RESUMO
OBJECTIVE: Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are rarely revealed by TA manifestations, leading to a risk of misdiagnosis of GCA and inappropriate treatments. This study was undertaken to describe the clinical, biologic, and histologic presentations and outcomes in cases of TA revealing AAV (TA-AAV) compared to controls with classic GCA. METHODS: In this retrospective case-control study, the characteristics of patients with TA-AAV were compared to those of control subjects with classic GCA. Log-rank test, with hazard ratios (HRs) and 95% confidence intervals (95% CIs), was used to assess the risk of treatment failure. RESULTS: Fifty patients with TA-AAV (median age 70 years) were included. Thirty-three patients (66%) presented with atypical symptoms of GCA (ear, nose, and throat involvement in 32% of patients, and renal, pulmonary, and neurologic involvement in 26%, 20%, and 16% of patients, respectively). Blood samples were screened for ANCAs at the time of disease onset in 33 patients, and results were positive in 88%, leading to a diagnosis of early TA-AAV in 20 patients. The diagnosis of AAV was delayed a median interval of 15 months in 30 patients. Compared to controls with GCA, patients with TA-AAV were younger (median age 70 years versus 74 years), were more frequently men (48% versus 30%), and had high frequencies of atypical manifestations and higher C-reactive protein levels (median 10.8 mg/dl versus 7.0 mg/dl). In patients with TA-AAV, temporal artery biopsy (TAB) showed fibrinoid necrosis and small branch vasculitis in 23% of patients each, whereas neither of these characteristics was evident in controls with GCA. Treatment failure-free survival was comparable between early TA-AAV cases and GCA controls, whereas those with delayed TA-AAV had a significantly higher risk of treatment failure compared to controls (HR 3.85, 95% CI 1.97-7.51; P < 0.0001). CONCLUSION: TA-AAV should be considered diagnostically in cases of atypical manifestations of GCA, refractoriness to glucocorticoid treatment, or early relapse. Analysis of TAB specimens for the detection of small branch vasculitis and/or fibrinoid necrosis could be useful. Detection of ANCAs should be performed in cases of suspected GCA with atypical clinical features and/or evidence of temporal artery abnormalities on TAB.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Arterite de Células Gigantes/fisiopatologia , Artérias Temporais/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Arterite/diagnóstico , Arterite/tratamento farmacológico , Arterite/patologia , Arterite/fisiopatologia , Astenia/fisiopatologia , Estudos de Casos e Controles , Tosse/fisiopatologia , Diagnóstico Tardio , Diagnóstico Diferencial , Diplopia/fisiopatologia , Feminino , Febre/fisiopatologia , França , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/patologia , Glucocorticoides/uso terapêutico , Cefaleia/fisiopatologia , Humanos , Arcada Osseodentária , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Polimialgia Reumática/fisiopatologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Couro Cabeludo , Sudorese , Artérias Temporais/patologia , Falha de Tratamento , Transtornos da Visão/fisiopatologia , Redução de PesoRESUMO
SIGNIFICANCE: Nonarteritic ischemic optic neuropathy (NAION) has been linked with vascular insufficiency, although the pathophysiology remains elusive. Optical coherence tomography angiography (OCTA) is a promising technology that noninvasively evaluates optic disc perfusion and that may help to characterize peripapillary vascular changes in NAION. PURPOSE: This study aimed to evaluate peripapillary vascularity in NAION eyes and to compare it with fellow unaffected eyes and healthy control eyes using OCTA. METHODS: In this cross-sectional study, OCTA of the optic nerve head was obtained in 10 nonacute unilateral NAION and 12 healthy age-matched controls using ZEISS Angioplex. Quantitative analysis of peripapillary retinal and choroidal vascularity of NAION eyes was done using the instrument's inbuilt algorithm and ImageJ software and compared with fellow and control eyes. RESULTS: Mean total peripapillary superficial retinal vessel and perfusion density as calculated by the instrument was significantly reduced in NAION eyes compared with fellow eyes (13.93 ± 4.27 mm/0.36 ± 0.07 for NAION eyes; 17.77 ± 1.26 mm/0.43 ± 0.08 for fellow eyes; P = .01/P = .05). Using the ImageJ software technique, the mean superficial retinal perfusion was found to be significantly reduced in NAION eyes (0.17 ± 0.07) compared with fellow eyes (0.25 ± 0.06; P < .01) and control eyes (0.25 ± 0.04; P < .01). At the level of choriocapillaris, it was not significantly affected in NAION eyes (0.37 ± 0.13) versus fellow (0.34 ± 0.14; P = .1) and control eyes (0.31 ± 0.34; P = .83). Analysis with the two techniques yielded differing results: the ImageJ analysis technique found a 32% reduction in superficial retinal perfusion in NAION eyes, whereas the instrument's inbuilt algorithm found a 16% reduction compared with fellow and control eyes (P ≤.01). CONCLUSIONS: Peripapillary vascularity can be estimated both at the retinal and choroidal levels using ImageJ software to analyze OCTA images. Retinal peripapillary vascularity is compromised in NAION eyes, but vascularity is not significantly affected at the choroidal level.
