Effectiveness and safety of adalimumab in Japanese patients with rheumatoid arthritis: retrospective analyses of data collected during the first year of adalimumab treatment in routine clinical practice (HARMONY study)

We retrospectively investigated the ability of adalimumab (ADA) to reduce disease activity, improve physical function, and retard the progression of structural damage in 167 patients with rheumatoid arthritis. Clinical and functional outcomes were compared between patients with or without prior biologic treatment and those with or without concomitant methotrexate (MTX) treatment. At week 52, 38.3% achieved clinical remission: 42.4 and 28.6% of patients achieved remission in those without and with previous biologics, respectively, while 42.7 and 12.5% of patients achieved remission in those with and without concomitant MTX, respectively. ADA treatment significantly reduced the rate of radiographic progression from 27.1 ± 46.0 (median 13.6; 25th-75th percentiles 8.3 to 28.9) at baseline to 0.8 ± 5.0 (median 0.0; 25th-75th percentiles -0.9 to 2.0) at week 52 (P < 0.0001). Radiographic progression was absent in 59.8% of patients. Sixty adverse events (34.21/100 patient-years) were reported, 16 of which were serious (9.12/100 patient-years). ADA therapy is highly effective for reducing disease activity, improving physical function, and limiting radiographic progression. It is generally safe and well tolerated by Japanese RA patients in routine clinical practice.     

Comparison of characteristics and therapeutic efficacy in rheumatoid arthritis patients treated by rheumatologists and those treated by orthopedic surgeons under a team medicine approach at the same institute

The treatment of rheumatoid arthritis (RA) has improved dramatically with the advent of the latest generation of disease-modifying antirheumatic drugs. Despite these advances, in some patients inflammation is not diminished sufficiently to prevent irreversible musculoskeletal damage, thereby necessitating surgical intervention to reduce pain and improve function. For RA treatment, Japanese orthopedic surgeons also prescribe medication. In this study, we examined whether this Japanese system is effective for RA treatment. We analyzed the clinical condition of RA patients treated by rheumatologists and those treated by orthopedists in a linked registry study using information from a large observational cohort of RA patients followed every half year from 2000 to 2010 (the IORRA cohort). Two groups of patients were compared: patients treated by rheumatologists (rheumatologic group) and patients treated by orthopedists (orthopedic group). The results revealed that patients in the orthopedic group were older, more likely to be female, and had a longer disease duration than patients in the rheumatologic group. The proportion of patients with a history of joint surgery was also much higher in the orthopedic group than in the rheumatologic group. The average scores on the Japanese version of the Health Assessment Questionnaire, and the remission ratio determined using a Boolean-based definition gradually increased from 2000 until 2010, and these findings were consistently better in the rheumatologic group than in the orthopedic group. These data suggest that patients treated primarily by orthopedists are more likely to have long-standing RA compared to patients treated by rheumatologists. Therefore, it is critical for rheumatologists and orthopedists to complement each other medically in the treatment of RA patients.     

Effects of Long-Term Pravastatin Treatment on Serum and Urinary Monocyte Chemoattractant Protein-1 Levels and Renal Function in Type 2 Diabetic Patients with Normoalbuminuria

To explore the renoprotective and anti-inflammatory effects of pravastatin, we analyzed the changes in renal function and urinary monocyte chemoattractant protein-1 (MCP-1) level as a renal tubulointerstitial inflammatory biomarker and serum MCP-1 level as a systemic inflammatory biomarker following the introduction of treatment with 10 mg/day of pravastatin in 10 hyperlipidemic type 2 diabetic patients with normoalbuminuria. Twelve months of the pravastatin treatment did not affect urinary levels of albumin, transferrin, N-acetylglucosaminidase, or MCP-1 in the hyperlipidemic diabetic patients, whereas the treatment significantly reduced serum levels of MCP-1 in the patients. The pravastatin treatment effectively lowered low-density lipoprotein cholesterol (LDL-C) levels in the hyperlipidemic diabetic patients to levels nearly to those in 11 non-hyperlipidemic type 2 diabetic patients with normoalbuminuria. Interestingly, serum MCP-1 levels were significantly lower in the hyperlipidemic patients treated with pravastatin than in the non-hyperlipidemic patients. No significant correlation was observed between serum LDL-C and MCP-1 levels in all the data in the hyperlipidemic patients before and after the pravastatin treatment and in the non-hyperlipidemic patients. These results collectively indicate that pravastatin may ameliorate systemic vascular inflammation rather than local renal inflammation in hyperlipidemic type 2 diabetic patients with normoalbuminuria, independent of its cholesterol-lowering effects.     

Hyponatremia at admission is associated with in-hospital death in patients with hip fracture

Purpose

Hyponatremia in hospitalized patients has been reported to be associated with in-hospital mortality. We studied patients treated at our hospital for hip fracture regarding the factors related to hyponatremia at admission.

