Clinical outcomes and complications of cementless reverse total shoulder arthroplasty during the early learning curve period.

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) is a treatment option for patients with severe osteoarthritis, rotator cuff arthropathy, or massive rotator cuff tear with pseudoparalysis. We are to deduce not only the early functional outcomes and complications of cementless RTSA during the learning curve period but also complication-based, and operation time-based learning curve of RTSA. METHODS: Between March 2010 and February 2014, we retrospectively evaluated 38 shoulders (6 male, 32 female). The average age of the patients was 73.0 years (range, 63 to 83 years), and the average follow-up was at 24 months (range, 12-53 months). The visual analog scale (VAS), University of California Los Angeles (UCLA) score and constant score were used to evaluate the clinical outcomes. We evaluated patients radiographically at 2 weeks, 3 months, 6 months, 1 year, and then annually thereafter for any evidence of complications. RESULTS: The VAS score improved from 4.0 to 2.8 (p = 0.013). The UCLA score improved from 16.0 to 27.9 (p = 0.002), and the constant score improved from 41.4 to 78.9 (p < 0.001), which were statistically significant. While active forward flexion, abduction, and internal rotation improved (p value = 0.001, < 0.01, 0.15), external rotation did not show significant improvement (p = 0.764). Postoperative complications included acromion fracture (one case), glenoid fracture (one case), peripristhetic humeral fracture (one case), axillary nerve injury (one case), infection (one case), and arterial injury (one case). Our study presented an intraoperative complication-based learning curve of 20 shoulders, and operation time-based learning curve of 15 shoulders. CONCLUSIONS: The clinical outcomes of RTSA were satisfactory with overall complication rates of 15.7%. An orthopedic surgeon within the learning curve period for the operation of RTSA should be cautious when selecting the patients and performing RTSA. TRIAL REGISTRATION: Retrospectively registered.

Arthroscopic treatment of greater tuberosity fractures : retrospective review of clinical and radiological outcomes.

The purpose of this retrospective study was to analyze the clinical and radiological outcomes and discuss the value of arthroscopic suture bridge technique in patients with isolated greater tuberosity fractures. Between October 2009 and July 2014, 37 patients with greater tuberosity fractures were analyzed. Thirteen of these patients were treated with arthroscopic reduction and fixation. Analysis of the clinical outcome was performed by comparing final range of motion, UCLA and Constant score. Radiological outcome was analyzed with time for union. Postoperative results were analyzed by range of motion, UCLA and constant score. Each figure resulted as: UCLA from 27 to 35 (average: 29); range of motion in forward flexion from 160° to 180° (average: 173°); Constant score from 69 to 100 (average: 73). Using arthroscopic treatment with a suture-bridge technique can be a useful method in terms of clinical and functional outcomes and be considered as a viable alternative to conventional open techniques.

Antibody to FcεRIα Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation.

PURPOSE: High-affinity receptor I (FcεRI) on mast cells and basophils plays a key role in the immunoglobulin E (IgE)-mediated type I hypersensitivity mediated by allergen cross-linking of the specific IgE-FcεRI complex. Thus, prevention of IgE binding to FcεRI on these cells is an effective therapy for allergic disease. We have developed a strategy to disrupt IgE binding to FcεRI using an antibody targeting FcεRIα. MATERIALS AND METHODS: Fab fragment antibodies, which lack the Fc domain, with high affinity and specificity for FcεRIα and effective inhibitory activity against IgE-FcεRI binding were screened. IgE-induced histamine, ß-hexosaminidase and Ca²âº release in basophils were determined by ELISA. A B6.Cg-Fcer1a(tm1Knt) Tg(FCER1A)1Bhk/J mouse model of passive cutaneous anaphylaxis (PCA) was used to examine the inhibitory effect of NPB311 on allergic skin inflammation. RESULTS: NPB311 exhibited high affinity to human FcεRIα (KD=4 nM) and inhibited histamine, ß-hexosaminidase and Ca²âº release in a concentration-dependent manner in hFcεRI-expressing cells. In hFcεRIα-expressing mice, dye leakage was higher in the PCA group than in controls, but decreased after NPB311 treatment. NPB311 could form a complex with FcεRIα and inhibit the release of inflammation mediators. CONCLUSION: Our approach for producing anti-FcεRIα Fab fragment antibody NPB311 may enable clinical application to a therapeutic pathway in IgE/FcεRI-mediated diseases.

