Autologous concentrated bone marrow injection for precollapse osteonecrosis of the femoral head concurrent with contralateral total hip arthroplasty: protocol for a clinical trial.

INTRODUCTION: The femoral head contralateral to the collapsed femoral head requiring total hip arthroplasty (THA) often manifests in the precollapse stage of osteonecrosis of the femoral head (ONFH). It is not yet demonstrated how autologous concentrated bone marrow injection may prevent collapse of the femoral head concurrent with contralateral THA. The primary objective is to evaluate the efficacy of autologous concentrated bone marrow injection for the contralateral, non-collapsed, femoral head in patients with bilateral ONFH, with the ipsilateral collapsed femoral head undergoing THA. METHODS AND ANALYSIS: This is a multicentre, prospective, non-randomised, historical-data controlled study. We will recruit patients with ONFH who are scheduled for THA and possess a non-collapsed contralateral femoral head. Autologous bone marrow will be collected using a point-of-care device. After concentration, the bone marrow will be injected into the non-collapsed femoral head following the completion of THA in the contralateral hip. The primary outcome is the percentage of femoral head collapse evaluated by an independent data monitoring committee using plain X-rays in two directions 2 years after autologous concentrated bone marrow injection. Postinjection safety, adverse events, pain and hip function will also be assessed. The patients will be evaluated preoperatively, and at 6 months, 1 year and 2 years postoperatively. ETHICS AND DISSEMINATION: This protocol has been approved by the Certified Committee for Regenerative Medicine of Tokyo Medical and Dental University and Japan's Ministry of Healthy, Labour and Welfare and will be performed as a class III regenerative medicine protocol, in accordance with Japan's Act on the Safety of Regenerative Medicine. The results of this study will be submitted to a peer-review journal for publication. The results of this study are expected to provide evidence to support the inclusion of autologous concentrated bone marrow injections in the non-collapsed femoral head in Japan's national insurance coverage. TRIAL REGISTRATION NUMBER: jRCTc032200229.

EEG and video documentation of benzodiazepine challenge in catatonic stupor: A case report.

INTRODUCTION: Catatonia, a psychomotor disorder characterized by diverse clinical signs, including stupor and mutism, remains elusive in its causes and a challenge to diagnose. Moreover, it is often underrecognized due to its resemblance to disorders of consciousness. However, when diagnosing catatonia, an antipsychotic medication may exacerbate the condition. The first-line treatment typically includes benzodiazepines and/or electroconvulsive therapy (ECT). CASE REPORT: A 60-year-old woman with systemic lupus erythematosus (SLE) and epilepsy presented with catatonic stupor. Despite stable treatment, she experienced an acute deterioration in consciousness, requiring hospitalization. Her condition improved markedly following a benzodiazepine challenge, as documented on EEG. This improvement was short-lived, but a second benzodiazepine challenge restored her from E1V1M1 (stupor) to E4V5M6 within minutes, as documented by a video recording. The patient was treated with lorazepam 1.5 mg/day orally and did not experience further relapses. DISCUSSION: The diagnosis of catatonia had been based on her scores on the Bush-Francis Catatonia Rating Scale (BFCRS; Screening, 6/14; Severity, 19), despite meeting only two DSM-5 criteria for catatonia (stupor and mutism). The diagnosis was supported by EEG and video documentation, excluding other potential differential diagnoses such as nonconvulsive status epilepticus and encephalopathy. Additional quantitative EEG analyses indicated that benzodiazepine administration increased brainwide alpha and beta band power significantly, suggesting that the benzodiazepine normalized attention, consciousness, and long-range synchronization. This report additionally emphasizes the significance of video recordings in managing catatonia, and it helps in accurately tracking symptoms, documenting comprehensively, and improving patient understanding, which is crucial for treatment adherence.

Six-month safety and effectiveness of tofacitinib in patients with rheumatoid arthritis in Japan: Interim analysis of post-marketing surveillance.

