10-Year Prospective Clinical and Radiological Evaluation After Matrix-Induced Autologous Chondrocyte Implantation and Comparison of Tibiofemoral and Patellofemoral Graft Outcomes.

BACKGROUND: Long-term outcomes in larger cohorts after matrix-induced autologous chondrocyte implantation (MACI) are required. Furthermore, little is known about the longer-term clinical and radiological outcomes of MACI performed in the tibiofemoral versus patellofemoral knee joint. PURPOSE: To present the 10-year clinical and radiological outcomes in patients after MACI and compare outcomes in patients undergoing tibiofemoral versus patellofemoral MACI. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between September 2002 and December 2012, 204 patients who underwent MACI were prospectively registered into a research program and assessed preoperatively and at 2, 5, and 10 years postoperatively. Of these patients, 168 were available for clinical review at 10 years, with 151 (of a total of 182) grafts also assessed via magnetic resonance imaging (MRI). Patients were evaluated using the Knee injury and Osteoarthritis Outcome Score, a visual analog scale for pain frequency and severity, satisfaction, and peak isokinetic knee extensor and flexor strength. Limb symmetry indices (LSIs) were calculated for strength measures. Grafts were scored on MRI scans via the MOCART (magnetic resonance observation of cartilage repair tissue) system, with a focus on tissue infill and an overall MRI graft composite score. RESULTS: All patient-reported outcome measures improved (P < .0001) up to 2 years after surgery. Apart from the significant increase (P = .004) in the peak isokinetic knee extensor LSI, no other patient-reported outcome measure or clinical score had changed significantly from 2 to 10 years. At the final follow-up, 92% of patients were satisfied with MACI to provide knee pain relief, with 76% satisfied with their ability to participate in sports. From 2 to 10 years, no significant change was seen for any MRI-based MOCART variable nor the overall MRI composite score. Of the 151 grafts reviewed via MRI at 10 years, 14 (9.3%) had failed, defined by graft delamination or no graft tissue on MRI scan. Furthermore, of the 36 patients (of the prospectively recruited 204) who were not available for longer-term review, 7 had already proceeded to total knee arthroplasty, and 1 patient had undergone secondary MACI at the same medial femoral condylar site because of an earlier graft failure. Therefore, 22 patients (10.8%) essentially had graft failure over the period. At the final follow-up, patients who underwent MACI in the tibiofemoral (vs patellofemoral) joint reported significantly better Knee injury and Osteoarthritis Outcome Score subscale scores for Quality of Life (P = .010) and Sport and Recreation (P < .001), as well as a greater knee extensor strength LSI (P = .002). Even though the tibiofemoral group demonstrated better 10-year MOCART scores for tissue infill (P = .027), there were no other MRI-based differences (P > .05). CONCLUSION: This study reports the long-term review of a prospective series of patients undergoing MACI, demonstrating good clinical scores, high levels of patient satisfaction, and acceptable graft survivorship at 10 years. Patients undergoing tibiofemoral (vs patellofemoral) MACI reported better long-term clinical outcomes, despite largely similar MRI-based outcomes.

Genome-wide association study identifying variants related to performance and injury in high-performance athletes.

A growing body of evidence exists supporting the role that genetic variation plays in athletic performance and injury. This study sought to identify genetic variants associated with performance and lower limb musculoskeletal injury in a high-level athletic cohort. A total of 126 Estonian National Team members (Olympic athletes and participants of International Championships) (104 males, 82.5%) underwent a genome-wide association analysis between 2017 and 2018, to identify single-nucleotide polymorphisms (SNPs) associated with performance and/or injury. The athletic cohort was stratified within each sport based on performance and whether they were a medalist (n = 29) or not (n = 97), whether they sustained an injury (n = 47) or not (n = 79), and the type of injury (patella tendinopathy n = 22, Achilles tendinopathy n = 17, hamstring injury n = 3, anterior cruciate ligament rupture n = 6). Three SNPs demonstrated strong genome-wide association with athletic performance (podium/medalist versus not), including DSG1 (rs10502567, OR 14.3) and DSG4 (rs73410248, OR 17.4), while 76 SNPs demonstrated suggestive significance. Overall, 37 SNPs gave genome-wide suggestive association with any type of injury, including PAPPA2 (rs11580456, OR 13.8) and MAS1 (rs220735, rs170219, OR 3.1) which demonstrated positive signal with multiple SNPs. Several genes demonstrated positive association for the specific injury types, including COL22A1 (rs3924862) and PLXNA2 (rs11799530), as well as PAPPA2 (rs11580456), DOK5 (rs73142922), GNG12 (rs28435277), and DAP (rs267959, rs2930047, rs1080440, rs267939). The current study identified genetic variants associated with high-level athletic performance and musculoskeletal injury. Further work is required to permit integration of this and future knowledge into individualized training practices, as well as injury mitigation and rehabilitation programs.

Defining the mutation sites in chickpea nodulation mutants PM233 and PM405.

