Is there a reduction in hip destruction under a treat-to-target strategy in patients with rheumatoid arthritis?

OBJECTIVES: The treatments for rheumatoid arthritis (RA) have been greatly improved, and the tight control of disease activity yields superior clinical outcomes. This study aimed to elucidate the accompanying changes in hip destruction following the implementation of a treat-to-target strategy for patients with RA. METHODS: We extracted 190 hips over two periods, i.e. the early period (1998-2003) and the late period (2013-19), with 103 and 87 hips, respectively. The observed rheumatic changes, such as inward migration, upward migration, and femoral head collapse, were quantitatively evaluated, while osteoarthritic changes, such as the formation of a capital drop, were investigated from radiographs before primary total hip arthroplasty. RESULTS: A comparison of the two periods' data showed that the degree of inward migration (-3.44 vs. -7.45 mm; P < .001) and upward migration (+4.3 vs. +0.95 mm; P < .001) significantly decreased in the late-period group. The collapse of the femoral head was not significantly different. The incidence of capital drops was significantly higher in the late-period group (7.8% vs. 27.5%; P < .001). CONCLUSIONS: The degree of inward and upward migration representative of rheumatic changes reduced, whereas the frequency of capital drops as osteoarthritic changes increased during the late period.

Risk factor analysis of vertebral fractures requiring surgery in patients with ankylosing spondylitis.

OBJECTIVES: This study aimed to determine the risk factors for vertebral fractures requiring surgery in patients with ankylosing spondylitis (AS). METHODS: We included 60 patients with AS diagnosed by using the modified New York criteria and who were treated in our department from April 2004 to March 2019. We evaluated age, sex, disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ankylosed sacroiliac joint, bamboo spine, number of ankylosed vertebrae, and treatment (nonsteroidal antiinflammatory drugs (NSAIDs)), prednisolone (PSL), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological disease-modifying antirheumatic drugs (bDMARDs), spine surgery for vertebral fracture) at the final follow-up of the nonsurgical group and the preoperative follow-up of the surgical group. RESULTS: At the final follow-up, the mean age was 49 years, 46 patients (75%) were male, and the mean disease duration was 27 years. Additionally, 8 (13.3%) and 43 patients (71%) underwent surgical and medical treatments, respectively. The group of surgery for vertebral fracture had significantly higher CRP levels, which was also significantly associated with vertebral fracture surgery by multivariate analysis. CONCLUSIONS: CRP was identified as a risk factor for vertebral fractures requiring surgery. Control of systemic inflammation in patients with AS may reduce the risk of vertebral fractures requiring surgery.

C10orf10/DEPP activates mitochondrial autophagy and maintains chondrocyte viability in the pathogenesis of osteoarthritis.

Osteoarthritis (OA), the most prevalent joint disease, is characterized by the progressive loss of articular cartilage. Autophagy, a lysosomal degradation pathway, maintains cellular homeostasis, and autophagic dysfunction in chondrocytes is a hallmark of OA pathogenesis. However, the cause of autophagic dysfunction in OA chondrocytes remains incompletely understood. Recent studies have reported that decidual protein induced by progesterone (C10orf10/DEPP) positively regulates autophagic functions. In this study, we found that DEPP was involved in mitochondrial autophagic functions of chondrocytes, as well as in OA pathogenesis. DEPP expression decreased in human OA chondrocytes in the absence or presence of pro-inflammatory cytokines, and was induced by starvation, hydrogen peroxide (H2 O2 ), and hypoxia (cobalt chloride). For functional studies, DEPP knockdown decreased autophagic flux induced by H2 O2 , whereas DEPP overexpression increased autophagic flux and maintained cell viability following H2 O2 treatment. DEPP was downregulated by knockdown of forkhead box class O (FOXO) transcription factors and modulated the autophagic function regulated by FOXO3. In an OA mouse model by destabilization of the medial meniscus, DEPP-knockout mice exacerbated the progression of cartilage degradation with TUNEL-positive cells, and chondrocytes isolated from knockout mice were decreased autophagic flux and increased cell death following H2 O2 treatment. Subcellular fractionation analysis revealed that mitochondria-located DEPP activated mitochondrial autophagy via BCL2 interacting protein 3. Taken together, our data demonstrate that DEPP is a major stress-inducible gene involved in the activation of mitochondrial autophagy in chondrocytes, and maintains chondrocyte viability during OA pathogenesis. DEPP represents a potential therapeutic target for enhancing autophagy in patients with OA.

