Effect of Demineralized Bone Matrix, Bone Marrow Mesenchymal Stromal Cells, and Platelet-Rich Plasma on Bone Tunnel Healing After Anterior Cruciate Ligament Reconstruction: A Comparative Micro-Computed Tomography Study in a Tendon Allograft Sheep Model.

BACKGROUND: The effect of demineralized bone matrix (DBM), bone marrow-derived mesenchymal stromal cells (BMSCs), and platelet-rich plasma (PRP) on bone tunnel healing in anterior cruciate ligament reconstruction (ACLR) has not been comparatively assessed. HYPOTHESIS: These orthobiologics would reduce tunnel widening, and the effects on tunnel diameter would be correlated with tunnel wall sclerosis. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 20 sheep underwent unilateral ACLR using tendon allograft and outside-in interference screw fixation. The animals were randomized into 4 groups (n = 5 per group): Group 1 received 4mL of DBM paste, group 2 received 10 million BMSCs in fibrin sealant, group 3 received 12 mL of activated leukocyte-poor platelet-rich plasma, and group 4 (control) received no treatment. The sheep were euthanized after 12 weeks, and micro-computed tomography scans were performed. The femoral and tibial tunnels were divided into thirds (aperture, midportion, and exit), and the trabecular bone structure, bone mineral density (BMD), and tunnel diameter were measured. Tunnel sclerosis was defined by a higher bone volume in a 250-µm volume of interest compared with a 4-mm volume of interest surrounding the tunnel. RESULTS: Compared with the controls, the DBM group had a significantly higher bone volume fraction (bone volume/total volume [BV/TV]) (52.7% vs 31.8%; P = .020) and BMD (0.55 vs 0.47 g/cm3; P = .008) at the femoral aperture and significantly higher BV/TV at femoral midportion (44.2% vs 32.9%; P = .038). There were no significant differences between the PRP and BMSC groups versus controls in terms of trabecular bone analysis or BMD. In the controls, widening at the femoral tunnel aperture was significantly greater than at the midportion (46.7 vs 41.7 mm2; P = .034). Sclerosis of the tunnel was common and most often seen at the femoral aperture. In the midportion of the femoral tunnel, BV/TV (r = 0.52; P = .019) and trabecular number (r S = 0.50; P = .024) were positively correlated with tunnel widening. CONCLUSION: Only DBM led to a significant increase in bone volume, which was seen in the femoral tunnel aperture and midportion. No treatment significantly reduced bone tunnel widening. Tunnel sclerosis in the femoral tunnel midportion was correlated significantly with tunnel widening. CLINICAL RELEVANCE: DBM might have potential clinical use to enhance healing in the femoral tunnel after ACLR.

Do clinical nurse specialist led stroke follow-up clinics reduce post-stroke hospital readmissions and recurrent vascular events?

BACKGROUND: Post-discharge stroke follow-up clinics intend to improve care and may reduce readmission. Pre-2013, there was no consistent post-stroke specialist follow up offered at Wellington Hospital. We tested whether the establishment of a clinical nurse specialist follow-up clinic reduced the 12-month readmission rate. METHODS: This is a sequential comparison of stroke patients admitted 1 year prior and 1 year after clinic establishment in 2013. The primary outcome was 12-month hospital readmission rate; main secondary outcomes were guideline adherence and recurrent vascular events. Patients were identified from hospital discharge records and underwent chart review. We adjusted results for differences in baseline characteristics. RESULTS: We identified 603 eligible patients; 288 pre- and 315 post-nurse clinic implementations. There was no difference based on study cohort in the 1-year readmission rate (adjusted odds ratio (aOR) = 1.14; 95% CI, 0.7-1.89; P = 0.583), or recurrent composite vascular events at 1 year (aOR = 1.56; 95% CI, 0.89-2.9; P = 0.159). When looking at clinic attendance as the main variable of interest, a pre-specified sub-group analysis, there was a significant difference in implementation of best medical therapy (aOR 2.66 (1.19-5.94); P = 0.017), and a trend towards reduction of vascular events and/or death at 1 year post discharge (aOR 0.53 (0.28-1.02); P = 0.056). CONCLUSIONS: There was no reduction in the 1-year hospital readmission or vascular event recurrence rate for patients admitted with stroke following the establishment of a specialist nurse-led stroke follow-up clinic. Actual clinic attendance, however, did appear to confer some benefit. This study suggests that more consistent and potentially earlier timed follow up is probably desirable.

Total Absence of Dystrophin Expression Exacerbates Ectopic Myofiber Calcification and Fibrosis and Alters Macrophage Infiltration Patterns.

Duchenne muscular dystrophy (DMD) causes severe disability and death of young men because of progressive muscle degeneration aggravated by sterile inflammation. DMD is also associated with cognitive and bone-function impairments. This complex phenotype results from the cumulative loss of a spectrum of dystrophin isoforms expressed from the largest human gene. Although there is evidence for the loss of shorter isoforms having impact in the central nervous system, their role in muscle is unclear. We found that at 8 weeks, the active phase of pathology in dystrophic mice, dystrophin-null mice (mdxßgeo) presented with a mildly exacerbated phenotype but without an earlier onset, increased serum creatine kinase levels, or decreased muscle strength. However, at 12 months, mdxßgeo diaphragm strength was lower, whereas fibrosis increased, compared with mdx. The most striking features of the dystrophin-null phenotype were increased ectopic myofiber calcification and altered macrophage infiltration patterns, particularly the close association of macrophages with calcified fibers. Ectopic calcification had the same temporal pattern of presentation and resolution in mdxßgeo and mdx muscles, despite significant intensity differences across muscle groups. Comparison of the rare dystrophin-null patients against those with mutations affecting full-length dystrophins may provide mechanistic insights for developing more effective treatments for DMD.

Hypoxia-induced retinal neovascularization in zebrafish embryos: a potential model of retinopathy of prematurity.

Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2-4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression.