Laura M. Epure

Calcification in human intervertebral disc degeneration and scoliosis

Calcification is a pathological process that may lead to impairment of nutrient supply and disc metabolism in degenerative and scoliotic intervertebral discs (IVDs). The purpose of this study was to assess the calcification potential of IVDs in degenerative disc disease (DDD) and adolescent idiopathic scoliosis (AIS). For this purpose, 34 IVDs from 16 adult patients with DDD and 25 IVDs from 9 adolescent patients with AIS were obtained at surgery. The concave and convex parts of the scoliotic discs were analyzed separately. Von Kossa staining was performed to visualize calcium deposits, while type X collagen (COL X) expression associated with endochondral ossification was measured by immunohistochemistry. Alkaline phosphatase activity and calcium and inorganic phosphate concentrations were used as indicators of calcification potential. Results showed the presence of calcium deposits and COL X in degenerative and scoliotic IVDs, but not in control discs, and the level of the indicators of calcification potential was consistently higher in degenerative and scoliotic discs than in control discs. The results suggest that disc degeneration in adults is associated with ongoing mineral deposition and that mineralization in AIS discs might reflect a premature degenerative process.

The efficacy of Link N as a mediator of repair in a rabbit model of intervertebral disc degeneration

IntroductionIntervertebral disc (IVD) degeneration is associated with proteolytic degradation of the extracellular matrix, and its repair requires both the production of extracellular matrix and the downregulation of proteinase activity. These properties are associated with several growth factors. However, the use of growth factors in clinical practice is limited by their high cost. This cost can be circumvented using synthetic peptides, such as Link N, which can stimulate the synthesis of proteoglycan and collagen by IVD cells in vitro. The purpose of the present study was to evaluate the effect of Link N in vivo in a rabbit model of IVD degeneration.MethodsNew Zealand white rabbits received annular puncture in two lumbar discs. Two weeks after puncture, both punctured discs of each rabbit were injected with either Link N or saline. After 2 weeks, nine rabbits were euthanized and the annulus fibrosus (AF) and nucleus pulposus (NP) of Link N-injected and saline-injected IVDs were removed and used to prepare total RNA. Following reverse transcription, quantitative PCR was performed for aggrecan, COL2A1, COL1A1, ADAMTS-4, ADAMTS-5 and MMP-3. After 12 weeks, 19 rabbits were euthanized and the injected IVDs were removed for biochemical and histological analysis. Proteinase K digests were analyzed for DNA and sulfated glycosaminoglycan content. Disc height was monitored radiographically biweekly.ResultsFollowing needle puncture, disc height decreased by about 25% over 2 weeks, and was partially restored by Link N injection. Puncture of the IVD resulted in a trend towards decreased proteoglycan content in both the NP and AF, and a trend towards partial restoration following Link N injection, although under the time course used this did not achieve statistical significance. Link N did not alter the DNA content of the discs. Link N injection led to a significant increase in aggrecan gene expression and a significant decrease in proteinase gene expression in both the NP and AF, when compared with saline alone.ConclusionsWhen administered to the degenerate disc in vivo, Link N stimulated aggrecan gene expression and downregulated metalloproteinase expression, and there was a trend towards increased proteoglycan content of the disc, in both the NP and AF. These are features needed for any agent designed to stimulate disc repair. In principle, therefore, Link N supplementation could be an option for treating disc degeneration.

Analysis of quantitative magnetic resonance imaging and biomechanical parameters on human discs with different grades of degeneration

To establish relationships between quantitative MRI (qMRI) and biomechanical parameters in order to help inform and interpret alterations of human intervertebral discs (IVD) with different grades of degeneration.

Comparison of US and Canadian Perioperative Outcomes and Hospital Efficiency After Total Hip and Knee Arthroplasty

