Cyclodextrins with Multiple Pyrenyl Groups: An Approach to Organic Molecules Exhibiting Bright Excimer Circularly Polarized Luminescence.

We report a simple and effective approach to organic molecules exhibiting bright circularly polarized luminescence (CPL) by combining a chiral cyclic molecular scaffold and multiple excimer-enabling moieties. An α-cyclodextrin (CyD) scaffold was modified with six pyrenyl groups to obtain pyrene-cyclodextrins (PCDs) in a one-step synthesis from commercially available compounds. The PCDs exhibited high molar extinction coefficients (ϵ≈105  M-1  cm-1 ), polarized emission with a good dissymmetry factor (|glum |≈10-2 ), and quantum yield (Φf ≈0.5). Owing to the excellent photophysical properties of the PCDs, the circularly polarized luminescence brightness (BCPL ) reached 340 M-1  cm-1 . Photophysical and chiroptical studies of the PCDs with only five pyrene units and with linkers of various lengths connecting the CyD with the pyrene units revealed that the formation of a pyrene excimer in a spatially crowded environment is crucial for CPL anisotropy. This study paves the way for the development of bright CPL organic molecules.

Relationship between achievement of physical activity goal and characteristics of patients with rheumatoid arthritis.

OBJECTIVES: We aimed to identify the relationship between achievement of a physical activity goal and the characteristics of patients with rheumatoid arthritis (RA). METHODS: Overall, 137 patients with RA who performed physical activity were enrolled. Statistical analysis was performed to examine relationship between patient characteristics and achievement of physical activity goal by univariate analysis, multivariate logistic regression analysis and the receiver operating characteristic method. RESULTS: The significant factors considered for univariate analysis performed to compare RA patients with and without achievement in physical activity goal were age, disease duration, BMI, global VAS, pain VAS, CRP, DAS28-CRP, and HAQ-DI. The significant related factors by multivariate logistic regression analysis were age (OR: 0.926), BMI (OR: 1.180), pain VAS (OR: 0.969), and HAQ-DI (OR: 0.229). The cutoff values were 62.0 years for age (sensitivity 72.5%, specificity 59.6%), 19.7 for BMI (sensitivity 91.2%, specificity 36.2%), 20.0 for pain VAS (sensitivity 63.7%, specificity 71.9%), and 0.30 for HAQ-DI (sensitivity 48.8%, specificity 89.5%). CONCLUSION: We aim to preserve activities of daily living in patients with RA. To achieve physical activity goal, we should control pain VAS, and HAQ-DI. Further, the patients the value of HAQ-DI should be kept very low.

Negative pressure wound therapy and skin grafting for necrotizing fasciitis in a patient with rheumatoid arthritis treated with abatacept: A case report.

Herein, we present a case of necrotizing fasciitis (NF) in a patient with rheumatoid arthritis (RA) treated with abatacept. Cultures of the patient's leg effusion revealed group A Streptococcus. Treatment included antibiological drugs, repeat debridement, negative pressure wound therapy (NPWT), and skin grafting. This case highlights the need for suspicion of severe bacterial infection for early diagnosis and effective treatment. NF with RA can be treated effectively with repeat debridement and NPWT.

Effects of denosumab treatment on bone mineral density and joint destruction in patients with rheumatoid arthritis.

We aimed to investigate the efficacy of denosumab for rheumatoid arthritis (RA). This study enrolled 70 RA patients who received denosumab 60 mg subcutaneous injection at baseline and at 6 months. Bone mineral densities (BMD) of the lumbar spine, total hip, femoral neck, and hand were measured by dual energy X-ray absorptiometry. Changes in total modified Sharp score (mTSS), erosion (EN) score, and joint space narrowing score at baseline from 12 months before and at 12 months from baseline. The mean values of BMD of the lumbar spine, total hip, femoral neck, and hand significantly increased by 7.3, 4.7, 3.9, and 5.4%, respectively, at 12 months. At 12 months from baseline, there were significant decreases in the values of mTSS (1.13 vs. 0.59; p = 0.002) and EN score (0.40 vs. 0.07; p < 0.001), compared with the values at baseline from 12 months before. The existing combined modality therapy with denosumab might be effective for osteoporosis and joint destruction in patients with RA.

