Real-world study comparing the efficacy of Janus kinase inhibitors in patients with difficult-to-treat rheumatoid arthritis.

OBJECTIVE: This study aimed to analyze the clinical efficacy of JAK inhibitors in difficult-to-treat rheumatoid arthritis (D2TRA) and non-D2TRA patients and evaluate the factors influencing their efficacy using real-world data. METHOD: Here, 159 JAK inhibitor-treated patients with rheumatoid arthritis were categorized into D2TRA and non-D2TRA groups. Data including the Clinical Disease Activity Index (CDAI) at initiation and 6 months after drug administration, drug retention months, and reason for discontinuation due to toxic adverse events were collected. RESULTS: The retention rates at 6 months were 64.0% (D2TRA) and 78.4% (non-D2TRA) and were significantly different between the two groups (p = 0.030). The discontinuation rate owing to toxic adverse events significantly differed between the two groups (p = 0.030). The CDAI-low disease activity (LDA) rates differed significantly between the two groups (non-D2TRA, 62.3%; D2TRA, 34%; p < 0.001). CDAI-LDA achievement at 6 months after drug introduction was significantly associated with the number of times that biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs were previously used and the CDAI at baseline in all patients treated with JAK inhibitors. However, no predictive factors were identified for D2TRA patients treated with JAK inhibitors. CONCLUSION: Compared to non-D2TRA patients, D2TRA patients demonstrated significantly lower drug retention rates, CDAI-LDA achievement rates, and safety of JAK inhibitors. No significant predictive factor for CDAI-LDA achievement 6 months after drug introduction was detected in D2TRA patients. Key Points • The retention of JAK inhibitors were significantly lower for the treatment of D2TRA patients in comparison with non-D2TRA patients. • The efficacy and safety of JAK inhibitors were significantly lower for the treatment of D2TRA patients. • Number of previous uses of b/tsDMARDs and CDAI at baseline were identified as the predictive factors for resistance to CDAI-LDA achievement to JAK inhibitor treatment. • No significant predictive factor for CDAI-LDA achievement 6 months after drug introduction was detected in D2TRA patients.

The medullary cavity morphology of the proximal femur influences the fixation pattern of the rectangular tapered short stem in total hip arthroplasty.

INTRODUCTION: This study aimed to evaluate differences in the pattern of fixation with a rectangular tapered short stem (Fitmore stem) due to proximal femoral medullary cavity morphology based on periprosthetic bone mineral density (BMD) and radiological findings. MATERIALS AND METHODS: We analyzed 105 consecutive patients (Dorr type A, 18; Dorr type B, 66; Dorr type C, 21) who underwent total hip arthroplasty using a Fitmore stem. Periprosthetic BMD was measured using dual-energy X-ray absorptiometry from 1 to 24 months postoperatively and radiological analysis was performed. Clinical outcomes were evaluated using the Harris hip score (HHS) and the University of California Los Angeles (UCLA) activity score preoperatively and 24 months postoperatively. RESULTS: At 24 months postoperatively, Dorr type C had significantly decreased BMD changes in Gruen zones 2, 6, and 7 compared to Dorr types A and B, and conversely, significantly increased BMD changes in zone 4 (p < 0.05). Dorr type C had significantly greater subsidence than the other types (p < 0.01) and significantly higher cortical hypertrophy in zone 3 (p < 0.01). Stress shielding was not significantly different between Dorr types. The preoperative and postoperative HHS and UCLA activity scores showed no significant differences between the Dorr types. CONCLUSIONS: In Dorr type C, BMD significantly decreased in the proximal femur with a rectangular tapered short stem, suggesting that the stem was fixed at the distal part. Careful observation of this prosthesis over time is needed in patients with Dorr type C.

Combined assessment of acetabular coverage and femoral head-neck shapes predicts osteoarthritis progression after periacetabular osteotomy.

