Endoscopically assisted transaxillary release of the scalene muscles for thoracic outlet syndromes: a comparison with or without first rib resection.

OBJECTIVES: There are several surgical techniques for thoracic outlet syndrome (TOS). However, there have been no reports of endoscopically assisted transaxillary release of the anterior and middle scalene muscles (EATRS), leaving the first rib intact for TOS. We hypothesized that EATRS would achieve a good Quick Disability of the Arm, Shoulder and Hand score. This study aims to present our experience with a new technique for TOS using endoscopy. METHODS: We chose two surgeries depending on the patient's TOS condition. If the costoclavicular space was under 12 mm, we selected endoscopically assisted transaxillary first rib resection (EAFRR). If the costoclavicular space was over 12 mm, we selected EATRS. Between January 2021 and December 2022, 31 consecutive surgeries for TOS were performed in our institution. Twenty-five patients underwent EAFRR, and six (19%) underwent EATRS. Since July 2022, EAFRR has been performed under differential lung ventilation. RESULTS: Complete and almost complete relief was achieved in 24 patients (77%), and partial relief was conducted in seven patients (23%) at a mean of 19.7 months after surgery. The symptoms improved in all cases. Intraoperative pneumothorax did not occur, and no other complications were observed. Both EAFRR and EATRS were effective and safe surgeries for TOS. Operative time was significantly shorter in EATRS than in EAFRR. CONCLUSIONS: We first report EATRS surgery for TOS. EATRS is indicated for patients whose costoclavicular space is preserved before surgery. Good surgical results were obtained after surgery for this indication.

Long-term follow-up for the atypical radial longitudinal deficiency: A case report.

We experienced an atypical case of radial longitudinal deficiency that did not fit into any classifications, including Blauth. The patient had a bilateral hypoplastic thumb, in which the index and middle fingers were missing in the right hand. We performed surgeries in four stages: centralization of the right hand, opponensplasty of the right thumb, opponensplasty of the left thumb, and distraction lengthening of the right ulnar. Twenty-five years after the initial treatment, the patient was satisfied with the treatment and had no significant difficulty with activities of daily living.

Midterm results of endoscopically assisted first rib resection in the zero position for thoracic outlet syndrome.

OBJECTIVES: We have hypothesized that an endoscopically assisted transaxillary approach in the zero position would be able to improve visualization and allow safe surgery for thoracic outlet syndrome. METHODS: We performed surgery only for patients with certain objective findings, including blood flow disruption, low blood flow and accelerated blood flow in the subclavian artery demonstrated using Doppler sonography, narrowing of the scalene interval width between the anterior and middle interscalene muscles (interscalene base) or costoclavicular space demonstrated using Duplex ultrasonography or computed tomography angiography. The present study included 45 consecutive patients (50 limbs) who underwent endoscopic transaxillary first rib resection with scalenotomy and brachial plexus neurolysis. We assessed the intraoperative parameters, including the interscalene base, blood loss, operation time, patient satisfaction, preoperative and postoperative Quick Disability of the Arm, Shoulder and Hand and complications. RESULTS: The mean intraoperatively measured interscalene base width was 6.4 mm. All patients showed improvement after surgery. The outcome was excellent in 40% of cases, good in 48%, fair in 12% and poor in none. Pneumothorax was present in 6%. There were no other complications and no recurrences. Among patients who had been followed up for at least 2 years, the Quick Disability of the Arm, Shoulder and Hand score was significantly improved (42 before surgery vs 12 at final follow-up), especially in athletes relative to non-athletes (0.2 vs 16). The present approach achieved complete relief in 43% of cases overall (91% in athletes and 16% in non-athletes). CONCLUSIONS: Endoscopically assisted transaxillary first rib resection and brachial plexus neurolysis in the zero position are useful and safe for thoracic outlet syndrome, especially in athletes.

