Synthesis of Novel Polymers with Biodegradability by Main-Chain Editing of Chiral Polyketones.

Although the use of biodegradable plastics is suitable for unrecoverable, single-use plastic, their high production cost and much lower variety compared to commodity plastics limit their application. In this study, we developed a new polymer with potential biodegradability, poly(ketone/ester), synthesized from propylene and carbon monoxide. Propylene and carbon monoxide are easily available at low costs from fossil resources, and they can also be derived from biomass. Using an atom insertion reaction to the main chain of the polymer, the main-chain editing of the polymer molecule proceeded with up to 89% selectivity for atom insertion over main-chain cleavage.

Krüppel-like factor 15 deficiency exacerbates osteoarthritis through reduced expression of peroxisome proliferator-activated receptor gamma signaling in mice.

OBJECTIVE: Krüppel-like zinc finger transcription factors (KLFs) play diverse roles in mammalian cell differentiation and development. In this study, we investigated the function of KLF15 in the progression of osteoarthritis (OA). METHODS: 0Destabilization of the medial meniscus (DMM) surgery was performed in 10-week-old male wild-type control (WT) mice and cartilage-specific KLF15 knockout (KO) mice. Histological analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining were performed. Morphological changes were measured using microcomputed tomography. Six mice from each group were analyzed (total number of mice analyzed: 60). In vitro, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blot analyses were performed. RESULTS: KLF15 KO DMM mice exhibited significant cartilage degradation compared to WT mice. According to the Osteoarthritis Research Society International cartilage OA-histopathology scoring system, the mean sum score in KLF15 KO mice was significantly higher than that in WT mice at 8 weeks after surgery. Immunohistochemistry results revealed KLF15 KO mice exhibited reduced peroxisome proliferator-activated receptor gamma (PPARγ) expression, increased pIKKα/ß, a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTS) 5, and Matrix metalloproteinases (MMP13) expression, and reduced Forkhead box O (FOXO1) and Light chain 3B (LC3B) expression. Inhibition of PPARγ phosphorylation accelerated the effects of interleukin (IL) 1ß-treatment in both KLF15 KO and WT chondrocytes, and activation of PPARγ expression canceled the IL1ß-induced catabolic effects. CONCLUSION: Our results indicated that the OA phenotype of KLF15 KO DMM mice was influenced by reduced PPARγ expression, including enhanced pIKKα/ß, ADAMTS5, and MMP13 expression, reduced autophagy, and increased apoptosis. KLF15 regulation may constitute a possible therapeutic strategy for the treating OA.

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 biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). METHODS: Retrospective analysis was conducted on data from the ANSWER cohort comprising 3,623 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 these, 450 (12.4%) met the first two criteria of EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared to those under 65, HR = 0.46, 95% CI: 0.31 to 0.69), higher rheumatoid factor (RF) titres (HR = 1.005, 95% CI: 1.00 to 1.01), higher clinical disease activity index (HR = 1.02, 95% CI: 1.01 to 1.03), lower methotrexate dosage (HR = 0.97, 95% CI: 0.95 to 0.99), and comorbidities like hypertension (HR = 1.53, 95% CI: 1.2 to 1.95) and diabetes (HR = 1.37, 95% CI: 1.09 to 1.73). Anti-interleukin 6 receptor antibodies (aIL-6R, HR = 0.53, 95% CI: 0.37 to 0.75) and JAKi (HR = 0.64, 95% CI: 0.46 to 0.90) were associated with fewer discontinuations due to ineffectiveness compared to tumour necrosis factor inhibitors. Oral glucocorticoids usage (HR = 1.65, 95% CI: 1.11 to 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.

LIGHT regulated gene expression in rheumatoid synovial fibroblasts.

