Associated correction of forefoot alignment with hindfoot fusion for pes planovalgus deformity.

BACKGROUND: The present study aimed to investigate changes in hallux alignment after corrective surgery for adult-acquired flatfoot deformity (AAFD). PATIENTS AND METHODS: The present study retrospectively investigated the changes of hallux alignment in 37 feet (33 patients) which were treated with double or triple arthrodesis of the hindfoot for AAFD between 2015 and 2021 and could be followed up to one year postoperatively. RESULTS: Hallux valgus (HV) angle significantly decreased by a mean 4.1° among the whole 37 subjects and by a mean 6.6° among the 24 subjects who had a preoperative HV angle of 15° or more. Those who had HV correction (HV angle correction ≥ 5°) demonstrated more near-normal postoperative alignment of the medial longitudinal arch and hindfoot than those without HV correction. CONCLUSIONS: Hindfoot fusion for AAFD could improve preoperative HV deformity to some degree. HV correction was associated with proper realignment of the midfoot and hindfoot. LEVEL OF EVIDENCE: Level IV; retrospective case series.

Factors affecting bone union after distal shortening oblique osteotomy of the lesser metatarsals.

Objectives: There have been few reports on factors affecting bone union after metatarsal osteotomies. The purpose of this study was to clarify the factors affecting bone union after distal shortening oblique osteotomy of the lesser metatarsals.Methods: Patients who underwent distal shortening oblique osteotomy of the lesser metatarsals were retrospectively investigated. Failure to achieve bone union at 6 months after surgery was defined as delayed union. Background characteristics and radiographic measurements were compared between patients with and those without delayed union, and factors affecting bone union were assessed using multivariate analysis.Results: Among 204 toes in 58 patients evaluated in this study, delayed union occurred in 28%. In multivariate analysis, corticosteroid use (odds ratio (OR), 3.68; 95% confidence interval (CI), 1.65-8.16; p< .01), larger preoperative overlap between the metatarsal and the proximal phalanx (OR, 1.11 (per 1 mm increase); 95% CI, 1.02-1.21; p= .02), and larger gap at the osteotomy site (OR, 3.02 (per 1 mm increase); 95% CI, 1.76-5.16; p< .01) were identified as independent risk factors of delayed union.Conclusion: The identified risk factors of delayed union after distal shortening metatarsal osteotomies were corticosteroid use, preoperative overlap between the metatarsal and the proximal phalanx, and a gap at the osteotomy site.

Lateral collapse of the tarsal navicular in patients with rheumatoid arthritis: Implications for pes planovarus deformity.

OBJECTIVES: In patients with rheumatoid arthritis (RA), the talonavicular joint is commonly involved and midfoot collapse can lead to progressive flattening of the arch. Despite a general awareness of the important structural role of the talonavicular joint in rheumatoid foot disease, details of its destructive pattern have not been elucidated. METHODS: We cross-sectionally investigated 176 RA patients (342 feet) and classified their feet into the following five groups according to radiographic findings: arthritis (RA changes with normal navicular shape), Müller-Weiss Disease (MWD) (collapse of the lateral aspect of the tarsal navicular), flat (flattened navicular), ankylosis (ankylosis of the talonavicular joint), and normal. We compared medical histories and radiographic measurements among all five groups. RESULTS: The arthritis group comprised 91 feet, 36 in the MWD group, nine in the flat group, 12 in the ankylosis group, and 194 classified as normal. The MWD group demonstrated a trend towards pes planovarus deformity in contrast to pes planovalgus deformity in the arthritis group. Corticosteroid use and the mean daily dosage were the highest in the MWD group. CONCLUSIONS: This report revealed a high prevalence of MWD-like changes to the navicular in RA patients and its association with pes planovarus deformity and corticosteroid usage.

Severe pes planovalgus successfully treated in a patient with mutilating rheumatoid arthritis using a new surgical approach involving medial malleolar resection and medial displacement of the talus: A case report.

We report the case of a 56-year-old female with mutilating rheumatoid arthritis, who developed severe pes planovalgus. The foot was successfully reconstructed through a combination of osteotomies, including medial displacement of the talus accompanied by resection of the medial malleolus. This maneuver enabled a ∼1-cm medial displacement of the hindfoot while minimizing the adverse effect on forefoot rotation.

Radiologic Patterning of Hallux Deformity in Rheumatoid Arthritis and Its Relationship to Flatfoot.

