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Revista Clinica Espanola Jun 2024Systematic review of current evidence to analyze the prevalence of extracranial large vessel vasculitis (LVV) using F-FDG PET/CT in patients with polymyalgia rheumatica...
OBJECTIVE
Systematic review of current evidence to analyze the prevalence of extracranial large vessel vasculitis (LVV) using F-FDG PET/CT in patients with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA).
MATERIALS AND METHODS
PubMed and EMBASE were searched and the results were screened by two reviewers. Study quality was assessed using a modified version of the Newcastle-Ottawa scale. Heterogeneity between studies was assessed using the I statistic and the Q test. Further subgroup analyses were performed by disease type, study quality, and F-FDG PET/CT uptake criteria. Publication bias was assessed by funnel plot and Egger's test.
RESULTS
268 publications were identified, of which 17 met the selection criteria and were included in the meta-analysis. The overall pooled prevalence of extracranial LVV by F-FDG PET/CT was 54.5% [95% CI: 42.6%-66.1%]. In patients with GCA the prevalence was significantly higher than in patients with PMR (60.1% vs. 41.8%, P = 0.006). Likewise, studies with a lower risk of bias reported a higher prevalence of extracranial LVV (61.1% vs. 46.9%; P = 0.010). No publication bias was observed.
CONCLUSIONS
The F-FDG PET/CT test may be useful in the detection of extracranial LVV, both in patients with PMR or GCA. Such involvement is more frequent in patients with GCA, and may vary depending on the quality of the studies.
PubMed: 38852739
DOI: 10.1016/j.rceng.2024.06.005 -
Rheumatology (Oxford, England) Jun 2024To assess the diagnostic value for GCA in adding the axillary arteries (AX) to the temporal artery (TA) ultrasound, particularly in patients with a cranial phenotype of...
OBJECTIVE
To assess the diagnostic value for GCA in adding the axillary arteries (AX) to the temporal artery (TA) ultrasound, particularly in patients with a cranial phenotype of the disease; and to investigate the utility of facial (FA), occipital (OC), subclavian (SC), and common carotid (CC) ultrasound in patients with suspected GCA.
METHODS
Patients with new-onset GCA and a positive ultrasound of the TA, AX, FA, OC, SC or CC, followed at the rheumatology departments of two academic centres, were retrospectively included.
RESULTS
230 patients were assessed. TA halo sign was identified in 206/230 (89.6%) cases, FA in 40/82 (48.8%), OC in 17/69 (24.6%), AX in 56/230 (24.3%), SC in 31/57 (54.4%), and CC in 14/68 (20.6%). Negative TA ultrasound was found in 24/230 (10.4%) patients: 22 had AX involvement, 1 exclusive OC involvement and 1 exclusive SC involvement. Adding AX evaluation to the TA ultrasound increased the diagnostic yield for GCA in 9.6%, whereas adding OC or SCs to the TA and AX ultrasound increased it in 1.4% and 1.8%, respectively. No value was found in adding the FA or CCs. Notably, 13 patients with cranial symptoms and 4 with exclusively cranial symptoms showed negative TA ultrasound but positive AX ultrasound.
CONCLUSION
Adding the evaluation of AXs to the TA ultrasound increased the number of patients diagnosed with GCA, even in cases of predominantly cranial symptoms. In the subset of patients where these arteries were assessed, no substantial benefit was found in adding the FA, OC, SC or CC arteries to the TA and AX ultrasonographic assessment.
PubMed: 38851880
DOI: 10.1093/rheumatology/keae321 -
Virology May 2024Glycoprotein 3 (GP3) serves as a structural protein in equine arteritis virus (EAV), forming a heterotrimeric complex that plays a pivotal role in virus tropism. In this...
