Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
3.
J Infect Chemother ; 29(2): 193-197, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36334836

RESUMO

INTRODUCTION: Pneumocystis pneumonia (PCP) is an opportunistic lung infection and has been reported among patients with rheumatoid arthritis (RA). An animal study revealed that sulfasalazine enhances Pneumocystis clearance from the lung by accelerating macrophage activity. METHODS: The self-controlled case series (SCCS) method was used to investigate the association between sulfasalazine use and PCP development in patients with RA without the effect of time-invariant, interpatient confounders. PCP episodes which developed in patients with RA at five hospitals between 2003 and 2019 were identified. PCP was defined by the following criteria: 1) detection of Pneumocystis jirovecii in respiratory specimens by polymerase chain reaction; 2) clinical symptoms (pyrexia, dry cough, dyspnea or hypoxia); 3) diffuse interstitial infiltrate on chest imaging; and 4) absence of PCP prophylaxis. The PCP incidence rate ratio (IRR) was compared between periods with and without sulfasalazine use by conditional Poisson regression. RESULTS: Fifty episodes of PCP were identified in 49 patients. Thirty patients received sulfasalazine at some point during their observation. While 49 episodes of PCP developed in 170.3 person-years without sulfasalazine use, only one episode of PCP developed in 103.7 person-years with sulfasalazine use. Sulfasalazine use was associated with a decreased PCP risk (adjusted IRR <0.01; 95% confidence interval <0.01-0.03) after adjusting for age and glucocorticoid, methotrexate, and tumor necrosis factor inhibitor administration. CONCLUSION: Our study demonstrated a preventive effect of sulfasalazine against PCP in patients with RA.


Assuntos
Artrite Reumatoide , Infecções Oportunistas , Pneumonia por Pneumocystis , Sulfassalazina , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Metotrexato , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/prevenção & controle , Pneumocystis carinii , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/prevenção & controle , Estudos Retrospectivos , Sulfassalazina/uso terapêutico , Humanos
4.
Medicine (Baltimore) ; 101(48): e32200, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36482523

RESUMO

RATIONALE: Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome are nonmalignant but life-threatening systemic inflammatory disorders. However, many patients are refractory to treatment, resulting in significant morbidity and mortality. Additionally, established treatment options are unavailable. Therefore, we present 2 cases of adults with the iMCD-TAFRO syndrome refractory to initial treatment but responded to Janus kinase (JAK) inhibitors with ruxolitinib. The report reveals that these rare adult cases of the refractory and treatment-resistant iMCD-TAFRO syndrome can be treated using JAK inhibitors. PATIENT CONCERNS: Case 1 is a 36-year-old previously healthy male patient who presented with fever and general fatigue for 2 weeks. Case 2 is a 42-year-old previously healthy female patient who presented with fever and general fatigue. DIAGNOSIS: The diagnosis met the 2015 criteria for TAFRO syndrome, as determined by All Japan TAFRO Syndrome Research Group in the Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare (MHLW) Japan. INTERVENTIONS: Treatment with tocilizumab and several immunosuppressants were ineffective. So, we performed ruxolitinib. OUTCOMES: Each patient received ruxolitinib, the general condition improved, and CRP levels decreased. LESSONS: These cases showed that ruxolitinib was effective for treatment-resistant/ refractory TAFRO syndrome. Further prospective studies are needed on using ruxolitinib with a small number of cases.


Assuntos
Hiperplasia do Linfonodo Gigante , Inibidores de Janus Quinases , Nefropatias , Humanos , Feminino , Masculino , Adulto , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Fibrose
8.
Arthritis Rheumatol ; 73(4): 677-686, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33118321

