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A 53-year-old woman with recurrent stomatitis, genital ulcers, and folliculitis was admitted to our hospital after experiencing visual disturbances for the past two weeks, and a non-throbbing headache for the past three days. She had also developed numbness in her left extremities. An ophthalmological examination revealed inflammatory changes in the eye. Cerebrospinal fluid analysis showed increased cell counts, protein, and interleukin-6 levels. Brain magnetic resonance imaging revealed multiple high signal intensities on T2-weighted (T2W)/fluid-attenuated inversion recovery (FLAIR) images of the pons and occipital and parietal lobes. The T2W/FLAIR high-signal-intensity lesion in the pons was hyperintense on diffusion-weighted imaging (DWI) and hypointense on apparent diffusion coefficient mapping (ADC), suggesting cytotoxic edema. Another high-signal-intensity lesion on T2W/FLAIR was isointense to hyperintense on DWI and hyperintense on ADC, indicating vasogenic edema. The vasogenic edema in the left occipital lobe contained a small core that was hyperintense on DWI and hypointense on ADC, suggesting cytotoxic edema. The patient was diagnosed with acute neuro-Behçet's disease (neuro-BD) and responded well to high-dose glucocorticoid and colchicine treatment. The present report emphasizes that patients with acute neuro-BD may present with cytotoxic edema in the pons and cerebral spheres. Further reports of similar cases would contribute to a better understanding of the role of cytotoxic edema in the pathophysiology of neuro-BD and help elucidate the mechanisms underlying a unique presentation characterized by a central cytotoxic edema core within vasogenic edema. (233 words).
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OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease. Methotrexate (MTX) and prednisolone (PSL) are used in combination for severe RA therapy. However, it can increase the risk of osteoporosis and osteonecrosis. Saireito (114) can be used to reduce PSL dose owing to its immunosuppressive effects. However, the effect of combination therapy of PSL+114 on the immune system of RA patients remains unknown. This study compared the effect of PSL alone and PSL+114 on peripheral blood mononuclear cell (PBMC) proliferation, T-cell subsets, and cytokine production in adult RA patients receiving MTX monotherapy. METHODS: We isolated PBMCs from 14 consenting RA patients, and cultured them with PSL (0.0001-1.0 µM) in combination with or without 114 (300 µg/mL) for 96 h in the presence of concanavalin A. We measured the proliferation rates of PBMC, proportions of CD4+, CD8+, and CD4+CD25+Foxp3+T-cells (induced T-regulatory cells), and concentrations of interferon-γ, interleukin (IL)-6, IL-10, IL-17A, and tumour necrosis factor in the culture supernatant. RESULTS: Compared to the blank, the PBMC proliferation rate significantly decreased at a reduced PSL concentration after 114 administration. The 50% inhibition concentration was 0.43 µM PSL for the PSL-only group as compared to 0.29 µM PSL for the PSL+114 co-administration group. The PSL+114 co-administration group had a significantly higher concentration of IL-6 compared to the PSL-only group. CONCLUSIONS: The use of 114 in combination with low-concentration PSL intensified its immunosuppressive effect. However, the concentration of IL-6 was elevated in the co-administration group, suggesting exacerbation of RA activity.
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Antirreumáticos , Artrite Reumatoide , Adulto , Humanos , Prednisolona/efeitos adversos , Antirreumáticos/efeitos adversos , Leucócitos Mononucleares , Interleucina-6 , Metotrexato/efeitos adversosRESUMO
Renal involvement is underestimated as an extramuscular manifestation of dermatomyositis (DM). Here, we describe a 67-year-old woman with anti-glycyl-transfer ribonucleic acid synthetase (anti-EJ) antibody and anti-ribonucleoprotein antibody-positive DM complicated by systemic sclerosis, who developed nephrotic syndrome concurrently with the exacerbation of DM, as indicated by incremental serum creatine kinase levels, high-intensity lesions on muscle magnetic resonance imaging, and active interstitial pneumonitis on chest computed tomography. Renal biopsy revealed the presence of immune-deposition in the glomerulus by immunofluorescence. To our knowledge, this is the first report describing the coexistence of anti-EJ antibody-positive DM and nephrotic syndrome. More reports of similar cases are warranted to substantiate the association.
