Vascular System Involvement Research Articles

Ischemic Stroke and Myocarditis Revealing Behçet’s Disease in a Young Adult: Diagnostic Challenges and Therapeutic Perspectives

Introduction: Behçet’s disease is a rare, systemic, inflammatory condition that primarily affects young adults. It is characterized by a variety of clinical manifestations. However, neurological and cardiac presentations remain uncommon and often delayed in diagnosis. This disease can lead to severe complications, such as ischemic strokes and myocarditis, highlighting the systemic and complex nature of the condition. Case presentation: A 27-year-old patient was hospitalized after experiencing an ischemic stroke and myocarditis, which revealed Behçet’s disease. He had a history of oral and cutaneous ulcers, without a prior diagnosis of Behçet. Upon admission, brain imaging confirmed an ischemic stroke, and echocardiography and cardiac MRI showed acute myocarditis. Biological tests confirmed elevated systemic inflammation, which guided the treatment plan. The initial treatment included corticosteroids, immunosuppressors (azathioprine), and cardioprotective therapy. The patient showed significant clinical improvements, although mild deficits persist. Discussion: Myocarditis in Behçet’s disease is a rare but severe manifestation resulting from inflammation of the heart walls, often associated with other systemic vascular involvement. Although less common than oral or cutaneous ulcers, myocarditis can lead to acute heart dysfunction and even heart failure if not treated promptly. It is generally caused by an excessive inflammatory response, often associated with immune system activation, which affects the coronary circulation and damages the cardiac muscle. Treatment for myocarditis in this context relies on high-dose corticosteroids to control inflammation, followed by long-term immunosuppressive medications like azathioprine. While the initial treatment often leads to a rapid improvement in cardiac function, the risk of long-term complications, such as dilated cardiomyopathy or heart failure, remains high. Close follow-up is therefore essential to prevent these complications and optimize the long-term cardiac prognosis of patients with this rare disease. Conclusion: The progression of myocarditis in Behçet’s disease can be favorable if diagnosed and treated early, with significant improvement in cardiac function achieved through the use of corticosteroids and immunosuppressive therapy. However, the long-term prognosis remains uncertain due to the risk of chronic cardiac complications, such as dilated cardiomyopathy or heart failure.

Cerebral arteriopathies of childhood and stroke - A focus on systemic arteriopathies and pediatric fibromuscular dysplasia (FMD).

Systemic vascular involvement in children with cerebral arteriopathies is increasingly recognized and often highly morbid. Fibromuscular dysplasia (FMD) represents a cerebral arteriopathy with systemic involvement, commonly affecting the renal and carotid arteries. In adults, FMD diagnosis and classification typically relies on angiographic features, like the 'string-of-beads' appearance, following exclusion of other diseases. Pediatric FMD (pFMD) is considered equivalent to adult FMD although robust evidence for similarities is lacking. We conducted a comprehensive literature review on pFMD and revealed inherent differences between pediatric and adult-onset FMD across various domains including epidemiology, natural history, histopathophysiology, clinical, and radiological features. Although focal arterial lesions are often described in children with FMD, the radiological appearance of 'string-of-beads' is highly nonspecific in children. Furthermore, children predominantly exhibit intimal-type fibroplasia, common in other childhood monogenic arteriopathies. Our findings lend support to the notion that pFMD broadly reflects an undefined heterogenous group of monogenic systemic medium-or-large vessel steno-occlusive arteriopathies rather than a single entity. Recognizing the challenges in categorizing complex morphologies of cerebral arteriopathy using current classifications, we propose a novel term for describing children with cerebral and systemic vascular involvement: 'cerebral and systemic arteriopathy of childhood' (CSA-c). This term aims to streamline patient categorization and, when coupled with advanced vascular imaging and high-throughput genomics, will enhance our comprehension of etiology, and accelerate mechanism-targeted therapeutic developments. Lastly, in light of the high morbidity in children with cerebral and systemic arteriopathies, we suggest that investigating for systemic vascular involvement is important in children with cerebral arteriopathies.