BACKGROUND: Like most legumes, chickpeas form specialized organs called root nodules. These nodules allow for a symbiotic relationship with rhizobium bacteria. The rhizobia provide fixed atmospheric nitrogen to the plant in a usable form. It is of both basic and practical interest to understand the host plant genetics of legume root nodulation. Chickpea lines PM233 and PM405, which harbor the mutationally identified nodulation genes rn1 and rn4, respectively, both display nodulation-deficient phenotypes. Previous investigators identified the rn1 mutation with the chickpea homolog of Medicago truncatula nodulation gene NSP2, but were unable to define the mutant rn1 allele. We used Illumina and Nanopore sequencing reads to attempt to identify and characterize candidate mutation sites responsible for the PM233 and PM405 phenotypes. RESULTS: We aligned Illumina reads to the available desi chickpea reference genome, and did a de novo contig assembly of Nanopore reads. In mutant PM233, the Nanopore contigs allowed us to identify the breakpoints of a ~ 35 kb deleted region containing the CaNSP2 gene, the Medicago truncatula homolog of which is involved in nodulation. In mutant PM405, we performed variant calling in read alignments and identified 10 candidate mutations. Genotyping of a segregating progeny population narrowed that pool down to a single candidate gene which displayed homology to M. truncatula nodulation gene NIN. CONCLUSIONS: We have characterized the nodulation mutation sites in chickpea mutants PM233 and PM405. In mutant PM233, the rn1 mutation was shown to be due to deletion of the entire CaNSP2 nodulation gene, while in mutant PM405 the rn4 mutation was due to a single base deletion resulting in a frameshift mutation between the predicted RWP-RK and PB1 domains of the NIN nodulation gene. Critical to characterization of the rn1 allele was the generation of Nanopore contigs for mutant PM233 and its wild type parent ICC 640, without which the deletional boundaries could not be defined. Our results suggest that efforts of prior investigators were hampered by genomic misassemblies in the CaNSP2 region of both the desi and kabuli reference genomes.

A 2-year prospective clinical and bone density evaluation, with a subset undergoing radiostereometric analysis, using the Absolut cemented stem.

BACKGROUND: Total hip arthroplasty (THA) is common though the investigation of new prostheses requires a practical, step-wise introduction. This study reports the 2-year clinical results and periprosthetic bone mineral density (BMD) changes, along with a subset undergoing Radiostereometric analysis (RSA), in patients undergoing primary cemented THA using a new highly polished, double tapered, collarless femoral stem (Absolut). METHODS: Between August 2013 and December 2016, 47 patients with a mean age of 74.2 years (range 36-89) underwent 51 THAs with the Absolut. All patients underwent clinical assessment pre-surgery and at 6 weeks, 3, 12 and 24 months using the Oxford and Harris Hip Scores, as well as Dual Energy X-ray Absorptiometry (DEXA) to assess BMD within 2-4 weeks post-surgery, 12 and 24 months. RSA was undertaken in a patient subset (the first n = 30) early post-surgery (1-2 days) and 3, 12 and 24 months. RESULTS: All clinical scores significantly improved (p < 0.05). RSA revealed a mean subsidence of 0.78 mm at 3 months, 1.23 mm at 12 months and 1.51 mm at 24 months. Anterior-posterior and medial-lateral translation was negligible. A significant increase (p = 0.020) in BMD was observed in Gruen zone 1, though no significant changes were observed for any other zone up until 2 years. Two patients acquired an early post-operative deep vein thrombosis that were treated accordingly and resolved, with no further complications or re-operations. CONCLUSION: The Absolut cemented femoral stem demonstrated good outcomes, BMD changes consistent with sound prosthesis integration and patterns of post-operative micromotion observed in other successful cemented stems.

A long-lasting guided bone regeneration membrane from sequentially functionalised photoactive atelocollagen.

The fast degradation of collagen-based membranes in the biological environment remains a critical challenge, resulting in underperforming Guided Bone Regeneration (GBR) therapy leading to compromised clinical results. Photoactive atelocollagen (AC) systems functionalised with ethylenically unsaturated monomers, such as 4-vinylbenzyl chloride (4VBC), have been shown to generate mechanically competent materials for wound healing, inflammation control and drug delivery, whereby control of the molecular architecture of the AC network is key. Building on this platform, the sequential functionalisation with 4VBC and methacrylic anhydride (MA) was hypothesised to generate UV-cured AC hydrogels with reduced swelling ratio, increased proteolytic stability and barrier functionality for GBR therapy. The sequentially functionalised atelocollagen precursor (SAP) was characterised via TNBS and ninhydrin colourimetric assays, circular dichroism and UV-curing rheometry, which confirmed nearly complete consumption of collagen's primary amino groups, preserved triple helices and fast (< 180 s) gelation kinetics, respectively. Hydrogel's swelling ratio and compression modulus were adjusted depending on the aqueous environment used for UV-curing, whilst the sequential functionalisation of AC successfully generated hydrogels with superior proteolytic stability in vitro compared to both 4VBC-functionalised control and the commercial dental membrane Bio-Gide®. These in vitro results were confirmed in vivo via both subcutaneous implantation and a proof-of-concept study in a GBR calvarial model, indicating integrity of the hydrogel and barrier defect, as well as tissue formation following 1-month implantation in rats. STATEMENT OF SIGNIFICANCE: Collagen-based membranes remain a key component in Guided Bone Regeneration (GBR) therapy, but their properties, e.g. proteolytic stability and soft tissue barrier functionality, are still far from optimal. This is largely attributed to the complex molecular configuration of collagen, which makes chemical accessibility and structure-function relations challenging. Here, we fabricated a UV-cured hydrogel network of atelocollagen, whereby triple helices were sequentially functionalised with two distinct ethylenically unsaturated monomers. The effects of the sequential functionalisation and UV-curing on the macroscopic properties, degradation behaviour and GBR capability were investigated in vitro and in vivo. The results highlight the key role of the sequential functionalisation and provide important insights for the design of future, longer-lasting resorbable membranes for GBR therapy.

