Effects of trypsinization and mineralization on intrasynovial tendon allograft healing to bone

The purpose of the current study was to develop a novel technology to enhance tendon‐to‐bone interface healing by trypsinizing and mineralizing (TM) an intrasynovial tendon allograft in a rabbit bone tunnel model. Eight rabbit flexor digitorum profundus (FDP) tendons were used to optimize the trypsinization process. An additional 24 FDP tendons were stratified into control and TM groups; in each group, 4 tendons were used for in vitro evaluation of TM and 8 were transplanted into proximal tibial bone tunnels in rabbits. The samples were evaluated histologically and with mechanical testing at postoperative week 8. Maximum failure strength and linear stiffness were not significantly different between the control and TM tendons. A thin fibrous band of scar tissue formed at the graft‐to‐bone interface in the control group. However, only the TM group showed obvious new bone formation inside the tendon graft and a visible fibrocartilage layer at the bone tunnel entrance. This study is the first to explore effects of TM on the intrasynovial allograft healing to a bone tunnel. TM showed beneficial effects on chondrogenesis, osteogenesis, and integration of the intrasynovial tendon graft, but mechanical strength was the same as the control tendons in this short‐term in vivo study. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:468–474, 2015.     

Prognostic value of pathologic fracture in patients with high grade localized osteosarcoma: A systemic review and meta‐analysis of cohort studies

Consensus has not been reached regarding the ability of pathologic fracture to predict local recurrence and survival in osteosarcoma. We aim to review the available evidence to examine the association between pathologic fracture and osteosarcoma prognosis. A comprehensive literature search for relevant studies published until March 2014 was performed using PubMed, Cochrane and Web of Science. The studies investigating pathologic fracture of osteosarcoma patients were systematically analyzed. The overall relative risk (RR) was estimated using a fixed‐effect model or random‐effect model according to heterogeneity between the trials. We included nine cohort studies involving 2,187 patients (311 with pathologic fracture and 1,876 without fracture) for the analysis of survival rate and local recurrence. Studies were assessed for quality using the Newcastle–Ottawa Assessment Scale. In the fixed‐effects model, the meta‐analysis showed that pathologic fracture in osteosarcoma patients predicted poor 3‐year overall survival (OS) (RR = 1.86, 95% CI: 1.37–2.53, p < 0.001) and 5‐year OS (RR = 1.34, 95% CI: 1.06–1.70, p = 0.016). Similarly, pathologic fracture was significantly correlated with worse 3‐year event free survival (EFS) (RR = 1.52, 95% CI: 1.21–1.92, p < 0.001) and 5‐year EFS (RR = 1.24, 95% CI: 1.03–1.49, p = 0.021), whereas no significant association was noted with local recurrence (RR = 1.30, 95% CI: 0.84–2.02, p = 0.233). The meta‐analysis confirmed that pathologic fracture in osteosarcoma was a prognostic marker for both OS and EFS but not for local recurrence. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:131–139, 2015.     

CD146 as a new marker for an increased chondroprogenitor cell sub‐population in the later stages of osteoarthritis

Cartilage‐derived mesenchymal stem cells (MSCs) have been isolated with different methods. In this study lateral and medial femoral condyles were respectively collected from patients with late‐stage osteoarthritis during the total knee arthroplasty. After digestion of the cartilage tissues with type II collagenase and analysis by fluorescence‐activated cell sorting (FACS) with CD146, a chondroprogenitor cell sub‐population were isolated and purified. The expression of other MSC‐associated markers in the CD146⁺ chondroprogenitors was analyzed by flow cytometry. Multi‐lineage differentiation capacity of CD146⁺ chondroprogenitors was compared with that of unsorted chondrocytes and adipose‐derived MSCs (ADMSCs). Higher percentage of CD146⁺ chondroprogenitors isolated from the medial femoral condyles was observed than that from the lateral. CD146⁺ chondroprogenitors expressed high levels of MSC‐specific surface antigens, and showed higher chondrogenesis capacity than ADMSCs and unsorted chondrocytes in a 3D cell pellet culture model. Thus CD146 might be a new cell surface marker for cartilage progenitor cell population in the late‐stage osteoarthritis. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:84–91, 2015.     

