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Foot impairment in rheumatoid arthritis (RA) may exacerbate sarcopenia from physical inactivity because of foot pain while walking. The present study aimed to investigate the prevalence of sarcopenia in patients with RA-associated foot impairment, and whether treatment with a foot orthosis improved physical activity and muscle quantity.Thirty-two patients with RA were diagnosed as sarcopenic or nonsarcopenic, and the prevalence of sarcopenia was determined. Eleven patients with sarcopenia were treated with a foot orthosis. The following parameters were compared between baseline and after 6 months of treatment: physical activity (walking, moderate-intensity activity, and vigorous-intensity activity), foot pain while walking, Health Assessment Questionnaire (HAQ) score, and body composition parameters, including muscle quantity.Sarcopenia was present in 25/32 patients (78.1%). The use of a foot orthosis improved walking activity (Patients with RA-associated foot impairment had a high rate of sarcopenia. Treatment with a foot orthosis increases light-intensity physical activity such as walking, but does not enhance moderate-to-vigorous-intensity activities or increase muscle quantity.

The incidence of anaphylactic reaction after the long-term use of abatacept has not been reported until now. Herein, we present a case of rheumatoid arthritis (RA) in which the patient experienced an anaphylactic reaction one year after initiation of treatment with abatacept. A 75-year-old woman visited our hospital with symptoms of bilateral knee pain and swelling. She was initially treated with methotrexate (6 mg/week increased to 8 mg/week). Two months later, because of inadequate response, self-injections of abatacept (subcutaneous; 125 mg every two weeks) were prescribed. However, 6 months later, because of frequent stomatitis, the methotrexate dose was decreased to 6 mg/week, which resulted in worsening of RA. We changed the route of abatacept administration from subcutaneous injection to intravenous infusion (500 mg/month as a drip). After 30 min of starting the drip, the patient experienced itchiness and drop in vital signs, which were managed using methylprednisolone (2 doses, 125 mg each), dopamine hydrochloride (8 mg/h), and oxygen therapy (flow decreased from 3 L/min to 1 L/min). Wheals and redness were treated with oral antihistamines. Six hours after the onset of the anaphylactic reaction, the vital signs were stabilized. On the subsequent day, the patient’s general state was confirmed to be normal. One month later, etanercept (25 mg) treatment was initiated. The patient is currently in remission. We recommend caution when changing the route of administration and dosage of abatacept in anti-cyclic citrullinated peptide antibody-positive patients or those with a history of mild infusion-related reaction.

Patients with rheumatoid arthritis (RA)-related foot impairment have a high rate of sarcopenia. Treatment using a foot orthosis (FO) enables not only a reduction in pain while walking but also an increase in physical activity, helping to prevent further loss of muscle mass. However, the primary goal of treating RA is to maximize patients' long-term quality of life (QOL). We investigated whether FO treatment both increases physical activity and improves QOL.Among 31 patients with RA-related foot impairment, 15 with sarcopenia were treated with an FO for 6 months. Foot-specific QOL (measuring using the Self-Administered Foot Evaluation Questionnaire), foot pain, activities of daily living, and physical activity (walking-intensity activity and moderate- to vigorous-intensity activity) were compared before treatment and after 6 months of treatment.Ten patients who completed 6 months of follow-up were analyzed. Significant QOL improvements were found in the Pain and Pain-Related category and the Physical Functioning and Daily Living category (P = 0.02-0.04); however, no significant changes were found in the Social Functioning, General Health and Well-Being, or Shoe-Related categories (P = 0.09-0.21). Foot pain and activities of daily living significantly improved (P = 0.01-0.04). Physical activity significantly increased for walking-intensity activity (P = 0.04) but did not change for moderate- to vigorous-intensity activity (P = 1.00).FO treatment in patients with RA-related foot impairment and sarcopenia increased light-intensity physical activity such as walking and improved physical QOL.

BackgroundAlthough drug therapy for rheumatoid arthritis (RA) has recently improved, treating patients with established disease, whose hands have three major deformities (thumb deformity, finger deformities, and ulnar drift), remains a challenge. The underlying complex pathophysiology makes understanding these deformities difficult, and comprehensive assessment methods require accumulated skill with long learning curves. We aimed to establish a simpler composite method to understand the pathophysiology of and alterations in the hand deformities of patients with RA.MethodsWe established a rheumatoid hand cohort in 2004 and clinically evaluated 134 hands (67 patients). We repeated the evaluations in 2009 (100 hands of 52 patients) and 2015 (63 hands of 37 patients) after case exclusion. Thumb deformities, finger deformities (swan-neck and boutonnière deformity), and ulnar drift were semi-quantitated and entered as parameters into a two-step cross-sectional cluster analysis for the data in 2004. The parameters in each cluster were plotted at each evaluation point. Two-way analysis of covariance was used to examine whether differences existed between evaluation points and clusters of deformity parameters.ResultsFive clusters most appropriately described hand deformity: (i) cluster 1, minimal deformity; (ii) cluster 2, type 1 thumb deformity; (iii) cluster 3, thumb deformity and severe boutonnière deformity; (iv) cluster 4, type 2 or 3 thumb deformity and severe ulnar drift; and (v) cluster 5, thumb deformity and severe swan-neck deformity. Clusters 1 and 2 had higher function than cluster 5, and cluster 3 had moderate function. Clusters 1–4 had similar disease duration but showed different paths of deformity progression from disease onset. Clusters 1 and 2 represented conservative deformity parameters and clusters 3, 4, and 5 represented progressive deformity parameters. Over time, thumb deformity evolved into other types of deformities and swan-neck deformity worsened significantly.ConclusionsOur comprehensive analysis identified five deformity patterns and a progressive course in the rheumatoid hand. Knowledge of the characteristics of progressive deformity parameters may allow rheumatologists to more easily implement practical interventions and determine functional prognosis.