RESUMO

OBJECTIVE: To establish predictive models for mortality in patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) using a combination of initial serum biomarker levels. METHODS: The Multicenter Retrospective Cohort of Japanese Patients with Myositis-Associated ILD (JAMI) database of 497 incident cases of PM/DM-ILD was used as a derivation cohort, and 111 cases were additionally collected as a validation cohort. Risk factors predictive of all-cause mortality were identified by univariate and multivariable Cox regression analyses using candidate serum biomarkers as explanatory variables. The predictive models for mortality were generated in patients with and those without anti-melanoma differentiation-associated gene 5 (MDA-5) antibody, using a combination of risk factors. Cumulative survival rates were assessed using Kaplan-Meier analysis, and were compared between subgroups using the Breslow test. RESULTS: In the derivation cohort, C-reactive protein (CRP) and Krebs von den Lungen 6 (KL-6) levels were identified as independent risk factors for mortality in both anti-MDA-5-positive and anti-MDA-5-negative patients. We then developed a prediction model based on anti-MDA-5 antibody status, CRP level, and KL-6 level, termed the "MCK model," to identify patients at low (<15%), moderate (15-50%), or high (≥50%) risk of mortality, based on the number of risk factors. The MCK model successfully differentiated cumulative survival rates in anti-MDA-5-positive patients (P < 0.01 for low versus moderate risk and P = 0.03 for moderate versus high risk) and in anti-MDA-5-negative patients (P < 0.001 for low versus moderate risk). The utility of the MCK model was replicated in the validation cohort. CONCLUSION: Our findings indicate that an evidence-based risk prediction model using CRP and KL-6 levels combined with anti-MDA-5 antibody status might be useful for predicting prognosis in patients with PM/DM-ILD.


Assuntos
Dermatomiosite/sangue , Doenças Pulmonares Intersticiais/sangue , Modelos Teóricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Dermatomiosite/complicações , Dermatomiosite/mortalidade , Feminino , Humanos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Mucina-1/sangue , Prognóstico , Estudos Retrospectivos , Medição de Risco
11.
Mod Rheumatol ; 30(3): 458-464, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31116052

RESUMO

Objectives: Interstitial lung disease (ILD) is a life-threatening extra-articular manifestation of rheumatoid arthritis (RA). We aimed to clarify the relationship between chronic ILD with a pattern of usual interstitial pneumonia (UIP) or non-UIP and mortality in RA patients.Methods: We retrospectively surveyed information of consecutive RA patients who visited our hospital from 2009 to 2014. The relationship between their mortality and chronic ILD (UIP or non-UIP) detected by high-resolution computed tomography was examined.Results: Of 2702 patients enrolled, 261 (9.7%) had chronic ILD and among these 120 had a UIP pattern. At the onset of RA, the prevalence of chronic ILD was 6%. Patients with chronic ILD had a higher mortality than those without. The most frequent cause of death was pneumonia including acute exacerbation (AE) of chronic ILD. Lung cancer death was frequently identified in deceased patients with chronic ILD with a UIP pattern compared with the other decedents (p=.062). The estimated mortality of lung cancer in patients with chronic ILD with a UIP pattern was five times higher than the general population.Conclusion: RA patients with ILD with a UIP pattern have a high mortality rate and are prone to die of AE or lung cancer.


Assuntos
Artrite Reumatoide/complicações , Doenças Pulmonares Intersticiais/patologia , Idoso , Causas de Morte , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
12.
Rheumatology (Oxford) ; 59(1): 112-119, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31382295

RESUMO

OBJECTIVE: To clarify the incidence, risk factors, and impact of malignancy in patients with PM/DM-associated interstitial lung disease (ILD). METHODS: This study used data from 497 patients with PM/DM-associated ILD enrolled in a multicentre, retrospective and prospective cohort of incident cases. Cancer-associated myositis (CAM) was defined as malignancy diagnosed within 3 years before or after PM/DM diagnosis. Demographic and clinical information was recorded at the time of diagnosis, and data about the occurrence of mortality and malignancy was collected. RESULTS: CAM was identified in 32 patients with PM/DM-associated ILD (6.4%). Patients with CAM were older (64 vs 55 years, P < 0.001), presented with arthritis less frequently (24% vs 49%, P = 0.01), and showed a lower level of serum Krebs von den Lungen-6 (687 vs 820 IU/l, P = 0.03) than those without CAM. The distribution of myositis-specific autoantibodies, including anti-melanoma differentiation-associated gene 5, anti-aminoacyl tRNA synthetase, and anti-transcriptional intermediary factor 1-γ antibodies, did not differ between the groups. Survival analysis demonstrated that CAM patients had a poorer survival than non-CAM patients (P = 0.006), primarily due to excess deaths by concomitant malignancy, while mortality due to ILD-related respiratory failure was similar between the groups (P = 0.51). CONCLUSION: Concomitant malignancy can occur in patients with PM/DM-associated ILD, and has significant impact on mortality. Older age, lack of arthritis, and a lower level of serum Krebs von den Lungen-6 at diagnosis are predictors of concomitant malignancy.