The Effect of Elbow and Forearm Position on the Resisted Wrist Extension Test and Incidence of Sensory Disturbance of the Superficial Radial Nerve in Patients with Lateral Epicondylitis.

Background: The aim of this study is to determine the effect of elbow and forearm position on the resisted wrist extension test (RWET) in patients with lateral epicondylitis. We also looked at the incidence of associated sensory disturbance of the superficial radial nerve (SRN) and the effect of treatment of lateral epicondylitis on sensory disturbance. Methods: Sixty-three consecutive patients (68 limbs) with lateral epicondylitis and an equal number of age and gender matched volunteers were investigated. Patients with lateral epicondylitis were subdivided into two groups based on history of corticosteroid injection. We performed the RWET in four limb positions namely elbow extended and forearm pronated (EP), elbow flexed and forearm pronated (FP), elbow extended and forearm supinated (ES), elbow flexed and forearm supinated (FS). Sensory disturbance in the SRN was assessed using a Wartenberg pin wheel. Results: The positivity rate of the RWET was significantly higher in the EP position (100%) compared to the FP (66%), ES (62%) and the FS (24%) positions in limbs with lateral epicondylitis. The RWET was positive only in one subject in the EP position in the control group (1.5%). Sensory disturbance in the SRN territory was present in 63.2% of limbs and only two subjects (2.9%) in the control group. The incidence of sensory disturbance was significantly higher (74.5% vs. 48.3%, p < 0.05) in patients who did not have a corticosteroid injection. Conclusions: The sensitivity and specificity of the RWET is better when it is performed with the elbow in extension with the forearm pronated (EP); 63.2% of limbs with lateral epicondylitis were noted to have an associated sensory disturbance of the SRN and a corticosteroid injection seems to decrease the incidence of sensory disturbances. Level of Evidence: Level II (Diagnostic).

Assessment of the severity of curly toe.

BACKGROUND: Curly/underlapping toe involves flexion, adduction, and varus deformity of the interphalangeal joints. There are no previous reports showing the relationship between physical examination and X-ray findings among patients with curly toe deformity. METHODS: We investigated the clinical findings of 116 consecutive patients associated with 239 underlapping toes. We compared the age and affected toes between patients whose deformities were pointed out at a pediatric medical examination (group 1) and those referred for medical treatment (group 2). The degree of curly toe deformity was graded by a physical examination and X-ray. RESULTS: The average age at presentation was 2.7 years. The affected toes were significantly different between groups 1 and 2 (p < .001). The morbidity of each toe differed significantly in group 2 (p < .005) but not in group 1. The correlation between the appearance grading and classification by X-ray was very strong using Spearman's rank correlation coefficient. The severity of curly toe was divided into mild in 104 toes, moderate in 105 toes, and severe in 17 toes. The methods of conservative treatment were observation only in 15 cases, manipulations in 30 cases, taping in 67 cases, and a brace in 9 cases. Surgery was performed in 8% of cases. CONCLUSION: Curly toe deformity of the third or fourth toes tend to be referred for medical treatment because of the abnormality. Our grading system using a physical examination and classification by X-ray was useful for assessing the severity of curly toe.

Forefoot Deformities in Patients with Rheumatoid Arthritis: Mid- to Long-Term Result of Joint-Preserving Surgery in Comparison with Resection Arthroplasty.

BACKGROUND: Joint-preserving surgery for the forefoot has been increasingly performed for rheumatoid arthritis (RA). We compared joint-preserving surgeries with resection arthroplasty for RA in the forefoot. METHODS: Forefoot surgeries were performed on 62 toes in 42 patients with RA (men: 2; women: 40) between 2002 and 2018. Three groups were compared: PP-31 toes treated with joint-preserving surgery involving the modified Mann method for the big toe and offset osteotomy for lesser toes, PR-15 toes treated with joint-preserving surgery for the big toe and resection arthroplasty for lesser toes, and RR-16 toes treated with resection arthroplasty for all the toes. RESULTS: The PP group had significantly higher mean scores on a scale for RA in the foot and ankle at the latest follow-up than the RR group (86 vs. 75 points; p < 0.05). Hallux valgus (angle > 20°) of the big toe at the latest follow-up recurred in 10 (32%), 9 (60%), and 16 (100%) patients in the PP, PR, and RR groups, respectively. A revision surgery was performed in one patient each in the PP and PR groups. CONCLUSIONS: Joint-preserving surgery is superior to resection arthroplasty in preventing function loss and the recurrence of hallux valgus.