Hallux deformities other than hallux valgus, especially those in the sagittal plane, have not yet been elucidated in the feet of patients with rheumatoid arthritis. The objectives of the present study were to classify rheumatoid arthritis hallux deformity in both the horizontal and the sagittal planes and investigate its relationship with flatfoot. Using a cross-sectional study design, we assessed patients with rheumatoid arthritis (527 feet in 274 patients) using radiographs and classified the deformity patterns of the great toes using cluster analysis. Of the 274 patients, the range of motion in the metatarsophalangeal joint was clinically investigated in 44 (16.1%) patients. The great toes could be divided into 5 clusters according to the characteristic configuration as follows: cluster I (normal type), cluster II (hallux valgus type), cluster III (boutonniere type), cluster IV (boutonniere with hallux valgus type), and cluster V (swan-neck type). Radiographic measurements revealed the characteristic deformities of each cluster, including splayed foot for cluster II; flat foot, metatarsal primus elevatus, and plantar displacement of the proximal phalanx for cluster III; and a mixture of these characteristics for cluster IV. Plantar displacement of the proximal phalanx, which was a specific characteristic of the boutonniere deformity, correlated significantly with the decreased dorsiflexion in the metatarsophalangeal joint. Our classification method revealed the relationship of hallux deformity in the sagittal plane to flatfoot and also demonstrated the usefulness of measuring basal phalanx displacement in predicting the range of motion of the metatarsophalangeal joint.

Correlation between knee and hindfoot alignment in patients with rheumatoid arthritis: The effects of subtalar joint destruction.

OBJECTIVES: Compensatory hindfoot alignment for deformities at the knee level has been demonstrated in patients with knee osteoarthritis. However, this phenomenon has not been elucidated in patients with rheumatoid arthritis (RA). The aim of this study is to investigate the relationship between knee deformity and hindfoot alignment and the effect of subtalar joint destruction in patients with RA. METHODS: We retrospectively investigated RA patients (110 patients, 205 limbs) using radiographs in the standing anteroposterior knee, standing lateral foot, and hindfoot alignment views. The grade of destruction at the knee and subtalar joints was assigned using Larsen's grading system. The correlation between the femorotibial and tibiocalcaneal angles and the effect of joint destruction on this correlation were analyzed using Pearson's correlation coefficients. RESULTS: There was moderate correlation between the femorotibial and tibiocalcaneal angles in a group of knees with a Larsen grade of ≥ 4 (r = 0.544, p = 0.0239). This correlation was stronger in a group with less damaged subtalar joints with a Larsen grade of ≤ 3 (r = 0.705, p = 0.0049). CONCLUSION: These findings emphasized the importance of examining foot and ankles in patients with RA who undergo total knee arthroplasty.

Vertebral fractures affect functional status in postmenopausal rheumatoid arthritis patients.

Functional disability is a major concern in patients with rheumatoid arthritis (RA). This retrospective study investigated the risk factors for vertebral fractures (VFs) in postmenopausal RA patients and determined the impact of VFs on functional status. Data from a cohort of 200 postmenopausal RA patients in a single hospital registry were analyzed. Demographic and clinical data, imaging data from spine radiographs, and bone mineral density (BMD) data were collected from the patients at baseline and at the final visit (a mean of 2.9 years after the first visit). Risk factors for incident VFs and their impact on the modified health assessment questionnaire (mHAQ) were analyzed. Twenty-eight patients (14%) developed new VFs (NVFs). Logistic regression analysis adjusted for age, BMI, and disease duration revealed that daily dose of prednisolone, femoral neck BMD, use of active vitamin D3, and use of a bisphosphonate at baseline were factors associated with NVF, with odds ratios (95% confidence interval) of 1.27 (1.05-1.54), 0.94 (0.91-0.97), 0.34 (0.13-0.89), and 0.31 (0.12-0.82), respectively. Patients with NVF exhibited worse mHAQ scores and a greater increase in mHAQ scores from baseline compared with those without NVF. In conclusion, incident VFs were associated with reduced functional status in postmenopausal patients with RA. It is important to prevent VFs to maintain the functional status of RA patients.

Systemic inflammatory responses after orthopedic surgery in patients with rheumatoid arthritis treated with tofacitinib.

