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1.
J Rheum Dis ; 31(2): 86-96, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38559796

RESUMO

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). Conclusion: In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

2.
J Int Med Res ; 49(4): 3000605211004201, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33823632

RESUMO

OBJECTIVES: The diagnosis of ankylosing spondylitis (AS) is often delayed, which affects various clinical outcomes. This study examined the real-world situation of patients with AS during diagnosis and treatment. METHODS: Data were obtained from 26 tertiary care hospitals in Korea using a self-report questionnaire. The questionnaire assessed symptoms, pain, extra-articular manifestations, the initial pattern of pain before diagnosis, factors leading to delayed referral to rheumatology, time until receiving an AS diagnosis, comorbid diseases, treatment status, and disease education needs. RESULTS: Between September and October 2019, 1012 patients with AS completed the survey. Of these, 75.8% were men and 51.8% were in their 30s or 40s. Median disease duration was 76 months. The median time to diagnosis with AS was 12 months. When pain occurred, the medical departments most frequently visited first were orthopedic (61.5%) and rheumatology (18.7%) departments. The likelihood of the first visit being to the orthopedic department and the frequency of biologics use increased with the disease duration. The rates of uveitis, depressed mood, and comorbid diseases were higher in the group with delayed diagnosis. CONCLUSIONS: Physicians should be aware of subtypes of AS that take longer to diagnose and comorbid diseases in the real-world clinical setting.


Assuntos
Autorrelato , Espondilite Anquilosante , Adulto , Feminino , Humanos , Masculino , República da Coreia/epidemiologia , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/epidemiologia , Inquéritos e Questionários
3.
Clin Rheumatol ; 39(12): 3625-3629, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32556935

RESUMO

The clinical relevance of the fabella, a sesamoid bone, has recently been investigated. Although many studies have documented the prevalence of the fabella, few large-scale studies have been conducted in an Asian, especially Korean, population. We conducted a retrospective survey of Koreans to determine the prevalence and distribution of the fabella and its association with osteoarthritic severity of the knee. From June 2016 to August 2017, a total of 2243 people who visited a rheumatology clinic for musculoskeletal evaluation was consecutively recruited. A total of 2126 subjects (1634 females and 492 males) was finally registered and analysed. Anteroposterior and lateral radiographs of both knees were analysed for presence, number and distribution of fabellae and Kellgren-Lawrence grade. The prevalence of the fabella was 57.2% (57.5% for females, 56.1% for males). Among subjects with a fabella, 21.2% had a unilateral distribution, and 78.8% had a bilateral distribution. The number of fabella was correlated with increasing age (r = 0.169, p < 0.001). In the group of subjects with a fabella, the Kellgren-Lawrence grade was significantly higher than in the group without a fabella (2.64 ± 1.38 vs. 1.89 ± 1.54, p < 0.001). The prevalence of fabella in Koreans was relatively high compared with the findings of previous studies, irrespective of the country studied or methodology used. The number of fabellae tended to increase with age. The osteoarthritic severity of the knee appeared worse in the group with a fabella. Key Points • The radiographical prevalence rate of fabella in Korea was about 58%, higher than the previous results. • The prevalence of fabella increased as the age of the subject increased regardless of gender. • The association between fabella and osteoarthritis is strongly suspected because the osteoarthritic changes in the knee of the subjects with fabella are significantly higher than in the subjects without fabella.


Assuntos
Osteoartrite do Joelho , Ossos Sesamoides , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Prevalência , República da Coreia/epidemiologia , Estudos Retrospectivos
4.
J Int Med Res ; 48(6): 300060520931323, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32589073

RESUMO

OBJECTIVES: Celecoxib is a selective cyclooxygenase (COX)-2 inhibitor that is commonly used to reduce the incidence of gastrointestinal (GI) complications in patients with rheumatoid arthritis (RA). CELBESTA® is a generic equivalent to CELEBREX®, a celecoxib preparation. This study compared the efficacy and safety of CELBESTA® and CELEBREX® in patients with RA. METHODS: This was a multicenter, double-blind, double-dummy, active-controlled, randomized, parallel-group, non-inferiority clinical trial. The primary endpoint was a change from baseline in self-assessed pain intensity determined using a 100-mm visual analog scale after 6 weeks of treatment. RESULTS: After a washout period, 119 eligible subjects were randomized to one of two groups (CELBESTA® group, n = 61; CELEBREX® group, n = 58). CELBESTA® was not inferior to CELEBREX® because the upper limit of two-sided 95% confidence interval (CI) for the difference between the two groups (difference in the least square [LS] mean, -8.68 mm; two-sided 95% CI -16.59 mm to -0.77 mm) was less than the non-inferiority margin (10 mm). There were no significant differences in GI complications and renal toxicity. CONCLUSIONS: CELBESTA® was not inferior to CELEBREX® with regard to the pain relief efficacy in RA patients, and the tolerability and safety profiles were excellent and at similar levels for both preparations.