IMPORTANCE The combination of an aging population, growing number of medical interventions, and surging economic burden of health care has renewed interest in reevaluating and exploring new health care models. OBJECTIVES To compare the performance of the US and Canadian health care systems by assessing major complications following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) and to measure the efficiency of both health care models by comparing the postoperative length of stay. DESIGN, SETTING, AND PARTICIPANTS With patients grouped according to the country where they underwent surgery, we queried the National Surgical Quality Improvement Program database to identify 55,335 Canadian and US patients who underwent primary elective THA or TKA between January 1, 2011, and December 31, 2012. MAIN OUTCOMES AND MEASURES Differences in patient demographics, as well as the rate of 30-day major complications and length of stay, were compared between patients hospitalized in the United States and Canada. RESULTS Baseline characteristics were similar between the groups. Most US patients underwent general anesthesia (THA, 61.8%; TKA, 59.4%); Canadian patients received more regional anesthesia (THA, 78.7%; TKA, 81.0%). Patients in the United States received more transfusions postoperatively (THA, 9.0% more; TKA, 6.4% more; P < .001) and had shorter hospitalizations (THA, 1.4 days less; TKA, 1.3 days less; P < .001) with a greater proportion of patients discharged to rehabilitation facilities (THA, 21.6% more; TKA, 26.6% more; P < .001). With results reported as incidence rate ratios (95% CIs), after adjusting for all other variables, risk factors, and adverse outcomes, having surgery in Canada increased the postoperative length of stay by 57% (1.57 [1.53-1.61]) for THA and 49% (1.49 [1.46-1.52]) for TKA. With results reported as odds ratios (95% CIs), major complications were significantly more common in Canada following TKA (1.65 [1.31-2.07]) but not THA (1.09 [0.79-1.51]). CONCLUSIONS AND RELEVANCE The rate of major complications was significantly higher in Canada following TKA, but there was no significant difference following THA. Patients undergoing the procedures in US hospitals also had substantially shorter lengths of hospital stay, perhaps reflecting more efficient postoperative care and discharge planning in those facilities.

Perioperative Complications and Length of Stay After Revision Total Hip and Knee Arthroplasties: An Analysis of the NSQIP Database

Goals of this study were (1) to determine the 30-day complications after aseptic revision hip arthroplasty (RHA) and aseptic revision knee arthroplasty (RKA) and (2) to identify patient-related risk factors predicting major complications and prolonged hospital stay beyond 7 days. The National Surgical Quality Improvement Program (NSQIP) database was used to identify patients with RHA (n=2643) or RKA (n=2425) from 2011 to 2012. The 30-day mortality rates for RHA and RKA were 1.0% and 0.1% (P<0.001) and the overall complication rates were 7.4% and 4.7% (P<0.001) for RHA and RKA, respectively. Multivariable analysis showed that preoperative anemia is the most important modifiable independent predictor for both major complications and prolonged hospital stay after RHA and RKA.

Hospital Discharge within 2 Days Following Total Hip or Knee Arthroplasty Does Not Increase Major-Complication and Readmission Rates.

BACKGROUND The rising costs of total knee arthroplasty (TKA) and total hip arthroplasty (THA) have resulted in a substantial economic burden on the U.S. health-care system. Recent efforts to contain these costs have targeted hospital length of stay. However, shorter hospital admissions have raised concerns over possible increases in complications and readmission rates. The purpose of this study was to assess whether early discharge, from 0 to 2 days postoperatively, was associated with increased 30-day major complications and readmissions compared with standard discharge, 3 to 4 days following THA or TKA. METHODS The National Surgical Quality Improvement Program (NSQIP) database was queried to identify all patients who underwent an elective, primary unilateral THA or TKA between 2011 and 2012. For each procedure, 2 groups were created consisting of patients discharged from 0 to 2 days (early discharge) and those discharged from 3 to 4 days (standard discharge). Patient demographics and perioperative variables were compared between both discharge groups. Multivariable logistic-regression models were used to assess the independent effect of length of stay on 30-day major-complication and readmission rates. RESULTS A total of 31,044 patients who underwent TKA and 19,909 patients who underwent THA were included. Overall, patients who were discharged early were younger and had fewer medical comorbidities and a lower American Society of Anesthesiologists (ASA) score. The multivariable logistic-regression model revealed that early discharge was not associated with increased odds of major complications following TKA (odds ratio [OR] = 0.95; 95% confidence interval [CI] = 0.75 to 1.20; p = 0.64). Furthermore, early discharge following THA was found to be an independent predictor against major complications (OR = 0.75; 95% CI = 0.58 to 0.95; p = 0.02). Lastly, early discharge was not an independent risk factor for hospital readmission following THA or TKA. CONCLUSIONS Early discharge was not an independent risk factor for 30-day major complications or readmissions following THA or TKA. Rather, increased major complications and readmissions were attributed to patient comorbidities and perioperative variables. Early discharge within the first 2 days postoperatively for risk-stratified patients appears feasible without compromising patient care. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Effect of Sterilization on Non-woven Polyethylene Terephthalate Fiber Structures for Vascular Grafts