OBJECTIVES: We evaluated the real-world safety/effectiveness of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), in patients with RA in Japan registered in a post-marketing surveillance study. METHODS: This interim analysis included data from July 2013 to December 2018. Adverse events (AEs), serious AEs (SAEs), Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)/Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] scores, and rates of SDAI/CDAI/DAS28-4(ESR)-defined remission and low disease activity were analysed using 6 months of data. Risk factors for serious infections were assessed by multivariable analyses. RESULTS: Safety and disease activity were evaluated in 6866 and 6649 patients, respectively. Overall, 32.73%/7.37% of patients reported AEs/SAEs. Clinically important AEs with tofacitinib included serious infections/infestations [3.13% of patients; incidence rate (IR; patients with events) 6.91/100 patient-years (PY)], herpes zoster (3.63%; IR 8.02/100 PY), and malignancies (0.68%; IR 1.45/100 PY). SDAI/CDAI/DAS28-4(ESR) scores and remission/low disease activity rates improved over 6 months. Male sex, older age, Steinbrocker's stage IV, history of infection, and diabetes mellitus at baseline were independent risk factors for serious infection. CONCLUSIONS: In patients with RA receiving tofacitinib in Japan, safety was consistent with the reported profile, and disease activity improved over 6 months. STUDY IDENTIFIER: NCT01932372.

Critical role of lectin pathway mediated by MBL-associated serine proteases in complement activation for the pathogenesis in systemic lupus erythematosus.

In complement activation system, although the classical pathway has shown to play a critical role for the pathogenesis of SLE, the role of lectin pathway has remained unknown in the pathogenesis of SLE. As Mannose-binding lectin-associated serine proteases (MASPs) are associated with activation of the lectin pathway, we conducted this study to clarify MASPs associations in the pathogenesis of SLE. We evaluated the serum level of MASPs (MASP-1 and MASP-2) in total 68 SLE patients consisting of 15 patients with biopsy-confirmed membranous lupus nephritis (M-LN), 35 patients with biopsy-confirmed proliferative lupus nephritis (P-LN), and 18 SLE patients without LN (non-LN). Our data showed that the serum levels of MASPs were reduced in both P-LN and non-LN although those of M-LN were not reduced. Our data show that the lectin pathway mediated by MASPs plays a critical role for the pathogenesis of SLE except for M-LN.

Transitions in vascular ultrasonography findings of temporal arteritis in a GCA case with progressive temporal headache and visual impairment.

The European League Against Rheumatism and the American College of Rheumatology have stated that the halo sign on vascular ultrasonography (v-US) is relevant in diagnosing giant cell arteritis (GCA) and is equivalent to temporal artery biopsy. However, there are only a few reports about transitions in v-US findings after glucocorticoid (GC) therapy. We report the transitions in the v-US findings in a case of GCA after GC therapy. The patient had rapidly progressive symptoms, and there were concerns about blindness. After GC therapy, we first observed improvement in headache and visual impairment symptoms within 1 week, followed by rapid improvement in laboratory findings within 2 weeks. Subsequently, there were improvements in v-US findings after more than 2 months. In conclusion, these findings showed a dissociation between improvements in clinical symptoms and v-US findings of the temporal artery. Additionally, this case suggests that regular examination of v-US findings is useful in evaluating GCA with evident vascular wall thickness before GC therapy.

Synovial Tissue Heterogeneity in Japanese Patients With Rheumatoid Arthritis Elucidated Using a Cell-Type Deconvolution Approach.

