Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rheumatoid arthritis: a retrospective review of 15 cases and analysis of risk factors.

OBJECTIVES: The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy. METHODS: We conducted a multicenter, case-control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy. RESULTS: PCP developed within 26 weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ≥65 years [hazard ratio (HR) 3.35, p = 0.037], coexisting lung disease (HR 4.48, p = 0.009), and concomitant methotrexate treatment (HR 4.68, p = 0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p < 0.001 for patients with two or more risk factors vs. those with no risk factor, and p = 0.001 for patients with one risk factor vs. those with no risk factor). CONCLUSION: Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present.

Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rheumatoid arthritis: a retrospective review of 15 cases and analysis of risk factors.

Objectives The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy. Methods We conducted a multicenter, case-control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy. Results PCP developed within 26 weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ≥ 65 years [hazard ratio (HR) 3.35, p = 0.037], coexisting lung disease (HR 4.48, p = 0.009), and concomitant methotrexate treatment (HR 4.68, p = 0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p < 0.001 for patients with two or more risk factors vs. those with no risk factor, and p = 0.001 for patients with one risk factor vs. those with no risk factor). Conclusion Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present.

Reduced long-term care cost by social participation among older Japanese adults: a prospective follow-up study in JAGES.

OBJECTIVES: Reducing costs related to functional disabilities and long-term care (LTC) is necessary in ageing societies. We evaluated the differences in the cumulative cost of public LTC insurance (LTCI) services by social participation. DESIGN: Prospective observational study. SETTING: Our baseline survey was conducted in March 2006 among people aged 65 or older who were not eligible for public LTCI benefits and were selected using a complete enumeration in Tokoname City, Japan. We followed up with their LTC services costs over a period of 11 years. Social participation was assessed by the frequency of participation in clubs for hobbies, sports or volunteering. We adopted a classical linear regression analysis and an inverse probability weighting (IPW), with multiple imputation of missing values. PARTICIPANTS: Functionally independent 5377 older adults. PRIMARY OUTCOME MEASURES: The cumulative cost of public LTCI services for 11 years. RESULTS: Even when adjusting for the confounding variables, social participation at the baseline was negatively associated with the cumulative cost of LTCI services. The IPW model showed that in respondents who participated in hobby activities once a week or more, the cumulative cost of LTCI services for 11 years was lower, approximately US$3500 per person, in comparison to non-participants. Similarly, that in respondents who participated in sports group or clubs was lower, approximately US$6000 than non-participants. CONCLUSIONS: Older adults' participation in community organisations may help reduce future LTC costs. Promoting participation opportunities in the community could ensure the financial stability of LTCI services.

Multicenter, observational clinical study of abatacept in Japanese patients with rheumatoid arthritis.

The aim of this study was to assess abatacept in rheumatoid arthritis (RA) patient. Patients (20 men, 89 women, aged 61.9 ± 10.4 y) who responded inadequately to conventional synthetic disease-modifying anti-rheumatic drug were treated with abatacept for 24-months. Disease activity score in 28 joints (DAS28-CRP) was evaluated. Of 109 patients, 82 (75.2%) were on methotrexate (MTX; mean dosage 9.0 ± 2.7 mg/week); 48 (44.0%) were naive to biologics and 61 (56.0%) had failed biologics. The 1- and 2-year retention rates were 77% and 53%, respectively. At 24-months, the DAS28-CRP remission rates were 54.5% in the biologic-naïve patients, and 28.2% in the biologic-failure patients (p < .01), while the structural remission rates were 83.9% and 73.1%, respectively (p = .461). Abatacept was equally effective in RA patients who were and were not on concomitant MTX. Biologic-naïve was associated with better clinical outcome. Abatacept was effective in patients who showed decreasing anti-CCP antibody titers or serum MMP-3 levels during treatment. Infection was the most frequent adverse effect of abatacept therapy. In conclusion, abatacept is more effective in biologic-naïve than in biologic-failure RA patients with or without concomitant use of MTX. Abatacept is more effective in RA patients with than without decreasing serum MMP-3 or anti-CCP antibody titers during treatment.

Exposure to positively- and negatively-charged plasma cluster ions impairs IgE-binding capacity of indoor cat and fungal allergens.

BACKGROUND: Environmental control to reduce the amount of allergens in a living place is thought to be important to avoid sensitization to airborne allergens. However, efficacy of environmental control on inactivation of airborne allergens is not fully investigated. We have previously reported that positively- and negatively-charged plasma cluster ions (PC-ions) reduce the IgE-binding capacity of crude allergens from Japanese cedar pollen as important seasonal airborne allergens. Cat (Felis domesticus) and fungus (Aspergillus fumigatus) are also important sources of common airborne allergens in living spaces throughout the year, and early sensitization with those allergens is considered to be a risk factor for future development of allergic rhinitis, pollinosis and asthma. The aim of this study is to examine whether the PC-ions reduce the IgE-binding capacity of a cat major allergen (Fel d 1) and fungal allergens in an experimental condition. METHODS: Fel d 1, crude fungal extract, or a fungal major allergen Asp f 1, was treated with PC-ions for 6 h in an experimental cylindrical apparatus. Sham-treated allergens were prepared in the same experimental apparatus without generation of PC-ions. The degradation of the PC-ions-treated Fel d 1 was analyzed by SDS-PAGE, and the IgE-binding capacity of the PC-ions-treated allergens was analyzed by ELISA inhibition assay. RESULTS: Exposure of Fel d 1, crude fungal extract and Asp f 1 to PC-ions significantly decreased protein content of Fel d 1 or Asp f 1, respectively. SDS-PAGE analysis suggested that the decreased Fel d 1 content upon exposure with PC-ions was attributable to protein degradation. ELISA inhibition indicated that the PC-ions treatment significantly impaired IgE-binding capacities of Fel d 1, crude fungal allergens, and Asp f 1 compared to sham treatment. DISCUSSION: Our data suggest that treatment with PC-ions not only reduce indoor cat and fungal allergens, but also impair their allergenicity. CONCLUSION: These results suggest that environmental control with PC-ions is useful for inactivation of indoor cat and fungal allergens.

