudoaneurysm underwent thrombin injection with simultaneous balloon occlusion. The mean hospital stay for patients after endovascular treatment was 11.06 ± 5.2 days, while for patients after surgical repair it was 17 ± 8.2 days. Endovascularly treated patients were transfused with red blood cells (13/40 32.5% vs. 2/13 15.4%) significantly more often than patients treated surgically, although surgically treated patients received more red blood cell concentrates per unit than endovascularly treated patients (1 ± 0.47 vs. 2 ± 0.93). During the one-year follow-up, no intermittent claudication was reported, and no patient required secondary endovascular or surgical repair. CONCLUSIONS:For patients who cannot tolerate vascular surgery due to advanced cardiovascular disease or are in a bailout situation, endovascular management of VCs following PCIs seems to be a feasible and safe treatment option, and represents an alternative to surgical repair in life-threatening situations. Endovascular treatment was associated with significantly fewer red blood cell concentrates per patient and fewer days in hospital than surgical treatment

Comparative study of pressure (ankle-brachial pressure index) and flow (strain gauge plethysmography and reactive hyperaemia) measurements in diagnosis of peripheral arterial disease in patients with severe aortic stenosis.

BackgroundThe measurement of the ankle-brachial pressure index is a straightforward method for the detection of peripheral disease in the lower limbs. Only a few old studies with small numbers of patients have been conducted comparing the gold standard, ankle-brachial pressure index measurement, with strain gauge plethysmography and reactive hyperaemia for detecting peripheral arterial disease. The purpose of this study was to evaluate the feasibility and accuracy of strain gauge plethysmography values compared with the Doppler ultrasound method, ankle-brachial pressure index, in the assessment of peripheral arterial disease, especially in patients with severe aortic stenosis.Methods221 ankle-brachial pressure index measurements and strain gauge plethysmography measurements of patients with suspected peripheral arterial disease, diagnosed peripheral arterial disease with or without aortic stenosis were compared.ResultsIrrespective of aortic stenosis in patients with and without peripheral arterial disease, the resting arterial blood flow was within the normal range. In patients with aortic stenosis, the time-to-peak flow couldn't detect peripheral arterial disease and was found to be a false negative. In patients without aortic stenosis, time-to-peak flow correlated well with the ankle-brachial pressure index for detecting peripheral arterial disease. Peak flow at 5 seconds was the one of the flow values that correlated with ankle-brachial pressure index and detected peripheral arterial disease in patients with and without aortic stenosis.ConclusionPeak flow at 5 seconds is one of flow value that correlated well with ankle-brachial pressure index in detecting peripheral arterial disease in patients with and without aortic stenosis. Detection of peripheral arterial disease in patients with severe aortic stenosis seems to be less sensitive with flow measurements than with ankle-brachial pressure index

Brief report - Telomere length is a poor biomarker to predict 1-year mortality or cardiovascular comorbidity in patients with transcatheter aortic valve replacement.

BackgroundTranscatheter aortic valve replacement (TAVR) is a therapeutic option for patients with aortic valve stenosis at increased surgical risk. Telomeres are an established marker for cellular senescence and have served to evaluate cardiovascular diseases including severe aortic valve stenosis. In our study, we hypothesized that telomere length may be a predictor for outcome and associated with comorbidities in patients with TAVR.Methods and resultsWe analyzed leucocyte telomere length from 155 patients who underwent TAVR and correlated the results with 1-year mortality and severe comorbidities. The cohort was subdivided into 3 groups according to telomere length. Although a trend for a positive correlation of telomere length with a lower EuroSCORE could be found, telomere length was not associated with survival, aortic valve opening area or cardiovascular comorbidities (peripheral, coronary or cerebrovascular disease). Interestingly, long telomeres were significantly correlated to a reduced left ventricular ejection fraction (LVEF).ConclusionIn elderly patients with severe aortic valve stenosis, leucocyte telomere length did not predict post-procedural survival. The correlation between long telomere length and reduced LVEF in these patients deserves further attention