Journey-Deuce bicompartmental knee arthroplasty with the addition of computer navigation achieves good clinical outcomes and implant survival at 10 years.

PURPOSE: To report 10-year outcomes and survivorship in patients undergoing bicompartmental knee arthroplasty (BCKA) using the Journey-Deuce prosthesis in a consecutive prospective case series. METHODS: Between November 2006 and November 2009, 41 patients with a mean age of 69.6 years (range 51-86) underwent 51 bicompartmental knee arthroplasties with the Journey-Deuce knee prosthesis. All patients presented with symptomatic medial and patellofemoral compartment osteoarthritis, with intact cruciate ligaments and a preserved lateral compartment on plain radiographs and Magnetic Resonance Imaging. Clinical assessment was undertaken pre-surgery and at 1, 2, 5 and 10 years post-surgery using the Oxford Knee Score (OKS), EuroQol Group 5-Dimension self-reported questionnaire (EQ-5D) and maximal active range of motion (ROM). RESULTS: 30 patients (37 knees) were followed-up at a mean time of 11.4 years (SD 1.1; range 10.5-14.0). Eight patients (ten knees) were deceased and three could not be contacted at final review. No major component revision was performed. Pre-operative OKS 25.4 (SD 5.2; range 15-40), knee flexion 116.4° (SD 10.3°; range 100°-140°) and EQ-5D 70.5 (SD 19.9; range 25-95). 10-year OKS 43.5 (SD 4.1; range 32-48), knee flexion 127.3° (SD 11.1°; range 105°-144°) and EQ-5D 77.4 (SD 9.3; range 60-100). The OKS (p < 0.0001), EQ-5D (p = 0.024) and active knee flexion ROM (p < 0.0001) all significantly improved from pre-surgery to 1-year post-surgery, with no further significant changes in these scores between any post-operative time period up until 10 years. 32% (7/22) of tibial and 45% (10/22) of femoral components showed progressive radiolucencies between 2 and 5-year and 10-year follow-up. CONCLUSIONS: This is the largest cohort of patients having undergone BCKA (with the Journey-Deuce prosthesis) with longest follow-up described in the literature. At 10 years, patients presented with significantly improved clinical outcomes, comparable to other surgical arthroplasty options. No major component revision was performed. Progressive radiolucencies were noted in 32% of tibial and 45% of femoral components without corresponding clinical signs of loosening. LEVEL OF EVIDENCE: Level III.

Is the grass always greener? Land surface phenology reveals differences in peak and season-long vegetation productivity responses to climate and management.

Vegetation phenology-the seasonal timing and duration of vegetative phases-is controlled by spatiotemporally variable contributions of climatic and environmental factors plus additional potential influence from human management. We used land surface phenology derived from the Advanced Very High Resolution Radiometer and climate data to examine variability in vegetation productivity and phenological dates from 1989 to 2014 in the U.S. Northwestern Plains, a region with notable spatial heterogeneity in climate, vegetation, and land use. We first analyzed interannual trends in six phenological measures as a baseline. We then demonstrated how including annual-resolution predictors can provide more nuanced insights into measures of phenology between plant communities and across the ecoregion. Across the study area, higher annual precipitation increased both peak and season-long productivity. In contrast, higher mean annual temperatures tended to increase peak productivity but for the majority of the study area decreased season-long productivity. Annual precipitation and temperature had strong explanatory power for productivity-related phenology measures but predicted date-based measures poorly. We found that relationships between climate and phenology varied across the region and among plant communities and that factors such as recovery from disturbance and anthropogenic management also contributed in certain regions. In sum, phenological measures did not respond ubiquitously nor covary in their responses. Nonclimatic dynamics can decouple phenology from climate; therefore, analyses including only interannual trends should not assume climate alone drives patterns. For example, models of areas exhibiting greening or browning should account for climate, anthropogenic influence, and natural disturbances. Investigating multiple aspects of phenology to describe growing-season dynamics provides a richer understanding of spatiotemporal patterns that can be used for predicting ecosystem responses to future climates and land-use change. Such understanding allows for clearer interpretation of results for conservation, wildlife, and land management.

Hierarchically Assembled Type I Collagen Fibres as Biomimetic Building Blocks of Biomedical Membranes.