BackgroundAlthough drug therapy in rheumatoid arthritis has recently improved, treating established rheumatoid hand, consisting of three major deformities—thumb deformity, finger deformities, and ulnar drift— remains a challenge. Underlying complex pathophysiology makes it difficult to comprehensively understand these deformities, and comprehensive assessment methods require accumulated skill and long learning curves. We aimed to establish an easier composite method of understanding the pathophysiology and to elucidate alterations in deformities.MethodsWe established a rheumatoid hand cohort in 2004 and clinically evaluated 134 hands (67 patients). We repeated the evaluations in 2009 (100 hands in 52 patients) and 2015 (63 hands in 37 patients) after case exclusion. Thumb deformities, finger deformities (swan-neck and boutonnière deformity), and ulnar drift were semi-quantified and entered as parameters into a two-step cluster (cross-sectional) analysis for the data in 2004. The parameters in each cluster were plotted at each evaluation point. Two-way analysis of covariance was performed to examine whether differences existed between evaluation points and clusters for the deformity parameters.ResultsFive clusters were most appropriate to clarify each deformity: cluster 1: minimal deformity; cluster 2: type 1 thumb deformity; cluster 3: thumb deformity and severe boutonnière deformity; cluster 4: type 2 or 3 thumb deformity and severe ulnar drift; cluster 5: thumb deformity and severe swan-neck deformity. Clusters 1 and 2 had higher function than cluster 5, and cluster 3 had moderate function. Clusters 1–4 had similar disease duration, and showed different paths of deformity progression from disease onset. We considered clusters 1 and 2 as a conservative subset and clusters 3, 4, and 5 as a progressive subset. Over time, thumb deformity type altered to other types, and swan-neck deformity worsened significantly.ConclusionsOur comprehensive assessment indicated five deformity patterns and a progressive course in rheumatoid hand. Knowledge of the characteristics of the progressive subset may allow rheumatologists to more easily determine practical interventions and functional prognosis.

Background Although drug therapy in rheumatoid arthritis has recently improved, treating established rheumatoid hand consisting of three major deformities—thumb deformity, finger deformities, and ulnar drift—remains a challenge. Underlying complex pathophysiology makes it difficult to comprehensively understand these deformities, and comprehensive assessment methods require accumulated skill and long learning curves. We aimed to establish an easier composite method of understanding the pathophysiology using data from our cohort and cluster analysis. Methods We established a rheumatoid hand cohort in 2004, and clinically evaluated 134 hands (67 patients). We repeated the evaluations in 2009 and 2015, which provided data for 297 hands and 43 hands for cross-sectional and longitudinal analyses, respectively. Thumb deformities, finger deformities (swan-neck and boutonnière deformity), and ulnar drift were semi-quantified and entered as parameters into a two-step cluster (cross-sectional) analysis. Parameter distributions were considered to clarify each cluster’s characteristics. Next, hands with cluster change over the study period were reviewed to clarify deformity progression (longitudinal analysis). We also performed a stratified analysis between the clusters and the affected period to clarify whether long affected period plays an important role in deformity progression. Results We identified seven clusters: cluster 1: mild finger deformities; cluster 2: type 1 thumb deformity; cluster 3: type 2 thumb deformity and severe ulnar drift; cluster 4: type 3 or 4 thumb deformity and low or moderate swan-neck deformity; cluster 5: various thumb deformities and severe boutonnière deformity; cluster 6: type 1 thumb deformity and severe swan-neck deformity; and cluster 7: type 6 thumb deformity. The ulnar drift parameters were equally distributed among the clusters except for cluster 3. Larger cluster numbers generally indicated lower function. At the study endpoint, cluster 1 had changed mainly to cluster 2 or 4, cluster 2 changed to cluster 3, and cluster 7 was considered the final morphology with the lowest hand function. Patients affected for > 30 years had increased risk of rapid disability progression. Conclusions Our comprehensive assessment indicated seven deformity patterns and a progressive course in rheumatoid hand. Using patterns may provide rheumatologists with easier information for practical interventions and to determine functional prognosis.

Objective: To estimate the normal circumference of the interphalangeal (IP) thumb joint and the proximal IP (PIP) joints from the index finger to the little finger using individual physical parameters such as body height and body weight. Methods: The maximum size on the ring gauge was recorded which caused resistance when the IP joint of the thumb or PIP joints of the index to small fingers were passed through the gauge. RG was defined as the ring gauge number with the same diameter as the circumference of the IP thumb joint and PIP finger joints from the index finger to the little finger. There were 300 healthy subjects and 600 hands. Univariate and multivariate analyses were used to analyze the relationships between RG and the parameters of age, sex, height, weight, and dominant hand, and regression equations were derived. Results: Age, sex and body weight were all statistically significant predictive factors of RG in all fingers. R2, the coefficient of determination in the regression equation, was almost 0.7 for all fingers, indicating that a moderate or strong correlation was observed between RG and the regression equation. Conclusions: The circumference of the IP thumb joint and PIP finger joints from the index finger to the little finger can be estimated in healthy individuals using a calculation formula that takes age, sex, body height and body weight into account.

Objective: The sacroiliac joint is an important source of low back pain and may be influenced by pathologies in adjoining structures such as the hip or the spine. This study aimed to investigate the influence of hip osteoarthritis on sacroiliac joint degeneration by examining the sacroiliac joints of hip osteoarthritis patients, focusing on the localization and quantity of vacuum phenomena. Materials and Methods: The preoperative computed tomography (CT) of 31 female hip replacement candidates (mean age 69.1) and pelvic CT of 34 age-matched controls (mean age 67.9) were used to reconstruct the sacroiliac joints three-dimensionally. The degeneration score of the sacroiliac joints on axial view, as well as the location and volume of vacuum phenomena in the three-dimensionally reconstructed sacroiliac joints, were analyzed. Results: The total sacroiliac joint degeneration scores were similar in hip osteoarthritis patients and controls but the breakdown of the score revealed that joint space narrowing and vacuum phenomena in the sacroiliac joint increase in hip osteoarthritis, while osteophytes decrease. Three-dimensional reconstruction revealed that the volume of vacuum phenomena in the sacroiliac joint was significantly larger in the hip osteoarthritis group and the vacuum areas were localized in the antero-superior region of the sacroiliac joint. Conclusion: Our results suggest that hip osteoarthritis and sacroiliac joint degeneration are related, and that with further investigation, the sacroiliac joint may become a new treatment target in hip osteoarthritis.

Supplemental material, JHS886719 Supplementary material for A modified Terrono classification for Type 1 thumb deformity in rheumatoid arthritis: a cross-sectional analysis by Shogo Toyama, Ryo Oda, Maki Asada, Satoru Nakamura, Masato Ohara, Daisaku Tokunaga and Yasuo Mikami in Journal of Hand Surgery (European Volume)

To examine the recurrence of deformity after silicone implant arthroplasty combined with resection arthroplasty for severe forefoot deformity in patients with rheumatoid arthritis.We reviewed the long-term results of this procedure for 27 feet in 15 patients. Their average age and disease duration at the time of operation were 58.6 years and 17.5 years, respectively, and the average follow-up period was 10.3 years.An improved hallux valgus angle (45.3° preoperatively, 23.6° 6 months after operation) was maintained. By contrast, deformity and dislocation of lesser toe had recurred at the final follow-up; the angle between the proximal phalanx and the metatarsal of the second toe improved 13.4° with recurrence of 22.5°, the angle between the proximal phalanx and ground surface improved 22.4° with recurrence of 34.5. Furthermore, claw toe deformity at the final follow-up was significantly worse in the group whose hallux valgus deformity was observed 6 months after operation.This procedure could maintain the alignment of the first metatarsophalangeal joint, but the recurrence of claw toe deformity is a problem and the relation between the first toe and the lesser toe is an important consideration.