Impact of COVID-19 on the Risk of Developing Dermatological Conditions

Introduction: The COVID-19 pandemic, caused by SARS-CoV-2, has impacted global health across various medical domains, including dermatology. Dermatological manifestations are increasingly recognized in COVID-19 patients. This study aimed to evaluate the risk of developing dermatological conditions in patients with COVID-19 compared to non-COVID patients. Methods: This retrospective cohort study analyzed electronic health records (EHRs) from January 1, 2020, to January 1, 2022, including two cohorts: COVID-19 patients with confirmed diagnoses and non-COVID patients. The primary outcome was the development of new dermatological conditions within three months of the index date. Risk differences and risk ratios (RRs) were calculated to compare the cohorts. Confounding factors such as age, sex, race, and ethnicity were controlled during the statistical analysis. Statistical significance was set at p < 0.05. Results: COVID-19 patients exhibited a significantly reduced risk for various dermatological conditions, including acne vulgaris (RR = 0.671), atopic dermatitis (RR = 0.649), and seborrheic dermatitis (RR = 0.606), among others. Certain rarer conditions, such as lichen planus (RR = 0.585) and basal cell carcinoma (RR = 0.517), also showed a decreased incidence. However, pallor was significantly more prevalent in COVID-19 patients (RR = 2.328), suggesting systemic vascular involvement. Conclusion: The findings indicate a reduced risk for many dermatological conditions in COVID-19 patients, possibly due to immune modulation and vascular alterations by the virus. Pallor’s increased prevalence in these patients underscores the broader systemic effects of COVID-19. These results contribute to our understanding of COVID-19's dermatological impacts, offering insights for better patient management and future research into the long-term effects on skin health.

Relationship between retinal microvascular impairment and subclinical atherosclerosis in SLE

ObjectivesPatients with SLE have higher cardiovascular (CV) risk compared with healthy controls (HC) and are characterised by accelerated atherosclerosis; intima media thickness (IMT), marker of subclinical atherosclerosis, is higher in...

Nailfold Capillaroscopy in Early Stages of Mixed Connective Tissue Disease in a Sample of Egyptian Patients

Introduction: Mixed connective tissue disease (MCTD) is a systemic autoimmune disease with a high titer of anti-U1 small nuclear ribonucleoprotein particles and a number of clinical pictures, mainly Raynaud's phenomenon. Nailfold capillaroscopy (NFC) is a noninvasive diagnostic tool for patients with different connective tissue diseases that permit detection of local microvascular changes that correlate with systemic vascular involvement. Aim of the Study: The aim of this study was to compare the results of NFC in patients with systemic sclerosis (SSc) and MCTD to determine the chief characteristics of skin microangiopathy in early MCTD and attempt to describe a characteristic MCTD pattern in Egyptian patients. Methodology: This cross-sectional study included forty patients diagnosed with MCTD according to Alarcón-Segovia and Villareal criteria and twenty patients with confirmed systemic sclerosis according to the American College of Rheumatology and the European League against Rheumatism classification criteria for Systemic Sclerosis. Nailfold examination for the study subjects was performed describing architectural derangement, capillary density changes, mega capillary and enlarged loops, microhemorrhages, and angiogenesis. Results: Of the sixty patients studied, 49 (81.7%) patients were females and 11 were males with a mean age of 31 years with a median of 29.5 and range 16–52 years. Three of the twenty patients diagnosed with systemic sclerosis had arthritis. Out of sixty patients, 53.3% had thickened skin, 19 patients exhibited puffy fingers, six patients showed rash, and none had swollen joints. The skin was significantly thicker in systemic sclerosis patients (85%) compared to 37.5% in the MCTD population. Patients presented with various features, the most common of which was fatigue (26.7%) and myositis (23% of patients). There is a significant negative correlation of −0.508 (P = 0.022) between the enlargement scores and illness duration in systemic sclerosis patients. Those patients also exhibited a statistically significant positive correlation of 0.520 (P = 0.019) between hemorrhage score and the number of tender joints. Alternatively, patients diagnosed with MCTD exhibited a significant positive correlation between the architectural changes scores of their joints and both the duration of their illness (0.347; P = 0.028) and the number of swollen joints (0.424; P = 0.006). MCTD patients also showed a significant correlation of 0.423 (P = 0.007) between their hemorrhage scores and their age at the time of the study. Conclusion: In this study, the results obtained were qualitatively satisfactory for clear delineation of the nailfold capillaries features in MCTD. Therefore, it aids in the recognition of alternations in nailfold capillaries making an early prediction of course of illness in MCTD patients possible and suggests a potential ability to differentiate from early SSc, thus helps in preventing morbidities and sequelae of the disease.