Assuntos
Corioide/irrigação sanguínea , Artérias Ciliares/fisiologia , Disco Óptico/irrigação sanguínea , Neuropatia Óptica Isquêmica/fisiopatologia , Vasos Retinianos/fisiologia , Adulto , Idoso , Arterite/fisiopatologia , Estudos Transversais , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Disco Óptico/diagnóstico por imagem , Neuropatia Óptica Isquêmica/diagnóstico , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Campos Visuais/fisiologiaRESUMO
Uteroplacental acute atherosis (AA) is a common spiral arterial lesion in preeclampsia, characterized by intramural foam cells, fibrinoid necrosis, and a perivascular immune cell infiltrate. A clear definition of this infiltrate is lacking. Therefore, our aim was to characterize lymphocytes in pre-defined zones regarding spiral arteries with or without AA, from preeclamptic and normotensive pregnancies. Lymphocytes were characterized in decidua basalis samples (n = 91), previously evaluated for AA, around spiral arteries in three pre-defined zones; 1) intramural, 2) perivascular and 3) interstitial. Adjacent serial sections were immunostained to identify different T-cell populations (CD3+, CD8+, FOXP3+), and NK-cells (CD56+). CD3+CD8- T-cells were also identified. These were presumed to be largely CD4+ T-cells. AA was associated with significantly higher intramural CD3+ cell concentrations in Zone 1, in both normotensives and preeclamptics. In preeclamptics only, this difference extended into Zone 2. Similar results were observed for CD3+CD8- cells. AA was also associated with increased intramural CD8+ concentration; however, the number of cells was low. Regulatory T-cells (FOXP3+) were generally scarce or absent in all pre-defined zones. Although intramural NK-cells (CD56+) were scarce, the intramural concentration was significantly lower in spiral arteries with AA compared to without AA in preeclamptics. Our main finding was that CD3+CD8-FoxP3- T-cells were associated with AA. We therefore suggest that T-cells, of a non-regulatory CD4+ subtype, could be involved in the formation of spiral artery AA in the decidua basalis. Whether AA gives rise to, or is partly mediated by increased T-cell concentration around the lesions, remains to be determined.
Assuntos
Arterite/imunologia , Linfócitos T CD8-Positivos/imunologia , Decídua/irrigação sanguínea , Pré-Eclâmpsia/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Artérias/imunologia , Artérias/fisiopatologia , Arterite/patologia , Arterite/fisiopatologia , Pressão Sanguínea/fisiologia , Complexo CD3/imunologia , Complexo CD3/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Decídua/imunologia , Feminino , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Humanos , Células Matadoras Naturais , Pré-Eclâmpsia/patologia , Gravidez , Linfócitos T Reguladores/metabolismoRESUMO
PURPOSE: The pathophysiology of nonarteritic anterior ischemic optic neuropathy (NAION) is not completely understood. Studies of the retinal vasculature phenotype in patients with NAION could help us to understand vascular abnormalities associated with the disease. DESIGN: Retrospective case series with matched control subjects. METHODS: Study population: 57 patients with NAION and 57 control subjects matched to NAION patients for sex, age, systemic hypertension, diabetes, and obstructive sleep apnea syndrome between September 2007 and July 2017. MAIN OUTCOME MEASURES: All patients and control subjects underwent a complete ocular examination and 45° funduscopic color photographs. The widths of the 6 largest arteries in zone B (between 0.5 and 1 optic disc diameter from the optic disc), summarized by the central retinal artery equivalent (CRAE), the widths of the 6 largest veins in zone B, summarized by the central retinal vein equivalent (CRVE), the arteriole to venule ratio, tortuosity, and fractal dimension were measured on the 2 groups using Vessel Assessment and Measurement Platform for Images of the Retina, a software tool for efficient semiautomatic quantification of the retinal vasculature morphology in fundus camera images. The Wilcoxon signed-rank test and MacNemar χ2 test for paired sample and generalized estimating equations for modeling the Vessel Assessment and Measurement Platform for Images of the Retina parameters as dependent variables were used. RESULTS: CRVE and fractal dimension (D0a) were significantly higher in the NAION group when compared with the control group, whereas the arteriole to venule ratio and vascular tortuosity were significantly lower. Compared with control subjects, acute NAION yielded an increased CRAE value (174 ± 33 vs 160 ± 13 µm) while resolution NAION yielded a decreased CRAE value (152 ± 12 vs 156 ± 33 µm). Acute NAION yielded an increased CRVE value (244 ± 35 vs 210 ± 21 µm) while resolution NAION yielded an unchanged CRVE value. We found no difference between groups for age, refraction, optic disc diameter, CRAE, or fractal dimension. CONCLUSIONS: Retinal vascular parameters were different in our sample between NAION and control patients, especially at the acute stage of the disease. Our results suggest a normalization of the same parameters at the resolution stage.
Assuntos
Neuropatia Óptica Isquêmica/fisiopatologia , Vasos Retinianos/patologia , Idoso , Idoso de 80 Anos ou mais , Arterite/fisiopatologia , Diabetes Mellitus/fisiopatologia , Feminino , Angiofluoresceinografia , Humanos , Hipertensão/fisiopatologia , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Disco Óptico/irrigação sanguínea , Fenótipo , Estudos Retrospectivos , Apneia Obstrutiva do Sono/fisiopatologia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologiaRESUMO
BACKGROUND: 18F-FDG PET/CT predicts cardiovascular disease. To analyze the predictive value of cardiovascular events from inflammation and arterial calcification in patients who underwent an 18F-FDG PET/CT for lung cancer. METHODS: A retrospective study of 274 patients with primary lung neoplasia. We determined: (i) TBR (target-to-background ratio), and (ii) the calcium score, at eight common arterial segments. We took as arteriosclerosis, a TBR ≥1.6 and ≥15 Calcium Score sum. We registered cardiovascular risk factors, comorbidities, histology, stage, treatment, status at the last clinical review, cause of death and cardiovascular event during the follow-up. RESULTS: The territory presenting the greatest uptake of 18F-FDG, was the thoracic aorta with an average of 1.77 (± 0.27 TBR) in the aortic arch, while the greatest degree of calcification was obtained in the abdominal aorta (52% with a Calcium Score ≥ 3). 24% of the patients presented a sum Calcium Score ≥15, and 17% a TBR ≥1.6. Patients with high TBR, (17%), had not a higher frequency of cardiovascular comorbidities beforehand, nor did they in the follow-up. However, those with a sum Calcium Score ≥15 (24%), were older, had more cardiovascular risk factors and ischemic events during follow-up. The calcium score, but not the TBR, predicted the emergence of a cardiovascular event (HR 4.9 IC95% 2.1-9.1, P < 0.05). CONCLUSION: In our cohort, a high Calcium Score was an independent predictor for developing cardiovascular events.
Assuntos
Arterite/fisiopatologia , Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Aorta Abdominal/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Aterosclerose/complicações , Aterosclerose/diagnóstico , Calcinose/complicações , Calcinose/diagnóstico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de RiscoRESUMO
Macular lymphocytic arteritis or lymphocytic thrombophilic arteritis (LTA) is a recently described cutaneous arteritis that is characterized by asymptomatic macules and patches of the extremities associated with lymphocytic arteritis at the deep dermal/subcuticular junction for which little information exists on demographics, evaluation, and management. There has been recent debate in the literature whether this disease is a new distinct entity, misdiagnosed cutaneous polyarteritis nodosa (cPAN), or a disease on a spectrum with cPAN. We systematically review the literature on demographic information, medical history, histopathology findings, and treatment management to analyze trends and clarify controversies in characterizations of LTA. Forty detailed cases of LTA have been published. We submit that, although literature is limited, a review of the data still suggests that LTA is distinct from cPAN and systemic PAN. In addition, to better reflect the pathophysiologic natural history of this condition and correct for the historical artifact of how the disease was identified, we encourage the disease to be referred to as LTA and discourage ongoing use of macular lymphocytic arteritis.
Assuntos
Arterite , Poliarterite Nodosa/diagnóstico , Pele/irrigação sanguínea , Arterite/diagnóstico , Arterite/patologia , Arterite/fisiopatologia , Arterite/terapia , Diagnóstico Diferencial , Gerenciamento Clínico , Humanos , Dermatopatias/diagnóstico , Dermatopatias/etiologia , Dermatopatias/patologiaAssuntos
Hemangioma/diagnóstico , Disco Óptico/irrigação sanguínea , Neoplasias do Nervo Óptico/diagnóstico , Neuropatia Óptica Isquêmica/diagnóstico , Arterite/diagnóstico , Arterite/fisiopatologia , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Neuropatia Óptica Isquêmica/fisiopatologia , Distúrbios Pupilares/diagnóstico , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologiaRESUMO
Purpose: To analyze retinal and choroidal microvasculature in patients with nonarteritic anterior ischemic optic neuropathy (NAION) by using optical coherence tomography angiography (OCT-A). Methods: In this case-control retrospective observational study, patients with atrophic NAION (at least 3 months after onset of symptoms) and normal subjects underwent a complete ophthalmic examination including spectral-domain OCT, visual field (VF), and OCT-A. Whole en face image vessel density (wiVD) was used to assess retinal blood flow of the radial peripapillary capillaries (RPCs), circumpapillary RPC vessel density (cpVD), superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC). Statistical correlations between wiVD measurements and visual acuity, VF parameters, retinal nerve fiber layer (RNFL), and combined thickness of retinal ganglion cell and inner plexiform layers were analyzed. Results: Twenty-four patients (26 eyes) with NAION and 24 age-matched normal controls (NCs) (24 eyes) were included. OCT-A showed significant reduction of the RPC wiVD (P < 0.0001) and the cpVD (P < 0.0001) in NAION eyes compared with NC and correlated with RNFL thickness (P = 0.002, P = 0.004), visual acuity (P = 0.042), and mean deviation of the VF (P = 0.001). Macular OCT angiograms showed capillary rarefaction in the SCP (P < 0.0001) and DCP (P < 0.0001) in the NAION group, both correlated with visual acuity (P = 0.02, P = 0.024). However, wiVD of the CC was not significantly different between the two groups in the peripapillary (P = 0.218) and macular (P = 0.786) areas. Conclusions: OCT-A provided detailed visualization of the peripapillary and macular retinal capillary rarefaction, correlated with VF and visual acuity loss. OCT-A could be a useful tool for quantifying and monitoring ischemia in NAION.