Unsuccessful Intervention of CT-Assisted Osteosynthesis for Stress Fractures of the Hook of the Hamate: A Report of 3 Cases.

CASE: We performed computed tomography (CT)-assisted dorsal approach osteosynthesis for stress fractures of the hook of the hamate using the dorsal approach in 3 high school baseball players in the hybrid operating room. Bony union was observed in all patients on CT. All patients were able to play baseball without pain for at least 6 months after surgery. However, refractures were observed in all patients at a mean 9.7 months after surgery. CONCLUSION: The indications of osteosynthesis for stress fractures of the hook of the hamate in baseball players should be carefully considered.

Differences in subtrochanteric and diaphyseal atypical femoral fractures in a super-aging prefectural area: YamaCAFe Study.

INTRODUCTION: Atypical femoral fractures (AFFs) have been correlated with long-term use of bisphosphonates (BPs), glucocorticoids (GCs), and femoral geometry. We investigated the incidence and characteristics of subtrochanteric (ST) and diaphyseal (DP) AFFs in all institutes in a super-aging prefectural area. MATERIALS AND METHODS: We performed a blinded analysis of radiographic data in 87 patients with 98 AFFs in all institutes in Yamagata prefectural area from 2009 to 2014. Among the 98 AFFs, 57 AFFs comprising 11 ST fractures in 9 patients and 46 DP fractures in 41 patients with adequate medical records and X-rays were surveyed for time to bone healing and geometry. RESULTS: Of the 87 patients, 67 received BPs/denosumab (77%) and 10 received GCs (11%). Surgery was performed in 94 AFFs. Among 4 AFFs with conservative therapy, 3 required additional surgery. In univariate regression analyses for ST group versus DP group, male-to-female ratio was 2/7 versus 1/40, mean age at fracture was 58.2 (37-75) versus 78 (60-89) years, rheumatic diseases affected 55.5% (5/9) versus 4.9% (2/41), femoral lateral bowing angle was 1.7 (0-6) versus 11.8 (0.8-24)°, GC usage was 67% (6/9) versus 4.9% (2/41), and bone healing time was 12.1 (6-20) versus 8.1 (3-38) months (p < 0.05). In multivariate analyses, higher male-to-female ratio, younger age, greater proportion affected by rheumatic diseases, and higher GC usage remained significant (p < 0.05). CONCLUSIONS: The incidence of AFFs in our prefectural area was 1.43 cases/100,000 persons/year. This study suggests that the onset of ST AFFs have greater correlation with the worse bone quality, vice versa, the onset of DP AFFs correlated with the bone geometry. The developmental mechanisms of AFFs may differ significantly between ST and DP fractures.

Rapid disappearance of gouty tophi of the foot by resection of massive gouty tophi of the opposite foot in a patient with hyperuricaemia: a case report.

Gouty tophi occur less frequently and disappear only with modern medication therapy for symptomatic or asymptomatic hyperuricaemia. However, the medication may require a long time to take effect due to the systemic urate pool associated with massive gouty tophi. We present the case of a 37-year-old woman who suffered from massive gouty tophi of both feet due to hyperuricaemia. After resection of the massive gouty tophi from her right foot and treatment with uricemia medication, the gouty tophi of her opposite foot disappeared rapidly due to reducing the patient's systemic urate pool with intensification of drug medication.

Strategy for the treatment of lateral epicondylitis of the elbow using denervation surgery.

