Reduced-dose versus high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis: predefined 2-year follow-up study.

OBJECTIVES: The LoVAS trial reported non-inferiority in remission induction rates between the reduced-dose and conventional high-dose glucocorticoid regimens plus rituximab for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 6 months; however, maintenance glucocorticoid requirements and long-term outcomes are unknown. METHODS: A total of 140 patients with new-onset ANCA-associated vasculitis without severe glomerulonephritis or alveolar haemorrhage were randomised to receive reduced-dose prednisolone (0.5 mg/kg/day) plus rituximab (375 mg/m2/week×4) or high-dose prednisolone (1 mg/kg/day) plus rituximab. After achieving remission, patients received the rituximab maintenance therapy (1 g/6 months). RESULTS: A total of 134 patients were analysed. Among patients who achieved remission with the protocolised treatments, the majority of patients in the reduced-dose group (89.7%) and 15.5% in the high-dose group discontinued prednisolone (median time to withdrawal, 150 and 375 days, respectively). During 24-month trial period, two patients in the reduced-dose group (2.8%) died, while five patients in the high-dose group (7.6%) died (p=0.225). Relapse occurred in nine patients in the reduced-dose group (13.0%) (two major and seven minor) and five in the high-dose group (7.6%) (two major and three minor) (p=0.311). Serious adverse events (SAEs) were less frequent in the reduced-dose group (36 events in 19 patients, 27.5%) than in the high-dose group (54 events in 30 patients, 46.2%) (p=0.025). CONCLUSION: At 24 months, frequencies of relapse did not differ between the groups, and SAEs were less frequent in the reduced-dose group due to the lower event rate in the 6-month induction phase. The bias to myeloperoxidase-ANCA positivity (85.8%) in the trial population should be noted. TRIAL REGISTRATION NUMBER: NCT02198248.

Association of methotrexate polyglutamates concentration with methotrexate efficacy and safety in patients with rheumatoid arthritis treated with predefined dose: results from the MIRACLE trial.

OBJECTIVES: The usefulness of methotrexate-polyglutamates (MTX-PGs) concentration for management of rheumatoid arthritis has been debated. We aimed to clarify the association of MTX-PGs concentration with efficacy and safety in MTX-naïve patients initiating MTX in a prospective interventional clinical trial. METHODS: The MIRACLE trial enrolled 300 MTX-naïve patients. Oral MTX was initiated and increased to the maximum tolerated dose by week 12. Patients who did not achieve remission according to the Simplified Disease Activity Index at week 24 were randomised to either the continued dose or reduced dose group and were started on subcutaneous adalimumab. We measured the concentrations of MTX-PGs in erythrocytes using liquid chromatography-tandem mass spectrometry and analysed the association of these concentrations with efficacy and safety. RESULTS: The mean concentration of total MTX-PGs increased with an increasing dose of MTX and continued to elevate for another 12 weeks after the dose was fixed. At week 24, the total MTX-PGs concentration was 110.5 (SD 43.8) nmol/L with MTX dose of 12.6 (3.0) mg/week (0.23 (0.07) mg/kg/week). During MTX monotherapy, the higher MTX-PGs concentration was an independent factor for lower disease activity; however, this association disappeared after adalimumab initiation in patients with continued MTX dose. Hepatotoxicity was related to the higher MTX-PGs concentration regardless of adalimumab use. The total MTX-PGs concentration was significantly elevated by lower estimated glomerular filtration rate, serum albumin and body mass index. CONCLUSIONS: The MIRACLE trial demonstrated that higher total MTX-PGs concentration in erythrocytes is related to the higher efficacy and lower safety of MTX. TRIAL REGISTRATION NUMBER: NCT03505008.

Low remission rates and high incidence of adverse events in a prospective VEXAS syndrome registry.