Autoreactivity of Peripheral Helper T Cells in the Joints of Rheumatoid Arthritis.

Autoreactive CD4 T cells are thought to play pivotal roles in the pathogenesis of rheumatoid arthritis (RA). Recently, a subset of CD4 T cells that express high levels of programmed death-1 (PD-1) but are distinct from follicular helper T cells have been identified in the joints of RA patients and named peripheral helper T (Tph) cells. Because PD-1 is expressed on T cells chronically stimulated with the Ags, we tested a hypothesis that Tph cells are the pathogenic autoreactive CD4 T cells in RA. We found that human Tph cells in RA joints produce proinflammatory effector cytokines, including IFN-γ, TNF-α, and GM-CSF, in addition to B cell-helping cytokines, such as IL-21 and CXCL13. Flow cytometric analysis showed different bias of TCR Vß usage between PD-1high Tph cells and PD-1low/neg CD4 T cells, including Th1 cells, in the joint or memory CD4 T cells in the peripheral blood, whereas there was little difference between the latter two subsets. In line with this, deep sequencing of TCR demonstrated an overlap of expanded clones between peripheral blood memory CD4 T cells and PD-1low/neg CD4 T cells but not Tph cells in the joint. Interestingly, Tph cells preferentially exhibited autologous MLR in vitro, which required recognition of self-MHC class II and was pronounced by blocking PD-1 signaling. Taken together, these results suggest that Tph cells are the pathogenic autoreactive CD4 T cells in RA, which expand locally in the joints and are regulated by PD-1 signaling.

"Grand-piano sign" as a femoral rotational indicator in both varus and valgus knees: a simulation study of anterior resection surface in total knee arthroplasty.

PURPOSE: The "Grand-piano sign" is a popular indicator of the appropriate rotational alignment of the femoral component during total knee arthroplasty (TKA). The aim of the study was to investigate the shape of the anterior femoral resection surface of varus and valgus knees. METHODS: A cohort of 80 varus knees and 40 valgus knees (hip-knee-ankle angle > 2° for varus and < - 2° for valgus knees) matched for age, sex, height, body weight, and KL grade was made using propensity score matching. Virtual TKA was performed using 3 patterns of components (anterior flange flexion angles of 3°, 5°, and 7°). The anterior femoral resection surface was evaluated for 3 patterns of rotational alignments: parallel to the surgical epicondylar axis (NR, neutral rotation), 3° internal rotation (IR), and 3°external rotation (ER) relative to the surgical epicondylar axis. In each anterior femoral resection surface, the vertical height of medial and lateral condyles was measured, and the ratio of the medial to the lateral height (M/L ratio) was evaluated. RESULTS: The M/L ratio in NR for both varus and valgus knees was 0.57 to 0.64, with no significant difference between the cohorts (p value > 0.05). The M/L ratio showed a similar pattern of increasing at IR and decreasing at ER in both varus and valgus knees. The variation in the M/L ratio with malrotation in valgus knees was smaller than in varus knees. CONCLUSION: During TKA, the anterior femoral resection surface was similar in varus and valgus knees; however, the variation with malrotation was smaller in valgus knees than in varus knees. TKA for valgus knees requires precise surgical technique and careful intraoperative assessment. LEVEL OF EVIDENCE: IV, Case series.

Complications After Orthopedic Surgeries in Patients with Rheumatoid Arthritis Treated with Janus Kinase Inhibitors: a Retrospective Observational Study.

