Post-renal acute kidney injury complicated by urinary tract obstruction due to massive blood clots and severe thrombocytopenia in a patient with systemic lupus erythematosus: A case report.

Systemic lupus erythematosus (SLE) is often seen with antiphospholipid antibody syndrome (APS), and these conditions may occur concurrently with severe immune thrombocytopenia and even acute kidney injury (AKI); however, post-renal AKI due to bleeding is uncommon. Here, we describe a case of post-renal AKI and anuria in a patient with SLE and APS, which were attributable to urinary tract obstruction due to massive blood clots caused by secondary immune thrombocytopenia. A 50-year-old Japanese woman was admitted to our hospital with anuria, abdominal tenderness, purpura in the trunk and in both legs, and severe thrombocytopenia. She had been receiving medical treatment for APS and SLE till the age of 45 years. Computed tomography revealed a blood clot without extravasation in both urinary tracts and she was diagnosed with post-renal AKI due to complete obstruction of the urinary system. Additionally, based on her medical history, elevated platelet-associated IgG levels, and increased megakaryocyte count, she was diagnosed with secondary immune thrombocytopenia complicated by SLE and APS. She also had elevated APS-related autoantibodies, including antiphosphatidylserine/prothrombin IgM, and IgG. However, concomitant serositis such as lupus enteritis or cystitis was not seen. She was treated with a combination of glucocorticoids, intravenous immunoglobulin, and continuous hemodialysis/hemofiltration, which resulted in rapid improvement of her symptoms and renal dysfunction. Secondary immune thrombocytopenia-induced massive bleeding of urinary tract can cause post-renal AKI. Appropriate diagnosis and aggressive treatment are necessary to improve prognosis in such patients.

The impact of glucocorticoid use on the outcomes of rheumatoid arthritis in a multicenter ultrasound cohort study.

OBJECTIVE: Glucocorticoids are effective in treating rheumatoid arthritis (RA) when used appropriately considering the balance of the risks and benefits, especially at low doses. We aimed to evaluate the response of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients having already been treated with glucocorticoids. METHODS: We reviewed RA patients treated with b/tsDMARDs in a prospective multicenter ultrasound cohort study. We compared the differences in the clinical characteristics at baseline and outcomes at 12 months between the two groups having been treated with and without glucocorticoids at baseline. The differences in the clinical characteristics and the treatments were balanced by the inverse probability weighting (IPW) with the propensity score. RESULTS: Of 307 patients with RA, 160 patients were treated with glucocorticoids at baseline. The median dose of glucocorticoids was equivalent to 5.0 mg/day of prednisolone. Significant differences were in age and concomitant methotrexate use, composite measures for the disease activity, and the ultrasound grayscale score at baseline. Patients treated with glucocorticoids had less frequent remissions defined by composite measures and ultrasound findings than those treated without glucocorticoids. These significant differences in the achievement of remissions remained robust even after adjusting differences in the clinical characteristics and the treatments between the two groups by IPW. CONCLUSION: RA patients treated with glucocorticoids had a higher disease activity at baseline and a poorer response to treatments with b/tsDMARDs than those without glucocorticoids. The states of patients requiring glucocorticoids might be associated with the poor response to the b/tsDMARDs.

New-onset Systemic Lupus Erythematosus Manifestation Following COVID-19: A Case Report and Literature Review.

Coronavirus disease 2019 (COVID-19) is a respiratory viral disease, and several cases of autoimmune diseases have been reported after infection. This report presents the case of a 38-year-old Japanese woman who developed systemic lupus erythematosus (SLE) following COVID-19. Clinical manifestations included dermatological complications, joint pain, and positive autoantibodies. The patient met the SLE classification criteria, and renal involvement was observed. Her symptoms improved with immunosuppressive therapy. A literature review identified 10 similar cases, those with lymphopenia and renal involvement. SLE should be considered in patients with persistent nonspecific symptoms after COVID-19 infection, particularly when hematologic and renal involvement are present.

C5a stimulation induces caspase-1 activation and mature IL-1ß production in human peripheral blood mononuclear cells.