BACKGROUND: A number of treatments for lateral epicondylitis of the elbow have been described. We have developed a strategy for the treatment of this condition. METHODS: We diagnosed lateral epicondylitis of the elbow in 86 patients. Conservative treatment resulted in resolution in 71 patients. Surgery was required in the remaining 15 patients. If the posterior branch of the posterior cutaneous nerve of the forearm showed a positive response to local anesthesia (block test), we performed denervation surgery on the posterior branch of the posterior cutaneous nerve of the forearm. Patients were asked to rate the degree of pain and sensory disturbance using a visual analog scale; the 11-item version of the Disabilities of the Arm, Shoulder and Hand measure; and the Patient-Rated Elbow Evaluation. RESULTS: A positive response to the block test was seen in 10 elbows (67%). After denervation surgery, pain relief was seen in 9 of 10 elbows (90%). The mean follow-up period was 30.4 months. At final follow-up, the average scores on the visual analog scale, 11-item version of the Disabilities of the Arm, Shoulder and Hand, and Patient-Rated Elbow Evaluation were 4.3 mm, 10.45 points, and 5.9 points, respectively. In the early period after denervation surgery, sensory disturbance was observed in 9 cases (90%). CONCLUSION: Our strategy of denervation surgery for lateral epicondylitis of the elbow was effective for pain relief among patients showing a positive response to the block test.

Analysis of intestinal immunity and flora in a collagen-induced mouse arthritis model: differences during arthritis progression.

Intestinal immunity and flora are reported to be associated with the onset of rheumatoid arthritis. However, differences in the intestinal immunity and flora dynamics between the initial peak and relapse of arthritis have not been investigated. Here we analyzed the lymphocyte populations in different lymphoid tissues, the IgA in feces, and the intestinal flora at the initial peak and the relapse phase of arthritis in a collagen-induced arthritis (CIA) mouse model. In this model compared with the control group, the percentage of RORγt+CD4+ T cells in the mesenteric lymph nodes (mLN) was increased at the initial peak but decreased at the relapse stage of arthritis, and the opposite changes were observed in the spleen. The percentage of Foxp3+CD4+ T cells was unchanged at the initial peak in both tissues but increased only in the mLN at the relapse stage. The IgA in feces increased with the progression of arthritis, and bacterial analysis revealed that some specific bacterial families were changed at the peak and relapse stages of arthritis. Finally, the immune dynamics under different arthritic conditions were examined by integrating these factors using principal component analysis (PCA). PCA showed that the immunological and intestinal flora profiles were different between the initial peak and the relapse of the arthritis. Our findings suggest that the intestinal immunity and the environment change drastically with the progress of arthritis.

Immunohistochemical Analysis of Inflammatory Rheumatoid Synovial Tissues Using Anti-Human Podoplanin Monoclonal Antibody Panel.

Podoplanin (PDPN) is a transmembrane sialoglycoprotein, which is expressed in several normal tissues and malignant tumors. Although PDPN expression in rheumatoid arthritis (RA) has been reported, the role of PDPN in RA and other arthritic conditions has not been fully elucidated. In this study, we examined PDPN expression in inflammatory synovial tissues using an anti-human PDPN (hPDPN) monoclonal antibody (mAb) panel to select the most useful one for evaluation of synovitis. Synovial tissue samples were obtained from 11 RA patients and 9 osteoarthritis (OA) patients undergoing joint surgery. PDPN-positive cells were immunostained by a panel of PDPN mAbs (NZ-1, LpMab-3, LpMab-7, LpMab-10, LpMab-12, LpMab-13, and LpMab-17), followed by cell grading of inflammation and cell counting of PDPN-positivity by a quantitative analyzer. Immunohistochemistry showed that PDPN was markedly expressed in both macrophage-like type A and fibroblast-like type B lining cells of the hyperplastic synovial lining cell layer, and macrophages and fibroblasts in the stroma of RA. Among anti-PDPN mAbs, LpMab-12 showed the highest score. In inflammatory OA synovium, PDPN expression was also detectable. Although LpMab-12 also showed the highest score in OA, the difference was not statistically significant. The inflammatory synovitis score of RA was significantly higher than that of OA. PDPN was expressed in inflammatory lining cells and sublining stroma of RA and OA synovium. In the seven anti-hPDPN antibodies examined, LpMab-12 was the most stainable antibody for PDPN in RA synovitis. Thus, LpMab-12 for PDPN has a possible and promising specific biomarker for evaluating synovitis in RA and inflammatory OA.

