Publications by authors named "Hiromu Ito"

290 Publications

Opening Wedge High Tibial Osteotomy with High Hinge Position Risks Lateral Hinge Fracture in Males with Posterolateral Tibial Condyle Protrusion.

Arthroscopy 2022 Aug 9. Epub 2022 Aug 9.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.

Purpose: The primary aim of this study was to evaluate the 3D morphology of the proximal tibia around the osteotomy plane in open-wedge high tibial osteotomy (OWHTO), focusing on the posterolateral (PL) and posteromedial (PM) tibial condyles, and to clarify the changes in morphological parameters due to differences in patient characteristics and hinge position. The secondary aim was to examine whether morphological features were associated with insufficient osteotomy, which increases the risk of lateral hinge fracture (LHF).

Methods: The PL and PM anteroposterior distance, asymmetry ratio, and discrepancy between PL and PM distances along the tibial osteotomy plane were measured. We investigated changes in the parameters due to differences in patient characteristics and hinge position. Osteotomy configurations and LHFs were evaluated using postoperative CT scans.

Results: The 3D preoperative plans of 117 knees (male, 41 knees; female, 76 knees) were evaluated. PL distances were larger than PM distances in almost all cases. The average asymmetry ratio was 1.35, and the standard deviation was 0.22. Higher hinge position was associated with a larger asymmetry ratio and discrepancy (p < 0.001). The asymmetry ratio and discrepancy were independently positively correlated with male sex (p = 0.002 and p = 0.001, respectively) and gentle posterior tibial slope (p < 0.001 and p < 0.001, respectively). Osteotomies with Type III LHFs showed lower osteotomy sufficiency than osteotomies without LHFs (p < 0.001).

Conclusion: PL tibial condyle protrusion was more pronounced in male patients and those with a high hinge position, and may result in insufficient PL osteotomy, which is a risk factor for Type III LHF during OWHTO. The optimal hinge position was located approximately 15 mm and 20 mm distal to the lateral tibial plateau in female and male patients, respectively.
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http://dx.doi.org/10.1016/j.arthro.2022.07.018DOI Listing
August 2022

An anatomical study for the location of suprascapular and spinoglenoid notches using three-dimensional computed tomography images of scapula.

JSES Int 2022 Jul 5;6(4):669-674. Epub 2022 May 5.

Department of Orthopaedics, Kurashiki Central Hospital, Kurashiki, Okayama, Japan.

Background: The optimal position for creating portals for arthroscopic suprascapular nerve decompression has not been sufficiently verified. Therefore, this study aimed to investigate the anatomical characteristics of the scapula for optimal portal creation using 3-dimensional computed tomography images. The posterolateral corner of the acromion was designated as the starting point for measurements because there is no secondary ossification center present.

Methods: This study included 223 patients (females, 129; males, 94) who underwent computed tomography of the shoulder joint. Three-dimensional images of the scapula were created, and the distance from the posterolateral corner of the acromion to the suprascapular and spinoglenoid notches was measured. Additionally, the correlation coefficient with height and the differences between the female and male groups were investigated.

Results: The distances from the posterolateral corner of the acromion to the suprascapular and spinoglenoid notches were 42.9 ± 4.6 and 31.5 ± 3.6 mm, respectively, and their correlation coefficients with height were 0.12 and 0.067, respectively. There was no significant difference in the distance from the posterolateral corner of the acromion to the suprascapular (42.5 ± 4.1 vs. 43.9 ± 5.1 mm,  = .098) and to the spinoglenoid (31.4 ± 3.3 mm vs. 32.0 ± 3.9 mm,  = .12) notches between the female and male groups.

Conclusion: Regardless of height and sex, the distances from the posterolateral corner of the acromion to the suprascapular and spinoglenoid notches were approximately 43 and 32 mm, respectively. Therefore, creating portals at these locations may be effective for arthroscopic suprascapular nerve decompression.
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http://dx.doi.org/10.1016/j.jseint.2022.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264012PMC
July 2022

Dynamics of Type I and Type II Interferon Signature Determines Responsiveness to Anti-TNF Therapy in Rheumatoid Arthritis.

Front Immunol 2022 6;13:901437. Epub 2022 Jun 6.

Department of Advanced Medicine for Rheumatic Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan.

The factors influencing long-term responses to a tumor necrosis factor inhibitor (TNFi) in rheumatoid arthritis (RA) patients currently remain unknown. Therefore, we herein conducted a multi-omics analysis of TNFi responses in a Japanese RA cohort. Blood samples were collected from 27 biological disease-modifying antirheumatic drug (DMARD)-naive RA patients at the initiation of and after three months of treatment with TNFi. Treatment responses were evaluated at one year. Differences in gene expression levels in peripheral blood mononuclear cells (PBMCs), plasma protein levels, drug concentrations, and the presence/absence of anti-drug antibodies were investigated, and a cell phenotypic analysis of PBMCs was performed using flow cytometry. After one year of treatment, thirteen patients achieved clinical remission (responders), while the others did not or switched to other biologics (non-responders). Differentially expressed genes related to treatment responses were enriched for the interferon (IFN) pathway. The expression of type I IFN signaling-related genes was higher in non-responders than in responders before and after treatment ( = 0.03, 0.005, respectively). The expression of type II IFN signaling-related genes did not significantly differ before treatment; however, it increased in non-responders and decreased in responders, with a significant difference being observed after three months of treatment ( = 1.2×10). The total number of lymphocytes and C-X-C Motif Chemokine Ligand 10 (CXCL10) protein levels were associated with the type I IFN signature ( = 6.7×10, 6.4×10, respectively). Hepatocyte growth factor (HGF) protein levels before treatment predicted fold increases in type II IFN ( = 0.03). These IFN signature-related indices (the number of lymphocytes, CXCL10, and HGF) significantly differed between responders and non-responders ( = 0.01, 0.01, and 0.04, respectively). A single-cell analysis revealed that the type I IFN signature was more highly enriched in monocytes than in other cell types. A deconvolution analysis of bulk-RNA sequence data identified CD4+ and CD8+ T cells as the main sources of the type II IFN signature in non-responders. Collectively, the present results demonstrated that the dynamics of the type I and II IFN pathways affected long-term responses to TNFi, providing information on its biological background and potential for clinical applications.
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http://dx.doi.org/10.3389/fimmu.2022.901437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208293PMC
June 2022

Facilitated harvesting of a radial artery superficial palmar branch flap for reconstruction of moderate finger skin defects.

J Plast Reconstr Aesthet Surg 2022 May 2. Epub 2022 May 2.

Department of Orthopedic Surgery, Kurashiki Central Hospital, Kurashiki, Japan.