OBJECTIVE: We aimed to gather real-world clinical evidence of detailed disease activity, treatments, remission rates, and adverse events (AEs) associated with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome in a prospective study. METHODS: Patients in Japan suspected of having VEXAS syndrome were enrolled in a registry study. A novel disease activity measure (VEXASCAF) assessing 11 symptoms associated with VEXAS syndrome was evaluated at enrolment and after 3 months. AEs, survival, CRP levels, and treatments were also recorded at enrolment and 3 months after enrolment. All exons of UBA1 were sequenced using a next-generation sequencer to determine the variant allele frequencies of pathogenic variants in the peripheral blood of all patients. RESULTS: Of the 55 registered patients, 30 patients were confirmed to have pathogenic variants of UBA1. All patients were male, with a median age of 73.5 years. VEXASCAF and CRP levels decreased significantly at 3 months post-enrolment, but the oral prednisolone dose did not change. Only two patients achieved complete remission according to FRENVEX at 3 months after enrolment. During the observation period of 6 months, 28 AEs were observed, including 3 deaths, 4 malignancies from two cases, 2 thromboses, and 13 infections (including 4 mycobacterial infections). Inflammation of the lung and cervical region (i.e. parotid and submandibular gland swelling, tonsillitis, cervical swelling, and pain) were the most common AEs. CONCLUSIONS: Patients with VEXAS syndrome required high-dose glucocorticoids to achieve remission, and complications-such as malignancy, thrombosis, and infection-occurred frequently within a short observation period.

Short-term and long-term outcomes of patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis.

OBJECTIVES: Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis characterized by frequent interstitial lung disease and reduced muscle involvement. This study aimed to determine the short-term and long-term outcomes of patients with MDA5-DM. METHODS: Information on baseline characteristics, treatments, and short-term and long-term outcomes of patients with MDA5-DM including survival, relapse, and the titer of anti-MDA5 antibody, was retrospectively collected. Descriptive statistics regarding clinical outcomes were calculated, and a comparison of clinical parameters between patients with and without relapse was performed. The short-term survival according to the use of Janus kinase inhibitors (JAKi) was also assessed. RESULTS: A total of 154 patients with MDA5-DM were included in the study. Forty patients (25.9%) died during the remission induction phase, with respiratory failure being the most common cause of mortality. Among the 114 patients who survived the remission induction phase, the 5-year cumulative survival and relapse-free survival rates were 96.8% and 77.4%, respectively, and 7.9% of patients achieved complete drug-free remission. Fifty-four patients achieved normalization of anti-MDA5 antibody titers and only two of them relapsed after normalization. In the severe patients, the 6-month survival rate became significantly higher after the emergence of the JAKi treatment compared with before its existence (p= 0.03). CONCLUSIONS: Although relapse often occurs, the long-term survival of MDA5-DM patients who survived the remission induction phase is generally favorable. The status of the anti-MDA5 antibody is associated with relapse. JAKi may improve the survival of refractory patients with severe MDA5-DM.

Impact of an artificial intelligence-aided endoscopic diagnosis system on improving endoscopy quality for trainees in colonoscopy: Prospective, randomized, multicenter study.

OBJECTIVE: This study was performed to evaluate whether the use of CAD EYE (Fujifilm, Tokyo, Japan) for colonoscopy improves colonoscopy quality in gastroenterology trainees. METHODS: The patients in this multicenter randomized controlled trial were divided into Group A (observation using CAD EYE) and Group B (standard observation). Six trainees performed colonoscopies using a back-to-back method in pairs with gastroenterology experts. The primary end-point was the trainees' adenoma detection rate (ADR), and the secondary end-points were the trainees' adenoma miss rate (AMR) and Assessment of Competency in Endoscopy (ACE) tool scores. Each trainee's learning curve was evaluated using a cumulative sum (CUSUM) control chart. RESULTS: We analyzed data for 231 patients (Group A, n = 113; Group B, n = 118). The ADR was not significantly different between the two groups. Group A had a significantly lower AMR (25.6% vs. 38.6%, P = 0.033) and number of missed adenomas per patient (0.5 vs. 0.9, P = 0.004) than Group B. Group A also had significantly higher ACE tool scores for pathology identification (2.26 vs. 2.07, P = 0.030) and interpretation and identification of pathology location (2.18 vs. 2.00, P = 0.038). For the CUSUM learning curve, Group A showed a trend toward a lower number of cases of missed multiple adenomas by the six trainees. CONCLUSION: CAD EYE did not improve ADR but decreased the AMR and improved the ability to accurately locate and identify colorectal adenomas. CAD EYE can be assumed to be beneficial for improving colonoscopy quality in gastroenterology trainees. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000044031).