Methods

Among 580 patients aged 60 years or above who were admitted to our hospital since January 1997 for treatment of hip fracture, 512 patients (110 males, 402 females) from whom serum sodium level at admission was available were studied. In 512 patients, the age at injury ranged from 60 to 103 (mean 82.6) years. Fracture types were femoral neck fracture in 191 patients, and trochanteric fracture in 321. These patients were divided into two groups by the blood sodium level at admission: a hyponatremia group with sodium levels lower than 135 mEq/L, and a normonatremia group with sodium levels within normal range. The age, gender, fracture type, residence before injury, pre-injury walking capability, anemia at admission, liver function, kidney function, inflammatory status, urinary glucose status, lung disease, ECG abnormality, systemic chronic disease, status of dementia, treatment modality, hospital stay (days), and in-hospital death were investigated. First a univariate study was conducted to identify the factors that differ significantly between the two groups. Then multivariate analysis was conducted using the parameters with significant difference as independent variables

Results

Hyponatremia was found in 49 of 512 (9.6 %) patients. In univariate analyses, six factors (age; residence before injury; anemia; dementia; treatment modality; in-hospital death) were significantly different between the hyponatremia group and normonatremia group. Multivariate analysis identified in-hospital death [odds ratio (OR) = 3.64, p = 0.035] and age (OR = 1.05, p = 0.029) as independently associated with hypernatremia.

Conclusion

Hyponatremia at admission is prevalent in old aged patients with fracture, and is related to in-hospital death.     

Primary amyloidoma in epidural and paravertebral space of the lumbar spine

Background context

Localized amyloid deposits result in a mass, that is, so-called amyloidoma; it has been reported in every anatomic site, although systemic amyloid deposition is much more common. However, primary lumbar epidural amyloidoma without bony involvement is extremely rare. To the best of our knowledge, only one case has been reported previously.

Purpose

To report and review the clinical presentations, imaging studies, and treatment of epidural and paravertebral amyloidoma.

Study design

A case report and review of the literature.

Methods

Lumbar epidural and paravertebral amyloidoma in a 75-year-old man with neurologic compromise is presented. Laminectomy with mass resection was performed.

Results

After surgery, almost complete neurologic improvement was observed. Histologically, definite diagnosis was obtained only after the specific staining of tissue. No sign of local recurrence was evident 1 year after surgery.

Conclusions

Primary amyloidoma, although rare, should be included in the differential diagnosis of epidural mass of the spine. Diagnosis before surgery is difficult as there were no characteristic findings in clinical and imaging studies. Special histologic technique and stains are useful to make a definite diagnosis.     

Genetic background of hyperphenylalaninemia in Nagasaki,Japan

Phenylketonuria (PKU) and related hyperphenylalaninemia (HPA) are caused by a deficiency in hepatic phenylalanine hydroxylase (PAH). The incidence of PKU in Nagasaki prefecture is higher than that in all parts of Japan (1/15 894 vs 1/120 000). To investigate the genetic background of patients with HPA in Nagasaki prefecture, mutation analysis was done in 14 patients with PKU or mild HPA. Homozygous or compound heterozygous PAH mutations were identified in all the patients. The spectrum of PAH mutations in the cohort was broad and similar to those in all parts of Japan and East Asian countries. R53H is the most common mutation in patients with mild HPA. The present results provide further support for genotype–phenotype correlations in patients with HPA. The high incidence of PKU in Nagasaki, the westernmost part of Japan, might be due to migration of people with PAH mutations from China and Korea, and geographic factors.     

Cloning and characterization of a TNF-like protein of Plecoglossus altivelis (ayu fish)

Ayu TNF cDNA contains an open reading frame of 708bp encoding 235 amino acids. Poly adeniration (A) signal and eight AU-rich sequences were present in 858bp 3' UTR. Southern blot analysis indicated that ayu TNF is single-copy gene. The genomic DNA sequence of ayu TNF, consisting of four exons and three introns, was shown to be conserved well throughout evolution from fish to mammals. The amino acid sequence of ayu TNF was shown to have 32-41% of amino acid identity to other known fish TNF, and about 30% of amino acid identity to mammalian TNFs. A phylogenetic analysis based on the amino acid sequence of TNF indicated that ayu has a distinctive evolutionary path. Also, two residues of cysteine important for the formation of the three-dimensional structure were conserved in ayu TNF. For the functional analysis, ayu TNF was inserted into expression vector pCold/TF, transferred into Chaperone Competent Cells BL21 (pKJE7); this produced soluble mature ayu recombinant TNF. Ayu recombinant TNF was shown to induce respiratory burst activity from ayu kidney. The above results indicate that ayu TNF plays an important role in phylaxis, as it does in mammals.     

Discrepancy between satisfaction with mastication, food acceptability, and masticatory performance in older adults

PURPOSE: The purpose of this study was to investigate the relationship between self-assessed satisfaction with mastication and food acceptability and masticatory performance in a large sample of older adults with various occlusal statuses. MATERIALS AND METHODS: The subjects were 708 community-dwelling, independently living elderly persons (351 men and 357 women) with a mean age of 66.0 (SD: 4.2) years. Satisfaction with masticatory function and food acceptability (apples, grilled beef, and hard rice crackers) were evaluated using questionnaires. Masticatory performance was determined using test gummy jellies developed for measuring masticatory performance. Subjects were grouped into 3 categories by posterior occlusal contacts according to the Eichner Index. The Kruskal-Wallis test and a multiple logistic regression analysis for dissatisfaction with masticatory function were conducted. RESULTS: Overall, posterior occlusal contacts, food acceptability, and masticatory performance were associated with satisfaction with masticatory function when evaluated with bivariate analysis. Multiple logistic regression analysis showed that the number of foods that could be eaten without difficulty was the most important explanatory variable for dissatisfaction with masticatory function (P < .01). In contrast, objective masticatory performance was not significantly associated with dissatisfaction with masticatory function (P = .057) after controlling for posterior occlusal contacts and food acceptance. CONCLUSIONS: The subjective masticatory function was associated not only with objective masticatory performance, but also with an individual's posterior occlusal contacts.