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1.
Trauma Case Rep ; 53: 101048, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38983368

ABSTRACT

Proximal phalanx fractures of the big toe involving angulation or dislocation of the articular surface require repositioning and fixation. We treated a patient with such a fracture using a novel wire-connected external fixator, the ICHI-FIXATOR® system. A 45-year-old male sustained an injury when slipping down the stairs and impacting his left big toe. Plain radiography and computed tomography revealed a proximal phalangeal fracture of the left big toe with dislocation of the articular surface and comminution. The surgical intervention was performed using 1.1-mm diameter C-wires and an external fixator. The patient regained ambulation and resumed work immediately after surgery. Four weeks postoperatively, all wires were removed on an outpatient basis. Eight months postoperatively, the patient experienced no pain during strenuous activities or exercises. This novel wire-connected external fixator provides reliable and secure fixation, facilitating a prompt return to normal daily activities. This technique may be an effective option for managing toe fractures.

2.
J Oral Rehabil ; 51(6): 924-930, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38356183

ABSTRACT

OBJECTIVE: To examine the association between rheumatoid arthritis (RA) and oral hypofunction (OHF) using propensity score matching (PSM) to adjust for differences between older adults with RA and the general older adult population. METHODS: We conducted a cross-sectional survey among 189 older adults with RA in 2019 (mean age, 71.9 ± 3.6) and 47 178 independent older adult residents in 2016 (mean age, 71.6 ± 4.0), respectively. The questionnaire covered information on socio-demographic characteristics and OHF for both groups. Age, sex, educational level and smoking history were used to determine PSM. Prevalence ratios (PRs) and 95% confidence intervals (CIs) of self-reported OHF (fewer remaining teeth, decreased masticatory function, deterioration of swallowing function and oral dryness) were estimated using Poisson regressions. RESULT: OHF was observed in 44.4% of patients with RA and 27.5% of residents. Before PSM, the prevalence of OHF among patients with RA was higher than that of residents (PR, 1.75; 95% CI, 1.50-2.05). After PSM, there were 189 patients with RA and residents, and the prevalence of OHF among patients with RA was still higher (PR, 1.61; 95% CI, 1.22-2.13). Poisson regression showed that the prevalence of 19 or fewer teeth (PR, 1.06; 95% CI, 0.82-1.36), difficulties eating tough foods (PR, 1.18; 95% CI, 0.90-1.55), difficulties swallowing tea or soup (PR, 1.77; 95% CI, 1.19-2.63), and dry mouth (PR, 2.79; 95% CI, 1.90-4.07) was higher among patients with RA than residents. CONCLUSION: Compared with the general older adult population, patients with RA have a higher prevalence of self-reported OHF.


Subject(s)
Arthritis, Rheumatoid , Propensity Score , Self Report , Humans , Cross-Sectional Studies , Female , Male , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/physiopathology , Arthritis, Rheumatoid/complications , Aged , Prevalence , Xerostomia/epidemiology , Aged, 80 and over , Surveys and Questionnaires
3.
Case Rep Orthop ; 2024: 5392926, 2024.
Article in English | MEDLINE | ID: mdl-38410683

ABSTRACT

Bite injuries frequently occur on human hands. Human bite injuries to the hand may lead to an infection because of limited soft tissue protection and wound contamination. However, no studies have reported severe bite injuries on hands treated by flaps. We report a case of an 80-year-old woman diagnosed with a major neurocognitive disorder. The patient accidentally had a self-bite injury accompanied with an open metacarpal fracture. Debridement and fixation of the first metacarpal fracture were performed. Afterward, skin necrosis occurred gradually on the dorsum of the hand. Therefore, a reverse posterior interosseous artery (PIA) flap was used, and the postoperative course was uneventful. Given the high risk of infection, human bite injuries, particularly hand bites, should be treated immediately. Delayed treatment for such injuries may lead to extensive soft tissue defects requiring reconstruction with flaps.