OBJECTIVE: To investigate the acute phase response to surgical stress in patients with rheumatoid arthritis (RA) treated with tofacitinib, a Janus kinase (JAK) inhibitor. METHODS: A retrospective matched pair analysis of 34 patients treated with tofacitinib and 34 patients treated with conventional disease-modifying anti-rheumatic drugs (csDMARDs) was performed. Patients were matched for age, sex, and type of surgery; body temperature, C-reactive protein (CRP) level, and white blood cell (WBC) count, neutrophil count, and lymphocyte count were compared between the tofacitinib and csDMARDs groups within 2 weeks after orthopedic surgery. Postoperative complications within 90 days were also assessed. RESULTS: No surgical site infection or delayed wound healing was observed in the tofacitinib group; whereas, one case of superficial infection was noted in the csDMARDs group. A similar postoperative increase in body temperature and CRP level was observed in both the groups. Postoperatively, the tofacitinib group showed an increase in WBC and neutrophils counts and a decrease in lymphocyte count, unlike the csDMARDs group. In contrast to two patients (2.6%) in the csDMARDs group, seven patients (20.6%) in the tofacitinib group had lymphocyte counts below 500 cells/µL within 2 weeks postoperatively. CONCLUSION: Tofacitinib did not suppress postoperative increase in body temperature and CRP level. Because of the postoperative decrease in lymphocyte count in patients treated with tofacitinib, the timing for resuming tofacitinib treatment after surgery should be carefully considered. Key Points • This study is the first to report the complications and systemic inflammatory responses after orthopedic surgery in patients treated with tofacitinib in comparison with matched pairs treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) • While tofacitinib does not suppress postoperative increase in body temperature and CRP level, the postoperative decrease in lymphocyte count in patients treated with tofacitinib is significant compared with patients treated with csDMARDs • Attention should be paid to a reduced lymphocyte count when to resume tofacitinib after surgery.

Wrist Arthrodesis in Rheumatoid Arthritis Using an LCP Metaphyseal Locking Plate versus an AO Wrist Fusion Plate.

OBJECTIVES: Although wrist arthrodesis using a plate is an established treatment with a well-documented successful union rate for severely destroyed wrists, plate-related complications are a matter of great concern. METHODS: We retrospectively compared wrist arthrodesis using an AO wrist fusion plate in nine and a locking compression plate (LCP) metaphyseal plate in seven cases of rheumatoid arthritis. RESULTS: The mean follow-up was 40.6 months in the AO wrist fusion plate group and 57.2 months in the LCP metaphyseal plate group. Bone union at the arthrodesis site was achieved in all cases in both groups. Comparison of the original position of the fusion on the immediate postoperative radiographs and the position on the most recent follow-up radiographs demonstrated good stability in both groups. Plate-related complications occurred in four cases in the AO wrist fusion plate group and no cases in the LCP metaphyseal plate group. Complications included pain over the plate, wound dehiscence and infection, extensor tendon adhesion, and fracture in one case each. CONCLUSION: Wrist arthrodesis using an LCP metaphyseal plate was favorable for rheumatoid arthritis patients with comparable stability to that of and a lower risk of plate-related complications than an AO wrist fusion plate.

Bilateral Stress Fractures of the Talus Associated with Adult-Acquired Flatfoot Deformities.

Adult-acquired flatfoot deformity is a progressive flattening of the arch of the foot that results from posterior tibial tendon insufficiency with a predilection for middle-aged women. A lateralized force vector associated with hindfoot valgus in adult-acquired flatfoot produces lateral ankle pain due to impingement at the lateral hindfoot, which can even lead to stress fractures of the distal fibula. Here, we present the rare case of a 73-year-old woman who presented with stress fractures of the bilateral taluses and unilateral distal fibula accompanied by severe adult-acquired flatfoot deformities.

[RANKL vaccination].

A therapeutic vaccine approach, targeting RANKL, can be used to inhibit bone destruction in pathological bone loss conditions such as osteoporosis, rheumatoid arthritis and bone metastasis. Compared to other therapeutic recombinant protein against pathological antigen such as monoclonal antibodies, soluble receptor or other antagonists, a vaccine needs small doses of protein to induce its affect. Once the immune response is established by vaccination, it is maintained by boosting with the vaccine. This RANKL vaccination would be a novel approach to any kind of pathological bone

LIGHT induces cell proliferation and inflammatory responses of rheumatoid arthritis synovial fibroblasts via lymphotoxin beta receptor.