Hip structure analysis by DXA of teriparatide treatment: A 24-month follow-up clinical study.

OBJECTIVE: The objective of this study was to perform a hip structure analysis (HSA) of teriparatide (TPTD) treatment in women with postmenopausal osteoporosis. METHODS: The study included 96 patients with postmenopausal osteoporosis and received 20 µg TPTD daily. HSA was performed by dual-energy X-ray absorptiometry. RESULTS: The percent changes from baseline for the cross-sectional moment of inertia, section modulus, buckling ratio, and femoral strength index based on HSA results were 9.8% (p < 0.01), 10.7%, 3.3%, and 14.9% (p < 0.01), respectively, at 24 months. CONCLUSION: Based on the HSA results obtained with DXA, TPTD was effective for hip structures.

Tramadol hydrochloride/acetaminophen combination versus non-steroidal anti-inflammatory drug for the treatment of perioperative pain after total knee arthroplasty: A prospective, randomized, open-label clinical trial.

BACKGROUND: While many of the commonly used treatments for perioperative pain after total knee arthroplasty (TKA) have been recognized as effective, there is still insufficient evidence for oral medication. In orthopedics, non-steroidal anti-inflammatory drugs (NSAIDs) have been commonly used for perioperative pain; however, serious adverse events have been reported. Conversely, tramadol hydrochloride/acetaminophen combination (TRAM/APAP) therapy has been shown to reduce pain, particularly for chronic pain in Japan. This study aimed to determine TRAM/APAP efficacy in comparison with NSAIDs for perioperative pain after TKA. METHODS: Two hundred eighty patients were enrolled in this study; 137 patients were treated with TRAM/APAP, and 143 patients were treated with NSAID from postoperative (PO) day 2. The primary endpoint was a comparison between the pain visual analog scale (VAS) change from baseline (PO day 2) and PO day 4, day 7, day 10, and day 14. The second endpoint was the number of days until the patient achieved independence from cane walking. RESULTS: Analysis of endpoints included 130 and 139 patients in the TRAM/APAP and NSAID groups, respectively. The pain VAS change in the TRAM/APAP group on any of the measurement days was significantly improved compared with the NSAID group (P < 0.01). Similarly, the TRAM/APAP group achieved cane-walking independence significantly faster than the NSAID group (P < 0.01). CONCLUSION: Efficacy for perioperative pain management after TKA of TRAM/APAP was shown to be superior to that of NSAID; TRAM/APAP was also effective in improving the progress of rehabilitation.

Platelet-rich plasma for the reduction of blood loss after total knee arthroplasty: a clinical trial.

PURPOSE: This study aims to clarify the effect of intra-articular platelet-rich plasma (PRP) in total knee arthroplasty (TKA) in preventing postoperative bleeding. METHODS: There were 315 knees that underwent TKA and were included in this study. The subjects were randomized by paramedical staffs. These were divided into the PRP group who received intra-articular PRP intraoperatively (n = 109) and the control group who did not (n = 206). We measured postoperative blood loss (drain bag volume), estimated blood loss, and change in hemoglobin (Hb) value at postoperative day 1, 2, 4, and 7. The clinical data were compared between the PRP group and the control group. RESULTS: The mean postoperative blood loss of 446.9 ± 149.7 mL in the PRP group was significantly less than that in the control group (550.7 ± 178.1 mL, p < 0.001). The mean postoperative estimated blood loss of 437.5 ± 221.3 mL in the PRP group was significantly less than that in the control group (552.2 ± 336.3 mL, p < 0.01). The mean change in Hb value (mg/dL) from baseline was -1.45 in the PRP group and -1.85 in the control group at postoperative 1 day (p < 0.05), -1.74 in the PRP group and -2.11 in the control group at postoperative day 2 (p < 0.05), -2.30 in the PRP group and -2.47 in the control group at postoperative day 4 (p < 0.05), and -1.98 in the PRP group and -2.46 in the control group at postoperative day 7 (p < 0.01). CONCLUSION: In this prospective randomized study, those that received PRP after TKA had significantly less postoperative blood loss and change in Hb level. PRP appears to be effective in reducing postoperative bleeding in TKA.