Background The recent classifications for posterior tibial tendon dysfunction (PTTD) stage II are based on forefoot deformity, but there is still no consensus regarding a detailed explanation of the clinical condition. The purposes of this study were to clarify the clinical condition of flatfoot deformity using three-dimensional (3D) computed tomography (CT) imaging under loading on both healthy and flat feet and to compare 3D movement of the forefoot in response to load. Methods Ten volunteers and 10 PTTD stage II patients with symptomatic flatfoot deformity were examined. CT scans of 20 healthy and 20 flat feet were performed under non-loading and full weight-bearing conditions. Images of the tibia and foot arch bones (talus, calcaneus, navicular, and first and fifth metatarsal bones) were reconstructed into 3D models. Rotations of individual tarsal bone or metatarsal bone were described by the Eulerian angles. Results Compared with healthy feet, flat feet experienced plantarflexion of the fifth metatarsal bone relative to the first metatarsal bone under loading conditions. We defined this phenomenon as synonymous with forefoot varus on the coronal plane. Conclusions The results of this study have clarified part of the clinical condition of the forefoot in flatfoot deformity and may have applications in basic research of the staging advancement and substage classification of PTTD.

Background:The treatment of rheumatoid hand, which is characterized by thumb deformity, finger deformities, and ulnar drift (UD), is challenging. Its pathophysiology is complex, and a comprehensive understanding of the optimal intervention for this condition requires high technical skill and extensive clinical experience. Moreover, the natural course of rheumatoid hand itself remains unclear.Objectives:This study was performed to comprehensively evaluate rheumatoid hand through the specific parameters of each deformity.Methods:A rheumatoid hand cohort was established in 2004. In total, 134 hands of 67 patients were registered and underwent clinical evaluations. All hands surgically treated during follow-up were excluded from the study, but the contralateral hands were assessed. Evaluations were repeated in 2009 (100 hands of 52 patients) and in 2015 (63 hands of 37 patients) among all available patients. Therefore, among the data obtained from the 3 study endpoints, 297 hands were available for the cross-sectional analysis and 43 hands were available for the longitudinal analysis.Thumb deformities and finger deformities (swan-neck and boutonnière) were semi-quantitated by the Nalebuff classification score, and UD was quantified using a metacarpophalangeal joint condition scoring method1). A two-step cluster analysis was performed with entered parameters, and the distribution of each parameter was considered to clarify the characteristics of each cluster. The hands with different clusters at each endpoint were recruited for the following longitudinal analysis. The natural course of rheumatoid hand was considered based on the cluster change.Results:Seven clusters were used in this study to emphasize the impact of thumb deformity on function. The characteristics of each cluster were as follows. Cluster 1: mild finger deformities and various severities of UD; Cluster 2: type 1 thumb deformity and various severities of UD; Cluster 3: type 2 thumb deformity and severe UD; Cluster 4: type 3 or 4 thumb deformity, low or moderate level of swan-neck deformity, and various severities of UD; Cluster 5: various types of thumb deformity, severe boutonnière deformity, and various severities of UD; Cluster 6: type 1 thumb deformity, severe swan-neck deformity, and various severities of UD; and Cluster 7: type 6 thumb deformity.The longitudinal analysis showed that Cluster 1 mainly changed to Cluster 2 or 4, indicating progression of thumb deformity. Cluster 2 changed to Cluster 3, indicating that thumb type 1 progressed to type 2 (Figure 1). When the affected period was shorter than 10 years, the incidence of severe hand deformity (including two or more affected joint areas and low hand function) was 30% (Figure 2).Figure 1.Figure 2.Conclusion:This study suggests the presence of seven patterns of deformity enabling a comprehensive understanding of rheumatoid hand. Furthermore, the results of the longitudinal analysis suggest a natural course of rheumatoid hand progression. Therefore, from the distribution of parameters of each deformity and its severity, rheumatologists can easily classify rheumatoid hand and determine its pathophysiology to choose the most effective intervention.References:[1]Toyama S, Oda R, Tokunaga D et al. A new assessment tool for ulnar drift in patients with rheumatoid arthritis using pathophysiological parameters of the metacarpophalangeal joint. Modern rheumatology 2019, 29: 113-8.Acknowledgments:This work was supported by JSPS KAKENHI Grant Numbers JP19K19914.Disclosure of Interests:None declared

Background:Sarcopenia is a progressive systemic skeletal muscle disorder associated with an increased likelihood of adverse outcomes including physical disability, falls, and mortality. The muscle mass of patients with rheumatoid arthritis (RA) is lower than that of age-matched healthy individuals, and a high prevalence rate of sarcopenia has been reported1). In particular, foot deformities may increase the prevalence rate of sarcopenia because of inactivity due to foot pain on walking. Treatment with a foot orthosis (FO) can reportedly reduce pain2); however, whether a FO can resolve inactivity and sarcopenia is unclear.Objectives:To elucidate the effectiveness of a FO on physical activity and sarcopenia in patients with RA.Methods:Thirty patients with RA with foot deformities were enrolled from April 2017 to December 2019. Sarcopenia was diagnosed using the algorithm of the European Working Group on Sarcopenia in Older People, and the cut-off values of the Asian Working Group for Sarcopenia were applied. We also collected the clinical variables of patients with concurrent RA and sarcopenia who continued to use a FO for 6 months. The primary outcome was physical activity determined by the International Physical Activity Questionnaire. The secondary outcomes were foot pain measured with a visual analog scale; activities of daily living (ADL) measured with the Health Assessment Questionnaire; and body mass index, body fat percentage, and the skeletal muscle mass index measured with a body composition device. The clinical variables were compared between baseline and 6 months after continuous treatment with a FO.Results:The prevalence rate of sarcopenia was 76.6% (23/30), and nine patients with RA continued to use the FO for 6 months. Table 1 shows outcomes at baseline and after 6 months of treatment with a FO. The only clinical variable that showed a significant difference was foot pain. Physical activities, ADL, and body compositions were maintained after 6 months.Table 1.Outcomes of 6-month treatment with FOBaseline6 monthsp valuePhysical activityIPAQWalking, MET-min/weekModerate, MET-min/weekVigorous, MET-min/week132 (66, 594)0 (0, 0)0 (0, 0)594 (396, 2376)0 (0, 0)0 (0, 0)0.071.000.32Foot painVAS score4.6 (3.1, 7.4)2.8 (1.1, 4.7)0.02ADLHAQ1.5 (1.1, 2.3)1.1 (0.9, 1.5)0.07Body compositionBMI, kg/m2BFP, %SMI, kg/m221.4 (20.7, 22.7)31.1 (24.2, 37.6)5.2 (4.8, 5.3)20.7 (19.3, 22.1)32.9 (26.3, 36.5)5.2 (5.0, 5.2)0.890.820.61IPAQ: International Physical Activity Questionnaire, VAS: visual analog scale, ADL: activities of daily living, HAQ: Health Assessment Questionnaire, BMI: body mass index, BFP: body fat percentage, SMI: skeletal muscle mass indexData are presented as median (lower quartile, upper quartile)Conclusion:The prevalence rate of sarcopenia in patients with RA with foot deformities was much higher than previous reported1). However, 6 months of treatment with a FO not only reduced foot pain but also maintained physical activity and muscle mass. Physical therapy has recently been recommended for patients with inflammatory arthritis. physical activity and muscle mass of patients with RA and concurrent foot deformities may be increased by combining physical therapy with orthotic treatment.References:[1]Tada M, et al. Matrix metalloprotease 3 is associated with sarcopenia in rheumatoid arthritis - results from the CHIKARA study. Int J Rheum Dis. 2018; 21 (11): 1962-9.[2]Hennessy K, et al. Custom foot orthoses for rheumatoid arthritis: A systematic review. Arthritis Care Res (Hoboken). 2012; 64 (3): 311-20.Acknowledgments:This work was supported by JSPS KAKENHI Grant Numbers JP19K11420.Disclosure of Interests:None declaredDOI: 10.1136/annrheumdis-2020-eular.3143