Retinal microvascular impairment in COVID-19 patients: A meta-analysis.

BackgroundThe coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has led to a global pandemic in an unprecedented time frame. Systemic vascular involvement in COVID‐19 has been identified, and SARS‐CoV‐2 has also been found to cause multiple organ ischemia and posterior ocular segment disease in mammals, raising concerns about the human retinal microvascular involvement in SARS‐CoV‐2.ObjectiveTo objectively assess the presence of retinal microvascular impairment in COVID‐19 patients by optical coherence tomography angiography (OCTA), so as to facilitate the clinical system management of COVID‐19 patients.MethodsWe searched PubMed, Cochrane Library, EMBASE, Ovid, CBM to collect eligible studies. The main outcomes included the vessel density (VD), area or perimeter of foveal avascular zone (FAZ), central foveal thickness (CFT), subfoveal choroidal thickness (SCT) in our meta‐analysis.ResultsWe eventually included five studies with a total of 401 participants. Our meta‐analysis showed that nonacute infectious COVID‐19 or post‐COVID‐19 patients presented significantly lower foveal VD of deep capillary plexus (WMD = −4.22, 95% CI [−8.00, −0.43]) and thinner SCT (WMD = −10.33, 95% CI [−19.08, −1.57]) than healthy controls. The foveal VD and parafoveal VD of superficial capillary plexus, parafoveal VD of deep capillary plexus, CFT, area, and perimeter of FAZ showed no significant differences between the groups.ConclusionThe patients of nonacute infectious COVID‐19 or post‐COVID‐19 displayed alterations in the retinal microvasculature and choroidal vessels, including a significantly lower foveal VD in deep capillary plexus and thinner SCT. The impairment may be a medium to long‐term process. Close ophthalmic surveillance is necessary for COVID‐19 patients or post‐COVID‐19 patients.

Quantitative changes in peripapillary, macular, and choriocapillaris microvasculature of patients with non-ocular Behçet's disease and relationship with systemic vascular involvement, an optical coherence tomography angiography study

BackgroundTo evaluate the changes in the peripapillary, macular and choriocapillaris microvasculatures in the eyes of patients with Behçet's disease (BD) without ocular involvement by optical coherence tomography angiography (OCT-A) and to investigate the relationship with systemic vascular involvement (SVI). MethodsThe study included 56 eyes of 33 patients with non-ocular BD and 61 eyes of 33 healthy subjects. The macular microvascular (MMV) vessel densities (VDs), FAZ parameters, Choriocapillaris flow area (CCFA), radial peripapillary capillary (RPC) VDs and optic nerve head (ONH) analyses were performed with OCT-A. MMV, RPC, ONH, and CCFA measurements were compared between the non-ocular BD patients and healthy controls. Then, the patient group was divided into two subgroups according to the presence of SVI. MMV, RPC, and CCFA measurements of these subgroups were compared with the healthy controls. ResultsWhile deep capillary plexus VD and foveal density decreased in MMV analysis in the BD group compared to the control group, CCFA was not different. In the RPC and ONH analysis, the VDs of the inside-disc small vessels and the VDs of the inside-disc all vessels were decreased while the cup/disk area ratio and cup volume were increased in the BD group compared to the healthy controls. Furthermore, the VDs of the inside-disc vessels were reduced in patients without SVI compared to those with SVI and healthy controls. ConclusionsThe RPC network, ONH and MMV architecture analysis by OCT-A revealed changes in the MMV, RPC, and ONH structures in non-ocular BD patients. Moreover, the decrease in RPC VDs and MMV VDs in patients without SVI suggested that the patients with BD without SVI had subclinical ocular involvement even in the absence of clinical ocular findings.