Glycoprotein 3 (GP3) serves as a structural protein in equine arteritis virus (EAV), forming a heterotrimeric complex that plays a pivotal role in virus tropism. In this study, we tested the membrane topology of GP3, both when expressed separately and during infection with recombinant tagged EAV GP3-HA. In our antibody accessibility experiment, we made a noteworthy discovery: GP3, when expressed separately, exhibits a dual topology. We introduced an additional N-glycosylation site, which was only partially used, providing further evidence for the dual topology of GP3. Intriguingly, this mutated GP3 was secreted into the medium, a result of the disruption of the ER retention motif RXR. The additional glycosylation site was not used when we examined the recombinant EAV virus with the same mutation. Despite the fact of higher expression levels of mutant GP3-HA, the protein was not secreted, and the recombinant mutant virus did not have growth delay compared to the EAV wild-type virus. This finding suggests that GP3 has a single type one membrane topology in virus infected cells, whereas the expression of GP3 in trans results in the dual topology of this protein. The RXR motif in the C-terminus is a co-factor of ER retention of the protein, but the main retention signal remains elusive.
PubMed: 38850896
DOI: 10.1016/j.virol.2024.110122 -
Orphanet Journal of Rare Diseases Jun 2024Increased arterial tortuosity has been associated with various cardiovascular complications. However, the extent and role of arterial tortuosity in non-atherosclerotic...
BACKGROUND
Increased arterial tortuosity has been associated with various cardiovascular complications. However, the extent and role of arterial tortuosity in non-atherosclerotic vascular diseases remain to be fully elucidated. This study aimed to assess arterial tortuosity index (ATI) in patients with non-atherosclerotic vascular diseases and the associated factors.
METHODS
This is a retrospective analysis of patients with non-atherosclerotic vascular diseases referred to the Malformation and Rare Vascular Disease Center at the University Hospital in Lausanne (Switzerland). Computed tomography angiography (CTA) images performed between October 2010 and April 2022 were retrieved and the aortic tortuosity index (ATI) was calculated. Patients were classified based on diagnosis into the following groups: arterial dissection & aneurysm, arteritis & autoimmune disease, hereditary connective tissue diseases, and fibromuscular dysplasia (FMD). Univariate and multivariate logistic regression analysis was used to determine potentially relevant predictors of aortic tortuosity.
RESULTS
The mean age upon computed tomography angiography (CTA) was 46.8 (standard deviation [SD] 14.6) years and 59.1% of the patients were female. Mean ATI was higher in patients over 60 years old (1.27), in those with arterial aneurysms (mean: 1.11), and in those diagnosed with hypertension (mean: 1.13). When only patients over 60 years old were considered, those diagnosed with connective tissue diseases had the highest ATI. At multivariate regression analysis, increasing age (p < 0.05), presence of arterial aneurysms (p < 0.05), and hypertension (p < 0.05) were independently associated with ATI.
CONCLUSIONS
The ATI may be a promising tool in diagnostic evaluation, cardiovascular risk stratification, medical or surgical management, and prognostic assessment in several non-atherosclerotic vascular conditions. Further studies with longitudinal design and larger cohorts are needed to validate the role of ATI in the full spectrum of vascular diseases.
Topics: Humans; Female; Male; Middle Aged; Retrospective Studies; Adult; Hypertension; Aneurysm; Computed Tomography Angiography; Vascular Diseases; Aged; Arteries; Age Factors
PubMed: 38849913
DOI: 10.1186/s13023-024-03231-9 -
Annals of Medicine and Surgery (2012) Jun 2024Takayasu Arteritis (TA) is a rare chronic inflammatory disease of unknown etiology that primarily affects large vessels, such as the aorta and its major branches. The...
INTRODUCTION AND IMPORTANCE
Takayasu Arteritis (TA) is a rare chronic inflammatory disease of unknown etiology that primarily affects large vessels, such as the aorta and its major branches. The disease typically presents with diverse symptoms, depending on the site and degree of arterial lesions. Delayed diagnosis is common, especially in younger populations.