MET and AXL inhibitor NPS-1034 exerts efficacy against lung cancer cells resistant to EGFR kinase inhibitors because of MET or AXL activation.

In non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, acquired resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKI) can occur through a generation of bypass signals such as MET or AXL activation. In this study, we investigated the antitumor activity of NPS-1034, a newly developed drug that targets both MET and AXL, in NSCLC cells with acquired resistance to gefitinib or erlotinib (HCC827/GR and HCC827/ER, respectively). Characterization of H820 cells and evaluation of NPS-1034 efficacy in these cells were also performed. The resistance of HCC827/GR was mediated by MET activation, whereas AXL activation led to resistance in HCC827/ER. The combination of gefitinib or erlotinib with NPS-1034 synergistically inhibited cell proliferation and induced cell death in both resistant cell lines. Accordingly, suppression of Akt was noted only in the presence of treatment with both drugs. NPS-1034 was also effective in xenograft mouse models of HCC827/GR. Although the H820 cell line was reported previously to have T790M and MET amplification, we discovered that AXL was also activated in this cell line. There were no antitumor effects of siRNA or inhibitors specific for EGFR or MET, whereas combined treatment with AXL siRNA or NPS-1034 and EGFR-TKIs controlled H820 cells, suggesting that AXL is the main signal responsible for resistance. In addition, NPS-1034 inhibited cell proliferation as well as ROS1 activity in HCC78 cells with ROS1 rearrangement. Our results establish the efficacy of NPS-1034 in NSCLC cells rendered resistant to EGFR-TKIs because of MET or AXL activation or ROS1 rearrangement.

Preventive effects of multi-lamellar emulsion on low potency topical steroid induced local adverse effect.

BACKGROUND: Topical steroid treatment induces diverse local Wand systemic adverse effects. Several approaches have been tried to reduce the steroid-induced adverse effects. Simultaneous application of physiological lipid mixture is also suggested. OBJECTIVE: Novel vehicles for topical glucocorticoids formulation were evaluated for the efficacy of reducing side-effects and the drug delivery properties of desonide, a low potency topical steroid. METHODS: Transcutaneous permeation and skin residual amount of desonide were measured using Franz diffusion cells. The in vivo anti-inflammatory activity was evaluated using murine model. RESULTS: Topical steroids formulation containing desonide, in either cream or lotion form, were prepared using multi-lamellar emulsion (MLE), and conventional desonide formulations were employed for comparison. MLE formulations did not affect the anti-inflammatory activity of the desonide in phobol ester-induced skin inflammation model, compared with conventional formulations. While the penetrated amounts of desonide were similar for all the tested formulations at 24 hours after application, the increased lag time was observed for the MLE formulations. Interestingly, residual amount of desonide in epidermis was significantly higher in lotion type MLE formulation. Steroid-induced adverse effects, including permeability barrier function impairment, were partially prevented by MLE formulation. CONCLUSION: Topical desonide formulation using MLE as a vehicle showed a better drug delivery with increased epidermal retention. MLE also partially prevented the steroid-induced side effects, such as skin barrier impairment.

Epigenetic regulation of the transcription factor Foxa2 directs differential elafin expression in melanocytes and melanoma cells.

Elafin, a serine protease inhibitor, induces the intrinsic apoptotic pathway in human melanoma cells, where its expression is transcriptionally silenced. However, it remains unknown how the elafin gene is repressed in melanoma cells. We here demonstrate that elafin expression is modulated via epigenetically regulated expression of the transcription factor Foxa2. Treatment of melanoma cells with a DNA methyltransferase inhibitor induced elafin expression, which was specifically responsible for reduced proliferation and increased apoptosis. Suppression of Foxa2 transcription, mediated by DNA hypermethylation in its promoter region, was released in melanoma cells upon treatment with the demethylating agent. Luciferase reporter assays indicated that the Foxa2 binding site in the elafin promoter was critical for the activation of the promoter. Chromatin immunoprecipitation assays further showed that Foxa2 bound to the elafin promoter in vivo. Analyses of melanoma cells with varied levels of Foxa2 revealed a correlated expression between Foxa2 and elafin and the ability of Foxa2 to induce apoptosis. Our results collectively suggest that, in melanoma cells, Foxa2 expression is silenced and therefore elafin is maintained unexpressed to facilitate cell proliferation in the disease melanoma.