Dogo Onsen Hospital

The clinical advantage of targeting index-based remission prior to Boolean remission was evaluated retrospectively. A total of 578 patients with rheumatoid arthritis (RA), who were treated for more than three years, were recruited. Patients who were treated to targeted index-based remission and composite measure remission criteria such as Boolean remission from the first consultation were divided according to the turn of attaining Boolean remission and index-based remission: G-IBR, a group that matched index-based remission at the same time Boolean remission is attained or earlier; G-BR_IF, a group that attained Boolean remission followed by index-based remission or failed; G-IR_BF, a group that could not attain Boolean remission despite attaining index-based remission; G-BothF, a group that failed to attain either Boolean remission or index-based remission. Background factors were statistically compared among groups. The Boolean remission rate in patients who attained index-based remission (BRR) and the rate of failure to attain index-based remission in patients who failed to attain Boolean remission (BFR) were statistically evaluated. Groups comprising 225, 231, and 482 in G-IBR; 160, 154, and 8 in G-BR_IF; 18, 18, and 75 in G-IR_BF; and 175, 175, and 13 in G-BothF when indexing the clinical disease activity index (CDAI), simplified disease activity index (SDAI), and 28-joints disease activity score with C-reactive protein (DAS28-CRP), respectively. Disease activity indices’ scores after Boolean remission were demonstrated to be significantly higher in the G-BR_IF group than in the G-IBR group. BRR was 92.6%, 92.8%, and 86.5%, while BFR was 71.3%, 71.3%, and 13.8% when indexing CDAI, SDAI, and DAS28-CRP, respectively. Targeting CDAI and SDAI remission prior to Boolean remission contributes to a stable clinical course. Se evaluó prospectivamente la ventaja clínica de centrarse en la remisión basada en índices de manera previa a la remisión booleana. Se seleccionó a un total de 578 pacientes con artritis reumatoide que habían sido tratados durante más de 3 años. Se dividió en grupos a los pacientes según los criterios de remisión: remisión basada en índices o remisión de medidas compuestas, tales como remisión booleana desde la primera consulta, de acuerdo con el plazo de logro: G-IBR, un grupo que equiparó la remisión basada en índices al mismo tiempo que logró la remisión booleana o antes; G-BR_IF, un grupo que logró la remisión booleana seguida de remisión basada en índices o que fracasó; G-IR_BF, un grupo que no logró la remisión booleana a pesar de lograr la remisión basada en índices; G-BothF, un grupo que no logró la remisión booleana ni la remisión basada en índices. Se compararon entre los grupos los factores antecedentes. Se evaluaron estadísticamente la tasa de remisión booleana en los pacientes que lograron la remisión basada en índices (BRR) y la tasa de fracaso en el logro de la remisión booleana (BFR). Los grupos estuvieron formados por 225, 231 y 482 en G-IBR; 160, 154 y 8 en G-BR_IF; 18, 18 y 75 en G-IR_BF y 175, 175 y 13 en G-BothF al indexar el índice de actividad de la enfermedad clínica (CDAI), el índice simplificado de actividad de la enfermedad (SDAI) y el índice DAS-28 con proteína C reactiva (DAS28-CRP), respectivamente. Las puntuaciones de los índices de actividad de la enfermedad tras la remisión booleana fueron significativamente más altas en el grupo G-BR_IF que en el grupo G-IBR. BRR fue del 92,6; 92,8 y 86,5%, mientras que BFR fue del 71,3; 71,3 y 13,8% al indexar CDAI, SDAI y DAS28-CRP, respectivamente. Centrarse en las remisiones CDAI y SDAI de forma previa a la remisión booleana contribuye a un curso clínico estable.

Aim of this study is to clarify associations between metrics of patient's clinical status statistically using retrospective cohort data. Patients with RA who were followed up more than 3years were recruited. Their EuroQol-5th dimension (EQ5D) as an index of quality of life (QOL), Health Assessment Questionnaire Disability Index (HAQ) as an index of functional capacity (FC), simplified disease activity index (SDAI), pain score using visual analog scale (PS-VAS), and fatigue score using visual analog scale (FS-VAS) were monitored every three months. Sharp/van der Heijde score (SHS) was calculated annually. Associations between average values of these factors at beginning of follow-up (baseline) and change from baseline to final year in follow-up (change), and patient's sex, age, and disease duration (DD) were evaluated statistically. A total of 447 patients were analyzed. EQ5D score correlated significantly with HAQ score both at baseline and change of that, and FS-VAS. HAQ score correlated significantly with EQ5D and HAQ score at baseline. SDAI score correlated significantly with SHS and FS-VAS at baseline. SHS correlated significantly with the SHS at baseline. PS-VAS correlated significantly with the PS-VAS, EQ5D at baseline, change of theEQ5D and HAQ scores. FS-VAS correlated significantly with change of the EQ5D score and FS-VAS at baseline. These results suggested that these clinical metrics are influenced by each variable at baseline. QOL and fatigue are correlated each other, as well as QOL and FC, whereas disease activity correlated with joint deformity level and fatigue. Key Points • It is questionable whether improvement of disease activity leads to improvements in functional capacity and QOL in treating rheumatoid arthritis. • We evaluated the association among metrics of clinical outcomes, such as EQ5D, HAQ, SDAI, SHS, pain score, and fatigue score using retrospective cohort data. • Results suggested that metrics are influenced by each items at baseline, and QOL and fatigue are correlated each other, as well as QOL and functional capacity.