Assuntos
Artrite Reumatoide , Sulfonamidas , Artrite Reumatoide/tratamento farmacológico , Celecoxib/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Método Duplo-Cego , Humanos , Pirazóis/efeitos adversos , Sulfonamidas/uso terapêutico , Resultado do Tratamento
5.
Korean J Intern Med ; 35(1): 231-239, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30685961

RESUMO

BACKGROUND/AIMS: The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. METHODS: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. RESULTS: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was -19.0 in the bDMARD group and -12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. CONCLUSION: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Biomarcadores , Exercício Físico , Humanos , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento
6.
Korean J Intern Med ; 35(2): 465-473, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31830775

RESUMO

BACKGROUND/AIMS: Biologics are very effective drugs for patients with ankylosing spondylitis (AS). However, there are patients who are not responding to biologics. This study aimed to evaluate the level of tumor necrosis factor α (TNF-α), interleukin (IL)-23, and IL-17 from synovial fluid in patients with AS and rheumatoid arthritis (RA) and differences of the level of those cytokines according to drugs. METHODS: Synovial fluid was obtained from 34 patients (42 samples) with AS and 45 patients (47 samples) with RA with active arthritis of the knee, and the cytokine levels were measured. The differences in the levels between patients treated with and without biologics (biologics and non-biologics groups, respectively) were analyzed in AS and RA. The correlations between cytokines were examined in the non-biologics and biologics groups. RESULTS: The TNF-α level in AS was significantly lower than that in RA (p = 0.016). The IL-17 and IL-23 levels were not different between AS and RA (p = 0.409 and p = 0.562, respectively). In AS and RA, TNF-α, IL-17, and IL-23 showed good correlation among each other in the non-biologics group. However, there was no significant correlation in biologics group. In some patients in the AS group, the IL-17 or IL-23 level was markedly elevated in the biologics group. CONCLUSION: Treatment with biologics affects the cytokine profile in inflammatory synovial fluid in patients with both AS and RA. Furthermore, IL-23 and IL-17 cytokine might be an important factor in some patients who are unresponsive to biologics in AS.


Assuntos
Artrite Reumatoide , Produtos Biológicos , Espondilite Anquilosante , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Citocinas , Humanos , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/tratamento farmacológico , Líquido Sinovial , Fator de Necrose Tumoral alfa
7.
Arthritis Res Ther ; 21(1): 122, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113455

RESUMO

BACKGROUND: To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA). METHODS: This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100. RESULTS: A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively). CONCLUSIONS: Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02715908 . Registered 22 March 2016.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Etanercepte/uso terapêutico , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Antirreumáticos/farmacocinética , Medicamentos Biossimilares/farmacocinética , Método Duplo-Cego , Etanercepte/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equivalência Terapêutica , Tempo , Resultado do Tratamento
8.
Rheumatol Int ; 35(11): 1817-23, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26342296