4.
Article in English | MEDLINE | ID: mdl-38352644

ABSTRACT

Background: An unstable trochanteric femoral fracture is a serious injury, with a 1-year mortality rate of 5.4% to 24.9%, for which there is currently no standard treatment method. The lag screw insertion site is one of the primary contact areas between the cortical bone and an intramedullary nail. We hypothesized that a posterolateral fracture causes intramedullary nail instability when the posterolateral fracture line interferes with lag screw insertion. The purpose of the present study was to investigate the effect of posterolateral fracture line morphology on intramedullary nail stability by simulating unstable trochanteric femoral fractures with a posterolateral fracture fragment. Methods: Eighteen custom-made synthetic osteoporotic bone samples were used in the present study. Nine samples had a posterolateral fracture line interfering with the lag screw insertion hole (Fracture A), and the other 9 had a fracture line 10 mm away from the hole (Fracture B). Cyclic loading (750 N) was applied to the femoral head 1,500 times. Movement of the end cap attached to the intramedullary nail was recorded. The amplitudes of motion in the coronal plane (coronal swing motion), sagittal plane (sagittal swing motion), and axial plane (total swing motion) were evaluated. The change in the neck-shaft angle was evaluated on photographs that were made before and after the test. Medial cortical displacement was measured before and after the test. Results: Two Fracture-A samples were excluded because the amplitude of sagittal swing motion was too large. The mean values for coronal, sagittal, and total swing motion were 1.13 ± 0.28 mm and 0.51 ± 0.09 mm (p < 0.001), 0.50 ± 0.12 mm and 0.46 ± 0.09 mm (p = 0.46), and 1.24 ± 0.24 mm and 0.69 ± 0.11 mm (p < 0.001) for Fractures A and B, respectively. The mean neck-shaft angle change was -8.29° ± 2.69° and -3.56° ± 2.35° for Fractures A and B, respectively (p = 0.002). The mean displacement of the medial cortex was 0.38 ± 1.12 mm and 0.12 ± 0.37 mm for Fractures A and B, respectively (p = 0.57). Conclusions: This study showed that an unstable trochanteric femoral fracture with a posterolateral fracture line that interferes with the lag screw insertion holes is a risk factor for increased intramedullary nail instability.

5.
Asian Spine J ; 17(6): 997-1003, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37946333

ABSTRACT

STUDY DESIGN: This experimental study was performed using human ligamentum flavum-derived cells (HFCs). PURPOSE: To investigate the intracellular signaling mechanism of interleukin-6 (IL-6) secretion in transforming growth factor-ß (TGF- ß)-stimulated HFCs. OVERVIEW OF LITERATURE: Lumbar spinal stenosis (LSS) is a prevalent disease among the elderly, characterized by debilitating pain in the lower extremities. Although the number of patients with LSS has increased in recent years, the underlying pathomechanism remains unclear. Clinical examinations typically rely on magnetic resonance imaging to diagnose patients, revealing ligamentum flavum hypertrophy. Some studies have suggested an association between ligamentum flavum hypertrophy and inflammation/fibrosis, and expression of TGF-ß and IL-6 has been observed in surgically obtained ligamentum flavum samples. However, direct evidence linking TGF-ß and IL-6 expression in HFCs is lacking. METHODS: HFCs were obtained from patients with LSS who had undergone decompression surgery. The cells were stimulated with TGF-ß and pretreated with either the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 or the p44/42 MAP kinase inhibitor FR180204. IL-6 secretion in the cell culture medium and IL-6 messenger RNA (mRNA) expression levels were analyzed using an enzyme-linked immunoassay and real-time polymerase chain reaction, respectively. RESULTS: TGF-ß administration resulted in a dose- and time-dependent stimulation of IL-6 release. Treatment with SB203580 and FR180204 markedly suppressed TGF-ß-induced IL-6 secretion from HFCs. Moreover, these inhibitors suppressed IL-6 mRNA expression in response to TGF-ß stimulation. CONCLUSIONS: Our findings indicate that TGF-ß induces IL-6 protein secretion and gene expression in HFCs through the activation of p38 or p44/42 MAP kinases. These results suggest a potential association between IL-6-mediated inflammatory response and tissue hypertrophy in LSS, and we provide insights into molecular targets for therapeutic interventions targeting LSS-related inflammation through our analysis of the MAP kinase pathway using HFCs.

6.
Mod Rheumatol Case Rep ; 8(1): 16-20, 2023 Dec 29.
Article in English | MEDLINE | ID: mdl-37750821

ABSTRACT

Infection with Mycobacterium marinum has several different clinical presentations. Most commonly, it appears as a solitary papulonodular lesion on an extremity. A rare presentation of osteoarticular M. marinum involving multiple small joints and tenosynovitis of the hand, which was misdiagnosed as rheumatoid arthritis, is reported. The patient was initially treated for seronegative rheumatoid arthritis but failed to respond to methotrexate. Magnetic resonance imaging showed arthritis and tenosynovitis. Subsequently, synovial biopsy led to histological and microbiological diagnosis. Antimycobacterial treatment should be started promptly in such cases. The combined use of rifampicin, ethambutol, and clarithromycin appears to be effective, and debridement is indicated in patients with deep-seated infections.