Assuntos
Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Microvasos/diagnóstico por imagem , Neuropatia Óptica Isquêmica/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica , Idoso , Arterite/diagnóstico por imagem , Arterite/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Neuropatia Óptica Isquêmica/fisiopatologia , Fluxo Sanguíneo Regional , Células Ganglionares da Retina/patologia , Estudos Retrospectivos , Acuidade Visual/fisiologia , Campos Visuais/fisiologiaRESUMO
Endocannabinoids (ECs) are involved in immunomodulation, neuroprotection and control of inflammation in the central nervous system (CNS). Activation of cannabinoid type 2 receptors (CB2) is known to diminish the release of pro-inflammatory factors and enhance the secretion of anti-inflammatory cytokines. Furthermore, the endocannabinoid 2-arachidonoyl glycerol (2-AG) has been proved to induce the migration of eosinophils in a CB2 receptor-dependent manner in peripheral blood and activate neutrophils independent of CB activation in humans. The aim of the current study was to investigate the influence of the endocannabinoid system in two different CNS inflammatory diseases of the dog, i.e. Steroid-Responsive Meningitis-Arteritis (SRMA) and Intraspinal Spirocercosis (IS). The two main endocannabinoids, anandamide (AEA) and 2-AG, were quantified by mass spectrometry in CSF and serum samples of dogs affected with Steroid- Responsive Meningitis-Arteritis in the acute phase (SRMA A), SRMA under treatment with prednisolone (SRMA Tr), intraspinal Spirocercosis and healthy dogs. Moreover, expression of the CB2 receptor was evaluated in inflammatory lesions of SRMA and IS and compared to healthy controls using immunohistochemistry (IHC). Dogs with SRMA A showed significantly higher concentrations of total AG and AEA in serum in comparison to healthy controls and in CSF compared to SRMA Tr (p<0.05). Furthermore, dogs with IS displayed the highest ECs concentrations in CSF, being significantly higher than in CSF samples of dogs with SRMA A (p<0.05). CSF samples that demonstrated an eosinophilic pleocytosis had the highest levels of ECs, exceeding those with neutrophilic pleocytosis, suggesting that ECs have a major effect on migration of eosinophils in the CSF. Furthermore, CB2 receptor expression was found in glial cells in the spinal cord of healthy dogs, whereas in dogs with SRMA and IS, CB2 was strongly expressed not only in glial cells but also on the cellular surface of infiltrating leukocytes (i.e. neutrophils, eosinophils, lymphocytes, plasma cells, and macrophages) at lesion sites. The present study revealed an upregulated endocannabinoid system in dogs with inflammatory CNS diseases, highlighting the endocannabinoid system as a potential target for treatment of inflammatory CNS diseases.
Assuntos
Arterite/veterinária , Doenças do Cão/fisiopatologia , Endocanabinoides/fisiologia , Meningite/veterinária , Doenças da Coluna Vertebral/veterinária , Infecções por Spirurida/veterinária , Animais , Arterite/sangue , Arterite/líquido cefalorraquidiano , Arterite/fisiopatologia , Cromatografia Líquida , Doenças do Cão/sangue , Doenças do Cão/líquido cefalorraquidiano , Cães , Endocanabinoides/sangue , Endocanabinoides/líquido cefalorraquidiano , Espectrometria de Massas , Meningite/sangue , Meningite/líquido cefalorraquidiano , Meningite/fisiopatologia , Doenças da Coluna Vertebral/sangue , Doenças da Coluna Vertebral/líquido cefalorraquidiano , Doenças da Coluna Vertebral/fisiopatologia , Infecções por Spirurida/sangue , Infecções por Spirurida/líquido cefalorraquidiano , Infecções por Spirurida/fisiopatologia , Espectrometria de Massas em TandemRESUMO
A more complete understanding of immune-mediated damage to the coronary arteries in children with Kawasaki disease (KD) is required for improvements in patient treatment and outcomes. We recently reported the transcriptional profile of KD coronary arteritis, and in this study sought to determine protein expression of transcriptionally up-regulated immune genes in KD coronary arteries from the first 2 months after disease onset. We examined the coronary arteries of 12 fatal KD cases and 13 childhood controls for expression of a set of proteins whose genes were highly up-regulated in the KD coronary artery transcriptome: allograft inflammatory factor 1 (AIF1), interleukin 18 (IL-18), CD74, CD1c, CD20 (MS4A1), Toll-like receptor 7 (TLR-7) and Z-DNA binding protein 1 (ZBP1). Immunohistochemistry and immunofluorescence studies were performed to evaluate protein expression and co-localization, respectively. AIF1 was expressed transmurally in KD arteritis and localized to macrophages and myeloid dendritic cells. CD74, which interacts with major histocompatibility complex (MHC) class II on antigen-presenting cells, localized to the intima-media. CD1c, a marker of myeloid dendritic cells, was expressed in a transmural pattern, as were IL-18 and CD20. ZBP1 and TLR-7 were up-regulated compared to controls, but less highly compared to the other proteins. These findings provide evidence of antigen presentation and interferon response in KD arteritis. In combination with prior studies demonstrating T lymphocyte activation, these results demonstrate the complexity of the KD arterial immune response.