Danger of frustrated sensors: Role of Toll-like receptors and NOD-like receptors in aseptic and septic inflammations around total hip replacements.

The innate immune sensors, Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), can recognize not only exogenous pathogen-associated molecular patterns (PAMPs), but also endogenous molecules created upon tissue injury, sterile inflammation, and degeneration. Endogenous ligands are called damage-associated molecular patterns (DAMPs), and include endogenous molecules released from activated and necrotic cells as well as damaged extracellular matrix. TLRs and NLRs can interact with various ligands derived from PAMPs and DAMPs, leading to activation and/or modulation of intracellular signalling pathways. Intensive research on the innate immune sensors, TLRs and NLRs, has brought new insights into the pathogenesis of not only various infectious and rheumatic diseases, but also aseptic foreign body granuloma and septic inflammation of failed total hip replacements (THRs). In this review, recent knowledge is summarized on the innate immune system, including TLRs and NLRs and their danger signals, with special reference to their possible role in the adverse local host response to THRs.

The Incidence of Atypical Femoral Fractures in Patients with Rheumatic Disease: Yamagata Prefectural Committee of Atypical Femoral Fractures (YamaCAFe) Study.

Atypical femoral fractures (AFFs) have been reported to occur with minimal or spontaneous subtrochanteric and femoral shaft fractures with a characteristic transverse pattern, compared with typical femoral fractures in young patients with high-energy trauma. AFFs are related to long-term use of bisphosphonates (BPs), glucocorticoids and rheumatic diseases. We have estimated a blind analysis of AFFs in rheumatic patients receiving BPs and glucocorticoids ordinary over a long time in all Yamagata prefectural area through radiographic examination. The 123 AFFs including suspected cases over six years were collected and reviewed by two independent orthopedic surgeons. We found 86 patients with a total of 99 AFFs between 2009 and 2014 (1.43 cases/100,000 person/year). Of these 99 AFFs, 11 were in 8 rheumatic patients including three patients with bilateral AFFs. The incidence of AFFs in rheumatic patients had trend to increase from 2012. The mean age of all 8 patients was 54.9 years. All 8 patients received BPs and 7/8 received prednisolone (PSL). The mean dose of PSL was 14 mg/day. Compared to patients with unilateral AFFs, those with bilateral AFFs in rheumatic patients were on a higher dose of PSL (20 mg/day vs. 7 mg/day) and had less femoral neck-shaft angle (129° vs. 136°, p < 0.05). In conclusion, the incidence of AFFs in rheumatic patients showed a trend to increase from 2012 to 2014 in Yamagata prefecture. Careful management of AFFs is of particular importance in rheumatic patients who have taken high doses of PSL and have small femoral neck-shaft angle.

Comparison of the Effects of Osteochondral Autograft Transplantation With Platelet-Rich Plasma or Platelet-Rich Fibrin on Osteochondral Defects in a Rabbit Model.