Scoliosis-related factors in patients with rheumatoid arthritis: A cross-sectional study.

OBJECTIVES: This study aimed to identify the prevalence of scoliosis and scoliosis-related factors of rheumatoid arthritis (RA). METHODS: In this study, 411 patients who underwent coronal total spine and lower limb radiography were enrolled. Patients with a Cobb angle ≥10° were diagnosed with scoliosis. Statistical analysis was performed to compare between patients with and those without scoliosis, and between patients without scoliosis and those with a Cobb angle >20°. RESULTS: The prevalence of scoliosis in patients with RA was 30.7%. The mean Cobb angles were 8.5° ± 7.2° in all the patients, 16.1° ± 8.6° in patients with scoliosis, and 5.1° ± 2.3° in patients without scoliosis. According to a multivariate analysis, the scoliosis-related factors of RA were age and vertebral fracture. Significant differences in age, corticosteroid use, and malalignment of lower limbs were observed between patients with a Cobb angle >20° and those without scoliosis. CONCLUSIONS: With RA treatment, the need for corticosteroid use is reduced and vertebral fracture is prevented. Moreover, the joints and spinal and lower limb alignments should be examined.

The efficacy of abatacept in Japanese patients with rheumatoid arthritis: 104 weeks radiographic and clinical results in clinical practice.

OBJECTIVE: We aimed to assess the efficacy of abatacept in Japanese patients with rheumatoid arthritis (RA) in clinical practice. METHODS: We examined 92 patients who received abatacept for 104 weeks. Analysis of radiographic efficacy was conducted using van der Heijde-modified total Sharp score (mTSS). Disease activity score was assessed using disease activity score in 28 joints (DAS28) and simplified disease activity index (SDAI) by last observation carried forward. RESULTS: The change in mTSS was 0.61 at 52 weeks and 0.27 at 52-104 weeks. Structural remission occurred in 64.9% at 52 weeks and 76.6% at 104 weeks. The significant risk factors for joint damage progression at 52 weeks were prednisolone use, baseline C-reactive protein level (CRP), and erythrocyte sedimentation rate (ESR), as well as average DAS28-CRP and DAS28-ESR scores, SDAI, CRP, ESR, and matrix metalloproteinase-3 (MMP-3) levels. The clinical remission rates were 47.8% by DAS28-CRP, 39.1% by DAS28-ESR, and 30.4% by SDAI at 52 weeks, were 59.8% by DAS28-CRP, 48.9% by DAS28-ESR, and 43.5% by SDAI at 104 weeks. CONCLUSION: This study suggested efficacy of abatacept treatment in Japanese patient with RA for 104 weeks in daily clinical practice. Abatacept lead to suppress joint destruction for 104 weeks.

Proximal rotational closing-wedge osteotomy of the first metatarsal in rheumatoid arthritis: clinical and radiographic evaluation of a continuous series of 35 cases.

OBJECTIVES: The introduction of powerful antirheumatic drugs has dramatically improved the treatment of rheumatoid arthritis (RA), leading clinicians to reconsider the benefits of joint preservation for rheumatoid forefoot deformities. We have employed joint-preserving forefoot surgeries, including rotational closing-wedge osteotomy of the first metatarsal. The aim of our study is to assess the short-term results of this procedure. METHODS: From January 2011 through December 2011, 35 feet were treated with this procedure. Subjective, functional, and radiographic outcomes were surveyed. RESULTS: The mean Japanese Society for Surgery of the Foot improved from a preoperative level of 52.6 to 68.7 postoperatively. The average hallux valgus and intermetatarsal angles improved from 47.3° preoperatively to 17.5° postoperatively, and from 16.7° preoperatively to 9.0° postoperatively, respectively. To assess the repositioning of pronation deformities of the first metatarsal, the position of the medial sesamoid was also surveyed according to the measurement system proposed by Hardy and Clapham. All feet except two were classified as grade V or higher preoperatively; 25 of these were grade IV or lower at the latest follow-up. CONCLUSIONS: Rotational closing-wedge osteotomy of the first metatarsal was beneficial for correcting forefoot deformities in RA over the short term.

