BackgroundOne of the sources of knee pain in osteoarthritis (OA) is believed to be related to local chronic inflammation of the knee joints, which involves the production of inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukin (IL)-6, and nerve growth factor (NGF) in the synovial membrane, and these cytokines are believed to promote pathological OA. In the present study, correlations between proinflammatory cytokines in knee synovial fluid and radiographic changes and functional scores and pain scores among OA patients were examined.MethodsSynovial fluid was harvested from the knees of 47 consecutive OA patients, and the levels of TNFα, IL-6, and NGF were measured using enzyme-linked immunosorbent assays. Osteoarthritic knees were classified using Kellgren-Lawrence (KL) grading (1-4). The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported physical function, pain, and stiffness.ResultsTNFα and IL-6 were detectable in knee synovial, whereas NGF was not. TNFα was not correlated with the KL grade, whereas IL-6 had a significantly negative correlation. We observed differences in the correlations between TNFα and IL-6 with WOMAC scores and their subscales (pain, stiffness, and physical function). TNFα exhibited a significant correlation with the total score and its 3 subscales, whereas IL-6 exhibited a moderately significant negative correlation only with the subscale of stiffness.ConclusionsThe present study demonstrated that the concentrations of proinflammatory cytokines are correlated with KL grades and WOMAC scores in patients with knee OA. Although TNFα did not have a significant correlation with the radiographic grading, it was significantly associated with the WOMAC score. IL-6 had a significant negative correlation with the KL grading, whereas it had only a weakly significant correlation with the subscore of stiffness. The results suggest that these cytokines play a role in the pathogenesis of synovitis in osteoarthritic knees in different ways: TNFα is correlated with pain, whereas IL-6 is correlated with joint function.

The aim of the study was to determine the frequency of amyloidosis detected by gastroduodenal biopsy in rheumatoid arthritis (RA) patients, and to investigate correlations between the results of gastroduodenal biopsy and abdominal fat and renal biopsies. A total of consecutive 1006 RA patients underwent gastroduodenal biopsy. The 71 patients who tested positive for gastrointestinal (GI) amyloidosis were asked to undergo renal and abdominal fat biopsies, and 21 did so. Renal biopsies were also performed on 12 patients with no amyloidosis but indicators of drug-induced renal damage, and abdominal fat biopsies were performed on 50 RA patients with no indication of amyloidosis. The prevalence of GI amyloidosis was 7.1%. Urinary abnormalities and GI symptoms were common in GI amyloidisis, and inflammatory markers were elevated. Sixty-one (86%) had either depressed creatinine clearance or urinary symptoms. Nineteen of the 21 patients (91%) with GI amyloidosis who underwent renal biopsies also had renal amyloid deposits. Eleven of the 21 (52%) had amyloidosis on abdominal fat biopsy. None of the 12 patients without GI amyloidosis had renal amyloidosis on renal biopsy, and none of the 50 patients without GI amyloidosis had amyloidosis on abdominal fat biopsy. Gastroduodenal biopsy reveals a high prevalence of amyloidosis in RA patients. Amyloidosis is often associated with signs of renal impairment. Results of GI biopsy are highly correlated with those of renal biopsy, but the results of fat biopsy are not. We recommend GI biopsy for RA patients for the screening of systemic amyloidosis.

In order to investigate the pathogenesis of mutilans-type rheumatoid arthritis (RA), we measured cytokine levels in the bone marrow serum of patients with RA. We studied 35 patients with non-mutilans RA, 19 with mutilans RA, and 20 patients with osteoarthritis (OA) undergoing joint surgery. At the time of surgery, iliac bone marrow and peripheral blood were sampled from all 74 patients and cytokine levels measured. The serum levels of five cytokines (IL-1beta, IL-2, IL-3, IL-6 and GM-CSF) were measured by ELISA. Haematologic and inflammatory factors were also measured. Levels of IL-2, IL-6 and GM-CSF in bone marrow serum were significantly higher in all RA patients than in those with OA. Mean (+/-SD) IL-2 levels were significantly higher in patients with mutilans-type RA (309.8+/-686.3 pg/ml) than in patients with other types of RA (66.5+/-173.1 pg/ml; P<0.01). IL-2 was detected significantly more often in patients with mutilans-type RA than in patients with other types of RA (P < 0.01). Inflammatory factors were higher in all RA groups than in OA patients. However, the haematologic and immunologic variables were no different between mutilans RA and other types of RA. No correlations were observed between IL-1beta, IL-2, IL-3, IL-6 and GM-CSF levels and these laboratory variables. In patients with mutilans-type RA, IL-2 levels in the bone marrow serum were significantly higher than in patients with other types of RA or with OA. This elevation does not appear to be related to systemic inflammation, as there was no correlation with other inflammatory factors.