Validity and risk of setting patient’s global assessment (PGA) ≤ 2 as a Boolean remission criteria substituting PGA ≤ 1 in treating rheumatoid arthritis (RA) was investigated. Patients were recruited from an area cohort, of whom attained Boolean remission (Boolean-1) or near remission with PGA ≤ 2 and the rest components were ≤ 1 (Boolean-2). Simplified disease activity index (SDAI) score was compared according to the criteria variations. A total of 517 patients were studied. Mean SDAI score of patients with Boolean-1 was significantly lower than that of patients with Boolean-2 at acquisition. The trend was evident in the patients who attained Boolean-1 remission. Mean SDAI score at acquisition, 6 months after, and 1 year after of patients who attained Boolean-2 first and then Boolean-1, was significantly inferior to that of patients who attained the remissions at the same time. The mean SDAI score at month 6 in the Boolean-2 was not SDAI remission at all. We concluded that setting PGA ≤ 2 as a remission criteria may not have statistical difference in disease activity from PGA ≤ 1, however, there was an determinant risk to misread that includes patient who losses clinical remission after acquisition.

Профессиональная этика - один из компонентов образовательной системы и части философии, который помогает нам выбрать правильный стиль поведения. Сильнее, чем традиция и привязанность, и основанная на логической этике, профессиональная этика разъясняет, что разрешено делать и что мы не должны делать, а также помогает относиться к ситуациям критически и беспристрастно, и регулярно совершенствовать систему ценностей. Именно поэтому, среди врачей общей практики этические проблемы занимают важное место. В развитых странах на эти проблемы обращено особое внимание, но есть также много проблем, которые еще требуют решения.

Anti-citrullinated protein antibodies (ACPAs) are highly specific to rheumatoid arthritis (RA), and strong associations between HLA-DRB1 alleles and ACPA levels have been detected in RA patients. We undertook this study to elucidate the associations between particular amino acid positions in HLA-DRB1 and ACPA levels in patients with RA. We analyzed ACPA data on a total of 4,371 Japanese ACPA-positive RA patients in whom HLA-DRB1 allele genotyping had been performed. Generalized linear regression analysis and omnibus testing were carried out to determine associations of HLA-DRB1 alleles, amino acid residues, or amino acid positions with levels of ACPA. HLA-DRB1*09:01 and HLA-DR15 were confirmed to be associated with ACPA levels. HLA-DRB1*08:03 and DRB1*14:06 were associated with reduced and increased ACPA levels, respectively. We detected a strong association between ACPA levels and amino acid position 74 (P = 1.9 × 10(-51) ). The association was mainly conferred by alanine residue (P = 4.5 × 10(-51) ). After adjustment for position 74, amino acid positions 60 and 57 were found to be associated with ACPA levels. Amino acid positions 74 and 57 had previously been reported to be associated with susceptibility to ACPA-positive RA in Asians. Combinations of the amino acid residues at position 74 and position 60 or 57 could induce improvement in Akaike's information criterion comparable to that induced by the 5 significant HLA-DRB1 alleles (HLA-DRB1*08:03, DRB1*09:01, DRB1*14:06, DRB1*15:01, and DRB1*15:02). Amino acid position 74 in HLA-DRB1 is strongly associated with ACPA levels in ACPA-positive RA, as well as with RA susceptibility. The mechanisms of ACPA production and susceptibility to ACPA-positive RA seem to partly overlap.

IntroductionProto-oncogene survivin is a member of the inhibitor of apoptosis (IAP) family of proteins. The presence of serous antibodies against survivin in patients with systemic sclerosis has been previously reported; however, there are few reports regarding the pathophysiological relationship between survivin and systemic sclerosis. We herein investigated the expression and function of survivin in SSc patients.MethodsWe performed immunohistochemistry analyses to determine the expression of XIAP, cIAP and survivin in skin lesions from patients with SSc and non-SSc. The expression levels of survivin in peripheral blood mononuclear cells (PBMCs) obtained from SSc patients and healthy controls were evaluated using RT-PCR and flow cytometry. Additionally, the function of survivin was verified with overexpression experiments using monocyte-derived dendritic cells (Mo-DCs).ResultsThe expression patterns of both XIAP and cIAP were similar, while only the survivin expression differed between the SSc and non-SSc skin lesions. Survivin-overexpressing cells were detected in the SSc dermis frequently. The positive rate of survivin in SSc dermis (64.3 %, 9/14) was higher than that in non-SSc dermis (11.2 %, 1/9). Furthermore, survivin+ cells expressed CD1a, one of the DC markers. Real-time PCR and FACS analyses revealed that the survivin-WT (wild type) expression levels in PBMCs, in particular CD14+ monocytes, from SSc patients were higher than that from healthy controls. Additionally, the overexpression experiments showed that survivin-WT-overexpressing CD1a+ Mo-DCs have the characteristics of promoting cell cycle progression and decreasing apoptotic cells.ConclusionsThese findings suggest that dermal survivin+ CD1a+ cell infiltration may be a potential biomarker of SSc skin lesions. PBMCs and monocytes from SSc patients also overexpressed survivin; therefore, dermal survivin+ DC may be derived from peripheral blood monocytes. Additionally, survivin may be involved in dermal CD1a+ DC proliferation through cell cycle activation and resistance to apoptosis. Survivin may be an important molecule for the pathogenesis of SSc.

