Flatfoot Surgery for Flexible Progressive Collapsing Foot Deformity With Inflammatory Joint Diseases: A Report of 3 Cases.

CASE: Three cases of inflammatory joint diseases (systemic lupus erythematosus and ongoing juvenile idiopathic arthritis) with painful flexible progressive collapsing foot deformity (PCFD) underwent flatfoot surgery. All cases maintained sufficient radiological correction and achieved good clinical condition at final follow-up. CONCLUSION: Although the prospect for recurrence of the deformity is not clear, even in inflammatory joint diseases, flat foot surgery such as flexor digitorum longs transfer, spring ligament reconstruction, and lateral column lengthening could have a possibility to be indicated against PCFD, as long as disease activity could be well suppressed by drug therapy, subsequently subtalar and talonavicular joints could be preserved.

Arthroscopic treatment of septic arthritis of the ankle joint caused by streptococcus in patients with chronic inflammatory diseases: two case reports.

This report describes the arthroscopic treatment of septic arthritis of the ankle joint in two patients with inflammatory diseases, including rheumatoid arthritis (RA) and nail psoriasis. We treated both the ankle joints with antibiotic administration and urgent arthroscopic synovectomy and irrigation, although the procedure was performed several days (4 and 6 days) after the time at which the infection would have occurred. Fortunately, no recurrence has been seen for more than 18 and 20 months, respectively, after surgery, without antibiotic administration. Although septic arthritis of the ankle joint accounts for a small proportion of joint arthritis cases, diagnosis as early as possible is important. Our experience suggests that arthroscopic synovectomy and irrigation are effective for septic ankle arthritis even in chronic inflammatory disease cases.

Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.

OBJECTIVES: To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biologic DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi). METHODS: Retrospective analysis was conducted on data from the ANSWER cohort comprising 3623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention. RESULTS: Of the 3623 RA patients, 450 (12.4%) met the first two criteria of the EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared with those under 65, hazard ratio [HR] = 0.46; 95% CI: 0.31, 0.69), higher rheumatoid factor (RF) titres (HR = 1.005; 95% CI: 1.00, 1.01), higher clinical disease activity index (HR = 1.02; 95% CI: 1.01, 1.03), lower methotrexate dosage (HR = 0.97; 95% CI: 0.95, 0.99), and comorbidities like hypertension (HR = 1.53; 95% CI: 1.2, 1.95) and diabetes (HR = 1.37; 95% CI: 1.09, 1.73). Anti-IL-6 receptor antibodies (aIL-6R, HR = 0.53; 95% CI: 0.37, 0.75) and JAKi (HR = 0.64; 95% CI: 0.46, 0.90) were associated with fewer discontinuations due to ineffectiveness compared with TNF inhibitors. Oral glucocorticoid usage (HR = 1.65; 95% CI: 1.11, 2.47) was linked to increased discontinuation due to toxic adverse events. CONCLUSION: Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention.

The 2023 Guidelines for the management and treatment of glucocorticoid-induced osteoporosis.

INTRODUCTION: Although synthetic glucocorticoids (GCs) are commonly used to treat autoimmune and other diseases, GC induced osteoporosis (GIOP) which accounts for 25% of the adverse reactions, causes fractures in 30-50% of patients, and markedly decreases their quality of life. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) published the revised guidelines for the management and treatment of steroid-induced osteoporosis, providing the treatment criteria based on scores of risk factors, including previous fractures, age, GC doses, and bone mineral density, for patients aged ≥18 years who are receiving GC therapy or scheduled to receive GC therapy for ≥3 months. MATERIALS AND METHODS: The Committee on the revision of the guidelines for the management and treatment of GIOP of the JSBMR prepared 17 clinical questions (CQs) according to the GRADE approach and revised the guidelines for the management and treatment of GIOP through systematic reviews and consensus conferences using the Delphi method. RESULTS: Bisphosphonates (oral and injectable formulations), anti-RANKL antibody teriparatide, eldecalcitol, or selective estrogen receptor modulators are recommended for patients who has received or scheduled for GC therapy with risk factor scores of ≥3. It is recommended that osteoporosis medication is started concomitantly with the GC therapy for the prevention of fragility fractures in elderly patients. CONCLUSION: The 2023 guidelines for the management and treatment of GIOP was developed through systematic reviews and consensus conferences using the Delphi method.

Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.