Subject(s)
Arthritis, Rheumatoid , Mycobacterium Infections, Nontuberculous , Tenosynovitis , Humans , Tenosynovitis/diagnosis , Tenosynovitis/microbiology , Tenosynovitis/pathology , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/pathology , Hand/pathology , Arthritis, Rheumatoid/diagnosis , Diagnostic Errors
7.
Exp Ther Med ; 25(6): 256, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37153894

ABSTRACT

Hydroxyapatite (HA) augments are used to treat trochanteric femoral fractures. However, the efficacy of HA augmentation has not been fully described in trochanteric femoral fracture surgery. In total, 85 patients were enrolled in the present study; all had trochanteric femoral fractures between January 2016 and October 2020, 45 with HA (HA group) and 40 without HA (N group). The intraoperative lag screw insertion torque was directly measured and the amount of lag screw telescoping with and without HA augmentation after surgery was analyzed. Maximum lag screw insertion torque (max-torque), bone mineral density in the opposite femoral neck (n-BMD), tip apex distance (TAD) of the lag screw, radiographic findings including fracture union, the amounts of lag screw telescoping and occurrence of complications were evaluated. A total of 12 patients were excluded if they were aged under 60 years old, had ipsilateral surgery and disorders in the hip joint, TAD of the lag screw ≥26 mm on postoperative radiographs and had measurement errors. A total of 73 fractures could be analyzed: HA group (n=36) and N group (n=37). Max-torque/n-BMD ratios were higher in the HA group compared with in the N group (7.23±2.71 vs. 5.93±1.91 g/cm2·N·m; P=0.04). The amounts of lag screw telescoping in the HA group were smaller compared with the N group (1.41±2.00 vs. 2.58±2.34; P=0.05). Evaluation of screw insertion torque showed maximum screw insertion torque correlated well with n-BMD in both groups, HA (R=0.57; P<0.01) and N group (R=0.64; P<0.01). No correlation was found between maximum screw insertion torque and TAD in both groups, HA (R=-0.10; P=0.62) and N group (R=0.02; P=0.93). All fractures were radiographically united without any complications. These results support the effectiveness of HA augmentation, indicating higher resistance against rotational instability and reduced lag screw telescoping in trochanteric femoral fracture treatment.

8.
J Hand Surg Asian Pac Vol ; 28(2): 197-204, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37120302

ABSTRACT

Background: This study aimed to investigate the relationship between postoperative clinical results and long-term morphological changes in patients with carpal tunnel syndrome (CTS) as observed on magnetic resonance imaging (MRI) before and after open carpal tunnel release (OCTR). Methods: We retrospectively analysed data for 28 hands that had undergone OCTR with at least 24 months of follow-up data. Two-point discrimination (2PD) test results were examined for the first three fingers, as were the distal motor latency (DML) and sensory conduction velocity (SCV) of the median nerve. We also calculated the cross-sectional area (CSA) of the carpal tunnel and the distance from the median nerve to the volar carpal bone at the hamate and the pisiform levels using MRI images. Variables were compared before and 24 months after OCTR. Results: Significant improvements in all variables were observed, including average 2PD scores (Finger I: 13.1 ± 6.2 vs. 7.7 ± 4.3, p < 0.01, Finger II: 11.9 ± 6.6 vs. 7.0 ± 3.5, p < 0.01, Finger III: 13.6 ± 6.1 vs. 7.8 ± 4.5, p < 0.01), average DML (8.3 ± 3.3 vs. 4.3 ± 0.6 m/s, p < 0.01), average SCV (30.8 ± 11.0 vs. 41.3 ± 5.3 m/s, p < 0.01), CSA of the carpal tunnel (hamate level: 194.9 ± 30.6 vs. 254.2 ± 47.6 mm2, p < 0.01, pisiform level: 244.2 ± 46.5 vs. 274.7 ± 75.1 mm2, p = 0.01) and the distance between the median nerve and volar carpal bone (hamate level: 8.7 ± 1.4 vs. 11.2 ± 1.6 mm, p < 0.01, pisiform level: 11.8 ± 1.7 vs. 13.8 ± 2.5 mm, p < 0.01). Conclusions: Our results demonstrate that OCTR is successful in achieving long-term decompression and recovery of the median nerve in patients with CTS. Level of Evidence: Level III (Therapeutic).