A woman with rheumatoid arthritis (RA) experienced glottic stenosis approximately two months after switching from etanercept to tocilizumab. Cricoarytenoid joint (CAJ) arthritis due to RA was diagnosed. An awake tracheostomy saved the relievable airway, and the administration of methylprednisolone and infliximab ameliorated the flare-up and glottic stenosis. A follow-up examination revealed the recovery of the patient's normal voice and good control of RA with infliximab and methotrexate. Although general physicians do not frequently encounter patients with symptomatic CAJ arthritis, this condition should be considered as it can be life-threatening. Therefore, when detected, it should be diagnosed and treated immediately.

A 68-year-old man with a 3-year history of rheumatoid arthritis (RA) developed gynecomastia 3 months after beginning oral low-dose methotrexate (MTX) therapy. Four months after MTX therapy was discontinued, the gynecomastia symptoms improved. Only eight cases of gynecomastia resulting from low-dose MTX administration have been reported worldwide, and no cases have previously been reported in Japan. Although it occurs infrequently, gynecomastia resulting from low-dose MTX therapy should be considered in male patients with RA.

ObjectiveTo validate the relationship between residual walking ability and monthly care cost as well as long-term care insurance (LTCI) certification level in elderly patients after surgical treatment for hip fractures in Japan.MethodsElderly patients aged >75 years who underwent surgical treatment for hip fractures in our hospital were included. The preand post-surgical (6-month) walking ability and LTCI certification and the presence or absence of dementia was determined from medical records and questionnaires. Walking ability was classified into 6 levels used in our daily medical practice. Based on these data, we correlated the relationship between walking ability and the LTCI certification level. Further, based on the official statistics pertaining to the average monthly costs per person at each LTCI certification level, we evaluated the relationship between walking ability and monthly care cost.ResultsA total of 105 cases (mean age, 80.2 years; 16 men; 39 patients with dementia) were included. The correlation between walking ability and average monthly cost per person as well as LTCI certification level at 6 months postoperatively (r=0.58) was demonstrated. The correlation was found in both groups with and without dementia.ConclusionThe ability to walk reduced the cost of care in elderly patients who experienced hip fracture, regardless of the presence of dementia.

BackgroundIn Japan in 2014 the market share for generic drugs was 50%, lower than that of Western nations, but the reasons why the patients themselves turn down the opportunity to switch to a generic drug when asked at the pharmacy are not clear. In addition, the use of bio-similar drugs became possible in Japan in 2015, but the degree of knowledge that patients have regarding them is unknown.ObjectivesTherefore we carried out a patient survey about generic and bio-similar drugs, and at the same time, we also conducted a questionnaire for doctors who prescribed them, and conducted a comparative study of patient's and doctor's awareness regarding these drugs.MethodsThe survey was carried out amongst 4151 patients being treated at 20 research group member facilities. It was an anonymous written survey. After the section on patient background (age, gender, disease history) was completed, patients were asked their impressions of generic drugs, their attitudes towards changing to a generic, whether or not they had ever experienced an adverse effect with a generic drug, what knowledge they had regarding bio-similar drugs, and if they had any interest in or experience with using bio-similar drugs.We also asked 32 physicians about permissions and restrictions on GE use, negative experience of GE, problems of GE, experience of BIO-S and future plans for use, conditions of BIO-S usage, etc.ResultsThe group was 78% female, the majority of whom were in their 60's, and most had disease history of more than 10 years. Those with a good impression of GE drugs comprised 41%, those with a bad impression 9.4%. 34% of patients had switched to GE drugs, those who would not or could not were 24%. Those who reported a bad experience (lessening of effectiveness, or an adverse effect) were 8%.Meanwhile, in GE survey of doctors, about 65% partially restricted the use of GE, and about 70% had experiences of weakening of effects and occurrence of adverse events when using GE. Regarding patient knowledge of BIO-S, 13% knew of them, and 44% replied that they had no interest in them, even after being shown explanatory materials about the drugs. 63% of patients said they would rely on their physicians's judgement regarding choosing BIO-S drugs, with 10% stating they would choose BIO-S based on cost benefits. On the other hand, approximately 40% of physicians have experience using BIO - S, while about 60% have experience explaining them to patients. About 60% replied that they plan to use BIO-Ss to be released in the future but on the condition of regular and detailed provision of safety information.ConclusionsDue to experience in using GE, physicians wish to receive detailed information on individual drugs, and desire it even more in the case of BIO-S drugs. RA patients with RA have received little information on BIO-S, and this can be thought to be a direct result of lack of information for prescribing physicians.Disclosure of InterestNone declared

A 68-year-old man with a 3-year history of rheumatoid arthritis (RA) developed gynecomastia 3 months after beginning oral low-dose methotrexate (MTX) therapy. Four months after MTX therapy was discontinued, the gynecomastia symptoms improved. Only eight cases of gynecomastia resulting from low-dose MTX administration have been reported worldwide, and no cases have previously been reported in Japan. Although it occurs infrequently, gynecomastia resulting from low-dose MTX therapy should be considered in male patients with RA.