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.

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.

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.

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.

Mid- to Long-Term Results of Total Knee Arthroplasty for Charcot Arthropathy of the Knee.

Background: Total knee arthroplasty (TKA) for Charcot arthropathy of the knee is considered controversial because of its higher complication rate compared with that of TKA for osteoarthritis. In this study, we investigated the clinical outcomes, survival rates, and complications of primary TKA for Charcot arthropathy. Methods: We conducted a retrospective analysis of nine patients (12 knees) with Charcot arthropathy who underwent TKA. The mean age of the patients was 63.9 ± 9.4 years (range, 52-83 years). The most frequent causative disease was diabetes mellitus (three patients). Patients' clinical outcomes, including the 2011 Knee Society Score and the range of motion, were compared between preoperative and the most recent postoperative data. The 5- and 10-year survival rates for aseptic revision, revision due to infection, and complications were examined. The mean follow-up period was 7.3 ± 3.9 years (range, 3-14 years). Results: The 2011 Knee Society Score and the knee flexion angle significantly improved after TKA surgery (P < 0.05). The 5-year survival rates for aseptic revision, revision due to infection, and complications were 100%, 91.7%, and 83.3%, respectively; the 10-year survival rates for these parameters were the same. One patient underwent revision for insert replacement due to periprosthetic infection, and the other patient had varus/valgus instability due to soft tissue loosening. Conclusions: The mid- to long-term results of TKA for Charcot arthropathy were generally favorable. Our findings indicate that TKA may be a viable treatment option for Charcot arthropathy.

Prediction of Postoperative Range of Motion after Mobile-Bearing Medial Unicompartmental Knee Arthroplasty from the Preoperative Range of Motion and Other Preoperative Factors.

Postoperative flexion after unicompartmental knee arthroplasty might be predicted from the preoperative range of motion and other preoperative factors, but this has not been sufficiently investigated. Between 2013 and 2017, 198 patients (198 knees) underwent unilateral knee arthroplasty with medial mobile-bearing unicompartmental knee arthroplasty. Range of motion was measured preoperatively and at the time of final follow-up. To investigate the accuracy of the prediction of preoperative to postoperative gain or loss of the flexion angle, we performed receiver operating characteristic analysis. Logistic regression analysis was used to evaluate other predictive factors. Change in flexion angle was significantly strongly and negatively correlated with the preoperative flexion angle (R = - 0.688; 95% confidence interval: -0.755 to -0.607; p < 0.001). Preoperative flexion angle was suggested to be a significant predictor of gain or loss of the flexion angle with the area under the curve of 0.781; the cutoff value calculated using the Youden index was 140 degrees. Logistic regression analysis showed that in addition to the preoperative flexion angle of the operated side, the postoperative flexion range was significantly affected by the patient's height and by the preoperative flexion angle of the contralateral knee. If the preoperative flexion angle in Oxford mobile-bearing medial unicompartmental knee arthroplasty is <140 degrees, the postoperative flexion angle may be improved; if it exceeds 140 degrees, the postoperative flexion angle may worsen. This predictive ability is further improved by consideration of the patient's height and the range of motion on the contralateral side.

Association of large joint involvement at the start of biological disease-modifying antirheumatic drugs and Janus kinase inhibitors with disease activity and drug retention in patients with rheumatoid arthritis: The ANSWER cohort study.

AIM: To investigate the association of large joint involvement (LJI) with disease activity and drug retention in patients with rheumatoid arthritis (RA) who started receiving a biological disease-modifying antirheumatic drug or Janus kinase inhibitor. METHODS: Patients with RA from a Japanese multicenter observational registry were enrolled. Our definition of large joints included the shoulder, elbow, hip, knee, and ankle joints. Linear mixed-effects models were used to examine changes in the clinical disease activity index (CDAI) score at Week 24 as the primary outcome, and drug retention rates were compared between patients with and without LJI using Cox proportional hazards models. We examined the potential effect modifications of changes in the CDAI by baseline characteristics. RESULTS: Overall, 2507 treatment courses from 1721 patients were included (LJI, 1744; no LJI, 763). Although LJI was associated with significantly higher changes in CDAI from baseline at Week 24 (difference in change in CDAI: -5.84 [-6.65 to -5.03], p < .001), CDAI was significantly higher in patients with LJI over time. Retention rates were similar in both groups. The association of LJI with changes in disease activity was more prominent in patients with a short disease duration, negative anti-citrullinated peptide antibodies, and interleukin-6 receptor inhibitor (IL-6Ri) use. CONCLUSION: Although LJI was associated with a greater reduction in disease activity from baseline, higher disease activity at baseline was not offset over time in patients with LJI, demonstrating that LJI is an unfavorable predictor. An early treat-to-target strategy using an IL-6Ri may be beneficial for patients with LJI.

Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan.

OBJECTIVES: This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity. DESIGN: Retrospective observational study of a nationwide database. SETTING: The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint. PARTICIPANTS: This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018. MAIN OUTCOME MEASURE: The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis. RESULTS: The median time to surgery was 9 months (IQR 4-22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years. CONCLUSION: ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact. TRIAL REGISTRATION NUMBER: Chiba University ID1049.

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.

Liver function and image evaluation after radiotherapy for liver metastases after resection of sigmoid colon cancer a case report.

INTRODUCTION: Radiotherapy is a treatment option in the management of patients with metastatic liver disease. The aim in this case was to evaluate radiation-induced dysfunctional liver lesions using 99mTc-GSA-SPECT, Gd-EOB-DTPA-enhanced MRI, and radiation dose distribution in a patient after radiation therapy. PRESENTATION OF CASE: After sigmoid colon resection, three liver metastases were treated with radiotherapy at the same time. Liver function after radiotherapy was determined to be A according to the Child-Turcott-Pugh classification. 99mTc-GSA-SPECT showed a wider reduction in uptake than Gd-EOB-DTPA MRI at all three sites. HH15 showed decreased liver function. DISCUSSION: In the 99mTc-GSA-SPECT and Gd-EOB-DTPA MRI hepatocyte phases, residual signals of normal hepatocytes were observed despite irradiation at three sites. Additional treatment could be considered for the two recurrent lesions because there was no deterioration of liver function in post-irradiation imaging findings and blood sampling. CONCLUSION: 99mTc-GSA-SPECT and EOB-MRI showed characteristic findings for evaluation of liver function after radiotherapy for multiple liver metastases, suggesting the need for both imaging evaluations. It is now possible to choose whether to perform local additional treatment (additional radiation, RFA) or other chemotherapy for liver metastases after recurrence.

Influence of Distal Reference Point of the Tibial Mechanical Axis on the Ankle and Hindlimb Alignment Change after Total Knee Arthroplasty.

The alignment philosophy in total knee arthroplasty (TKA) has tended to shift from the gold standard of mechanically aligned technique to personalized alignment, such as the kinematically aligned (KA) technique. However, the influences of different surgical techniques on lower limb alignment relative to the ground are not fully investigated. This study investigated the influence of the ankle and hindlimb alignment change after mechanically aligned TKA and KA-TKA. The varus osteoarthritic patients who underwent TKAs were divided into a mechanically aligned TKA group (group M, n = 50) and a KA-TKA group (group K, n = 50). Radiographic parameters (hip-knee-calcaneus [HKC] angle, hip-knee-ankle [HKA] angle, talar tilt angle [TTA], and tibiocalcaneal angle [TCA]) were investigated using full-length standing radiographs. The deviation angle (ΔTA; angle between the tibial mechanical axis [TMA] and the ground tibial mechanical axis [gTMA]) and the change of ΔTA (cΔTA) were also assessed. These parameters were compared between the two groups, along with the correlation between the preoperative HKA angle and other parameters. ΔTA, TTA, and TCA showed no differences between the groups pre- and postoperatively, and no significant changes were observed postoperatively. The preoperative HKA angle showed a significant negative correlation with cΔTA in both groups (group M: r = -0.33, p = 0.02; group K: r = -0.29, p = 0.04) although no correlation was observed the with preoperative TTA and TCA. Despite no change in ΔTA after surgery, the preoperative varus deformity was associated with a change in the deviation between gTMA and TMA after surgery. A severely varus knee may be inappropriate for ground KA-TKA.

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.

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.

Impact of Dose Perturbations Around Brachytherapy Seeds in External-Beam Radiotherapy Planning: A Fundamental and Clinical Validation Using Treatment Planning System-Based Monte Carlo Simulations.

