CD30-targeted therapy induces apoptosis of inflammatory cytokine-stimulated synovial fibroblasts and ameliorates collagen antibody-induced arthritis in mice.

OBJECTIVE: It has been reported that levels of soluble CD30 in serum and joint fluid are significantly elevated in patients with rheumatoid arthritis (RA). This study aimed to investigate whether CD30 could be a therapeutic target for RA. METHODS: The expression and localization of CD30 were examined by immunohistochemical and double immunofluorescence staining on synovial tissue samples obtained from patients with RA or osteoarthritis (OA) during surgery. Changes in CD30 expression of fibroblast-like synoviocytes (FLS) from RA patients with or without TNFα and IL-1ß stimulation were examined by the polymerase chain reaction (PCR) and flow cytometry. Collagen antibody-induced arthritis (CAIA) was created in DBA/1 mice, and the therapeutic effect of brentuximab vedotin (BV) was examined by clinical score, histological findings and measurement of serum levels of SAA, IL-6, and TNFα. RESULTS: CD30 expression was significantly higher in samples from patients with RA than from those with OA. Double immunofluorescence showed a low rate of co-localization of CD30 with CD20 or CD90, but a high rate of co-localization of CD30 and CD138. CD30 mRNA expression was upregulated 11.7-fold in FLS following stimulation by inflammatory cytokines. The clinical scores of CAIA mice were significantly lower following both BV treatments, however, the histological scores of CAIA mice were significantly lower only following treatment with high dose BV (70 mg/kg). CONCLUSIONS: CD30 was expressed on immunocompetent cells in synovial tissue from RA patients and in cytokine-stimulated FLS in vitro. High dose BV (70 mg/kg) showed significant therapeutic effects in ameliorating inflammation and joint destruction in CAIA mice, but low dose BV (30 mg/kg) was insufficient.

The trend of treatment and conveyance system for upper extremity replantation in Japan: A nationwide population-based study from the Japan trauma data bank.

BACKGROUND: In Japan, microsurgical skill development and a system to transfer patients to an appropriate hospital for upper extremity amputation have been promoted; however, information about trends of replantation is limited. Therefore, the aim of this study was to clarify the trends in the treatment for upper extremity amputation using the Japan Trauma Data Bank (JTDB). METHODS: Data derived from JTDB (2004-2015) were used to quantify trends in the volume of replantation for upper extremity amputation including finger amputation. Trauma was diagnosed based on the Abbreviated Injury Scale code; a subgroup of patients who underwent replantation was delineated. We investigated patient demographics, infection rate, and characteristics of treating facilities. RESULTS: A total of 1240 patients underwent upper extremity amputation. Among these, 510 (41.1%) underwent replantation, and the rate of replantation did not change over the study period. The average age of patients who underwent or did not undergo replantation was 45.5 and 47.2 years, respectively. The proportion of the patients who were transferred to another hospital for treatment significantly decreased between 2004 (28.5%) and 2015 (16.3%) (P < 0.01). Time taken for transfer from the accident site to hospitals increased. The rate of patients who underwent replantation differed among different hospitals; however, higher-volume hospitals were more likely to perform replantation. CONCLUSION: The rate of patients transferred to another hospital decreased between 2004 and 2015; however, the rate of patients who underwent replantation remained unchanged. This suggests that the number of patients who were transported directly from the accident site to an appropriate hospital has increased, whereas the indication for care in each hospital remains unchanged. Common criteria for amputations are needed to address the differing rates of replantation among hospitals.

Treatment for postoperative infection of pathological femoral fracture after radiotherapy: two case reports and review of the literature.

