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1.
J Invest Dermatol ; 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38086428

RESUMO

The immunologic drivers of cutaneous lupus erythematosus (CLE) and its clinical subtypes remain poorly understood. We sought to characterize the immune landscape of discoid lupus erythematosus and subacute CLE using multiplexed immunophenotyping. We found no significant differences in immune cell percentages between discoid lupus erythematosus and subacute CLE (P > .05) with the exception of an increase in TBK1 in discoid lupus erythematosus (P < .05). Unbiased clustering grouped subjects into 2 major clusters without respect to clinical subtype. Subjects with a history of smoking had increased percentages of neutrophils, disease activity, and endothelial granzyme B compared with nonsmokers. Despite previous assumptions, plasmacytoid dendritic cells (pDCs) did not stain for IFN-1. Skin-eluted and circulating pDCs from subjects with CLE expressed significantly less IFNα than healthy control pDCs upon toll-like receptor 7 stimulation ex vivo (P < .0001). These data suggest that discoid lupus erythematosus and subacute CLE have similar immune microenvironments in a multiplexed investigation. Our aggregated analysis of CLE revealed that smoking may modulate disease activity in CLE through neutrophils and endothelial granzyme B. Notably, our data suggest that pDCs are not the major producers of IFN-1 in CLE. Future in vitro studies to investigate the role of pDCs in CLE are needed.

2.
Arthritis Rheumatol ; 74(10): 1687-1698, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35583812

RESUMO

OBJECTIVE: The pathogenesis of cutaneous lupus erythematosus (CLE) is multifactorial, and CLE is difficult to treat due to the heterogeneity of inflammatory processes among patients. Antimalarials such as hydroxychloroquine (HCQ) and quinacrine (QC) have long been used as first-line systemic therapy; however, many patients do not respond to treatment with antimalarials and require systemic immunosuppressants that produce undesirable side effects. Given the complexity and the unpredictability of responses to antimalarial treatments in CLE patients, we sought to characterize the immunologic profile of patients with CLE stratified by subsequent treatment outcomes to identify potential biomarkers of inducible response. METHODS: We performed mass cytometry imaging of multiple immune cell types and inflammation markers in treatment-naive skin biopsy samples from 48 patients with CLE to identify baseline immunophenotypes that may predict the response to antimalarial therapy. Patients were stratified according to their response to treatment with antimalarials, as HCQ responders, QC responders, or nonresponders. RESULTS: HCQ responders demonstrated increased CD4+ T cells compared to the QC responder group. Patients in the nonresponder group were found to have decreased Treg cells compared to QC responders and increased central memory T cells compared to HCQ responders. QC responders expressed increased phosphorylated stimulator of interferon genes (pSTING) and interferon-κ (IFNκ) compared to HCQ responders. Phosphorylated STING and IFNκ were found to be localized to conventional dendritic cells (cDCs), and the intensity of pSTING and IFNκ staining was positively correlated with the number of cDCs on a tissue and cellular level. Neighborhood analysis revealed decreased regulatory cell interactions in nonresponder patients. Hierarchical clustering revealed that nonresponder patients could be further differentiated based on expression of pSTAT2, pSTAT3, pSTAT4, pSTAT5, phosphorylated interferon regulatory factor 3 (pIRF3), granzyme B, pJAK2, interleukin-4 (IL-4), IL-17, and IFNγ. CONCLUSION: These findings indicate differential immune cell compositions between patients with CLE, offering guidance for future research on precision-based medicine and treatment response.


Assuntos
Antimaláricos , Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Sistêmico , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Granzimas , Humanos , Hidroxicloroquina/efeitos adversos , Imunossupressores/uso terapêutico , Fator Regulador 3 de Interferon , Interferons , Interleucina-17 , Interleucina-4 , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Cutâneo/patologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Quinacrina/farmacologia , Quinacrina/uso terapêutico
3.
J Neurointerv Surg ; 14(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33593798

RESUMO

BACKGROUND: The purpose of this cross-sectional study was to determine the percentage of the US population with 60 min ground or air access to accredited or state-designated endovascular-capable stroke centers (ECCs) and non-endovascular capable stroke centers (NECCs) and the percentage of NECCs with an ECC within a 30 min drive. METHODS: Stroke centers were identified and classified broadly as ECCs or NECCs. Geographic mapping of stroke centers was performed. The population was divided into census blocks, and their centroids were calculated. Fastest air and ground travel times from centroid to nearest ECC and NECC were estimated. RESULTS: Overall, 49.6% of US residents had 60 min ground access to ECCs. Approximately 37.7% (113 million) lack 60 min ground or air access to ECCs. Approximately 84.4% have 60 min access to NECCs. Ground-only access was available to 77.9%. Approximately 738 NECCs (45.4%) had an ECC within a 30 min drive. CONCLUSION: Nearly one-third of the US population lacks 60 min access to endovascular stroke care, but this is highly variable. Transport models and planning of additional centers should be tailored to each state depending on location and proximity of existing facilities.