The complement component C5a contributes to the recruitment of immune cells to inflamed tissues and local inflammation. The proinflammatory cytokine interleukin (IL)-1ß is also related to inflammatory disorders through inflammasome activation. However, the association between inflammasome activation and C5a is unclear. Human peripheral blood mononuclear cells (PBMCs) were stimulated with C5a and measured for IL-1ß secretion by enzyme-linked immunosorbent assay (ELISA). The pro-IL-1ß expression in cell lysates was also examined by Western blot analysis. Similarly, magnetic bead-isolated CD14+ monocyte-depleted and lymphocyte-depleted PBMCs were stimulated with C5a, and immunoblot analysis was performed using an anti-cleaved-IL-1ß (p17) antibody. FACS was performed to detect caspase-1-activated cells. C5a-stimulated PBMCs produced IL-1ß in C5a concentration-dependent manner. The protein levels of pro-IL-1ß in the cell lysates were significantly increased. Furthermore, the cleaved-IL-1ß (p17) was faintly detected in the same lysates. Active caspase-1 was demonstrated in C5a-simulated CD14+ monocytes by FACS. Cleaved-IL-1ß (p17) was demonstrated in the supernatant of C5a-stimulated PBMCs. Lymphocyte-depleted PBMCs stimulated with C5a but monocyte-depleted PBMCs produced cleaved-IL-1ß (p17). C5a induced the production of mature IL-1ß in PBMCs. The IL-1ß production is mediated mainly by caspase-1 activation in CD14+ monocytes. These results suggest that C5a alone potentiates mature IL-1ß production mainly in monocytes.

Real-World Effectiveness of Belimumab in Patients with Active Lupus.

This study evaluated the real-world effectiveness of belimumab (BLM) in the treatment of systemic lupus erythematosus (SLE) patients with moderate to high disease activity. This retrospective cohort study enrolled 129 Japanese patients with moderate to high SLE disease activity who received BLM between January 2013 and March 2023. The clinical outcomes, including the flare-free survival, SLE Disease Activity Index 2000 (SLEDAI-2K) score, and prednisone-equivalent dose, in the BLM and mycophenolate mofetil (MMF) treatment groups were compared before and after treatment. Safety data for BLM were collected. Additionally, we compared the effectiveness of BLM and intravenous cyclophosphamide (IV-CY) treatment using the stabilized inverse probability of treatment weighting (IPTW) method based on the propensity scores. This observational study enrolled 129 patients with moderate/severe SLE: 48 patients received belimumab, 45 received IV-CY, and 36 received MMF and prednisolone for remission induction therapy. The median follow-up for the BLM group was 17.0 months. Among them, 19 received BLM plus MMF. BLM significantly reduced the mean SLEDAI-2K (from mean baseline to 52 weeks: 49.2% reduction from 12.8 to 6.5) and prednisone daily dose (from mean baseline to 52 weeks: 21.9% reduction from 12.8 to 10.0 mg/day). The flare-free survival at 52 weeks was not significantly different between the BLM and MMF groups. There was no significant difference in the flare-free survival rates or reduction rates of the SLEDAI-2K between the patients treated with BLM and those treated with BLM plus MMF. In the propensity score-matched comparative analyses, there was no significant difference in the flare-free survival rates or an estimated decline in the SLEDAI-2K scores between the patients with lupus treated with BLM and IV-CY. BLM may be a promising alternative treatment option for lupus patients with moderate or high disease activity who do not respond to conventional treatments.

Colchicine-resistant sacroiliitis in a Japanese patient with familial Mediterranean fever.