Background Ulnar drift (UD) in rheumatoid arthritis (RA) is the most common and difficult to manage deformity in the rheumatoid hand; it is reported that 44% of patients develop UD within the first 10 years. Nevertheless, the assessment of UD is challenging; the Fearnley classification method, first reported in 1951, is still used for evaluation. However, it is sometimes difficult to determine the best surgical procedure simply based on the Fearnley classification, which only evaluates reducibility. Therefore, we have been using both the Fearnley classification as a ‘gold standard’ and an original scoring method that enables us to easily treat the deteriorated condition contributing to UD. Objectives To establish and verify a new assessment tool for UD in rheumatoid hand. Methods We established an observational cohort of 67 patients (134 rheumatoid hands) beginning in 2004, among the RA outpatients who had any apparent finger deformity in either hand. Fifty-two patients (100 hands) had follow-up in 2009, and thirty-seven patients (63 hands) completed follow-up in 2015. For evaluation of UD, we used both the Fearnley classification as a ‘gold standard’ and an original scoring method which assesses four parameters of the metacarpophalangeal joint. Cluster analysis using UD parameters divided hands into groups. For functional assessment, we used the modified Kapandji index (MKI). The MKI enables us to assess unilateral hand functional mobility within a few minutes. Changes in UD over time, correlation of the Fearnley stage and cluster with MKI, and reliability of the parameters with clustering were analysed. Results The 10 year follow-up rate was 55.2%, and UD increased and worsened over time (p Conclusions Our UD evaluation method is quite simple but is closely related to function. Additionally, it enables dividing UD hands into five stages. Thus, our assessment should be beneficial compared to the Fearnley classification in considering treatments of UD. Acknowledgements The authors thank all the researchers involoved in this 10 year observational study. Disclosure of Interest None declared

To establish a new assessment tool for ulnar drift (UD) in rheumatoid arthritis (RA).We established an observational cohort of 67 patients (134 rheumatoid hands) beginning in 2004. Fifty-two patients (100 hands) had follow-up in 2009 and 37 patients (63 hands) completed follow-up in 2015. UD was evaluated with the Fearnley classification and our scoring method, which assesses four parameters of the metacarpophalangeal joint. Cluster analysis using UD parameters divided hands into groups. Changes in UD over time, correlation of the Fearnley stage and cluster with a functional assessment, and reliability of the parameters were analyzed.UD increased and worsened over time according to the trend test. A dendrogram indicated five clusters would be appropriate. Both the Fearnley classification and cluster were associated with function; however, our method related to function more linearly (R-squared: 0.42). We found one type of hand in which bone destruction precedes the joint dislocation and one type in which joint dislocation progresses with little deviation during UD progression.Our UD evaluation appeared to be simple and related to function. Additionally, it enables dividing UD hands into five stages. Thus, our assessment should be beneficial compared to the Fearnley classification in considering treatments of UD.

Objective: Nalebuff’s type I deformity of the rheumatoid thumb, which is the most common thumb deformity with rheumatoid arthritis, can be classified into three stages according to the range of motion of the thumb. However, a functional assessment for each stage has never been undertaken. Methods: The ranges of motion of the thumb metacarpophalangeal and interphalangeal joints were evaluated to determine Nalebuff’s clinical stage, and both the Modified Kapandji Index (MKI) and the simple test for evaluating hand function (STEF) were used to evaluate hand function in 32 rheumatoid arthritis patients with type I deformity. We assessed hand function in each stage, and examined the relationship between the three clinical stages and dysfunction of the hand. Results: The scores for both MKI and STEF were significantly reduced in parallel with advancing stage of thumb deformity. Conclusion: Nalebuff’s staging system is also useful for reflecting the level of thumb function.

Insoles are frequently used in orthotic therapy as the standard conservative treatment for symptomatic flatfoot deformity to rebuild the arch and stabilize the foot. However, the effectiveness of therapeutic insoles remains unclear. In this study, we assessed the effectiveness of therapeutic insoles for flatfoot deformity using subject-based three-dimensional (3D) computed tomography (CT) models by evaluating the load responses of the bones in the medial longitudinal arch in vivo in 3D.We studied eight individuals (16 feet) with mild flatfoot deformity. CT scans were performed on both feet under non-loaded and full-body-loaded conditions, first with accessory insoles and then with therapeutic insoles under the same conditions. Three-dimensional CT models were constructed for the tibia and the tarsal and metatarsal bones of the medial longitudinal arch (i.e., first metatarsal bone, cuneiforms, navicular, talus, and calcaneus). The rotational angles between the tarsal bones were calculated under loading with accessory insoles or therapeutic insoles and compared.Compared with the accessory insoles, the therapeutic insoles significantly suppressed the eversion of the talocalcaneal joint.This is the first study to precisely verify the usefulness of therapeutic insoles (arch support and inner wedges) in vivo.