RESUMO

The aim of this study was to compare anti-tumor necrosis factor-α (TNFα) treatment status in rheumatoid arthritis (RA) patients with the Korean National Health Insurance (KNHI) reimbursement eligibility criteria and with American College of Rheumatology (ACR) recommendations, Japan College of Rheumatology (JCR) guidelines and British Society for Rheumatology (BSR) guidelines. Between December 2011 and August 2012, outpatients from 17 South Korean general hospitals diagnosed with RA according to the 1987 ACR criteria were enrolled into a noninterventional, cross-sectional, observational study. Of 1700 patients (1414 female (83.2 %), mean age of 56.6 ± 12.0, mean disease duration 97.9 ± 91.8 months), 306 (18.0 %) had used anti-TNFα agents, and 224 (13.2 %) were currently using an anti-TNFα agent. Of 1394 anti-TNFα-naive patients, 32 (2.3 %) met KNHI reimbursement guidelines, 148 (10.6 %) met ACR recommendations, and 127 (9.1 %) and 126 (9.0 %) were considered eligible for anti-TNFα agents according to JCR and BSR guidelines, respectively. The main discrepancy was the higher active joint count required by the KNHI eligibility criteria. In the opinion of treating rheumatologists, the KNHI reimbursement criteria ineligibility accounted for 15.3 % (n = 213) of the reasons for not initiating anti-TNFα agents in anti-TNFα-naive group. The anti-TNFα user group showed significantly higher disease activity than the anti-TNFα-naive group based on DAS28 score. In comparison with the ACR recommendations and JCR and BSR guidelines, fewer patients met KNHI reimbursement eligibility criteria for anti-TNFα agents. The current amendment of the KNHI criteria based on DAS28 score will improve an access to biologic agents including anti-TNFα treatment for South Korean patients with active RA.


Assuntos
Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Custos de Medicamentos , Definição da Elegibilidade/economia , Reembolso de Seguro de Saúde/economia , Programas Nacionais de Saúde/economia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Estudos Transversais , Revisão de Uso de Medicamentos , Definição da Elegibilidade/normas , Feminino , Fidelidade a Diretrizes/economia , Hospitais Gerais/economia , Humanos , Reembolso de Seguro de Saúde/normas , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/normas , Guias de Prática Clínica como Assunto , República da Coreia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia
9.
Inflamm Res ; 61(6): 541-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22476561

RESUMO

OBJECTIVE: We investigated whether promoter -2518 single nucleotide polymorphism (SNP) of the monocyte chemoattractant protein-1 (MCP-1) gene contributes to susceptibility and clinical features or severity in Behçet's disease (BD) patients. METHODS: One hundred and thirty-two BD patients and 113 healthy subjects, matched by sex and age, were enrolled. Promoter -2518 polymorphism of the MCP-1 gene was analyzed using automated sequencing. Clinical severity in BD patients was classified into mild, moderate, and severe features and assessed by total severity scores. Clinical features and severity was also compared according to genotypes using either the chi-squared or Fisher's exact test and Mann-Whitney test, as indicated. RESULTS: There were no significant differences in alleles (G allele vs. A allele, p=0.845) and genotypes with -2518 SNP (GG vs. GA vs. AA, p=0.916) between BD patients and controls. No clinical features were associated with genotypes with -2518 polymorphism of MCP-1. However, the frequency of either GA or AA genotype in patients with moderate lesions and moderate to severe lesions was significantly increased compared with that in patients with the GG genotype (p=0.044 and p=0.038, respectively). Total severity scores in the AA genotype were higher than those in the GG and GA genotypes (p=0.039 and p=0.003, respectively). Moreover, patients with either the GA or AA genotype had higher scores than those with the GG genotype (p=0.041). CONCLUSIONS: This study demonstrated that genotypes with A allele with -2518 polymorphism of the MCP-1 gene might have increased risk of severity of clinical features, but not susceptibility to BD.


Assuntos
Síndrome de Behçet/genética , Quimiocina CCL2/genética , Adulto , Síndrome de Behçet/patologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Índice de Gravidade de Doença
10.
Rheumatol Int ; 28(8): 783-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18092167

RESUMO

Three-prime repair exonucleases 1 and 2 (TREX1 and TREX2) play a role in the metabolism and clearance of DNA. The objective of this study was to confirm whether polymorphisms of TREX1 and TREX2 are associated with genetic susceptibility to systemic lupus erythematosus (SLE), and examine associations with autoantibodies (auto-Abs) in SLE. We investigated the genetic variants in 24 Korean individuals by direct sequencing. The genotype distributions of single-nucleotide polymorphisms (SNPs) and haplotypes were analyzed with multiple logistic regression models while controlling for covariates. We identified 12 and 5 SNPs of TREX1 and TREX2, of which -20260G>C, -389T>C, -381C>T, and +531C>T SNPs of TREX1; -23386G>C, -14703G>A, -7279C>T, and +1747C>T SNPs of TREX2; and each of three haplotypes were selected for larger scale genotyping (n = 1,053). No statistically significant association with the risk of SLE was observed in TREX1 and TREX2. TREX1 polymorphism -20260G>C showed protective effect on the production of anti-Ro Ab, and +531C>T in exon 16 and ht2 [G-T-C-T] showed also protective effect on the production of anti-dsDNA Ab, although the effect of +531C>T disappeared after multiple correction.