Radial artery superficial palmar branch harvesting is technically challenging, especially for inexperienced hand surgeons. The short pedicle and a damaged recipient digital artery require proximal digital artery dissection and relatively long pedicles. Herein, we describe a facilitated flap elevation technique and its application in various cases. From 2013 to 2021, 10 patients with finger injuries received radial artery superficial palmar flaps. We assessed flap survival, sizes, complications, two-point discrimination, and the Semmes-Weinstein monofilament test results. The main shortcoming of a radial artery superficial palmar flap is its short pedicle. Therefore, we developed a long skin flap design in the long axis direction, and the accompanying vein was dissected proximally to the radial artery to obtain a long pedicle. All flaps survived. The median flap dimension was 5.0 × 2.2 cm (maximum size: 6.0 × 2.0 + 5.0 × 2.0 cm [for a bilobed flap]). While nerve reconstruction was performed in one patient, all patients had preserved sensation. A sufficiently long pedicle can be obtained by dissecting the accompanying vein proximally to the radial artery. Perforators found in the skin around the scaphoid tubercle in all cases suggest value in including this region in flap design. To obtain a longer pedicle, the flap was developed with the long-skin design in the long-axis direction. Although the accompanying vein is usually thin and difficult to anastomose with the finger vein, its proximal dissection led to the accompanying vein of the radial artery that facilitated the harvesting of a sufficiently long vein.
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http://dx.doi.org/10.1016/j.bjps.2022.04.092DOI Listing
May 2022

Optimal strategies and cost-benefit analysis of the [Formula: see text]-player weightlifting game.

Sci Rep 2022 05 19;12(1):8482. Epub 2022 May 19.

Graduate School of Science and Technology, Shizuoka University, Hamamatsu, Shizuoka, 423-8561, Japan.

The study of cooperation has been extensively studied in game theory. Especially, two-player two-strategy games have been categorized according to their equilibrium strategies and fully analysed. Recently, a grand unified game covering all types of two-player two-strategy games, i.e., the weightlifting game, was proposed. In the present study, we extend this two-player weightlifting game into an [Formula: see text]-player game. We investigate the conditions for pure strategy Nash equilibria and for Pareto optimal strategies, expressed in terms of the success probability and benefit-to-cost ratio of the weightlifting game. We also present a general characterization of [Formula: see text]-player games in terms of the proposed game. In terms of a concrete example, we present diagrams showing how the game category varies depending on the benefit-to-cost ratio. As a general rule, cooperation becomes difficult to achieve as group size increases because the success probability of weightlifting saturates towards unity. The present study provides insights into achieving behavioural cooperation in a large group by means of a cost-benefit analysis.
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http://dx.doi.org/10.1038/s41598-022-12394-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120137PMC
May 2022

Systemic Chronic Diseases Coexist with and Affect Locomotive Syndrome: The Nagahama Study.

Mod Rheumatol 2022 May 12. Epub 2022 May 12.

Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Objectives: The concept of locomotive syndrome was proposed to highlight older adults who require nursing care services due to the malfunctioning of their locomotive organs. With the coming of a super-aging society, there is a growing need to understand relation between systemic chronic diseases and locomotive syndrome.

Methods: We analyzed the second-visit dataset of the Nagahama Study. The association analysis was performed to identify the chronic diseases that were risk factors associated with the occurrence and the progression of locomotive syndrome in both the cross-sectional and longitudinal studies.

Results: Hypertension, stroke, coronary heart disease, rheumatoid arthritis, chronic renal failure, osteoporosis, anemia, and gastroesophageal reflux disease were independently correlated with locomotive syndrome through the deterioration of body pain, social activity, and cognitive function in the cross-sectional study. Multiple chronic diseases had additive effects and significantly increased the risk of locomotive syndrome. In the longitudinal study, osteoporosis and kidney disease were significantly correlated with the worsening of the total GLFS-25 score.

Conclusions: Locomotive syndrome coexisted with various systemic chronic diseases, especially cardiovascular diseases. Osteoporosis and kidney disease were significantly correlated with the progression of locomotive dysfunction. The management of various chronic diseases may be useful to prevent locomotive syndrome and vice versa.
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http://dx.doi.org/10.1093/mr/roac039DOI Listing
May 2022

Machine learning-based prediction of relapse in rheumatoid arthritis patients using data on ultrasound examination and blood test.

Sci Rep 2022 05 4;12(1):7224. Epub 2022 May 4.

Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Recent effective therapies enable most rheumatoid arthritis (RA) patients to achieve remission; however, some patients experience relapse. We aimed to predict relapse in RA patients through machine learning (ML) using data on ultrasound (US) examination and blood test. Overall, 210 patients with RA in remission at baseline were dichotomized into remission (n = 150) and relapse (n = 60) based on the disease activity at 2-year follow-up. Three ML classifiers [Logistic Regression, Random Forest, and extreme gradient boosting (XGBoost)] and data on 73 features (14 US examination data, 54 blood test data, and five data on patient information) at baseline were used for predicting relapse. The best performance was obtained using the XGBoost classifier (area under the receiver operator characteristic curve (AUC) = 0.747), compared with Random Forest and Logistic Regression (AUC = 0.719 and 0.701, respectively). In the XGBoost classifier prediction, ten important features, including wrist/metatarsophalangeal superb microvascular imaging scores, were selected using the recursive feature elimination method. The performance was superior to that predicted by researcher-selected features, which are conventional prognostic markers. These results suggest that ML can provide an accurate prediction of relapse in RA patients, and the use of predictive algorithms may facilitate personalized treatment options.
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http://dx.doi.org/10.1038/s41598-022-11361-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068780PMC
May 2022

Comparison of conventional and transtrapezial palmar approaches for screw fixation of scaphoid waist fractures: a clinical study.

J Hand Surg Eur Vol 2022 Apr 26:17531934221095435. Epub 2022 Apr 26.

Department of Orthopaedic Surgery, Kurashiki Central Hospital, Kurashiki, Japan.

We investigated two palmar approaches for screw fixation of acute scaphoid waist fractures: the conventional percutaneous or transtrapezial approach. Thirty cases who underwent operation from 2013 to 2021 were reviewed (conventional group, 15; transtrapezial approach group, 15). Cross-sections were constructed along the long axis of the scaphoid on postoperative computed tomography to evaluate the screw position, relative to the centre point in the distal-third, midwaist and proximal-third of the bone. The screw could be inserted centrally in the proximal and distal regions using the transtrapezial approach. In the conventional approach, the screw was inserted radially in the distal region, but tended to be positioned centrally in the midwaist and proximal regions. As central placement of the screw in the proximal fragment offers a biomechanical advantage, both approaches can be options for some fracture patterns, while for others, the fracture pattern could influence which approach is better. IV.
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http://dx.doi.org/10.1177/17531934221095435DOI Listing
April 2022

High prevalence of rheumatoid arthritis and its risk factors among Tibetan highlanders living in Tsarang, Mustang district of Nepal.