BACKGROUND: Although osteochondral autograft transplantation (OAT) provides satisfactory outcomes for osteochondral defects, for large defects OAT is often inadequate because of graft availability. Osteochondral allograft transplantation is an alternative treatment for large defects, but this approach is limited by graft storage constraints and carries disease transmission risks. Platelet-rich fibrin (PRF) is a second-generation platelet concentrate, and its positive effect on articular cartilage has been reported. However, the effect of PRF with OAT of osteochondral defects is unknown. PURPOSE: To compare the effects of OAT with platelet-rich plasma (PRP) and PRF on osteochondral defects in a rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-two juvenile rabbits were divided into control, PRP, and PRF groups. In the control and PRP groups, a cylindrical osteochondral defect (5 mm in diameter and 2 mm in depth) was created on the patellar groove, and an osteochondral graft (3.5 mm in diameter and 5 mm in length) harvested from the contralateral side was inserted into the distal portion of the defect. After wound closure, either normal saline or PRP was injected in the knee. In the PRF group, a PRF clot was placed in the defect before grafting. The surgical site was macroscopically and histologically assessed after 3 and 12 weeks. RESULTS: At 3 weeks, the PRF group (n = 8) was macroscopically healed compared with the other 2 groups (control, n = 7; PRP, n = 6) ( P < .005). Histologically, osteochondral graft cartilage of the PRF group had normal cellularity and higher amounts of safranin O staining relative to the other 2 groups ( P < .005). At 12 weeks, all 3 groups (n = 8 per group) were macroscopically healed with normal or nearly normal cartilage, and osteochondral graft cartilage was histologically hyaline cartilage. In contrast, the PRF group healed with hyaline-like cartilage at nongrafted defects, whereas the other 2 groups healed with fibrocartilage ( P < .001). CONCLUSION: OAT with PRF maintained hyaline cartilage, and the nongrafted defect healed with hyaline-like cartilage. CLINICAL RELEVANCE: PRF has the potential to improve clinical outcomes of OAT used to treat osteochondral lesions.

Distribution of Podoplanin in Synovial Tissues in Rheumatoid Arthritis Patients Using Biologic or Conventional Disease-Modifying Anti-Rheumatic Drugs.

OBJECTIVE: Podoplanin (PDPN) mediates tumor cell migration and invasion, which phenomena might also play a role in severe rheumatoid arthritis (RA). Therefore, the precise cellular distribution of PDPN and it's relationships with inflammation was studied in RA treated with biologic disease-modifying anti-rheumatic drugs (DMARD) or conventional DMARDs (cDMARD). METHODS: PDPN+ cells were immunostained by NZ-1 mAb, and scored (3+; >50%/ area, 2+; 20%- 50%, 1+; 5%-20%, 0: <5%) in synovial tissues from RA treated with biologic DMARDs (BIO, n=20) or cDMARD (n=20) for comparison with osteoarthritis (OA, n=5), followed by cell grading of inflammation and cell-typing. RESULTS: Inflammatory synovitis score was 1.4 in both BIO and cDMARD, compared to only 0.2 in OA. PDPN+ cells were found in the lining layer (BIO 1.6, cDMARD 1.3, OA 0.2) and lymphoid aggregates (BIO 0.6, cDMRD 0.7, OA 0.2), and correlated with RA-inflammation in BIO- and cDMARD-groups in both area (r=0.7/0.9, r=0.6/0.7, respectively p<0.05). PDPN was expressed in CD68+ type A macrophage-like and 5B5+ type B fibroblast-like cells in the lining layer, and in IL- 17+ cells in lymphoid aggregates in RA. CONCLUSION: PDPN was markedly increased in the immunologically inflamed RA synovitis, which was surgically treated due to BIO- and cDMARD-resistant RA. PDPN may have potential of a new marker of residual arthritis in local joints for inflammation-associated severe RA.

Complications of Distal Radius Fractures Treated by Volar Locking Plate Fixation.