Assuntos
Doenças Pulmonares Intersticiais/mortalidade , Miosite/mortalidade , Neoplasias/mortalidade , Fatores Etários , Aminoacil-tRNA Sintetases/imunologia , Autoanticorpos/sangue , Feminino , Humanos , Incidência , Japão/epidemiologia , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Mucina-1/sangue , Miosite/sangue , Miosite/etiologia , Neoplasias/sangue , Neoplasias/complicações , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco
13.
Phys Rev E ; 100(2-1): 022102, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31574625

RESUMO

Three-dimensional observation of Brownian particles under shear flow is performed with a stereo microscope to examine the nature of the Brownian motion that occurs in the presence of shear flow. From the three-dimensional trajectories of the particles, we clearly demonstrate the occurrence of anomalous diffusion in the flow direction and the coupling of the displacements in the flow and velocity gradient directions. Furthermore, we experimentally obtain the probability distribution function and current density, which also exhibit characteristic features, and compare the obtained results with theoretical results derived using the Fokker-Planck equation.

14.
Mod Rheumatol ; 29(3): 436-440, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29652202

RESUMO

OBJECTIVE: To evaluate the effect of sulfasalazine (SSZ) on the presence of Pneumocystis jirovecii (P. jirovecii) in the lungs of rheumatoid arthritis (RA) patients. METHODS: We retrospectively studied episodes of suspected P. jirovecii pneumonia (PJP) which were examined for P. jirovecii with polymerase chain reaction (PCR). We employed a test negative design case-control study; the cases were episodes of suspected PJP that were positive for PCR, and the controls were episodes of suspected PJP that were negative for PCR. The odds ratio for the positive PCR result associated with SSZ use was estimated by Firth's logistic regression. RESULTS: Between 2003 and 2017, 36 cases and 83 controls were identified. While none of the cases received SSZ before the episode, 18 of the controls received the drug. In the primary analysis involving all the episodes, SSZ use was negatively associated with PCR positivity (adjusted odds ratio, 0.087; confidence interval, <0.001-0.789). The sensitivity analysis, excluding those who received PJP prophylaxis, showed the same association as the primary analysis (adjusted odds ratio 0.085, 95% CI <0.001-0.790). CONCLUSION: This study demonstrated that SSZ use is associated with the absence of P. jirovecii in the lung, suggesting the preventive efficacy of the drug against PJP.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Pneumonia por Pneumocystis/epidemiologia , Sulfassalazina/uso terapêutico , Adulto , Idoso , Antirreumáticos/farmacologia , Feminino , Humanos , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/efeitos dos fármacos , Pneumocystis carinii/patogenicidade , Sulfassalazina/farmacologia
15.
Semin Arthritis Rheum ; 48(4): 573-578, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30057321

RESUMO

OBJECTIVES: To evaluate the prophylactic effect of sulfasalazine against Pneumocystis jirovecii pneumonia (PJP) among rheumatoid arthritis (RA) patients. METHODS: We used a nationwide Japanese multicenter RA database to extract data from 2005 and 2014. To identify PJP cases, we selected patients hospitalized for PJP and verified their diagnosis. Two control groups, one unmatched and the other matched for age, sex, glucocorticoid, methotrexate, and tacrolimus dosage, and the use (and type, if used) of biological disease-modifying antirheumatic drug were selected by incidence-density sampling. The odds ratios for PJP associated with sulfasalazine use and other clinical factors were estimated by exact and standard conditional logistic regression. RESULTS: From 18,668 participants, 60 cases, 356 unmatched controls, and 337 matched controls were selected. None of the cases received sulfasalazine before PJP onset. A comparison of the cases with the unmatched controls showed that sulfasalazine use carried a decreased risk of PJP (adjusted odds ratio 0.18, 95% confidence interval 0.00-0.92). A comparison of the cases and matched controls also showed that sulfasalazine use had a decreased risk of PJP (0.08, 0.00-0.36). In an analysis of the cases and unmatched controls who did not receive sulfasalazine, an increased risk of PJP was associated with lung disease (3.88, 1.89-7.95) and the use of glucocorticoid (5.71, 2.68-12.19), methotrexate (5.25, 2.01-13.74), and tumor necrosis factor inhibitors (2.32, 1.10-4.93). CONCLUSIONS: The results of this nested case-control study demonstrated the preventive effect of sulfasalazine against PJP. The results await confirmation by future prospective studies.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Pneumonia por Pneumocystis/prevenção & controle , Sulfassalazina/uso terapêutico , Idoso , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Humanos , Incidência , Japão , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/epidemiologia , Risco
16.
Clin Rheumatol ; 37(8): 2269-2274, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29876690