The articular involvement in patients with familial Mediterranean fever (FMF) represents a clinical characteristic of acute monoarthritis with pain and hydrarthrosis, which always resolves spontaneously. Colchicine prevents painful arthritis attacks in most FMF cases. Spondyloarthritis is rarely associated with Japanese patients with FMF. Here, we report a Japanese male patient with FMF-related axial joint involvement. A 43-year-old male Japanese patient who presented with recurrent febrile episodes with hip joint and back pain was referred to our hospital. He carried heterozygous variants in exon 2 (L110P/E148Q) of the MEFV gene. FMF was suspected, and oral administration of colchicine (1 mg/day) was initiated. Colchicine treatment improved his febrile attack with hip joint pain. He was diagnosed as having FMF based on the Tel-Hashomer diagnostic criteria for FMF since he fulfilled one major criterion (repeated febrile attack accompanied by hip joint pain) and one minor criterion (improvement with colchicine treatment). Although the human leucocyte antigen-B27 allele was not detected, sacroiliitis-related symptoms progressed despite the ongoing colchicine treatment. Salazosulphapyridine and methotrexate were administered in addition to colchicine; however, these treatments were not effective. Canakinumab treatment successfully resolved this unique aspect of sacroiliitis, and the patient was finally diagnosed with FMF-associated axial joint involvement.

Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study.

Background: The ORAL Surveillance trial showed a potentially higher incidence of malignancy and major adverse cardiovascular events (MACEs) associated with tofacitinib than those associated with tumor necrosis factor (TNF) inhibitors (TNFis). However, few studies have compared the safety of non-TNFis or other Janus kinase (JAK) inhibitors (JAKis). This study was aimed at comparing the incidence rates (IRs) of malignancies and MACEs in patients with rheumatoid arthritis (RA) treated using interleukin-6 (IL-6) inhibitors (IL-6is) or JAKis. Methods: We retrospectively analyzed 427 patients with RA who were treated using an IL-6i (n = 273) or a JAKi (n = 154). We determined the IRs of malignancy and MACEs, and the standardized incidence ratio (SIR) of malignancies and investigated factors related to malignancy and MACEs. After adjusting the clinical characteristic imbalance by propensity score matching (PSM), we compared the IRs of adverse events between the JAKi and IL-6i groups. Results: After PSM, the observational period was determined to be 605.27 patient-years (PY), and the median observational period was determined to be 2.28 years. We identified seven cases of malignancy (IR: 2.94 per 100 PY) in the JAKi-treated group and five cases (IR: 1.36 per 100 PY) in the IL-6i-treated group after PSM. The IR of MACEs was 2.56 and 0.83 (per 100 PY) in the JAKi- and IL-6i-treated groups. The IRRs of JAKi-treated patients versus IL-6i-treated patients were 2.13 (95% confidence interval (CI): 0.67-7.42) for malignancy and 3.03 (95% CI: 0.77-15.21) for MACE. There were no significant differences in IRR for malignancy and MACE between both groups after PSM. Univariate and multivariable Cox regression analyses revealed that older age and JAKi use were independent risk factors for malignancy, while older age, hypertension, and JAKi use were independent risk factors for MACEs. The overall malignancy SIR was significantly higher in the JAKi-treated group compared to the general population (2.10/100 PY, 95% CI: 1.23-2.97). Conclusion: The IRs of malignancy and MACE in patients with RA after PSM were comparable between IL-6i-treated and JAKi-treated patients. However, the SIR of malignancy in JAKi treatment was significantly higher than in the general population; therefore, further safety studies comparing JAKi to non-TNFi biologic disease-modifying antirheumatic drugs (bDMARDs) are needed.

Effectiveness of Colchicine or Canakinumab in Japanese Patients with Familial Mediterranean Fever: A Single-Center Study.