J Physiol Anthropol 2022 Apr 2;41(1):12. Epub 2022 Apr 2.

Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.

Background: In Tsarang (at 3560 m), which is located in Mustang, 62.7% of the residents answered that they had a subjective medical history of arthritis, and 41.1% of the residents answered that their families had a subjective medical history of arthritis on a survey conducted in 2017. The expression of hypoxia-inducible factor (HIF) and its effects are deeply involved in hypoxic adaptation in Tibetan highlanders. At the same time, HIF is also related to the onset of rheumatoid arthritis. Therefore, the adaptive mechanism acquired by Tibetan highlanders may promote the development of rheumatoid arthritis. The prevalence of rheumatoid arthritis is estimated to be approximately 0.5-1.0% worldwide. The objective of this study was to estimate the prevalence of rheumatoid arthritis in Tsarang residents using existing diagnostic criteria and to explore its risk factors.

Methods: An epidemiological survey was conducted in Tsarang in 2019. Data obtained from anthropometry and questionnaires were statistically analyzed. Biochemical measurements using blood samples were also performed, and the results were used to assess arthritis status. Residents' joint status was scored, and arthritis was assessed based on the clinical disease activity index and ACR/EULAR 2010 criteria.

Results: Twenty-seven males and 50 females participated in this survey. In Tsarang, ACR/EULAR 2010 classified 4.3% of males and 7.1% of females as having rheumatoid arthritis, indicating a very high estimated prevalence. We also performed a multivariate analysis to explore its risk factors, and two factors, older age (standardized parameter estimate = 4.84E-01, 95% CI = [9.19E-02, 8.76E-01], p = 0.0170) and a history of living in urban areas (standardized parameter estimate = - 5.49E-01, 95% CI = [- 9.21E-01, 1.77E-01], p = 0.0050), significantly contributed to the higher ACR/EULAR 2010 score in females. In addition, three factors, having no spouse (standardized parameter estimate = 3.17E-01, 95% CI = [5.74E-02, 5.77E-01], p = 0.0179), having a smoking habit (standardized parameter estimate = 2.88E-01, 95% CI = [1.71E-02, 5.59E-01], p = 0.0377), and a history of living in urban areas (standardized parameter estimate = - 3.69E-01, 95% CI = [- 6.83E-01, - 5.60E-02], p = 0.0219), resulted in significantly higher clinical disease activity index scores in females. Furthermore, smoking habits were found to significantly increase blood hyaluronic acid in both males (standardized parameter estimate = 6.03E-01, 95% CI = [3.06E-01, 9.01E-01], p = 0.0020) and females (standardized parameter estimate = 4.87E-01, 95% CI = [5.63E-02, 9.18E-01], p = 0.0291).

Conclusions: In this study, we evaluated the symptoms of arthritis and estimated the prevalence of rheumatoid arthritis using classification criteria for Tibetan highlanders who have adapted to the hypoxic environment and fostered their own culture. The high prevalence of rheumatoid arthritis among Tsarang residents suggests that the hypoxic adaptation mechanism involving HIF in Tibetan highlanders may promote the onset or exacerbation of rheumatoid arthritis. The high prevalence of rheumatoid arthritis among Tibetan highlanders may be related not only to the environmental factors analyzed in this study but also to hypoxic adaptation genes. Further investigation is needed to clarify the genetic factors involved.
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http://dx.doi.org/10.1186/s40101-022-00283-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976395PMC
April 2022

Physical and Financial Impacts Caused by the COVID-19 Pandemic Exacerbate Knee Pain: A Longitudinal Study of a Large-Scale General Population.

Mod Rheumatol 2022 Mar 30. Epub 2022 Mar 30.

Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Objectives: This study aimed to evaluate the changes in knee pain, a dominant cause of physical disability, following the coronavirus disease (COVID-19) pandemic, and to identify factors affecting the changes in knee pain.

Methods: We analyzed the pre- and post-COVID-19 longitudinal dataset of the Nagahama Study. Knee pain was assessed using the Knee Society Score (KSS). The estimated KSS from the age and sex using regression model in the pre- and post-COVID-19 dataset was compared. Factors including the activity score, educational level, and various impacts of COVID-19 were analyzed for correlation analyses with changes in KSS.

Results: Data collected from 6409 participants showed statistically significant differences in KSS, pre- (mean = 22.0; SD = 4.4) and post-COVID-19 (mean = 19.5; SD = 6.4). Low activity score (p = 0.008), low educational level (p < 0.001) and undesirable financial impact (p = 0.030) were independently associated with knee pain exacerbation.

Conclusion: The harmful effects of the COVID-19 pandemic on knee pain were suggested. People should be encouraged to engage in physical activities, such as walking, even despite the state of emergency. Furthermore, social support for economically disadvantaged groups may improve healthcare access, preventing the acute exacerbations of knee pain.
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http://dx.doi.org/10.1093/mr/roac022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992315PMC
March 2022

Drug Treatment Algorithm and Recommendations from the 2020 update of the Japan College of Rheumatology Clinical Practice Guidelines for the Management of Rheumatoid Arthritis-Secondary Publication.

Mod Rheumatol 2022 Mar 16. Epub 2022 Mar 16.

Department of Internal Medicine, Division of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.

Objective: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) (JCR CPG for RA) according to recent changes in the medical environment in Japan. This article is a digest version of the guidance.

Methods: We used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. A consensus was formed by CPG panel members.

Results: We identified 36 important clinical questions regarding drug treatment and developed corresponding recommendations for RA. The recommendations included the following RA medications: non-steroidal anti-inflammatory drugs, corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, biological disease-modifying antirheumatic drugs, anti-RANKL antibodies, and JAK inhibitors, as well as the tapering and discontinuation of these medications. Recommendations regarding the efficacy and safety of treatments in the elderly and patients with comorbidities were also developed. Finally, we used these recommendations to create an original algorithm for drug treatment for RA based on the Treat-to-Target approach.

Conclusion: The 2020 JCR CPG for RA provides a useful tool for rheumatologists, health care professionals, and patients with RA, enabling shared decision making in a variety of clinical situations.
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http://dx.doi.org/10.1093/mr/roac017DOI Listing
March 2022

Non-Drug and Surgical Treatment Algorithm and Recommendations for the 2020 Update of the Japan College of Rheumatology Clinical Practice Guidelines for the Management of Rheumatoid Arthritis - Secondary Publication.

Mod Rheumatol 2022 Mar 16. Epub 2022 Mar 16.