Wet spinning is an established fibre manufacturing route to realise collagen fibres with preserved triple helix architecture and cell acceptability for applications in biomedical membranes. However, resulting fibres still need to be chemically modified post-spinning to ensure material integrity in physiological media, with inherent risks of alteration of fibre morphology and with limited opportunities to induce fibrillogenesis following collagen fixation in the crosslinked state. To overcome this challenge, we hypothesised that a photoactive type I collagen precursor bearing either single or multiple monomers could be employed to accomplish hierarchically assembled fibres with improved processability, macroscopic properties and nanoscale organisation via sequential wet spinning and UV-curing. In-house-extracted type I rat tail collagen functionalised with both 4-vinylbenzyl chloride (4VBC) and methacrylate residues generated a full hydrogel network following solubilisation in a photoactive aqueous solution and UV exposure, whereby ~85 wt.% of material was retained following 75-day hydrolytic incubation. Wide-angle X-ray diffraction confirmed the presence of typical collagen patterns, whilst an averaged compression modulus and swelling ratio of more than 290 kPa and 1500 wt.% was recorded in the UV-cured hydrogel networks. Photoactive type I collagen precursors were subsequently wet spun into fibres, displaying the typical dichroic features of collagen and regular fibre morphology. Varying tensile modulus (E = 5 ± 1 - 11 ± 4 MPa) and swelling ratio (SR = 1880 ± 200 - 3350 ± 500 wt.%) were measured following post-spinning UV curing and equilibration with phosphate-buffered saline (PBS). Most importantly, 72-h incubation of the wet spun fibres in PBS successfully induced renaturation of collagen-like fibrils, which were fixed following UV-induced network formation. The whole process proved to be well tolerated by cells, as indicated by a spread-like cell morphology following a 48-h culture of L929 mouse fibroblasts on the extracts of UV-cured fibres.

An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.

PURPOSE: To investigate the mid-term outcomes of an accelerated return to full weight bearing (WB) after matrix-induced autologous chondrocyte implantation (MACI). METHODS: This randomized study allocated 35 patients (37 knees) to a 6 week (n = 18) or 8 week (n = 19) return to full WB after MACI. Patients were evaluated pre-operatively and at 1, 2 and minimum 5 years (range 5.5-7 years), using the KOOS, SF-36, visual analogue pain scale, 6-min walk test and active knee range of motion (ROM). Peak isokinetic knee extensor and flexor strength was assessed, with limb symmetry indices (LSIs) calculated. Magnetic resonance imaging (MRI) was undertaken to evaluate the repair tissue, and an MRI composite score was calculated. RESULTS: While no group differences (n.s.) were observed, significant improvement was observed for all patient-reported outcome measures (p < 0.05), 6-min walk distance (p = 0.040), active knee flexion (p = 0.002) and extension (p < 0.0001) ROM, and the LSI for peak knee extensor strength (p < 0.0001). At final review, 87.5% (6 weeks) and 82.4% (8 weeks) of patients were satisfied overall. A non-significant decline (n.s.) was observed for the MRI composite score from 1-year post-surgery to final review, with no significant MRI-based differences (n.s.) between groups. At final review, two grafts (6-week n = 1, 8-week n = 1) demonstrated MRI-based graft failure, while an additional patient had progressed toward knee arthroplasty (8.1% failure rate at minimum 5 years). CONCLUSIONS: The 6-week return to full WB after MACI provided comparable clinical and MRI-based outcomes beyond 5 years post-surgery, without jeopardizing the graft. This 6-week WB protocol is faster than those previously proposed and studied. LEVEL OF EVIDENCE: II.

Long-term Prospective Clinical and Magnetic Resonance Imaging-Based Evaluation of Matrix-Induced Autologous Chondrocyte Implantation.

BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging midterm clinical outcomes, although published studies presenting longer-term clinical and radiological outcomes, across varied tibiofemoral and patellofemoral graft locations, are scarce. PURPOSE: To present the clinical and radiological outcomes a minimum of 10 years after surgery in a consecutive series of patients who underwent MACI in the tibiofemoral or patellofemoral knee joint. Secondly, to investigate any association between outcomes and patient characteristics, graft parameters, and injury and surgery history. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Overall, 87 patients (99 grafts: 57 medial femoral condyle, 24 lateral femoral condyle, 11 trochlea, 7 patella) were prospectively evaluated clinically and with magnetic resonance imaging (MRI) before surgery and at 2, 5, and minimum 10 years after MACI (mean, 13.1 years; range, 10.5-16 years). Patients were evaluated with a range of patient-reported outcome measures (PROMs), including the Knee injury and Osteoarthritis Outcome Score (KOOS) and patient satisfaction. The 6-minute walk test, active knee range of motion, and peak isokinetic knee extensor and flexor strength were assessed. Limb symmetry indices (LSIs) were calculated for strength measures. MRI was undertaken to evaluate the repair tissue, and an MRI composite score was calculated. RESULTS: All PROMs significantly improved (P < .05) over the pre- to postoperative period. Apart from KOOS Sport (P = .018) and the LSI for peak isokinetic knee extensor strength (P = .005), which significantly improved, no significant change (P > .05) was observed from 2 years after surgery to final follow-up (range, 10.5-16 years) in all other PROMs, 6-minute walk distance, active knee range of motion, and the LSI for peak isokinetic knee flexor strength. At final follow-up, while the mean LSIs for peak isokinetic knee flexor and extensor strength were 96.9% and 95.7%, respectively, 74.7% of patients were satisfied with their ability to participate in sports, and 88.5% were satisfied overall. A nonsignificant decline was observed for tissue infill (P = .211) and the MRI composite score (P = .099) from 2 years to final review. At final MRI review, 9 grafts (9.1%) had failed. While no significant association (P > .05) was observed between clinical or MRI-based outcomes and patient demographics (age, body weight, body mass index), defect size, or the duration of preoperative symptoms, the number of previous surgical procedures was significantly and negatively associated with KOOS Symptoms (P = .015), KOOS Sport (P = .011), and the degree of tissue infill (P = .045). CONCLUSION: MACI provided high levels of satisfaction and adequate graft survivorship as visualized on MRI at 10.5 to 16 years after surgery.