CASE PRESENTATION
A 39-year-old Syrian female presented with an initial stroke. She had no prior medical history and was otherwise healthy. On examination, she had an absent left radial pulse, a carotid bruit, and muscle weakness. Blood tests showed an elevated ESR and CRP. Computed tomography of the brain revealed a right large cerebral infarction. Multislice computed tomography angiography showed diffuse arterial wall thickening, stenosis, and occlusion of several major vessels, including the left internal carotid artery, right internal carotid artery, and left subclavian artery.
CLINICAL DISCUSSION
The patient was diagnosed with TA based on the American College of Rheumatology criteria. She was treated with prednisolone, methotrexate, and aspirin, and her symptoms improved significantly.
CONCLUSION
This case highlights the importance of considering TA in the differential diagnosis of ischemic stroke, especially in young patients with atypical presentations. Early identification and management are essential to preclude critical sequelae.
PubMed: 38846855
DOI: 10.1097/MS9.0000000000002098 -
Therapeutic Advances in Musculoskeletal... 2024Rheumatologists are increasingly utilizing ultrasound for suspected giant cell arteritis (GCA) or Takayasu arteritis (TAK). This enables direct confirmation of a... (Review)
Review
Rheumatologists are increasingly utilizing ultrasound for suspected giant cell arteritis (GCA) or Takayasu arteritis (TAK). This enables direct confirmation of a suspected diagnosis within the examination room without further referrals. Rheumatologists can ask additional questions and explain findings to their patients while performing ultrasound, preferably in fast-track clinics to prevent vision loss. Vascular ultrasound for suspected vasculitis was recently integrated into rheumatology training in Germany. New European Alliance of Associations for Rheumatology recommendations prioritize ultrasound as the first imaging tool for suspected GCA and recommend it as an imaging option for suspected TAK alongside magnetic resonance imaging, positron emission tomography and computed tomography. Ultrasound is integral to the new classification criteria for GCA and TAK. Diagnosis is based on consistent clinical and ultrasound findings. Inconclusive cases require histology or additional imaging tests. Robust evidence establishes high sensitivities and specificities for ultrasound. Reliability is good among experts. Ultrasound reveals a characteristic non-compressible 'halo sign' indicating intima-media thickening (IMT) and, in acute disease, artery wall oedema. Ultrasound can further identify stenoses, occlusions and aneurysms, and IMT can be measured. In suspected GCA, ultrasound should include at least the temporal and axillary arteries bilaterally. Nearly all other arteries are accessible except the descending thoracic aorta. TAK mostly involves the common carotid and subclavian arteries. Ultrasound detects subclinical GCA in over 20% of polymyalgia rheumatica (PMR) patients without GCA symptoms. Patients with silent GCA should be treated as GCA because they experience more relapses and require higher glucocorticoid doses than PMR patients without GCA. Scores based on intima-thickness (IMT) of temporal and axillary arteries aid follow-up of GCA, particularly in trials. The IMT decreases more rapidly in temporal than in axillary arteries. Ascending aorta ultrasound helps monitor patients with extracranial GCA for the development of aneurysms. Experienced sonologists can easily identify pitfalls, which will be addressed in this article.
PubMed: 38846756
DOI: 10.1177/1759720X241251742 -
European Radiology Experimental Jun 2024Three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) is a largely adopted non-invasive technique for assessing cerebrovascular diseases. We aimed to...
BACKGROUND
Three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) is a largely adopted non-invasive technique for assessing cerebrovascular diseases. We aimed to optimize the 7-T TOF-MRA acquisition protocol, confirm that it outperforms conventional 3-T TOF-MRA, and compare 7-T TOF-MRA with digital subtraction angiography (DSA) in patients with different vascular pathologies.
METHODS
Seven-tesla TOF-MRA sequences with different spatial resolutions acquired in four healthy subjects were compared with 3-T TOF-MRA for signal-to-noise and contrast-to-noise ratios as well as using a qualitative scale for vessel visibility and the quantitative Canny algorithm. Four patients with cerebrovascular disease (primary arteritis of the central nervous system, saccular aneurism, arteriovenous malformation, and dural arteriovenous fistula) underwent optimized 7-T TOF-MRA and DSA as reference. Images were compared visually and using the complex-wavelet structural similarity index.