OBJECTIVES: The current study compared the outcome after orthopedic surgeries in patients with RA receiving JAKi versus biologic disease-modifying anti-rheumatic drugs (bDMARDs). METHODS: This was a retrospective observational study of Japanese patients with RA. Sixty-two patients with RA using JAKi preoperatively underwent orthopedic surgeries. Using propensity score matching, these 62 patients were matched with 62 patients using bDMARDs preoperatively. The number of adverse events was counted. We also examined whether the drug-withholding period in the JAKi-treated group was associated with the occurrence of major postoperative adverse events, namely inflammatory flares and delayed wound healing (DWH). RESULTS: JAKi-treated patients had a higher incidence of postoperative flares than bDMARDs-treated patients (29% vs 12.1%, p=0.01). The incidences of postoperative complications other than flares were not significantly different between the two groups. Among the JAKi-treated group, a longer perioperative drug-withholding period (≥11 days) was associated with a higher incidence of postoperative flares (p=0.04). The incidences of DWH and SSI were not associated with the duration of the JAKi withholding period. CONCLUSION: JAKi-treated patients had a higher incidence of postoperative flares than bDMARDs-treated patients. A total of 11 days or more of drug withdrawal was associated with postoperative flares.

Similar short-term KOOS between open-wedge high tibial osteotomy and total knee arthroplasty in patients over age 60: A propensity score-matched cohort study.

OBJECTIVES: The purpose of the present study was to evaluate improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) after open-wedge high tibial osteotomy (HTO) in comparison with total knee arthroplasty (TKA) in cohorts over age 60 matched by pre-operative age, gender, body mass index (BMI), hip-knee-ankle angle (HKAA), KOOS sub-scores, and osteoarthritis (OA) grade. METHODS: Propensity score matching was performed between 162 HTO patients and 134 TKA patients. When calculating the propensity score by multivariate logistic regression analysis, the following pre-operative confounders were included: age, gender, BMI, HKAA, KOOS sub-scores, and OA grade. Consequently, a total of 55 patients were included in each group. The Student's t-test was used to analyse differences in the post-operative KOOS sub-scores between groups. RESULTS: After propensity score matching, all matched pre-operative valuables were identical, with no significant differences between the HTO and TKA groups. None of the post-operative KOOS sub-scores at 1 year after surgery showed a significant difference between the HTO and TKA groups. Both groups demonstrated significant and comparable post-operative improvement in every KOOS sub-score. CONCLUSIONS: In patients over age 60, there was no significant difference in short-term pain relief and improvements in activity and quality of life between HTO and TKA after propensity score matching including pre-operative age, KOOS sub-scores, and OA grade. HTO is a joint preservation procedure that is valid for knee OA even in individuals over age 60.

Improved surgical procedure of primary constrained total knee arthroplasty which enables use of the femoral diaphyseal straight extension stem.

BACKGROUND: In performing primary constrained total knee arthroplasties (TKA) to imbalanced knees, the offset stem is sometimes compelled to use, although this is associated with surgical difficulties. We developed a modified procedure which might be able to fit the anteroposterior (AP) and mediolateral (ML) position of the femoral component simultaneously with the straight stem. Purposes of this study were to evaluate usefulness of the modified procedure both in computer simulations and actual surgeries. METHODS: We included 32 knees that had undergone primary TKA using constrained implants because of the coronal imbalance. In the component-first procedure, the distal femur was prepared to fit the AP and ML position of the femoral component simultaneously at first, as in primary TKA. Finally, the stem hole is created based on the femoral component position (the component-first procedure). The femoral component and extension stem were simulated using the three-dimensional planning software (ZedKnee) following the component-first procedure. We investigated the suitability of the straight stem through computer simulation and evaluation of actual surgeries. Clinical and radiographical outcomes were also evaluated at the latest follow-up. RESULTS: The component-first procedure enabled the AP and ML position of the femoral component to be fitted simultaneously with the straight stem in simulations and actual surgeries in all cases. The stem diameter was not significantly different between simulations and actual surgeries (13.9 and 13.7 mm on average, respectively, p = 0.479) and almost similar from intraclass correlation coefficient analysis (kappa value 0.790). Clinical and radiographical outcomes were almost similar to primary TKA cases and there was no case of component loosening, cortical bone hypertrophy around the stem and stem-tip pain. CONCLUSIONS: Our improved surgical procedure may facilitate use of the constrained implant for more cases of primary TKA in imbalanced knees without the usual surgical difficulties. TRIAL REGISTRATION: Retrospectively registered.