Post-fatigue fracture resistance of premolar teeth restored with endocrowns: An in vitro investigation.

OBJECTIVES: To evaluate the post-fatigue load-to-failure and failure modes of endodontically treated premolar teeth restored with endocrowns fabricated from different CAD/CAM materials. MATERIALS AND METHODS: A total of 60 extracted human, single-rooted premolar teeth were endodontically treated and sectioned horizontally 2 mm above the cementoenamel junction. Sectioned teeth were restored using two reconstruction designs: endocrowns (Cendo) or post-crowns (Cpost) (n = 30 p/g). In each group, reconstructions were fabricated from 3 different CAD/CAM substrates (n = 10 p/g); a resin-based composite (Cera), a lithium disilicate glass ceramic (LiSi) and a monolithic, translucent zirconia (Zir). Additional 10 intact teeth were used as control. Restored teeth were subjected to dynamic fatigue test (10-50 N, 600,000 cycles) and thermocycling (5-55 °C, 1500 cycles). Load-to-failure and failure mode was determined following application of a static, 45° oblique compressive load on each specimen. One-way and Two-way analysis of variance (ANOVA), Tukey's post hoc and chi-square tests were used to determine statistically significant interactions among experimental and control groups. RESULTS: All specimens survived the mechanical and thermal fatigue tests. A statistically significant interaction between reconstruction design and material type was observed (p  <  0.001). CpostZir and CendoCera groups exhibited significantly higher post-fatigue load-to-failure when compared to other materials of the same reconstruction design (p ≤ 0.001). The highest frequency of catastrophic failures was observed with Zir reconstructions in both designs. Intact teeth exhibited significantly higher load-to-failure when compared to all groups (p ≤ 0.042) except CpostZir (p = 0.345). CONCLUSION: Single piece, CAD/CAM resin composite endocrowns can present a reliable option for restoring endodontically treated premolar teeth. CLINICAL SIGNIFICANCE: Endocrowns can be as effective as post-crowns provided appropriate preparation; material selection; and bonding protocols are utilized. Clinicians need to be cautious when prescribing zirconia endocrowns to restore premolar teeth owing to the low fracture resistance and high risk of catastrophic failures.

Development and characterisation of dental composites containing anisotropic fluorapatite bundles and rods.

OBJECTIVES: To develop dental composites incorporating fluorapatite (FA) crystals as a secondary filler and to characterise degree of conversion, key mechanical properties and fluoride release. METHODS: FA rod-like crystals and bundles were hydrothermally synthesised and characterised by scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS), X-ray diffraction (XRD) and 19F MAS-NMR. Composites were formulated containing BisGMA/TEGDMA/BisEMA and barium-aluminium-silicate glass (0FA). FA crystals were incorporated at 10 (10FA), 20 (20FA), 30 (30FA) and 40wt% (40FA) maintaining a filler content of 80wt% (63-67vol%). Degree of conversion (DC), flexural strength (FS), flexural modulus (FM), fracture toughness (K1C), Vickers hardness (HV) and 2-body wear were measured. Fluoride release was measured in neutral and acidic buffers. RESULTS: XRD and 19F MAS-NMR confirmed that only FA was formed, whilst SEM revealed the presence of single rods and bundles of nano-rods. DC ranged between 56-60% (p>0.05). FA composites showed lower FM and lower FS (p<0.05), but comparable wear resistance and HV (p>0.05) to 0FA. 30FA and 40FA showed similar K1C to 0FA (p>0.05), with SEM showing evidence of toughening mechanisms, whereas 10FA and 20FA showed lower K1C (p<0.05). FA containing composites released fluoride that was proportional to the amount of FA incorporated (p<0.05) but only under acidic conditions. SIGNIFICANCE: The addition of FA to the experimental composites reduced strength and stiffness but not the DC, hardness or wear rate. 30FA and 40FA had a higher K1C compared to other FA groups. Fluoride release occurred under an accelerated acidic regime, suggesting potential as a bioactive 'smart' composite.

POST-OPERATIVE SPORT PARTICIPATION AND SATISFACTION WITH RETURN TO ACTIVITY AFTER MATRIX-INDUCED AUTOLOGOUS CHONDROCYTE IMPLANTATION IN THE KNEE.