Background: To investigate the clinical features of Japanese patients with Familial Mediterranean Fever (FMF), we evaluated the frequency of attacks, treatment responses, and adverse effects in 27 patients with FMF treated with colchicine or canakinumab in a real-world clinical setting. Methods: We retrospectively reviewed 27 Japanese patients with FMF treated at our institute between April 2012 and June 2023. All patients were diagnosed with FMF according to the Tel-Hashomer criteria. We performed genetic analyses of the MEFV gene using targeted next-generation sequencing. The clinical response was monitored through the number of attacks, and inflammatory markers were monitored through the C-reactive protein (CRP), and serum amyloid A (SAA) concentrations. Colchicine resistance was defined as the presence of at least one attack/month despite administration of the maximum tolerated dose of colchicine for at least 6 months, and C-reactive protein and serum amyloid A levels above the normal range between attacks. Results: A total of 27 patients diagnosed with FMF were enrolled in this study and the median follow-up period was 36.4 months. The median attack frequency was 1.0 (interquartile range: 0.33-1.0) every 3 months before treatment initiation. All the patients (n = 27) were treated with colchicine. Among the 27 patients, 20 (71.8%) showed a clinical response and 7 (25.9%) showed an incomplete response with sufficient doses of colchicine (n = 5) and non-sufficient doses (n = 2). Two patients on non-sufficient doses were unable to increase colchicine to the maximum dose due to diarrhea and liver dysfunction. All seven patients achieved a reduction in attack frequency after the initiation of canakinumab. No serious adverse events associated with canakinumab treatment were observed. In these seven patients with colchicine-resistant FMF (crFMF), the MEFV exon 10 variant was not detected, and the absence ratio of the MEFV variant was significantly higher compared to those without crFMF. Conclusions: Colchicine was effective in 71.8% (20/27) of Japanese patients with FMF; however, the remaining patients (7/27) had crFMF. Canakinumab effectively controlled febrile attacks in crFMF, even in the absence of pathogenic MEFV exon 10 variants.

Drug Retention Rates and the Safety of Janus Kinase Inhibitors in Elderly Patients with Rheumatoid Arthritis.

BACKGROUND: We examined the real-world drug retention rate and safety data of Janus kinase inhibitors (JAKis) in elderly patients with rheumatoid arthritis (RA). METHODS: This study enrolled 133 RA patients (≥65 years) with sufficient clinical data who were initiated with JAKis during the study period. These patients were divided into two groups: the very elderly group (≥ 75 years) and the elderly group (65 ≤ years < 75). The drug retention rates of JAKis were compared using Kaplan-Meier curves. RESULTS: The discontinuation rates of JAKis were as follows: lack of effectiveness 27 (20.3%), adverse events (AEs) 29 (21.8%), and remission 2 (1.5%). There was no significant difference in the overall drug retention rate between the very elderly group (≥75 years) and the elderly group. Furthermore, the overall drug retention rates of JAKis were not affected by gender, methotrexate use, and anti-citrullinated protein/peptide antibody (ACPA) status. The discontinuation rates of JAKis due to AEs were comparable both in the very elderly group (≥75 years) and the elderly group (65 ≤ years < 75). Whereas chronic lung disease and hypoalbuminemia were independently associated with discontinuation rates due to AEs, the overall drug retention rates were significantly lower in patients treated with the approved dose of JAKis than in those treated with a reduced or tapered dose. CONCLUSIONS: Our results suggest that the overall drug retention rate of JAKis in very elderly patients (≥75 years) was comparable with that in elderly patients (65 ≤ years < 75). The discontinuation rates of JAKis due to AEs were also comparable both in very elderly group patients and elderly patients.

Drug Retention Rates of Janus Kinase Inhibitors in Rheumatoid Arthritis Patients with Therapy-Induced Lymphopenia.