BACKGROUND: Synovial hyperplasia caused by rheumatoid arthritis (RA), an autoimmune inflammatory disease, leads to the destruction of the articular cartilage and bone. A member of the tumor necrosis factor superfamily, Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells (LIGHT) has been shown to correlate with the pathogenesis of RA. METHODS: We used cDNA microarray analysis to compare the expression of genes in rheumatoid fibroblast-like synoviocytes with and without LIGHT stimulation. RESULTS: Significant changes in gene expression (P-values < 0.05 and fold change ≥ 2.0) were associated mainly with biological function categories of glycoprotein, glycosylation site as N-linked, plasma membrane part, integral to plasma membrane, intrinsic to plasma membrane, signal, plasma membrane, signal peptide, alternative splicing, and topological domain as extracellular. CONCLUSIONS: Our results indicate that LIGHT may regulate the expression in RA-FLS of genes which are important in the differentiation of several cell types and in cellular functions.

Predicting postoperative coronal alignment after fixed-bearing unicompartmental knee arthroplasty using a new morphological assessment method: the arithmetic hip-knee-ankle angle.

PURPOSE: Only a few reports have been published so far on factors that predict postoperative coronal alignment after unicompartmental knee arthroplasty (UKA). The purpose of this study is to clarify the relationship between the arithmetic hip-knee-ankle angle (aHKA) and postoperative coronal alignment after medial fixed-bearing UKA. METHODS: One hundred and one consecutive patients (125 knees) who underwent medial fixed-bearing UKA were assessed. Pre- and postoperative coronal HKA angles, lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and the thickness of the tibial and femoral bone cut were measured. aHKA was calculated as 180° - LDFA + MPTA. Correlations between postoperative HKA angle and aHKA, LDFA, and MPTA were investigated by single regression analysis. After the patients were divided into three groups according to the postoperative HKA angle, i.e., HKA angle > 180°, 175° < HKA angle ≤ 180°, and HKA angle ≤ 175°, aHKA, LDFA, MPTA, preoperative HKA angle, and the thickness of the distal femoral as well as tibial bone cut were compared among the three groups. RESULTS: aHKA and MPTA were positively correlated with postoperative HKA angle, while no correlation was found between postoperative HKA angle and LDFA. Among the three groups classified by postoperative HKA angle, significant differences were found in aHKA, MPTA, and preoperative HKA angle, while no significant difference was found in LDFA and the amount of distal femoral and tibial osteotomies. CONCLUSIONS: aHKA was correlated with postoperative HKA angle after medial fixed-bearing UKA, which was probably due to the influence of MPTA.

Accuracy of portable navigation during THA in patients with severe developmental dysplasia of hip.

INTRODUCTION: Correct cup placement in total hip arthroplasty (THA) for patients with developmental dysplasia of the hip (DDH) is considerably difficult. This study aimed to analyze the orientation accuracy of cup insertion during THA using a portable navigation system in patients with DDH. MATERIALS AND METHODS: In this retrospective cohort study, we analyzed data from 64 patients who underwent THA using infrared stereo camera-matching portable navigation. Patients underwent THA via the anterolateral approach in the lateral decubitus position. Navigation records for intraoperative cup angles, postoperative cup angles measured on computed tomography (CT) images, and cup angle measurement differences were measured and compared between patients with non-DDH/mild DDH and severe DDH. Furthermore, the predictive factors for outliers of accurate acetabular cup placement were analyzed. RESULTS: The average measurement absolute abduction differences (postoperative CT-navigation record) were 3.9 ± 3.5° (severe DDH) and 3.3 ± 2.6° (non-DDH/ mild DDH), and the anteversion differences were 4.7 ± 3.4° (severe DDH) and 2.3 ± 2.1° (non-DDH/ mild DDH). The anteversion difference was different between the two groups. Multivariate analysis showed that the navigation difference (absolute difference in anteversion between postoperative CT and navigation records of > 5°) was significantly associated with severe DDH (odds ratio [OR]: 3.3; p = 0.049, 95% confidence interval [CI]: 1.0-11.1) and posterior pelvic tilt (OR: 1.1; p = 0.042, 95% CI: 1.0-1.27). CONCLUSIONS: In patients with severe DDH, it is important to pay close attention during THA using portable navigation. However, the average difference was < 5º even in patients with severe DDH, and the accuracy may be acceptable in a clinical setting when the cost is considered.