Efficacy of total joint arthroplasty in patients with established rheumatoid arthritis: improved longitudinal effects on disease activity but not on health-related quality of life.

Though excellent clinical results have been reported for total joint arthroplasty (TJA) in rheumatoid arthritis (RA) patients, the longitudinal effects of TJA on pain, physical function, and health-related quality of life in RA patients remain unknown. This study aimed to assess changes in disease activity and health-related quality of life after TJA in patients with established RA. We analyzed the effect of total knee arthroplasty (TKA) and total hip arthroplasty (THA) on RA disease activity in an observational cohort of RA patients. Of the registered RA patients, 333 TKA and 77 THA patients were followed for 5 years after surgery. RA disease activity and health-related quality of life were measured using the Disease Activity Score 28 (DAS28) and a Japanese version of the Stanford health assessment questionnaire (J-HAQ). The mean DAS28 in TKA patients decreased from 4.66 (preoperatively) to 4.02 (3 years postoperatively) and to 3.94 (5 years postoperatively); the mean DAS28 in THA patients decreased from 4.41 (preoperatively) to 3.99 (3 years postoperatively) and to 3.92 (5 years postoperatively). The mean J-HAQ for TKA remained essentially unchanged, ranging from 1.48 (preoperatively) to 1.45 (3 years postoperatively) and to 1.47 (5 years postoperatively); the mean J-HAQ for THA also remained unchanged, ranging from 1.74 (preoperatively) to 1.74 (3 years postoperatively) and to 1.73 (5 years postoperatively). Of the total J-HAQ score, the lower limb score improved while the upper limb score worsened. Although TKA and THA improve clinical outcomes in damaged knees and hips and have a positive secondary systemic effect on RA disease activity, they have not had a continuously good effect on the measures of health-related quality of life. We conclude that tight control of RA disease activity is indicated for those patients with TKA and/or THA.

Prosthetic joint infection after total hip or knee arthroplasty in rheumatoid arthritis patients treated with nonbiologic and biologic disease-modifying antirheumatic drugs.

The aim of this study was to identify risk factors for acute surgical-site infection (SSI) after total joint arthroplasty in rheumatoid arthritis (RA) patients treated with nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs). We performed a retrospective study of all consecutive total hip (THA) and total knee (TKA) arthroplasties performed during a 5-year period (THA 81; TKA 339). Multivariate logistic regression analysis was performed to identify SSI risk factors. Of the patients undergoing THA or TKA, 24 cases (5.7%) developed a superficial incisional SSI requiring the use of antibiotics and three cases (0.7%) developed an organ/space SSI necessitating surgical treatment to remove the artificial joint prosthesis. Multivariate logistic regression analysis revealed that the use of biologic DMARDs [P = 0.0007, odds ratio (OR) = 5.69; 95% confidence interval (CI) 2.07-15.61] and longer RA duration (P = 0.0003, OR = 1.09; 95% CI 1.04-1.14) were the only significant risk factors for acute SSI. Furthermore, an analysis that individually evaluated major agents (n > 10) adjusted for disease duration indicated that tumor necrosis factor alpha blockers increased the risk of SSI (infliximab P = 0.001, OR = 9.80, 95% CI 2.41-39.82; etanercept P = 0.0003, OR = 9.16, 95% CI 2.77-30.25). We found that the use of infliximab or etanercept and longer disease duration were associated with an increased risk of acute SSI in RA patients. Prospective studies are thus needed to determine the safety of biologic DMARDs in the perioperative period.