Assuntos
Arterite/imunologia , Vasos Coronários/imunologia , Expressão Gênica , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/metabolismo , Apresentação de Antígeno , Antígenos CD/genética , Antígenos CD1/genética , Antígenos CD20/genética , Arterite/fisiopatologia , Proteínas de Ligação ao Cálcio , Aneurisma Coronário/imunologia , Vasos Coronários/fisiopatologia , Proteínas de Ligação a DNA/genética , Feminino , Imunofluorescência , Perfilação da Expressão Gênica , Glicoproteínas/genética , Humanos , Imuno-Histoquímica , Lactente , Interleucina-18/genética , Masculino , Proteínas dos Microfilamentos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/mortalidade , Proteínas de Ligação a RNA , Sialiltransferases/genética , Receptor 7 Toll-Like/genéticaAssuntos
Angioplastia com Balão/instrumentação , Aortite/cirurgia , Arterite/cirurgia , Estenose das Carótidas/cirurgia , Pescoço/irrigação sanguínea , Stents , Síndrome do Roubo Subclávio/cirurgia , Síncope/etiologia , Insuficiência Vertebrobasilar/cirurgia , Adulto , Aortite/diagnóstico por imagem , Aortite/fisiopatologia , Arterite/diagnóstico por imagem , Arterite/fisiopatologia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Angiografia Cerebral/métodos , Circulação Cerebrovascular , Doença Crônica , Circulação Colateral , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Recidiva , Síndrome do Roubo Subclávio/diagnóstico por imagem , Síndrome do Roubo Subclávio/fisiopatologia , Síncope/fisiopatologia , Resultado do Tratamento , Grau de Desobstrução Vascular , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/fisiopatologiaRESUMO
Abdominal aortic aneurysm (AAA) is a life-threatening disease associated with high morbidity, and high mortality in the event of aortic rupture. Major advances in open surgical and endovascular repair of AAA have been achieved during the past 2 decades. However, drug-based therapies are still lacking, highlighting a real need for better understanding of the molecular and cellular mechanisms involved in AAA formation and progression. The main pathological features of AAA include extracellular matrix remodelling associated with degeneration and loss of vascular smooth muscle cells and accumulation and activation of inflammatory cells. The inflammatory process has a crucial role in AAA and substantially influences many determinants of aortic wall remodelling. In this Review, we focus specifically on the involvement of monocytes and macrophages, summarizing current knowledge on the roles, origin, and functions of these cells in AAA development and its complications. Furthermore, we show and propose that distinct monocyte and macrophage subsets have critical and differential roles in initiation, progression, and healing of the aneurysmal process. On the basis of experimental and clinical studies, we review potential translational applications to detect, assess, and image macrophage subsets in AAA, and discuss the relevance of these applications for clinical practice.
Assuntos
Aneurisma da Aorta Abdominal , Macrófagos , Monócitos , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/fisiopatologia , Arterite/patologia , Arterite/fisiopatologia , Descoberta de Drogas , Matriz Extracelular/patologia , Matriz Extracelular/fisiologia , Humanos , Macrófagos/patologia , Macrófagos/fisiologia , Monócitos/patologia , Monócitos/fisiologia , Remodelação Vascular/efeitos dos fármacosRESUMO
Systemic vasculitides are caused by inflammation of blood vessels and can affect any organ and any part of the gastrointestinal tract, hepatic and biliary system, as well as the pancreas. These disorders can cause a wide array of gastrointestinal manifestations, from asymptomatic elevated transaminase levels and mild abdominal pain to potentially life-threatening bowel perforations and peritonitis. A diagnosis based solely on gastrointestinal symptoms is challenging as these manifestations are not specific. Conversely, diagnostic and therapeutic delays can be rapidly detrimental. In this article, we review the epidemiology, characteristics and management of the main gastrointestinal manifestations of systemic vasculitides, including polyarteritis nodosa and antineutrophil cytoplasm antibody-associated vasculitides, as well as isolated vasculitides limited to the gastrointestinal tract.