OBJECTIVES: To determine whether drug-induced lymphocytopenia is associated with drug retention rates of JAKi (tofacitinib or baricitinib) in rheumatoid arthritis (RA) patients. METHODS: Patients with RA who were initiated with tofacitinib (n = 38) or baricitinib (n = 74) between July 2015 and July 2022 and continued for at least 4 months were enrolled in this study. Absolute lymphocyte count (ALC) value was obtained pre-treatment and monthly after initiation of JAKi (up to 4 months). Associations between ALC nadir at an early phase (up to 4 months) from JAKi initiation and drug retention rates were analysed. RESULTS: 112 patients (87 females; age, 71.2 ± 14.0 years; disease duration, 9.2 ± 10.5 months; DAS28-CRP, 3.60 ± 1.12; DAS28-ESR, 4.43 ± 1.29; CDAI, 17.9 ± 12.9; C-reactive protein, 3.07 ± 3.43 mg/dL; and lymphocyte count, 1361.9 ± 538.7 per µL) treated with tofacitinib or baricitinib were retrospectively analysed. Lymphocytopenia (>10% decline in lymphocyte count to pre-treatment basal levels) was observed in a quarter of RA patients treated with JAKi (tofacitinib; 16 baricitinib; 14). RA patients with lymphopenia were associated with the lower drug retention rates of tofacitinib compared to those without lymphocytopenia. The reduced drug retention rates in patients with lymphocytopenia were attributed to the discontinuation of tofacitinib due to AEs. Whereas lymphocytopenia was not associated with lower drug retention rates of baricitinib. Pre-treatment absolute lymphocyte counts did not affect the drug retention rates of JAKi in patients with RA. CONCLUSIONS: These findings suggest that lymphopenia during the first 4 months from the initiation of JAKi is associated with reduced drug retention rates in patients with RA due to AEs, which is exclusively associated with the use of tofacitinib.

Case report: Rapid development of amyloid A amyloidosis in temporal arteritis with SAA1.3 allele; An unusual case of intestinal amyloidosis secondary to temporal arteritis.

Temporal arteritis (TA) is a large-vessel vasculitis mostly seen in older patients. Amyloid A (AA) amyloidosis secondary to a chronic inflammation induces multiple organ dysfunctions, including a dysfunction of the gastrointestinal tract. Herein, we present a case of TA complicated by AA amyloidosis that was resistant to oral and intravenous steroids. An 80-year-old man with a history of new-onset headache, jaw claudication, and distended temporal arteries was referred to our department. On admission, the patient presented with tenderness and a subcutaneous temporal nodule in both temple arteries. Ultrasonography of the nodule revealed an anechoic perivascular halo surrounding the right temporal artery. Following the diagnosis of TA, high-dose prednisolone therapy was initiated. However, the patient presented with recurrent abdominal pain and refractory diarrhea. Due to the unclear origin of refractory diarrhea, an extensive workup, including biopsy of the duodenal mucosa, was performed. Endoscopy revealed chronic inflammation in the duodenum. Immunohistochemical analysis of duodenal mucosal biopsy samples revealed AA amyloid deposition resulting in the diagnosis of AA amyloidosis. After tocilizumab (TCZ) administration, refractory diarrhea reduced; however, the patient died of intestinal perforation 1 month after the start of TCZ administration. Gastrointestinal involvement was the main clinical manifestation of AA amyloidosis in the present case. This case highlights the importance of bowel biopsy screening for amyloid deposition in patients with unexplained gastrointestinal tract symptoms, even in a recent onset of large-vessel vasculitis. In the present case, the carriage of the SAA1.3 allele likely contributed to the rare association of AA amyloidosis with TA.

Transcription factor Fli-1 impacts the expression of CXCL13 and regulates immune cell infiltration into the kidney in MRL/lpr mouse.