Sagittal femoral bowing contributes to distal femoral valgus angle deviation in malrotated preoperative radiographs.

BACKGROUND: The coronal whole-leg radiograph is generally used for preoperative planning in total knee arthroplasty. The distal femoral valgus angle (DFVA) is measured for distal femoral bone resection using an intramedullary guide rod. The effect of coronal and sagittal femoral shaft bowing on DFVA measurement in the presence of malrotation or knee flexion contracture has not been well reported. The objectives of this study were: (1) to investigate the effects of whole-leg malrotation and knee flexion contracture on the DFVA in detail, (2) to determine the additional effect of coronal or sagittal femoral shaft bowing. METHODS: We studied 100 consecutive varus and 100 valgus knees that underwent total or unicompartmental knee arthroplasty. Preoperative CT scans were used to create digitally reconstructed radiography (DRR) images in neutral rotation (NR, parallel to the surgical epicondylar axis), and at 5° and 10° external rotation (ER) and internal rotation (IR). The images were also reconstructed at 10° femoral flexion. The DFVA was evaluated in each DRR image, and the angular variation due to lower limb malposition was investigated. RESULTS: The DFVA increased as the DRR image shifted from IR to ER, and all angles increased further from extension to 10° flexion. The DFVA variation in each position was 1.3° on average. A larger variation than 2° was seen in 12% of all. Multivariate regression analysis showed that sagittal femoral shaft bowing was independently associated with a large variation of DFVA. Receiver operating characteristic analysis showed that more than 12° of sagittal bowing caused the variation. CONCLUSION: If femoral sagittal bowing is more than 12°, close attention should be paid to the lower limb position when taking whole-leg radiographs. Preoperative planning with whole-leg CT data should be considered.

Transverse osteotomy closer to tibial plateau is associated with larger postoperative change in valgus laxity after open-wedge high tibial osteotomy.

PURPOSE: To identify the factors impacting changes in valgus laxity between before and after open-wedge high tibial osteotomy (OW-HTO) using quantitative valgus stress radiographs. METHODS: A total of 40 knees from 38 patients who underwent OW-HTO were assessed. The study population comprised 14 men and 24 women, with a mean age of 61.5 years. Valgus stress radiographs before and 1 year after OW-HTO were performed using a Telos device. The difference between pre- and postoperative joint line convergence angle (JLCA) was expressed as ΔJLCA (post-pre). As indicators of the proximal detachment of superficial medial collateral ligament (sMCL) on radiographs, two distances were defined: the distance from the level of the osteotomy starting point to the tangent line of the proximal tibial plateau (Distance A), or to the medial edge of the proximal tibial plateau (Distance B). Correlations between ΔJLCA and radiographic parameters or KOOS sub-scores were assessed using Spearman's rank correlation coefficient analysis. Receiver operator curves were generated to evaluate the predictive strength of the significant factor for an increase in ΔJLCA > 1°. RESULTS: Pre-operative OA severity consisted of Kellgren-Lawrence grade 2 (n = 18), 3 (n = 16), and 4 (n = 6). The average ΔJLCA (post-pre) was 0.5°, and ranged from - 1.4° to + 3.0°. The maximum systemic measurement error and limits of agreement were 0.07° and 0.20°, respectively. There were significant correlations between ΔJLCA and Distance A (36.9 ± 3.9 mm, R = - 0.46, p = 0.002), between ΔJLCA and Distance B (39.9 ± 4.0 mm, R = - 0.49, p = 0.001). The cut-off value for Distance A was determined to be 35 mm below the tibial plateau; the AUC was 0.804, with a sensitivity of 0.75 and a specificity of 0.82. Distance B correlated strongly with Distance A (R = 0.96, p < 0.001). There was no significant correlation between ΔJLCA and KOOS sub-scores 1 year after OW-HTO. CONCLUSIONS: Transverse osteotomy closer to tibial plateau was associated with larger valgus joint laxity postoperatively. This finding implies that sMCL proximal detachment, which was related to the level of the osteotomy starting point on the proximal tibia, potentially affected postoperative valgus laxity. LEVEL OF EVIDENCE: IV.

