Michael C. Parry

Kainate receptors are involved in synaptic plasticity

The ability of synapses to modify their synaptic strength in response to activity is a fundamental property of the nervous system and may be an essential component of learning and memory. There are three classes of ionotropic glutamate receptor, namely NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid) and kainate receptors; critical roles in synaptic plasticity have been identified for two of these. Thus, at many synapses in the brain, transient activation of NMDA receptors leads to a persistent modification in the strength of synaptic transmission mediated by AMPA receptors. Here, to determine whether kainate receptors are involved in synaptic plasticity, we have used a new antagonist, LY382884 ((3S, 4aR, 6S, 8aR)-6-((4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid), which antagonizes kainate receptors at concentrations that do not affect AMPA or NMDA receptors. We find that LY382884 is a selective antagonist at neuronal kainate receptors containing the GluR5 subunit. It has no effect on long-term potentiation (LTP) that is dependent on NMDA receptors but prevents the induction of mossy fibre LTP, which is independent of NMDA receptors. Thus, kainate receptors can act as the induction trigger for long-term changes in synaptic transmission.

Thresholds for indirect DNA damage across cellular barriers for orthopaedic biomaterials.

Cobalt-chromium particles and ions can induce indirect DNA damage and chromosome aberrations in human cells on the other side of a cellular barrier in tissue culture. This occurs by intercellular signalling across the barrier. We now show that the threshold for this effect depends on the metal form and the particle composition. Ionic cobalt and chromium induced single strand breaks at concentrations equivalent to those found in the blood of patients with well functioning metal on metal hip prostheses. However, they only caused double strand breaks if the chromium was present as chromium (VI), and did not induce chromosome aberrations. Nanoparticles of cobalt-chromium alloy caused DNA double strand breaks and chromosome aberrations, of which the majority were tetraploidy. Ceramic nanoparticles induced only single strand breaks and/or alkaline labile sites when indirectly exposed to human fibroblasts. The assessment of reproductive risk from maternal exposure to biomaterials is not yet possible with epidemiology. Whilst the barrier model used here differs from the in vivo situation in several respects, it may be useful as a framework to evaluate biomaterial induced damage across physiological barriers.

Ninety-day mortality after elective total hip replacement: 1549 PATIENTS USING ASPIRIN AS A THROMBOPROPHYLACTIC AGENT

Thromboprophylaxis after elective orthopaedic surgery remains controversial. Recent guidelines from the National Institute for Clinical Excellence (NICE) have suggested that low molecular weight heparin should be given to all patients undergoing total hip replacement. The British Orthopaedic Association is currently debating this guideline with NICE, as it is not clear whether published evidence supports this view. We present the early mortality in our unit after total hip replacement using aspirin as chemical thromboprophylaxis. The 30-day and 90-day mortality after primary total hip arthroplasty was zero. We compare this with that reported previously from our unit without using chemical thromboprophylaxis. With the introduction of routine aspirin thromboprophylaxis, deaths from cardiovascular causes have dropped from 0.75% to zero. These results demonstrate that there is a strong argument for the routine administration of aspirin after elective total hip replacement.

Early death following primary total knee arthroplasty.

BACKGROUND Total knee arthroplasty carries major risks, including death. Conventional studies have compared the mortality rate following total knee arthroplasty with standardized mortality ratios or age and sex-matched populations. The purpose of the present study was to compare the mortality rate in a population of patients who were managed with total knee arthroplasty with that in patients who were awaiting surgery. METHODS All patients undergoing primary total knee arthroplasty from 2000 to 2007 at a single institution were recorded. In the same period, all patients who were added to the waiting list for total knee arthroplasty were recorded. The mortality rate and time to death were calculated, and death certificates were retrieved for those who died within thirty or ninety days after the index event. RESULTS Two thousand, six hundred and ninety-five patients undergoing primary total knee arthroplasty were used for the thirty-day mortality calculation, and 2527 were used for the ninety-day mortality calculation. These patients were compared with 5857 and 5689 patients who were added to the waiting list for the thirty-day and ninety-day mortality calculations, respectively. There was no difference between the populations in terms of age or sex (p > 0.05). The thirty-day mortality following surgery was significantly greater for the surgery group (0.371%; 95% confidence interval, 0.202% to 0.682%) than for the waiting list group (0.0683%; 95% confidence interval, 0.0266% to 0.1755%) (odds ratio, 5.45; 95% confidence interval, 1.81 to 16.43). The ninety-day mortality was also significantly greater for the surgery group (0.792%; 95% confidence interval, 0.513% to 1.219%) than for the waiting list group (0.387%; 95% confidence interval, 0.256% to 0.585%) (odds ratio, 2.05; 95% confidence interval, 1.13 to 3.74). CONCLUSIONS Primary total knee arthroplasty is associated with an increased risk of death at thirty and ninety days after the operation when compared with a population awaiting the same procedure. Increasing age was a risk factor for death following total knee arthroplasty.