OBJECTIVE: Friend leukaemia virus integration 1 (Fli-1) regulates chemokine/cytokine expression and thus plays an important role in the development of lupus nephritis. Chemokine CXC ligand 13 (CXCL13) is a chemokine that promotes the formation of ectopic lymphoid structures and has been reported to be associated with the pathogenesis of lupus nephritis. The relationship between Fli-1 and CXCL13 is unknown. This study aims to elucidate whether Fli-1 impacts CXCL13 expression and contributes to the progression of lupus-like nephritis in adult MRL/lpr mouse. METHODS: Serum CXCL13 levels were measured in adult wild-type (WT) MRL/lpr mice and Fli-1 heterozygote knockout (Fli-1+/-) MRL/lpr mice (4 months old or older) using ELISA. Renal mRNA expression (CXCL13 and related molecules) was measured using real-time PCR method. Kidneys were removed, stained and evaluated using a pathology scoring system. The grade of CXCL13 or CXC-chemokine receptor type 5 (CXCR5)-positive immune cell infiltration into the kidney was evaluated using immunostaining with anti-CXCL13 or anti-CXCR5 antibodies. We also used immunofluorescence staining with CXCL13- and CD11b-specific antibodies to detect the infiltration of CXCL13/CD11b double-positive immune cells. RESULTS: Serum CXCL13 levels in Fli-1+/- MRL/lpr mice were significantly lower than that in WT MRL/lpr mice (545.5 and 960.5 pg/mL, p=0.02). Renal expression of CXCL13 mRNA and SRY-related HMG box4 (Sox4) (an important factor for B-cell development) levels were significantly lower in Fli-1+/- MRL/lpr mice. Renal histology scores in WT MRL/lpr mice revealed significantly increased glomerular inflammation. Despite similar interstitial immune cell infiltration into the kidney, the number of CXCL13- and CXCR5-positive cells was significantly lower in Fli-1+/- MRL/lpr mice than in WT mice. Furthermore, immunofluorescence staining revealed that Fli-1+/-MRL/lpr mice had significantly fewer CXCL13/CD11b double-positive immune cells. CONCLUSION: Fli-1 regulates renal Sox4 mRNA expression and infiltration of CXCR5-positive cells as well as CXCL13/CD11b double-positive immune cells into the kidney, which affects CXCL13 expression and lupus-like nephritis.

Atypical Familial Mediterranean Fever Presenting with Recurrent Upper Back Pain: A Case Report.

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease that is characterized by recurrent episodes of fever, serositis, and synovitis. FMF synovitis attacks resemble the clinical presentation of acute monoarthritis with pain and hydrarthrosis, which always resolve spontaneously. In most cases, colchicine will prevent these painful arthritis attacks in FMF. However, distinguishing these arthritis episodes from other febrile attacks with various clinical manifestations, including serositis, is important. We describe a Japanese patient with FMF who presented a febrile attack with severe abdominal and upper back pain (peri-scapula lesion), without any other joint involvement. A 44-year-old female patient presented with recurrent episodes of fever with abdominal and back pain. She carried heterozygous variants in exon 3 of the MEFV gene (P369S/R408Q). She was diagnosed with FMF according to Tel-Hashomer's diagnostic criteria for FMF. Colchicine treatment improved her febrile attcks with peritonitis, however, severe back pain was sustained. This unique aspect of severe pain attack was successfully resolved by canakinumab treatment, which is a specific interleukin-1ß monoclonal antibody, and was finally diagnosed as FMF-related shoulder joint synovitis. Further investigations were needed to evaluate the effectiveness of interleukin-1 antagonists against colchicine-resistant arthritis in FMF patients.

Clinical Features and Outcomes of Japanese Patients with Giant Cell Arteritis: A Comparison with Takayasu Arteritis.

BACKGROUND: Giant cell arteritis (GCA) and Takayasu arteritis (TA) are distinct types of large-vessel vasculitis; however, the clinical features of the diseases have some similarities. Limited data are available regarding Japanese patients with GCA and TA. The present study aimed to compare the clinical features and outcomes of Japanese patients with GCA and TA and the effects of large vessel involvement (LVI). METHODS: We performed a retrospective cohort study of the patients with GCA (n = 15) and TA (n = 30) who visited our department from April 2012 to June 2022. Signs and symptoms attributed to the disease, treatment, clinical outcomes, and mortality were recorded using a standardized database. RESULTS: The median age of onset was significantly higher in the GCA group at 24 years (range, 16-72 years) in the TA group and 77 years (range, 57-89 years) in the GCA group (p < 0.001). There were no significant differences in survival rates or the cumulative rates of cardiovascular events between the GCA and TA groups. However, relapse-free survival rates were significantly higher in patients with GCA than in patients with TA. Seven of the 15 patients with GCA had large vessel involvement, which did not affect the survival rates. Prednisolone (PSL) doses were significantly decreased after induction therapy in both groups, and the rates of achieving steroid tapering (PSL < 5.0 mg/day) were significantly higher in patients with GCA compared with those in patients with TA. CONCLUSIONS: Our study demonstrated no significant difference in the survival rates of Japanese patients with GCA and TA. The relapse-free survival rates were significantly higher in the GCA group than in the TA group. LVI may not be associated with disease relapse or survival rate in Japanese patients with GCA.