Assuntos
Acidente Vascular Cerebral , Estudos Transversais , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Estados Unidos/epidemiologia
4.
J Neurointerv Surg ; 13(4): 324-330, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33593797

RESUMO

BACKGROUND: There are no reports that describe complete flow control using concurrent transient rapid ventricular pacing or intravenous (IV) adenosine and afferent arterial balloon flow arrest to aid transvenous embolization of cerebral arteriovenous malformations (AVM). We describe our experience with the use of this technique in patients undergoing transvenous AVM embolization. METHODS: Consecutive patients in whom transvenous embolization was attempted at our institute between January 2017 and July 2019 were included. Anatomical AVM features, number of embolization stages, technique of concurrent transient rapid ventricular pacing and afferent arterial balloon flow arrest, complications, and clinical and radiological outcomes were recorded and tabulated. RESULTS: Transvenous AVM embolization was attempted in 12 patients but abandoned in two patients for technical reasons. Complete embolization was achieved in 10 patients, five of whom had infratentorial AVMs. All 10 had a single primary draining vein. Rapid ventricular pacing was used in nine cases; IV adenosine injection was used in one case to achieve cardiac standstill. Complete AVM nidus obliteration was achieved with excellent neurologic outcome in nine cases, with transvenous embolization alone in two cases, and with staged transarterial followed by transvenous embolization in the others. Two patients developed hemorrhagic complications intraprocedurally. One patient was managed conservatively and the other operatively with AVM excision and hematoma evacuation; both made an excellent recovery without any neurologic deficits at 3 months. CONCLUSION: Complete flow control using concurrent transient rapid ventricular pacing with afferent arterial balloon flow arrest technique is safe and feasible for transvenous embolization of select AVMs.


Assuntos
Adenosina/administração & dosagem , Fístula Arteriovenosa/terapia , Oclusão com Balão/métodos , Velocidade do Fluxo Sanguíneo/fisiologia , Embolização Terapêutica/métodos , Malformações Arteriovenosas Intracranianas/terapia , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/fisiopatologia , Feminino , Seguimentos , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
5.
J Neurointerv Surg ; 13(3): 247-250, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32620576

RESUMO

BACKGROUND: Patients with cerebral aneurysms treated with the Pipeline embolization device (PED) are maintained on dual antiplatelet therapy (DAPT) to prevent thromboembolic complications. Rates of minor, "nuisance" bleeding in these patients remain unknown. We sought to evaluate the frequency and factors associated with this bleeding and its effect on DAPT compliance. METHODS: We performed a multicenter retrospective cohort study on consecutive cases of intracranial aneurysms treated with PED. Patient characteristics, aneurysm characteristics, and bleeding complications were analyzed. Severity of bleeding was defined according to a previously published classification defining nuisance bleeding as easy bruising, bleeding from small cuts, petechia, and ecchymosis. RESULTS: 245 PED aneurysm procedures on 243 patients were retrospectively collected from three academic centers over a 4.25-year period. Sixty-seven patients (27%) had nuisance bleeds. Patients with a higher risk of nuisance bleeding were older (59.1±3.4 vs . 54.7±2.2, P=0.032). Patients with nuisance bleeds were more likely to have their DAPT regimen changed or dose lowered (29% vs 8.3%, P<0.001), were on DAPT for less time (10.0 months±2.60 vs. 14.6 months±1.95, P=0.005) and were more likely to have aneurysm occlusion at 6 months (P<0.001). Stepwise logistic regression found age predictive of a nuisance bleed (OR=1.033) CONCLUSIONS: Nuisance bleeding was a common complaint of PED-treated aneurysm patients maintained on DAPT. Increasing age and aneurysmal occlusion at 6 months were the only factors predictive of nuisance bleeds. Clinicians were more likely to adjust antiplatelet regimens or stop DAPT early given a nuisance bleed.