BACKGROUND: Returning to a satisfactory activity level is expected by patients after cartilage repair, and may define overall surgical success. PURPOSE: To investigate: 1) the level and improvement in activity in patients at two years after matrix-induced autologous chondrocyte implantation (MACI), 2) what factors are associated with post-operative (and improvement in) activity level, and 3) whether patients are satisfied with their ability to participate in recreational and/or sporting activities. STUDY DESIGN: Prospective cohort. METHODS: One hundred and fifty patients that underwent MACI were included in this analysis (83 tibiofemoral and 67 patellofemoral). All patients completed the Tegner Activity Scale (TAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) pre-surgery and at two years (range: 24-26 months) post-surgery, as well as a questionnaire evaluating satisfaction with their ability to return to recreational and sporting activities. RESULTS: The TAS significantly improved (p<0.001) from 2.97 (SD 0.92, range 0-7) to 4.09 (SD 1.49, range 0-9), while the KOOS Sport significantly improved (p<0.0001) from 27.5 (SD 23.1, range 0-95) to 61.1 (SD 27.3, range 0-100). Overall, 88 patients (59%) improved ≥ 1 point on the TAS, while 121 patients (81%) improved ≥ 10 points on the KOOS Sport, previously reported as the minimal detectable change for each. Patient age, duration of symptoms (DOS) and gender were associated with post-operative activity level, though body mass index (BMI), defect size and concomitant procedures were not. Overall, 128 patients (85%) were satisfied with their ability to return to recreational activities, with 99 (66%) satisfied with sport participation. The two-year TAS, and TAS improvement, were significantly associated with satisfaction in performing recreational activities (two-year TAS, rho=-0.42, p<0.0001; TAS improvement, r=-0.33, p<0.0001) and sport participation (two-year TAS, rho=-0.49, p<0.0001; TAS improvement, r=-0.37, p<0.0001). CONCLUSIONS: The TAS and KOOS Sport significantly improved after MACI, though only 59% of patients improved ≥ 1 point on the TAS. Despite this, 85% and 66% of patients were satisfied with their ability to return to recreational activities and participate in sport, respectively. Age, DOS and gender were associated with activity, and overall these findings can be used to provide realistic activity expectations to patients undergoing MACI. LEVEL OF EVIDENCE: Level 3, prospective cohort study.

The Genetic Variations Associated With Time to Aseptic Loosening After Total Joint Arthroplasty.

BACKGROUND: Total joint arthroplasty (TJA) is one of the most frequent surgical procedures performed in modern hospitals, and aseptic loosening is the most common indication for revision surgeries. We conducted a systemic exploration of potential genetic determinants for early aseptic loosening. METHODS: Data from 423 patients undergoing TJA were collected and analyzed. Three analytical groups were formed based on joint arthroplasty status. Group 1 were TJA patients without symptoms of aseptic loosening of at least 1 year, group 2 were patients with primary TJA, and group 3 were patients receiving revision surgery because of aseptic loosening. Genome-wide genotyping comparing genotype frequencies between patients with and without aseptic loosening (group 3 vs groups 1 and 2) was conducted. A case-control association analysis and linear modeling were applied to identify the impact of the identified genes on implant survival with time to the revision as an outcome measure. RESULTS: We identified 52 single-nucleotide polymorphisms (SNPs) with a genome-wide suggestive P value less than 10-5 to be associated with the implant loosening. The most remarkable odds ratios (OR) were found with the variations in the IFIT2/IFIT3 (OR, 21.6), CERK (OR, 12.6), and PAPPA (OR, 14.0) genes. Variations in the genotypes of 4 SNPs-rs115871127, rs16823835, rs13275667, and rs2514486-predicted variability in the time to aseptic loosening. The time to aseptic loosening varied from 8 to 16 years depending on the genotype, indicating a substantial effect of genetic variance. CONCLUSION: Development of the aseptic loosening is associated with several genetic variations and we identified at least 4 SNPs with a significant effect on the time for loosening. These data could help to develop a personalized approach for TJA and loosening management.

Minimum 10-Year Clinical and Radiological Outcomes of a Randomized Controlled Trial Evaluating 2 Different Approaches to Full Weightbearing After Matrix-Induced Autologous Chondrocyte Implantation.

BACKGROUND: Longer term outcomes after matrix-induced autologous chondrocyte implantation (MACI) are lacking, while early postoperative weightbearing (WB) management has traditionally been conservative. PURPOSE: To investigate the longer term clinical and radiological outcomes after an 8-week (vs 12-week) WB protocol after MACI. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A randomized study design allocated 70 patients to an 8- (n = 34) or 12-week (n = 36) approach to full WB after MACI of the medial or lateral femoral condyle. Patients were evaluated preoperatively; at 3, 12, and 24 months after surgery; and at 5 and 10 years after surgery. At 10 years (range, 10.5-11.5 years), 60 patients (85.7%; 8 weeks: n = 29; 12 weeks: n = 31) were available for review. Clinical outcomes included patient-reported outcomes, maximal isokinetic knee extensor and flexor strength, and functional hop capacity. High-resolution magnetic resonance imaging (MRI) was undertaken to assess the quality and quantity of repair tissue per the MOCART (magnetic resonance observation of cartilage repair tissue) system. A combined MRI composite score was also evaluated. RESULTS: Clinical and MRI-based scores for the full cohort significantly improved (P < .05) over the 10-year period. Apart from the Tegner activity score, which improved (P = .041), as well as tissue structure (P = .030), which deteriorated, there were no further statistically significant changes (P > .05) from 5 to 10 years. There were no 10-year differences between the 2 WB rehabilitation groups. At 10 years, 81.5% and 82.8% of patients in the 8- and 12-week groups, respectively, demonstrated good-excellent tissue infill. Graft failure was observed on MRI at 10 years in 7 patients overall, which included 4 located on 10-year MRI (8 weeks: n = 1; 12 weeks: n = 3) and a further 3 patients (8 weeks: n = 1; 12 weeks: n = 2) not included in the current analysis who proceeded to total knee arthroplasty. At 10 years, 93.3% of patients were satisfied with MACI for relieving their pain, with 83.3% satisfied with their ability to participate in sport. CONCLUSION: MACI provided high satisfaction levels and tissue durability beyond 10 years. The outcomes of this randomized trial demonstrate a safe 8-week WB rehabilitation protocol without jeopardizing longer term outcomes.