OBJECTIVES: This multicentre, retrospective study aimed to compare retention and reasons for discontinuation between Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs in patients with elderly-onset rheumatoid arthritis (EORA). METHODS: Patients with RA enrolled in a Japanese multicentre observational registry between 2015 and 2022 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding factors by indication for initiation of tumor necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), cytotoxic T-lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) blockers, or JAKi, a propensity score based on baseline characteristics was used to compare drug retention. To assess the reasons for discontinuation, retention rates for ineffectiveness, adverse events, and remission were analyzed as secondary outcomes. RESULTS: A total of 572 patients with 835 treatment courses were identified (314 TNFi, 175 IL-6i, 228 CTLA4-Ig, and 118 JAKi). After adjusting for differences in baseline characteristics, drug retention was significantly higher for IL-6i (HR = 0.38, 95%CI = 0.27-0.55, p< 0.01) as compared with TNFi. Discontinuation due to lack of effectiveness was lower with the JAKi (HR = 0.38, 95%CI = 0.22-0.66, p< 0.01) and the IL-6i (HR = 0.29, 95%CI = 0.19-0.46, p< 0.01) as compared with the TNFi although the CTLA4-Ig had a similar HR to TNFi. The adjusted incidence of discontinuation due to adverse event was higher in the JAKi (HR = 2.86, 95%CI = 1.46-5.59, p< 0.01) than the TNFi. CONCLUSIONS: In EORA patients, IL-6i and JAKi had longer retention and less discontinuation due to ineffectiveness than TNFi. The potential risks of JAKi should be approached with an individualized perspective.

Iguratimod suppresses sclerostin and receptor activator of NF-κB ligand production via the extracellular signal-regulated kinase/early growth response protein 1/tumor necrosis factor alpha pathway in osteocytes and ameliorates disuse osteoporosis in mice.

Disuse osteoporosis is a prevalent complication among patients afflicted with rheumatoid arthritis (RA). Although reports have shown that the antirheumatic drug iguratimod (IGU) ameliorates osteoporosis in RA patients, details regarding its effects on osteocytes remain unclear. The current study examined the effects of IGU on osteocytes using a mouse model of disuse-induced osteoporosis, the pathology of which crucially involves osteocytes. A reduction in distal femur bone mass was achieved after 3 weeks of hindlimb unloading in mice, which was subsequently reversed by intraperitoneal IGU treatment (30 mg/kg; five times per week). Histology revealed that hindlimb-unloaded (HLU) mice had significantly increased osteoclast number and sclerostin-positive osteocyte rates, which were suppressed by IGU treatment. Moreover, HLU mice exhibited a significant decrease in osteocalcin-positive cells, which was attenuated by IGU treatment. In vitro, IGU suppressed the gene expression of receptor activator of NF-κB ligand (RANKL) and sclerostin in MLO-Y4 and Saos-2 cells, which inhibited osteoclast differentiation of mouse bone marrow cells in cocultures. Although IGU did not affect the nuclear translocation or transcriptional activity of NF-κB, RNA sequencing revealed that IGU downregulated the expression of early growth response protein 1 (EGR1) in osteocytes. HLU mice showed significantly increased EGR1- and tumor necrosis factor alpha (TNFα)-positive osteocyte rates, which were decreased by IGU treatment. EGR1 overexpression enhanced the gene expression of TNFα, RANKL, and sclerostin in osteocytes, which was suppressed by IGU. Contrarily, small interfering RNA-mediated suppression of EGR1 downregulated RANKL and sclerostin gene expression. These findings indicate that IGU inhibits the expression of EGR1, which may downregulate TNFα and consequently RANKL and sclerostin in osteocytes. These mechanisms suggest that IGU could potentially be used as a treatment option for disuse osteoporosis by targeting osteocytes.

Early full weight-bearing and gait exercise after cemented total ankle arthroplasty with modified antero-lateral approach.