Paradoxical triiodothyronine suppression of S14 transcription in permanent hepatic cell lines.

Both in vivo and in primary rat hepatocyte culture, carbohydrate and triiodothyronine (T(3)) rapidly induce transcription of the rat S14 gene. To determine if regulation of this gene by T(3) is similar in human liver cells, we transfected the S14 upstream region into HepG2 cells. We chose this cell line because many others have used this cell line to study the effect of thyroid hormone on hepatic gene expression. We found that changing media glucose concentration did not affect S14 transcription. Furthermore, addition of T(3) to HepG2 cells caused a marked reduction of rat S14 transcription. This paradoxical reduction was dependent on cotransfection of the T(3) receptor. We obtained similar results in the other human hepatoma cell lines, HuH-7 and Hep3B. The paradoxical response was not limited to human cells. We found a similar response in the nonmalignant permanent mouse liver cell line, AML-12. This paradoxical response was specific to the S14 gene because transfection of all the cell lines with a CAT or luciferase reporter driven by a mouse mammary tumor virus promoter containing 1 or 4 copies of a palindromic thyroid hormone response element (TRE) showed marked induction by T(3). Our results show that T(3) abnormally regulates the S14 gene in proliferating liver cell lines of diverse origins. This paradoxical regulation by T(3) is caused by an interaction between T(3) and the thyroid hormone receptor. The factors that lead to this paradoxical response are not active in primary hepatocytes and normal intact liver.

CD40-CD40 ligand signal induces the intercellular adhesion molecule-1 expression through nuclear factor-kappa B p50 in cultured salivary gland epithelial cells from patients with Sjögren's syndrome.

The purpose of this study is to clarify signal transduction of expression of the intercellular adhesion molecule-1 (ICAM-1) via CD40-CD40 ligand in salivary glands of patients with Sjögren's syndrome (SS). We used cultured salivary gland epithelial cells (SG cells) from 15 SS patients and 8 controls obtained by labial minor salivary gland biopsy. First, ICAM-1 expression was determined with reverse transcriptase-polymerase chain reaction and flow cytometry in the presence or absence of soluble CD40L (sCD40L). Next, SG cells were transfected with plasmids of pGL1.3-Luc inserted with promoter region of ICAM-1, pGL1.3kB(-)-Luc mutated in nuclear factor kappa-B (NF-kappaB) binding site of pGL1.3-Luc and pNF-kappaB-Luc by lipofection method. Luciferase activity of the cells was measured in the presence or absence of sCD40L or sCD40L and an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC). Finally NF-kappaB family proteins of cell nuclear extracts were determined. ICAM-1 expression was significantly enhanced with sCD40L at the mRNA and protein level. Activity of pNF-kappaB-Luc and pGL1.3-Luc was significantly elevated by stimulation with sCD40L and suppressed by PDTC. NF-kappaB p50 protein level was elevated by stimulation with sCD40L and suppressed by PDTC. Our results suggest that sCD40L enhances the ICAM-1 expression by activation of NF-kappaB p50 in the SS SG cells.

A case of idiopathic hypertrophic cranial pachymeningitis manifested only by positive rheumatoid factor and abnormal findings of the anterior falx.

In this report, we present a rare case of a 52-year-old man with a unique form of hypertrophic pachymeningitis involving the anterior part of the falx and who was positive for rheumatoid factor. The clinical symptom was only headache, without any cranial nerve palsies or ataxia. Diagnosis was made by gallium scintigraphy and magnet resonance imaging but was not confirmed by dural biopsy. Treatment with corticosteroid alone was extremely effective for him, while in most cases hypertrophic pachymeningitis recurs or progresses despite the treatment.

Corticosteroid-resistant multiple colonic ulcers in a patient with systemic lupus erythematosus/systemic sclerosis overlap syndrome effectively treated with intravenous cyclophosphamide pulse therapy.

Abstract We report a rare case of a 17-year-old female with overlap syndrome (systemic lupus erythematosus and systemic sclerosis) who developed severe abdominal pain and bloody diarrhea accompanied by central nervous system lupus. Colonoscopy revealed multiple irregular and linear ulcers throughout the colon, which were resistant to corticosteroid pulse therapy and plasma exchange. The patient finally recovered after treatment with a relatively low dose of monthly intravenous cyclophosphamide (250 mg/m(2)) pulse therapy.