Nobuo Kuramoto

Public perception of and willingness to perform bystander CPR in Japan

AIM Immediate bystander cardiopulmonary resuscitation (CPR) is the most essential factor for life saving in out-of-hospital cardiac arrest patients. We investigated the characteristics associated with willingness to attempt CPR among the Japanese general population. METHODS We randomly selected 2400 persons from all over Japan and conducted a questionnaire survey regarding their knowledge, experiences of and attitudes toward CPR. We performed descriptive statistics followed by multivariable logistic regression analyses. RESULTS A total of 1132 persons (47%) completed the questionnaire. Only 13% of the subjects were willing to attempt bystander CPR for their families and friends, and 7% were willing to attempt bystander CPR for strangers. Willingness to attempt CPR was independently associated with office workers or skilled workers [odds ratio (OR) 1.8; 95% confidence interval (CI): 1.1-2.7], having trained in CPR [OR: 3.1; 95% CI: 2.1-4.6], actual experience with CPR [OR: 3.8; 95% CI: 1.7-8.3], and having friends with heart diseases [OR: 1.8; 95% CI: 1.05-3.0]. Having trained in CPR was independently associated with younger age [OR: 1.6; 95% CI: 1.2-2.1], office workers or skilled workers [OR: 1.5; 95% CI: 1.1-2.0], having drivers license [OR: 1.7; 95% CI: 1.2-2.4] and awareness of AED placement in a public space [OR: 2.1; 95% CI: 1.4-3.1]. CONCLUSION Experience of CPR training closely associated with willingness to attempt CPR, and awareness of AED in a public space are significant factors in CPR training. AED placement might call attention to CPR training and develops willingness to attempt CPR.

Epidemiology of potentially inappropriate medication use in elderly patients in Japanese acute care hospitals

The elderly receive many medications which may have adverse effects. Little evidence is available about the epidemiology of potentially inappropriate medications being prescribed to the elderly in Japan as defined by the Beers criteria, or whether or not these medications result in harm when used in this population.

Carbamylated albumin is one of the target antigens of anti-carbamylated protein antibodies

Abstract Objectives. Anti-carbamylated protein (anti-CarP) antibodies are detected in RA patients. Fetal calf serum is used as an antigen source in anti-CarP ELISA, and the precise target antigens have not been found. We aimed to identify the target antigens of anti-CarP antibodies. Methods. Western blotting of anti-CarP antibodies was conducted. Anti-carbamylated human albumin (CarALB) antibody was detected by in-house ELISA for 493 RA patients and 144 healthy controls (HCs). An inhibition ELISA of anti-CarP antibodies by CarALB and citrullinated albumin (citALB) was performed using eight RA patients’ sera. Serum CarALB was detected by liquid chromatography–tandem mass spectroscopy (LC/MS/MS), and the serum MPO concentration was measured by ELISA. Results. We focused on carbamylated albumin because it corresponded to the size of the thickest band detected by western blotting of anti-CarP antibodies. Anti-CarALB antibody was detected in 31.4% of RA patients, and the correlation of the titres between anti-CarALB and anti-CarP was much closer than that between anti-citALB and anti-CCP antibodies (ρ = 0.59 and ρ = 0.16, respectively). The inhibition ELISA showed that anti-CarP antibodies were inhibited by CarALB, but not by citALB. CarALB was detected in sera from RA patients by LC/MS/MS. The serum MPO concentration was correlated with disease activity and was higher in RA patients with anti-CarALB antibody than in those without. Conclusion. We found that carbamylated albumin is a novel target antigen of anti-CarP antibodies, and it is the first reported target antigen that has not been reported as the target of ACPA.

Anti-carbamylated Protein Antibodies Are Detectable in Various Connective Tissue Diseases

Objective. Anti-carbamylated protein (anti-CarP) antibodies are possible diagnostic biomarkers of anticitrullinated protein antibody (ACPA)-negative rheumatoid arthritis (RA). We aimed to elucidate the prevalence of anti-CarP antibodies in non-RA connective tissue diseases (CTD) because CTD are important in the differential diagnosis of ACPA-negative RA. Methods. The sera from 266 patients with RA and 616 patients with CTD and 80 healthy controls were examined using an in-house anti-CarP ELISA. Results. The prevalence and the level of anti-CarP antibodies in several CTD were comparable to those in ACPA-negative RA. Conclusion. Anti-CarP antibodies are not useful for differentiating ACPA-negative RA from CTD.