BACKGROUND: According to the conventional postoperative procedure after total ankle arthroplasty (TAA) against end-stage osteoarthritis (OA) and rheumatoid arthritis (RA), mobilization and weight-bearing is currently started after completion of wound healing. Recently, early mobilization for dorsiflexion after TAA with modified antero-lateral approach was reported to be feasible and safe. To investigate the further possibility of expediting rehabilitation, this study evaluated the feasibility and safety of early full weight-bearing and gait exercise after cemented TAA utilizing a modified antero-lateral approach. MATERIALS AND METHODS: This retrospective, observational study investigated 23 consecutive ankles (OA: 14 ankles, RA: 9 ankles) that had received cemented TAA with a modified antero-lateral approach. These ankles were divided into three groups [1. conventional postoperative protocol: 8 ankles, 2. early dorsiflexion protocol: 7 ankles, 3. early dorsiflexion+full weight-bearing protocol: 8 ankles]. In group 3, after early dorsiflexion mobilization (day 3), full weight-bearing/gait exercise was started from 7 days after surgery (10 days after if malleolar osteotomy was added). Postoperative wound complications were observed and recorded. Number of days for hospitalization was also evaluated. Range of motion (ROM) of dorsiflexion/plantar flexion was measured. Patients also completed a self-administered foot evaluation questionnaire (SAFE-Q) and the scale of Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot score preoperatively and at final follow-up. RESULTS: No postoperative complications related to wound healing were observed even after early full weight-bearing and gait exercise. Days for hospitalization was significantly shortened in early full weight-bearing and gait exercise group (group 3) from 35-38 days to 24 days. ROM for both dorsiflexion and plantar flexion significantly increased in group 3, furthermore all indices of SAFE-Q score also showed stronger significant improvement in group 3. JSSF score improved significantly after TAA in all groups. CONCLUSION: Within this small number of cases, early full weight-bearing and gait exercise from 7 days after cemented TAA was feasible and safe with the modified antero-lateral approach. Combination of early dorsiflexion mobilization and weight-bearing/gait exercise contributed to shortening the hospitalization day, and improving ROM for both dorsiflexion and plantar flexion after surgery. Innovations in postoperative procedures for rehabilitation after TAA can be expected.

IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study.

OBJECTIVES: Anaemia, a common comorbidity of RA, is related to high disease activity and poor prognosis. It is unknown which biologic/targeted synthetic (b/ts)-DMARDs are optimal for patients with anaemia and RA in regulating anaemia and controlling disease activity. METHODS: We investigated the change in haemoglobin (Hb) levels, drug retention rates and disease activities after the administration of b/ts-DMARDs with different modes of action [TNF inhibitors (TNFis), immunoglobulin fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), IL-6 receptor inhibitors (IL-6Ris) and Janus kinase inhibitors (JAKis)] in patients with RA stratified by baseline Hb levels using the multicentre observational registry for patients with RA in Japan (ANSWER cohort). RESULTS: A total of 2093 patients with RA were classified into three groups based on tertiles of the baseline Hb levels (Hblow, anaemic; Hbint, intermediate; Hbhigh, non-anaemic). IL-6Ri increased Hb levels in all groups (the mean change at 12 months in Hblow was +1.5 g/dl, Hbint +0.7 g/dl and Hbhigh +0.1 g/dl). JAKis increased the Hb level in patients with anaemia and RA and retained or decreased the Hb level in non-anaemic patients (the mean change at 12 months in Hblow was +0.6 g/dl, Hbint 0 g/dl and Hbhigh -0.3 g/dl). In patients with anaemia and RA, overall adjusted 3-year drug retention rates were higher in JAKi followed by IL-6Ri, CTLA4-Ig and TNFi (78.6%, 67.9%, 61.8% and 50.8%, respectively). Change of disease activity at 12 months was not different among different b/ts-DMARDs treatments. CONCLUSION: IL-6Ri and JAKi can effectively treat patients with anaemia and RA in a real-world setting.

Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice.

NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti-NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.

Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6-CXCR2 pathway.

OBJECTIVE: To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms. METHODS: Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 106 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (-) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery. RESULTS: Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors. CONCLUSION: SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation.

Drug retention of biologics and Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study.