Assessment of microvascular involvement in lupus nephritis patients by retinal OCT-angiography and kidney biopsies.

Ocular and renal microvascular damage in lupus nephritis (LN) share similar physiopathological pathways that have investigated using traditional fundus examination and high-resolution colour electroretinography. Optical coherence tomography angiography (OCTA) is a recent, non-invasive technique for imaging the microvasculature of retina and choroid. Aim of the study was to investigate through OCTA analysis the relationship between retinal microvascular alterations and renal functional and histologic features. Systemic lupus erythematosus (SLE) patients with LN, SLE without renal involvement and healthy controls were recruited and accomplished an ophthalmological evaluation, including OCTA. SLE-LN patients underwent a rheumatological evaluation, including disease-related clinical and laboratory features collection and kidney biopsy examination. This cross-sectional study enrolled forty-six eyes of 23 LN patients, thirty-two eyes of 16 SLE patients and forty-two eyes of 21 controls. Thirteen SLE-LN patients (56.5%) displayed lupus retinopathy, 10 at moderate (77%) and 3 at severe stage (23%) by fundus oculi examination. Analysis of OCTA data showed with high/moderate accuracy a reduction of retinal capillary vessel density in both SLE and SLE-LN patients compared to controls in superficial and deep plexi. A reduction in fovea thickness and an increase in foveal avascular zone were also detected. OCTA data of LN patients correlated with LN duration, disease activity, kidney function and the presence of LN-vascular lesions at kidney biopsy. Our results suggest the role of OCTA in early detection of systemic vascular involvement in SLE-LN patients and related kidney functional-histological impairment.

Prognostic significance of atherosclerosis of one or two vascular systems in patients with high and very high cardiovascular risk

Aim.To study the prognostic significance of atherosclerosis of one and several vascular systems in patients with high and very high cardiovascular risk (CVR).Material and methods. The study included 171 patients with high (26,9%) and very high (73,1%) CVR. All patients underwent duplex ultrasound of the carotid and lower limb arteries. The composite endpoint (CE) was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and coronary revascularization.Results.The follow-up period lasted 31,1 (17,8; 47,9) months. CE events occurred in 29 (16,9%) patients: cardiovascular death — 3 (1,75%) patients; nonfatal myocardial infarction — 7 (4,09%) patients; nonfatal stroke — 6 (3,51%) patients; coronary revascularization — 13 (7,60%) patients. Cumulative survival of patients with high and very high CVR with atherosclerotic plaques in the same vascular system did not significantly differ from that in patients with intact peripheral arteries (p=0,977). The event-free survival of patients with combined lesions of the carotid and lower limb arteries was significantly lower in comparison with patients with one vascular system involvement (p=0,011). The combined lesion of the carotid and lower limb arteries was associated with an increase in the relative risk (RR) of adverse cardiovascular events (RR, 3,15 (95% CI, 1,02-9,74; p=0,046), adjusted for sex, age, and peripheral arterial disease symptoms.Conclusion.In patients with high and very high CVR, atherosclerotic lesion of two vascular systems of peripheral arteries is associated with an increase in the RR of adverse cardiovascular events, adjusted for sex, age, and peripheral arterial disease symptoms. The presence of atherosclerotic plaques in one vascular bed was not associated with an increase in the risk of CE events.

SARS-CoV-2 leads to a small vessel endotheliitis in the heart.