Background This study evaluates dose perturbations caused by nonradioactive seeds in clinical cases by employing treatment planning system-based Monte Carlo (TPS-MC) simulation. Methodology We investigated dose perturbation using a water-equivalent phantom and 20 clinical cases of prostate cancer (10 cases with seeds and 10 cases without seeds) treated at Fujita Health University Hospital, Japan. First, dose calculations for a simple geometry were performed using the RayStation MC algorithm for a water-equivalent phantom with and without a seed. TPS-independent Monte Carlo (full-MC) simulations and film measurements were conducted to verify the accuracy of TPS-MC simulation. Subsequently, dose calculations using TPS-MC were performed on CT images of clinical cases of prostate cancer with and without seeds, and the dose distributions were compared. Results In clinical cases, dose calculations using MC simulations revealed hotspots around the seeds. However, the size of the hotspot was not correlated with the number of seeds. The maximum difference in dose perturbation between TPS-MC simulations and film measurements was 3.9%, whereas that between TPS-MC simulations and full-MC simulations was 3.7%. The dose error of TPS-MC was negligible for multiple beams or rotational irradiation. Conclusions Hotspots were observed in dose calculations using TPS-MC performed on CT images of clinical cases with seeds. The dose calculation accuracy around the seeds using TPS-MC simulations was comparable to that of film measurements and full-MC simulations, with differences within 3.9%. Although the clinical impact of hotspots occurring around the seeds is minimal, utilizing MC simulations on TPSs can be beneficial to verify their presence.

Pseudarthrosis of Pelvic Fracture With Charcot Arthropathy Successfully Treated With Constrained Total Hip Arthroplasty.

Charcot arthropathy is a rapidly progressive and destructive form of arthropathy caused by various neurological diseases. Total hip arthroplasty (THA) is usually contraindicated in patients with Charcot arthropathy; however, recent studies have reported good results following THA in this patient population. Herein, we report a case of Charcot arthropathy secondary to syphilis in a patient who was successfully treated with constrained THA, a new type of THA. A 56-year-old man was injured in a car accident, and a displaced acetabular fracture was revealed three weeks later. He was treated conservatively but soon developed greater displacement of the fracture and femoral head destruction. The patient was referred to our hospital for further treatment. The patient had pelvic pseudarthrosis secondary to Charcot arthropathy at the time of the first visit to our hospital. First, THA was performed with the acetabular reconstruction of the deficient bone. However, the acetabular implant was displaced one week postoperatively. THA revision was performed using a constrained cup. Postoperatively, the patient exhibited good hip stability without dislocation. However, displacement of the acetabular cup occurred one year after the second surgery. We performed a re-revision of THA using a new type of constrained cup that offers a high level of constraint to maintain range of motion (ROM) and prevent dislocations. The patient was able to walk with a T-cane one year postoperatively. Herein, we report a difficult case of revision THA in a patient with Charcot arthropathy concomitant with syphilis. THA is usually contraindicated in patients with Charcot arthropathy; however, we propose that THA using constrained cups that offer a wider ROM may be a useful therapeutic strategy for the treatment of Charcot arthropathy.

Successful Total Knee Arthroplasty for Hoffa and Proximal Tibial Fractures: Report of Three Complex Cases After Failed Osteosynthesis Procedures.

BACKGROUND Distal femoral and proximal tibial fractures often lead to nonunion and post-traumatic osteoarthritis, and total knee arthroplasty (TKA) has emerged as an effective alternative for older patients. This report includes 3 cases of successful TKA treatment. The cases involve a 42-year-old man and a 62-year-old man with Hoffa coronal fractures of the distal femur, and a 50-year-old man with a proximal tibial fracture. These patients underwent multiple osteosynthesis procedures before receiving TKA. CASE REPORT Case 1: A 42-year-old man with a displaced Hoffa's fracture had persistent knee pain. Nonunion post-initial fixation led to reoperation with iliac bone grafting and plate fixation. TKA using a Posterior Stabilized (PS)-type implant resulted in improved motion and function after 3 years. Case 2: A 62-year-old man suffered lateral condyle and ligament injuries from a displaced Hoffa's fracture. Despite plate fixation, dislocation occurred, requiring conversion. TKA with long-stem hinge-type implant, using augmentation block, led to enhanced stability and outcomes at 2 years. Case 3: A 50-year-old man's tibial nonunion, treated with plate fixation, resulted in infection and bone fusion. TKA using a constrained PS-type implant insert addressed the lateral tibial adhesions via iliotibial band (ITB) release and treated severe tibial plateau damage. Positive results were seen at 1 year. CONCLUSIONS The challenges of pseudarthrosis, like bone defects and compromised tissue, highlight the need for precise implant selection based on evaluations of bone quality, defects, knee stability, and hyperextension, rather than resorting to overly-constrained implants.

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.

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.

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

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