Radiologic outcome and patient-reported function after intramedullary nailing: a comparison of the retropatellar and infrapatellar approach.

Objectives: The purpose of this study was to compare the patient-reported functional outcomes after intramedullary nailing of the tibia through a retropatellar or infrapatellar approach. Radiographic assessment of nail entry point and accuracy of fracture reduction were included to aid in the identification of variables that may explain any difference in patient-reported outcomes. Design: A retrospective radiographic and questionnaire-based assessment of patient-reported outcomes and complications after tibial nailing for trauma or limb reconstruction through a retropatellar or infrapatellar approach. Setting: Regional limb reconstruction unit within a university teaching hospital. Patients/Participants: Two consecutive series of 38 patients with intramedullary tibial nails inserted through a retropatellar approach, and 36 patients with a tibial nail inserted through an infrapatellar approach. Intervention: Tibial nail insertion through either a retropatellar or infrapatellar approach. Main Outcome Measures: Patient-reported outcomes and complication rates and radiographic assessment of fracture reduction and nail insertion entry point. Results: No significant difference was seen in Kujala score as a measure of anterior knee pain (P = 0.217), either in the physical (P = 0.372) or mental (0.504) components of the SF-12 between the groups, although there was a trend toward symptomatic intrusive knee pain in the infrapatellar group. A more accurate fracture reduction, both in terms of angulation (P = 0.003) and translation (P = 0.010) in the coronal plane, was seen in the retropatellar group. The entry point for nail insertion was more accurate in both the sagittal (P = 0.011) and coronal (P = 0.014) planes. Conclusions: Retropatellar tibial nail insertion is not associated with more anterior knee pain when compared with infrapatellar nail insertion but is associated with more accurate nail insertion and fracture reduction. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Early Death Following Primary Total Hip Arthroplasty

This study aims to describe the timing, cause of death, and excess surgical mortality associated with primary total hip arthroplasty when compared to a population awaiting primary total hip arthroplasty. Mortality rates were calculated at cutoffs of 30 and 90 days post-operation or following the addition to the waiting list. Cause of death was recorded from the death certificate. An excess surgical mortality of 0.256% at 30 days (P = 0.002) and 0.025% at 90 days post-operation (P = 0.892), unaffected by age or gender, was seen with myocardial infarction and pneumonia the cause of death in the majority of cases. By using a more appropriate control population, an excess surgical mortality at 30 days post-operation is demonstrated; the effect diminishes at 90 days post-operation.

Repair of Torn Avascular Meniscal Cartilage Using Undifferentiated Autologous Mesenchymal Stem Cells: From In Vitro Optimization to a First-in-Human Study