Highlights • We report a case of spontaneous flexor tendon rupture in a patient with SLE. • Nonunion of the hamate hook is one of the causes of flexor tendon rupture. • SLE patients have an increased risk for osteoporosis and insufficiency fractures. • Tenosynovitis and long-term steroid use can affect tendon integrity in SLE. • SLE can lead to both tendon degeneration and insufficiency fracture of the hamate., Introduction Spontaneous flexor tendon rupture is usually caused by trauma, systemic diseases, or carpal bone and joint disorders. Here we report a case of spontaneous flexor tendon rupture occurring in a systemic lupus erythematosus (SLE) patient following nonunion of the hamate hook after an insufficiency fracture, and which was also associated with tendon degeneration caused by SLE. Case presentation A 57-year-old woman was diagnosed with SLE 22 years ago and being treated with oral prednisolone. She became unable to flex her left little finger without any history of trauma or sporting activity. CT showed nonunion of the hamate hook. MRI showed rupture of the flexor digitorum profundus tendon of the little finger. We performed tendon transfer and excision of the hamate hook. She recovered active flexion of the little finger at 4 months postoperatively with full satisfaction. Discussion There was no history of trauma that could have caused nonunion of the hamate hook. We considered that the insufficiency fracture of the hamate hook occurred as a result of osteoporosis caused by SLE and long-term steroid use. Nonunion of the hamate hook caused mechanical attrition of the tendons, and in combination with the tendon degeneration caused by SLE, further resulted in rupture of the flexor tendon. Conclusion When we encounter a case of spontaneous flexor tendon rupture in a patient with systemic disease such as SLE or long-term steroid use, attention should be paid to the state of the carpal bones and joints as they sometimes accompany unexpected causes.

Aim The aim of the present study was to investigate the influence of anti-tumor necrosis factor (anti-TNF) agents on gait function in patients with rheumatoid arthritis (RA). Methods Nine subjects with RA who were being treated with anti-TNF agents, participated in this study. A motion capture system was utilized, and data from the force plate and captured three dimensional motions were analyzed.Gait evaluation was performed before and 5.8 ± 2.6 months after introducing the anti-TNF agent. Stride, gait velocity and joint moments were calculated. In addition, an index of balancing weight of the lower extremities was determined. Results Stride length averaged 45.8 cm at baseline and 53.1 cm at the time of follow-up, and gait velocity averaged 0.9 m/s at baseline and 1.1 m/s at the time of follow-up. At heal contact, the joint moment of hip extension increased from 0.37 to 0.49, while ankle joint dorsiflexion moment increased from 0.08 to 0.13. During mid-stance, knee joint extension moment decreased from 0.16 to 0.06. At toe-off, hip joint flexion moment increased from 0.60 to 0.80, and ankle joint dorsiflexion moment increased from 0.80 to 1.05. The index of balancing weight of the lower extremities increased from 19.6 to 20.9 N. Conclusion The induction of anti-TNF therapies improved alterations in shock absorption in the early stance phase, balancing weight of the lower extremities in mid-stance, and increased push-off power in the later stance phase.

Background:The objective of this study was to evaluate the bone rotation of each joint in the hindfoot and compare the load response in healthy feet with that in flatfeet by analyzing the reconstructive three-dimensional (3D) CT image data during weightbearing.Methods:CT scans of 21 healthy feet and 21 feet with flatfoot deformity were taken in non-load condition followed by full-body weightbearing load condition. The images of the hindfoot bones were reconstructed into 3D models. The volume merge method in three planes was used to calculate the position of the talus relative to the tibia in the tibiotalar joint, the navicular relative to the talus in talonavicular joint, and the calcaneus relative to the talus in the talocalcaneal joint.Results:The talar position difference to the load response relative to the tibia in the tibiotalar joint in a flatfoot was 1.7 degrees more plantarflexed in comparison to that in a healthy foot ( p = 0.031). The navicular position difference to the load response relative to the talus in the talonavicular joint was 2.3 degrees more everted ( p = 0.0034). The calcaneal position difference to the load response relative to the talus in the talocalcaneal joint was 1.1 degrees more dorsiflexed ( p = 0.0060) and 1.7 degrees more everted ( p = 0.0018).Conclusion:Referring to previous cadaver study, regarding not only the cadaveric foot, but also the live foot, joint instability occurred in the hindfoot with load in patients with flatfoot.Clinical Relevance:The method used in this study might be applied to clinical analysis of foot diseases such as the staging of flatfoot and to biomechanical analysis to evaluate the effects of foot surgery in the future. Level of Evidence: III

Mycoplasma fermentans has been suspected as one of the causative pathogenic microorganisms of rheumatoid arthritis (RA) however, the pathogenic mechanism is still unclear. We, previously, reported that glycolipid-antigens (GGPL-I and III) are the major antigens of M. fermentans. Monoclonal antibody against the GGPL-III could detect the existence of the GGPL-III antigens in synovial tissues from RA patients. GGPL-III antigens were detected in 38.1% (32/84) of RA patient's tissues, but not in osteoarthritis (OA) and normal synovial tissues. Immunoelectron microscopy revealed that a part of GGPL-III antigens are located at endoplasmic reticulum. GGPL-III significantly induced TNF-alpha and IL-6 production from peripheral blood mononulear cells, and also proliferation of synovial fibroblasts. Further study is necessary to prove that M. fermentans is a causative microorganism of RA; however, the new mechanisms of disease pathogenesis provides hope for the development of effective and safe immunotherapeutic strategies based on the lipid-antigen, GGPL-III, in the near future.

In this study, we investigated the usefulness of contrast-enhanced MRI with maximum intensity projection (MIP) as a convenient tool for detecting early rheumatoid arthritis (RA). A total of 21 patients with undiagnosed arthritis of the hands at the initial visit were enrolled in a prospective study over a 1-year period. The number of swollen joints found during physical examination at this first visit, the results of serological tests and the number of synovitis joints diagnosed on MIP images were compared between the RA group and non-RA group. Of the 21 patients, 17 (81%) from the initial study who were followed up for an additional 1 year entered this study. Of these, 5 met the conditions for diagnosis of RA during follow-up, and 12 did not. MIP images were used to review the arthritis of RA patients, and a significant difference was found in the number of synovitis inflammations detected with MIP images when compared with findings after physical examinations. The two criteria of positive CARF and/or anti-CCP antibody and symmetrical synovitis in bilateral hands on MIP images allowed the prediction of RA with 100% sensitivity and 75% specificity. Thus, MIP is a useful tool for making early diagnosis of RA because it yields clear visualization even with just one image.

15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-gamma ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ(2) can suppress interleukin (IL)-1beta-induced prostaglandin E(2) (PGE(2)) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE(2) synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis. In this study, we investigated the feedback mechanism of the arachidonate cascade in mouse osteoblastic cells, MC3T3-E1 cells, which differentiate into mature osteoblasts. Treatment with 15d-PGJ(2) led to a significant increase in IL-1alpha-induced COX-2 expression and PGE(2) production in a dose dependent manner. The effect of 15d-PGJ(2) was stronger than that of TRO. However, it did not affect the expression of COX-1. In addition, cell viability of MC3T3-E1 cells was not changed in the condition we established. This means that 15d-PGJ(2) exerts a positive feedback regulation of the arachidonate cascade of PGE(2) in osteoblastic cells. These results may provide important information about the pathogenesis and treatment of bone resorption in a variety of diseases such as RA and osteoporosis.