Specific HLA class II alleles are strongly associated with susceptibility to rheumatoid arthritis (RA); however, how HLA class II regulates susceptibility to RA has remained unclear. Recently, we found a unique function of HLA class II molecules: their ability to aberrantly transport cellular misfolded proteins to the cell surface without processing to peptides. Rheumatoid factor (RF) is an autoantibody that binds to denatured IgG or Fc fragments of IgG and is detected in 70-80% of RA patients but also in patients with other diseases. Here, we report that intact IgG heavy chain (IgGH) is transported to the cell surface by HLA class II via association with the peptide-binding groove and that IgGH/HLA class II complexes are specifically recognized by autoantibodies in RF-positive sera from RA patients. In contrast, autoantibodies in RF-positive sera from non-RA individuals did not bind to IgGH/HLA class II complexes. Of note, a strong correlation between autoantibody binding to IgG complexed with certain HLA-DR alleles and the odds ratio for that allele's association with RA was observed (r = 0.81; P = 4.6 × 10(-5)). Our findings suggest that IgGH complexed with certain HLA class II alleles is a target for autoantibodies in RA, which might explain why these HLA class II alleles confer susceptibility to RA.

Objectives Anti-cytokine therapy is reportedly useful in amyloid A (AA) amyloidosis complicating rheumatic diseases. However, to date no studies have directly compared the utility of tumour necrosis factor (TNF) inhibition to that of interleukin-6. The aim of our retrospective study was to compare the clinical utility of tocilizumab (TCZ) and anti-TNF (TNF inhibitor) therapy.Methods We studied 42 patients treated with anti-cytokine agents at our hospital: 31 had received a single agent, ten had received two agents and one had received three agents. Patients were divided into a TCZ group (22 patients) and a TNF inhibitor group (32 patients). The main parameters compared were treatment retention rate, serum amyloid A (SAA) profile, renal function profile and clinical disease activity index.Results The 5-year retention rates were 90.4 (TCZ group) and 34.3 % (TNF inhibitor group) (p = 0.0154, log-rank test). The median SAA fell from 219.2 μg/mL at treatment initiation to 5.0 μg/mL at last observation (TCZ), and from 143.6 to 38.1 μg/mL (TNF inhibitor) (p = 0.0194). Estimated glomerular filtration rate was improved in 72.7 (TCZ) and 34.4 % (TNF inhibitor) of patients (p = 0.0062). The rates of clinical remission or low disease activity at last observation for the TCZ and TNF inhibitor groups were 72.7 and 40.7 % (p = 0.0201), respectively.Conclusions Based on these results, we conclude that TCZ was of greater clinical utility than anti-TNF therapy in our patients with AA amyloidosis complicating rheumatic diseases.

ObjectivesTo investigate the duration of remission and low disease activity (LDA) after cessation of tocilizumab (TCZ) treatment in rheumatoid arthritis patients who showed remission or LDA as assessed by DAS28 in response to preceding TCZ monotherapy, and to explore the factors contributing to prolonged efficacy duration.MethodsDisease activity was monitored for 56 weeks. The rate of continued efficacy was estimated by Kaplan–Meier curves.ResultsA total of 187 patients were eligible. At baseline of this study, median disease duration was 7.8 years, preceding TCZ treatment period was 4.0 years and DAS28 was 1.5. The rate of continued LDA at 52 weeks was 13.4 % according to the Kaplan–Meier estimate. 19 patients (10 %) were completely drug-free and 17 patients (9.1 %) fulfilled DAS28 remission at 52 weeks. Multivariate Cox regression analysis identified low serum IL-6 and normalisation of MMP-3 levels at cessation of TCZ as independent predictive markers for longer duration of LDA. In patients with low serum IL-6 (<12.9 pg/mL) and normal MMP-3 levels, the rate of continued LDA reached 38.0 % at 52 weeks.ConclusionsTCZ monotherapy may induce biologics-free remission or LDA without concomitant use of synthetic DMARDs. Serum levels of IL-6 and MMP-3 are useful markers for identifying patients who could discontinue TCZ without acute disease flare.