OBJECTIVE: Recent advances in single-cell RNA sequencing technology have improved our understanding of the immunological landscape of rheumatoid arthritis (RA). We aimed to stratify the synovium from East Asian patients with RA by immune cell compositions and gain insight into the inflammatory drivers of each synovial phenotype. METHODS: Synovial tissues were obtained from East Asian patients in Japan with RA (n = 41) undergoing articular surgery. The cellular composition was quantified by a deconvolution approach using a public single-cell-based reference. Inflammatory pathway activity was calculated by gene set variation analysis, and chromatin accessibility was evaluated using assay of transposase accessible chromatin-sequencing. RESULTS: We stratified RA synovium into three distinct subtypes based on the hierarchical clustering of cellular composition data. One subtype was characterized by abundant HLA-DRAhigh synovial fibroblasts, autoimmune-associated B cells, GZMK+ GZMB+ CD8+ T cells, interleukin (IL)1-ß+ monocytes, and plasmablasts. In addition, tumor necrosis factor (TNF)-α, interferons (IFNs), and IL-6 signaling were highly activated in this subtype, and the expression of various chemokines was significantly enhanced. Moreover, we found an open chromatin region overlapping with RA risk locus rs9405192 near the IRF4 gene, suggesting the genetic background influences the development of this inflammatory synovial state. The other two subtypes were characterized by increased IFNs and IL-6 signaling, and expression of molecules associated with degeneration, respectively. CONCLUSION: This study adds insights into the synovial heterogeneity in East Asian patients and shows a promising link with predominant inflammatory signals. Evaluating the site of inflammation has the potential to lead to appropriate drug selection that matches the individual pathology.

Polyarteritis nodosa diagnosed in a young male after COVID-19 vaccine: A case report.

In response to the coronavirus disease 2019 pandemic, the coronavirus disease 2019 vaccine was rapidly developed and the effectiveness of the vaccine has been established. However, various adverse effects have been reported, including the development of autoimmune diseases. We report a case of new-onset polyarteritis nodosa in a 32-year-old male following the coronavirus disease 2019 vaccination. The patient developed limb pain, fever, pulmonary embolism, multiple subcutaneous nodules, and haematomas. Skin biopsy revealed necrotising inflammation accompanied by fibrinoid necrosis and high inflammatory cell infiltration in the walls of medium to small arteries. The symptoms resolved following corticosteroid treatment. Although it is difficult to prove a relationship between the vaccine and polyarteritis nodosa, similar cases have been reported and further reports and analyses are therefore necessary.

Risk factors associated with relapse after methotrexate dose reduction in patients with rheumatoid arthritis receiving golimumab and methotrexate combination therapy.

AIM: To identify risk factors for relapse after methotrexate (MTX) dose reduction in rheumatoid arthritis (RA) patients receiving golimumab (GLM)/MTX combination therapy. METHOD: Data on RA patients ≥20 years old receiving GLM (50 mg) + MTX for ≥6 months were retrospectively collected. MTX dose reduction was defined as a reduction of ≥12 mg from the total dose within 12 weeks of the maximum dose (≥1 mg/wk average). Relapse was defined as Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) score ≥3.2 or sustained (≥ twice) increase of ≥0.6 from baseline. RESULTS: A total of 304 eligible patients were included. Among the MTX-reduction group (n = 125), 16.8% of patients relapsed. Age, duration from diagnosis to the initiation of GLM, baseline MTX dose, and DAS28-CRP were comparable between relapse and no-relapse groups. The adjusted odds ratio (aOR) of relapse after MTX reduction was 4.37 (95% CI 1.16-16.38, P = 0.03) for prior use of non-steroidal anti-inflammatory drugs (NSAIDs), and the aORs for cardiovascular disease (CVD), gastrointestinal disease and liver disease were 2.36, 2.28, and 3.03, respectively. Compared to the non-reduction group, the MTX-reduction group had a higher proportion of patients with CVD (17.6% vs 7.3%, P = 0.02) and a lower proportion of prior use of biologic disease-modifying antirheumatic drugs (11.2% vs. 24.0%, P = 0.0076). CONCLUSION: Attention should be given to RA patients with history of CVD, gastrointestinal disease, liver disease, or prior NSAIDs-use when considering MTX dose reduction to ensure benefits outweigh the risks of relapse.

In lupus cystitis, is the urinary tract dilated or obstructed?