Early initiation of angiotensin-converting enzyme inhibitor in patients with scleroderma renal crisis: A nationwide inpatient database study.

OBJECTIVES: To evaluate the effectiveness of early initiation of angiotensin-converting enzyme inhibitor (ACEi) in patients with scleroderma renal crisis (SRC). METHODS: This was a retrospective cohort study using a nationwide inpatient database in Japan from July 2010 to March 2020. All hospitalized patients with SRC were divided into those who received ACEi within two days of admission (early ACEi group) and those who did not (control group). Propensity-score overlap weighting analysis was performed to adjust for confounding factors. The primary outcome was the composite of in-hospital mortality or hemodialysis dependence at discharge. RESULTS: Of the 475 eligible patients, 248 (52.2%) were in the early ACEi group and 227 (47.8%) were in the control group. After overlap weighting, the primary outcome was significantly lower in the early ACEi group than in the control group (40.1% vs. 49.0%; odds ratio, 0.69; 95% confidence interval, 0.48-1.00; P= 0.049). CONCLUSIONS: The present study showed that early initiation of ACEi was associated with lower composite outcome of in-hospital mortality or hemodialysis dependence at discharge in patients with SRC. Further prospective studies are warranted to verify the present findings.

Mechanistic Study of Reduction of Nitrite to NO by the Copper(II) Complex: Different Concerted Proton-Electron Transfer Reactivity between Nitrite and Nitro Complexes.

The literature contains numerous reports of copper complexes for nitrite (NO2-) reduction. However, details of how protons and electrons arrive and how nitric oxide (NO) is released remain unknown. The influence of the coordination mode of nitrite on reactivity is also under debate. Kundu and co-workers have reported nitrite reduction by a copper(II) complex [J. Am. Chem. Soc. 2020, 142, 1726-1730]. In their report, the copper(II) complex reduced nitrite using a phenol derivative as a reductant, resulting in NO, a hydroxyl copper(II) complex, and the corresponding biphenol. Also, the involvement of proton-coupled electron transfer was proposed by mechanistic studies. Herein, density functional theory calculations were performed to determine a mechanism for reduction of nitrite by a copper(II) complex. As a result of geometry optimization of an initial complex, two possible structures were obtained: Cu-ONO and Cu-NO2. Two possible reaction pathways initiated from Cu-ONO or Cu-NO2 were then considered. The calculation results indicated that the Cu-ONO pathway is energetically favorable. When changes in the electronic structure were considered, both pathways were found to involve concerted proton-electron transfer (CPET). In addition, an intrinsic reaction coordinate analysis revealed that the two pathways were achieved by different types of CPET. Furthermore, an intrinsic bond orbital analysis clearly indicated that, in the Cu-ONO pathway, the chemical events involved proceeded concertedly yet asynchronously.

Safety and Efficacy of Sedation During Emergency Endoscopy for Upper Gastrointestinal Bleeding: A Propensity Score Matching Analysis.