OBJECTIVES: This multicentre retrospective study in Japan aimed to assess the retention of biological disease-modifying antirheumatic drugs and Janus kinase inhibitors (JAKi), and to clarify the factors affecting their retention in a real-world cohort of patients with rheumatoid arthritis. METHODS: The study included 6666 treatment courses (bDMARD-naïve or JAKi-naïve cases, 55.4%; tumour necrosis factor inhibitors (TNFi) = 3577; anti-interleukin-6 receptor antibodies (aIL-6R) = 1497; cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig) = 1139; JAKi=453 cases). The reasons for discontinuation were divided into four categories (ineffectiveness, toxic adverse events, non-toxic reasons and remission); multivariate Cox proportional hazards modelling by potential confounders was used to analyse the HRs of treatment discontinuation. RESULTS: TNFi (HR=1.93, 95% CI: 1.69 to 2.19), CTLA4-Ig (HR=1.42, 95% CI: 1.20 to 1.67) and JAKi (HR=1.29, 95% CI: 1.03 to 1.63) showed a higher discontinuation rate due to ineffectiveness than aIL-6R. TNFi (HR=1.28, 95% CI: 1.05 to 1.56) and aIL-6R (HR=1.27, 95% CI: 1.03 to 1.57) showed a higher discontinuation rate due to toxic adverse events than CTLA4-Ig. Concomitant use of oral glucocorticoids (GCs) at baseline was associated with higher discontinuation rate due to ineffectiveness in TNFi (HR=1.24, 95% CI: 1.09 to 1.41), as well as toxic adverse events in JAKi (HR=2.30, 95% CI: 1.23 to 4.28) and TNFi (HR=1.29, 95%CI: 1.07 to 1.55). CONCLUSIONS: TNFi (HR=1.52, 95% CI: 1.37 to 1.68) and CTLA4-Ig (HR=1.14, 95% CI: 1.00 to 1.30) showed a higher overall drug discontinuation rate, excluding non-toxicity and remission, than aIL-6R.

Angioleiomyoma mimicking a swollen bursa on first metatarsophalangeal joint accompanying with hallux valgus deformity.

We present a case of a patient who underwent a modified scarf osteotomy and tumour excision based on a preoperative diagnosis of hallux valgus deformity and accompanying bursitis. Subsequent histopathological examination revealed that the tumour was an angioleiomyoma. While tumours around the first metatarsophalangeal (MTP) joint are typically associated with gouty nodules, infections, or swollen bursa (bursitis) in patients with hallux valgus deformity, the occurrence of soft tissue tumours in this area is rare. Moreover, angioleiomyoma is an even rarer form of soft tissue tumour and is seldom suspected prior to resection. To our knowledge, there have been no reports of angioleiomyoma arising in the first MTP joint. However, it is important to consider the possibility of an atypical tumour in cases where soft tissue masses are present, even in patients with hallux valgus deformity, and to perform at least imaging tests such as ultrasound and magnetic resonance imaging before surgery. This prospect should always be kept in mind.

Early mobilization of dorsiflexion from 3 days after cemented total ankle arthroplasty with modified antero-lateral approach.

BACKGROUND: According to the conventional postoperative procedure after total ankle arthroplasty (TAA), mobilization is currently started after completion of wound healing. To investigate the possibility of expediting rehabilitation, this study evaluated the feasibility and safety of early mobilization of dorsiflexion after cemented TAA utilizing a modified antero-lateral approach. MATERIALS AND METHODS: This retrospective, observational study investigated 14 consecutive ankles that had received cemented TAA. Mobilization of dorsiflexion was started from 3 days after surgery. Postoperative wound complications including blister formation, eschar formation, wound dehiscence, peri-incisional decreased sensation were observed and recorded. Range of motion (ROM) of dorsiflexion/plantar flexion was measured. Patients also completed a self-administered foot evaluation questionnaire (SAFE-Q) and the scale of Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot score preoperatively and at final follow-up. RESULTS: No postoperative complications related to wound healing were observed. ROM for dorsiflexion, SAFE-Q score, and JSSF score improved significantly after TAA. CONCLUSION: Within this small number of cases, early mobilization of dorsiflexion from 3 days after cemented TAA was feasible and safe with the modified antero-lateral approach. Innovations in postoperative procedures for rehabilitation after TAA can be expected.

Modified scarf osteotomy with capsular interposition as salvage for resection or silicone implant arthroplasty in patients with rheumatoid arthritis. A report of three cases.

This study investigated modified scarf osteotomy as a salvage procedure after resection arthroplasty or silicone implant arthroplasty to preserve mobility of the first metatarsophalangeal (MTP) joint after hallux valgus surgery in patients with rheumatoid arthritis (RA). We investigated three feet with rheumatoid forefoot deformities that showed recurrence of forefoot deformity or breakage of the implant after resection or silicone implant arthroplasty in the first MTP joint. All feet were treated using modified scarf osteotomy with capsular interposition. All cases achieved obvious correction after modified scarf osteotomy despite resection of the first MTP joint and consequently showed both radiographic and clinical improvements. Modified scarf osteotomy offers potential as a definitive salvage procedure after resection arthroplasty or silicone implant arthroplasty for forefoot deformity in patients with RA, because the procedure can realign the first MTP joint obviously with preservation of the range of motion. Concomitant medial capsular interposition into the newly formed first MTP joint is also recommended where possible, to protect the edges of the proximal basal phalanx and distal first metatarsal and also to smoothen the motion of newly formed first MTP joint.

