Effects of interleukin-6 on the metabolism of connective tissue components in rheumatoid synovial fibroblasts

Objective. High levels of interleukin-6 (IL-6) have been found in the synovial fluid of patients with rheumatoid arthritis (RA). We undertook the present study to investigate the role of IL-6 in this disease. Methods. We examined the effects of IL-6, in comparison with IL-1, on the biosynthesis of extracellular matrix macromolecules and of matrix-degrading proteinases in rheumatoid synovial fibroblasts. Results. In rheumatoid synovial fibroblasts, IL-6 by itself enhanced the production of plasminogen activator, its inhibitor, and tissue inhibitor of metalloproteinases, whereas it did not modulate the biosynthesis of precursor of matrix metalloproteinase 1 (proMMP-1) (tissue collagenase), proMMP-3 (stromelysin), or connective tissue components. However, IL-1–induced production of proMMP-1 and proMMP-3 was preferentially augmented by IL-6. Conclusion. These results suggest that in RA, IL-6 may participate along with IL-1 in fine tuning of the catabolism of connective tissue components, by modulating the balance between connective tissue–degrading enzymes and their inhibitors.     

Identification of novel prognostic factors focusing on clinical outcomes in patients with non-small cell lung cancer after stereotactic body radiotherapy

Stereotactic body radiotherapy (SBRT) has attracted extensive attention as an effective treatment for patients with early-stage non-small cell lung cancer. However, the factors affecting prognosis after SBRT have not been fully elucidated. The aim of the present study was to investigate the prognostic factors associated with overall survival (OS) and local control (LC) after SBRT. Between March 2003 and March 2020, 497 patients with primary or oligo-metastatic lung cancer who underwent SBRT treatment were retrospectively reviewed. Univariate analysis was performed against various factors related to patient and tumor characteristics using Kaplan-Meier method. Furthermore, the factors with statistically significant differences identified via univariate analysis underwent a stratified Cox proportional hazard regression analysis. The median follow-up period for all patients was 26.17 months (range, 0.36-194.37), and the 5-year OS and LC rates were 66.3 and 86.0%, respectively. Multivariate analysis showed that surfactant protein-D (SP-D), tumor CT values (TCTV) and iodine density values (IDV) were independent prognostic factors for OS, and histology, TCTV and IDV were for LC. Although histology was not selected as a prognostic factor related to OS, it was indicated that patients with squamous cell carcinoma were associated with the SP-D high group compared with the SP-D normal group. In addition, TCTV was correlated to water density values, which tended to decrease with increasing IDV. From these findings, SP-D and TCTV were identified as potential new candidate prognostic factors after SBRT, and it is possible that combining SP-D and histology, and TCTV and IDV may improve the accuracy of prognostic prediction.     

Influence of normal to high stroke volume on congestive heart failure development after transcatheter aortic valve implantation:case series

Aortic stenosis(AS)is the most common valvular disease in the older adults'population,and its prevalence will likely continue to increase with the aging society.[1]Surgical aortic valve replacement(SAVR)for elderly patients is known as a high-risk procedure.[2-4]Transcatheter aortic valve implantation(TAVI)is a reasonable alternative to SAVR for older and inoperable patients with AS,and TAVI significantly improves outcomes in elderly patients with severe AS and serious comorbidities,[5,6]TAVI achieves a 20%relative reduction in mortality compared with SAVR.     

Amenamevir,a novel helicase–primase inhibitor,for treatment of herpes zoster: A randomized,double‐blind,valaciclovir‐controlled phase 3 study

Amenamevir is a potent helicase–primase inhibitor and a novel class of antiviral agent other than nucleoside compounds, such as aciclovir, valaciclovir and famciclovir. This study is the first randomized, double‐blind, valaciclovir‐controlled phase 3 study to evaluate the efficacy and safety of amenamevir in Japanese patients with herpes zoster when treated within 72 h after onset of rash. A total of 751 patients were randomly assigned to receive either amenamevir 400 mg or 200 mg p.o. once daily or valaciclovir 1000 mg three times daily (daily dose, 3000 mg) for 7 days. The primary efficacy end‐point was the proportion of cessation of new lesion formation by day 4 (“day 4 cessation proportion”). The day 4 cessation proportions for amenamevir 400 and 200 mg and valaciclovir were 81.1% (197/243), 69.6% (172/247) and 75.1% (184/245), respectively. Non‐inferiority of amenamevir 400 mg to valaciclovir was confirmed by a closed testing procedure. Days to cessation of new lesion formation, complete crusting, healing, pain resolution and virus disappearance were evaluated as secondary end‐points. No significant differences were observed in any of the treatment groups. Amenamevir 400 and 200 mg were well tolerated as well as valaciclovir. The proportions of patients who experienced drug‐related adverse events were 10.0% (25/249), 10.7% (27/252) and 12.0% (30/249) with amenamevir 400 and 200 mg and valaciclovir, respectively. In conclusion, amenamevir 400 mg appears to be effective and well tolerated for treatment of herpes zoster in immunocompetent Japanese patients.     

The wound/burn guidelines – 6: Guidelines for the management of burns

Burns are a common type of skin injury encountered at all levels of medical facilities from private clinics to core hospitals. Minor burns heal by topical treatment alone, but moderate to severe burns require systemic management, and skin grafting is often necessary also for topical treatment. Inappropriate initial treatment or delay of initial treatment may exert adverse effects on the subsequent treatment and course. Therefore, accurate evaluation of the severity and initiation of appropriate treatment are necessary. The Guidelines for the Management of Burn Injuries were issued in March 2009 from the Japanese Society for Burn Injuries as guidelines concerning burns, but they were focused on the treatment for extensive and severe burns in the acute period. Therefore, we prepared guidelines intended to support the appropriate diagnosis and initial treatment for patients with burns that are commonly encountered including minor as well as moderate and severe cases. Because of this intention of the present guidelines, there is no recommendation of individual surgical procedures.