BACKGROUND AND AIM: This study aimed to compare patients with and without sedation during emergency endoscopy for upper gastrointestinal bleeding (UGIB) and to clarify the safety and efficacy of sedation in emergency endoscopy. METHODS: We retrospectively collected 389 patients who underwent emergency endoscopy for UGIB at Ureshino Medical Center from 2016 to 2021. Patients were divided into two groups: sedation group during emergency endoscopy and nonsedation group. Clinical characteristics, patient status on admission, and UGIB etiology were evaluated. Treatment outcomes and adverse events were evaluated using propensity score matching (PSM), and risk factors for mortality from UGIB were investigated using Cox multivariate analysis. RESULTS: The sedation group was significantly younger, composed of a higher proportion of males, and had chronic liver disease. Blood pressure and hemoglobin level on admission were significantly higher in the sedation group. The main cause of bleeding was peptic ulcer, which was significantly higher in the nonsedation group. PSM created 133 matched pairs. The success rate of endoscopic hemostasis was similar in both groups, and procedure time was significantly shorter in the sedation group than in the nonsedation group (17.6 ± 10.0 versus 20.2 ± 10.2 min, P = 0.04). There were no significant differences in adverse events between groups. Cox multivariate analyses revealed that red blood cell transfusion [hazard ratio (HR) 4.45, P < 0.02] and rebleeding (HR 3.30, P = 0.03) were associated with increased risk of 30-day mortality from UGIB. CONCLUSIONS: Sedation reduced the procedure time during emergency endoscopy for UGIB. Sedation during emergency endoscopy for UGIB is acceptable for safe endoscopic procedures.

Management of chronic rheumatic diseases in women 18-45 years of age in Asia Pacific: insights from patient and clinician surveys.

OBJECTIVE: Perspectives of women aged 18-45 years with chronic rheumatic diseases (CRD), and clinicians, in the Asia-Pacific (APAC) region are reported. METHODS: Online surveys were completed by women, pregnant in the past 2-5 years, with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and rheumatologists, obstetricians, orthopaedic surgeons who medically manage CRDs. RESULTS: Among 210 (RA 122, PsA 48, axSpA 40) patients, 52% (n = 109/210) delayed their decision to have children, most commonly due to concerns of passing on disease to offspring. 33% (n = 70/210) discussed family planning with a healthcare professional at diagnosis. Patients most often initiated discussions. 94% (n = 193/205) stopped treatment around pregnancy due to fear of fetal harm. 66% (n = 139/210) of patients felt they did not receive all relevant information on the impact of CRDs and treatment on pregnancy. Among 335 clinicians who participated, 82% (n = 143/174) of rheumatologists, 86% (n = 72/84) of obstetricians and 43% (n = 33/77) of orthopaedic surgeons agreed good disease control during pregnancy was their primary goal. 69% (n = 120/174) of rheumatologists were 'very comfortable' with prescribing tumour necrosis factor inhibitors (TNFi) for women aged 18-45 years. Comfort levels generally decreased with the onset of family planning. More obstetricians and orthopaedic surgeons supported avoiding TNFi during pregnancy than rheumatologists (40% [n = 34/84]/38% [n = 29/77] versus 16% [n = 28/174]). Access to more TNFi safety data during pregnancy was considered paramount for increasing clinician comfort. CONCLUSIONS: Patients and physicians need current information and multidisciplinary discussions for improved management of CRD in women in APAC.

Incidence of opportunistic infections in patients with rheumatoid arthritis treated with different molecular-targeted drugs: A population-based retrospective cohort study.

OBJECTIVES: We compared the incidences of four opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with molecular-targeted drugs from big claims data. MATERIALS AND METHODS: We identified 205,906 patients with RA who were prescribed molecular-targeted drugs in 2010-17 from the National Database of Japan and calculated the incidence of four OIs (Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster). RESULTS: The total number of Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster patients with biological disease-modifying antirheumatic drugs or tofacitinib treatment history in RA was 765, 1158, 834, and 18,336, respectively. The incidence rates of each OI for all biological disease-modifying antirheumatic drugs were 0.14, 0.14, 0.09, and 2.40 per 100 person-years, respectively, while for tofacitinib they were 0.22, 0.22, 0.07, and 7.00 per 100 person-years. No big difference was observed among biological disease-modifying antirheumatic drugs. All OIs showed higher incidence in those >65 years, but Pneumocystis pneumonia, nontuberculous mycobacterial infection, and herpes zoster showed no difference between those 65-74 years old and those >75 years old. The median of occurrence was the third, seventh, ninth, and thirteenth month after treatment, respectively. CONCLUSIONS: We counted real incidence rates of OIs for the whole nation from big claims data.