Angular accuracy of plain radiographic measurements in leg alignment: Teleoroentgenogram versus orthoroentgenogram.

BACKGROUND: The purpose of the present study was to evaluate the accuracy of the measurements associated with leg alignment on a teleoroentgenogram and an orthoroentgenogram. METHODS: The models being irradiated were manufactured and represented 10° varus and 15° varus leg alignment, in which the true values of hip-knee-ankle angle (HKAA), mechanical axis (MA) length, and percentage of MA (%MA) were already known. HKAA, MA length, and %MA were measured in various radiographic conditions of the teleoroentgenogram and orthoroentgenogram. Then, the differences between the radiographic measurement values and the corresponding true values were analyzed. RESULTS: Regarding HKAA, the teleoroentgenogram provided accurate angular measurements with minimal differences between the measurement and true value in both the 10° and 15° varus models, irrespective of the radiographic condition. In the orthoroentgenogram, the modified method measured accurate HKAA; however, the standard method showed significant angular measurement errors with a 0.6° and 1.0° difference from the true value in the 10° and 15° varus models, respectively. This angular measurement error of HKAA in the standard orthoroentgenogram became significantly larger with object-to-image distance. Regarding MA length, the orthoroentgenogram exhibited accurate length measurements. In contrast, the teleoroentgenogram showed a significant length measurement error for the MA length. Regarding %MA, significant differences from the true values of 2.0% and 2.4% were observed in the modified orthoroentgenograms of the 10° and 15° varus models, respectively. The teleoroentgenogram and standard orthoroentgenogram reproduced the accurate measurement value of %MA in the 10° and 15° varus models. CONCLUSION: A teleoroentgenogram is a reliable modality for accurate angular measurements such as HKAA and %MA. An orthoroentgenogram has the potential to measure both HKAA and length accurately if the radiographic condition was modified; however, measurement error in %MA may occur.

Smaller femoral neck anteversion in varus knees than in healthy and valgus knees.

It is important to investigate anatomical differences of the femur and tibia three-dimensionally between varus and valgus knees to enhance surgical approaches and better understand structural factors related to specific patterns of osteoarthritis progression. Three-dimensional femoral and tibial bone models were reconstructed from transverse computed-tomography scans in varus osteoarthritis (43 knees), valgus osteoarthritis (40 knees), and healthy (32 knees) groups. Different coordinate systems were defined in each femoral bone model ("Knee" and "Hip" Coordinate System). Femoral neck inclination, lateral bowing, anterior bowing, and neck anteversion were measured and compared between knee and hip coordinate systems. Those parameters were also compared between varus, valgus, and healthy groups. The tibial anterior and lateral bowing, external torsion and the fibular axis relative to the tibial mechanical axis were measured and compared between varus and valgus groups. Femoral neck anteversion was significantly 1-2° greater in the hip coordinate system compared to the knee coordinate system. Femoral neck anteversion was significantly smaller in varus knees than in healthy or valgus knees, with average difference of approximately 5°. The knee and hip joint are often rotated externally relative to the trunk axis in patients with varus osteoarthritis, perhaps maintaining the geometric relations between pelvis and proximal femur (including peripheral hip muscles) regardless of knee deformities. The fibular axis was inclined slightly valgus and posteriorly in two groups. The results may inform hypotheses on, and future studies of, skeletal morphologic development and factors contributing to the progression of knee osteoarthritis.

Intracellular biosynthesis of lipids and cholesterol by Scap and Insig in mesenchymal cells regulates long bone growth and chondrocyte homeostasis.