Meniscal cartilage tears are common and predispose to osteoarthritis (OA). Most occur in the avascular portion of the meniscus where current repair techniques usually fail. We described previously the use of undifferentiated autologous mesenchymal stem cells (MSCs) seeded onto a collagen scaffold (MSC/collagen‐scaffold) to integrate meniscal tissues in vitro. Our objective was to translate this method into a cell therapy for patients with torn meniscus, with the long‐term goal of delaying or preventing the onset of OA. After in vitro optimization, we tested an ovine‐MSC/collagen‐scaffold in a sheep meniscal cartilage tear model with promising results after 13 weeks, although repair was not sustained over 6 months. We then conducted a single center, prospective, open‐label first‐in‐human safety study of patients with an avascular meniscal tear. Autologous MSCs were isolated from an iliac crest bone marrow biopsy, expanded and seeded into the collagen scaffold. The resulting human‐MSC/collagen‐scaffold implant was placed into the meniscal tear prior to repair with vertical mattress sutures and the patients were followed for 2 years. Five patients were treated and there was significant clinical improvement on repeated measures analysis. Three were asymptomatic at 24 months with no magnetic resonance imaging evidence of recurrent tear and clinical improvement in knee function scores. Two required subsequent meniscectomy due to retear or nonhealing of the meniscal tear at approximately 15 months after implantation. No other adverse events occurred. We conclude that undifferentiated MSCs could provide a safe way to augment avascular meniscal repair in some patients. Registration: EU Clinical Trials Register, 2010‐024162‐22. Stem Cells Translational Medicine 2017;6:1237–1248

Cement in Cement Revision of the Femoral Component Using a Collarless Triple Taper: A Midterm Clinical and Radiographic Assessment

This study describes the midterm clinical and radiological results of the cement in cement technique for the femur using a collarless triple taper. Radiographic assessment was made retrospectively from 44 patients at two time points. Clinical outcomes included the Oxford Hip Score, EQ5D and Self Reported Patient Satisfaction Scale. Implant and patient survival were also recorded. The mean clinical follow up period was 5years 3months and the radiological follow up 2years 10months. The mean OHS was 34, the mean EQ5D 0.814 and the mean SAPS 94. Kaplan-Meier survival with revision, as the end point was 95.2% at 11years with a survivorship of 76.5% with death as the end point. Cement in cement revision using a collarless triple tapered stem demonstrates promising results both clinically and radiologically at midterm follow up.

Comparison of Acetabular Bone Resection, Offset, Leg Length and Post Operative Function Between Hip Resurfacing Arthroplasty and Total Hip Arthroplasty

Controversy exists regarding the amount of acetabular bone resection, biomechanics and function of patients receiving either total hip arthroplasty (THA) or hip resurfacing arthroplasty (HRA). A cohort of patients undergoing 36 mm ceramic-on-ceramic THA (89) or metal-on-metal HRA (86) were compared. No difference was observed when the ratio of native femoral head size was compared to the implanted acetabular component size (1.15 ± 0.1 HRA c.f. 1.13 ± 0.1 THA). No difference was observed in acetabular offset, vertical centre of rotation or function (OHS mean 47 in both groups) but leg length discrepancy (1.8 mm c.f. 5.5 mm) and femoral offset did differ (0.6 mm c.f. 4.1 mm). This demonstrates that 36 mm ceramic-on-ceramic THA is not associated with more bone resection than HRA and achieves equivalent function whilst avoiding the problems of metal-on-metal bearings.

Computer Hexapod-Assisted Orthopaedic Surgery for the Correction of Tibial Deformities.

Summary: We describe the intraoperative use of the Taylor Spatial Frame to correct complex multiplanar deformities of the tibia before definitive internal stabilization using minimally invasive techniques. Thirteen consecutive procedures were performed in 12 patients. All deformities of the tibia were assessed with standardized radiographs allowing estimation of the center of rotation of angulation (CORA) or multiple CORA for multiplanar deformities. The cause of the deformity included both posttraumatic and metabolic conditions. A wide range of deformities was deemed appropriate for correction with this technique. All underwent acute intraoperative correction through single or multiple osteotomies mediated by the Taylor Spatial Frame before definitive internal stabilization using a locked intramedullary nail. Deformity correction and restoration of the tibial mechanical axis was achieved in all cases. There were no cases of nonunion. There was only one superficial infection necessitating removal of implants following union of the osteotomies. Two patients developed a common peroneal nerve palsy, 1 had full recovery at 18 months and 1 had partial recovery. Another patient developed a tibial artery pseudoaneurysm treated successfully with a percutaneous stent. This series demonstrates the use of the Taylor Spatial Frame for acute intraoperative correction of complex tibial deformities and definitive internal stabilization.