Assuntos
Terapia Antiplaquetária Dupla/efeitos adversos , Embolização Terapêutica/efeitos adversos , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/terapia , Hemorragias Intracranianas/epidemiologia , Stents Metálicos Autoexpansíveis/efeitos adversos , Adulto , Idoso , Prótese Vascular/efeitos adversos , Prótese Vascular/tendências , Estudos de Coortes , Terapia Antiplaquetária Dupla/tendências , Embolização Terapêutica/tendências , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico , Hemorragias Intracranianas/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents Metálicos Autoexpansíveis/tendências , Resultado do Tratamento , Adulto Jovem
6.
J Neurointerv Surg ; 12(12): 1214-1218, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32601261

RESUMO

BACKGROUND: Middle meningeal artery (MMA) embolization is an emerging therapy for the resolution of subacute or chronic subdural hematoma (CSDH). CSDH patients are often elderly and have several comorbidities. We evaluated our experience with transradial access (TRA) for MMA embolization using predominantly Onyx under conscious sedation. METHODS: Data for consecutive patients who underwent transradial MMA embolization for CSDH during a 2-year period (2018-2019) were analyzed from a single-center, prospectively-maintained database. Patient demographics, comorbidities, ambulatory times, subdural hematoma resorption status, and guide catheter type were recorded. Conversion to femoral access and complication rates were also recorded. Univariate and multivariate analyses were performed. RESULTS: Forty-six patients (mean age, 71.7±14.4 years) were included in this study. Mean CSDH size was 14±5.5 mm. Most (91.3%) TRA embolizations were performed with 6-French 0.071-inch Benchmark guide catheters (Penumbra). MMA embolization was successful in 44 patients (95.7%) (including two cases of TRA conversion). Twenty-one (48%) patients had a severe Charlson Comorbidity Index (>5). Symptomatic improvement was noted in 39 of 44 patients (88.6%). Mean length of stay was 4±3 days. Patients were ambulated immediately postprocedure. At mean follow-up (8±4 weeks), 86.4% of patients had complete or partial CSDH resolution. Persistent use of antiplatelet agents after the procedure was associated with failed or minimal CSDH resorption (5 of 6, 83.3% vs 9 of 38 23.7% with complete or near-complete resolution; P=0.009). CONCLUSION: Transradial Onyx MMA embolization under conscious sedation is safe and effective for CSDH treatment. TRA may be especially useful in elderly patients with numerous comorbidities.


Assuntos
Embolização Terapêutica/métodos , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/terapia , Artérias Meníngeas/diagnóstico por imagem , Polivinil/administração & dosagem , Artéria Radial/diagnóstico por imagem , Tantálio/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
J Neurointerv Surg ; 12(6): 585-590, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31959632

RESUMO

BACKGROUND: A Pipeline embolization device (PED; Medtronic, Dublin, Ireland) can be deployed using either a biaxial or a triaxial catheter delivery system. OBJECTIVE: To compare the use of these two catheter delivery systems for intracranial aneurysm treatment with the PED. METHODS: A retrospective study of patients undergoing PED deployment with biaxial or triaxial catheter systems between 2014 and 2016 was conducted. Experienced neurointerventionalists performed the procedures. Patients who received multiple PEDs or adjunctive coils were excluded. The two groups were compared for PED deployment time, total fluoroscopy time, patient radiation exposure, complications, and cost. RESULTS: Eighty-two patients with 89 intracranial aneurysms were treated with one PED each. In 49 cases, PEDs were deployed using biaxial access; triaxial access was used in 33 cases. Time (min) from guide catheter run to PED deployment was significantly shorter in the biaxial group (24.0±18.7 vs 38.4±31.1, P=0.006) as was fluoroscopy time (28.8±23.0 vs 50.3±27.1, P=0.001). Peak radiation skin exposure (mGy) in the biaxial group was less than in the triaxial group (1243.7±808.2 vs 2074.6±1505.6, P=0.003). No statistically significant differences were observed in transient and permanent complication rates or modified Rankin Scale scores at 30 days. The triaxial access system cost more than the biaxial access system (average $3285 vs $1790, respectively). Occlusion rates at last follow-up (mean 6 months) were similar between the two systems (average 88.1%: biaxial, 89.2%: triaxial). CONCLUSION: Our results indicate near-equivalent safety and effectiveness between biaxial and triaxial approaches. Some reductions in cost and procedure time were noted with the biaxial system.