Subject(s)
Carpal Tunnel Syndrome , Magnetic Resonance Imaging , Median Nerve , Humans , Carpal Tunnel Syndrome/diagnostic imaging , Carpal Tunnel Syndrome/surgery , Median Nerve/diagnostic imaging , Median Nerve/surgery , Retrospective Studies , Wrist/surgery
9.
Heliyon ; 9(3): e14046, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36915544

ABSTRACT

Background: Forged unsintered hydroxyapatite and poly l-lactic acid (F-u-HA/PLLA) screw is bioactivite, bioabsorbable, and radiopaque with high mechanical strength. Its efficacy has been previously demonstrated in the treatment of lateral humeral condylar, lateral tibial condylar, ankle, and patellar fractures. However, studies on its efficacy in treatment of calcaneal fractures is lacking. This study aimed to compare the postoperative results of F-u-HA/PLLA screw fixation and locking plate fixation for intra-articular calcaneal fractures. Methods: From January 2013 to December 2019, 47 closed intra-articular fractures treated with either F-u-HA/PLLA screws (group S, 18 feet in 17 patients) or locking plates (group P, 29 feet in 28 patients) in a single trauma center were retrospectively reviewed. The sinus tarsi approach was used in both groups. The time to bone union, step-off, varus deformity, Bohler's angle, and width and height of the calcaneus were assessed after surgery. Ankle joint range of motion (ROM) and postoperative complications were also assessed. Results: All fractures were successfully treated. The Kaplan-Meier curves of the two groups showed similar trends. The log-rank test showed no significant difference in the time to bone union between the two groups (p = 0.48). In the Cox proportional hazards model adjusted for preoperative width and Bohler's angle, the hazard ratio for bone union was not statistically significant (HR: 1.13, 95%CI: 0.50-2.56, p = 0.78). Other variables included step-off (group S: 2.0 vs group P: 2.2 mm, p = 0.84), varus deformity (2.0° vs. 3.0°, p = 0.7), Gissane's angle (103.5° vs 104.0°, p = 0.84), width (38.0 vs 34.8 mm, p = 0.12), height (42.1 vs 44.0 mm, p = 0.07), and ankle ROM degrees (dorsal flexion, 20.0° vs. 20.0°, p = 0.13; plantar flexion 40.0° vs 40.0°, p = 0.56), which were not significantly different between groups P and S. The Bohler's angle was smaller in group S than in group P (20.5° vs 27.0°, p < 0.01). No skin necrosis or infection was observed in either group. Conclusion: Postoperative results of F-u-HA/PLLA screw fixation using the sinus tarsi approach for intra-articular calcaneal fractures were as good as those of locking plate fixation.

10.
J Knee Surg ; 36(5): 483-490, 2023 Apr.
Article in English | MEDLINE | ID: mdl-34624908

ABSTRACT

Concomitant anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstruction has been reported as an effective technique for providing rotational control of the knee. However, the intraoperative risk of collision with an ACL tunnel during the drilling for the femoral ALL tunnel has been described. The purpose of this study was to investigate the various femoral drilling procedures to avoid tunnel collisions during combined double-bundle ACL and ALL reconstruction. Nine cadaveric knees were used in this study. ACL drilling was performed through the anteromedial portal to footprints of the posterolateral bundle at 120° (PL120) and 135° (PL135) knee flexion and the anteromedial bundle at 120° (AM120) and 135° (AM135) knee flexion. ALL drilling was performed at 0° (Cor0-ALL) and 30° (Cor30-ALL) coronal angles using a Kirschner wire (K-wire). The distance between the ALL footprint and ACL K-wire outlets, axial angles of ALL K-wires colliding with ACL K-wires, and distances from the ALL footprint to the collision point were measured. From these values, the safe zone, defined as the range of axial angles in which no collisions or penetrations occurred, was identified by simulation of tunnels utilized for reconstruction grafts in each drilling procedure. The point-to-point distance from the ALL footprint to the K-wire outlet was significantly greater in the AM120 than the AM135 (13.5 ± 3.1, 10.8 ± 3.2 mm; p = 0.048) and in the PL135 than the PL120 (18.3 ± 5.5, 16.1 ± 6.5 mm; p = 0.005) conditions, respectively. During an ACL drilling combination of PL135/AM120, a safe zone of > 45° in Cor30-ALL was identified. With a narrow safe zone during the PL135/AM120 combination only, the risk of femoral tunnel collisions in combined double-bundle ACL and ALL reconstruction is high. AM drilling at 120° and PL drilling at > 135° knee flexion, combined with ALL drilling at 30° coronal angle and > 45° axial angle, may reduce this risk.


Subject(s)
Anterior Cruciate Ligament Injuries , Plastic Surgery Procedures , Humans , Anterior Cruciate Ligament/surgery , Cadaver , Knee Joint/surgery , Femur/surgery , Anterior Cruciate Ligament Injuries/surgery
11.
Mod Rheumatol ; 33(2): 271-278, 2023 Mar 02.
Article in English | MEDLINE | ID: mdl-35389481

ABSTRACT

OBJECTIVES: We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. METHODS: Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. RESULTS: At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. CONCLUSION: The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Biological Products , Humans , Methotrexate/adverse effects , Abatacept/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Treatment Outcome , Drug Therapy, Combination , Biological Products/therapeutic use
12.
J Pharmacol Sci ; 151(1): 1-8, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36522118

ABSTRACT

Bone remodeling mediated by bone-forming osteoblasts (OBs) and bone-resorbing osteoclasts (OCs) maintains bone structure and function. Excessive OC activation leads to bone-destroying diseases such as osteoporosis and bone erosion of rheumatoid arthritis (RA). Differentiation of OCs from bone marrow cells (BMCs) is regulated by the bone microenvironment. The proinflammatory cytokine interleukin (IL)-1ß reportedly enhances osteoclastogenesis and plays important roles in RA-associated bone loss. The present study investigated the effect of IL-1ß on OC formation via microenvironmental cells. Treating mouse BMCs with IL-1ß in the presence of receptor activator of NF-κB ligand and macrophage colony-stimulating factor increased the number of OCs. Real-time RT-PCR revealed increased expression of the IL-1ß, IL-1RI, and IL-1RII genes in non-OCs compared with OCs. Removing CD45- cells which cannot differentiate into OCs, from mouse BMCs reduced the IL-1ß-mediated enhancement of osteoclastogenesis. IL-1ß treatment upregulated the expression of inducible nitric oxide synthase, insulin-like growth factor 2 (IGF2), and the chemokines stromal cell derived factor 1, C-X3-C motif ligand 1 (CX3CL1), and CXCL7 in non-OCs. Neutralizing antibodies against these chemokines and IGF2 suppressed osteoclastogenesis in the presence of IL-1ß. These results suggest that IL-1ß enhances osteoclastogenesis by upregulating IGF2 and chemokine expression in non-OCs.


Subject(s)
Osteoclasts , Osteogenesis , Mice , Animals , Osteogenesis/genetics , Ligands , Cells, Cultured , Osteoclasts/metabolism , Osteoblasts/metabolism , Cell Differentiation/genetics , RANK Ligand/genetics , RANK Ligand/metabolism
13.
SICOT J ; 8: 27, 2022.
Article in English | MEDLINE | ID: mdl-35748723

ABSTRACT

INTRODUCTION: Microsoft Kinect V2® (Kinect) is a peripheral device of Xbox® and acquires information such as depth, posture, and skeleton definition. In this study, we investigated whether Kinect can be used for human gait analysis. METHODS: Ten healthy volunteers walked 20 trials, and each walk was recorded by a Kinect and infrared- and marker-based-motion capture system. Pearson's correlation and overall agreement with a method of meta-analysis of Pearson's correlation coefficient were used to assess the reliability of each parameter, including gait velocity, gait cycle time, step length, hip and knee joint angle, ground contact time of foot, and max ankle velocity. Hip and knee angles in one gait cycle were calculated in Kinect and motion capture groups. RESULTS: The coefficients of correlation for gait velocity (r = 0.92), step length (r = 0.81) were regarded as strong reliability. Gait cycle time (r = 0.65), minimum flexion angle of hip joint (r = 0.68) were regarded as moderate reliability. The maximum flexion angle of the hip joint (r = 0.43) and maximum flexion angle of the knee joint (r = 0.54) were regarded as fair reliability. Minimum flexion angle of knee joint (r = 0.23), ground contact time of foot (r = 0.23), and maximum ankle velocity (r = 0.22) were regarded as poor reliability. The method of meta-analysis revealed that participants with small hip and knee flexion angles tended to have poor correlations in maximum flexion angle of hip and knee joints. Similar trajectories of hip and knee angles were observed in Kinect and motion capture groups. CONCLUSIONS: Our results strongly suggest that Kinect could be a reliable device for evaluating gait parameters, including gait velocity, gait cycle time, step length, minimum flexion angle of the hip joint, and maximum flexion angle of the knee joint.