Assuntos
Gastroenteropatias/etiologia , Vasculite Sistêmica/fisiopatologia , Arterite/diagnóstico , Arterite/epidemiologia , Arterite/fisiopatologia , Arterite/terapia , Diagnóstico Diferencial , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Gastroenteropatias/terapia , Saúde Global , Humanos , Vasculite Sistêmica/diagnóstico , Vasculite Sistêmica/epidemiologia , Vasculite Sistêmica/terapiaRESUMO
Ischemic optic neuropathy (ION) describes a state of hypoxic injury of the optic nerve. Clinically, ION is divided into anterior and posterior forms defined by the presence or absence of optic disc swelling, respectively. It is further classified as arteritic when secondary to vasculitis, and nonarteritic when not. The site of vascular occlusion for anterior ION from giant cell arteritis is the short posterior ciliary arteries, but mechanical vascular obstruction does not play a role in most nonarteritic cases. Histologically, ION is characterized by axon and glial necrosis, edema, and a sparse mononuclear response. Like other ischemic injuries, the morphologic alternations in the nerve are time dependent. A variant of ION called cavernous degeneration (of Schnabel) features large cystic spaces filled with mucin. Several conditions can histologically mimic cavernous degeneration of the optic nerve. The scarcity of cases of ION examined histologically has contributed to an incomplete understanding of its pathogenesis.
Assuntos
Nervo Óptico/patologia , Neuropatia Óptica Isquêmica/patologia , Arterite/diagnóstico , Arterite/fisiopatologia , Diagnóstico Diferencial , Humanos , Disco Óptico/patologia , Disco Óptico/fisiopatologia , Nervo Óptico/fisiopatologia , Neuropatia Óptica Isquêmica/classificação , Neuropatia Óptica Isquêmica/fisiopatologiaRESUMO
PURPOSE: Diabetic patients have a greater risk of nonarteritic anterior ischemic optic neuropathy (NAION) than nondiabetic patients. We compare visual outcomes, prevalence of bilateral/sequential ION, and predictors of visual outcomes in NAION between diabetic and nondiabetic patients. DESIGN: Case-control study. PARTICIPANTS: All 231 patients with NAION seen by the Neuro-Ophthalmology Service, Wilmer Eye Institute, between 2002 and 2011 were screened for study inclusion. METHODS: Patients presenting within 4 weeks of symptom onset (30 with diabetes mellitus, 62 control patients) were included in baseline demographic assessments of vascular risk factors. Interval and final visual outcomes (logarithm of the minimum angle of resolution [logMAR] visual acuity [VA]) were evaluated in the 81 patients in this group with clinical follow-up for ≥3 months, and population average logistic regression models were used to determine risk factors for worse visual outcomes. MAIN OUTCOME MEASURES: Visual acuity at last follow-up. RESULTS: The median follow-up duration was 38.7 weeks in diabetic patients and 52.9 weeks in nondiabetic patients. The majority (92.5%) of patients presented within 2 weeks of symptom onset. In nondiabetic patients, the most prevalent risk factor for NAION was hyperlipidemia (62.9%); for diabetic patients, NAION risk factors included hypertension (83.3%), hyperlipidemia (83.3%), and small cup-to-disc ratio (63.3%). Sequential NAION occurred in 36.8% of diabetic patients and 20.9% of nondiabetic patients. At last follow-up, 48% of diabetic and 62% of nondiabetic patients had VA better than 20/40. Similar proportions of diabetic and nondiabetic patients (8 [27%] diabetic and 14 [22.5%] nondiabetic patients) recorded a final follow-up vision of 1.0 logMAR or worse at a minimum of 3 months. Ischemic heart disease (odds ratio [OR], 7.21; P < 0.001) and greater age (OR, 1.05; P = 0.045) were associated with increased risk for final VA <20/200 in the multiple regression model (OR, 4.35; P = 0.011). CONCLUSIONS: The VA at presentation and at final follow-up in diabetic patients with NAION were not significantly different from nondiabetic controls, although diabetic patients had a higher prevalence of cardiovascular risk factors. Ischemic heart disease and greater age, but not diabetes, independently correlated with worse VA outcome.