A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis.

In clinical studies, the next-generation anti-tumor necrosis factor-alpha (TNF-α) single domain antibody ozoralizumab showed high clinical efficacy shortly after the subcutaneous injection. To elucidate the mechanism underlying the rapid onset of the effects of ozoralizumab, we compared the biodistribution kinetics of ozoralizumab and adalimumab after subcutaneous injection in an animal model of arthritis. Alexa Fluor 680-labeled ozoralizumab and adalimumab were administered by subcutaneous injection once (2 mg/kg) at five weeks after induction of collagen-induced arthritis (CIA) in an animal arthritis model. The time-course of changes in the fluorescence intensities of the two compounds in the paws and serum were evaluated. The paws of the CIA mice were harvested at four and eight hours after the injection for fluorescence microscopy. Biofluorescence imaging revealed better distribution of ozoralizumab to the joint tissues than of adalimumab, as early as at four hours after the injection. Fluorescence microscopy revealed a greater fluorescence intensity of ozoralizumab in the joint tissues than that of adalimumab at eight hours after the injection. Ozoralizumab showed a significantly higher absorption rate constant as compared with adalimumab. These results indicate that ozoralizumab enters the systemic circulation more rapidly and is distributed to the target tissues earlier and at higher levels than conventional IgG antibodies. Our investigation provides new insight into the mechanism underlying the rapid onset of the effects of ozoralizumab in clinical practice.

Improvement of Knee Alignment and Function After Corrective Surgery for Hindfoot Deformity: A Report of 3 Cases.

CASE: Marked varus or valgus hindfoot deformities in 3 patients with ankle osteoarthritis or rheumatoid arthritis were treated by corrective surgery using total ankle arthroplasty or distal tibia oblique osteotomy. All cases achieved not only sufficient correction and satisfactory clinical/radiographic hindfoot improvement but also improvements in both knee alignment and function. CONCLUSION: Corrective surgery for hindfoot deformity can potentially change or improve ipsilateral knee alignment and function, representing an unexpected benefit of hindfoot realignment.

Modified Scarf Osteotomy with Medial Capsular Interposition Combined with Metatarsal Shortening Offset Osteotomy: A Comparison of Patients with Noninflammatory Arthritis and Rheumatoid Arthritis of the Foot.

BACKGROUND: Patients who have noninflammatory arthritis of the feet may develop destructive changes on the first metatarsal head and painful dislocation of the metatarsophalangeal (MTP) joint of 1 or more lesser toes. This aim of this study was to compare feet with noninflammatory arthritis and those with rheumatoid arthritis (RA) with respect to the clinical and radiographic outcomes after treatment of these destructive deformities with a modified Scarf osteotomy with medial capsular interposition into the newly formed first MTP joint, combined with metatarsal shortening offset osteotomy. METHODS: A retrospective observational study of 93 feet (31 with noninflammatory arthritis and 62 with RA) was performed. Hallux and lesser-toe scores on the Japanese Society for Surgery of the Foot (JSSF) scoring system, a self-administered foot evaluation questionnaire (SAFE-Q), and preoperative and postoperative radiographic parameters were evaluated. RESULTS: There were significant improvements at the time of the final follow-up in the mean scores on the hallux and lesser-toe scales of the JSSF system and in the SAFE-Q score. The postoperative JSSF lesser-toes function score was better for the feet with noninflammatory arthritis feet than the feet with RA. There was no significant difference in the hallux valgus angle (HVA) between 1 month postoperatively and the final follow-up for both groups. Furthermore, the HVA showed a strong correlation between the 1-month and final follow-up values. CONCLUSIONS: The combination of the modified Scarf osteotomy with medial capsular interposition and shortening metatarsal offset osteotomy was useful and safe in feet with noninflammatory arthritis. The HVA at 1 month after surgery is useful to predict the HVA within 5 years after surgery. The postoperative clinical score for the lesser toes was better in the feet with noninflammatory arthritis. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Characteristics of Intermetatarsal Angle Between the Second and Fifth Metatarsals (M2-M5A) in the Rheumatoid Foot.