14.
J Pharmacol Sci ; 149(3): 93-99, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35641033

ABSTRACT

Osteoporosis is caused by an imbalance in bone remodeling due to abnormal osteoclast (OC) formation and activation. Hypoxia at the site of inflammation promotes OC formation and activation in various species, including humans. We previously reported that insulin-like growth factor 2 (IGF2) plays an important role in osteoclastogenesis under hypoxia. In our present study, we focused on the mechanism of osteoclastogenesis in regard to IGF2 signaling under hypoxia. We confirmed that the addition of IGF2 promoted osteoclastogenesis under normoxic conditions. Conversely, IGF2-neutralizing antibodies inhibited osteoclastogenesis under both normoxic and hypoxic conditions. IGF2 addition increased levels of phosphorylated Akt (Thr308 and Ser473) and NF-κB (Ser536), indicating activation of the Akt-NF-κB pathway. IGF2 also increased the expression of inducible nitric oxide synthase, which promotes osteoclastogenesis via nitric oxide production. Expression levels of genes encoding inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6, were upregulated, indicating that IGF2 promotes osteoclastogenesis by increasing the expression of inflammatory cytokines via activation of the Akt-NF-κB pathway. These results suggest that IGF2 is a promising therapeutic target for osteoporosis and rheumatoid arthritis.


Subject(s)
Cytokines , Hypoxia , Insulin-Like Growth Factor II , Osteogenesis , Cytokines/metabolism , Humans , Insulin-Like Growth Factor II/metabolism , NF-kappa B/metabolism , Osteoporosis , Proto-Oncogene Proteins c-akt
15.
Immunol Res ; 70(2): 208-215, 2022 04.
Article in English | MEDLINE | ID: mdl-35014010

ABSTRACT

Gliostatin/thymidine phosphorylase (GLS/TP) is known to have angiogenic and arthritogenic activities in the pathogenesis of rheumatoid arthritis (RA). The novel oral Janus kinase (JAK) inhibitor baricitinib has demonstrated high efficacy in RA. However, the effect of baricitinib on fibroblast-like synoviocytes (FLSs), a key component of invasive synovitis, has not been still elucidated. This study investigated whether GLS/TP production could be regulated by JAK/signal transducers and activators of transcription (STAT) signaling in FLSs derived from patients with RA. FLSs were cultured and stimulated by interferon (IFN)γ in the presence of baricitinib. Expression levels of GLS/TP were determined using reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunocytochemistry. Phosphorylation of STAT proteins was investigated by Western blot. In cultured FLSs, GLS/TP mRNA and protein levels were significantly induced by treatment with IFNγ and these inductions were suppressed by baricitinib treatment. Baricitinib inhibited IFNγ-induced STAT1 phosphorylation, while JAK/STAT activation played a pivotal role in IFNγ-mediated GLS/TP upregulation in RA. These results suggested that baricitinib suppressed IFNγ-induced GLS/TP expression by inhibiting JAK/STAT signaling, resulting in the attenuation of neovascularization, synovial inflammation, and cartilage destruction.


Subject(s)
Arthritis, Rheumatoid , Janus Kinase Inhibitors , Synoviocytes , Arthritis, Rheumatoid/metabolism , Azetidines , Cells, Cultured , Fibroblasts , Humans , Janus Kinase Inhibitors/metabolism , Janus Kinase Inhibitors/pharmacology , Purines , Pyrazoles , Sulfonamides , Thymidine Phosphorylase/genetics , Thymidine Phosphorylase/metabolism
16.
J Orthop Sci ; 27(6): 1271-1277, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34404612

ABSTRACT

BACKGROUND: Meniscal ramp lesion (RL) is the peripheral lesion of the posterior horn of the medial meniscus (PHMM) associated with anterior cruciate ligament (ACL) tear. The purpose of this study was to evaluate the accuracy of pre-operative magnetic resonance imaging (MRI) evaluation in diagnosing RL and to identify whether the difficulty in diagnosis differs depending on the location of RL. METHODS: ACL-injured patients undergoing ACL reconstruction from January 2017 to January 2019 were enrolled. A methodical arthroscopic exploration to identify RL was conducted intra-operatively using three steps, namely, the anterior visualization step, the inter-condylar visualization step, and the posteromedial step. The location of the RLs was evaluated and classified into two types as follows: Red-red zone (RR) - a meniscal tear of the red-red zone of the PHMM. Menisco-capsular junction (MCJ) - a lesion at the menisco-capsular junction of the PHMM, which is more peripheral than RR. Furthermore, the accuracy of 1.5-T MRI evaluation to diagnose RL by two testers using sagittal proton-density fat-saturated images was calculated. RESULTS: Of the 81 patients enrolled, 11 had RL: 5 cases each were at the MCJ and RR, and 1 case was at both locations. The sensitivity of MRI for detecting RL was 27.3-45.5%, whereas the specificity was 84.3-95.7% in total. The sensitivity of MRI in detecting RL at the RR and MCJ was 40.0-80.0%, 0-20.0%, respectively. The intra-observer reliability of the MRI evaluation was moderate (κ coefficient: 0.40-0.46), while the inter-observer reliability was fair to moderate (κ coefficient: 0.27-0.41). CONCLUSIONS: A low sensitivity of the MRI in detecting RL at the MCJ was observed, and the reliability of the MRI evaluation for diagnosis of RL was not high. Therefore, methodical arthroscopic exploration is essential to diagnose RL even when it is not suspected on pre-operative MRI.