The assessment of canal flare index and proximal femoral bone density can improve stem selection for peri-prosthetic bone maintenance after total hip arthroplasty.

INTRODUCTION: Bone maintenance after total hip arthroplasty (THA) is important for implant success. This study aimed to investigate the relationship between patient characteristics and periprosthetic bone maintenance after THA for better implant selection. MATERIALS AND METHODS: This retrospective cohort study enrolled 112 consecutive patients who underwent THA using full hydroxyapatite (HA) compaction with short (n = 55) or short-tapered wedge (n = 61) stems. Periprosthetic bone mineral density (BMD) was compared between the two groups after propensity score matching, and the relationship between periprosthetic BMD changes and patient background was analyzed. RESULTS: Both groups showed similar periprosthetic BMD changes after adjusting for patient background using propensity score matching. Canal flare index > 3.7 in patients that underwent THA using tapered-wedge stem (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.3-7.9, p = 0.013) and baseline zone 1 BMD > 0.65 in patients that received with short HA compaction stems (OR, 430.0; 95% CI 1.3-1420, p = 0.040) were associated with proximal periprosthetic bone maintenance after THA. CONCLUSION: Considering their predictive value, canal flare index and zone 1 BMD assessment might be useful strategies for implant selection during THA.

What effect does preoperative flexion contracture have on the component angles in unicompartmental knee arthroplasty?

PURPOSE: The indication for unicompartmental knee arthroplasty (UKA) has been extended to cases with some degree of preoperative knee flexion contracture recently. The purpose of this study was to clarify the effect of flexion contracture on component angles. MATERIALS AND METHODS: Thirty-five fixed-bearing UKAs using the spacer block technique with preoperative flexion contracture (Group FC) and 35 UKAs using the same technique without preoperative flexion contracture (Group NC) were included. Using radiographs, the coronal femoral component angle, coronal tibial component angle, sagittal femoral component angle, and sagittal tibial component angle were determined. Also, extension and flexion angles of the knee as well as coronal Hip-Knee-Ankle (HKA) angles in long-leg standing radiographs were measured. The data about the thickness of the selected insert were also collected. The above results were compared between the two groups. RESULTS: The femoral component tended to be placed in a more varus and flexed position in Group FC, while no significant difference was found about the tibial component angles. While there was no significant difference in pre- and postoperative knee flexion angles between the two groups, flexion contracture remained postoperatively in Group FC. Preoperative HKA angle was greater in Group FC while the difference was no longer significant postoperatively. Regarding the thickness of the selected insert, thicker inserts tended to be used in Group FC. CONCLUSIONS: In fixed-bearing UKA with the spacer block technique, the femoral component tended to be placed in a flexed and varus position in the knees with preoperative flexion contracture.

Trends of disease activity in Japanese patients over 75 years with rheumatoid arthritis from 2014 to 2021- the ANSWER cohort study.

OBJECTIVES: To investigate if disease activity among elderly RA patients over 75 years has changed over time in the real-world clinical setting. METHODS: Data from an observational multicentre registry of RA patients in Japan were analyzed. The primary outcome was to evaluate the changes in the proportion of very elderly RA patients (over 75 years) who achieved remission and low disease activity, from 2014 to 2021. The secondary outcome was to identify factors associated with remission and low disease activity by comparing demographic and clinical characteristics among the patients who had a study visit within the study period, using multivariate logistic regression. RESULTS: A total of 32 161 patient visits were identified from 2014 to 2021. The proportion of patients over 75 years increased from 16.5% to 26.9%, with biologics and targeted-synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) usage increasing and glucocorticoids usage decreasing, while conventional-synthetic DMARDs usage remained relatively stable. The proportion of RA patients over 75 years achieving remission and low disease activity significantly increased from 62.2% to 78.2% (p for trend < 0.001). A negative factor associated with achieving remission and low disease activity was glucocorticoid usage, seropositivity, and history of previous b/tsDMARDs use while MTX usage was associated positively, independent of other predictors. CONCLUSIONS: In our cohort, disease activity among very elderly RA patients has improved over time. The study suggests the importance of using a treat-to-target approach in very elderly RA patients to improve clinical outcomes.

Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study.

OBJECTIVE: This multicentre, retrospective study compared the efficacy and safety of tofacitinib, baricitinib, peficitinib and upadacitinib in real-world clinical settings after minimizing selection bias and adjusting the confounding patient characteristics. METHOD: The 622 patients were selected from the ANSWER cohort database and treated with tofacitinib (TOF), baricitinib (BAR), peficitinib (PEF) or upadacitinib (UPA). The patient's background was matched using propensity score-based inverse probability of treatment weighting (IPTW) among four treatment groups. The values of Clinical Disease Activity Index (CDAI), C-reactive protein (CRP), and modified Health Assessment Questionnaire (mHAQ) after drug initiation and the remission or low disease activity (LDA) rates of CDAI at 6 months after drug initiation were compared among the four groups. Further, the predictive factor for TOF and BAR efficacy was analysed. RESULTS: The retention and discontinuation rates until 6 months after drug initiations were not significantly different among the four JAK inhibitors treatment groups. Mean CDAI value, CDAI remission rate, and CDAI-LDA rate at 6 months after drug initiation were not significantly different among treatment groups. Baseline CDAI (TOFA: OR 1.09, P < 0.001; BARI: OR 1.07, P < 0.001), baseline CRP (TOFA: OR 1.32, P = 0.049), baseline glucocorticoid dose (BARI: OR 1.18, 95% CI 1.01-1.38, P = 0.035), a number of previous biological or targeted synthetic disease-modifying antirheumatic drugs (biological/targeted synthetic DMARDs) (BARI: OR 1.36, P = 0.004) were predictive factors for resistance to CDAI-LDA achievement to JAK inhibitor treatment. CONCLUSION: The efficacy and safety of TOF, BAR, PEF and UPA were not significantly different for the treatment of patients with rheumatoid arthritis.

Effect of Hydrophobicity and Salt on the Temperature Responsiveness of Polymeric Micelles Consisting of Hydrophobic and Sulfobetaine Chains.

The effect of the hydrophobicity of the core part and salt on the temperature responsiveness of polymeric micelles composed of sulfobetaine and hydrophobic blocks was investigated. Poly(sulfopropyl dimethylammonium propylacrylamide) (PSPP) was used as the sulfobetaine; poly(2-ethylhexyl acrylate) (PEHA), poly(n-butyl acrylate) (PnBA), poly(ethyl acrylate) (PEA), or poly(n-hexyl acrylate) (PnHA) was used as the hydrophobic polymer. Measurement of the transmittance revealed that the transition temperature of the sulfobetaine homopolymer could be controlled by adjusting the concentration, the degree of polymerization (DP), and the concentration of the added salt. The effect of the anionic species of the added salt due to the chemical structural properties of the sulfobetaine chain was consistent with the order of ionic species with strong structural destruction in the Hofmeister series. The temperature response and micelle formation behavior of the polymeric micelles according to the hydrophobicity of the core part and the preparation method were examined by static light scattering (SLS), fluorescence measurement with pyrene, dynamic light scattering (DLS), transmittance, and atomic force microscopy (AFM). Micelles that had EHA (solubility in water was 0.01 g/100 mL) as the core and did not show temperature responsiveness expressed temperature responsiveness at a lower hydrophobicity (solubility of nBA in water was 0.14 g/100 mL). nBA-b-SPP did not show temperature responsiveness due to the block ratio. However, when micelles were prepared by dialysis, smaller and more stable micelles could be formed in an equilibrium state, and temperature responsiveness was observed. Their transition temperature can be controlled by adjusting the ratio of the sulfobetaine blocks, the hydrophobicity of the core part, the concentration of the polymer aqueous solution, and the concentration of the added salt. Furthermore, like the sulfobetaine homopolymer, the effect depended on the anionic species of the added salt.

Targeting the neutral hip-to-calcaneus axis in kinematically aligned total knee arthroplasty is feasible with fewer alignment outliers for varus osteoarthritic patients.