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BACKGROUND: Discordance between patient global assessment (PGA) and physician global assessment (PhGA) of rheumatoid arthritis (RA) disease activity is mainly determined by pain and functional disabilities. This study aimed to investigate the shift in PGA-PhGA discordance and the variables associated with future positive discordance (PGA > PhGA) based on the NinJa database in Japan. METHODS: We examined 7557 adults with RA registered in both NinJa 2014 and 2018, with a discordance cutoff of 3 on a 10-cm scale. The affected joint distribution was investigated using the joint indices x, y, and z, which were calculated as indices for the upper joint, lower joint, and large joint involvement, respectively. The variables in NinJa 2014 that were associated with positive discordance in NinJa 2018 were examined using binary stepwise logistic regression analysis. RESULTS: Due to the small number of patients with RA categorized as having negative discordance (PGA < PhGA), we focused on patients with RA categorized as having either concordance or positive discordance. Logistic regression analysis revealed that positive discordance in NinJa 2018 was associated with age, pain, modified Health Assessment Questionnaire (mHAQ) score, corticosteroid use, and existent positive discordance and was inversely associated with C-reactive protein (CRP) and x at baseline (NinJa 2014). The same findings were observed when patients with RA were divided based on the discordance status at baseline. Persistence (positive discordance to positive discordance) was associated with pain and mHAQ scores but inversely associated with CRP. CONCLUSIONS: Positive discordance may persist. Circumventing this requires adequate management of pain and functional impairment.
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Artrite Reumatoide , Médicos , Adulto , Humanos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Japão/epidemiologia , Dor , Índice de Gravidade de DoençaRESUMO
The immune response to citrullinated peptides in the mucosa has been suggested to play an important role in the transition from pre-onset rheumatoid arthritis (RA) to clinically evident RA. Although there are reports indicating the presence of anti-citrullinated peptide antibodies in the saliva, few studies have reported citrullinated peptide detection in human saliva. This study aimed to identify citrullinated peptides in human saliva and discuss their clinical significance. Saliva samples were collected from 11 patients with RA and from 20 healthy individuals. Citrullinated peptides were detected using an anti-modified citrulline (AMC) antibody. Saliva from the healthy individuals was subjected to two-dimensional protein electrophoresis to isolate citrullinated peptides, which were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and mass spectrometry by peptide mass fingerprinting. The results were corroborated by immunoprecipitation (IP)-western blotting. The signal intensities of the bands precipitated with anti-cytokeratin 13 (CK13) and AMC antibodies were quantified. The signal intensity ratio of the band produced by the AMC antibody was divided by that of the band produced by the anti-CK13 antibody to calculate the citrullinated CK13 (Cit-CK13) ratio. A citrullinated peptide band corresponding to a molecular weight of approximately 50 kDa was detected in the saliva of healthy individuals, and identified as CK13 via mass spectrometry and IP-western blotting. No significant difference was observed between the salivary Cit-CK13 ratios of patients with RA and healthy participants (p = 0.605). This is the first study to show that Cit-CK13 is present in human saliva, and that there is no significant difference between the Cit-CK13 ratios of patients with RA and healthy individuals, suggesting that salivary Cit-CK13 content and RA development may not be associated. The physiological and pathological roles of Cit-CK13 in the oral cavity, and its responsiveness to mucosal immunity, remain unknown and will be the subject of further investigation.