During enchondral ossification, mesenchymal cells express genes regulating the intracellular biosynthesis of cholesterol and lipids. Here, we have investigated conditional deletion of Scap or of Insig1 and Insig2 (Scap inhibits intracellular biosynthesis and Insig proteins activate intracellular biosynthesis). Mesenchymal condensation and chondrogenesis was disrupted in mice lacking Scap in mesenchymal progenitors, whereas mice lacking the Insig genes in mesenchymal progenitors had short limbs, but normal chondrogenesis. Mice lacking Scap in chondrocytes showed severe dwarfism, with ectopic hypertrophic cells, whereas deletion of Insig genes in chondrocytes caused a mild dwarfism and shortening of the hypertrophic zone. In vitro studies showed that intracellular cholesterol in chondrocytes can derive from exogenous and endogenous sources, but that exogenous sources cannot completely overcome the phenotypic effect of Scap deficiency. Genes encoding cholesterol biosynthetic proteins are regulated by Hedgehog (Hh) signaling, and Hh signaling is also regulated by intracellular cholesterol in chondrocytes, suggesting a feedback loop in chondrocyte differentiation. Precise regulation of intracellular biosynthesis is required for chondrocyte homeostasis and long bone growth, and these data support pharmacological modulation of cholesterol biosynthesis as a therapy for select cartilage pathologies.

FOXO1 transcription factor regulates chondrogenic differentiation through transforming growth factor ß1 signaling.

The forkhead box O (FOXO) proteins are transcription factors involved in the differentiation of many cell types. Type II collagen (Col2) Cre-Foxo1-knockout and Col2-Cre-Foxo1,3,4 triple-knockout mice exhibit growth plate malformation. Moreover, recent studies have reported that in some cells, the expressions and activities of FOXOs are promoted by transforming growth factor ß1 (TGFß1), a growth factor playing a key role in chondrogenic differentiation. Here, using a murine chondrogenic cell line (ATDC5), mouse embryos, and human mesenchymal stem cells, we report the mechanisms by which FOXOs affect chondrogenic differentiation. FOXO1 expression increased along with chondrogenic differentiation, and FOXO1 inhibition suppressed chondrogenic differentiation. TGFß1/SMAD signaling promoted expression and activity of FOXO1. In ATDC5, FOXO1 knockdown suppressed expression of sex-determining region Y box 9 (Sox9), a master regulator of chondrogenic differentiation, resulting in decreased collagen type II α1 (Col2a1) and aggrecan (Acan) expression after TGFß1 treatment. On the other hand, chemical FOXO1 inhibition suppressed Col2a1 and Acan expression without suppressing Sox9 To investigate the effects of FOXO1 on chondrogenic differentiation independently of SOX9, we examined FOXO1's effects on the cell cycle. FOXO1 inhibition suppressed expression of p21 and cell-cycle arrest in G0/G1 phase. Conversely, FOXO1 overexpression promoted expression of p21 and cell-cycle arrest. FOXO1 inhibition suppressed expression of nascent p21 RNA by TGFß1, and FOXO1 bound the p21 promoter. p21 inhibition suppressed expression of Col2a1 and Acan during chondrogenic differentiation. These results suggest that FOXO1 is necessary for not only SOX9 expression, but also cell-cycle arrest during chondrogenic differentiation via TGFß1 signaling.

Patient-specific prediction of joint line convergence angle after high tibial osteotomy using a whole-leg radiograph standing on lateral-wedge insole.

PURPOSE: To assess the usefulness of a whole-leg radiograph standing on lateral-wedge insole (LWI) for predicting the change in joint line convergence angle (JLCA) before vs. after high tibial osteotomy (HTO). METHODS: Forty knees with medial osteoarthritis underwent open-wedge HTO. Pre-operatively, all patients had whole-leg radiographs taken in three different conditions: supine, standing, and standing on LWI inclined at 20°. A standing whole-leg radiograph was also obtained post-operatively. Radiological measurements including JLCA and percentage of mechanical axis (%MA) were compared. Using pre-operative radiographs, correction angles were calculated with the target %MA at 62.5%. Correlations between the difference in calculated correction angle among the three pre-operative conditions and the change in JLCA before vs. after HTO were assessed. RESULTS: In the pre-operative standing conditions, the mean JLCA of 3.8° was significantly decreased to 3.2° using LWI, which did not differ from post-operative JLCA of 3.1°. Mean %MA significantly shifted laterally from 20.6 to 24.8% using LWI, and was strongly correlated with the change in JLCA (coefficient, 0.83). Calculated correction angles differed significantly among the three pre-operative conditions. The difference in calculated correction angle between standing with and without LWI was strongly correlated to the change in standing JLCA before vs. after HTO (coefficient, 0.73). CONCLUSION: Larger differences in calculated correction angles between pre-operative radiographs standing with and without LWI predicted larger changes in JLCA after HTO. Whole-leg radiograph standing on LWI is a promising modality for correct pre-operative planning considering patient-specific changes in JLCA before vs. after HTO. LEVEL OF EVIDENCE: IV.