Healthcare resource utilisation and economic burden of patients with adequate and inadequate responses to biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis in Japan.

OBJECTIVE: To compare healthcare resource utilisation (HCRU) and direct costs between responders vs non-responders to advanced therapies for rheumatoid arthritis (RA). METHODS: Patients initiating ≥1 advanced therapy (Oct 2018-Sept 2019) with ≥1 RA claim (6-month pre-index period), ≥2 RA claims (any period), and ≥12 months follow-up were identified from the Medical Data Vision claims database. HCRU and all-cause and RA-related costs (direct medical, emergency department [ED], laboratory, and pharmacy) were compared between responders vs non-responders. Adjusted incidence rate ratios (IRRs) for HCRU or cost were calculated via multivariable analyses. RESULTS: Among 2,446 patients (non-responders [n=1,817]; responders [n=629]), non-responders had significantly longer hospitalisation days (IRR: 1.8 [95% CI: 1.2-2.6]), and significantly more ED visits (2.5 [1.5-4.2]) and prescriptions (1.1 [1.1-1.2]). Mean all-cause hospital/outpatient medical costs were significantly higher for non-responders (1.4 [1.3-1.6], ¥530,895 vs ¥357,009 [$;3,992 vs $;2,684] for responders; ¥173,886 [$;1,307] difference); RA-related medical costs showed a similar trend (¥351,306 vs ¥253,030 [$;2,641 vs $1,902]; ¥98,276 [$;739] difference). No differences between responders and non-responders were observed in mean all-cause and RA-related pharmacy costs. CONCLUSIONS: Non-responders to advanced therapies had greater HCRU and all-cause/RA-related direct costs as compared with responders, suggesting a need for more effective RA therapies to reduce the economic burden associated with non-response.

Antiphospholipid antibody positivity and the thrombotic risk in Japanese patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: It has been reported that 21.0-51.7% of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) patients were antiphospholipid antibody (aPL)-positive. However, the clinical significance of aPL positivity in AAV is not fully understood. METHODS: We retrospectively assessed patients with AAV diagnosed from 2013 to 2020 at our hospital. Positivity of aPL was defined as positivity of anti-cardiolipin antibody, anti-cardiolipin ß2 glycoprotein 1 complex antibody, and/or lupus anticoagulant at least one time during the follow-up periods. The thrombotic risk of aPL positivity was examined by multivariate analyses with the Cox regression model. RESULTS: A total of 93 patients with a median age of 71.9 years were included in the study. The median follow-up period was 35.4 months. Thirty-one patients (33.3%) were aPL-positive. Twenty-two thrombotic events occurred in 17 patients (18.3%). Thrombotic events occurred more frequently in aPL-positive patients than in aPL-negative patients (P = 0.011). Multivariate analyses with two different models identified aPL positivity as a thrombotic risk factor (hazard ratios 4.302 and 5.956, 95% confidence intervals 1.546-11.968 and 1.940-18.281, respectively). CONCLUSIONS: The proportion of aPL-positive patients was 33.3%, and aPL positivity increased the thrombotic risk in Japanese patients with AAV.

CCR4 predicts the efficacy of abatacept in rheumatoid arthritis patients through the estimation of Th17 and Treg cell abundance.

OBJECTIVE: Predicting the efficacy of biological disease-modifying anti-rhematic drugs (bDMARDs) is challenging. In this study, we aimed to explore markers that predict the efficacy of abatacept in rheumatoid arthritis (RA) patients. METHODS: Thirty RA patients receiving abatacept were recruited, and peripheral blood mononuclear cells (PBMCs) from the participants were subjected to DNA microarray analysis. The expression of CCR4, which was selected by the result of DNA microarray, was determined by flow cytometry in 16 newly diagnosed treatment-naïve RA patients. CCR4 expression on each helper T cell subset was also measured. RESULTS: CCR4 was upregulated in the abatacept responder. The expression levels of CCR4 were significantly correlated with the improvement of clinical disease activity index (CDAI). CCR4 expression was predominantly observed in CD4+ T cells in PBMCs. The percentage of CCR4-expressing CD4+ T cells was significantly higher in RA patients than in healthy individuals. Interestingly, Th17 and Treg cells expressed high levels of CCR4 compared to non-Th17-related helper T cells. CONCLUSION: CCR4 is a Th17- and Treg-related gene, and the high CCR4 expression in peripheral blood samples may predict the efficacy of abatacept in RA.