BackgroundSARS-CoV-2 infection (COVID-19 disease) can induce systemic vascular involvement contributing to morbidity and mortality. SARS-CoV-2 targets epithelial and endothelial cells through the ACE2 receptor. The anatomical involvement of the coronary tree is not explored yet.MethodsCardiac autopsy tissue of the entire coronary tree (main coronary arteries, epicardial arterioles/venules, epicardial capillaries) and epicardial nerves were analyzed in COVID-19 patients (n = 6). All anatomical regions were immunohistochemically tested for ACE2, TMPRSS2, CD147, CD45, CD3, CD4, CD8, CD68 and IL-6. COVID-19 negative patients with cardiovascular disease (n = 3) and influenza A (n = 6) served as controls.FindingsCOVID-19 positive patients showed strong ACE2 / TMPRSS2 expression in capillaries and less in arterioles/venules. The main coronary arteries were virtually devoid of ACE2 receptor and had only mild intimal inflammation. Epicardial capillaries had a prominent lympho-monocytic endotheliitis, which was less pronounced in arterioles/venules. The lymphocytic-monocytic infiltrate strongly expressed CD4, CD45, CD68. Peri/epicardial nerves had strong ACE2 expression and lympho-monocytic inflammation. COVID-19 negative patients showed minimal vascular ACE2 expression and lacked endotheliitis or inflammatory reaction.InterpretationACE2 / TMPRSS2 expression and lymphomonocytic inflammation in COVID-19 disease increases crescentically towards the small vessels suggesting that COVID-19-induced endotheliitis is a small vessel vasculitis not involving the main coronaries. The inflammatory neuropathy of epicardial nerves in COVID-19 disease provides further evidence of an angio- and neurotrophic affinity of SARS-COV2 and might potentially contribute to the understanding of the high prevalence of cardiac complications such as myocardial injury and arrhythmias in COVID-19.FundingNo external funding was necessary for this study.

Anti-vinculin antibodies in scleroderma (SSc): a potential link between autoimmunity and gastrointestinal system involvement in two SSccohorts.

Systemic sclerosis (SSc) is an autoimmune disorder and commonly presents with vascular system involvement and motility disorders in the gastrointestinal (GI) tract. Vinculin is a cytoskeletal protein that plays major roles in cell-cell adhesion and is expressed in the neuromuscular apparatus of the gut. Antibodies to vinculin have been identified as a biomarker of irritable bowel syndrome (IBS). Our aim was to evaluate serum anti-vinculin antibodies in patients with SSc. Patients were recruited from two SSc centers: group I (GI-enriched group), University of Leeds, UK, and Group II (vascular predominant), University of California, Los Angeles.Serum samples of patients recruited from two SSc centres, Group I ( GI enriched group), University of Leeds, UK and Group II (Vascularpredominant), University of California, Los Angeles) were collected. Samples from age- and sex-matched healthy volunteers (N = 88) were used ascontrols. Group I (GI-enriched group, N = 83) patients were 58 [50-67] years old; 83% were females with a median body mass index (BMI) of 20.3 (21.2 ± 4.5) [18-23]. Group II (vascular-enriched group, N = 72) patients were 58 [50-67] years old; 80% were female, and BMI was 23.9 (21.3-26.9). More subjects in group I had prominent GI involvement (N = 55, 66%) than group II (12, 16%), p ˂ 0.0001. Anti-vinculin antibody levels in SSc group I (1.3 [0.9]) were significantly higher than in HC (0.7 [0.8]; p = 0.002). When pooled, circulating anti-vinculin levels in both SSc groups remained significantly higher than in the HC group (p = 0.02). Higher anti-vinculin levels were associated with higher GI-visual analogue scale (GI-VAS) scores and specifically with GI-VAS scores of ≥ 4 (p < 0.0001). This study demonstrates that elevated anti-vinculin antibody levels are common in SSc and suggests a potential link between increased anti-vinculin levels and GI tract symptoms. • Anti-vinculin antibodies are elevated in systemic sclerosis and are relatively common. • In these SSc patients, anti-vinculin antibodies are associated with higher levels of GI symptoms in SSc. • A potential link between anti-vinculin antibodies and vascular system involvement was shown.