RESUMO

To compare Pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA) with PCP in patients with non-RA connective tissue diseases (CTDs) in order to clarify the characteristics of the former. We extracted consecutive patients satisfying the following criteria for "clinical PCP": (1) positive plasma ß-D-glucan, (2) PCP-compatible computed tomography findings of the lung, and (3) successful treatment with antipneumocystic antibiotics. Patients who underwent methylprednisolone "pulse" therapy or sufficient antibiotics to cure bacterial pneumonia were excluded. We used the t test, U test, or Fischer's exact probability test to compare the two groups and Jonckheere-Terpstra's test and Ryan's procedure for the trend test. Thirty-five cases were extracted. The underlying rheumatic diseases were RA in 25 and non-RA CTDs in ten. At the onset of clinical PCP, the lymphocyte counts were 884 vs 357/mm3 (p < 0.001), PC-PCR positivity 64% vs 100% (p = 0.029), glucocorticoid dose 4.0 vs 17.5 mg PSL/day (p < 0.001), and methotrexate dose 8 vs 0 mg/week (p = 0.003). The PC-PCR-negative patients, observed only in the RA group, were all receiving methotrexate (MTX) therapy except one patient who was receiving high-dose prednisolone alone. All PC-PCR-positive patients were receiving glucocorticoid, TNF inhibitor, or a non-MTX immunosuppressant. No patient with MTX alone had positive PC-PCR results. Clinical PCP in RA patients differed from that in non-RA CTD patients and may be understood as only a part of the rheumatoid-specific interstitial lung injury spectrum influenced by multiple, synergistic factors including MTX, Pneumocystis, and RA itself.


Assuntos
Artrite Reumatoide/complicações , Doenças do Tecido Conjuntivo/complicações , Imunossupressores/administração & dosagem , Doenças Pulmonares Intersticiais/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Idoso , Antibacterianos/uso terapêutico , Artrite Reumatoide/microbiologia , Doenças do Tecido Conjuntivo/microbiologia , Feminino , Glucocorticoides/administração & dosagem , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento , beta-Glucanas/sangue
17.
Rheumatology (Oxford) ; 57(7): 1212-1221, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29596687

RESUMO

OBJECTIVE: To identify initial predictors of poor survival in patients with PM/DM-associated interstitial lung disease (ILD). METHODS: We established a multicentre retrospective cohort of incident cases of PM/DM-associated ILD from 44 institutions across Japan (Multicentre Retrospective Cohort of Japanese Patients with Myositis-associated ILD, JAMI). Inclusion criteria were an onset age ⩾16 years; PM/DM or clinically amyopathic DM according to the published criteria; imaging evidence of ILD; and availability of serum samples for assays of autoantibodies such as anti-melanoma differentiation-associated gene 5 and anti-aminoacyl tRNA synthetase. We collected demographic data and clinical characteristics recorded at the time of diagnosis, as well as follow-up survival data. Predictors of ILD-related mortality were identified by univariate and multivariate analyses. RESULTS: JAMI enrolled a cohort of 497 patients with PM (15%), classic DM (32%) and clinically amyopathic DM (53%). During the observation period (median 20 months), 76 died of respiratory insufficiency directly related to ILD. Univariate analysis revealed several initial parameters associated with ILD mortality, including demographic, clinical, laboratory, imaging and autoantibody variables. We used multivariate analysis with a stepwise selection of parameters to generate an appropriate predictive model, and identified the following independent risk factors for ILD mortality: age at onset ⩾60 years [hazard ratio (HR) = 4.3, 95% CI: 2.4, 7.5], CRP ⩾1 mg/dl (HR = 2.6, 95% CI: 1.5, 4.8), peripheral capillary oxygen saturation <95% (HR = 2.0, 95% CI: 1.2, 3.4) and anti-melanoma differentiation-associated gene 5 antibody (HR = 7.5, 95% CI: 2.8, 20.2). CONCLUSION: We established a large cohort of incident cases of PM/DM-associated ILD, and successfully identified independent predictors of short-term ILD mortality.