Autologous tissue graft is one of the treatment options for a large rotator cuff defect. To develop appropriate strategies for enhanced solid graft integration at the bone-tendon interface and tendon-tendon interface, clarifying the fate of the graft and host cells that contribute to repair and remodeling is necessary. We have developed a new grafting model using green fluorescent protein-transgenic rats and wild-type rats to simulate autologous transplantation for examining the behavior of the host and graft cells in the remodeling process after tendon grafting. We found that the host cells commenced proliferation in the graft at 1 day after grafting. The host cells infiltrated into the graft from the subacromial synovium, proximal tendon, and bone-tendon insertion. The number of graft-derived cells decreased with time. Our result clearly demonstrated that host cells, rather than graft cells, were essential for rotator cuff remodeling after tendon grafting for rotator cuff defect.

Upper cervical involvement is common in patients with rheumatoid arthritis (RA). Anterior atlanto-axial subluxation (aAAS) sometimes occurs at an early stage of the disease. We hypothesized that not only antero-posterior instability but lateral instability may occur with atlanto-axial involvement in RA. To prove this hypothesis, we evaluated the lateral instability of the atlanto-axial joint in RA, using dynamic open-mouth view radiographs. Thirty RA patients and a control group of 22 non-RA outpatients were enrolled in this study. The patients underwent lateral view radiographs of the cervical spine during flexion and extension, and antero-posterior (AP) open-mouth views during maximum right and left bending of the neck. The anterior atlanto-dental interval (AADI) was measured to evaluate antero-posterior instability of the atlanto-axial joint, and atlanto-dental lateral shift (ADLS) was defined to evaluate dynamic lateral instability. In the RA group, AADI averaged 3.2 mm in flexion, and in eight patients, it exceeded 3 mm in flexion (aAAS). In the control group, the AADI averaged 1.0 mm in flexion. The ADLS in the RA group averaged 14.8%, and this was significantly greater than in the control group, in which it averaged 6.1%. The ADLS averaged 20.6% in the RA subgroup with aAAS, and 12.7% in the RA subgroup without aAAS. In both subgroups, the ADLS was significantly greater than that of the control group. In this study, dynamic lateral instability of the atlanto-axial joint in RA was demonstrated. The results suggest that an evaluation of the dynamic lateral instability of the atlanto-axial joint can be useful for early diagnosis of atlanto-axial lesions in RA.

As treatment for subluxation due to rheumatoid arthritis (RA), rehabilitation by hand therapy is one option, but the number of therapist is not sufficient. Therefore, a device for rehabilitation of thumb metacarpophalangeal (MP) joint subluxation has been developed. To improve the device, it is necessary to measure in close proximity to the actual rehabilitation. Therefore, the authors tried to measure two kinds of rehabilitation by using motion capture and a contact force sensor. To measure rehabilitation movements, three markers were attached to the metacarpal bone, six markers were attached to each side of the interphalangeal (IP) joint, MP joint and proximal phalanx of the right thumb of the subjects, and a finger model was created by these markers. Further, three markers were placed on the left index of the therapist, and force direction was calculated by these markers. Measurement was conducted on healthy subjects, Rehabilitation was performed by the person who is not a therapist, but received the guidance of the doctor who is coauthor. As a result, the authors could measure rehabilitation by hand therapy, force, point of action and displacement. The results suggest that rehabilitation with traction twice as efficient as that without traction. Furthermore, it was found that rehabilitation is possible with calculated force, and the force is reproducible by the actuator in the device.

We report a case of carpal tunnel syndrome caused by volar dislocation of the lunate in a patient with rheumatoid arthritis. A 74-year-old woman complained of numbness in her fingers. Carpal tunnel syndrome was diagnosed, and carpal tunnel release was performed. However, the symptoms recurred. Three-dimensional computed tomography and magnetic resonance imaging revealed volar dislocation of the lunate and synovitis around the distal radioulnar joint, respectively. Resection of the lunate and the Sauvé-Kapandji procedure were effective.

Although epidemiological studies on epiphyseal injury have been reported, such studies have not been made systematically in Japan. In this study, we examined the incidence of epiphyseal injury in paediatric patients treated at five general hospitals and three private clinics. We treated the patients with limb injuries between January 1992 and December 1997, and reviewed them at least 18 months after the original injuries. The original radiograms and the completed case records were classified according to age and sex of the injured children, site of the fracture, type of treatment, and its complications. Epiphyseal injuries accounted for 17.9% of all paediatric fractures. The most frequently injured epiphysis was the phalanges of hands, 21.9% of all physeal injuries. Salter-Harris type I accounted for 28.6% of physeal injuries; type II (60.9%) revealed the largest number of cases in this study, compared with type III (6.7%) and type IV (3.7%). Type V was not recognized. Most physeal injuries were treated conservatively. Either weight-bearing joints or elbow joints were treated surgically. Complications of physeal injuries were seen in seven cases. Five cases involved the upper limb, and the other two cases involve the lower limb. Although deformity or malfunction caused by physeal injuries was remained, only one case needed a corrective osteotomy. Other six cases revealed a fair prognosis.

Limb lengthening by the callotasis method has been clinically applied to patients who suffered from limb length inequality, micromelia, angular deformation and partial bone defect on long bones. However, this technique was time consuming and led to various complications, such as infection at the pin insertion sites, limitation of the range of motion in adjacent joints, muscular weakness and peripheral neuroparalysis. This study was undertaken to investigate whether alternating current electric (AC) stimulation could shorten the maturation period during callotasis. The tibiae of 20 immature male Japanese white rabbits were osteotomized and fixed with external lengthener (Orthofix M100; Orthofix Srl, Bussolengo, Italy). The experimental schedule lasted 5 weeks consisting of 1 week for the latency period, 2 weeks for distraction and 2 weeks for maturation. Twenty rabbits were equally divided into two groups: the control group and the electrical stimulation (ES) group. The control group was not stimulated with an AC stimulator. The ES group was stimulated for 5 weeks just after osteotomy. The obtained results revealed radiologically, electrophysiologically and histologically that AC stimulation accelerated the maturation of lengthened callus and that it could shorten the time course of callus lengthening.

Spontaneous flexor tendon rupture is an unusual complication of systemic lupus erythematosus (SLE) and has not previously been reported. While tendon ruptures in association with SLE have been focused on the previous studies, upper extremity tendon ruptures are infrequently reported in the literature. Here, we present an uncommon case of spontaneous flexor tendon rupture of the ring and little fingers in a patient with SLE and discuss the mechanism of injury and its surgical treatment.