RESULTS
Contrast-to-noise ratio was higher at 7 T (4.5 ± 0.8 (mean ± standard deviation)) than at 3 T (2.7 ± 0.9). The mean quality score for all intracranial vessels was higher at 7 T (2.89) than at 3 T (2.28). Angiogram quality demonstrated a better vessel border detection at 7 T than at 3 T (44,166 versus 28,720 pixels). Of 32 parameters used for diagnosing cerebrovascular diseases on DSA, 27 (84%) were detected on 7-T TOF-MRA; the similarity index ranged from 0.52 (dural arteriovenous fistula) to 0.90 (saccular aneurysm).
CONCLUSIONS
Seven-tesla TOF-MRA outperformed conventional 3-T TOF-MRA in evaluating intracranial vessels and exhibited an excellent image quality when compared to DSA. Seven-tesla TOF-MRA might improve the non-invasive diagnostic approach to several cerebrovascular diseases.
RELEVANCE STATEMENT
An optimized TOF-MRA sequence at 7 T outperforms 3-T TOF-MRA, opening perspectives to its clinical use for noninvasive diagnosis of paradigmatic pathologies of intracranial vessels.
KEY POINTS
• An optimized 7-T TOF-MRA protocol was selected for comparison with clinical 3-T TOF-MRA for assessing intracranial vessels. • Seven-tesla TOF-MRA outperformed 3-T TOF-MRA in both quantitative and qualitative evaluation. • Seven-tesla TOF-MRA is comparable to DSA for the diagnosis and characterization of intracranial vascular pathologies.
Topics: Humans; Magnetic Resonance Angiography; Male; Female; Middle Aged; Cerebrovascular Disorders; Adult; Angiography, Digital Subtraction; Aged; Signal-To-Noise Ratio; Imaging, Three-Dimensional
PubMed: 38844683
DOI: 10.1186/s41747-024-00463-z -
Aging Jun 2024Estrogen is thought to have a role in slowing down aging and protecting cardiovascular and cognitive function. However, high doses of estrogen are still positively...
High estrogen induces trans-differentiation of vascular smooth muscle cells to a macrophage-like phenotype resulting in aortic inflammation via inhibiting VHL/HIF1a/KLF4 axis.
Estrogen is thought to have a role in slowing down aging and protecting cardiovascular and cognitive function. However, high doses of estrogen are still positively associated with autoimmune diseases and tumors with systemic inflammation. First, we administered exogenous estrogen to female mice for three consecutive months and found that the aorta of mice on estrogen develops inflammatory manifestations similar to Takayasu arteritis (TAK). Then, estrogen intervention was performed on mouse aortic vascular smooth muscle cells (MOVAS cells). Stimulated by high concentrations of estradiol, MOVAS cells showed decreased expression of contractile phenotypic markers and increased expression of macrophage-like phenotypic markers. This shift was blocked by tamoxifen and Krüppel-like factor 4 (KLF4) inhibitors and enhanced by Von Hippel-Lindau (VHL)/hypoxia-inducible factor-1α (HIF-1α) interaction inhibitors. It suggests that estrogen-targeted regulation of the VHL/HIF-1α/KLF4 axis induces phenotypic transformation of vascular smooth muscle cells (VSMC). In addition, estrogen-regulated phenotypic conversion of VSMC to macrophages is a key mechanism of estrogen-induced vascular inflammation, which justifies the risk of clinical use of estrogen replacement therapy.
Topics: Kruppel-Like Factor 4; Animals; Kruppel-Like Transcription Factors; Macrophages; Mice; Hypoxia-Inducible Factor 1, alpha Subunit; Muscle, Smooth, Vascular; Female; Estrogens; Von Hippel-Lindau Tumor Suppressor Protein; Myocytes, Smooth Muscle; Cell Transdifferentiation; Phenotype; Aorta; Inflammation
PubMed: 38843385
DOI: 10.18632/aging.205904 -
Frontiers in Medicine 2024Giant cell arteritis (GCA) is characterized by inflammation of large and medium vessels. First-line therapy for the treatment of GCA are glucocorticoids, which are...