Chemically Driven Ion Exchanging Synthesis of Na5YSi4O12-Based Glass-Ceramic Proton Conductors.

We have developed 12-membered silica-tetrahedra-ringed Na5YSi4O12-type sodium ion conducting glass-ceramics on the basis of the composition Na3+3x-yR1-xPySi3-yO9 (R: rare earth elements; denoted as Narpsio); especially, the material of Na4Y0.6P0.2Si2.8O9 with the combined parameters of (x, y) = (0.4, 0.2) gives rise to the maximum conductivity of 1 × 10-1 Scm-1 at 300 °C. Because glass-ceramics generally have the advantage of structural rigidity and chemical durability over sintered polycrystalline ceramics, the present study employed glass-ceramic Narpsio to perform chemically driven ion exchange of Na+ with protonated water molecules with an aim to produce a proton conductor. The ion exchange was carried out in a hydrochloric acid solution by changing immersion time, temperature, and acid concentration. The ion exchanged Na4Y0.6P0.2Si2.8O9-based glass-ceramics were analyzed by the complex impedance method, and the proton conductivity was found to exhibit 3 × 10-4 Scm-1 at 300 °C with the activation energy of 59 kJ/mol. The dependence of humidity-sensitive conductivity of the ion exchanged bulk glass-ceramics was also examined; the conductivity increased almost linearly from 0.6 × 10-4 Scm-1 in dry air to 1.5 × 10-4 Scm-1 in 75% humid ambience at 300 °C. Thus, the ion exchanged glass-ceramics can be considered to be high temperature proton conductors as well as humidity sensors.

Case report: Unusual development of hepatocellular carcinoma during immunosuppressive treatments against rheumatoid arthritis overlapping Sjögren's syndrome; cirrhotic steatohepatitis with liver inflammation and fibrosis lurks in autoimmune disorders.

The sequential progression from chronic liver disease to cirrhosis may be a risk factor for hepatocellular carcinoma (HCC) development. Although HCC originates from hepatitis B virus- or hepatitis C virus-associated liver cirrhosis, it has recently been reported in patients with non-alcoholic steatohepatitis (NASH) with advanced fibrosis. However, little is known about the pathophysiological mechanisms linking HCC to rheumatic disorders, including rheumatoid arthritis (RA). Herein, we describe the case of HCC with NASH complicated by RA and Sjögren's syndrome (SS). A fifty-two-year-old patient with RA and diabetes was referred to our hospital for further examination of a liver tumor. She received methotrexate (4 mg/week) for 3 years and adalimumab (40 mg/biweekly) for 2 years. On admission, laboratory data showed mild thrombocytopenia and hypoalbuminemia, with normal hepatitis virus markers or liver enzymes. Anti-nuclear antibodies were positive with high titers (x640), and anti-SS-A/Ro (187.0 U/ml; normal range [NR]: ≤6.9 U/mL) and anti-SS-B/La (320 U/ml; NR: ≤6.9 U/mL) antibodies were also high. Abdominal ultrasonography and computed tomography revealed liver cirrhosis and a tumor in the left lobe (S4) of the liver. She was diagnosed with HCC based on imaging findings, and elevated levels of protein induced by vitamin K absence- II (PIVKA-II) were detected. She underwent laparoscopic partial hepatectomy, and histopathological examination revealed steatohepatitis HCC with background liver cirrhosis. The patient was discharged on the 8th day post-operation without any complications. At the 30 months follow-up, no significant evidence of recurrence was observed. Our case suggests that clinical screening for HCC is needed in patients with RA who are at a high risk of NASH, as they may progress to HCC even without elevated liver enzymes.

Adult-onset Still's Disease with Acute Kidney Injury Requiring Hemodialysis: A Case Report and Literature Review.