Department of Internal Medicine, Division of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.

Objectives: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) and prepare an algorithm for non-drug and surgical treatments. This article is a digest version of the guidelines.

Methods: The Japanese Ministry of Health, Labour and Welfare's research group, in collaboration with the JCR, used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. The consensus was formed by CPG panel members.

Results: We raised 19 clinical questions regarding non-drug and surgical treatments for RA and developed recommendations. The treatments included exercise therapy; occupational therapy; joint injection of corticosteroids; and orthopedic surgeries including cervical spine surgery, wrist and foot arthroplasty, ankle arthrodesis, and replacement arthroplasty of the shoulder, elbow, finger, hip, knee, and ankle. Recommendations regarding the risks of surgery and perioperative discontinuation of medications have also been developed. Based on these recommendations, we created an original algorithm for the non-drug and surgical treatment of RA.

Conclusions: These recommendations are expected to serve rheumatologists, health care professionals, and patients with RA as tools for shared decision-making to treat residual limb joint symptoms and functional impairment.
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http://dx.doi.org/10.1093/mr/roac019DOI Listing
March 2022

Individual variations and sex differences in hemodynamics and percutaneous arterial oxygen saturation (SpO) in Tibetan highlanders of Tsarang in the Mustang district of Nepal.

J Physiol Anthropol 2022 Mar 15;41(1). Epub 2022 Mar 15.

Department of International Health and Medical Anthropology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.

Background: Many studies have indicated specific low-hemoglobin (Hb) adaptation to high altitude in the Tibetan population, but studies focusing on physiological variations within this population are limited. This study aimed to investigate the relationships between SpO and related factors, including individual variations and sex differences, to assess the generality of high-altitude adaptation in the Tibetan population of Tsarang.

Methods: The participants were 31 male and 41 female community-dwelling people aged ≥18 years living in Tsarang, in the Mustang district of Nepal. Height, weight, SpO, Hb concentration, finger temperature, heart rate, and blood pressure were measured. Lifestyle information was obtained by interview.

Results: Men had significantly higher systolic blood pressure (p = 0.002) and Hb (p < 0.001) than women. There was no significant correlation between SpO and other parameters in men. In women, SpO was negatively correlated with heart rate (p = 0.036), Hb (p = 0.004), and finger temperature (p = 0.037). In multiple regression analysis, a higher SpO was marginally correlated with lower age (β = -0.109, p = 0.086) and higher Hb (β = 0.547, p = 0.053) in men. In women, higher SpO was significantly correlated with lower heart rate (β = -0.045, p = 0.036) and Hb (β = -0.341, p = 0.018). Mean hemoglobin (95% confidence interval) was 13.6 g/dl (13.1-14.0 g/dl), which is lower than that found previously in Andeans and almost equal to that in Japanese lowlanders measured using the same device. In some participants of both sexes, hemoglobin was >17.0 g/dl.

Conclusion: Higher SpO was marginally correlated with younger age and higher Hb in men and with lower heart rate and lower Hb in women. Hemoglobin concentration was similar to that found previously in lowlanders, but higher in some individuals. These results indicate individual variation and sex differences in the hemodynamics of high-altitude adaptation in Tibetan highlanders of Tsarang, as well as low-Hb adaptation to high altitude equal to that of other Tibetans.
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http://dx.doi.org/10.1186/s40101-022-00282-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8925233PMC
March 2022

Differential efficacy of TNF inhibitors with or without the immunoglobulin fragment crystallizable (Fc) portion in rheumatoid arthritis: the ANSWER cohort study.

Rheumatol Int 2022 07 10;42(7):1227-1234. Epub 2022 Mar 10.

Department of Advanced Medicine for Rheumatic Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Rheumatoid factor (RF) binds to the fragment crystallizable (Fc) portion of immunoglobulin. It could bind to the Fc portion of anti-TNF inhibitors (TNFi) and attenuate the clinical efficacy. We tried to determine whether the therapeutic efficacy of TNFi with Fc might be lower than that of TNFi without Fc in rheumatoid arthritis (RA) patients with high titres of RF. The Kansai Consortium for Well-being of Rheumatic Disease Patients (ANSWER) cohort is an observational multi-center registry of patients with RA in the Kansai district of Japan. RA patients treated with TNFi were included and divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, and etanercept) and TNFi without Fc (certolizumab pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) was compared by Mann-Whitney U test between TNFi with and without Fc in each RF titre group. Multiple linear regression analysis was used to analyze the effect of TNFi without Fc for the change of DAS28-ESR adjusted after potential confounders. A total of 705 RA patients were classified into four groups (RF; RF 0-15.0 IU/mL, RF; 15.0-55.0, RF; 55.0-166, RF; 166-7555). In RF, RA patients treated with TNFi without Fc had a significantly lower DAS28-ESR than those treated with TNFi with Fc [3.2 (2.3-4.2) vs. 2.7 (2.0-3.0)] after 12 months. This effect of TNFi without Fc for the change of DAS28-ESR after 12 months treatment retained in multivariate analysis in RF. TNFi without Fc may be more efficacious than TNFi with Fc in RA patients with high RF titres.
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http://dx.doi.org/10.1007/s00296-021-05086-wDOI Listing
July 2022

Ultrasonographic Changes of the Knee Joint Reflect Symptoms of Early Knee Osteoarthritis in General Population; The Nagahama Study.

Cartilage 2022 Jan-Mar;13(1):19476035221077403

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objective: Radiographic changes in knee osteoarthritis (OA) are not always associated with symptoms, especially in its early stages. Ultrasonography (US) can detect early changes in the knee joint, but the changes that reflect symptoms have not been fully elucidated. This study aimed to identify US-detectable changes in the knee that are often associated with knee symptoms and demonstrate the feasibility of early diagnosis in symptomatic knee OA using US.

Design: In this cross-sectional community-based study, 1,667 participants aged ≥60 years (1,103 women [66%]) were included. All participants concurrently underwent US and radiography of the knee and completed the Knee Society Knee Scoring System (KSS) questionnaire. Simple and multiple regression analyses were used to examine the associations between US findings and KSS symptom subscales.

Results: Among all participants, medial meniscus protrusion and medial osteophytes, age, and body mass index showed significant associations with KSS symptom scores. Among 894 participants with Kellgren-Lawrence (KL) grade ≤1, medial osteophytes and age were significantly associated with KSS symptom score. US measures were more related to KSS symptoms than KL grades.

Conclusions: Among the knee US-detectable changes, medial osteophytes were strongly associated with knee symptoms. Osteophytes are reliable predictors of symptomatic early knee OA, even in participants with few radiographic OA changes.
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http://dx.doi.org/10.1177/19476035221077403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137311PMC
April 2022

Ultrasound-guided interscalene block anesthesia performed by an orthopedic surgeon: a study of 1322 cases of shoulder surgery.