BACKGROUND
Giant cell arteritis (GCA) is characterized by inflammation of large and medium vessels. First-line therapy for the treatment of GCA are glucocorticoids, which are effective while potential adverse effects should be considered, especially during long-term use. The aim was to investigate the incidence of glucocorticoids' adverse effects and potential predictors for them.
MATERIALS AND METHODS
138 GCA patients were retrospectively evaluated for newly developed glucocorticoid adverse effects in 2020. Potential predictors, defined as initial glucocorticoid pulse therapy, relapse of GCA and concomitant polymyalgia rheumatica as well as parameters of inflammation and endothelial dysfunction, including pulse-wave velocity and intima-media-thickness, were measured in 2012.
RESULTS
Potential new glucocorticoid adverse effects per patient was 1 (25th-75th 0-3) of which chronic kidney disease progression (29%), bone fractures (23.2%), cataracts (18.1%), dementia, and arterial hypertension (each at 12.3%) were most commonly recorded. Significant associations were found between occurrence of any relapse and new diabetes mellitus and between initial glucocorticoid pulse therapy and new dementia (all with < 0.05). In multivariate regression analysis, any relapse was a predictor for developing diabetes mellitus (OR 9.23 [95% CI 1.33-64.05], = 0.025). However, no correlations were observed between endothelial dysfunction or inflammatory parameters and development of new glucocorticoid adverse effects.
CONCLUSION
GCA relapses may be associated for development of diabetes mellitus potentially by increasing glucocorticoid doses. Parameters of inflammation and endothelial dysfunction are not suited predictors for glucocorticoid adverse effects.
PubMed: 38841591
DOI: 10.3389/fmed.2024.1382946 -
Arthritis Research & Therapy Jun 2024A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus... (Review)
Review
BACKGROUND
A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature.
METHODS
Retrospective analysis of GCA patients treated with JAKi for relapsing disease at thirteen centers in Spain and one center in United States (01/2017-12/2022). Outcomes assessed included clinical remission, complete remission and safety. Clinical remission was defined as the absence of GCA signs and symptoms regardless of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values. Complete remission was defined as the absence of GCA signs and symptoms along with normal ESR and CRP values. A systematic literature search for other JAKi-treated GCA cases was conducted.
RESULTS
Thirty-five patients (86% females, mean age 72.3) with relapsing GCA received JAKi therapy (baricitinib, n = 15; tofacitinib, n = 10; upadacitinib, n = 10). Before JAKi therapy, 22 (63%) patients had received conventional synthetic immunosuppressants (e.g., methotrexate), and 30 (86%) biologics (e.g., tocilizumab). After a median (IQR) follow-up of 11 (6-15.5) months, 20 (57%) patients achieved and maintained clinical remission, 16 (46%) patients achieved and maintained complete remission, and 15 (43%) patients discontinued the initial JAKi due to relapse (n = 11 [31%]) or serious adverse events (n = 4 [11%]). A literature search identified another 36 JAKi-treated GCA cases with clinical improvement reported for the majority of them.
CONCLUSIONS
This real-world analysis and literature review suggest that JAKi could be effective in GCA, including in patients failing established glucocorticoid-sparing therapies such as tocilizumab and methotrexate. A phase III randomized controlled trial of upadacitinib is currently ongoing (ClinicalTrials.gov ID NCT03725202).
Topics: Humans; Giant Cell Arteritis; Female; Janus Kinase Inhibitors; Aged; Male; Retrospective Studies; Recurrence; Treatment Outcome; Pyrimidines; Piperidines; Azetidines; Pyrazoles; Sulfonamides; Purines; Aged, 80 and over; Middle Aged; Heterocyclic Compounds, 3-Ring
PubMed: 38840219
DOI: 10.1186/s13075-024-03314-9