INTRODUCTION: Postoperative osteoarthritis (OA) progression is a major determinant of failure after curved periacetabular osteotomy (CPO). A large postoperative combination angle, i.e., the combination of computed tomography-based anterior center edge and alpha angles, is associated with femoroacetabular impingement after CPO, but its association with postoperative OA progression is unclear. We aimed to identify the anatomical parameters that can lead to OA progression after CPO and the impact of the combination angle on the same. MATERIALS AND METHODS: We included 90 hips that were subjected to CPO at our center between March 2013 and March 2018. Seventeen hips showed OA progression with an increase in the Tönnis classification after surgery; 73 hips showed no progression. Radiographic anatomical parameters, including the lateral and anterior center edge angles, femoral and acetabular anteversion, and combination angle, and clinical outcomes, including modified Harris Hip Scores (mHHSs), postoperative anterior impingement, and range of motion, were compared between the two groups. Statistical significance was set at P < 0.05. RESULTS: Postoperative OA progression was significantly affected by preoperative OA evidence (P = 0.017), acetabular anteversion < 5.0° (P = 0.003), and a combination angle > 107.0° (P = 0.025). Patients with radiographic OA progression were associated with poor mHHSs (P = 0.017) and high frequencies of anterior impingement with a limited hip flexion and internal rotation angle. CONCLUSIONS: OA progression after CPO may be associated with preoperative evidence of OA and postoperative acetabular retroversion as well as a large combination angle. Surgeons should focus on the potential effects of preoperative OA grades, postoperative reduction in acetabular anteversion, and postoperative combination angle.

Comparison of short-term clinical results between modified kinematically-aligned and guided motion bicruciate stabilized total knee arthroplasty.

BACKGROUND: Both kinematically-aligned (KA) total knee arthroplasty (TKA) and bicruciate stabilized (BCS) TKA aim to reproduce the physiological knee kinematics. In this study, we compared the femoro-tibial component rotational mismatch between patients who underwent modified KA-TKA and those who received guided-motion BCS-TKA, and its influence on the clinical outcomes. METHODS: In this retrospective study, 77 consecutive patients were included and divided into two groups: subjects who underwent modified KA-TKA with Persona (KA Group; n = 42) and those who received BCS-TKA with JOURNEY II (BCS group; n = 35). Range of motion, the 2011 Knee Society Score (KSS), the rotational alignment of the femoral and tibial components, and the correlations between the rotational mismatch and the 2011 KSS subscales were examined. RESULTS: The postoperative objective knee indicators (P = 0.0157), patient satisfaction (P = 0.0039) and functional activity scores (P = 0.0013) in the KA group were significantly superior to those in the BCS group 1 year postoperatively. There was no significant difference between the two groups observed in the rotational mismatch. In the BCS group, significant negative correlations were identified between the rotational mismatch and objective indicators, patient satisfaction, and functional activity scores but not in the KA group. CONCLUSIONS: The short-term clinical results following KA-TKA showed superior objective knee indicators, patient satisfaction and functional activity scores. A negative correlation was observed between component rotational mismatch and the 2011 KSS subscales in the BCS group, compared to no relationship found between the two in the KA group. These findings suggested that KA-TKA has a relatively higher tolerance for rotational mismatch than BCS-TKA.

Intraoperative lateral laxity greater than 4° is associated with inferior functional improvement in posterior-stabilised total knee arthroplasty.

PURPOSE: The study aimed to determine the impact of intraoperative lateral laxity at extension on clinical and functional outcomes 1 year after posterior-stabilised total knee arthroplasty (PS-TKA). METHODS: In total, 91 varus-type osteoarthritic knees that underwent PS-TKA using the medial preservation gap technique were included. After the femoral trial component placement and patellofemoral joint reduction, the soft-tissue balance was assessed using an offset-type tensor with a 40-lb joint-distraction force. Patients were divided into the following three groups according to the intraoperative lateral laxity at extension (i.e., varus ligament balance) using the mean ± 1 standard deviation: Groups A, ≤0°; B, 0-4°; and C, >4°. The 2011 Knee Society Score (KSS) and 3-m timed up-and-go test (TUG) time 1-year postoperatively, and their improvements were compared among the groups. RESULTS: While significant improvements were observed in all subscales of the 2011 KSS and TUG post-TKA (p < 0.05), the improvement of functional activities and TUG time were significantly lower in Group C than in Group B (p < 0.05). However, no significant differences were observed in symptom improvement, patient satisfaction or patient expectation scores among the groups. CONCLUSION: An excessive lateral laxity (varus angle) >4° at extension was associated with lower improvement in functional ability 1-year postoperatively. Therefore, excessive intraoperative lateral laxity should be avoided in PS-TKA. LEVEL OF EVIDENCE: Level IV.

Rotating Hinge Knee Arthroplasty for Charcot Joints of the Knees in Patients With Charcot-Marie-Tooth Disease: A Report of Two Cases.