Assuntos
Prótese Vascular , Catéteres , Embolização Terapêutica/métodos , Aneurisma Intracraniano/terapia , Stents Metálicos Autoexpansíveis , Adulto , Idoso , Prótese Vascular/economia , Prótese Vascular/normas , Catéteres/economia , Estudos de Coortes , Embolização Terapêutica/economia , Embolização Terapêutica/normas , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/economia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Stents Metálicos Autoexpansíveis/economia , Stents Metálicos Autoexpansíveis/normas , Resultado do Tratamento
8.
World Neurosurg ; 133: e434-e442, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31525478

RESUMO

OBJECTIVE: To assess the association of degree of contrast stasis in intracranial aneurysms (IAs) immediately after Pipeline embolization device (PED; Medtronic, Dublin, Ireland) deployment with 6- and 12-month angiographic occlusion rates. METHODS: This retrospective cohort study included consecutive patients undergoing PED deployment for saccular IA treatment at a large-volume cerebrovascular center over a 4-year 9-month period. Angiographic images obtained immediately after PED deployment were graded according to amount of intra-aneurysmal contrast flow during the late venous phase: 0 = no stasis; 1 = <50% contrast stasis; 2 = 50%-75% stasis; and 3 = >75%-99% stasis. Follow-up occlusion rates were determined by digital subtraction angiography, computed tomographic angiography, or magnetic resonance angiography. RESULTS: The study included 119 patients in whom 182 PEDs were deployed to treat 141 aneurysms. A single PED was deployed in 105 (74.5%) aneurysms. The internal carotid artery was the commonest aneurysm site (119 [85%]). Fifty-two (36.9%) aneurysms were grade 0; 33 (23.4%) were grade 1; 46 (32.6%) were grade 2; and 10 (7.1%) were grade 3 immediately post-treatment. A 6-month follow-up angiogram available for 101 aneurysms showed complete occlusion (no flow into the aneurysm) in 74 (73.3%) aneurysms. A 12-month follow-up study available for 132 aneurysms showed complete occlusion in 79.5%. At last follow-up, occlusion rates were not significantly different for different contrast stasis grades (P = 0.60). Mean angiographic follow up for all IAs was 23v±v17.7 months. IA size, sex, age, and smoking were not significant predictors of occlusion. CONCLUSIONS: The degree of aneurysm contrast stasis immediately after PED deployment is not statistically associated with 6- and 12-month angiographic occlusion rates.


Assuntos
Embolização Terapêutica/instrumentação , Hemorreologia , Aneurisma Intracraniano/terapia , Stents , Adulto , Idoso , Angiografia Digital , Angiografia Cerebral , Meios de Contraste/farmacocinética , Embolização Terapêutica/métodos , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Método Simples-Cego , Trombose/etiologia , Resultado do Tratamento
9.
J Neurointerv Surg ; 12(3): 260-265, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31444289

RESUMO

INTRODUCTION: Accurate estimation of the incidence of large vessel occlusion (LVO) is critical for planning stroke systems of care and approximating workforce requirements. This systematic review aimed to estimate the prevalence of LVO among patients with acute ischemic stroke (AIS), with emphasis on definitions and methods used by different studies. METHODS: A systematic literature review was performed to search for articles on the prevalence of LVO and AIS. All articles describing the frequency of LVO frequency among AIS patients were included. Studies without consecutive recruitment or confirmation of LVO with CT angiography or MR angiography were excluded. Heterogeneity of the studies was assessed; meta-regression was performed to estimate the effect of LVO definition and study methods on LVO prevalence. RESULTS: 18 articles met the inclusion criteria: 5 studies presented population based estimates; 13 provided single hospital experiences (5 prospective, 8 retrospective). The AIS denominator (number of all AIS) from which LVO rates were generated was variable. Nine different definitions were used, based on occlusion site. Significant heterogeneity existed among the studies (I2=99%, P<0.001). The prevalence of LVO among patients with suspected AIS ranged from 13% to 52%. Overall prevalence was 30.0% (95% CI 25.0% to 35.0%). Pooled prevalence of LVO among suspected AIS patients was 21% (95% CI 19% to 30%). Based on meta-regression, the method of AIS denominator determination significantly influenced heterogeneity (P=0.018). CONCLUSION: The heterogeneity of LVO estimates was remarkably high. The method of AIS denominator determination was the most significant predictor of LVO estimates. Studies with a standardized LVO definition and methods of AIS estimation are necessary to estimate the true prevalence of LVO among patients with AIS.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Transtornos Cerebrovasculares/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Transtornos Cerebrovasculares/epidemiologia , Humanos , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia
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