PURPOSE: Assessment of the conventional mechanical axis (MA) (hip-to-talus axis) is reported to result in constitutional varus in the native knee. However, the ground MA (hip-to-calcaneus axis), which is the line from the hip center to the bottom of the calcaneus, passes through the center of the knee joint in the native knee and is a possible alternative target for total knee arthroplasty (TKA) assessments. Therefore, this study aimed to present a "ground kinematically aligned (KA)-TKA." In this technique, the femoral component is placed on the cylindrical axis using the calipered technique and the tibial component is placed to give a neutral ground MA. Radiographical investigation was used to determine whether physiological alignment can be individually achieved with ground KA-TKA; this was compared with that of a tibia-restricted modified KA-TKA, referring to conventional MA (hip-to-talus axis) results. METHODS: As the primary endpoint, this prospective cohort study compared the ground MA ratios of the knee joints in 40 ground KA-TKAs (G group: Coronal Plain Alignment of the Knee (CPAK) 28 type I, 7 II, 1 IV, and 4 V) with those of the preceding 60 modified KA-TKAs (M group: CPAK 46 type I, 12 II, and 2 V) performed for patients with varus osteoarthritis (OA). The number of outliers differing over ± 5% from the neutral were compared between groups using the χ2-test. The Hip-knee-ankle (HKA) angle, coronal femoral/tibial component alignment (FCA/TCA), and joint line orientation angle (JLOA) were compared between the groups using non-paired t-tests. Statistical significance was set at p < 0.05. RESULTS: The G group had a higher ratio of the ground MA passing through the knee center than the M group did; outliers differing over ± 5% from the neutral of the ground MA were 2/40 cases in the G group and 20/60 cases in the M group, which was a significant difference (p = 0.001). The HKA angle, FCA/TCA, and JLOA were not significantly different between the groups. CONCLUSIONS: Targeting the ground MA in KA-TKA for patients with varus OA was feasible and has the potential to provide a physiological alignment more similar to the native knee in TKA than other kinematic alignment techniques. LEVEL OF EVIDENCE: Level III.

Comparison study of periprosthetic bone remodeling between simultaneous bilateral total hip arthroplasty and unilateral total hip arthroplasty: a matched cohort study.

PURPOSE: The load-bearing pattern of periprosthetic bone may differ between patients who underwent simultaneous bilateral and unilateral total hip arthroplasty (THA). We investigated the differences in periprosthetic bone remodeling after simultaneous bilateral total hip arthroplasty and unilateral total hip arthroplasty. METHODS: This retrospective cohort study enrolled 154 consecutive patients undergoing THA using full hydroxyapatite (HA) compaction short stems. Patient characteristics including age, body mass index, University of California Los Angeles (UCLA) activity score, and bone shape of the proximal femur were adjusted by propensity score matching. Subsequently, periprosthetic bone mineral density changes were compared between simultaneous bilateral and unilateral THA. RESULTS: We found that bone mineral density loss in the simultaneous bilateral THA group was significantly higher in zones 6 and 7 at 24 months after THA (zone 6, p = 0.019; zone 7, p = 0.041). Periprosthetic bone mineral density loss was not associated with clinical factors, including age, body mass index, and daily activity. Additionally, we demonstrated that periprosthetic bone mineral density loss was higher in zones 1, 4, 6, and 7 of patients with a normal hip on the contralateral side after unilateral THA (zone 1, p = 0.041; zone 4, p = 0.041; zone 6, p = 0.037; zone7, p = 0.019). CONCLUSIONS: The postoperative periprosthetic bone remodeling was lower in patients who underwent simultaneous bilateral THA than in those who underwent unilateral THA, even though patient characteristics were adjusted by propensity matching. Further observation of periprosthetic bone mineral density loss is needed to clarify the differences between the groups.

Ground kinematically aligned total knee arthroplasty: new personalized technique which enables a stable knee with deep flexion.

