Successful treatment of chronic lupus myocarditis with prednisolone and mizoribine

A 36-year-old female patient who was diagnosed with chronic myocarditis as an initial manifestation of systemic lupus erythematosus (SLE) was admitted to our hospital. At her third occurrence of heart failure, we performed an endomyocardial biopsy and proved chronic myocarditis with SLE. Subsequently, she was treated with prednisolone and the immunosuppressive agent mizoribine (MZR), and her cardiac function improved. We describe for the first time treatment with MZR for chronic cardiac involvement of SLE

Successful treatment of sepsis-induced disseminated intravascular coagulation in a patient with idiopathic thrombocytopenic purpura using recombinant human soluble thrombomodulin

Disseminated intravascular coagulation (DIC) may complicate a variety of disorders that contribute to mortality, particularly those related to bleeding. It is therefore very difficult to manage DIC in patients with known bleeding disorders. We treated a 62-year-old woman with idiopathic thrombocytopenic purpura (ITP) complicated with sepsis-induced DIC. She had been diagnosed with ITP 8 months prior to admission. Laboratory tests showed an elevation of d-dimer and endotoxin, while pyelonephritis was shown by abdominal computed tomography. Escherichia coli was detected by blood culture. Based on these findings, the patient was diagnosed with sepsis-induced DIC due to urinary tract infection. Thrombocytopenia was refractory despite the use of antibiotics and platelet transfusion, but it was promptly improved in response to recombinant human soluble thrombomodulin (rTM). We suggest that rTM provides a new therapeutic strategy for DIC patients with high hemorrhagic risk

Decrement of serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis (RA) patients achieving remission after 6 months of etanercept treatment: Comparison with CRP, IgM-RF, MMP-3 and anti-CCP Ab.

OBJECTIVE: The aim of this study was to evaluate whether serum COMP can estimate the therapeutic response of RA after 6 months of treatment with etanercept. METHODS: Forty-five RA patients receiving 25mg of etanercept twice a week for 6 months were registered in this prospective observational study. Clinical response to the therapy was evaluated by DAS 28. Laboratory variables- COMP, CRP, ESR, IgM-RF, MMP-3, and anti-CCP Ab -were assessed at baseline and after 6 months of treatment. We assessed the correlations between serum COMP and other variables and whether serum COMP is associated with DAS28 remission. RESULTS: Serum COMP correlated with DAS28-ESR (p2.6). The decrement of serum COMP at 6 months was significant in the remission group (N=10) but not in the non-remission group (N=35). On the other hand, CRP, ESR and MMP-3 decreased at 6 months regardless of remission status. IgM-RF titer as well as anti-CCP Ab titer did not differ at 6 months. CONCLUSIONS: Serum COMP at baseline reflects clinical disease activity of RA. Serum COMP is a valuable serologic marker to identify the subset of RA patients achieving remission during treatment with etanercept

Real-world comparative effectiveness and safety of tofacitinib and baricitinib in patients with rheumatoid arthritis

Objective: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting.Methods: A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks.Results: The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, −0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated.Conclusions: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings

Prediction of DAS28-ESR remission at 6 months by baseline variables in patients with rheumatoid arthritis treated with etanercept in Japanese population

We tried to determine which baseline variables are responsible for remission induction at 6 months in unselected rheumatoid arthritis (RA) patients of Japanese population treated with etanercept. One hundred forty-one patients with RA who were administered etanercept were registered. Thirty-four patients were started on etanercept monotherapy, 60 patients on cotherapy with methotrexate (MTX) (MTX cotherapy), and 47 patients on cotherapy with other non-MTX nonbiologic disease-modifying antirheumatic drugs (DMARDs) (non-MTX cotherapy). None of the patients were treated with both MTX and non-MTX nonbiologic DMARDs at entry. Outcome was set as achievement of disease activity score 28 (DAS28)-ESR remission at 6 months. We examined association of gender, DAS at baseline, MTX cotherapy at baseline, non-MTX cotherapy at baseline, and prednisolone use at baseline with achievement of remission at 6 months by logistic regression analysis. All subjects were classified as having high (N = 109) or moderate disease activity (N = 32) at entry. One hundred twenty out of 141 patients (85.1%) continued treatment with etanercept at 6 months. Continuation rate was statistically higher in MTX cotherapy (93.3%) compared with etanercept monotherapy (73.5%), and tended to be higher than with non-MTX cotherapy (85.1%). Logistic regression analysis identified that MTX cotherapy at entry and moderate disease activity at entry were independent variables for remission induction at 6 months. Accordingly, DAS28-ESR at 6 months was significantly lower with MTX cotherapy as compared with etanercept monotherapy or non-MTX cotherapy. To a lesser extent, DAS28-ESR with non-MTX cotherapy at 6 months was lower than with etanercept monotherapy. In this study of unselected patients, use of MTX and moderate disease activity at entry were associated with higher likelihood of response to etanercept. Non-MTX nonbiologic DMARDs may be an alternative in RA patients administrated etanercept who are intolerant to MTX

HTLV-I production based on activation of integrin/ligand signaling in HTLV-I-infected T cell lines derived from HAM/TSP patients.