Assuntos
Diabetes Mellitus/fisiopatologia , Neuropatia Óptica Isquêmica/fisiopatologia , Acuidade Visual/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Arterite/epidemiologia , Arterite/fisiopatologia , Estudos de Casos e Controles , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Neuropatia Óptica Isquêmica/complicações , Neuropatia Óptica Isquêmica/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Nonarteritic anterior ischemic optic neuropathy (NAION) is a devastating ocular condition causing permanent vision loss. Little is known about risk factors for developing this disease. We assessed demographic, systemic, and ocular factors associated with NAION. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Beneficiaries between 40 and 75 years old without NAION at baseline enrolled in a large U.S. managed care network. METHODS: Enrollees were monitored continuously for ≥2 years between 2001 and 2014 to identify those newly diagnosed with NAION (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 377.41). All persons were under ophthalmic surveillance and all cases had ≥1 confirmatory ICD-9-CM code for NAION during follow-up. MAIN OUTCOME MEASURES: Multivariable Cox regression modeling was used to generate hazard ratios (HRs) with 95% confidence intervals (CIs) to describe the statistical relationship between selected demographic characteristics, systemic and ocular conditions, and the hazard of developing NAION. RESULTS: Of 1 381 477 eligible enrollees, 977 (0.1%) developed NAION during a mean ± standard deviation (SD) follow-up of 7.8±3.1 years. The mean ± SD age for NAION cases at the index date was 64.0±9.2 years vs. 58.4±9.4 years for the remainder of the beneficiaries. After adjustment for confounding factors, each additional year older was associated with a 2% increased hazard of NAION (HR = 1.02; 95% CI: 1.01-1.03). Female subjects had a 36% decreased hazard of developing NAION (HR = 0.64; 95% CI: 0.55-0.74) compared with male subjects. Compared with whites, Latinos had a 46% decreased hazard of developing NAION (HR = 0.54; 95% CI: 0.36-0.82), whereas African ancestry was not significantly associated with NAION (HR = 0.91; 95% CI: 0.72-1.15). Systemic diseases associated with NAION included hypertension (HR = 1.62; 95% CI: 1.26-2.07) and hypercoagulable states (HR = 2.46; 95% CI: 1.51-4.00). Although diabetes mellitus (DM) was not significantly associated with NAION compared with those without DM (P = 0.45), patients with end-organ involvement from DM had a 27% increased hazard of NAION relative to those with uncomplicated DM (HR = 1.27; 95% CI: 1.01-1.59). Ocular diseases associated with NAION were age-related macular degeneration (HR = 1.29; 95% CI: 1.08-1.54) and retinal vein occlusion (HR = 3.94; 95% CI: 3.11-4.99). CONCLUSIONS: Our study identified several modifiable risk factors that may be associated with NAION. Should future studies confirm these findings, they may offer opportunities to prevent or treat this debilitating condition.
Assuntos
Arterite/epidemiologia , Neuropatia Óptica Isquêmica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Arterite/diagnóstico , Arterite/fisiopatologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Programas de Assistência Gerenciada , Pessoa de Meia-Idade , Neuropatia Óptica Isquêmica/diagnóstico , Neuropatia Óptica Isquêmica/fisiopatologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Acuidade Visual/fisiologiaRESUMO
BACKGROUND: To evaluate the effect of high-dose intravenous steroids, as well as normobaric oxygen therapy, in the management of recent onset non-arteritic anterior ischemic optic neuropathy (NAION). METHOD: Ninety eyes of 90 patients diagnosed with NAION within 14 days of onset were included in this single masked randomized clinical trial. Thirty patients were randomized into each set as group 1 (control), group 2 (steroids), and group 3 (oxygen). Controls received placebo; group 2 received methylprednisolone 500 mg twice a day for 3 days followed by 2 weeks of oral prednisolone 1 mg/kg/day; group 3 received 100 % normobaric oxygen with mask, at a flow rate of 5 liters per minute for 1 hour twice a day for two weeks. Functional and structural outcomes were analyzed at 1 and 6 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measure, and mean deviation (MD) of visual field (VF) test and peripaillary retinal nerve fiber layer thickness (PRNFLT) were secondary outcome measures. RESULTS: The mean BCVA at the time of presentation was 1.02 ± 0.63, 1.05 ± 0.7, and 0.76 ± 0.5 LogMAR in groups 1, 2, and 3, respectively (p = 0.293); corresponding values were 0.8 ± 0.45, 0.84 ± 0.45, and 0.58 ± 0.4 at month 1 (p = 0.127, 0.19, and 0.168, respectively). BCVA improved to 0.71 ± 0.46, 0.73 ± 0.36, and 0.59 ± 0.41 LogMAR at the 6-month follow-up point (p = 0.039, 0.048, and 0.195, respectively). The mean deviation (MD) at the time of presentation was 19.26 ± 7.02, 20.51 ± 4.68, and 19.3 ± 7.17 in the control, steroid, and oxygen groups, respectively (p = 0.65). Corresponding values at month 1 were 20.26 ± 8.52, 19.52 ± 7.08, and 18.3 ± 7.45, (p = 0.656); and at month 6 were 18.42 ± 8.17, 17.66 ± 6.44 and 16.53 ± 6.32, respectively (p = 0.635). PRNFLT at presentation was 166 ± 57, 184 ± 57, and 193 ± 65 micrometer in the control, steroid, and oxygen groups, respectively (p = 0.265); which decreased to 73 ± 11, 87 ± 26, and 79 ± 19 at the final foll-w up (all p < 0.001). There were no statistically significant differences between the three groups in terms of final visual function and structure. CONCLUSION: The lack of demonstrable improvement in the structural and functional outcomes of NAION with high-dose IV steroids, or normobaric oxygen, in this randomized controlled trial calls into question the administering of systemic steroid or normobaric oxygen in this condition.