Effect of total knee arthroplasty on disease activity in patients with established rheumatoid arthritis: 3-year follow-up results of combined medical therapy and surgical intervention.

Though excellent clinical results have been reported for total knee arthroplasty (TKA) in rheumatoid arthritis (RA) patients, the medium-term effect of TKA on RA disease activity remains unknown. This analysis aimed to assess changes in disease activity after TKA in patients with established RA. We analyzed the systemic effects of TKA on RA disease activity 3 years after intervention. Routine clinical and laboratory assessments were recorded at baseline, less than less than 0.5 years after TKA, and 3 years after TKA. Of the registered RA patients, 130 TKA patients were followed for 3 years after surgery. RA disease activity was measured using the Disease Activity Score 28 (DAS28). Patients were divided into three groups by preoperative baseline DAS28: low (DAS28 ≤ 3.2, n = 8), moderate (DAS28 > 3.2 but ≤5.1, n = 68), and high (DAS28 > 5.1, n = 54) disease activity. The postoperative DAS28 (<0.5 years [DAS1] and 3 years [DAS3] after surgery) scores of each patient were compared to their baseline (DAS0) scores using the paired t-test. The mean DAS28 decreased from 4.85 (DAS0) to 4.14 (DAS1; P = 1.07E-12), and this decrease was sustained at 3 years (DAS3 = 3.97; P = 4.73E-15). Subanalysis results revealed a systemic effect of TKA on disease activity in patients with moderate or high disease activity (DAS0 = 4.33; DAS1 = 3.72 [P = 5.94E-06]; DAS3 = 3.81 [P = 7.89E-06]; and DAS0 = 5.79; DAS1 = 4.86 [P = 1.14E-08]; DAS3 = 4.37 [P = 1.03E-11], respectively). While no significant changes in medication were noted, the average dose of prednisolone tended to decrease over time. We conclude that TKA, which is known to result in good clinical outcomes for damaged knees, has a secondary systemic effect on RA disease activity. Combination therapy consisting of medical treatment and surgical intervention is thought to effectively improve the condition of RA patients who have destructive arthritis in the knee joint, with the effect lasting for at least 3 years.

Complications and features after joint surgery in rheumatoid arthritis patients treated with tumour necrosis factor-alpha blockers: perioperative interruption of tumour necrosis factor-alpha blockers decreases complications?

OBJECTIVE: TNF-alpha blockers reportedly increase the risk of complications in rheumatic patients following surgery. Whereas deep venous thrombosis (DVT) is a significant complication after orthopaedic surgery of the lower limbs, the risk for DVT in RA patients receiving TNF blockers remains unclear. The aim of this study was to identify complications that can be attributed to the use of TNF-alpha blocker therapy. METHODS: In a retrospective 1:1 pair-matched case-control study, 64 anti-TNF-treated RA surgeries (TNF group) and 64 surgeries treated with conventional DMARDs (DMARDS group) were evaluated for surgical site infection (SSI), DVT and recurrence of arthritis (flare-up). Multivariate logistic regression analysis was performed to test the association of SSI or DVT with the putative risk factors. RESULTS: Regression analysis identified the use of TNF blockers as a risk factor for SSI [P = 0.036; odds ratio (OR) = 21.80] and development of DVT (P = 0.03; OR = 2.83) after major orthopaedic surgery: 12.5% (8/64) of the patients in the TNF group had SSI, whereas 2% (1/64) of those in the DMARDs group had SSI. Fifty-one per cent (23/45) of the TNF group, but only 26% (12/45) of the DMARDs group was DVT positive. Flare-ups during the perioperative period were found in 17.2% (11/64) of all patients, and no delay in wound healing occurred in either group. CONCLUSIONS: These data suggest that the use of TNF blockers is a likely cause of SSI and DVT development in RA patients following major orthopaedic surgery.