PURPOSE: This study aimed to evaluate kinematically aligned total knee arthroplasty (KA-TKA) targeting the neutral ground mechanical axis (MA) (hip-to-calcaneus axis), the line from the hip centre to the bottom of the calcaneus, (ground KA-TKA) in terms of its comparison with tibia-restricted modified KA-TKA (modified KA-TKA). METHODS: This retrospective cohort study included 106 consecutive patients who underwent unilateral KA-TKA for varus osteoarthritis (OA) (60 modified KA-TKAs and 46 ground KA-TKAs). After 1:1 propensity score matching, 60 patients (30 pairs) were matched between the groups with comparable demographic data. The hip-knee-ankle (HKA) angle, coronal femoral component alignment (FCA), and coronal tibial component alignment (TCA) were compared between groups. Intraoperative soft tissue balance, including the joint component gap and varus/valgus balance, was also compared between the groups. One year postoperatively, the clinical outcomes, including the range of motion and 2011 Knee Society Score, were compared between groups. RESULTS: The HKA angle and FCA/TCA were not significantly different between groups. Whereas the varus/valgus balance showed no significant differences between groups, smaller joint component gaps were found throughout the range of motion in the ground KA-TKA group than in the modified KA-TKA group. Despite no difference in clinical scores between groups, a significantly deeper postoperative flexion angle was achieved in the ground KA-TKA group than in the modified KA-TKA group (p < 0.05). CONCLUSION: Targeting neutral ground MA in KA-TKA for patients with varus OA has the potential to provide a better flexion angle with stable intraoperative soft tissue balance.

Prosthetic orientation, limb alignment, and soft tissue balance with bi-cruciate stabilized total knee arthroplasty: a comparison between the handheld robot and conventional techniques.

PURPOSE: This study aimed to examine the prosthetic orientations, limb alignment, intraoperative soft tissue balance, and early clinical outcomes associated with the use of the relatively new handheld robot technique compared to those associated with the use of the conventional alignment guide for bi-cruciate stabilized total knee arthroplasty (TKA). METHODS: This retrospective cohort study compared the prosthetic orientation and limb alignment of 35 patients who underwent TKA using robotic assistance (robot group) with those of patients who underwent TKA using a conventional alignment guide (control group). The coronal femoral component alignment (FCA), coronal tibial component alignment (TCA), and the hip-knee-ankle (HKA) angle were compared between groups. Intraoperative soft tissue balance, including the joint component gap and varus/valgus balance assessed by an offset-type tensor, were also compared between groups. One year postoperatively, the clinical outcomes, including the range of motion and 2011 Knee Society Score (KSS), were compared between groups. RESULTS: The HKA angle and FCA were 0.1° varus and 0.1° varus, respectively, in the robot group and 1.3° varus and 1.3° varus, respectively, in the control group. The difference in the HKA angle and the FCA, but not the TCA, between groups was statistically significant (p < 0.05). The intraoperative soft tissue balance showed more stable joint component gaps and varus/valgus balances throughout the range of motion in the robot group than in the control group. Clinical outcomes of the robot group showed superior 2011 KSS subscales compared to those of the control group. CONCLUSION: The accuracy of the implantations and stable soft tissue balance in the robot group were superior to those of the control group. The robot group also had superior patient-reported scores for early clinical outcomes.

The influence of stem alignment on the bone mineral density around the Polarstem following total hip arthroplasty.