JSES Int 2022 Jan 12;6(1):149-154. Epub 2021 Oct 12.

Department of Orthopaedics, Kurashiki Central Hospital, Okayama, Japan.

Background: Interscalene blocks are becoming increasingly common for shoulder surgeries. This study primarily aimed to demonstrate the efficacy and complications and the secondarily to investigate the anesthesia-related time and patient satisfaction of an ultrasound-guided interscalene block performed by an orthopedic surgeon.

Methods: We retrospectively reviewed the medical records of 1322 consecutive patients (arthroscopic, 1225 cases; open, 97 cases) with a mean age of 64.2 years, who underwent shoulder surgery (arthroscopic or opensurgery) under an ultrasound-guided interscalene block performed by an orthopedic surgeon at a single institution between December 2012 and December 2019. We investigated patient satisfaction, block success rates, and complications and also compared the anesthesia-related time of an interscalene block with that of general anesthesia (428 cases, arthroscopic, 257 cases; open, 171 cases) for shoulder surgery with patients in the beach chair position during the same period. Difference between total anesthesia time and surgical time was defined as anesthesia-related time.

Results: Approximately 98.3% of patients were satisfied with an interscalene block, and the block success rate on the first attempt was 99.9%. Total complication incidence was 2.3%, with no recorded life-threatening complications. Anesthesia-related times were significantly shorter in the interscalene block group than those in the general anesthesia group (45 ± 14 min vs. 100 ± 26 min,  < .001).

Conclusion: An ultrasound-guided interscalene block performed by an orthopedic surgeon for shoulder surgery is effective and safe, requires less time, and has a high patient acceptance rate, making it a feasible and alternative to the block performed by anesthesiologists.
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http://dx.doi.org/10.1016/j.jseint.2021.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811386PMC
January 2022

Role of Lysine-Specific Demethylase 1 in Metabolically Integrating Osteoclast Differentiation and Inflammatory Bone Resorption Through Hypoxia-Inducible Factor 1α and E2F1.

Arthritis Rheumatol 2022 06 27;74(6):948-960. Epub 2022 Apr 27.

Kyoto University Graduate School of Medicine, Kyoto, Japan.

Objective: Hypoxia occurs in tumors, infections, and sites of inflammation, such as in the affected joints of patients with rheumatoid arthritis (RA). It alleviates inflammatory responses and increases bone resorption in inflammatory arthritis by enhancing osteoclastogenesis. The mechanism by which the hypoxia response is linked to osteoclastogenesis and inflammatory bone resorption is unclear. This study was undertaken to evaluate whether the protein lysine-specific demethylase 1 (LSD1) metabolically integrates inflammatory osteoclastogenesis and bone resorption in a state of inflammatory arthritis.

Methods: LSD1-specific inhibitors and gene silencing with small interfering RNAs were used to inhibit the expression of LSD1 in human osteoclast precursor cells derived from CD14-positive monocytes, with subsequent assessment by RNA-sequencing analysis. In experimental mouse models of arthritis, inflammatory osteolysis, or osteoporosis, features of accelerated bone loss and inflammatory osteolysis were analyzed. Furthermore, in blood samples from patients with RA, cis-acting expression quantitative trait loci (cis-eQTL) were analyzed for association with the expression of hypoxia-inducible factor 1α (HIF-1α), and associations between HIF-1α allelic variants and extent of bone erosion were evaluated.

Results: In human osteoclast precursor cells, RANKL induced the expression of LSD1 in a mechanistic target of rapamycin-dependent manner. Expression of LSD1 was higher in synovium from RA patients than in synovium from osteoarthritis patients. Inhibition of LSD1 in human osteoclast precursors suppressed osteoclast differentiation. Results of transcriptome analysis identified several LSD1-mediated hypoxia and cell-cycle pathways as key genetic pathways involved in human osteoclastogenesis. Furthermore, HIF-1α protein, which is rapidly degraded by the proteasome in a normoxic environment, was found to be expressed in RANKL-stimulated osteoclast precursor cells. Induction of LSD1 by RANKL stabilized the expression of HIF-1α protein, thereby promoting glycolysis, in conjunction with up-regulation of the transcription factor E2F1. Analyses of cis-eQTL revealed that higher HIF-1α expression was associated with increased bone erosion in patients with RA. Inhibition of LSD1 decreased pathologic bone resorption in mice, both in models of accelerated osteoporosis and models of arthritis and inflammatory osteolysis.

Conclusion: LSD1 metabolically regulates osteoclastogenesis in an energy-demanding inflammatory environment. These findings provide potential new therapeutic strategies targeting osteoclasts in the management of inflammatory arthritis, including in patients with RA.
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http://dx.doi.org/10.1002/art.42074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156537PMC
June 2022

Acromial and humeral head osteolysis following superior capsular reconstruction using autologous tensor fascia lata graft.

J Shoulder Elbow Surg 2022 Jul 19;31(7):1479-1487. Epub 2022 Jan 19.

Department of Orthopaedics, Kurashiki Central Hospital, Okayama, Japan.

Background: Graft tear is a critical complication following superior capsular reconstruction (SCR) as it directly links with clinical outcomes. No previous reports have described acromial and humeral head osteolysis following SCR. Acromial and humeral head osteolysis may incidentally occur after SCR using autologous tensor fascia lata graft. This study aimed to demonstrate the incidence of osteolysis following SCR using autologous tensor fascia lata graft and investigate the factors that affect osteolysis.

Methods: This retrospective cohort study included patients who underwent SCR for irreparable rotator cuff tears between June 2014 and June 2019. The patients were divided into 2 groups-those with no osteolysis and those with osteolysis-and were compared. For subanalysis, patients in the osteolysis group were further divided into 3 groups according to the location of the osteolysis-acromial osteolysis, humeral head osteolysis, and acromial and humeral head osteolysis-to clarify the factors determining the location of osteolyses. The shoulder range of motion was evaluated preoperatively and 24 months postoperatively. Additionally, the following items were evaluated: condition of the subscapularis tendon, Hamada classification (grade 2 or 3), critical shoulder angle, acromiohumeral distance measured preoperatively and 24 months postoperatively, graft size, and graft thickness. In addition, the graft condition was evaluated using magnetic resonance imaging 12 months postoperatively.