We report two cases wherein rotating hinge knee (RHK) arthroplasty was performed for Charcot joints that developed secondary to Charcot-Marie-Tooth disease (CMT).  Case 1 was of a 74-year-old woman with CMT. She presented with muscle weakness and sensory disturbances of the distal lower limbs, deformity, and significant medial instability of the bilateral knees. She was then diagnosed with Charcot joints of the knees secondary to CMT, which were treated with RHK arthroplasty. Five years postoperatively, there was no instability, and she was able to stand unassisted without pain. Case 2 was a 90-year-old woman with CMT who presented with muscle weakness and sensory disturbances of the distal lower limbs, deformity, and significant medial instability of the bilateral knees. She was then diagnosed with Charcot joints of the knees secondary to CMT, which were also treated with RHK arthroplasty. One year postoperatively, there was no instability, and she was able to walk smoothly using a walker. These clinical cases indicate that RHK arthroplasty can be a good therapeutic option for Charcot joints of the knees in patients with CMT.

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.

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.

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.

Intravenous perampanel as an alternative to the oral formulations in Japanese patients with epilepsy.

OBJECTIVE: Perampanel is an oral anti-seizure medication, which is approved in Japan for focal-onset seizures, with/without focal to bilateral tonic-clonic seizures, as monotherapy/adjunctive therapy in patients aged 4 years and older. Treatment for generalized tonic-clonic seizures as adjunctive therapy in patients aged 12 years and older is approved as well. We evaluated the feasibility of intravenous (IV) administration of perampanel as an alternative to oral administration. METHODS: Study 240 (NCT03754582) was an uncontrolled, open-label study of IV perampanel, conducted in 21 Japanese patients with epilepsy who received a stable dose of 8-12 mg/day of oral perampanel. Patients received 30-minute IV infusions at equivalent daily doses of oral perampanel for 4 days, then were switched back to oral perampanel. Safety, tolerability, plasma concentration, and maintenance of efficacy throughout the transition between IV and oral dosing of perampanel were assessed. As supportive data, a subgroup analysis was also conducted using data from healthy Japanese subjects (n = 18) who were enrolled in Study 050 (NCT03376997) investigating the pharmacokinetics and safety of IV perampanel in healthy subjects who received an IV infusion (30-, 60-, or 90-minute) of perampanel 12 mg and a single oral administration of perampanel 12-mg tablet. RESULTS: In Study 240, the transition between 30-minute IV and oral perampanel dosing was associated with a ≤1.4-fold increase in the mean change in maximum observed concentration of perampanel. Seizure outcomes demonstrated no considerable changes in efficacy before, during, or after 30-minute IV dosing of perampanel. The safety profiles were similar between IV and oral formulations. In Study 050, the pharmacokinetics of 30- or 60-minute IV infusion of perampanel further support the interchangeability between oral and IV formulations in the Japanese subjects. SIGNIFICANCE: These results support that 30-minute IV perampanel may be a potential short-term alternative to oral formulations for patients with epilepsy.

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.

Heterogeneous Cells as well as Adipose-Derived Stromal Cells in Stromal Vascular Fraction Contribute to Enhance Anabolic and Inhibit Catabolic Factors in Osteoarthritis.

The stromal-vascular fraction (SVF), comprising heterogeneous cell populations and adipose-derived stromal cells (ADSCs), has therapeutic potential against osteoarthritis (OA); however, the underlying mechanism remains elusive. This study aimed to investigate the therapeutic effects of heterogeneous cells in rabbit SVF on rabbit chondrocytes. Rabbit SVF and ADSCs were autografted into knees at OA onset. The SVF (1 × 105) and low-dose ADSCs (lADSC; 1 × 104) groups adjusted for their stromal cell content were compared. Animals were euthanized 8 and 12 weeks after OA onset for macroscopic and histological analyses of OA progression and synovitis. Immunohistochemical and real-time polymerase chain reaction assessments were conducted. In vitro, immune-fluorescent double staining was performed for SVF to stain macrophages with F4/80, CD86(M1), and CD163(M2). OA progression was markedly suppressed, and synovitis was reduced in the SVF groups (OARSI histological score 8 W: 6.8 ± 0.75 vs. 3.8 ± 0.75, p = 0.001; 12 W: 8.8 ± 0.4 vs. 5.4 ± 0.49, p = 0.0002). The SVF groups had higher expression of collagen II and SOX9 in cartilage and TGF-ß and IL-10 in the synovium, lower expression of MMP-13, and lower macrophage M1/M2 ratio than the lADSC groups. Immunofluorescent double staining revealed a markedly higher number of M2 than that of M1 macrophages in the SVF. The therapeutic effects of SVF on chondrocytes were superior than those of lADSCs, with enhanced anabolic and inhibited catabolic factors. Heterogeneous cells, mainly M2 macrophages in the SVF, enhanced growth factor secretion and chondrocyte-protective cytokines, thus benefiting chondrocytes and knee joint homeostasis. Overall, the SVF is a safe, relatively simple, and a useful treatment option for OA.

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.

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.