OBJECTIVES: Lupus cystitis is a rare but serious complication of systemic lupus erythematosus (SLE) that can cause permanent bladder dysfunction, leading to irreversible deterioration of kidney function. We report two cases of SLE with lupus cystitis who showed different images from the same cause of disease. METHODS: Patient 1, a 67-year-old woman diagnosed with SLE presented with persistent dysuria for 3 weeks with sudden headache and vomiting. She was hospitalized because of acute kidney injury; the serum creatinine level was 10.68 mg/dL. Computed tomography (CT) showed significant bilateral ureteral stenosis and bilateral hydronephrosis. Patient 2, a 45-year-old woman diagnosed with SLE presented with dysuria requiring self-catheterization. CT showed significant bilateral ureteral dilatation and bilateral hydronephrosis. RESULTS: In patient 1, the right kidney was afunctional. Left nephrostomy was performed on Day 2. Her serum creatinine returned to the normal range. In patient 2, After admission, she changed to an indwelling bladder catheter. Her serum creatinine level improved from 2.04 to 1.31 mg/dL. CONCLUSION: In patients with lupus cystitis, the urinary tract is commonly dilated, but stenosis has been seen in rare case. Physicians should be careful in diagnosing it.

Efficacy and safety of avacopan in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: A subanalysis of a randomized Phase 3 study.

OBJECTIVES: This subgroup analysis of the randomized, double-blind, Phase 3 ADVOCATE study evaluated the efficacy and safety of avacopan compared with tapered prednisone in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis. METHODS: Patients with microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) received either avacopan 30 mg twice daily for 52 weeks plus prednisone-matching placebo or tapered prednisone over 20 weeks plus avacopan-matching placebo for 52 weeks. The two primary efficacy endpoints were clinical remission at Week 26 and sustained remission at Week 52. RESULTS: Compared with the overall population (N = 330), Japanese patients (N = 21) were older and had worse renal function, and a higher proportion were female and had MPA. The proportion of Japanese patients with clinical remission at Week 26 was 9/11 (81.8%) with avacopan vs. 7/10 (70.0%) with prednisone (overall population: 72.3% vs. 70.1%) and with sustained remission at Week 52 was 8/11 (72.7%) vs. 4/10 (40.0%), respectively (overall population: 65.7% vs. 54.9%). The safety profile of avacopan was similar in Japanese patients and the overall study population. CONCLUSIONS: The efficacy and safety of avacopan in Japanese patients with MPA or GPA were comparable to that observed in the overall ADVOCATE study population.

Safety and effectiveness of baricitinib for rheumatoid arthritis in Japanese clinical practice: 24-week results of all-case post-marketing surveillance.

OBJECTIVES: To assess the safety and effectiveness of baricitinib treatment for rheumatoid arthritis (RA) in real-world clinical practice. METHODS: This ongoing all-case post-marketing surveillance study (starting September 2017) includes all patients with RA treated with baricitinib in Japan. Safety and effectiveness (disease activity) were assessed for 24 weeks. RESULTS: Safety analyses to February 2021 included 4731 patients (initial baricitinib dose: 4 mg/day, n = 3058; 2 mg/day, n = 1661; other, n = 12); 1059 (22.38%) were ≥75 years and 3362 (71.06%) previously received biologic therapy. The overall observational period was 1863.14 patient-years; 1174 (24.82%) patients discontinued baricitinib before Week 24, mostly for lack of effectiveness (n = 478; 10.10%). Adverse events occurred in 1271 (26.87%) patients [serious: 203 (4.29%); death: 18 (0.38%)]. The incidence of herpes zoster, hepatic function disorder, and serious infection was 3.09%, 2.77%, and 1.90%, respectively. Malignancy occurred in 17 patients (0.36%) and major adverse cardiovascular events in seven patients (0.15%). Among patients with effectiveness data, at least 26.57% (Boolean) achieved remission at Week 24. CONCLUSIONS: This large nationwide surveillance study evaluated the safety and effectiveness of 24 weeks of baricitinib for RA in real-world clinical practice. Continued surveillance of long-term safety is ongoing.

Nation-wide cohort study of remission induction therapy using rituximab in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: Effectiveness and safety in the first 6 months.