Results: In total, 57 patients were enrolled and followed up for a minimum of 2 years (follow-up rate, 92% [57 of 62 cases]). Overall, the incidence of osteolysis following SCR was 35.1% (20 of 57 cases; acromial osteolysis in 7, humeral head osteolysis in 3, and acromial and humeral head osteolysis in 10). Compared with the group with no osteolysis, the osteolysis group had no inferior clinical outcomes or higher graft tear rates. The proportions of Hamada grade 3 (P = .041) and involvement of the subscapularis tendon (P = .020) were significantly higher in the osteolysis group. The relative risks of subscapularis involvement and Hamada grade 3 for osteolysis were 2.9 and 5.1, respectively. In the subanalysis, the factors determining the location of the osteolysis could not be clarified.

Conclusions: This study suggested that the progression of the Hamada classification and condition of the subscapularis tendon affect the occurrence of osteolyses. However, these osteolyses were not associated with clinical outcomes, including graft tear rate and shoulder range of motion.
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http://dx.doi.org/10.1016/j.jse.2021.12.019DOI Listing
July 2022

Hinge fractures reaching the tibial plateau can be caused by forcible opening of insufficient posterior osteotomy during open-wedge high tibial osteotomy.

Knee Surg Sports Traumatol Arthrosc 2022 Jan 4. Epub 2022 Jan 4.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Purpose: The purpose of this study was to use the finite element method (FEM) to reproduce fracture lines that reach the lateral tibial plateau during open-wedge high tibial osteotomy (OWHTO) in patients with Type III lateral hinge fracture (LHF). It was hypothesized that the FEM could clarify biomechanical causes of Type III LHF, enabling prevention of adverse complications.

Methods: This study used the nonlinear FEM to analyze the data of eight knees in eight patients (two males and six females) with Type III LHF among 82 patients who underwent OWHTO, as well as the data of eight individuals with no LHF. To predict the onset of Type III LHF, simulation models were also developed in which posterior osteotomy sufficiency varied from 50% to perfect, the latter defined as osteotomy reaching the hinge point.

Results: Real-life instances of Type III LHF caused by insufficient posterior osteotomy were reproduced in all patient-specific FEM models, and these models accurately predicted fracture types and locations. During opening of the osteotomy gap, the fracture line reached the lateral tibial plateau, and extended vertically from the end of the insufficient posterior osteotomy, avoiding the rigid proximal tibiofibular joint. In contrast, sufficient posterior osteotomy resulted in a lack of LHF. Posterior osteotomy extension ≥ 70% of the width of the osteotomy plane was the cut-off value to prevent Type III LHF.

Conclusion: Forced opening of insufficient posterior osteotomy was found to be a biomechanical cause of Type III LHF that extended perpendicularly to the lateral tibial plateau, avoiding the proximal tibiofibular joint. The clinical significance of this study is that sufficient posterior osteotomy during OWHTO, defined as at least 70% of the width of the osteotomy plane, can prevent Type III LHF.
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http://dx.doi.org/10.1007/s00167-021-06816-0DOI Listing
January 2022

Static Mediolateral Tilt of the Joint Line after Total Knee Arthroplasty Does Not Reflect Dynamic Tilt during a Stair Ascent Activity.

J Knee Surg 2021 Dec 24. Epub 2021 Dec 24.

Department of Orthopedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

The correlation between static and dynamic mediolateral (ML) tilts of the joint line in the coronal plane remains unknown after total knee arthroplasty (TKA). The purpose was to evaluate the ML tilt as measured by two-dimensional to three-dimensional registration during stair ascent in TKA patients, and to examine the correlation between the dynamic ML tilt and radiographic measurements of static indices. Thirty-two knees that underwent TKA using the mechanical alignment method were included. Continuous sagittal fluoroscopy was taken from before initial contact (IC) until after the toe-off (TO) phase during the stair ascent. The ML tilt of the tibial component relative to the ground was analyzed in terms of dynamic alignment using image-matching techniques, whereas static alignment was measured using standing long-leg radiographs. The correlation between static and dynamic ML tilts was evaluated. In the fluoroscopic analysis, the joint line was neutral (0.0 degree, standard deviation [SD] = 3.4 degrees) around IC phases, then was tilted valgus (5.5° valgus, SD = 2.6 degrees) in the mid-stance (MS) phase. After the TO phase, the joint line became almost neutral (0.4 degrees valgus, SD = 3.1 degrees). The dynamic ML tilt was significantly more varus during the IC phase and significantly more valgus in MS and TO phases than the static ML tilt (1.4 degrees valgus, SD = 2.0 degrees). No correlation was found between static and dynamic ML tilts in weight-bearing phases. During stair ascent, the static tilt had no correlation with the dynamic tilt in weight-bearing phases despite being in the same range. Static lower limb alignment does not reflect coronal alignment during motion. Further research should be conducted to determine whether the horizontal dynamic ML tilt can improve long-term durability and clinical outcomes after TKA.
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http://dx.doi.org/10.1055/s-0041-1740999DOI Listing
December 2021

Tenderness of the knee is associated with thinning of the articular cartilage evaluated with ultrasonography in a community-based cohort: The Nagahama study.

Mod Rheumatol 2021 Sep 4. Epub 2021 Sep 4.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objectives: This study aimed to elucidate the association between joint line tenderness (JLT) of the knee and knee joint structural changes evaluated with ultrasonography (US) for the early diagnosis of knee osteoarthritis (KOA).

Methods: This cross-sectional study included 121 participants (age 71.7 ± 5.8 years, 75 women) from a community-based population. Bilateral structural changes in the knee joint were evaluated with US, and the presence or absence of JLT was evaluated using a pressure algometer. Logistic regression analysis was performed to evaluate the odds ratios (ORs) of US findings for the presence of JLT. Moreover, when the analysis was limited to knees with pre-/early radiographic KOA, the ORs were also calculated using logistic regression analysis.

Results: Among the 242 knees, 38 had medial JLT, which was significantly associated with female sex (OR 11.87) and loss of cartilage thickness of the distal medial femoral condyle (CTh-MFC) (OR 0.12). Among 96 knees with Kellgren-Lawrence grade ≤ 2, 18 knees had medial JLT, which was also significantly associated with loss of CTh-MFC (OR 0.07) and medial osteophytes (OR 2.01).

Conclusions: JLT is significantly associated with thinning of the femoral cartilage and larger osteophytes in elderly patients, even in those with pre-/early radiographic KOA.
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http://dx.doi.org/10.1093/mr/roab040DOI Listing
September 2021

The real-world effectiveness of anti-RANKL antibody denosumab on the clinical fracture prevention in patients with rheumatoid arthritis: The ANSWER cohort study.

Mod Rheumatol 2022 Jul;32(4):834-838

Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by localized and generalized bone loss. The risk of fractures is doubled in patients with RA. Denosumab, an anti-RANKL monoclonal antibody, is used for those with osteoporosis at high risk fracture and it has inhibitory effect of progressive bone erosion in patients with RA. While the increase in bone mineral density by denosumab has been reported in patients with RA, preventive effect of fracture by denosumab remains unknown. This study aimed to evaluate the efficacy of denosumab in treating clinical fracture risk in patients with RA.