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Artrite Reumatoide , Proteômica , Autoanticorpos , Citrulina/metabolismo , Humanos , Queratina-13 , Peptídeos/metabolismo , Peptídeos CíclicosRESUMO
We investigated the relationship between distal interphalangeal (DIP) joint involvement and disease activity in 10,038 patients with adult-onset rheumatoid arthritis (RA). The affected joint distribution was investigated using the joint indices (JI) x, y, and z, corresponding to the upper and lower joints, and the predominance of large-joint involvement, respectively. DIP joint involvement (defined by the presence of tenderness and/or swelling in DIP joints) was present in 206 (2.1%) of 10,038 patients with RA. Patients with RA exhibiting DIP joint involvement were significantly younger, and more frequently women. DIP joint involvement was positively associated with Disease Activity Score-28 using C-reactive protein, and clinical variables related to high RA disease activity, including JIs x and y, and was negatively associated with JI z. JI x was significantly higher than JI y in RA patients with DIP joint involvement. An odds ratio analysis revealed that small-to-medium sized and upper-extremity joints ranked first, second, and fourth among the eight variables significantly associated with DIP joint involvement. The correlation coefficients revealed that small-sized and upper-extremity joints ranked first and second among the five significant variables. DIP joint involvement, albeit rare, is significantly associated with high RA disease activity with predominance of small-sized and upper-extremity joints.
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BACKGROUND: Methotrexate (MTX) is used as anchor drug for patients with early and established rheumatoid arthritis (RA). Vitamin K2 administration was also reported to be associated with decreased disease activity in RA. OBJECTIVES: Immunosuppressive pharmacodynamics of vitamin K2 combined with MTX was investigated. METHODS: Mitogen-activated peripheral blood mononuclear cells (PBMCs) were used to evaluate immunosuppressive pharmacodynamics of drugs in vitro. RESULTS: Vitamin K2 alone dose-dependently suppressed T cell mitogen-activated proliferation of PBMCs of both healthy subjects and RA patients. 446.5 and 2232.5 ng/mL vitamin K2 significantly decreased the IC50 values of MTX on the proliferation of PBMCs of RA patients, with little influences on the pharmacodynamics of MTX in the healthy PBMCs. 4465 ng/mL vitamin K2 potentiated the pharmacodynamics of MTX in both RA patients and healthy PBMCs. The additional effects of vitamin K2 to potentiate the suppressive effects of MTX seemed not to be related to the regulation of CD4+ CD25+ T cells or CD4+ CD25+ Foxp3+ Treg cells. MTX alone at 100 ng/mL significantly decreased the percentage of CD4+ T cells in PBMCs of healthy subjects (p < 0.001) with a slight influence in that of RA patients (not significant) and the combination did not show synergistic inhibitory effect. Vitamin K2 alone tended to suppress the secretion of IL-17, IFN-γ, and TNF-α from the activated PBMCs of RA patients with smaller influences on the cytokine productions from healthy PBMCs. These additional effects of vitamin K2 were also observed in combination with MTX. CONCLUSION: The above information may partially elucidate the potentiation effects of vitamin K2 on the immunosuppressive efficacy of MTX.
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Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Metotrexato/farmacologia , Vitamina K 2/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/metabolismo , Quimioterapia Combinada , Feminino , Voluntários Saudáveis , Humanos , Concentração Inibidora 50 , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Vitamina K 2/administração & dosagem , Vitamina K 2/uso terapêutico , Adulto JovemRESUMO
OBJECTIVE: To investigate the immunosuppressive effect of vitamin K2 against mitogen-activated peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients. MATERIALS AND METHODS: Concanavalin A-stimulated PBMC culture procedure was used to evaluate the pharmacodynamics of vitamin K2 in vitro. Methotrexate was set up as the positive control. The proliferation of PBMCs was detected by MTT assay. Relationship between IC50 values of drugs on PBMC proliferation and patient-related factors including laboratory data was analyzed by nonparametric Spearman correlation test. RESULTS: Vitamin K2 inhibited the proliferation of mitogen-activated PBMCs of RA patients with an IC50 value of 3,288.47 ± 4,910.02 ng/mL (mean ± SD). There was a significant correlation between IC50 values of vitamin K2 and patient-related factors of RA patients (p < 0.05), such as C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide antibody (ACPA), matrix metalloproteinase-3, Pre-DAS-28 (CRP), and ∆DAS-28 (CRP). It would be possible to predict the pharmacodynamics of vitamin K2 in RA patients according to the above factors. Methotrexate inhibited the proliferation of mitogen-activated PBMCs of RA patients with a IC50 value of 22.83 ± 12.47 ng/mL (mean ± SD). IC50 values of methotrexate only showed significant correlation with ACPA (p = 0.0158, r = 0.6905), which suggests that ACPA might be a suitable predictor of the pharmacodynamics of methotrexate. CONCLUSION: The above information suggests that vitamin K2 could provide a benefit for the treatment of RA patients via its immunosuppressive function.