Subject(s)
Anterior Cruciate Ligament Injuries , Tibial Meniscus Injuries , Humans , Menisci, Tibial/surgery , Tibial Meniscus Injuries/diagnostic imaging , Tibial Meniscus Injuries/surgery , Tibial Meniscus Injuries/complications , Reproducibility of Results , Arthroscopy/methods , Anterior Cruciate Ligament Injuries/surgery , Magnetic Resonance Imaging
17.
Mod Rheumatol ; 32(3): 528-533, 2022 Apr 18.
Article in English | MEDLINE | ID: mdl-34894248

ABSTRACT

OBJECTIVES: We aimed to examine the psychosocial characteristics of patients with rheumatoid arthritis (RA) by remission status and determine the impacts of social support on severity of depressive symptoms. METHODS: We enrolled RA patients aged 40-79 years who visited university hospitals' outpatient clinics. Severity of depressive symptoms (Beck Depression Inventory-II), physical disability (Health Assessment Questionnaire), and support were evaluated. Furthermore, RA disease activity was evaluated by 28-point Disease Activity Score (DAS28) calculation. The independent impacts of instrumental and emotional social support on depressive symptoms by remission status defined as DAS28 score < 2.6 were estimated by multivariable regression analysis. RESULTS: This study included 360 RA patients. In the remission group, emotional support showed a statistically significant negative impact on depressive symptoms, whereas instrumental support had an extremely limited contribution to severity of depressive symptoms. In the non-remission group, instrumental support showed a negative tendency of impact on severity of depressive symptoms, whereas emotional support had a wide range of influence. CONCLUSIONS: Favourable association between emotional support and depressive symptoms is confirmed only among RA patients in remission status. The influence of emotional support in non-remission patients and that of instrumental support regardless of remission status are inconclusive.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Depression/etiology , Depression/psychology , Humans , Remission Induction , Severity of Illness Index , Social Support
18.
Am J Pathol ; 191(12): 2072-2079, 2021 12.
Article in English | MEDLINE | ID: mdl-34560064

ABSTRACT

Bone homeostasis depends on the balance between bone resorption by osteoclasts (OCs) and bone formation by osteoblasts. Bone resorption can become excessive under various pathologic conditions, including rheumatoid arthritis. Previous studies have shown that OC formation is promoted under hypoxia. However, the precise mechanisms behind OC formation under hypoxia have not been elucidated. The present study investigated the role of inducible nitric oxide synthase (iNOS) in OC differentiation under hypoxia. Primary bone marrow cells obtained from mice were stimulated with receptor activator of NF-κB ligand and macrophage colony-stimulating factor to induce OC differentiation. The number of OCs increased in culture under hypoxia (oxygen concentration, 5%) compared with that under normoxia (oxygen concentration, 20%). iNOS gene and protein expression increased in culture under hypoxia. Addition of an iNOS inhibitor under hypoxic conditions suppressed osteoclastogenesis. Addition of a nitric oxide donor to the normoxic culture promoted osteoclastogenesis. Furthermore, insulin-like growth factor 2 expression was significantly altered in both iNOS inhibition experiments and nitric oxide donor experiments. These data might provide clues to therapies for excessive osteoclastogenesis under several hypoxic pathologic conditions, including rheumatoid arthritis.