Anti-EJ, anti-MDA5 double-positive chronic clinically amyopathic dermatomyositis: a case report

Anti-aminoacyl-tRNA synthetase (ARS) and antimelanoma differentiation-associated gene 5 (MDA5) antibodies are known to be myositis-specific autoantibodies (MSAs). These antibodies are closely associated with interstitial lung disease (ILD) [1, 2]. These MSAs are, in general, mutually exclusive; therefore, coexistence of these antibodies is rare. In 2016, a 53-year-old Japanese woman was admitted to our department with a dry cough and dyspnoea, worsening over 2 months. She had been diagnosed with clinically amyopathic DM associated with ILD in 2001. Initially, she had heliotrope rash, facial erythema, Gottron papules with some shallow ulcers, mechanic’s hands and periungual erythema. Skin biopsy from the Gottron papule showed interface dermatitis. She had RP but no arthritis. Although muscle pain or weakness was not present, there was a slight elevation of creatine kinase (range of 200–250 U/l) on the blood test and myogenic changes on electromyographic examination in biceps and tibialis anterior (muscle MRI and biopsy were not performed). Initial treatment with prednisolone 30 mg/day (0.8 mg/kg/day) and ciclosporin improved the skin lesions and ILD. She later experienced three episodes of ILD flare-up (in 2002, 2005 and 2007), but increasing prednisolone from maintenance dose of 7-8 mg/day to 30-55 mg/day (0.8-1.0 mg/kg/day) in combination with either ciclosporin or i.v. CYC therapy (500 mg/m monthly) was successful in inducing remission of ILD each time. The disease was well controlled with prednisolone 7–8 mg/day and tacrolimus 4 mg/day for 8 years. Antiglycyl-tRNA synthetase (anti-EJ) antibody was detected by RNA immunoprecipitation in 2001 and 2005. On admission in 2016, the patient showed heliotrope rash, Gottron papules and mechanic’s hands. Muscle weakness and pain were not present. Lung auscultation identified considerable fine crackles bilaterally. Laboratory tests included creatine kinase (71 U/l), lactate dehydrogenase (411 U/l) and CRP (2.1 mg/dl). Investigations for respiratory infection were negative, including sputum specimen culture [1–3], b-D-glucan assay, Aspergillus galactomannan assay and IFN-c release assay for tuberculosis (QuantiFERON-TB). Chest CT showed newly developed peripheral random groundglass attenuation (GGA), marked reticulation, traction bronchiectasis and volume loss in the lower lung field bilaterally (Fig. 1A). Although anti-EJ antibody had been detected twice previously, RNA immunoprecipitation on admission was negative (Fig. 1B). Anti-MDA5 antibody was detected by ELISA and confirmed by protein immunoprecipitation. We retrospectively screened frozen sera from 2001 and 2005, identifying anti-MDA5 antibody in both samples by ELISA and protein immunoprecipitation (Fig. 1C). We realized that anti-EJ and anti-MDA5 antibodies had coexisted from the onset of disease, but that anti-EJ antibody became negative during the clinical course. Acute exacerbation of ILD related to clinically amyopathic DM with anti-MDA5 antibody was diagnosed, and we thererfore treated our patient with intensive combined immunosuppressive therapy of high-dose prednisolone, tacrolimus and biweekly i.v. CYC therapy. However, her respiratory status deteriorated, and highflow nasal cannula oxygen therapy was introduced 7 weeks after admission. Follow-up chest CT at the time showed newly developed random GGA (Fig. 1D). Plasmapheresis was then introduced. Subsequent chest CT showed no remarkable deterioration. Plasmapheresis was performed once every 2–3 days, and up to seven times in total, but discontinued when catheter-related infection was suspected. The patient’s respiratory condition stabilized, and high-flow nasal cannula oxygen therapy was successfully withdrawn. Coexistence of anti-ARS and anti-MDA5 antibodies is rare, because MSAs are, in general, mutually exclusive [3]. Only one report has described a case of DM with both anti-ARS (anti-PL-7) and anti-MDA5 antibodies [4]. To the best of our knowledge, ours is the second case with both anti-ARS (anti-EJ) and anti-MDA5 antibodies, but is also unique in that the antibody profile and clinical phenotype changed during the long clinical course. Clinical features of ILD with anti-ARS antibody (ARS-ILD) or anti-MDA5 antibody (MDA5-ILD) have been well reported. Patients with ARS-ILD respond well to glucocorticoid therapy but suffer from more frequent recurrence than anti-ARS-negative patients [1, 5]. ARSILD chest CT is characterized by reticulation, GGA and traction bronchiectasis, which are predominantly distributed in the lower lobe, peripheral and/or peribronchovascular areas. Progression of fibrosis and volume loss of the lower lobe are often observed during a long clinical course [1, 2]. MDA5-ILD is distinguished by rapidly progressive ILD and poor short-term prognosis, especially among Asian populations, and therefore often requires intensive combined immunosuppressive therapy from the outset [5, 6]. Chest CT of MDA5-ILD is reportedly characterized by lower consolidation or a random GGA pattern and absence of intralobular reticular opacities and traction bronchiectasis [7]. Key message