OBJECTIVE: To investigate the effects of LIGHT (lymphotoxin-like, exhibits inducible expression and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes) on the proliferation and gene expression of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). METHODS: We measured LIGHT levels in RA synovial fluids (SF) by ELISA, and compared them with those in osteoarthritis (OA) SF. Levels of LIGHT and its receptors in RA-FLS and synovium were assessed using real-time quantitative polymerase chain reaction (PCR). RA-FLS proliferation was examined by a bromodeoxyuridine assay. Expression of intercellular adhesion molecule-1 (ICAM-1) and several chemokines, such as interleukin 8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1alpha (MIP-1alpha), was examined by real-time quantitative PCR, ELISA, and flow cytometry. The effects of LIGHT on nuclear factor-kappaB (NF-kappaB) activation were investigated using immunofluorescence and Western blotting. RESULTS: LIGHT was upregulated in both SF and synovium of RA patients compared with OA patients. Herpes virus entry mediator (HVEM) and lymphotoxin beta receptor (LTbetaR), but not LIGHT, were detected in RA-FLS. LIGHT significantly promoted RA-FLS proliferation and induced expression of MCP-1, IL-8, MIP-1alpha, and ICAM-1 by RA-FLS. As well, LTbetaR small interfering RNA (siRNA), but not HVEM siRNA, inhibited these effects of LIGHT. LIGHT induced IkappaBa degradation and NF-kappaB translocation, and a NF-kappaB inhibitor suppressed the effects of LIGHT on RA-FLS. CONCLUSION: Our findings suggest that LIGHT signaling via LTbetaR plays an important role in the pathogenesis of RA by affecting key processes such as the proliferation and activation of RA-FLS. Regulation of LIGHT-LTbetaR signaling may represent a new therapeutic target for RA treatment.

Regional differences in chondrocyte metabolism in osteoarthritis: a detailed analysis by laser capture microdissection.

OBJECTIVE: To determine the change in metabolic activity of chondrocytes in osteoarthritic (OA) cartilage, considering regional difference and degree of cartilage degeneration. METHODS: OA cartilage was obtained from knee joints with end-stage OA, at both macroscopically intact areas and areas with various degrees of cartilage degeneration. Control cartilage was obtained from age-matched donors. Using laser capture microdissection, cartilage samples were separated into superficial, middle, and deep zones, and gene expression was compared quantitatively in the respective zones between OA and control cartilage. RESULTS: In OA cartilage, gene expression changed markedly with the site. The expression of cartilage matrix genes was highly enhanced in macroscopically intact areas, but the enhancement was less obvious in the degenerated areas, especially in the upper regions. In contrast, in those regions, the expression of type III collagen and fibronectin was most enhanced, suggesting that chondrocytes underwent a phenotypic change there. Within OA cartilage, the expression of cartilage matrix genes was significantly correlated with SOX9 expression, but not with SOX5 or SOX6 expression. In OA cartilage, the strongest correlation was observed between the expression of type III collagen and fibronectin, suggesting the presence of a certain link(s) between their expression. CONCLUSION: The results of this study revealed a comprehensive view of the metabolic change of the chondrocytes in OA cartilage. The change of gene expression profile was most obvious in the upper region of the degenerated cartilage. The altered gene expression at that region may be responsible for the loss of cartilage matrix associated with OA.

Zonal gene expression of chondrocytes in osteoarthritic cartilage.

OBJECTIVE: To determine the chondrocyte metabolism in respective zones of osteoarthritic (OA) cartilage. METHODS: OA cartilage was obtained from macroscopically intact areas of 4 knee joints with end-stage OA. The cartilage was divided into 3 zones, and gene expression profiles were determined in the respective zones by a custom-designed microarray that focused on chondrocyte-related genes. For the genes whose expression was significantly different among the zones, the expression was compared between OA and control cartilage in the respective zones by an analysis using laser capture microdissection and real-time polymerase chain reaction (PCR). For some genes, the correlation of expression was investigated in specific cartilage zones. RESULTS: A total of 198 genes (approximately 40% of those investigated) were found to be expressed at significantly different levels among the zones. Expression of 26 of those genes was evaluated by laser capture microdissection and real-time PCR, which confirmed the validity of microarray analysis. The expression of cartilage matrix genes was mostly enhanced in OA cartilage, at similar levels across the zones but at different magnitudes among the genes. The expression of bone-related genes was induced either in the superficial zone or in the deep zone, and positive correlations were found among their expression in the respective zones. The expression of 5 proteinase genes was most enhanced in the superficial zone, where their expression was correlated, suggesting the presence of a common regulatory mechanism(s) for their expression. CONCLUSION: In OA cartilage, the metabolic activity of chondrocytes differed considerably among zones. Characteristic changes were observed in the superficial and deep zones.

Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients.

BACKGROUND: The epidermal growth factor (EGF) and EGF receptor (EGFR) families play important roles in the hyperplastic growth of several tissues as well as tumor growth. Since synovial hyperplasia in rheumatoid arthritis (RA) resembles a tumor, involvement of the EGF/EGFR families in RA pathology has been implied. Although several reports have suggested that ErbB2 is the most important member of the EGFR family for the synovitis in RA, it remains unclear which members of the EGF family are involved. To clarify the EGF-like growth factors involved in the pathology of RA, we investigated the expression levels of seven major EGF-like growth factors in RA patients compared with those in osteoarthritis (OA) patients and healthy control subjects. METHODS: The expression levels of seven EGF-like growth factors and four EGFR-like receptors were measured in mononuclear cells isolated from bone marrow and venous blood, as well as in synovial tissues, using quantitative RT-PCR. Further evidence of gene expression was obtained by ELISAs. The proinflammatory roles were assessed by the growth-promoting and cytokine-inducing effects of the corresponding recombinant proteins on cultured fibroblast-like synoviocytes (FLS). RESULTS: Among the seven EGF-like ligands examined, only amphiregulin (AREG) was expressed at higher levels in all three RA tissues tested compared with the levels in OA tissues. The AREG protein concentration in RA synovial fluid was also higher than that in OA synovial fluid. Furthermore, recombinant human AREG stimulated FLS to proliferate and produce several proinflammatory cytokines, including angiogenic cytokines such as interleukin-8 and vascular endothelial growth factor (VEGF), in a dose-dependent manner. The VEGF mRNA levels in RA synovia and VEGF protein concentrations in RA synovial fluid were significantly higher than those in the corresponding OA samples and highly correlated with the levels of AREG. CONCLUSION: The present findings suggest that AREG functions to stimulate synovial cells and that elevated levels of AREG may be involved in the pathogenesis of RA.

Enlarged psoas muscle and iliopsoas bursitis associated with a rapidly destructive hip in a patient with rheumatoid arthritis.

A 39-year-old man with rheumatoid arthritis developed femoral neuropathy secondary to iliopsoas bursitis. The adjacent hip joint was severely damaged. Magnetic resonance imaging showed enlargement and inflammation of the psoas muscle at the same side of iliopsoas bursitis. Iliopsoas bursitis and abnormal findings of the psoas muscle disappeared while the symptoms improved.

Production of interleukin-6 and interleukin-8 by nurse-like cells from rheumatoid arthritis patients after stimulation with monocytes.

It has been reported that nurse-like cells (NLCs) play a critical role in the pathogenesis of rheumatoid arthritis (RA). The interaction between NLCs established from RA patients (RA-NLCs), and freshly isolated blood monocytes was analyzed to further elucidate the pathogenesis of RA. RA-NLC lines were established from the synovium of RA patients. The RA-NLCs were cultured with monocytes freshly isolated from peripheral blood of healthy donors, and induction of interleukin (IL)-6 and IL-8 as well as the mRNA expression of these cytokines was examined. The levels of IL-6 were over 400 times higher in the supernatant from coculture of RA-NLCs and monocytes than in those from cultures of RA-NLCs alone. Anti-tumor necrosis factor (TNF)-alpha monoclonal antibody inhibited the induction of both cytokine in a dose-dependent fashion, although there was no detectable level of TNF-alpha in the supernatant from coculture. In addition, coculture of RA-NLCs and monocytes without direct cell contact did not induce cytokine production. To determine IL-6 producing cells, RA-NLCs and monocytes were separated into each fraction after coculture for 24 h. Cocultured RA-NLCs contained approximately 80 times higher IL-6 mRNA than the RA-NLCs cultured alone. The levels of IL-8 were also much higher (about 900 times) in the supernatant from coculture than in those from cultures of RA-NLCs alone. Cocultured RA-NLCs expressed IL-8 mRNA about 620 times higher than those cultured alone. These results indicate that NLCs produce high levels of IL-6 and IL-8 after cell-cell interaction with monocytes/macrophages via membrane-bound TNF-alpha, and that activation of NLCs by monocytes/macrophages may be involved in the pathogenesis of RA through maintenance of synovial inflammation.