Microvascular dysfunction in COVID-19: the MYSTIC study

RationalePre-clinical and autopsy studies have fueled the hypothesis that a dysregulated vascular endothelium might play a central role in the pathogenesis of ARDS and multi-organ failure in COVID-19.ObjectivesTo comprehensively characterize and quantify microvascular alterations in patients with COVID-19.MethodsHospitalized adult patients with moderate-to-severe or critical COVID-19 (n = 23) were enrolled non-consecutively in this prospective, observational, cross-sectional, multi-center study. Fifteen healthy volunteers served as controls. All participants underwent intravital microscopy by sidestream dark field imaging to quantify vascular density, red blood cell velocity (VRBC), and glycocalyx dimensions (perfused boundary region, PBR) in sublingual microvessels. Circulating levels of endothelial and glycocalyx-associated markers were measured by multiplex proximity extension assay and enzyme-linked immunosorbent assay.Measurements and main resultsCOVID-19 patients showed an up to 90% reduction in vascular density, almost exclusively limited to small capillaries (diameter 4–6 µm), and also significant reductions of VRBC. Especially, patients on mechanical ventilation showed severe glycocalyx damage as indicated by higher PBR values (i.e., thinner glycocalyx) and increased blood levels of shed glycocalyx constituents. Several markers of endothelial dysfunction were increased and correlated with disease severity in COVID-19. PBR (AUC 0.75, p = 0.01), ADAMTS13 (von Willebrand factor-cleaving protease; AUC 0.74, p = 0.02), and vascular endothelial growth factor A (VEGF-A; AUC 0.73, p = 0.04) showed the best discriminatory ability to predict 60-day in-hospital mortality.ConclusionsOur data clearly show severe alterations of the microcirculation and the endothelial glycocalyx in patients with COVID-19. Future therapeutic approaches should consider the importance of systemic vascular involvement in COVID-19.

Nailfold Capillaroscopy of Resting Peripheral Blood Flow in Exfoliation Glaucoma and Primary Open-Angle Glaucoma

Systemic blood flow alterations have been described using video nailfold capillaroscopy (NFC) in high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) variants of primary open-angle glaucoma (POAG). To date, no previous studies have explored alterations in nailfold capillary blood flow in exfoliation glaucoma (XFG). To investigate the measure of peripheral blood flow as a surrogate marker of systemic vascular involvement in patients with XFG, HTG, and NTG, as well as in individuals serving as controls, using NFC. A cross-sectional clinic-based study at the New York Eye and Ear Infirmary of Mount Sinai was conducted from July 6, 2017, to May 18, 2018. A total of 111 participants (30 XFG, 30 NTG, 30 HTG, and 21 controls) received a comprehensive ophthalmic examination to confirm eligibility. Exclusion criteria were the presence of connective tissue disease, uncontrolled diabetes, history of bleeding disorders, and/or history of trauma or surgery to the nondominant hand. Resting capillary blood flow at the nailfold of the fourth digit of the nondominant hand in patients with NTG, HTG, XFG, and controls, using NFC. Two participants were excluded owing to poor nailfold image quality, resulting in 109 participants. Sixty-two participants (57%) were women and 79 (72%) were white. Mean (SD) age of the participants was 67.9 (11.7) years. Mean (SD) resting peripheral capillary blood flow at the nailfold for controls was 70.9 (52.4) picoliters/s (pL/s); HTG, 47.5 (41.9) pL/s; NTG, 40.1 (16.6) pL/s; and XFG, 30.6 (20.0) pL/s. Multivariable analysis of the differences of flow in HTG vs control participants showed values of -18.97 (95% CI, -39.22 to 1.27; P = .07) pL/s, NTG vs controls of -25.17 (95% CI, -45.92 to -4.41; P = .02) pL/s, and XFG vs controls of -28.99 (95% CI, -51.35 to -6.63; P = .01) pL/s. Decreased resting peripheral capillary blood flow may occur in patients with XFG and NTG compared with individuals without glaucoma. These findings may contribute to understanding the possible systemic nature of glaucoma.