BACKGROUND: Increasing of intermetatarsal angle between the first and second metatarsals (M1-M2A) has been reported as a risk factor for recurrence of hallux valgus (HV) deformity, on the other hand, increasing of intermetatarsal angle between the second and fifth metatarsals (M2-M5A) has been reported as a risk factor for resubluxation of the metatarsophalangeal (MTP) joint of the lesser toe after rheumatoid forefoot surgery. In this study, parameters related to increasing M2-M5A were investigated, as compared with M1-M2A and M1-M5A. METHODS: Radiographic parameters including M1-M2A, M1-M5A, and M2-M5A were retrospectively evaluated for 119 lower limbs from 68 patients with rheumatoid arthritis (RA). To clarify the clinical importance of these intermetatarsal angles, relationships with results from the timed up-and-go (TUG) test were also investigated. RESULTS: M1-M5A showed no correlation with mid-hind foot parameters, whereas M1-M2A and M2-M5A correlated with valgus/varus parameters. An increased M1-M2A was associated with lateral shift of the loading axis in the tibial plafond, whereas an increased M2-M5A was associated with medial shift, but M1-M5A showed no associations. M2-M5A/M1-M2A was significantly lower (1.7) in the normal TUG group than in the delayed TUG group (2.8) (p=0.045). CONCLUSIONS: Different patterns of spread are seen for the forefoot. One has a predominantly increased M1-M2A with lateral shift of the loading point in the tibial plafond, whereas the other has a predominantly increased M2-M5A with medial shift of the loading point in the tibial plafond. M2-M5A also should be calculated, and M2-M5A/M1-M2A might be meaningful in understanding physical mobility in RA patients.

Differential efficacy of TNF inhibitors with or without the immunoglobulin fragment crystallizable (Fc) portion in rheumatoid arthritis: the ANSWER cohort study.

Rheumatoid factor (RF) binds to the fragment crystallizable (Fc) portion of immunoglobulin. It could bind to the Fc portion of anti-TNF inhibitors (TNFi) and attenuate the clinical efficacy. We tried to determine whether the therapeutic efficacy of TNFi with Fc might be lower than that of TNFi without Fc in rheumatoid arthritis (RA) patients with high titres of RF. The Kansai Consortium for Well-being of Rheumatic Disease Patients (ANSWER) cohort is an observational multi-center registry of patients with RA in the Kansai district of Japan. RA patients treated with TNFi were included and divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, and etanercept) and TNFi without Fc (certolizumab pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) was compared by Mann-Whitney U test between TNFi with and without Fc in each RF titre group. Multiple linear regression analysis was used to analyze the effect of TNFi without Fc for the change of DAS28-ESR adjusted after potential confounders. A total of 705 RA patients were classified into four groups (RF1; RF 0-15.0 IU/mL, RF2; 15.0-55.0, RF3; 55.0-166, RF4; 166-7555). In RF4, RA patients treated with TNFi without Fc had a significantly lower DAS28-ESR than those treated with TNFi with Fc [3.2 (2.3-4.2) vs. 2.7 (2.0-3.0)] after 12 months. This effect of TNFi without Fc for the change of DAS28-ESR after 12 months treatment retained in multivariate analysis in RF4. TNFi without Fc may be more efficacious than TNFi with Fc in RA patients with high RF titres.

Drug efficacy and safety of biologics and Janus kinase inhibitors in elderly patients with rheumatoid arthritis.

Elderly patients with rheumatoid arthritis (RA) are frequently associated with higher disease activity and impaired physical function, although they show intolerance for conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, because of their comorbidities. However, the present treatment recommendation based on randomized controlled trials is not distinguished by age or comorbidities. Therefore, this review aimed to investigate the efficacy and safety of biological DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) in elderly patients. Present bDMARDs, including tumor necrosis factor inhibitors (TNFi), cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (abatacept), interleukin (IL)-6 receptor antibody (tocilizumab and salirumab), and anti-CD20 antibody (rituximab), may be similarly or slightly less effective or safe in elderly patients compared with younger patients. Oral glucocorticoid use, prolonged disease duration, and very old patients appear to be associated with an increased risk of adverse events, such as serious infection. Some recent cohort studies demonstrated that non-TNFi showed better retention than TNFi in elderly patients. Both TNFi and non-TNFi agents may not strongly influence the risk of adverse events such as cardiovascular events and malignancy in elderly patients. Regarding JAKi, the efficacy appears to be similar, although the safety (particularly for serious infections, including herpes zoster) may be attenuated by aging.