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Artrite Reumatoide , Mitógenos , Artrite Reumatoide/tratamento farmacológico , Humanos , Imunossupressores/química , Imunossupressores/farmacologia , Leucócitos Mononucleares , Mitógenos/farmacologia , Vitamina K 2RESUMO
Sinomenine (SN) is a plant-derived alkaloid isolated from Caulis Sinomenii. It has been approved by the State Food and Drug Administration of China for treating rheumatoid arthritis (RA) nearly 20 years ago. To investigate the anti-RA mechanism of SN, a lot of scholars reported the immunosuppressive effect of SN on T lymphocytes. We continued to evaluate the suppressive function of SN by using human peripheral blood mononuclear cells (PBMCs) isolated from RA patients. As the positive control, 10 ng/ml of methylprednisolone (MP) showed the antiproliferation effect on mitogen-activated PBMCs of RA patients significantly (*p < .05). Meanwhile, MP decreased the frequency of CD4+ CD25+ T cells and suppressed the secretion of inflammatory Th1/Th2/Th17 cytokines such as IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α. However, SN at concentrations of 0.3-30 µM, showed little suppressive effects on the proliferation of PBMCs of RA patients. We did not observe any suppressive effects of SN on percentages of CD4+ T cells and CD4+ CD25+ T cells in the mitogen-activated PBMCs of RA patients. The influence of SN on the percentage of CD4+ CD25+ Foxp3+ T cells was also limited. Finally, even 30 µM of SN did not influence the secretion of Th1/Th2/Th17 cytokine significantly. The present study provided evidence that anti-RA mechanism of SN seems not to be related with the suppressive effects on peripheral T cells.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Citocinas/antagonistas & inibidores , Leucócitos Mononucleares/efeitos dos fármacos , Morfinanos/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Idoso , Antirreumáticos/farmacologia , Artrite Reumatoide/sangue , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Morfinanos/farmacologia , Linfócitos T Reguladores/metabolismo , Resultado do TratamentoRESUMO
Neuropsychiatric (NP) manifestations of systemic lupus erythematosus (SLE) are diverse, but involvement of basal ganglia is rare. We describe here a 28-year-old woman with NPSLE presenting aseptic meningitis accompanied by elevated interleukin-6 levels in the cerebrospinal fluid, who developed symmetrical basal ganglia lesions, containing a cytotoxic oedematous core, surrounded by vasogenic oedema upon magnetic resonance imaging. We were able to observe these lesions from a de novo appearance during the disease onset to its disappearance during immunosuppressive treatment. Reversibility upon immunosuppressive treatment indicated that autoimmune mediated mechanisms could contribute to the basal ganglia lesions in NPSLE.
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Gânglios da Base/patologia , Edema/diagnóstico , Edema/etiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Adulto , Gânglios da Base/efeitos dos fármacos , Edema/tratamento farmacológico , Feminino , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/etiologia , Avaliação de SintomasRESUMO
We describe a case of eosinophilic temporal arteritis in a 61-year-old woman with hypereosinophilic syndrome, who developed subcutaneous nodules in the temporal areas and digital cyanosis with small nodules on the sides of her fingers. Ultrasound revealed occlusion and corkscrew-like changes of the temporal and digital arteries, respectively. Temporal artery biopsy revealed eosinophilic vasculitis without giant cell formation. Angiography showed occlusion of the ulnar and digital arteries. Administration of low-dose corticosteroid improved the temporal artery swelling and digital cyanosis. More reports of similar cases are required to characterize this type of non-giant cell eosinophilic vasculitis that affects the peripheral arteries.