Influence of concomitant methotrexate use on the clinical effectiveness, retention, and safety of abatacept in biologic-naïve patients with rheumatoid arthritis: Post-hoc subgroup analysis of the ORIGAMI study.

OBJECTIVES: We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. METHODS: Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. RESULTS: At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. CONCLUSION: The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.

Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study.

OBJECTIVES: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.

Ultrasound of shoulder and knee improves the accuracy of the 2012 EULAR/ACR provisional classification criteria for polymyalgia rheumatica.

OBJECTIVE: Recent studies suggest that the knee is frequently involved in PMR. In this study, we aimed to determine whether the US assessment of the shoulder and knee discriminates between PMR and other differential diagnoses and improves the accuracy of the 2012 EULAR/ACR provisional classification criteria for PMR. METHODS: We consecutively enrolled 81 untreated patients who received a diagnosis of PMR. These patients were divided into two groups based on the final diagnosis made at 1-year follow-up: PMR-definite group (n = 60) and PMR-mimic group (n = 21). We also enrolled age/sex-matched untreated RA patients with shoulder pain from an independent cohort (RA group, n = 60). All patients underwent comprehensive US assessment of the shoulder and knee for synovitis, bursitis, tenosynovitis, tendinitis and ligament inflammation at baseline. RESULTS: US scores for tenosynovitis, tendinitis and ligament inflammation better discriminated the PMR-definite group from the PMR-mimic and RA groups than do those for synovitis or bursitis. Among logistic regression models to identify US variables that were associated with the PMR-definite group, the best fitted model included two US variables: the bilateral involvement of the shoulder (long head of biceps, supraspinatus or subscapularis tendon) and the bilateral involvement of the knee (popliteus tendon or medial or lateral collateral ligament). Incorporating these two items into the 2012 EULAR/ACR provisional classification criteria numerically increased the accuracy to classify the PMR-definite group. CONCLUSION: US assessment of the tendon/ligament-related lesions in the shoulder and knee may improve the accuracy of the 2012 EULAR/ACR provisional classification criteria for PMR.

A randomised, double-blind, placebo-controlled phase III trial on the efficacy and safety of tocilizumab in patients with familial Mediterranean fever.

OBJECTIVES: To evaluate the efficacy and safety of tocilizumab (TCZ), an interleukin 6 receptor monoclonal antibody, in a subset of Japanese patients with familial Mediterranean fever (FMF). METHODS: We performed a double-blind, randomised, parallel-group trial, followed by an open-label extension trial, in patients with colchicine-resistant or -intolerant FMF (crFMF) (UMIN000028010). Patients were randomly assigned (1:1) to receive TCZ (162 mg every week) or placebo, administered subcutaneously, for 24 weeks. Rescue treatment was allowed if the rescue criteria were met. The primary endpoint was the number of fever attacks over the 24 weeks of treatment. Secondary endpoints included the frequency of accompanying symptoms during attacks, serum CRP and SAA values, and adverse events (AEs). The open-label extension study evaluated the long-term safety and efficacy of TCZ in patients who had completed the preceding study (UMIN000032557). RESULTS: We randomly assigned 23 patients to either TCZ (n=1) or placebo (n=12). The TCZ-placebo rate ratios were 0.691 (95% confidence intervals (CI), 0.189-2.531; p=0.577) for the fever attacks, based on the group rates per week. The recurrence of attacks was significantly lower in the TCZ group (hazard ratio = 0.457; 95% CI, 0.240-0.869). Fever attacks, accompanying symptoms, serum CRP and SAA values were controlled in most of the patients who received long-term TCZ. In these trials, the numbers and severity of AEs did not differ between groups. CONCLUSIONS: Although a primary endpoint was not met in the preceding trial, long-term administration of TCZ showed stable efficacy and safety for patients with crFMF.