INTRODUCTION: Bone mineral density is important in detecting implant loosening after total hip arthroplasty. The Polarstem can improve postoperative bone mineral density changes, but no information exists on the influence of postoperative stem alignment. Therefore, we investigated the relationship between bone mineral density change and stem alignment following total hip arthroplasty using a cementless Polarstem. MATERIALS AND METHODS: This retrospective study included 42 patients (50 hips) who underwent total hip arthroplasty using a cementless Polarstem. Bone mineral density around the stem was measured according to the established Gruen zone classification using dual-energy X-ray absorptiometry. Measurements were performed 2 months postoperatively (baseline) and 6, 12, 18, and 24 months postoperatively. Bone mineral density changes at each follow-up were calculated as (bone mineral density at follow-up/at 2 weeks) × 100 (%). The stem varus, anterior tilt, and anteversion angles were measured using computed tomography. The correlation coefficient between bone mineral density changes and stem alignment were investigated. RESULTS: The 24-month postoperative bone mineral density increased in zones 4 (106.0%) and 5 (107.3%) and decreased in zones 1 (89.6%) and 7 (90.6%). The mean stem varus angle, anterior tilt, and anteversion error were - 0.3° ± 1.8°, 1.9° ± 2.2°, and 6.8° ± 5.4°. Negative correlations were observed between the stem varus angle and 24-month postoperative bone mineral density change in zone 1 (r = - 0.34, p = 0.02), and the stem anteversion error and 24-month postoperative bone mineral density change in zone 1 (r = - 0.48, p < 0.01) and zone 7 (r = - 0.31, p = 0.03). CONCLUSIONS: The cementless Polarstem may have a positive effect on postoperative bone mineral density in the distal femur. However, varus malalignment and anteversion error of the stem could have a negative influence on the bone mineral density changes in the proximal femur.

Comparing the accuracy of three-dimensional mini-optical portable navigation and accelerometer-based portable navigation system for acetabular cup placement during total hip arthroplasty.

INTRODUCTION: This study compared the accuracy of three dimensional (3D) mini-optical navigation and accelerometer-based portable navigation systems for cup positioning during a total hip arthroplasty (THA) in the supine position. MATERIALS AND METHODS: This retrospective cohort study assessed data for 77 hips using 3D mini-optical navigation (n = 37) and accelerometer-based portable navigation (n = 40). The patients underwent THA through the mini-anterolateral approach in the supine position using a portable navigation system. We assessed the preoperative target angles, recorded intraoperative cup angles, postoperative CT imaging angles, cup angle measurement errors, and other clinical parameters. RESULTS: The mean absolute differences in radiographic inclination were similar between 3D mini-optical navigation and accelerometer-based portable navigation systems during THA in the supine position (2.8° ± 1.7° vs 2.8° ± 1.9°, p = 0.637). The mean absolute differences in radiographic anteversion were also similar (2.6° ± 2.3° vs 2.5° ± 1.9°, p = 0.737). Cup malalignment (absolute difference of inclination or anteversion between postoperative CT and preoperative target angle of > 5°) was significantly associated with body mass index (BMI) in accelerometer-based portable navigation but not in 3D mini-optical navigation. CONCLUSIONS: This is the first study to compare the accuracy of cup positioning between 3D mini-optical and accelerometer-based navigations in THA in the supine position. Both portable navigation systems accurately identified the orientation of cup placement. The accuracy of 3D mini-optical navigation is not affected by high BMI and may be preferred over other options in such patients.

Accuracy comparison of cup positioning during total hip arthroplasty using Hip Align and AR-Hip in the supine position.

INTRODUCTION: The aim of this study is to compare the accuracy of acetabular cup positioning between the accelerometer-based navigation system and the augmented reality-based navigation system during THA in the supine position. MATERIALS AND METHODS: This retrospective study included 66 patients (70 hips) who underwent THA using two types of portable navigation system, Hip Align or AR-Hip, in the spine position. The absolute difference between the intraoperative navigation record and postoperative measurement using computed tomography data was evaluated. Preoperative clinical factors that decreased the accuracy of cup positioning by ≥ 3° were analyzed via multiple logistic regression analyses. RESULTS: The average absolute error of inclination was 2.8 ± 2.6° in Hip Align and 2.7 ± 1.8° in AR-Hip, and absolute anteversion error was 2.5 ± 2.0° in Hip Align and 2.6 ± 2.2° in AR-Hip, and there was no significantly different between the two navigation systems. There was a significant association between the absolute measurement error (≥ 3°) of cup inclination and patients' BMI in the Hip Align group [odds ratio (OR) 1.350; 95% confidence interval (CI) 1.035-1.760; p = 0.027], but not in the AR-Hip group. CONCLUSIONS: The accuracy of the acetabular cup positioning between the Hip Align and AR-Hip showed no difference during THA in the spine position. The high BMI could have negative influence on the accuracy of cup positioning in THA using Hip Align, thus AR-Hip could be designable for obesity patients.

