Local delivery of mutant CCL2 protein‐reduced orthopaedic implant wear particle‐induced osteolysis and inflammation in vivo

Total joint replacement (TJR) has been widely used as a standard treatment for late‐stage arthritis. One challenge for long‐term efficacy of TJR is the generation of ultra‐high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade which may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here, we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle‐induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle‐induced osteolysis and the effects of 7ND treatment were evaluated using micro‐CT, histology, and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle‐induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle‐induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:58–64, 2016.     

Aggravation of spinal cord compromise following new osteoporotic vertebral compression fracture prevented by teriparatide in patients with surgical contraindications

Summary

Patients with spinal cord deficits following new unstable osteoporotic compression fracture and surgical contraindications were considered to receive conservative treatment. Teriparatide was better than alendronate at improving bone mineral density and bone turnover parameters, as well as preventing aggravation of spinal cord compromise.

Introduction

This study compared the preventive effects of teriparatide and alendronate on aggravation of spinal cord compromise following new unstable osteoporotic vertebral compression fracture (OVCF) in patients with surgical contraindications.

Methods

This was a 12-month, randomized, open-label study of teriparatide versus alendronate in 49 patients with new unstable OVCF and surgical contraindications. Neurological function was evaluated using modified Japanese Orthopedic Association (mJOA) score (11-point scale, the maximum score of 11 implies normalcy). Visual analog scale (VAS) scores, kyphotic angles, anterior-border heights and diameters of the spinal canal of the fractured vertebrae, any incident of new OVCFs (onset of OVCF during follow-up), spine bone mineral density (BMD), and serum markers of bone resorption and bone formation were also examined at baseline and 1, 3, 6, and 12 months after initiation of the medication regimen.

Results

At 12 months, mean mJOA score had improved in the teriparatide group and decreased in the alendronate group. Mean concentrations of bone formation and bone resorption biomarkers, mean spine BMD, and mean anterior-border height and spinal canal diameter of the fractured vertebrae were significantly greater in the teriparatide group than in the alendronate group. Mean VAS score, mean kyphotic angle of the fractured vertebrae, and incidence of new OVCFs were significantly smaller in the teriparatide group than in the alendronate group.

Conclusions

In patients with neurological deficits following new unstable OVCF and with surgical contraindications, teriparatide was better than alendronate at improving the BMD and the bone turnover parameters, as well as preventing aggravation of spinal cord compromise.

     

Surgical management of spinal liposarcoma: a case series of 7 patients and literature review

European Spine Journal - Liposarcoma, one of the most common soft tissue sarcomas originates from primitive mesenchymal cells. But spinal involvement of either primary or metastatic liposarcoma is...     

Recurrent rhabdomyolysis and glutaric aciduria type I: a case report and literature review

Background

Glutaric acidemia type I (GA-I) is a rare metabolic disorder caused by mutation of the glutaryl- CoA dehydrogenase (GCDH) gene. The occurrence of rhabdomyolysis with GA-I is extremely rare.

Methods

We reported a child with recurrent rhabdomyolysis and undiagnosed glutaric acidemia type I (GA-I). And a literature review was performed.

Results

A 4.5-year-old girl was admitted to our hospital due to recurrent rhabdomyolysis for 3 times within three years. At the third admission, she was diagnosed with GA-I by biochemical testing and mutation analysis. The girl was found to have a serine to leucine replacement mutation of the GCDH gene in exon 8 at position 764. Other three patients with rhabdomyolysis and GA-I were discovered by literature searching.

Conclusions

This report highlights that patients with GA-I may have an increased risk of rhabdomyolysis.

     

3D打印技术在特殊类型房间隔缺损诊疗中的应用

目的应用3D打印技术制作房间隔缺损(ASD)解剖模型,探讨3D打印模型在特殊类型ASD诊疗中的临床应用价值。方法收集25例继发孔型ASD患者,均行CTA检查,将扫描数据输入FitMe影像处理软件进行三维重建,将重建数据输入3D打印机进行打印。根据3D打印模型进行模拟介入治疗并制定介入手术方案。结果 25例ASD模型均制作成功。对7例多孔型ASD采用ASD封堵器介入治疗成功,4例下腔型ASD采用PDA封堵器封堵成功,其余病例由于缺损直径过大或结构特殊未行介入治疗。结论 3D打印ASD模型技术具有可行性,对于较为复杂的ASD可通过术前模拟介入治疗以提高手术成功率。     

Allergen-Dependent Differences in ILC2s Frequencies in Patients With Allergic Rhinitis

PurposeGroup 2 innate lymphoid cells (ILC2s) are a novel population of lineage-negative cells that induce innate type 2 responses by producing the critical Th2-type cytokines IL-5 and IL-13 in response to IL-25 and IL-33 stimulation. ILC2s accumulation in the peripheral blood of patients with allergic rhinitis (AR) is controversial; the precise role of ILC2s in the immunopathogenesis of AR is still not clear. We investigated the role of ILC2s in phenotypic AR sensitized to distinct allergens.MethodsFlow cytometric analysis of the peripheral blood of 7 healthy controls (HCs), 9 patients monosensitized to house dust mite (HDM), and 8 patients monosensitized to mugwort was performed to quantify ILC2s frequency. Peripheral blood mononuclear cells (PBMCs) were isolated from HDM-AR and mugwort-AR patients, and Lineage^- and Lineage⁺ cells were separated using a fluorescence-activated cell sorter (FACS). IL-5 and IL-13 levels in the supernatants of PBMCs, and Lineage^- and Lineage⁺ cells stimulated with IL-25 and/or IL-33 combined with IL-2 in vitro were assessed using the Milliplex magnetic bead kit.ResultsThe percentage of ILC2s was significantly elevated in HDM-AR patients compared to mugwort-AR patients and HCs, while no significant difference was found between mugwort-AR patients and HCs. IL-33±IL-25 plus IL-2 induced a significantly greater release of IL-5 and IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. IL-25 plus IL-2 also induced a significantly greater release of IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. Stimulation with IL-33 and/or IL-25 combined with IL-2 also induced a significantly greater IL-5 and IL-13 release from Lineage^- cells compared to Lineage⁺ cells.ConclusionsAR patients sensitized to HDM or mugwort allergen have distinct phenotypic and functional profiles in ILC2s frequencies. ILC2s mediate major type 2 immunity in the development of HDM-AR and may be a potential therapeutic target.