Does Preparation of the Subtalar Joint for Primary Union Affect Clinical Outcome in Patients Undergoing Intramedullary Nail for Rheumatoid Arthritis of the Hindfoot and Ankle?

This study aimed to evaluate whether preparation of the subtalar joint affects the clinical outcomes after tibiotalocalcaneal arthrodesis using an intramedullary nail with fins for rheumatoid ankle/hindfoot deformity. Fifty-three joints in 51 patients who underwent tibiotalocalcaneal arthrodesis using an intramedullary nail with fins for rheumatoid arthritis at 2 institutions were included. Ten patients were male and 41 were female, with a mean age at surgery and follow-up period of 61.3 years and 71.6 months, respectively. Radiographic bone union was evaluated at the most recent visit. Univariate and multivariable analyses were performed to determine the risk factors associated with nonunion. The mean postoperative Japanese Society for Surgery of the Foot ankle/hindfoot scale was 65.3 (range, 5-84). The tibiotalar nonunion rate was 0%, whereas the subtalar nonunion rate was 43.3% (23 joints). Revision surgery was performed in 5, all of which were due to painful subtalar nonunion. Absence of subtalar curettage and earlier postoperative weightbearing were significantly associated with subtalar nonunion (p = .0451 and p = .0438, respectively). Subtalar nonunion after tibiotalocalcaneal arthrodesis for rheumatoid hindfoot is associated with higher revision rate. To decrease the risk of subtalar nonunion after tibiotalocalcaneal arthrodesis with an intramedullary nail in rheumatoid patients, curettage for the subtalar joint should be performed, and full weightbearing should be delayed until at least 26 days postoperatively.

CCAAT/enhancer-binding protein ß regulates the repression of type II collagen expression during the differentiation from proliferative to hypertrophic chondrocytes.

CCAAT/enhancer-binding protein ß (C/EBPß) is a transcription factor that promotes hypertrophic differentiation by stimulating type X collagen and matrix metalloproteinase 13 during chondrocyte differentiation. However, the effect of C/EBPß on proliferative chondrocytes is unclear. Here, we investigated whether C/EBPß represses type II collagen (COL2A1) expression and is involved in the regulation of sex-determining region Y-type high mobility group box 9 (SOX9), a crucial factor for transactivation of Col2a1. Endogenous expression of C/EBPß in the embryonic growth plate and differentiated ATDC5 cells were opposite to those of COL2A1 and SOX9. Overexpression of C/EBPß by adenovirus vector in ATDC5 cells caused marked repression of Col2a1. The expression of Sox9 mRNA and nuclear protein was also repressed, resulting in decreased binding of SOX9 to the Col2a1 enhancer as shown by a ChIP assay. Knockdown of C/EBPß by lentivirus expressing shRNA caused significant stimulation of these genes in ATDC5 cells. Reporter assays demonstrated that C/EBPß repressed transcriptional activity of Col2a1. Deletion and mutation analysis showed that the C/EBPß core responsive element was located between +2144 and +2152 bp within the Col2a1 enhancer. EMSA and ChIP assays also revealed that C/EBPß directly bound to this region. Ex vivo organ cultures of mouse limbs transfected with C/EBPß showed that the expression of COL2A1 and SOX9 was reduced upon ectopic C/EBPß expression. Together, these results indicated that C/EBPß represses the transcriptional activity of Col2a1 both directly and indirectly through modulation of Sox9 expression. This consequently promotes the phenotypic conversion from proliferative to hypertrophic chondrocytes during chondrocyte differentiation.

Synovial-tissue resident macrophages play proinflammatory functions in the pathogenesis of RA while maintaining the phenotypes in the steady state.