Adult-onset Still's disease (AOSD) is characterized by high spiking fever, evanescent rash, and arthritis. However, AOSD rarely presents with severe acute kidney injury (AKI). We herein present the case of a 56-year-old woman with new-onset AOSD who rapidly developed AKI. A physical examination and laboratory data revealed spiking fever, evanescent rash, thrombocytopenia, hyperferritinemia, and azotemia. The patient was diagnosed with AOSD complicated by AKI and macrophage activation syndrome. Treatment with high-dose steroids, hemodialysis, and plasma exchange successfully resolved her AKI. In this report, we review previously published reports on AOSD accompanied by AKI and discuss this rare complication in AOSD.

Rapid Clinical Improvement of Multicentric Castleman Disease (MCD) with Renal Involvement Following Treatment with Tocilizumab: AA Amyloidosis as a Possible Renal Involvement of MCD.

Castleman disease (CD) is a lymphoproliferative disorder that manifests as hypergammaglobulinemia and severe inflammation with multiorgan involvement. However, renal involvement has been infrequently described in CD. We present a case of a 63-year-old Japanese male patient with multicentric CD (MCD) in whom kidney involvement, including impaired renal function and massive proteinuria, is present. He had a 2-year history of inflammatory arthritis and was referred to our clinic with newly developed proteinuria, renal dysfunction, and elevated levels of acute-phase proteins. Abdominal computed tomography scan revealed hepatosplenomegaly, including mesenteric and inguinal lymph node enlargements. The patient underwent inguinal lymph node resection. Excisional biopsy of the inguinal lymph node showed multiple lymphoid follicles and expansion of interfollicular areas by marked plasmacytosis consistent with mixed type CD. The patient was diagnosed with human herpes virus 8-negative MCD according to the international diagnostic criteria for CD. Diagnostic renal biopsy was not performed following the medical viewpoint. Tocilizumab (TCZ) treatment was highly effective in reducing proteinuria and stabilizing renal function, as well as improving other clinical symptoms. The patient responded to TCZ treatment, and the renal involvement was rapidly improved. Our preliminary immunohistochemical analysis indicated AA amyloid deposits in urinary epithelial cells suggesting a possible renal involvement of AA amyloidosis. TCZ could potentially be one of the therapeutic options in patients with MCD with renal involvement.

Severe Enteritis after Cyclophosphamide Administration in a Patient with Microscopic Polyangiitis: A Case Report and Literature Review.

Severe enteritis is a rare side effect of cyclophosphamide (CPA) therapy, and only two cases have been reported to date. We herein report a 60-year-old man who developed severe enteritis after intravenous CPA administration for microscopic polyangiitis. He was successfully treated by discontinuation of CPA administration and long-term intensive supportive care. A diagnosis of CPA-associated enteritis was made based on the clinical course and imaging and pathological findings. This review of three cases of CPA-related enteritis, including our case, suggests that prompt CPA discontinuation and intensive systemic management are necessary when patients have gastrointestinal symptoms after CPA administration.

Effectiveness of combination tocilizumab and glucocorticoids as an induction therapy in patients with Takayasu arteritis: An observational study.

BACKGROUND: The efficacy of tocilizumab (TCZ) in the treatment of Takayasu arteritis (TA) was demonstrated in randomized controlled trials. The objective of this study was to analyse the effectiveness of combining TCZ with glucocorticoids (GC) as induction therapy in patients with TA. METHOD: This was a retrospective observational study including 32 patients with newly diagnosed TA. Clinical effectiveness of TCZ in maintaining relapse-free remission and GC-tapering were compared between patients who were treated with TCZ plus GC and those who were treated with GC with or without immunosuppressants. RESULTS: The study comprised 32 patients (27 women/5 men) with a median age of 25.5 years (range, 13-72). In the TCZ group (n = 14), patients received TCZ in combination with GC as an induction therapy. In the non-TCZ group (n = 18), patients were treated with single-agent GC or GC plus immunosuppressant. In the matched analysis, relapse-free survival rate was significantly higher in the TCZ group as compared to the non-TCZ group during GC taper. CONCLUSION: TCZ, in combination with GC, would be an effective alternative induction regimen for patients with TA.