Collagen gel contraction as a measure of fibroblast function in an animal model of subsynovial connective tissue fibrosis

Carpal tunnel syndrome (CTS) is a peripheral neuropathy characterized by non‐inflammatory fibrosis of the subsynovial connective tissues (SSCT). A rabbit model of CTS was developed to test the hypothesis that SSCT fibrosis causes the neuropathy. We used a cell‐seeded collagen‐gel contraction model to characterize the fibrosis in this model in terms of cellular mechanics, specifically to compare the ability of SSCT cells from the rabbit model and normal rabbits to contract the gel, and to assess the effect of transforming growth factor‐β1,which is upregulated in CTS, on these cells. SSCT fibrosis was induced in six retired breeder female rabbits which were sacrificed at 6 weeks (N = 3) and 12 weeks (n = 3). An additional two rabbits served as controls. SSCT was harvested according to a standard protocol. Gels seeded with SSCT cells from rabbits sacrificed at 6 weeks had significantly higher tensile strength (p < 0.001) and Young's modulus (p < 0.001) than gels seeded with cells from rabbits sacrificed at 12 weeks or control animals. TGF‐β1 significantly increased the decay time constant (p < 0.001), tensile strength (p < 0.001), and Young's modulus (p < 0.001) regardless of the cell source. This model may be useful in screening therapeutic agents that may block SSCT fibrosis, identifying possible candidates for CTS treatment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:668–674, 2015.     

DEGS2 polymorphism associated with cognition in schizophrenia is associated with gene expression in brain

A genome-wide association study of cognitive deficits in patients with schizophrenia in Japan found association with a missense genetic variant (rs7157599, Asn8Ser) in the delta(4)-desaturase, sphingolipid 2 (DEGS2) gene. A replication analysis using Caucasian samples showed a directionally consistent trend for cognitive association of a proxy single-nucleotide polymorphism (SNP), rs3783332. Although the DEGS2 gene is expressed in human brain, it is unknown how DEGS2 expression varies during human life and whether it is affected by psychiatric disorders and genetic variants. To address these questions, we examined DEGS2 messenger RNA using next-generation sequencing in postmortem dorsolateral prefrontal cortical tissue from a total of 418 Caucasian samples including patients with schizophrenia, bipolar disorder and major depressive disorder. DEGS2 is expressed at very low levels prenatally and increases gradually from birth to adolescence and consistently expressed across adulthood. Rs3783332 genotype was significantly associated with the expression across all subjects (F_3,348=10.79, P=1.12 × 10⁻³), particularly in control subjects (F_1,87=13.14, P=4.86 × 10⁻⁴). Similar results were found with rs715799 genotype. The carriers of the risk-associated minor allele at both loci showed significantly lower expression compared with subjects homozygous for the non-risk major allele and this was a consistent finding across all diagnostic groups. DEGS2 expression showed no association with diagnostic status after correcting for multiple testing (P>0.05). Our findings demonstrate that a SNP showing genome-wide association study significant association with cognition in schizophrenia is also associated with regulation of DEGS2 expression, implicating a molecular mechanism for the clinical association.     

Efficacy of and Patient Compliance with a Ketogenic Diet in Adults with Intractable Epilepsy: A Meta-Analysis

Background and Purpose

Despite the successful use of a ketogenic diet in pediatric epilepsy, its application in adults has been limited. The aim of this meta-analysis was to summarize the findings of relevant published studies in order to identify the efficacy of and compliance with a ketogenic diet and its main subtypes (i.e., classic ketogenic diet and modified Atkins diet) in adults with intractable epilepsy, and to provide useful information for clinical practice.

Methods

Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies of the efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy; the included studies were reviewed. Meta-analyses were performed using STATA to determine combined efficacy rates and combined rates of compliance with the ketogenic diet and its main subtypes.

Results

In total, 12 studies qualified for inclusion, and data from 270 patients were evaluated.The results of the meta-analysis revealed combined efficacy rates of all types of ketogenic diet, a classical ketogenic diet, and a modified Atkins diet were 42%, 52%, and 34%, respectively; the corresponding combined compliance rates were 45%, 38%, and 56%.

Conclusions

The results indicate that a ketogenic diet is a promising complementary therapy in adult intractable epilepsy, and that while a classical ketogenic diet may be more effective, adult patients are likely to be less compliant with it than with a modified Atkins diet.     

药护协同管理在急性心肌梗死患者溶栓治疗中的实践

目的 探讨药护协同管理在急性心肌梗死患者溶栓治疗中的实践效果.方法 将100例急性心肌梗死溶栓治疗的患者按数字随机法分为常规组(n=50)和协同管理组(n=50),常规组按照常规护理,协同管理组在此基础上实施药护协同管理,干预6个月后比较治疗效果.结果 两组入院后明确诊断至开始溶栓时间、冠脉有效灌注率和住院天数比较,协同干预组显著优于常规组,48h内恶性心律失常发生例数协同组显著少于常规组,差异有统计学意义(均P＜0.05).两组患者溶栓治疗后12h、24 h、48 h、7d的LVEF值比较,差异有统计学意义(均P＜0.05);出院后6个月心脏不良事件发生比例比较,差异无统计学意义(P＞0.05).结论 药护协同管理能够有效缩短急性心肌梗死患者入院后至溶栓的时间,提高冠脉有效灌注,减少48 h内恶性心律失常发生和缩短住院天数,促进心功能恢复.