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Arterite de Células Gigantes/complicações , Síndrome Hipereosinofílica/complicações , Doenças Vasculares Periféricas/complicações , Biópsia , Feminino , Dedos/irrigação sanguínea , Arterite de Células Gigantes/patologia , Humanos , Síndrome Hipereosinofílica/patologia , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/patologia , Artérias Temporais/patologiaRESUMO
AIM: To assess the utility of serum levels of phosphatidylserine-specific phospholipase A1 (PS-PLA1 ), a lipase involved in the production of lysophosphatidylserine with multi-immunomodulatory effects, in systemic lupus erythematosus (SLE). METHOD: Serum PS-PLA1 was measured in 161 patients with SLE (including 54 untreated patients), 80 disease controls (35 active rheumatoid arthritis [RA], 23 Sjögren's syndrome [SS], and 22 systemic sclerosis [SSc]), and 237 healthy controls. RESULTS: Serum PS-PLA1 was significantly higher in SLE patients than in healthy controls, RA and SS patients. Although PS-PLA1 was significantly elevated in SSc and SS patients compared with healthy controls, PS-PLA1 was significantly higher in untreated SLE patients than in treated SLE patients and disease control patients. Receiver operating characteristic analysis revealed that a cut-off value of 18.2 ng/mL distinguished untreated SLE from disease control, with sensitivity and specificity of 71.4% and 57.5%, respectively. PS-PLA1 was significantly correlated with SLE Disease Activity Index (SLEDAI) and immunoglobulin G (IgG), and inversely correlated with white blood cell counts, lymphocyte counts, total complement hemolytic activity (CH50), complements C3, and C4 in SLE patients overall. Stepwise multiple regression identified SLEDAI, CH50, and IgG as significant parameters. In SLEDAI-based disease activity groups, PS-PLA1 was significantly higher in SLE patients with high disease activity than in those with low disease activity. PS-PLA1 decreased significantly in parallel with SLEDAI in 35 SLE patients whose paired serum samples were available pre- and post-treatment. CONCLUSION: Serum PS-PLA1 is associated with disease activity of SLE, indicating its possible use as a biomarker for monitoring SLE disease activity.
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Lúpus Eritematoso Sistêmico/sangue , Fosfolipases A1/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Fosfolipases A1/imunologia , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença , Regulação para CimaRESUMO
BACKGROUND: Previous studies suggest that RA activity is sensitive to seasonal changes. This study explored the influence of season on RA activity, particularly the distribution of affected joints, using a nationwide database in Japan. METHODS: We investigated 12,839 patients whose RA activity was recorded in spring (n = 3250), summer (n = 916), fall (n = 1021), and winter (n = 7652). Disease activity score (DAS) 28-CRP, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were used as indices of disease activity. Disease activity was also assessed according to DAS28-CRP scores (remission, low, moderate, or high). The affected joint distribution was investigated using novel joint indices (x, y, z), where x and y are indices for the upper and lower joints, respectively, and z is the index for large joint predominance. RESULTS: Mean DAS28-CRP and median SDAI and CDAI scores were highest in spring and lowest in fall. There was a significant difference in the DAS28-CRP for fall versus spring and winter. Fall was associated with a higher remission rate, and spring and winter with high and moderate RA activity, respectively. Significant differences in x, y, SDAI, and CDAI scores were found for spring versus summer, fall, and winter, in addition to fall versus winter (except in y). There was no seasonal difference in the z index. CONCLUSIONS: RA activity in the upper and lower extremities may be highest in spring, followed by winter. Seasonal changes should be considered in patients with RA to better understand their symptoms.
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Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Estações do Ano , Índice de Gravidade de Doença , Idoso , Bases de Dados Factuais/tendências , Progressão da Doença , Feminino , Humanos , Japão/epidemiologia , Articulações/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Gastric antral vascular ectasia (GAVE) is a rare cause of chronic gastric hemorrhaging and iron deficiency anemia and is characterized by a distinctive endoscopic appearance. The main treatment of GAVE is endoscopic; however, medication is necessary in refractory cases. We herein report a 69-year-old woman with systemic sclerosis (SSc) who developed recurrent severe anemia after endoscopic treatment of GAVE that was successfully managed using intravenous cyclophosphamide (IVCY). The recurrence of GAVE after discontinuation of IVCY was successfully managed using a combination of IVCY and endoscopic treatment, without blood transfusion. Long-term IVCY may be indicated for refractory GAVE associated with SSc.