18.
Mod Rheumatol ; 26(2): 259-64, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26156043

RESUMO

OBJECTIVE: We sought to identify clinical features at diagnosis that can distinguish isolated polymyalgia rheumatica (PMR) without giant cell arteritis (GCA) from PMR with GCA, and clinical features at diagnosis of isolated PMR that can predict subsequent relapse and corticosteroid discontinuation. METHODS: A retrospective study of 115 patients with isolated PMR and 29 patients with GCA was performed. A comparison between isolated PMR patients, GCA patients (with or without PMR), and PMR with GCA patients was performed. Predictors of relapse and corticosteroid discontinuation were identified using a logistic regression in the patients with isolated PMR. RESULTS: Matrix metalloproteinase-3 (MMP-3) level was significantly different among the patient groups. MMP-3: 230.5 ± 201.5 ng/mL in isolated PMR, 80.5 ± 47.5 ng/mL in GCA (p < 0.01), and 96.8 ± 54.8 ng/mL in PMR with GCA (p = 0.03). In the patients with isolated PMR, female gender (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.16-6.41; p < 0.05) and creatinine (Cr) < 50 µmol/L (OR, 2.48; 95% CI, 1.02-5.99; p < 0.05) were significant prognostic factors that predicted relapse. CONCLUSION: A low level of MMP-3 is an excellent positive predictor for PMR with GCA. Among patients with isolated PMR, female gender and Cr < 50 µmol/L were significant prognostic factors that predicted relapse.


Assuntos
Arterite de Células Gigantes/diagnóstico , Metaloproteinase 3 da Matriz/sangue , Polimialgia Reumática/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Diagnóstico Diferencial , Feminino , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/complicações , Humanos , Japão , Masculino , Polimialgia Reumática/sangue , Polimialgia Reumática/complicações , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores Sexuais
19.
Mod Rheumatol ; 25(2): 264-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25156777

RESUMO

OBJECTIVES: To validate Routine Assessment of Patient Index Data 3 (RAPID3) using a Japanese version of Multidimensional Health Assessment Questionnaire (MDHAQ) with Japanese rheumatoid arthritis (RA) patients and to describe the characteristics of RAPID3 by comparison with Disease Activity Score 28 (DAS28) and Clinical Disease Activity Index (CDAI). METHODS: The original MDHAQ was translated into Japanese with minor cultural modifications and was translated back in English. Test-retest reliability was evaluated in 50 Japanese RA patients and further validation was performed in 350 Japanese RA patients recruited by seven rheumatologists. RAPID3, CDAI, and DAS28 were assessed on two consecutive visits. RESULTS: The test-retest reliability and the internal reliability of RAPID3 were excellent. Spearman's correlation coefficients between RAPID3 score versus CDAI score and DAS28 score were 0.761and 0.555. However, the agreement measured by kappa (weighted) for RAPID3 category versus CDAI category and for RAPID3 category versus DA28 category were 0.225 (0.382) and 0.187 (0.336). The sensitivity and specificity of "RAPID3 ≤ 3 and swollen joint ≤ 1" for predicting Boolean remission were 90.0% and 93.4%, respectively. CONCLUSIONS: RAPID3 obtained by Japanese MDHAQ was validated with Japanese RA patients and the remission criteria were found to have excellent clinical utility in usual care.


Assuntos
Artrite Reumatoide/diagnóstico , Avaliação da Deficiência , Inquéritos e Questionários , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença
20.
Mod Rheumatol ; 25(6): 958-61, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24252025

RESUMO

Medical management of systemic sclerosis (SSc)-associated chronic intestinal pseudo- obstruction (CIPO) has often proved inadequate. Percutaneous endoscopic colostomy (PEC) has been proposed as a method of treatment, but it is associated with a relatively high incidence of serious complications. We report herein a very severe case of SSc-associated CIPO in which complications were successfully controlled by long tube placement via a gastrostomy. Transgastric long tube placement may offer a relatively safe alternative to PEC in treating severe SSc-associated CIPO.


Assuntos
Gastrostomia , Pseudo-Obstrução Intestinal/cirurgia , Escleroderma Sistêmico/cirurgia , Feminino , Humanos , Pseudo-Obstrução Intestinal/complicações , Pessoa de Meia-Idade , Escleroderma Sistêmico/complicações , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...