OBJECTIVES: The aim of this article is to evaluate the effectiveness and safety of rituximab (RTX) for microscopic polyangiitis and granulomatosis with polyangiitis in Japan. METHODS: In this prospective observational study, all patients with microscopic polyangiitis and granulomatosis with polyangiitis administered RTX were enrolled at each institution. During the observation period of 2 years, data up to 6 months were analysed. Cox proportional hazards analysis was used to assess the factors associated with an outcome. RESULTS: Of the 75 patients who received RTX for remission induction therapy, 53 achieved remission by the sixth month and 50 were in remission at the sixth month. During therapy, 38 serious adverse events were observed in 24 patients, 21 serious infections in 16 patients, and 9 patients died. No factors were associated with remission; however, there was a significant difference between patients with and without remission in serious adverse events (22.6% vs. 54.5%), serious infections (11.3% vs. 45.4%), and death (1.9% vs. 36.4%). The hazard ratio (95% confidence interval) for serious infection was 3.49 (1.29-9.74) for patients aged ≥ 75 years and 3.53 (1.31-9.53) for pulmonary complications. Four patients maintained remission for 6 months. CONCLUSIONS: The effectiveness and safety of RTX for microscopic polyangiitis and granulomatosis with polyangiitis for up to 6 months was demonstrated.

Systematic review and meta-analysis for 2023 clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of ANCA-associated vasculitis.

OBJECTIVES: The objective of this study is to provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis by the Japan Research Committee for Intractable Vasculitis. METHODS: PubMed, CENTRAL, and the Japan Medical Abstracts Society databases were searched for articles published between 2015 and 2020 to update the systematic review for existing clinical questions, while PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society were searched for articles published between 2000 and 2020 to conduct a systematic review for newly developed clinical questions. The certainty of evidence was assessed with the GRADE approach. RESULTS: For remission induction, when used in conjunction with cyclophosphamide or rituximab, reduced-dose glucocorticoid lowered the risk of serious adverse events compared to standard-dose glucocorticoid. Avacopan improved sustained remission at 12 months compared to high-dose glucocorticoid. Addition of plasma exchange to remission induction therapy did not reduce the risk of death, end-stage kidney disease, or relapse. For remission maintenance, rituximab reduced the risk of relapse compared to azathioprine. Long-term rituximab or azathioprine reduced the risk of relapse compared to short-term rituximab or azathioprine, respectively. CONCLUSIONS: This systematic review provided evidence required to develop the 2023 clinical practice guideline for the management of ANCA-associated vasculitis.

Changes in anti-MDA5 antibody titres and serum cytokine levels before and after diagnosis of anti-MDA5 antibody-positive dermatomyositis.

OBJECTIVES: Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM is characterized by rapidly progressive interstitial lung disease and has a poor prognosis. We aimed to investigate whether anti-MDA5 antibody titres and cytokine levels predict clinical course, and evaluate changes in both parameters before and after diagnosis. METHODS: This was a retrospective, single-centre study in 38 patients with anti-MDA5 antibody-positive DM. We compared clinical characteristics and laboratory data at diagnosis between patients in the treatment response (n = 23) and non-response (n = 15) groups, and between those in the relapse (n = 5) and non-relapse (n = 24) groups. We also measured serum anti-MDA5 antibody titres and cytokine levels before and after diagnosis. RESULTS: The non-response group was older, had a higher ground-glass opacity score, lower PaO2/FiO2, higher CRP level, and higher anti-MDA5 antibody titre than the response group. No cytokines significantly differed between groups at diagnosis. The relapse group had a significantly higher anti-MDA5 antibody titre than the non-relapse group. In the survivor group, the anti-MDA5 antibody titre and levels of IFN-α, IFN-γ, monocyte chemotactic protein-1 (MCP-1), IL-6, IL-33, CRP, and ferritin were significantly lower 6 months post-treatment than at diagnosis. Macrophage-associated cytokines such as IL-6, IL-8, IL-18 and MCP-1 increased after anti-MDA5 antibody positivity in three patients who were anti-MDA5 antibody-positive before diagnosis. CONCLUSION: The anti-MDA5 antibody titre at diagnosis may predict the clinical course. Levels of macrophage-associated cytokines significantly declined at 6 months post-treatment, and they may have increased after anti-MDA5 antibody titre positivity.