Lower extremity and carotid artery disease in COPD

In view of their common chronic inflammatory process, we sought to determine the linkage between peripheral artery disease and chronic obstructive pulmonary disease (COPD). 107 COPD patients (mean±sd age 64.6±10.4 years, 52.2% male) and 22 control smokers without previously diagnosed peripheral artery disease underwent standardised angiological examination for lower extremity artery disease (LEAD) and carotid artery disease. LEAD was significantly more prevalent in COPD patients than in controls (80.4% versus 54.5%, p=0.002). Among COPD patients, 57.0%, 12.2%, 10.3% and 0.9% were found to be in Fontaine stages I, IIA, IIB and III, respectively. As with carotid artery disease, its frequency increased from 36.4% in controls to 58.9% in COPD patients (p=0.003). Carotid plaque burden, LEAD Fontaine degrees as well as pulse wave index and ankle–brachial index manifested significant impairment over percentage predicted forced expiratory volume in 1 s (FEV1 % pred) (p=0.02, p<0.001, p=0.01 and p<0.001, respectively). Multivariate analysis revealed that COPD Global Initiative for Chronic Obstructive Lung Disease status was the strongest independent predictor for the presence of plaque in lower extremity arteries (odds ratio 1.63, 95% CI 1.19–2.25, p=0.003) and carotids (odds ratio 1.66, 95% CI 1.14–2.44, p=0.009). As compared with control smokers, peripheral artery disease is diagnosed in a sizeable proportion of COPD patients and exhibits significant distributive differences over FEV1 % pred that exceed the susceptibility conferred by common cardiovascular stressors

Asthma is associated with atherosclerotic artery changes.

Asthma is a chronic airway inflammation with a potential systemic impact. Atherosclerosis is a chronic inflammatory artery disease. The aim of our study was to prove if there is a correlation between the occurrence of asthma and increased atherosclerotic vessel disorders. Vessel status was compared between mild-to-moderate, severe allergic asthma and matched controls. Measurements of artery stiffness were calculated by central pulse wave velocity, ultrasonographic strain imaging and ankle-brachial index. Atherosclerotic plaque burden was assessed by colour-coded duplex sonography. Additionally, analysis of cardiovascular and asthma blood markers was conducted. Arterial stiffness expressed as an increased central pulse wave velocity and decreased circumferential and radial strains as well as the prevalence of media sclerosis were significantly higher among asthma patients compared to controls. Atherosclerotic plaque burden was relevantly increased in asthma groups vs. controls (severe asthma: 43.1%, mild-to-moderate asthma: 25.0%, control: 14.3% of study participants). Except for the elevated IgE and fibrinogen concentrations as well as leukocyte number there were no relevant differences in the blood parameters between the groups. Allergic asthma is associated with distinct atherosclerotic artery changes compared to the respectively matched control collective. The severity of asthma correlates with more pronounced pathological vessel alternations

Brief report – Telomere length is a poor biomarker to predict 1-year mortality or cardiovascular comorbidity in patients with transcatheter aortic valve replacement

Background: Transcatheter aortic valve replacement (TAVR) is a therapeutic option for patients with aortic valve stenosis at increased surgical risk. Telomeres are an established marker for cellular senescence and have served to evaluate cardiovascular diseases including severe aortic valve stenosis. In our study, we hypothesized that telomere length may be a predictor for outcome and associated with comorbidities in patients with TAVR. Methods and results: We analyzed leucocyte telomere length from 155 patients who underwent TAVR and correlated the results with 1-year mortality and severe comorbidities. The cohort was subdivided into 3 groups according to telomere length. Although a trend for a positive correlation of telomere length with a lower EuroSCORE could be found, telomere length was not associated with survival, aortic valve opening area or cardiovascular comorbidities (peripheral, coronary or cerebrovascular disease). Interestingly, long telomeres were significantly correlated to a reduced left ventricular ejection fraction (LVEF). Conclusion: In elderly patients with severe aortic valve stenosis, leucocyte telomere length did not predict post-procedural survival. The correlation between long telomere length and reduced LVEF in these patients deserves further attention

Python data structures and algorithms: improve the performance and speed of your applications

<p>* to be corrected to 0.100 due to multiple testing.</p

Demographic and clinical data of the study population at baseline.

<p>Demographic and clinical data of the study population at baseline.</p