Assuntos
Glucocorticoides/administração & dosagem , Metilprednisolona/administração & dosagem , Neuropatia Óptica Isquêmica/terapia , Oxigenoterapia , Idoso , Arterite/tratamento farmacológico , Arterite/fisiopatologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Neuropatia Óptica Isquêmica/fisiopatologia , Células Ganglionares da Retina/patologia , Método Simples-Cego , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologiaRESUMO
Described herein is a case report of a severe lesion of the arterial system in non-specific aortoarteritis: lesion of the aortic arch branches, thoracoabdominal segment of the aorta, abdominal aorta, visceral and renal arteries, thus underlining a multiple nature of the lesion of the aorta and its branches in the pathology concerned. Diagnosis of lesions of the aorta and its branches was made by means of multispiral computed tomography (MSCT), being the most informative method of examination in this cohort of patients, making it possible to accurately diagnose both the degree of the lesion and its extension, to choose an optimal surgical policy, to carry out dynamic follow up of the condition of the reconstructed arterial segments.
Assuntos
Aortite , Arterite , Implante de Prótese Vascular , Metotrexato/administração & dosagem , Hemissuccinato de Metilprednisolona/administração & dosagem , Antirreumáticos/administração & dosagem , Aorta Abdominal/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Aortite/diagnóstico , Aortite/tratamento farmacológico , Aortite/fisiopatologia , Aortite/cirurgia , Arterite/diagnóstico , Arterite/tratamento farmacológico , Arterite/fisiopatologia , Arterite/cirurgia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Terapia Combinada , Feminino , Humanos , Artérias Mesentéricas/diagnóstico por imagem , Artérias Mesentéricas/cirurgia , Recidiva , Artéria Renal/diagnóstico por imagem , Artéria Renal/cirurgia , Reoperação/métodos , Artéria Subclávia/diagnóstico por imagem , Artéria Subclávia/cirurgia , Tomografia Computadorizada Espiral/métodos , Resultado do Tratamento , Adulto JovemRESUMO
Blood flow generates wall shear stress (WSS) which alters endothelial cell (EC) function. Low WSS promotes vascular inflammation and atherosclerosis whereas high uniform WSS is protective. Ivabradine decreases heart rate leading to altered haemodynamics. Besides its cardio-protective effects, ivabradine protects arteries from inflammation and atherosclerosis via unknown mechanisms. We hypothesised that ivabradine protects arteries by increasing WSS to reduce vascular inflammation. Hypercholesterolaemic mice were treated with ivabradine for seven weeks in drinking water or remained untreated as a control. En face immunostaining demonstrated that treatment with ivabradine reduced the expression of pro-inflammatory VCAM-1 (p<0.01) and enhanced the expression of anti-inflammatory eNOS (p<0.01) at the inner curvature of the aorta. We concluded that ivabradine alters EC physiology indirectly via modulation of flow because treatment with ivabradine had no effect in ligated carotid arteries in vivo, and did not influence the basal or TNFα-induced expression of inflammatory (VCAM-1, MCP-1) or protective (eNOS, HMOX1, KLF2, KLF4) genes in cultured EC. We therefore considered whether ivabradine can alter WSS which is a regulator of EC inflammatory activation. Computational fluid dynamics demonstrated that ivabradine treatment reduced heart rate by 20 % and enhanced WSS in the aorta. In conclusion, ivabradine treatment altered haemodynamics in the murine aorta by increasing the magnitude of shear stress. This was accompanied by induction of eNOS and suppression of VCAM-1, whereas ivabradine did not alter EC that could not respond to flow. Thus ivabradine protects arteries by altering local mechanical conditions to trigger an anti-inflammatory response.
Assuntos
Artérias/efeitos dos fármacos , Arterite/prevenção & controle , Benzazepinas/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Animais , Artérias/fisiologia , Arterite/fisiopatologia , Fenômenos Biomecânicos , Fármacos Cardiovasculares/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Frequência Cardíaca/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/fisiopatologia , Ivabradina , Fator 4 Semelhante a Kruppel , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Mecânico , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Non-arteritic anterior ischemic optic neuropathy (NAION) is a relatively common optic neuropathy in adults over the age of 50, typically causing sudden, painless, unilateral vision loss and always resulting in swelling of the optic nerve head. Though several anatomic and vascular risk factors have been identified, much remains unknown about its pathophysiology and there is no proven treatment. This article reviews the risk factors, clinical presentation, and therapies that have been investigated for NAION. In addition, we provide an update from recent rodent and primate models, which offer new insight into the pathophysiology of this disease and provide a platform for treatment trials.