Concordance between practice and published evidence in the management of ANCA-associated vasculitis in Japan: A cross-sectional web-questionnaire survey.

OBJECTIVES: We conducted a descriptive study of the physicians' evidence-practice gap for adults covered by the 2017 clinical practice guidelines for the management of antineutrophil cytoplasmic antibody-associated vasculitis in Japan. METHODS: This web-based survey, conducted between January and February 2021, involved physicians who had treated at least five patients in the preceding year at a regional core hospital. The outcome was the physicians' experience in treating patients with microscopic polyangiitis or granulomatosis with polyangiitis [prevalence with 95% confidence intervals (CIs)], defined as treating at least 60% of their patients with the recommended therapy during the year. A modified Poisson regression analysis was performed to explore the factors associated with concordance. RESULTS: The 202 participants included 49 pulmonologists, 65 nephrologists, 61 rheumatologists, and other physicians. The concordance was 31.5% (95% CI, 25.1-38.5) of physicians who used cyclophosphamide or rituximab for the induction of remission. Rheumatology showed the highest concordance with published evidence (risk ratio = 2.4; 95% CI, 1.10-5.22, p = .03). CONCLUSIONS: These results suggest an evidence-practice gap, which varies substantially among subspecialties. Further studies and a new promotional initiative are necessary to close this gap in clinical practice.

Clinical characteristics of patients with spondyloarthritis and inflammatory bowel disease versus inflammatory bowel disease-related arthritis.

The purpose of this study was to clarify the clinical characteristics of spondyloarthritis (SpA) patients with inflammatory bowel disease (IBD) compared to those without IBD. Furthermore, among patients with SpA and IBD, we aimed to clarify what clinical characteristics lead rheumatologists to diagnose "IBD-related arthritis." Utilizing SpA and psoriatic arthritis (PsA) patients' data from an international, cross-sectional, observational study, we analyzed information on demographics and disease characteristics, dichotomizing patients by IBD status. The presence or absence of IBD was determined based on data collection of treating rheumatologists. Patients with SpA (including PsA) and IBD were also categorized based on treating rheumatologists' definitive diagnosis in regard to SpA type, and compared by whether the patients had IBD-related arthritis or not. Among 4465 SpA patients, 287 (6.4%, 95%CI 5.7-7.2%) were identified with IBD. Compared to SpA patients without IBD, patients with SpA and IBD had a longer diagnostic delay (5.1 vs. 2.9 years, p < 0.001). In patients with SpA and IBD, 111 (38.7%, 95%CI 33.0-44.6%) were diagnosed with IBD-related arthritis. Multivariable analyses showed that HLA-B27 positivity [OR = 0.35, (95%CI 0.15-0.80)], psoriasis [OR = 0.14, (95%CI 0.04-0.50)], IBD as first symptom of SpA [OR = 3.32, (95%CI 1.84-6.01)], and need for IBD-specific treatment [OR = 5.41, (95%CI 2.02-14.50)] were independently associated with the definitive diagnosis of IBD-related arthritis. Collaboration with gastroenterologists is needed to shorten the diagnostic delay in patients with SpA and IBD. The recognition of the factors for the diagnosis of "IBD-related arthritis" may lead to the elucidation of the pathogenesis.

Effect of Prophylactic Dose of Trimethoprim-Sulfamethoxazole on Serum Creatinine in Japanese Patients With Connective Tissue Diseases.