OBJECTIVE: Activity of integrin/ligand signaling leading to activation of small GTPases might regulate the efficiency of cell-to-cell spread of human T lymphotropic virus type I (HTLV-I) through the virological synapse. We compared both activity of small GTPases and involvement of integrin/ligand signaling in extracellular release of HTLV-I virions between each three HTLV-I-infected T cell lines derived from HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and from other origins as a control. METHODS: Activity of small GTPases (Rho, Rac and Cdc42) was analyzed by pull-down assay with suppressive effect of both HTLV-I production and HTLV-I tax mRNA expression by anti-integrin-blocking antibodies. RESULTS: All small GTPases were strongly activated in all cell lines derived from HAM/TSP patients, but not in control cell lines except one cell line. Treatment of all cell lines derived from HAM/TSP patients, but not all control cell lines, with anti-integrin-blocking antibodies significantly suppressed the level of HTLV-I p19 antigen in culture supernatants without downregulation of HTLV-I tax mRNA expression. CONCLUSION: Significant involvement with integrin/ligand signaling in extracellular release of HTLV-I virions in cell lines derived from HAM/TSP patients suggests that HTLV-I-infected cells in HAM/TSP patients have the potential for the efficient spread of HTLV-I to uninfected cells

Disulfide-mediated apoptosis of human T-lymphotrophc virus type-I (HTLV-I)-infected cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.

BACKGROUND: This study was conducted to construct a basis for a therapeutic strategy against human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) using a compound that contained a disulfide moiety, prosultiamine, which is a homologue of allithiamine originally synthesized by allicin and thiamine-thiol, for the targeting of HTLV-I-infected cells. METHODS: First, we analysed the apoptotic pathway in allicin or prosultiamine treatment against an HTLV-I-infected T-cell line (HCT-1), derived from an HAM/TSP patient, by flow cytometry and western blot. Second, we evaluated the effect of targeting HTLV-I-infected cells in a prosultiamine in vitro treatment and in a clinical trial in HAM/TSP patients by quantitative PCR analysis of HTLV-I proviral load. RESULTS: Prosultiamine, like allicin, induced caspase-dependent apoptosis against HCT-1 cells. The fact that the loss of mitochondrial membrane potential was recovered in z-VAD-fmk-pretreated HCT-1 cells with prosultiamine treatment suggested that prosultiamine can induce caspase-dependent apoptosis through the mitochondrial pathway. On the basis of data showing that prosultiamine in vitro treatment against peripheral blood CD4(+) T-cells of HAM/TSP patients induced a significant decrease of HTLV-I proviral copy numbers by apoptosis of HTLV-I-infected cells, we treated six HAM/TSP patients with intravenous administration of prosultiamine for 14 days. As a result of this treatment, the copy numbers of HTLV-I provirus in peripheral blood decreased to approximately 30-50% of their pretreatment levels with some clinical benefits in all patients. CONCLUSIONS: Our results suggest that prosultiamine has the potential to be a new therapeutic tool that targets HTLV-I-infected cells in HAM/TSP

Comparative analysis of renal decline rates in microscopic polyangiitis: unveiling the slowly progressive phenotype

Although rapidly progressive glomerulonephritis (RPGN) is the main renal phenotype of microscopic polyangiitis (MPA), we aim to clarify the clinical features of slowly progressive MPA. This retrospective observational study included 12 patients diagnosed with MPA in our hospital between January 2012 and February 2022. We investigated the differences in surrogate markers, rate of decline of estimated glomerular filtration rate (eGFR) between the slowly progressive and rapidly progressive MPA groups. Of the 12 patients with MPA, 3 (25.0%) had slowly progressive MPA: MPA within 30% decrease in eGFR 3 months pretreatment, all of whom developed RPGN during the course. Patients with slowly progressive MPA had lower levels of C-reactive protein, myeloperoxidase anti-neutrophil cytoplasmic antibodies, and interleukin-6; higher levels of sialylated carbohydrate antigen KL-6. Slowly progressive MPA is not uncommon in our hospital. A linear relationship was found between slower rate of eGFR decline and lower surrogate markers of disease activity. Some MPA cases have slowly progressive glomerulonephritis leading to RPGN, which may be clinically characterized by low disease activity. It may be useful to measure myeloperoxidase anti-neutrophil cytoplasmic antibody in chronic kidney disease with concomitant urinary abnormalities to diagnose MPA with slowly progressive glomerulonephritis