Theoretical Investigation into Selective Benzene Hydroxylation by Ruthenium-Substituted Keggin-Type Polyoxometalates.

Benzene hydroxylation catalyzed by ruthenium-substituted Keggin-type polyoxometalates [RuV(O)XW11O39]n- (RuVOX; X = Al, Ga, Si, Ge, P, As, S; heteroatoms; 3 ≤ n ≤ 6) is investigated using the density functional theory approach. As a possible side reaction, the water oxidation reaction is also considered. We found that the rate-determining step for water oxidation by RuVOX requires a higher activation free energy than the benzene hydroxylation reaction, suggesting that all of the RuVOX catalysts show high chemoselectivity toward benzene hydroxylation. Additionally, the heteroatom effect in benzene hydroxylation by RuVOX is discussed. The replacement of Si by X induces changes in the bond length of µ4O-X, resulting in a change in the activation free energy for benzene hydroxylation by RuVOX. Consequentially, RuVOS is expected to be the most effective catalyst among the (RuVOX) catalysts for the benzene hydroxylation reaction.

Usefulness of discharge standards in outpatients undergoing sedative endoscopy: a propensity score-matched study of the modified post-anesthetic discharge scoring system and the modified Aldrete score.

BACKGROUND: This study aimed to evaluate the usefulness of discharge standards in outpatients undergoing sedative endoscopy by comparing the modified post-anesthetic discharge scoring system (MPADSS) and the modified Aldrete score. METHODS: We prospectively enrolled 376 outpatients who underwent gastrointestinal endoscopy under midazolam sedation; 181 outpatients were assessed regarding discharge after sedative endoscopy using the MPADSS (group M), and 195 patients were assessed by the modified Aldrete score (group A). The clinical characteristics, types of endoscopy, endoscopic outcomes, and anesthesia outcomes were evaluated between the two groups. We compared discharge score, recovery time, and adverse events using propensity-score matching. RESULTS: Propensity-score matching created 120 matched pairs. The proportion of patients who had a recovery time within 60 min after endoscopy was significantly higher in group A than that in group M (42.5% versus 25.0%, respectively; P < 0.01). The proportion of patients who required > 120 min of recovery time after endoscopy was significantly lower in group A than that in group M (0.0% versus 5.0%, respectively; P = 0.03). However, significantly more patients had drowsiness at discharge in group A compared with group M (19.1% versus 5.0%, respectively; P < 0.01). There was no significant difference in the adverse event rate within 24 h of discharge between the groups. CONCLUSIONS: Patients assessed by the modified Aldrete score were allowed to discharge earlier than those assessed by the MPADSS. However, a patient's level of consciousness should be assessed carefully, especially in patients who visit the hospital alone.

Illustrations of rheumatoid arthritis symptoms to promote communications between patients and physicians.

OBJECTIVES: To develop an illustrative tool presenting visualized rheumatoid arthritis (RA) symptoms using pictures to promote a better understanding between patients and physicians. METHODS: The tool named 'Okomarigoto Sheet' was developed through an Internet survey of patients with RA and certified rheumatologists by repeated in-person interviews. RESULTS: An Internet survey on the reality of communication between patients with RA and physicians in 200 patients and 200 certified rheumatologists revealed various local and systemic symptoms of RA and difficulties in sharing those symptoms between patients and physicians during a short consultation. Interviews from patients and certified rheumatologists suggested that illustrations of symptoms would be helpful for better communication between them; therefore, an illustrative tool presenting visualized RA symptoms was drafted. The draft illustrations were refined through multiple rounds of interviews with the patients. The final version of the tool was discussed and evaluated at a joint meeting of patients and rheumatologists. CONCLUSIONS: A picture sheet presenting RA symptoms was developed. Future prospective studies should evaluate the usefulness of the sheet in clinical practice to promote better communication between patients and physicians.