Non-woven polyethylene terephthalate (PET) fibers produced via melt blowing and compounded into a 6 mm diameter 3D tubular scaffold were developed with artery matching mechanical properties. This work compares the effects of ethylene oxide (EtO) and low temperature plasma (LTP) sterilization on PET surface chemistry and biocompatibility. As seen through X-ray photoelectron spectroscopy (XPS) analysis, LTP sterilization led to an increase in overall oxygen content and the creation of new hydroxyl groups. EtO sterilization induced alkylation of the PET polymer. The in vitro cytotoxicity showed similar fibroblastic viability on LTP- and EtO-treated PET fibers. However, TNF-α release levels, indicative of macrophage activation, were significantly higher when macrophages were incubated on EtO-treated PET fibers. Subcutaneous mice implantation revealed an inflammatory response with foreign body reaction to PET grafts independent of the sterilization procedure.

Midterm Outcomes of the Recently FDA Approved Ceramic on Ceramic Bearing in Total Hip Arthroplasty Patients Under 65 Years of Age.

The present study aimed to evaluate the mid-term results of the fourth generation of ceramic on ceramic (CC) bearing. Demographics, surgical technique, complications, clinical and radiologic outcomes were analyzed in a series of 133 consecutive CC total hip arthroplasties (THAs) with a newest generation CC bearings to determine if these provide safe and well performing bearings. At the last follow-up, there were no cases of ceramic fracture or chipping and no revision surgery necessary for bearing related complication. One hip underwent two staged revision for infection and another underwent revision for dislocation, resulting in an overall 98.5% survival rate at a mean of 6 years. The newest generation of CC bearings provides a reliable and safe bearing in young, active patients undergoing THA.

Biocompatibility of Candidate Materials for the Realization of Medical Microdevices

The propulsion of ferromagnetic micro-carriers in the blood vessels by magnetic gradients generated from a magnetic resonance imaging (MRI) system is of special interest for targeted interventions such as chemotherapy or chemo-embolization. As such, Fe-Co alloys for its highest magnetization saturation, and single crystal Ni-Mn-Ga powder and Terfenol-D for their deformation in magnetic field are evaluated for their biocompatibility. The toxicity of these materials is evaluated with MTT cell viability tests. The tests show that Fe-Co (Permendur and Vacoflux 17) alloys are toxic within 24 hours while the single crystal Ni-Mn-Ga powder becomes toxic after 48 hours. The Terfenol-D, despite its high degradation, has 90% cell viability after 72 hours. These results indicate that such candidate materials to be considered in untethered micro-carriers or devices in the blood vessels, would require, depending upon the time spent in the blood vessels, further processes to be viable for such applications

The Potential of N-Rich Plasma-Polymerized Ethylene (PPE:N) Films for Regulating the Phenotype of the Nucleus Pulposus.

We recently developed a nitrogen-rich plasma-polymerized biomaterial, designated “PPE:N” (N-doped plasma-polymerized ethylene) that is capable of suppressing cellular hypertrophy while promoting type I collagen and aggrecan expression in mesenchymal stem cells from osteoarthritis patients. We then hypothesized that these surfaces would form an ideal substrate on which the nucleus pulposus (NP) phenotype would be maintained. Recent evidence using microarrays showed that in young rats, the relative mRNA levels of glypican-3 (GPC3) and pleiotrophin binding factor (PTN) were significantly higher in nucleus pulposus (NP) compared to annulus fibrosus (AF) and articular cartilage. Furthermore, vimentin (VIM) mRNA levels were higher in NP versus articular cartilage. In contrast, the levels of expression of cartilage oligomeric matrix protein (COMP) and matrix gla protein precursor (MGP) were lower in NP compared to articular cartilage. The objective of this study was to compare the expression profiles of these genes in NP cells from fetal bovine lumbar discs when cultured on either commercial polystyrene (PS) tissue culture dishes or on PPE:N with time. We found that the expression of these genes varies with the concentration of N ([N]). More specifically, the expression of several genes of NP was sensitive to [N], with a decrease of GPC3, VIM, PTN, and MGP in function of decreasing [N]. The expression of aggrecan, collagen type I, and collagen type II was also studied: no significant differences were observed in the cells on different surfaces with different culture time. The results support the concept that PPE:N may be a suitable scaffold for the culture of NP cells. Further studies are however necessary to better understand their effects on cellular phenotypes.