Objectives: At normal doses of trimethoprim-sulfamethoxazole (TMP/SMX), trimethoprim inhibits tubular creatinine secretion, leading to a rapid but reversible increase in serum creatinine (SCr). Although patients with connective tissue diseases are often in the state of immunosuppression and TMP/SMX is an important prophylactic drug, clinicians often have to stop or reduce the dosage due to concerns regarding its effect on renal function. This study aimed to evaluate the effect of a prophylactic dose of TMP/SMX on SCr in Japanese patients with connective tissue diseases, the extent of SCr level elevation and the independent risk factors for creatinine elevation. Methods: A retrospective cohort study was undertaken. Participants included patients with connective tissue diseases who were treated with a prophylactic dose of TMP/SMX between 2004 and 2018. Using single and multiple regression analyses, the risk factors that affected SCr elevation were evaluated. Results: A total of 262 patients, females, n = 181; age, median (range) = 59 (19-89) years, were included. The median baseline SCr level before treatment was 0.62 (0.16-2.1) mg/dL. The median SCr elevation value was 0.07 (-0.54 to 0.84) mg/dL in 4 weeks after TMP/SMX initiation. Five (2%) participants had ⩾0.3 mg/dL SCr elevation. Multiple regression analyses, including age, baseline SCr, diuretic use, nonsteroidal anti-inflammatory drug use and diabetes mellitus, indicated that baseline SCr and advanced age were independent risk factors of SCr elevation. Conclusions: These results demonstrated that baseline SCr and advanced age were associated with SCr elevation by a prophylactic dose of TMP/SMX. However, a prophylactic dose of TMP/SMX rarely elevated the SCr level significantly. Therefore, other causes can be considered if patients show an SCr elevation ⩾0.3 mg/dL.

Nation-wide survey of the treatment trend of microscopic polyangiitis and granulomatosis with polyangiitis in Japan using the Japanese Ministry of Health, Labour and Welfare Database.

OBJECTIVES: In Japan, clinical records of patients with intractable diseases, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), are compiled into a database. This study aimed to understand the current treatment status and changes in treatment regimens from our previous survey. METHODS: Using data from 2012 and 2013, patients with new-onset MPA and GPA were extracted and analysed. RESULTS: We analysed 1278 MPA and 215 GPA patients. The average age was 71.7 and 62.7 years, respectively. Methylprednisolone pulse therapy was used in 51.2% of MPA patients and 40.5% of GPA patients; the initial prednisolone-equivalent glucocorticoid dose was 39.5 mg/day in MPA and 46.6 mg/day in GPA. Concomitant intravenous or oral cyclophosphamide (CY) was administered to 22.6% of MPA and 56.3% of GPA. Young age, bloody sputum, low serum creatinine, and high C-reactive protein levels were independently associated with CY use in MPA. Compliance with treatment protocol for Japanese patients with myeloperoxidase (MPO)-anti-neutrophilic cytoplasmic antibody-associated vasculitis study criteria or the 2011 clinical practice guidelines for rapidly progressive glomerulonephritis was 42.7% and 49.7%, respectively. CONCLUSIONS: MPA was more prevalent than GPA in the registry. Compared to patients with GPA, MPA patients were older and used CY less frequently. No apparent changes in treatment trends were observed from the previous survey.

Expanding the spectrum of reactive arthritis (ReA): classic ReA and infection-related arthritis including poststreptococcal ReA, Poncet's disease, and iBCG-induced ReA.

Reactive arthritis (ReA) is a form of sterile arthritis that occurs secondary to an extra-articular infection in genetically predisposed individuals. The extra-articular infection is typically an infection of the gastrointestinal tract or genitourinary tract. Infection-related arthritis is a sterile arthritis associated with streptococcal tonsillitis, extra-articular tuberculosis, or intravesical instillation of bacillus Calmette-Guérin (iBCG) therapy for bladder cancer. These infection-related arthritis diagnoses are often grouped with ReA based on the pathogenic mechanism. However, the unique characteristics of these entities may be masked by a group classification. Therefore, we reviewed the clinical characteristics of classic ReA, poststreptococcal ReA, Poncet's disease, and iBCG-induced ReA. Considering the diversity in triggering microbes, infection sites, and frequency of HLA-B27, these are different disorders. However, the clinical symptoms and intracellular parasitism pathogenic mechanism among classic ReA and infection-related arthritis entities are similar. Therefore, poststreptococcal ReA, Poncet's disease, and iBCG-induced ReA could be included in the expanding spectrum of ReA, especially based on the pathogenic mechanism.