TAFRO syndrome complicated with occlusion of multiple cerebral arteries

Abstract Thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly (TAFRO) syndrome is a recently proposed disease entity that is considered to be a variant of Castleman’s disease. Here, we report a 42-year-old woman with fever, pleural effusion, massive ascites, severe oedema, hepatosplenomegaly, renal failure and thrombocytopenia who developed broad cerebral infarction with severe stenoses of the bilateral internal carotid arteries during the early course of treatment. To our knowledge, this is the first report of TAFRO syndrome with severe cerebral infarction, which suggests cerebral artery vasculitis.

Simultaneous development of cutaneous vasculitis and an autoimmune bullous skin disease during anti-TNF therapy for rheumatoid arthritis: a case report and review of the literature

Abstract Tumour necrosis factor inhibitors (TNFi) have led to a paradigm shift in the treatment for various diseases including rheumatoid arthritis (RA). During the course of treatment, however, they sometimes cause adverse autoimmune disorders such as lupus, psoriasis and vasculitis. Here, we report a case in which a patient with RA under etanercept (ETN) treatment developed simultaneous ulcerations and blisters on the extremities. Skin biopsies showed leucocytoclastic vasculitis (LCV) at the ulcerative lesion, and subepidermal blistering with linear deposits of IgG and C3 at the basement membrane zone of the blister suggesting a pemphigoid disease. Such simultaneous development of LCV and pemphigoid in an RA patient has not previously been reported. We reviewed 71 cases of vasculitis and 7 cases of pemphigoid diseases during anti-TNF therapy. The prevalence of pemphigoids in RA patients appeared to be comparable to that in healthy individuals. This case showed that TNFi treatment may be involved in two distinct autoimmune reactions, in which vasculitis is related to the augmentation of pemphigoid.

A concomitant case of pathologically proven IgG4-related disease and ANCA-associated vasculitis: case report

Abstract A 63-year-old male visited our hospital after bilateral apical lung masses were detected on medical check-up chest X-ray. Histopathology of the resected mass revealed storiform fibrosis with an increased number of immunoglobulin G4 (IgG4)-positive plasma cells, compatible with IgG4-related disease (IgG4-RD). The patient was subsequently followed up without treatment for 3 years. Later, at age 66, he revisited our hospital because of scleritis, proteinuria, and myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) positivity (179 U/ml). A renal biopsy revealed pauci-immune necrotising crescentic glomerulonephritis. After high-dose prednisolone (PSL) was started, the patient’s scleritis subsided and his MPO-ANCA level and proteinuria were decreased. Subclass-based indirect immunofluorescence revealed that the patient’s serum was positive for IgG1-type ANCA but negative for IgG4-type ANCA. Including the present case, there have been nine reported cases involving both biopsy-proven IgG4-RD and ANCA-associated vasculitis (AAV). In all these concomitant cases of IgG4-RD and AAV, PSL and immunosuppressants were used to control AAV. Deliberate care should be taken to distinguish between IgG4-RD and AAV at diagnosis as they have overlapping features and can, though very rarely, occur concomitantly.

Anti-centromere antibody exhibits specific distribution levels among anti-nuclear antibodies and may characterize a distinct subset in rheumatoid arthritis

Anti-centromere antibody (ACA) is one of the classical anti-nuclear antibody (ANA) staining patterns. However, characteristics of ACA in comparison with the other ANA patterns and clinical features of ACA-positive subjects have not been elucidated. Here, we examined all ANA patterns by indirect immunofluorescence for 859 rheumatoid arthritis (RA) patients. Together with the ANA data of 9,575 healthy volunteers, we compared distributions of the ANA levels. ACA was the only ANA that demonstrated a definite bimodal distribution of levels. ACA showed significantly higher levels than the other ANA staining patterns in both RA and healthy population (p < 0.0001). ACA-positivity was associated with old age and was observed more in females. We further recruited another cohort of 3,353 RA patients and confirmed the findings. ACA was also associated with Raynaud’s phenomenon (p = 6.8 × 10−11) in RA. As a conclusion, ACA displays a specific ANA staining pattern with a bimodal distribution, and ACA-positive RA may constitute a distinct subset with specific clinical features.

Clinical Images: Chronic Nonbacterial Osteomyelitis

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