Identification of novel sarcoma risk genes using a two-stage genome wide DNA sequencing strategy in cancer cluster families and population case and control cohorts.

BACKGROUND: Although familial clustering of cancers is relatively common, only a small proportion of familial cancer risk can be explained by known cancer predisposition genes. METHODS: In this study we employed a two-stage approach to identify candidate sarcoma risk genes. First, we conducted whole exome sequencing in three multigenerational cancer families ascertained through a sarcoma proband (n = 19) in order to prioritize candidate genes for validation in an independent case-control cohort of sarcoma patients using family-based association and segregation analysis. The second stage employed a burden analysis of rare variants within prioritized candidate genes identified from stage one in 560 sarcoma cases and 1144 healthy ageing controls, for which whole genome sequence was available. RESULTS: Variants from eight genes were identified in stage one. Following gene-based burden testing and after correction for multiple testing, two of these genes, ABCB5 and C16orf96, were determined to show statistically significant association with cancer. The ABCB5 gene was found to have a higher burden of putative regulatory variants (OR = 4.9, p-value = 0.007, q-value = 0.04) based on allele counts in sarcoma cases compared to controls. C16orf96, was found to have a significantly lower burden (OR = 0.58, p-value = 0.0004, q-value = 0.003) of regulatory variants in controls compared to sarcoma cases. CONCLUSIONS: Based on these genetic association data we propose that ABCB5 and C16orf96 are novel candidate risk genes for sarcoma. Although neither of these two genes have been previously associated with sarcoma, ABCB5 has been shown to share clinical drug resistance associations with melanoma and leukaemia and C16orf96 shares regulatory elements with genes that are involved with TNF-alpha mediated apoptosis in a p53/TP53-dependent manner. Future genetic studies in other family and population cohorts will be required for further validation of these novel findings.

Deformation and retentive force following in vitro cyclic fatigue of cobalt-chrome and aryl ketone polymer (AKP) clasps.

OBJECTIVE: To compare the retention force of individual clasps made from cobalt chromium (CoCr) or new aryl ketone polymer (AKP) material, Ultaire™ AKP, following prolonged fatigue testing along ideal and non-ideal paths of removal and to assess 3D deformation of the active and passive clasp tips. METHODS: CoCr and AKP clasps were manufactured in their standard, respective processes, digitally scanned prior to testing, then cycled 15,000 times over an e.max analogue crown in artificial saliva. Retentive load was measured in situ, as a function of cycles. Clasps were rescanned to assess deformation and along with their antagonists subjected to SEM to assess localised wear. RESULTS: Distortion of the CoCr clasps was consistently larger than Ultaire™ AKP clasps, irrespective of removal path. CoCr clasps had significantly higher retentive forces than AKP clasps, for both removal paths. Ultaire™ AKP clasps showed a lower but relatively constant retentive force. The non-ideal path of removal affected retentive forces for both clasp materials. SEM showed localised removal of glaze for e.max crowns used with CoCr clasps. SIGNIFICANCE: Ultaire™ AKP clasps showed significantly less permanent deformation and lower retentive force than CoCr clasps. Unlike CoCr, the Ultaire™ AKP clasps did not work harden, nor had as large a reduction in retentive force and accompanying permanent deformation; the retentive force for the Ultaire™ AKP clasps was consistent over 15,000 cycles of fatigue mimicking prolonged clinical use. The AKP material was more robust; showing minimal deformation even in non-ideal paths of removal, as many patients would routinely use.

Quantifying Ecological Integrity of Terrestrial Systems to Inform Management of Multiple-Use Public Lands in the United States.