Subject(s)
Cell Hypoxia/physiology , Nitric Oxide Synthase Type II/physiology , Osteoclasts/physiology , Animals , Bone Resorption/genetics , Bone Resorption/metabolism , Cell Differentiation/drug effects , Cell Differentiation/genetics , Cell Hypoxia/drug effects , Cells, Cultured , Enzyme Induction/drug effects , Enzyme Induction/genetics , Hypoxia/genetics , Hypoxia/metabolism , Hypoxia/pathology , Male , Mice , Mice, Inbred C57BL , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Osteoclasts/drug effects , Osteogenesis/drug effects , Osteogenesis/genetics , Oxygen/pharmacology , Signal Transduction/drug effects , Signal Transduction/physiology , omega-N-Methylarginine/pharmacology
19.
J Exp Orthop ; 8(1): 51, 2021 Jul 19.
Article in English | MEDLINE | ID: mdl-34278532

ABSTRACT

PURPOSE: High-grade pivot shift in the anterior cruciate ligament (ACL) injured knee is a risk factor for postoperative residual pivot shift. Procedures in addition to ACL reconstruction such as anterolateral ligament (ALL) reconstruction have been performed for patients with a high-risk of residual pivot shift. The aim of this study was to investigate the effect of the addition of ALL reconstruction to primary double-bundle ACL reconstruction in patients with preoperative high-grade pivot shift to improve stability as evaluated by quantitative measurement. METHODS: Patients with ACL injuries who showed preoperative grade 3 subjective pivot shift and who underwent primary double-bundle ACL reconstruction combined with ALL reconstructions were retrospectively enrolled. Anterior tibial translation (ATT) in the Lachman test, and acceleration and external rotational angular velocity (ERAV) in the pivot shift were measured as quantitative values. Quantitative values before surgical intervention for ACL-injured knees (ACLD) and uninjured contralateral knees (intact), after temporary fixation of the isolated ACL grafts (ACLR), and subsequently after temporary fixation of both ACL and ALL grafts (ACLR + ALLR) were measured with the patient under general anaesthesia. RESULTS: In total, 18 patients were included. The ATT was lower in ACLR and ACLR + ALLR than in intact (P = .008 and .005), while there was no significant difference between ACLR and ACLR + ALLR (P > .05). The acceleration of ACLR + ALLR was lower than that for ACLR (P = .008), while there was no significant difference between intact and ACLR or ACLR + ALLR (P > .05). The ERAV of ACLR was higher than that of intact (P < .001), while that of ACLR + ALLR was lower than that of ACLR (P < 0.001), and there was no significant difference in ERAV between intact and ACLR + ALLR (P > 0.05). CONCLUSION: According to quantitative assessment of the pivot shift, the addition of ALL reconstruction to primary double-bundle ACL reconstruction improved residual knee instability and restored knee stability during surgery. Combination of ALL reconstruction with primary double-bundle ACL reconstruction was effective for patients with ACL injuries exhibiting a preoperative grade 3 subjective pivot shift. LEVEL OF EVIDENCE: IV.

20.
Arch Gerontol Geriatr ; 96: 104455, 2021.
Article in English | MEDLINE | ID: mdl-34126437

ABSTRACT

PURPOSE: To determine whether frailty associated factors differ between community dwellers and older adult patients with rheumatoid arthritis (RA). METHODS: We used the cross-sectional data for patients with RA from the RA epidemiological quality-of-life study (n = 210, mean age 71.8 ± 3.7 years) and community dwellers from the Japan Gerontological Evaluation Study (n = 53,255, mean age 71.7 ± 4.0 years). Frailty status was assessed using the Kihon Checklist (KCL), and the primary outcome was frailty (KCL score ≥8 points). Information on predictor variables, including age, sex, marital status, educational level, body mass index (BMI), drinking and smoking status and social participation were obtained from a standardized questionnaire. We employed Poisson regression to calculate the prevalence ratio (PR) of frailty according to its predictors. RESULTS: We found frailty in 37.6% of the patients with RA and 15.7% of the community dwellers. In the multivariate models, BMI and social participation were independently associated with frailty in patients with RA (BMI <18.5: PR, 1.62; 95% confidence interval [CI] 1.09-2.41. BMI ≥25.0: PR, 1.81; 95% CI 1.20-2.71. Active social participation: PR, 0.61; 95% CI 0.42-0.87) and community dwellers (BMI <18.5: PR, 1.77; 95% CI 1.67-1.88. BMI ≥25.0: PR, 1.27; 95% CI 1.22-1.33. Active social participation: PR, 0.46; 95% CI 0.44-0.48). All other predictors were significantly associated with frailty in the community dwellers. CONCLUSION: Maintaining appropriate body weight and participating in social activities are important for preventing frailty in patients with RA as well as community dwellers.


Subject(s)
Arthritis, Rheumatoid , Frailty , Aged , Arthritis, Rheumatoid/epidemiology , Cross-Sectional Studies , Frail Elderly , Frailty/epidemiology , Humans , Japan/epidemiology , Social Participation , Surveys and Questionnaires
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