INTRODUCTION: Radiation-induced pathological fractures show high nonunion and infection rates. Successful treatment of postoperative infections of these fractures without limb amputation is extremely rare. METHODS: We report two cases of postoperative infection of pathological femoral fracture after radiation therapy for soft tissue tumors. Considering the poor condition of the irradiated site, a two-staged operation was selected to create the optimal situation for bone union. The treatment involved the Masquelet technique, latissimus dorsi (LD) flap, and a free vascularized fibula graft (FVFG). In the first stage, we drastically resected the necrotic bone and the surrounding infected tissue and placed antibiotic polymethylmethacrylate space on the bone gap according to the Masquelet technique. Next, we used an Ilizarov external fixator as a temporizing stabilizer and performed the LD flap. Six weeks later, in the second stage, we changed the external fixation to plate fixation; packed the artificial bone (ß-TCP) and autograft bone to the induced membrane; and performed FVFG on the other side of the plate. As postoperative therapy, toe touch was allowed immediately, and partial weight bearing was started 2 months after second surgery. RESULTS: Both patients achieved bone union and were able to walk without postoperative complications. At the 2-year follow-up, there was no recurrence of infection. CONCLUSION: Our treatment is effective for controlling postoperative infection of radiation-induced pathological fracture.

The effect of mechanical stress on enthesis homeostasis in a rat Achilles enthesis organ culture model.

Tendons and ligaments are jointed to bones via an enthesis that is essential to the proper function of the muscular and skeletal structures. The aim of the study is to investigate the effect of mechanical stress on the enthesis. We used ex vivo models in organ cultures of rat Achilles tendons with calcaneus including the enthesis. The organ was attached to a mechanical stretching apparatus that can conduct cyclic tensile strain. We made the models of 1-mm elongation (0.5 Hz, 3% elongation), 2-mm elongation (0.5 Hz, 5% elongation), and no stress. Histological evaluation by Safranin O staining and Toluidin Blue and Picro Sirius red staining was conducted. Expression of sex-determining region Y-box 9 (Sox9), scleraxis (Scx), Runt-related transcription factor 2 (Runx2), and matrix metalloproteinase 13 (Mmp13) were examined by real-time polymerase chain reaction and immunocytochemistry. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling and live/dead staining and was conducted for evaluation of the apoptosis and cell viability. The structure of the enthesis was most maintained in the model of 1-mm elongation. The electronic microscope showed that the enthesis of the no stress model had ill-defined borders between fibrocartilage and mineralized fibrocartilage, and that calcification of mineralized fibrocartilage occurred in the model of 2-mm elongation. Sox9 and Scx was upregulated by 1-mm elongation, whereas Runx2 and Mmp13 were upregulated by 2-mm elongation. Apoptosis was inhibited by low stress. The results of this study suggested that 1-mm elongation can maintain the structure of the enthesis, while 2-mm elongation promotes degenerative changes.

The Masquelet technique for septic arthritis of the small joint in the hands: Case reports.

Septic arthritis in distal interphalangeal (DIP) joints sometimes occurs in association with mucous cysts or after the surgical treatment of mallet fingers. Recently, several studies have demonstrated the effectiveness of the Masquelet technique in the treatment of bone defects caused by trauma or infection. However, only few studies have reported the use of this technique for septic arthritis in small joints of the hand, and its effectiveness in treating septic arthritis in DIP joints remains unclear. We report the clinical and radiological outcomes of three patients who were treated with the Masquelet technique for septic arthritis in DIP joints. One patient had uncontrolled diabetes and another had rheumatoid arthritis treated with methotrexate and prednisolone. The first surgical stage involved thorough debridement of the infection site, including the middle and distal phalanx. We placed an external fixator from the middle to the distal phalanx and then packed the cavity of the DIP joint with antibiotic cement bead of polymethylmethacrylate (40 g) including 2 g of vancomycin and 200 mg of minocycline. At 4-6 weeks after the first surgical stage, the infection had cleared, and the second surgical stage was performed. The external fixator and cement bead were carefully removed while carefully preserving the surrounding osteo-induced membrane. The membrane was smooth and nonadherent to the cement block. In the second surgical stage, an autogenous bone graft was harvested from the iliac bone and inserted into the joint space, within the membrane. The bone graft, distal phalanx, and middle phalanx were fixed with Kirschner wires and/or a soft wire. Despite the high risk of infection, bone union was achieved in all patients without recurrence of infection. Although the Masquelet technique requires two surgeries, it can lead to favorable clinical and radiological outcomes for infected small joints of the hand.