Treatments for rheumatoid arthritis (RA) have improved since methotrexate and biological agents were approved; however, few longitudinal analyses have tracked joint destruction, deformity progression, or functional impairments that directly affect the activities of daily living. Due to the consequences of functional impairments, we conducted this study to glean more information regarding deformity progression over time.This study enrolled 134 hands in 67 RA patients with hand deformities in 2004. After 5 years, 100 hands in 52 patients were eligible for the final assessment. Analyses consisted of morphological and radiographical evaluations of deformities, functional evaluations by questionnaires and the modified Kapandji index, and activity evaluations.In this period, the type I deformity (Nalebuff and Millender, Orthop Clin North Am 6(3):753-63, 1975) was the most common thumb deformity. Swan-neck and boutonnière finger deformities also progressed. At the 5-year follow-up, questionnaire score worsened, when disease activity was high.Our study showed that there was a marked progression in hand deformities in RA patients over a 5-year period. In order to assist RA patients in performing the activities of daily living, medical and rehabilitative interventions should target the restoration of functional loss through joint destruction as well as the prevention of disease progression.

We report a case of rheumatoid arthritis treated by bilateral flexible hinge toe implant arthroplasty, using grommets only on one side, which resulted in bilateral fractures requiring removal of the implants 6.5 years after the surgery. Both implants were completely fractured at the bottom of the distal stems. Macroscopically, synovitis was present around both fractured stems, although the severity of synovitis and fragmentation of the fractured implant was relatively mild on the right side in which grommets were used. The shape of the body of the fractured implant was relatively preserved on the right side in which grommets were used. There was no damage or fracture of the grommets. The grommet might have acted to prevent pressures and scratches that would cause synovitis and deformity of the body of the implant, but might not completely prevent fractures of implants.

Background The acquisition of flatfoot by an adult is thought to primarily be caused by posterior tibial tendon dysfunction, although some other causes, such as congenital flexible flatfoot or an accessory navicular, may also be responsible. The objective of this study was to evaluate the bone rotation of each joint in the medial longitudinal arch (MLA) and compare the response in healthy feet with that in flat feet by analyzing the reconstructive three-dimensional (3D) CT image data during weightbearing. Methods CT scans of 20 healthy feet and 24 feet with flatfoot deformity were taken in non-load condition followed by full-body weightbearing condition. Images of the tibia and MLA bones (first metatarsal bone, cuneiforms, navicular, talus, and calcaneus) were reconstructed into 3D models. The volume merge method in three planes was used to calculate the bone-to-bone relative rotations. Findings Under loading conditions, the flatfoot dorsiflexed more in the first tarsometatarsal joint, and everted more in the talonavicular and talocalcaneal joints compared with the healthy foot. The total relative rotation was larger in the flatfoot compared with the healthy foot only in the first tarsometatarsal joint. Interpretation Supporting the MLA in the sagittal direction and the subtalar joint in the coronal direction may be useful for treating flatfoot deformity. The first tarsometatarsal joint may play an important role in diagnosing or treating flatfoot deformity.

We present a rare case of spontaneous tendon rupture of the extensor digitorum communis (EDC) in a patient with systemic lupus erythematosus (SLE). Inflammation in SLE presents as periarthritis, which may develop into Jaccoud’s arthropathy. We bridged the ruptured tendon of the EDC (III) at the metacarpophalangeal (MP) joint of this patient with a tendon graft. This case demonstrates that this portion of the MP joint can be a site of tendon rupture of fingers in SLE patients.

It is difficult to evaluate the kinematics of flat foot from 2D images, and no definitive methods have so far been established to diagnose flat foot. This study evaluated hindfoot kinetics through the progression of posterior tibial tendon dysfunction (PTTD) in patients with stages II and III PTTD flat foot compared with those in normal patients under dorsiflexion and plantarflexion conditions using 3D computed tomography (CT) reconstruction images.CT images were taken of 26 normal and 32 flat feet in neutral, plantarflexion, and dorsiflexion positions of the ankle joint, from which 3D virtual models were made of each hindfoot bone. The 3D bone motion of these models was calculated using volume merge methods in three major planes.Tibiotalar-joint motion in ankle-joint plantarflexion became less plantarflexed (normal -41.2°, stage II -33.5°, stage III -25.3°) and less adducted (normal -13.9°, stage II -10.7°, stage III -5.6°) as the stage progressed. Talocalcaneal-joint motion in stage III became more plantarflexed (normal -0.8°, stage II -3.0°, stage III -8.7°) and more adducted (normal -0.3°, stage II -4.7°, stage III -10.3°) as the stage progressed. Talonavicular-joint motion in stage III became more plantarflexed (normal -7.2°, stage II -7.6°, stage III -14.9°) and more adducted (normal 1.0°, stage II -7.3°, stage III -17.9°) as the stage progressed.Tibiotalar-joint plantarflexion decreased and talocalcaneal and talonavicular-joint adduction increased in the maximal ankle-joint plantarflexion in stage II in comparison with normal cases. Tibiotalar-joint plantarflexion and adduction were decreased and of the talocalcaneal and talonavicular joints increased in stage III in comparison with stage II cases.

Study design A case-series study. Objectives To measure the 3-dimensional (3D) morphology and kinematics of the craniovertebral junction (CVJ) using a 3D computed tomography (CT) model; to reveal abnormal patterns and the relationships between pathology and kinematics. Summary of background data Evaluations using radiography, 2-dimensional (2D) CT and magnetic resonance imaging have limitations because of the complex 3D structure of the CVJ. Methods Twenty-four rheumatoid arthritis patients (21 females, 3 males) with cervical involvement underwent CT scanning of the cervical spine from the basilar process of the occipital bone to the first thoracic vertebra in neutral and flexed positions. The 3D morphology of the occipital condyle, atlas, and axis were classified based on the type of deformity observed. Periodontoid lesions (continuous bony lesions between the atlas and the odontoid process) were also noted. The 3D kinematics in the atlanto-occipital and atlantoaxial joints were evaluated using the volume merge method. Results Deformities in the atlanto-occipital joints appeared more frequently than those in the atlantoaxial joints. The most common instability pattern was flexural rotation during flexion at the CVJ. The direction of translational motions during flexion was posterior in the atlanto-occipital joint and anterior and caudal in the atlantoaxial joint. Conclusion The results suggest that bilateral occipital condyle deformation, unilateral and bilateral mass collapse, and periodontoid lesions may affect flexion/extension rotational instability in the atlantoaxial joint. In addition, unilateral occipital condyle deformation and atlantoaxial joint stability may affect sagittal translational instability to the posterior side in the atlanto-occipital joint. The noninvasive 3D CT imaging technique employed here would be useful for predicting the prognosis of patients with rheumatoid deformities at the CVJ.