Methods: Patients with RA who received denosumab treatment between 2013 and 2019 were retrospectively evaluated using the ANSWER (Kansai Consortium for the Well-Being of Rheumatic Disease Patients) cohort data. Fracture rates were evaluated between 0 and 6 months (reference period) versus > 6 months (post-reference period) of denosumab use.

Results: A total of 873 patients with RA received denosumab, and their characteristics were as follows: 88% females, mean age 68 years, and average disease duration 14.5 years. The hazard rates of all clinical fractures were 0.69 (per 100 person-years) in the reference period and 0.35 in the post-reference period, indicating a 49.2% decrease (p = 0.03).

Conclusions: Denosumab suppresses the risk of clinical fractures in patients with RA.
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http://dx.doi.org/10.1093/mr/roab043DOI Listing
July 2022

Increased Ratio of CD14CD80 Cells/CD14CD163 Cells in the Infrapatellar Fat Pad of End-Stage Arthropathy Patients.

Front Immunol 2021 26;12:774177. Epub 2021 Nov 26.

Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Objectives: This study sought to identify the ratio of M1/M2 cells in the infrapatellar fat pads (IFP) and subcutaneous fat tissues (SC) of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. The clinical features of OA and RA patients treated with or without biological disease-modifying anti-rheumatic drugs (bDMARDs) were also assessed.

Methods: IFP and SC were collected from patients with OA and RA who are undergoing total knee arthroplasty (TKA). CD14-positive cells were then isolated from these samples. Flow cytometry was used to determine the number of CD14CD80 cells and CD14CD163 cells. The expression levels of lipid transcription factors, such as sterol regulatory element-binding protein 1 (SREBP1) and liver X receptor alpha (LXRA), and inflammatory cytokines were also evaluated.

Results: Twenty OA patients and 22 RA patients were enrolled in this study. Ten of the RA patients (45.4%) received bDAMRDs before TKA. On average, a fivefold increase in the number of CD14-positive cells and lower expression levels of and were observed in OA IFP relative to OA SC; however, these results were not obtained from the RA samples. The median ratio of CD14CD80 cells/CD14CD163 cells of OA IFP was 0.87 (0.76-1.09, interquartile range), which is higher to that of OA SC with a lower ratio ( = 0.05835).

Conclusions: The quantity and quality of CD14-positive cells differed between IFP and SC in arthropathy patients. To our knowledge, this is the first study to characterize the ratio of M1/M2 cells in the IFP and SC of end-stage OA and RA patients. The increased ratio of CD14CD80 cells/CD14CD163 cells in the IFP from patients with OA and RA treated with bDMARDs indicated that inflammation was localized in the IFP. As adipose tissue-derived innate immune cells were revealed as one of the targets for regulating inflammation, further analysis of these cells in the IFP may reveal new therapeutic strategies for inflammatory joint diseases.
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http://dx.doi.org/10.3389/fimmu.2021.774177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662627PMC
February 2022

Biomechanical Comparison of Kinematic and Mechanical Knee Alignment Techniques in a Computer Simulation Medial Pivot Total Knee Arthroplasty Model.

J Knee Surg 2021 Dec 10. Epub 2021 Dec 10.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Several concepts may be used to restore normal knee kinematics after total knee arthroplasty. One is a kinematically aligned (KA) technique, which restores the native joint line and limb alignment, and the other is the use of a medial pivot knee (MPK) design, with a ball and socket joint in the medial compartment. This study aimed to compare motions, contact forces, and contact stress between mechanically aligned (MA) and KA (medial tilt 3° [KA3] and 5° [KA5]) models in MPK. An MPK design was virtually implanted with MA, KA3, and KA5 in a validated musculoskeletal computer model of a healthy knee, and the simulation of motion and contact forces was implemented. Anteroposterior (AP) positions, mediolateral positions, external rotation angles of the femoral component relative to the tibial insert, and tibiofemoral contact forces were evaluated at different knee flexion angles. Contact stresses on the tibial insert were calculated using finite element analysis. The AP position at the medial compartment was consistent for all models. From 0° to 120°, the femoral component in KA models showed larger posterior movement at the lateral compartment (0.3, 6.8, and 17.7 mm in MA, KA3, and KA5 models, respectively) and larger external rotation (4.2°, 12.0°, and 16.8° in the MA, KA3, and KA5 models, respectively) relative to the tibial component. Concerning the mediolateral position of the femoral component, the KA5 model was positioned more medially. The contact forces at the lateral compartment of all models were larger than those at the medial compartment at >60° of knee flexion. The peak contact stresses on the tibiofemoral joint at 90° and 120° of knee flexion were higher in the KA models. However, the peak contact stresses of the KA models at every flexion angle were <20 MPa. The KA technique in MPK can successfully achieve near-normal knee kinematics; however, there may be a concern for higher contact stresses on the tibial insert.
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http://dx.doi.org/10.1055/s-0041-1740392DOI Listing
December 2021

Correction to: Factors associated with anxiety and depression in rheumatoid arthritis patients: a cross-sectional study.

Adv Rheumatol 2021 Dec 2;61(1):73. Epub 2021 Dec 2.

Department of Human Health Sciences, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

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http://dx.doi.org/10.1186/s42358-021-00231-2DOI Listing
December 2021

Correction to: Femoral bowing affects varus femoral alignment but not patient satisfaction in mechanically aligned total knee arthroplasty.

Eur J Orthop Surg Traumatol 2021 Nov 29. Epub 2021 Nov 29.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

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http://dx.doi.org/10.1007/s00590-021-03175-xDOI Listing
November 2021

Femoral bowing affects varus femoral alignment but not patient satisfaction in mechanically aligned total knee arthroplasty.

Eur J Orthop Surg Traumatol 2021 Nov 15. Epub 2021 Nov 15.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Purpose: This study evaluated whether patients with particular lower limb morphological factors have femoral and tibial component malpositioning during mechanically aligned total knee arthroplasty (TKA) and lower postoperative satisfaction.

Methods: This study included 146 knees in 117 Asian patients undergoing TKA for medial osteoarthritis. Preoperative bony morphological factors such as the angle between the femoral mechanical and anatomical axes (MA-AA angle), angle between the anatomical axes of the proximal and distal femur (lateral bowing femoral angle, LBFA), mechanical lateral distal femoral angle, medial proximal tibial angle, and % anatomical axis of the tibia were evaluated, as well as preoperative and 1-year postoperative 2011 Knee Society scores (KSSs).