Iguratimod versus salazosulfapyridine in rheumatoid arthritis patients with an inadequate response to methotrexate: Adjusted with propensity score matching.

OBJECTIVES: Methotrexate (MTX) is recommended as a first-line conventional synthetic disease-modifying antirheumatic drug (csDMARD) for treating rheumatoid arthritis (RA). This retrospective study sought to identify an add-on csDMARD treatment strategy for RA patients with MTX-inadequate response (IR). METHODS: We collected the cases of RA patients treated with salazosulfapyridine (SASP) or iguratimod (IGU) as the additional csDMARD for MTX-IR during a 24-month follow-up. We performed propensity score matching to evaluate the retention rate, clinical efficacy, and safety profile (n = 54, each group). RESULTS: The retention rates at 24 months were 38.5% (MTX+SASP group) and 67.8% (MTX+IGU group). At 3 and 6 months, the MTX+IGU group's 28 joint-disease activity score (DAS28) was significantly decreased versus the MTX+SASP group, and at 3 months the MTX+IGU group's good-responder percentage (22.9%) was significantly higher versus the MTX+SASP group's good-responder percentage (10.7%). Conversely, compared to the MTX+SASP group, the MTX+IGU group showed a greater reduction in the estimated glomerular filtration rate from baseline during follow-up. CONCLUSIONS: IGU is a useful add-on csDMARD for RA patients with MTX-IR; its high retention rate and good clinical response make it a useful combination therapy for controlling RA disease activity. However, the renal function should be monitored during follow-up.

Paracrine effect of the stromal vascular fraction containing M2 macrophages on human chondrocytes through the Smad2/3 signaling pathway.

The adipose-derived stromal vascular fraction (SVF) is composed of a heterogeneous mix of adipose-derived stem cells (ADSCs), macrophages, pericytes, fibroblasts, blood, and other cells. Previous studies have found that the paracrine effects of SVF cells may be therapeutic, but their role in osteoarthritis treatment remains unclear. This study aimed to investigate the therapeutic effect of SVF cells on chondrocytes. Chondrocytes were seeded on culture plates alone (control) or cocultured with SVF or ADSCs on cell culture inserts. After 48 h of coculture, chondrocyte collagen II, tissue inhibitors of metalloproteinases-3 (TIMP-3), and matrix metalloproteinases-13 (MMP-13) messenger RNA (mRNA) expression levels were evaluated using reverse-transcription polymerase chain reaction, and the transforming growth factor-ß (TGF-ß) levels in the supernatant were measured using ELISA. Immunohistochemical staining and flow cytometry were used to evaluate the macrophages in the SVF. These macrophages were characterized according to phenotype using the F4/80, CD86, and CD163 markers. To determine whether the Smad2/3 signaling pathways were involved, the chondrocytes were pre-treated with a Smad2/3 phosphorylation inhibitor and stimulated with the SVF, and then Smad2/3 phosphorylation levels were analyzed using western blot. The mRNA expression levels of various paracrine factors and chondrocyte pellet size were also assessed. Collagen II and TIMP-3 expression were higher in the SVF group than in the ADSC group and controls, while MMP-13 expression was the highest in the ADSC group and the lowest in the controls. TGF-ß levels in the SVF group were also elevated. Immunohistochemical staining and flow cytometry revealed that the macrophages in the SVF were of the anti-inflammatory phenotype. Western blot analysis showed that the SVF increased Smad2/3 phosphorylation, while Smad2/3 inhibitors decreased phosphorylation. Smad2/3 inhibitors also reduced the expression of various other paracrine factors and decreased chondrocyte pellet size. These findings suggested that the paracrine effect of heterogeneous cells, such as anti-inflammatory macrophages, in the SVF partly supports chondrocyte regeneration through TGF-ß-induced Smad2/3 phosphorylation.