Background: Knowledge of normal bone motion of the foot is important for understanding the gait as well as for various pathologies; however, the pattern of 3D motion is not completely understood. The aim of this study was to quantify the in vivo motion of the tibiotalar joint, talocalcaneal joint, and talonavicular joint in normal adult feet using a noninvasive (e.g., nonsurgical) measurement technique. Materials and Methods: CT images were taken of both feet of ten normal young adults (six males, four females) in neutral, plantarflexion, and dorsiflexion positions of the ankle joint, from which 3D virtual models were made of each mid-hind foot bones. The 3D bone motion of these models was calculated using volume merge methods in three major planes. These data were used to analyze the relationship between the motion of the ankle joint and each other joint. Results: Tibiotalar rotation was observed in dorsiflexion, abduction, and eversion during maximal dorsiflexion of the ankle joint. Talocalcaneal and talonavicular rotation was very small because the ankle joint motion was limited to the sagittal plane. Tibiotalar rotation was also observed in plantarflexion and adduction during maximal plantarflexion of the ankle joint, and talocalcaneal rotation was very small. Talonavicular rotation was observed in plantarflexion and inversion. The motion of the x-axis and the z-axis of tibiotalar joint, and the x-axis and the y-axis of the talonavicular and talocalcaneal joint were associated with the ankle motion. Conclusion: Bone motion could be easily and accurately calculated using volume merge methods more effectively than it could with other methods. Clinical Relevance: The data elucidates the baseline segmental motion for comparison with symptomatic subjects which could help us to better understand pathokinematics of various foot and ankle pathologies.

The purpose of the current study is to establish the dynamic close-mouth view radiograph method. Seven healthy volunteers were enrolled. Dynamic open-mouth and close-mouth view radiographs were obtained. The odontoid lateral mass interval and the dynamic atlantodental lateral shift (ADLS) were measured. The ADLS was 9.4+/-5.3% by the close-mouth view, showing a significantly greater percentage than that of 5.3+/-4.0% by the open-mouth view. The dynamic close-mouth view can be useful for diagnosis of atlantoaxial lateral instability.

Recently, for a recurrent patellar dislocation, medial patellofemoral ligament (MPFL) reconstruction has come to be commonly performed, yet the precise in vivo MPFL biomechanics still remains to be clarified. The purpose of this study was to analyze the length change pattern of MPFL in vivo. The subjects were comprised of ten male and ten female healthy volunteers. The length of the MPFL was measured using an open-MRI both from a leg extended position and a highly knee-flexed position in order to analyze the length change pattern of the MPFL. The MPFL length for men and women resulted in an average of 52 ± 3 mm and 43 ± 2 mm at the knee extended position, respectively. The length change pattern of the MPFL presented a slight change at up to a flexion angle of 60° and a decrease at over 60°. In terms of morphology, the fiber bundle of the MPFL experienced linear tension at a knee flexion angle of 60°. We determined that the MPFL length in vivo exhibited a specific length change pattern. MPFL mainly contributes to the medial constraint of a patella with a knee flexion of 0° to 60°, wherein it is expected to have the strongest strain at 60°. However, more studies are needed to obtain a better understanding of cases with a history of patellar dislocation.

Background Drug resistance mediated by P-glycoprotein (P-gp) is one of the major reasons for the failure of rheumatoid arthritis (RA) therapy with disease modifying anti-rheumatic drugs and glucocorticoids. In the present study, we aimed to investigate the in vitro effectiveness of small interfering RNA (siRNA) to render rat fibroblast-like synoviocytes (FLS) susceptible to drugs. We also attempted the electroporation-mediated transfer of siRNA against multidrug resistance (MDR) genes into rat knee joints. Methods FLS were transfected with siRNAs corresponding to MDR1a and MDR1b genes. FLS were treated with dexamethasone (DEX) and lipopolysaccharide. The mRNA and protein levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β were measured. Both siRNAs were co-transduced into rat knee joints by an electroporation method and evaluated the target gene expressions in the synovium. Results Each siRNA could sequence-specifically reduce the target gene expression by over 70% and effectively suppressed P-gp expression and function in the FLS. Both gene expression and protein production of the inflammatory cytokines in the cells transfected with siRNA were reduced by a greater amount compared to in control cells. The in vivo electroporation-mediated transduction of siRNA could significantly inhibit the target gene expressions. Conclusions MDR1a/1b gene silencing by siRNA could effectively inhibit P-gp in rat FLS, resulting in a significant enhancement of the anti-inflammatory effects of DEX. The in vivo siRNA transduction could successfully silence MDR gene expression in the rat synovium. These findings indicate that the siRNA targeting MDR gene could be a useful tool for treating refractory arthritis in RA. Copyright © 2009 John Wiley & Sons, Ltd.

15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-gamma ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ(2) can suppress interleukin (IL)-1beta-induced prostaglandin E(2) (PGE(2)) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE(2) synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis. In this study, we investigated the feedback mechanism of the arachidonate cascade in mouse osteoblastic cells, MC3T3-E1 cells, which differentiate into mature osteoblasts. Treatment with 15d-PGJ(2) led to a significant increase in IL-1alpha-induced COX-2 expression and PGE(2) production in a dose dependent manner. The effect of 15d-PGJ(2) was stronger than that of TRO. However, it did not affect the expression of COX-1. In addition, cell viability of MC3T3-E1 cells was not changed in the condition we established. This means that 15d-PGJ(2) exerts a positive feedback regulation of the arachidonate cascade of PGE(2) in osteoblastic cells. These results may provide important information about the pathogenesis and treatment of bone resorption in a variety of diseases such as RA and osteoporosis.

In 1992, the authors developed a non-weightbearing unilateral ambulatory hip abduction brace, which was named the new pogo-stick brace for unilateral Legg-Calve -Perthes' disease. The hip abduction angle of the new pogo-stick brace was adjustable 45 degrees . The advantage of this brace was that even in the sitting position, the hip abduction angle was maintained. Twenty patients were treated with unilateral LCPD using the new pogo-stick brace. In the Catterall classification, one patient was classified as group 2, 17 as group 3, two as group 4. In Herring classification, one patient was classified as group A, 17 as group B, two as group C. Ultrasonography was performed to determine containment of the hip joints, and the abduction angle of the new pogo-stick brace was adjusted to get better containment, every 2 months. Mose's and acetabular head index methods were used for radiographic evaluation, and classified into good, fair and poor groups both at the primary healing and at the final follow-up. Total evaluation was defined as worse group between Mose's method and acetabular head index method. The average time from onset of disease to the primary healing was 25 months. The average bracing period was 21 months. The average follow-up period was 94 months. At the final follow-up appointment, patients who were classified into good and fair groups were 85% in Mose's method, 95% in acetabular head index method, 85% in total evaluation. In Stulberg classification, the total number of patients who were classified into classes I and II was 85%. The outcome of the new pogo-stick brace was not worse than that of any other treatment method, and was better than that of other unilateral ambulatory braces.