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Ciclofosfamida/administração & dosagem , Ectasia Vascular Gástrica Antral/tratamento farmacológico , Imunossupressores/administração & dosagem , Escleroderma Sistêmico/complicações , Administração Intravenosa , Idoso , Feminino , Humanos , Recidiva , Resultado do TratamentoRESUMO
OBJECTIVES: The discordance between patient global assessment (PGA) and physician global assessment (PhGA) of rheumatoid arthritis (RA) disease activity may be problematic in clinical practice. The aim of this study was to identify determinants of this discordance using a nationwide RA database in Japan (NinJa) with special attention to large joint involvement. METHODS: We investigated 12 043 adults with RA and used a discordance cutoff of 3 cm. Large joint involvement was investigated using novel joint indices (x, y, z), where x and y were the indices for upper and lower joints, respectively, and z was for large joint predominance. Predictors of PGA-PhGA discordance and determinants of PGA and PhGA were analyzed by multivariate logistic and linear regression models, respectively. RESULTS: Multivariate logistic regression identified age, pain and high modified Health Assessment Questionnaire score as predictors of positive discordance (PGA ≥ PhGA), whereas parameters of disease activity in RA (C-reactive protein, x and y), class 3-4 functional status, and z were found to predict against positive discordance. Linear regression analysis revealed that PGA was mainly determined by pain, whereas PhGA was determined by various other factors. CONCLUSIONS: RA care providers should focus on pain and functional disability to decrease PGA-PhGA discordance. High disease activity and large joint involvement decreased PGA-PhGA discordance, indicating that the number and distribution of affected joints influenced the perception of disease activity by patients with RA and their physicians.
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Artrite Reumatoide/diagnóstico , Avaliação da Deficiência , Articulações/patologia , Medição da Dor , Pacientes/psicologia , Médicos/psicologia , Autorrelato , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/patologia , Artrite Reumatoide/psicologia , Biomarcadores/sangue , Proteína C-Reativa/análise , Distribuição de Qui-Quadrado , Bases de Dados Factuais , Feminino , Humanos , Japão , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Variações Dependentes do Observador , Razão de Chances , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: This study aimed to evaluate the long-term outcomes of neoadjuvant chemoradiotherapy with S-1 in patients with locally advanced rectal cancer. METHODS: A multi-institutional, prospective, phase II trial was conducted between April 2009 and August 2011. The study enrolled 37 patients with histologically proven rectal carcinoma (T3-4 N0-3 M0) who underwent neoadjuvant chemoradiotherapy with S-1. Total mesorectal excision with D3 lymphadenectomy was performed 4-8 weeks after completion of neoadjuvant chemoradiotherapy with S-1 in 36 patients. We then analyzed late adverse events, overall survival, and disease-free survival. RESULTS: The median patient age was 59 years (range: 32-79 years); there were 24 men and 13 women. Ten patients had Stage II disease, and 27 had Stage III disease. Severe late adverse events occurred in 7 patients (18.9%). The 5-year disease-free survival was 66.7%, and the 5-year overall survival was 74.7%. The median follow-up period was 57 months. Local recurrences developed in 5 patients (13.5%), and distant metastases developed in 8 (21.6%). CONCLUSION: Neoadjuvant-synchronous chemoradiotherapy with S-1 for locally advanced rectal cancer is feasible in terms of adverse events and long-term outcomes. (UMIN Clinical Trial Registry: UMIN000003396).
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Central nervous system (CNS) involvement in granulomatosis with polyangiitis (GPA), including pachymeningitis and CNS vasculitis, is uncommon. Although intracerebral hemorrhage (ICH) has been reported in GPA, simultaneous multiple ICH (SMICH) is rare. We describe the case of a 50-year-old woman with a history of a limited form of GPA with chronic pachymeningitis who presented with acute-onset headache accompanied by nausea and vomiting, and who developed consciousness impairment. Computed tomography revealed bilateral subcortical ICH. Sinus thrombosis was not apparent on angiography. The patient was treated with high-dose corticosteroid therapy. The cause of the steroid-responsive SMICH in this case was unknown, but it might have been CNS vasculitis. Patients with GPA may present with SMICH, which is considered an indication for immunosuppressive therapy.