Results: MA-AA angle and LBFA were significantly larger in knees with varus femoral component alignment versus neutral alignment. Preoperative MA-AA angle was underestimated in patients with larger MA-AA angle or LBFA, especially by inexperienced surgeons. Tibial morphological factors did not affect tibial component alignment. Changes in 2011 KSSs were similar among groups by lower limb alignment or femoral and tibial component alignment.

Conclusion: Femoral bowing affects varus femoral component alignment by obscuring preoperative planning, but it had little impact on patient satisfaction when mechanical alignment is targeted during TKA.
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http://dx.doi.org/10.1007/s00590-021-03164-0DOI Listing
November 2021

Functional characteristics of female patients based on ambulatory ability 1 year after total knee arthroplasty.

Knee 2021 Dec 2;33:298-304. Epub 2021 Nov 2.

Rehabilitation Unit, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan; Department of Orthopedic Surgery, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.

Background: Total knee arthroplasty (TKA) is commonly performed to reduce knee pain and improve physical function. Compared with the values for healthy, age-matched women, previous studies have reported large deficits in functional ability, such as muscle strength and ambulatory ability, in women 1 year post-TKA. Ambulatory ability is to move around, particularly by walking and is clinically assessed by the timed up and go test (TUG).

Aim: This study aimed to clarify the characteristics of knee functions in female patients whose ambulatory ability recovered to a normal level at 1 year after TKA.

Methods: This cross-sectional study included 151 female patients who underwent TKA. The muscle strength of the lower extremity was measured, and the 2011 Knee Society Scoring (2011 KSS) system was used postoperatively. The TUG was conducted to assess ambulatory ability after TKA; then the patients were classified into the fast and slow ambulation groups based on previously reported gait-speed values of healthy female individuals. Then, we identified significant indicators of ambulatory ability at 1 year after TKA.

Results: Forty-nine percent of patients after TKA achieved the level of ambulatory ability of a healthy female. Logistic regression analysis identified that the non-operative side knee extensor strength and the functional activity score, as assessed by the 2011 KSS, were variables significantly associated with the mid-term ambulatory ability after TKA.

Conclusion: Female patients with high non-operative knee extensor strength and a functional activity score at 1 year postoperatively can achieve better ambulatory ability than those of healthy, age-matched females.
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http://dx.doi.org/10.1016/j.knee.2021.10.015DOI Listing
December 2021

Effect of Impaired T Cell Receptor Signaling on the Gut Microbiota in a Mouse Model of Systemic Autoimmunity.

Arthritis Rheumatol 2022 04 25;74(4):641-653. Epub 2022 Feb 25.

Kyoto University, Kyoto, Japan, and Osaka City University, Osaka, Japan.

Objective: T cell receptor (TCR) signaling abnormalities and gut dysbiosis are thought to be involved in the development of systemic lupus erythematosus (SLE). However, it is not known whether these mechanisms are interrelated. This study was undertaken to explore the impact of defective TCR signaling on microbiota-driven immune responses and the consequent triggering of systemic autoimmunity.

Methods: The responses of B6SKG mice harboring a mutation in ZAP-70 leading to spontaneous development of SLE were evaluated under specific pathogen-free (SPF) and germ-free (GF) conditions. The gut microbiome was analyzed using 16S ribosomal RNA sequencing. Secretory IgA production in the gut and follicular helper T (Tfh) cell development in the spleen and Peyer's patches were analyzed. Interleukin-17 (IL-17)-deficient mice and segmented filamentous bacteria (SFB)-specific TCR-transgenic mice were used to examine the role of IL-17 and thymic selection.

Results: SLE development in B6SKG mice was significantly more attenuated under GF conditions than under SPF conditions. The gut microbiota in B6SKG mice was altered, which was associated with the expansion of SFB and consequent development of SLE by driving Th17 cell differentiation, which was in turn blunted by IL-17 deficiency. Notably, although systemic Tfh development and autoantibody IgG response were enhanced, local gut Tfh and IgA responses were impaired. Moreover, experiments in SFB-specific TCR-transgenic mice revealed that this differential response was caused by altered thymic selection of self- and microbiota-reactive TCR because of defective TCR signaling.

Conclusion: Our findings indicate that defective TCR signaling alters the gut microbiota and promotes systemic autoimmunity by driving Th17 cell differentiation.
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http://dx.doi.org/10.1002/art.42016DOI Listing
April 2022

Factors associated with anxiety and depression in rheumatoid arthritis patients: a cross-sectional study.

Adv Rheumatol 2021 10 29;61(1):65. Epub 2021 Oct 29.

Department of Human Health Sciences, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: The management of anxiety and depression symptoms in rheumatoid arthritis (RA) patients is vital. Previous study findings on this topic are conflicting, and the topic remains to be thoroughly investigated. This study aimed to clarify the association of RA disease activity with anxiety and depression symptoms after controlling for physical disability, pain, and medication.

Methods: We conducted a cross-sectional study of RA patients from the XXX Rheumatoid Arthritis Management Alliance cohort. We assessed patients using the Disease Activity Score (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), and Hospital Anxiety and Depression Scale (HADS). Anxiety and depression symptoms were defined by a HADS score ≥ 8. We analyzed the data using multivariable logistic regression analyses.

Results: Of 517 participants, 17.6% had anxiety symptoms and 27.7% had depression symptoms. The multivariable logistic regression analysis demonstrated that DAS28 was not independently associated with anxiety symptoms (odds ratio [OR] [95% confidence interval; CI] 0.93 [0.48-1.78]; p = 0.82) and depression symptoms (OR [95% CI] 1.45 [0.81-2.61]; p = 0.22). However, DAS28 patient global assessment (PtGA) severity was associated with anxiety symptoms (OR [95% CI] 1.15 [1.02-1.29]; p = 0.03) and depression symptoms (OR [95% CI] 1.21 [1.09-1.35]; p < 0.01). Additionally, HAQ-DI scores ≤ 0.5 were associated with anxiety symptoms (OR [95% CI] 3.51 [1.85-6.64]; p < 0.01) and depression symptoms (OR [95% CI] 2.65 [1.56-4.50]; p < 0.01). Patients using steroids were more likely to have depression than those not using steroids (OR [95% CI] 1.66 [1.03-2.67]; p = 0.04).

Conclusions: No association was found between RA disease activity and anxiety and depression symptoms in the multivariable logistic regression analysis. Patients with high PtGA scores or HAQ-DI scores ≤ 0.5 were more likely to experience anxiety and depression symptoms, irrespective of disease activity remission status. Rather than focusing solely on controlling disease activity, treatment should focus on improving or preserving physical function and the patient's overall sense of well-being.
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http://dx.doi.org/10.1186/s42358-021-00223-2DOI Listing
October 2021
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