The current study investigated the incidence of complications after surgery for distal radial fractures. This multicenter retrospective study was conducted at 11 institutions. A total of 824 patients who had distal radius fractures that were treated surgically between January 2010 and August 2012 were identified. The study patients were older than 18 years and were observed for at least 12 weeks after surgery for distal radius fractures with a volar locking plate. Sex, age, fracture type according to AO classification, implants, wrist range of motion, grip strength, fracture consolidation rate, and complications were studied. Analysis included 694 patients, including 529 women and 165 men, with a mean age of 64 years. The mean follow-up period was 27 weeks. The fracture consolidation rate was 100%. There were 52 complications (7.5%), including 18 cases of carpal tunnel syndrome, 12 cases of peripheral nerve palsy, 8 cases of trigger digit, 4 cases of tendon rupture (none of the flexor pollicis longus), and 10 others. There was no rupture of the flexor pollicis longus tendon because careful attention was paid to the relationship between the implant and the tendon. Peripheral nerve palsy may have been caused by intraoperative traction in 7 cases, temporary fixation by percutaneous Kirschner wires in 3 cases, and axillary nerve block in 1 case; 1 case appeared to be idiopathic. Tendon ruptures were mainly caused by mechanical stress. [Orthopedics.2016; 39(5):e893-e896.].

Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll-like receptor 2 cascade and inflammasomes.

Toll-like receptor 2 (TLR2) and nucleotide-binding and oligomerization domain-like receptors with a pyrin domain 3 (NLRP3) inflammasomes have been presumed to participate in the pathogenesis of aseptic implant loosening. The aim of this study is to analyze the cellular localization of TLR2 and NLRP3 inflammasomes in the periprosthetic tissue from aseptically loose hip implants as well as the expression of these molecules in macrophages stimulated in vitro with titanium particles (Ti) coated with lipoteichoic acid (LTA). Using immunohistochemistry, immunoreactivity of TLR2 and NLRP3 inflammasomes was found in macrophages within the foreign body granulomatosis. Using RAW264.7 cells, stimulation with Ti increased the messenger RNA (mRNA) levels of TLR2 and TNF-α. Stimulation with LTA-coated Ti enhanced mRNA levels of NLRP3 and IL-1ß, whereas reinforced secretion of IL-1ß was not detected in spite of marked release of TNF-α. Finally, the same cells with silenced Irak2, an adaptor protein in the TLR2 cascade, suppressed this NLRP3 upregulation. This study suggests that TLR2 and NLRP3 inflammasomes are factors involved in cross-talk mediating the foreign body type response to wear particles. In addition, discrepant behavior in the release between TNF-α and IL-1ß release may explain the variable pathomechanisms of aseptic implant loosening without acute inflammatory reactions.

Isocitrate dehydrogenase 2 mutation is a frequent event in osteosarcoma detected by a multi-specific monoclonal antibody MsMab-1.

Somatic mutations of isocitrate dehydrogenase (IDH) 1 and IDH2 occur in gliomas, acute myeloid leukemia, and cartilaginous tumors. Somatic mosaic IDH1/2 mutations are also reported in Ollier disease and Maffucci syndrome, which are characterized by multiple central cartilaginous tumors. Although IDH1/2 mutation analysis against osteosarcoma has been performed in several studies, no IDH1/2 mutation has been reported. Herein, we newly report the IDH2-R172S mutation in three of 12 (25%) osteosarcoma patients, which was detected by direct DNA sequencing. No monoclonal antibody (mAb) has been reported against IDH2-R172S mutation. However, we demonstrate that the IDH2-R172S peptide was recognized by our established multi-specific anti-mutated IDH1/2 mAb, MsMab-1, in enzyme-linked immunosorbent assay. Western blot analysis revealed that MsMab-1 reacts with PA tag combined recombinant proteins of IDH2-R172S. Furthermore, MsMab-1 stained IDH2-R172S-expressing osteosarcoma tissues in immunohistochemistry. The MsMab-1 stained nine of 32 (28.1%) osteosarcomas in a tissue microarray. This report is the first describing IDH2 mutations in osteosarcoma, which can be detected by MsMab-1 mAb. Taken together, these results show that MsMab-1 can be anticipated for use in immunohistochemical determination of IDH1/2 mutation-bearing osteosarcoma.