Vascular anomalies in the mesenteric circulation of patients with Crohn’s disease: a pilot study

Crohn’s disease (CD) is a chronic inflammatory bowel disease and its pathogenesis is still not well understood. Previous studies suggested the possibility of the involvement of vascular system, but, todate, the mesenteric circulation has poor been investigated, especially in complicated CD cases requiring colectomy. We investigated the mesenteric circulation in a case-control pilot study, including 19 controls and 7 patients affected by complicated cases of CD. Cases and controls underwent selective angiography of both superior and inferior mesenteric district. Transit time was found either significantly shortened in 2/7 cases (29%), or prolonged 5/7 (71%) (P=0.0034 in the superior mesenteric district; P=0.0079 in the inferior mesenteric district), respectively due to the presence of A-V malformations and of a miscellaneous of venous abnormalities, which included thrombosis, hypoplasia and extra-truncular venous malformations. Our study demonstrates the presence of congenital or acquired vascular anomalies in a small sample of CD patients not responder to current treatment and with severe complications. The present pilot study warrants further investigations.

The Relationship of Complexity of Coronary Artery Disease and Complexity of Peripheral Arterial Disease

Background: Atherosclerosis is a disease of the large and medium-sized arteries causing luminal narrowing (focal or diffuse). Aim of the Work: Measure the relationship between coronary artery disease complexity using SYNTAX score and peripheral arterial disease complexity using TASC II score. Patients and Methods: The study was designed as a prospective single center cross-sectional study conducted at Ain shams university hospitals. The study included 50 patients referred for elective coronary angiography in the time period from August 2016 till July 2017. Results and conclusion: Patients with complex PAD had complex CAD. This finding suggested that PAD and CHD are different clinical manifestations of atherosclerosis and systemic pan vascular involvement is present in patients with complex lesions. (P-value 0.046).

Association between uric acid and renal function in hypertensive patients: which role for systemic vascular involvement?

The role of systemic vascular involvement in mediating the association between serum uric acid (SUA) and renal function in hypertension has not been explored. Main purpose of our study was to investigate whether morphofunctional vascular changes, assessed as carotid intima-media thickness (cIMT) and aortic pulse wave velocity (aPWV), might mediate the association between SUA and renal damage. We enrolled 523 hypertensive subjects with or without chronic kidney disease and divided population into tertiles of SUA based on sex-specific cutoff values. cIMT and aPWV were higher in uppermost SUA-tertile patients when compared to those in the lowest ones (all P < .001). Uricemia strongly correlated with cIMT and aPWV at univariate analysis (P < .001) and with cIMT after adjustment for confounders (P < .001). Adjustment for cIMT attenuated the relationship between SUA and estimated glomerular filtration rate (P = .019). Systemic vascular changes seem partially to mediate the association between SUA and renal function in hypertensive patients, regardless of kidney function.

Plectin reinforces vascular integrity by mediating crosstalk between the vimentin and the actin networks

Mutations in the cytoskeletal linker protein plectin result in multisystemic diseases affecting skin and muscle with indications of additional vascular system involvement. To study the mechanisms underlying vascular disorders, we established plectin-deficient endothelial cell and mouse models. We show that apart from perturbing the vimentin cytoskeleton of endothelial cells, plectin deficiency leads to severe distortions of adherens junctions (AJs), as well as tight junctions, accompanied by an upregulation of actin stress fibres and increased cellular contractility. Plectin-deficient endothelial cell layers were more leaky and showed reduced mechanical resilience in fluid-shear stress and mechanical stretch experiments. We suggest that the distorted AJs and upregulated actin stress fibres in plectin-deficient cells are rooted in perturbations of the vimentin cytoskeleton, as similar phenotypes could be mimicked in wild-type cells by disruption of vimentin filaments. In vivo studies in endothelium-restricted conditional plectin-knockout mice revealed significant distortions of AJs in stress-prone aortic arch regions and increased pulmonary vascular leakage. Our study opens a new perspective on cytoskeleton-controlled vascular permeability, where a plectin-organized vimentin scaffold keeps actomyosin contractility 'in-check' and maintains AJ homeostasis.