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Hemorragia Cerebral/complicações , Granulomatose com Poliangiite/complicações , Meningite/complicações , Feminino , Humanos , Hipertrofia/complicações , Meningite/tratamento farmacológico , Pessoa de Meia-IdadeRESUMO
AIM: To determine whether the age at onset of rheumatoid arthritis (RA) has increased in Japan using a nationwide database (National Database of Rheumatic Diseases by iR-net in Japan, NinJa). METHOD: We analyzed the data of RA patients who had been diagnosed with early RA (disease duration < 2 years) and newly registered in 2003, 2008 or 2013. RESULTS: The numbers of patients who developed RA in 2002-2003, 2007-2008, and 2012-2013 were 536, 812 and 1864, respectively. The mean age at RA onset increased significantly from 55.8 years in 2002-2003 and 57.0 years in 2007-2008 to 59.9 years in 2012-2013. The peak age shifted from the 50-59 years age group in 2002-2003 to the 60-69 years age group in 2012-2013. There was no apparent difference in the age at RA onset between male and female RA patients. Notably, in the period 2002-2003, the prevalence of RA was markedly higher in the age group of 50-59 years, which included the first 'baby boomers', than in the age groups of 30-39 and 40-49 years, even with consideration of the variations in the age composition of the general population. CONCLUSIONS: We have demonstrated that the age at RA onset in Japan has increased significantly over the last decade. This can be attributed to Japan's aging population. In addition, the high prevalence of RA among the first baby boomers suggests that environmental factors might also have contributed to the increase in age at RA onset in Japan.
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Artrite Reumatoide/epidemiologia , Adulto , Distribuição por Idade , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/diagnóstico , Bases de Dados Factuais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
Treatment results of locally advanced rectal cancer without preoperative chemoradiotherapy (CRT) in Japan do not differ from those of Western countries. Preoperative CRT with new anticancer agents may decrease local recurrence rate and prevent distant metastases, thus improving survival. We conducted a trial to evaluate feasibility of neoadjuvant CRT using S-1 in patients with locally advanced rectal cancer. A multi-institutional (17 specialized centres), interventional, phase II trial was conducted from April 2009 to August 2011. Patients fulfilling the following requirements before neoadjuvant CRT were included: histologically proven rectal carcinoma; tumour in the upper or lower rectum; cancer classified as T3-4 N0-3 M0. Neoadjuvant CRT with S-1 (80 mg/m2/day on days 1-5, 8-12, 22-26, and 29-33) and irradiation (total 45 Gy/25 fr, 1.8 Gy/day, on days 1-5, 8-12, 15-19, 22-26, and 29-33) was performed. Total mesorectal excision with D3 lymphadenectomy was performed during weeks 4 and 8 after completion of neoadjuvant CRT. The primary endpoint was completion rate of neoadjuvant CRT. Secondary endpoints were response rate to neoadjuvant CRT, short-term clinical outcomes, curative resection rate, and pathologic response (grade 2/3). Of the 37 patients included, 86.5% completed neoadjuvant CRT (95% CI, 75.5-97.5%), and 10.8% (4) experienced an adverse event (grade 3/4). Response rate (RECIST 1.0) was 56.8% (95% CI, 40.8-72.7%), and pathologic response rate was 48.6% (95% CI, 32.5-64.8%). This study demonstrated that neoadjuvant-synchronous S-1+radiotherapy for locally advanced rectal cancer was feasible in terms of pathologic response and adverse events. Registration number: UMIN-CTR, No. C003396.
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Lemmel's syndrome encompasses a range of conditions in which a juxtapapillary duodenal diverticulum exerts mechanical and functional effects on the common bile and pancreatic ducts, leading to jaundice and pancreatitis. In this report, we describe a very rare case of carcinoma of the ampulla of Vater that was detected during postoperative follow-up in a patient who had undergone choledochojejunostomy following a diagnosis of Lemmel's syndrome. We present our clinical and pathological experiences with the diagnosis and treatment of this case as well as a review of the present literature concerning Lemmel's syndrome.