Assuntos
Autoanticorpos/imunologia , Exodesoxirribonucleases/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/enzimologia , Lúpus Eritematoso Sistêmico/imunologia , Fosfoproteínas/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Anticorpos Antinucleares , Criança , Mapeamento Cromossômico , Estudos de Coortes , Haplótipos , Humanos , Coreia (Geográfico) , Lúpus Eritematoso Sistêmico/genética , Pessoa de Meia-Idade , Análise de Regressão
12.
J Korean Med Sci ; 21(3): 585-7, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16778412

RESUMO

Bucillamine is a disease modifying anti-rheumatic drug, structurally similar to D-penicillamine. Although D-penicillamine-induced pemphigus has been not infrequently demonstrated, pemphigus associated with bucillamine was rarely reported. We describe a patient complicating pemphigus vulgaris after bucillamine treatment in rheumatoid arthritis (RA) and polymyositis (PM) overlap syndrome. PM and RA overlap syndrome was diagnosed three years ago and bucillamine was administrated for 20 months. Skin lesions including erythematous flaccid blisters on her chest, axillae, and back were occurred and were compatible with pemphigus vulgaris by typical pathology. Withdrawal from bucillamine and prednisolone treatment made rapid improvement of pemphigus lesions.


Assuntos
Antioxidantes/efeitos adversos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Cisteína/análogos & derivados , Pênfigo/induzido quimicamente , Pênfigo/patologia , Polimiosite/complicações , Polimiosite/tratamento farmacológico , Artrite , Biópsia , Cisteína/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Pele/patologia , Síndrome
13.
Korean J Intern Med ; 20(2): 180-2, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16134777

RESUMO

Eosinophilic fasciitis (EF) is scleroderma-like disease without Raynaud's phenomenon or visceral involvement. It is characterized by painful swelling of the extremities, accompanied by rapid weight gain, fever and myalgia. The acute state of disease is associated with significant peripheral blood eosinophilia, an elevated erythrocyte sedimentation rate and hypergammaglobulinemia. EF is also frequently associated with hematological abnormalities, including malignant lymphoproliferative diseases, but rarely associated with autoimmune thyroiditis. In the present study we report a case of eosinophilic fasciitis associated with autoimmune thyroiditis.


Assuntos
Eosinofilia/etiologia , Fasciite/etiologia , Tireoidite Autoimune/complicações , Biópsia , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Fasciite/diagnóstico , Feminino , Antebraço , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Tireoidite Autoimune/diagnóstico
14.
Rheumatol Int ; 26(1): 83-5, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15750823

RESUMO

Erythromelalgia is a kind of cutaneous manifestation, which appears as a thrombotic complication in patients with myeloproliferative disorders such as essential thrombocythemia and polycythemia vera. It is characterized by red, congested distal extremities and a painful burning sensation, and is usually confined to the feet and one or more toes or fingers. A 28-year-old woman visited our hospital due to severe pain in the left thumb, index fingers and right toes. Her right toes and left thumb were erythematous, congested, and warm. She had a high blood pressure level of 190/100 mmHg, and laboratory evaluation revealed marked thrombocytosis. Bone-marrow findings were compatible with essential thrombocythemia. Renal angiography showed obvious stenosis in unilateral right renal artery. Her erythromelalgia immediately disappeared following interventional therapy along with aspirin. A careful history and appropriate evaluation of underlying diseases are important, because erythromelalgia as a microscopic thrombotic complication may be accompanied by vascular stenosis and all the resulting manifestations.


Assuntos
Eritromelalgia/diagnóstico , Hipertensão Renovascular/diagnóstico , Obstrução da Artéria Renal/diagnóstico , Trombocitose/diagnóstico , Adulto , Angiografia/métodos , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Medula Óssea/patologia , Clopidogrel , Diagnóstico Diferencial , Quimioterapia Combinada , Eritromelalgia/tratamento farmacológico , Eritromelalgia/etiologia , Feminino , Humanos , Hipertensão Renovascular/complicações , Inibidores da Agregação Plaquetária/uso terapêutico , Artéria Renal/patologia , Obstrução da Artéria Renal/complicações , Trombocitose/complicações , Trombocitose/tratamento farmacológico , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Resultado do Tratamento
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