Mediastinal Malignant Melanoma Markedly Shrinking in Response to Nivolumab

Primary malignant melanoma (MM) of the mediastinum is rare, and there is a lack of consensus regarding the preferred treatment because non-cutaneous MM demonstrates an inferior response to systemic therapy. Herein, we describe the case of a 73-year-old man with MM of the anterior mediastinum with multiple liver metastases. Even though the size of lesions increased rapidly following diagnosis, nivolumab monotherapy caused remarkable tumor shrinkage. This is the first report of mediastinal MM showing a significant response to nivolumab. We, therefore, suggest that immunotherapy may be one of the treatment options for primary mediastinal MM.     

Adverse Tissue Reactions and Metal Ion Behavior After Small‐Head Metasul Hip Arthroplasty: A Long‐Term Follow‐Up Study

ObjectiveTo investigate the long‐term survivorship, incidence of adverse reactions to metal debris (ARMD), and metal ion behavior in patients who underwent small‐head Metasul metal‐on‐metal (MoM) total hip arthroplasty (THA).MethodsBetween February 1998 and September 2003, a retrospective study was performed on 43 consecutive patients (43 hips) who underwent unilateral cementless Metasul MoM THAs at our institution. Of them, 35 patients (nine males and 26 females) who were available for follow‐up more than 15 years after THA were enrolled in this study and underwent metal artifact reduction sequence magnetic resonance imaging (MARS‐MRI) to identify ARMD. The mean age at surgery of the patients was 59.7 years old (range, 31–83). Clinical and radiographic outcomes were evaluated retrospectively. Clinical examinations were conducted using the Harris Hip Score (HHS). Serum cobalt (Co) and chromium (Cr) ion levels and Co/Cr ratio were assessed at different postoperative periods of <5, 5–10, 11–14, and ≥15 years.ResultsThe mean follow‐up period for the 35 patients included was 18.1 years (range, 15–22). The mean HHS significantly improved from 44.6 ± 11.3 points preoperatively to 89.4 ± 7.9 points at the final follow‐up (P < 0.0001). ARMD was found in 20% of the patients using MARS‐MRI. No signs of stem loosening were found clinically or radiographically, whereas cup loosening and ARMD were observed in three patients (9%), for whom revision THAs were performed. The Kaplan–Meier survival rates with revision for any reason as the endpoint were 90.9% at 5 years, 84.8% at 10 years, 84.8% at 15 years (95% CI, 67.1–93.6), and 70.3% at 20 years (95% CI, 43.6–87.0). The survival rates with revision for ARMD as the endpoint were 100% at 5 years, 96.6% at 10 years, 96.6% at 15 years (95% CI, 77.2–99.7), and 80.1% at 20 years (95% CI, 45.3–95.2). Serum Co ion level peaked at 5–10 years after THA, which was significantly higher than that <5 years; however, it decreased to the initial level after 15 years. In contrast, serum Cr ion level significantly increased at 5–10 years and then remained almost constant. Significant differences in Cr ion levels (1.0 vs 2.0 μg/L, P = 0.024) and Co/Cr ratio (1.3 vs 0.9, P = 0.037) were found between non‐ARMD and ARMD patients at >11 years postoperatively.ConclusionOur results suggest that increased Cr ion levels and decreased Co/Cr ratio may be signs of ARMD in patients who underwent small‐head Metasul MoM THA.     

Self-Pierce Riveting of Three Thin Sheets of Aluminum Alloy A5052 and 980 MPa Steel

Self-pierce riveting of three thin sheets of 980 MPa steel and 5052 aluminum alloy was performed to investigate the effect of sheet configuration on the deforming behaviors of the sheets and the rivet and joint strength. When the lower sheet was aluminum alloy, the joining range was relatively wide, i.e., the interlock hooking the rivet leg tended to be large. In the sheet configuration in which the upper and lower sheets were A5052 and the middle sheet was 980 MPa steel, the rivet leg spread out moderately and the joint without defects was obtained. In the lower 980 MPa steel sheet, fracture tended to occur due to the low ductility of the lower sheet, and the joining range was narrow with the small interlock although the three sheets were joined by an appropriate die shape. In joint strength of joined three sheets, fracture occurred in the lower-strength aluminum alloy sheet if interlocks of about 300 μm and 150 μm could be formed in the lower aluminum alloy sheet and 980 MPa steel sheet, respectively.     

Wound,pressure ulcer and burn guidelines – 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.     

Analysis of whole-blood antioxidant capacity after chronic and localized irradiation using the i-STrap method

Ionizing radiation exposure affects the redox state in vivo. Recently, whole-blood antioxidant capacity (WBAC) has been reported to decrease in a dose-dependent manner after acute total body irradiation (TBI). However, changes in WBAC after localized and chronic irradiations have not been reported. This study analyzed changes to WBAC in mice after either localized irradiation (irradiation of the left hind leg only) or chronic TBI using the i-STrap method. Leg-localized irradiation exerted limited effects on WBAC, while WBAC decreased in a dose rate-dependent manner after TBI. Further, the WBAC reached the minimum value in a shorter period at a smaller dose rate. Our results suggest that changes in WBAC do not directly reflect absorbed dose, but may reflect radiation-induced biological damage at the systemic level. This study will contribute to the understanding of radiation-induced injuries and diseases, and will facilitate the establishment of biomarkers for radiation exposure.     

Cytolytic Recombinant Vesicular Stomatitis Viruses Expressing STLV-1 Receptor Specifically Eliminate STLV-1 Env-Expressing Cells in an HTLV-1 Surrogate Model In Vitro

Human T-cell leukemia virus type 1 (HTLV-1) causes serious and intractable diseases in some carriers after infection. The elimination of infected cells is considered important to prevent this onset, but there are currently no means by which to accomplish this. We previously developed “virotherapy”, a therapeutic method that targets and kills HTLV-1-infected cells using a cytolytic recombinant vesicular stomatitis virus (rVSV). Infection with rVSV expressing an HTLV-1 primary receptor elicits therapeutic effects on HTLV-1-infected envelope protein (Env)-expressing cells in vitro and in vivo. Simian T-cell leukemia virus type 1 (STLV-1) is closely related genetically to HTLV-1, and STLV-1-infected Japanese macaques (JMs) are considered a useful HTLV-1 surrogate, non-human primate model in vivo. Here, we performed an in vitro drug evaluation of rVSVs against STLV-1 as a preclinical study. We generated novel rVSVs encoding the STLV-1 primary receptor, simian glucose transporter 1 (JM GLUT1), with or without an AcGFP reporter gene. Our data demonstrate that these rVSVs specifically and efficiently infected/eliminated the STLV-1 Env-expressing cells in vitro. These results indicate that rVSVs carrying the STLV-1 receptor could be an excellent candidate for unique anti-STLV-1 virotherapy; therefore, such antivirals can now be applied to STLV-1-infected JMs to determine their therapeutic usefulness in vivo.