Risk of sudden sensorineural hearing loss in patients with psoriasis: a retrospective cohort study.

Psoriasis, a common immune-mediated disease, affects approximately 2% of the population worldwide. Sudden sensorineural hearing loss (SSNHL) might be a manifestation of systemic vascular involvement in autoimmune disease. However, to the best of our knowledge, there is no systematic English-language examination of the risk of SSNHL in patients with psoriasis. We tested the hypothesis that psoriasis is a risk factor for developing SSNHL. Using Taiwan's National Health Insurance Research Database, we conducted a retrospective cohort study to compare patients diagnosed with psoriasis from January 1, 2001 through December 31, 2006 (n=28,817) with gender-, age-, and comorbidities-matched controls (n=28,817). We followed each patient until the end of 2011 and evaluated the incidence of SSNHL for at least 6 years after the initial psoriasis diagnosis. The incidence of SSNHL was 1.51 times higher in the psoriasis cohort than in the control cohort (7.12 vs 4.73 per 10,000 person-years). Using Cox proportional hazard regressions, the adjusted hazard ratio (AHR) was 1.51 (95% confidence interval [CI] 1.18-1.93). Comorbid hypertension was an independent risk factor for SSNHL (AHR 1.49; 95% CI 1.05-2.13). However, the incidence rate ratios (IRRs) for each comorbidity subgroup in the psoriasis and control cohorts were not significantly different. Psoriasis was significantly associated with a higher risk of developing SSNHL. We suggest that physicians advise patients with psoriasis to seek medical attention if they have hearing impairments, because they may also have a higher risk of developing SSNHL.

Plectin reinforces vascular integrity by mediating crosstalk between the vimentin and the actin networks.

ABSTRACTMutations in the cytoskeletal linker protein plectin result in multisystemic diseases affecting skin and muscle with indications of additional vascular system involvement. To study the mechanisms underlying vascular disorders, we established plectin-deficient endothelial cell and mouse models. We show that apart from perturbing the vimentin cytoskeleton of endothelial cells, plectin deficiency leads to severe distortions of adherens junctions (AJs), as well as tight junctions, accompanied by an upregulation of actin stress fibres and increased cellular contractility. Plectin-deficient endothelial cell layers were more leaky and showed reduced mechanical resilience in fluid-shear stress and mechanical stretch experiments. We suggest that the distorted AJs and upregulated actin stress fibres in plectin-deficient cells are rooted in perturbations of the vimentin cytoskeleton, as similar phenotypes could be mimicked in wild-type cells by disruption of vimentin filaments. In vivo studies in endothelium-restricted conditional plectin-knockout mice revealed significant distortions of AJs in stress-prone aortic arch regions and increased pulmonary vascular leakage. Our study opens a new perspective on cytoskeleton-controlled vascular permeability, where a plectin-organized vimentin scaffold keeps actomyosin contractility ‘in-check’ and maintains AJ homeostasis.

Cavernous haemangioma of the retina

A 29-year-old man was found to have an incidental finding of peripheral cavernous haemangioma of the retina (CHR). Fundus examination revealed peripheral retinopathy with fine haemorrhage. Traditional appearance of CHR was demonstrated by fluorescein angiography. OCT showed the saccular appearance with an overlying epiretinal membrane, consistent with CHR. All other investigations were negative and there was no suggestion of systemic dermatological or neurological involvement.CHR is a rare and usually incidental finding associated with a small risk of associated systemic vascular and neurological involvement. We have demonstrated the fundal and OCT appeaance of peripheral CHR, which is an important clinical and diagnostic finding.