The concept of ecological integrity has been applied widely to management of aquatic systems, but still is considered by many to be too vague and difficult to quantify to be useful for managing terrestrial systems, particularly across broad areas. Extensive public lands in the western United States are managed for diverse uses such as timber harvest, livestock grazing, energy development, and wildlife conservation, some of which may degrade ecological integrity. We propose a method for assessing ecological integrity on multiple-use lands that identifies the components of integrity and levels in the ecological hierarchy where the assessment will focus, and considers existing policies and management objectives. Both natural reference and societally desired environmental conditions are relevant comparison points. We applied the method to evaluate the ecological integrity of shrublands in Nevada, yielding an assessment based on six indicators of ecosystem structure, function, and composition, including resource- and stressor-based indicators measured at multiple scales. Results varied spatially and among indicators. Invasive plant cover and surface development were highest in shrublands in northwest and southeast Nevada. Departure from reference conditions of shrubland area, composition, patch size, and connectivity was highest in central and northern Nevada. Results may inform efforts to control invasive species and restore shrublands on federal lands in Nevada. We suggest that ecological integrity assessments for multiple-use lands be grounded in existing policies and monitoring programs, incorporate resource- and stressor-based metrics, rely on publicly available data collected at multiple spatial scales, and quantify both natural reference and societally desired resource conditions.

Association Between Isokinetic Knee Strength and Perceived Function and Patient Satisfaction With Sports and Recreational Ability After Matrix-Induced Autologous Chondrocyte Implantation.

BACKGROUND: Returning to a sound level of activity after matrix-induced autologous chondrocyte implantation (MACI) is important to patients. Evaluating the patient's level of satisfaction with his or her sports and recreational ability is critical. PURPOSE: To investigate (1) satisfaction with sports and recreational ability after MACI and (2) the role that knee strength plays in self-reported knee function and satisfaction. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Isokinetic knee strength was assessed in 97 patients at 1, 2, and 5 years after MACI to calculate hamstrings-quadriceps ratios and peak knee extensor and flexor torque limb symmetry indices (LSIs). The Sports and Recreation subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS Sports/Rec) was completed. A satisfaction scale was used to evaluate how satisfied the patients were with their ability to return to recreational activities and their ability to participate in sport. Associations between knee strength LSI, KOOS Sports/Rec, and satisfaction with recreational and sporting activities were assessed through use of multivariable linear and logistic regression, with adjustment for confounders. Mediation analysis was conducted to assess the extent to which self-reported knee function mediated associations between strength LSI and satisfaction. RESULTS: Satisfaction with the ability to return to recreational activities was achieved in 82.4%, 85.6%, and 85.9% of patients at 1, 2, and 5 years, respectively, and satisfaction with sports participation was achieved in 55.7%, 73.2%, and 68.5% of patients at 1, 2, and 5 years, respectively. Knee extension torque LSIs were associated with KOOS Sports/Rec after adjustment for confounders over 1, 2, and 5 years (5-year regression coefficient, 6.0 points; 95% CI, 1.4-10.7; P = .012). KOOS Sports/Rec was associated with the likelihood of being satisfied at all time points (recreation: 5-year adjusted odds ratio [OR], 2.26; 95% CI, 1.48-3.46; P < .001; and sports: 5-year adjusted OR, 1.98; 95% CI, 1.47-2.68; P < .001). In a multivariable mediation model, the knee extension torque LSI was associated with satisfaction directly (standardized coefficient, 0.16; 95% CI, 0.03-0.28; P = .017) and indirectly via KOOS Sports/Rec (standardized coefficient, 0.19; 95% CI, 0.01-0.38; P = .027), the latter representing 55% of the total association of knee extension torque LSI with satisfaction. CONCLUSION: Knee extensor symmetry was associated with satisfaction in recreational and sporting ability, both directly and indirectly, via self-reported sports and recreation-related knee function. Restoring strength deficits after MACI is important for achieving optimal outcomes.

Intracoronal stress transfer through enamel following RBC photopolymerisation: A synchrotron X-ray study.

OBJECTIVES: To measure the spatial distribution of crystallographic strain in tooth enamel induced by the photo-polymerisation of a dimethacrylate resin based composite cavity restoration. METHODS: Six sound first premolar teeth, allocated into two groups (n=3), were prepared with mesio-occlusal distal cavities. The enamel was machined at the point of maximum convexity on the outer tooth to create a vertical fin of thickness 100µm and 0.5mm depth to allow for synchrotron X-ray diffraction measurements. 2D diffraction patterns were used to determine crystallite orientation and quantify changes in the hydroxyapatite crystal lattice parameters, before and after photo-polymerisation of a composite material placed in the cavity, to calculate strain in the respective axis. The composite was photo-polymerised with either relatively high (1200mWcm-2, group 1) or low (480mWcm-2, group 2) irradiances using LED or quartz halogen light sources, respectively. A paired t-test was used to determine significant differences in strain between irradiance protocols at ɑ=0.001. RESULTS: Photo-polymerisation of the composite in the adjacent cavity induced significant changes in both the crystallographic c and a axes of the enamel measurement area. However the magnitude of strain was low with ∼0.1% difference before and after composite photo-polymerisation. Strain in enamel was not uniformly distributed and varied spatially as a function of crystallite orientation. Increased alignment of crystallites perpendicular to the cavity wall was associated with higher c axis strain. Additionally, strain was significantly greater in the c (p<0.001) and a axis (p<0.001) when using a high irradiance photo-polymerisation protocol. SIGNIFICANCE: Although cuspal deflection is routinely measured to indirectly assess the 'global' effect of composite shrinkage on the tooth-restoration complex, here we show that absolute strains generated in enamel are low, indicating strain relief mechanisms may be operative. The use of low irradiance protocols for photo-polymerisation resulted in reduced strain.