Synovial tissue-resident macrophages (STRMs) maintain normal joint homeostasis in a steady state. However, it is unclear whether STRMs still play homeostatic roles or change the functions in the joint of rheumatoid arthritis (RA), where infiltrating peripheral blood monocyte-derived macrophages (PBMoMs) play proinflammatory roles. In the present study, we examined changes in the phenotypes and functions of STRMs in response to RA-related stimuli in vitro. STRMs were prepared from non-inflammatory osteoarthritis (OA) joint synovium, which is histologically indistinguishable from normal joint synovium. PBMoMs were prepared and used for comparison. After stimulation with plate-bound IgG, which mimics anti-citrullinated protein antibody immunocomplex formed in RA joints, or with combinations of RA-related inflammatory mediators, namely tumor necrosis factor-α (TNF-α) and prostaglandin E2 or interferon-γ, PBMoMs downregulated surface markers and genes associated with anti-inflammatory macrophages, and upregulated cytokine and marker genes of proinflammatory macrophages in RA. On the other hand, STRMs hardly changed the expression of surface molecules and marker genes but altered the pattern of cytokine gene expression after stimulation like PBMoMs. Furthermore, in vitro stimulated STRMs promote proinflammatory functions of cocultured synovial fibroblasts. Thus, STRMs might play proinflammatory roles in RA joints, while maintaining their phenotypes in the steady state.

Arthroscopic Treatment of Septic Arthritis of the Ankle Caused by Group B Streptococcus: A Case Report.

BACKGROUND The incidence of septic arthritis of a native joint caused by group B streptococcus (GBS, Streptococcus agalactiae) has been on the rise in non-pregnant women. GBS commonly colonizes the female genital tract. However, only a few reports have discussed serious cases of GBS infection, endocarditis, and joint infection associated with the Papanicolaou (Pap) smear test, which is routinely conducted to detect cervical cancer. Specifically, to the best of our knowledge, there have been few reports about arthroscopic treatment for septic arthritis of the ankle caused by GBS. CASE REPORT A 60-year-old woman, who had previously completed the treatment of total laparoscopic hysterectomy with bilateral adnexectomy and postoperative chemotherapy for ovarian cancer, underwent a routine Pap smear test. Four weeks later, she suddenly presented with high fever and abdominal pain. The pain and swelling in her left ankle gradually worsened. Finally, septic arthritis of the ankle was diagnosed, and thus the patient underwent emergent arthroscopic irrigation and debridement. GBS was isolated from both the ankle fluid and blood culture. After surgical intervention and intravenous antibiotic administration, the patient's symptoms gradually improved. Four months later, the patient had no ankle pain or restriction of ankle motion. CONCLUSIONS Although cervical cytology tests are essential in screening for cervical cancer, transient bacteremia can be induced by the tests. Thus, physicians must watch out for the development of septic arthritis caused by GBS when patients present with fever or swollen joints after a recent Pap smear test. Emergent diagnosis and appropriate surgical intervention is also important.

Steroid-induced osteonecrosis of the humeral head in a 20-year-old man treated with an osteochondral autograft: A case report.

To our knowledge, only one previous report described the treatment of osteochondral autograft for steroid-induced osteonecrosis of the humeral head (ONHH) in a middle-aged patient. The present report describes a 20-year-old man who was found to have avascular osteonecrosis of the right humeral head after corticosteroid pulse treatment, followed by oral corticosteroid therapy. The patient complained of serious right shoulder pain and limited range of motion (ROM). Anteroposterior (AP) radiographs of the right shoulder revealed a crescent sign at the humeral head, indicating subchondral bone collapse with a linear sclerotic change and normal articular surface of the glenoid. The case was categorized as Stage 3 according to the Cruess classification. In general, Cruess classification Stage 3 is treated with humeral head replacement and shoulder arthroplasty. The patient underwent surgical treatment involving osteochondral autograft transplantation. Autografts were harvested from the right knee. At the 1.5-year follow-up, the patient was pain-free and showed an improved active ROM. Furthermore, AP radiographs demonstrated that the glenohumeral joint space was maintained, and no progression of humeral head collapse was observed. This case may be helpful in decision-making if young patients with ONHH require surgical treatment. Furthermore, osteochondral autograft transplantation may be an effective treatment for ONHH.