Characterization of synovial fluid from periprosthetic infection in revision total joint arthroplasty by single-molecule microscopy

Periprosthetic joint infection is among the most common and severe complications in total joint arthroplasty. Today, a combination of different methods is used for diagnosis because no single method with sufficient sensitivity and specificity is available. In this study, we explored the usability of single-molecule microscopy to characterize synovial fluid samples from periprosthetic joint infections. Patients (n = 27) that needed revision arthroplasty underwent the routine diagnostic procedures for periprosthetic joint infection of the University Hospital in Bonn. Additionally, the diffusion rate of two probes, dextran and hyaluronan, was measured in small volumes of periprosthetic synovial fluid samples using single-molecule microscopy. To evaluate the suitability of single-molecule microscopy to detect PJI the AUC for both markers was calculated. The diffusion rate of hyaluronan in periprosthetic synovial fluid from patients with septic loosening was faster than in samples from patients with aseptic loosening. Single-molecule microscopy showed excellent diagnostic performance, with an area under the receiver operating characteristic curve of 0.93, and allowed the detection of periprosthetic joint infection in patients that would be challenging to diagnose with current methods. For the first time, single-molecule microscopy was used to detect periprosthetic joint infection. Our results are encouraging to study the value of single-molecule microscopy in a larger patient cohort. The speed and accuracy of single-molecule microscopy can be used to further characterize synovial fluid, potentially allowing intraoperative diagnosis of periprosthetic joint infections in the future.     

Implant surface alters compartmental-specific contributions to fixation strength in rats

Mechanical fixation of the implant to host bone is an important contributor to orthopedic implant survivorship. The relative importance of bone-implant contact, trabecular bone architecture, and cortical bone geometry to implant fixation strength has never been directly tested, especially in the settings of differential implant surface properties. Thus, using a rat model where titanium rods were placed into the intramedullary canal of the distal femur, we determined the relative contribution of bone-implant contact and peri-implant bone architecture to the fixation strength in implants with different surface roughness: highly polished and smooth (as-received) and dual acid-etched (DAE) implants. Using a training set that maximized variance in implant fixation strength, we initially examined correlation between implant fixation strength and outcome parameters from microcomputed tomography and found that osseointegration volume per total volume (OV/TV), trabecular bone volume per total volume (BV/TV), and cortical thickness (Ct.Th) were the single best compartment-specific predictors of fixation strength. We defined separate regression models to predict implant fixation strength for as-received and DAE implants. When the training set models were applied to independent validation sets, we found strong correlations between predicted and experimentally measured implant fixation strength, with r² = .843 in as received and r² = .825 in DAE implants. Interestingly, for as-received implants, OV/TV explained more of the total variance in implant fixation strength than the other variables, whereas in DAE implants, Ct.Th had the most explanatory power, suggesting that surface topography of implants affects which bone compartment is most important in providing implant fixation strength.     

Model predictive control of a collaborative manipulator considering dynamic obstacles

Collaborative robots have to adapt its motion plan to a dynamic environment and variation of task constraints. Currently, they detect collisions and interrupt or postpone their motion plan to prevent harm to humans or objects. The more advanced strategy proposed in this article uses online trajectory optimization to anticipate potential collisions, task variations, and to adapt the motion plan accordingly. The online trajectory planner pursues a model predictive control approach to account for dynamic motion objectives and constraints during task execution. The prediction model relates reference joint velocities to actual joint positions as an approximation of built-in robot tracking controllers. The optimal control problem is solved with direct collocation based on a hypergraph structure, which represents the nonlinear program and allows to efficiently adapt to structural changes in the optimization problem caused by moving obstacles. To demonstrate the effectiveness of the approach, the robot imitates pick-and-place tasks while avoiding self-collisions, semistatic, and dynamic obstacles, including a person. The analysis of the approach concerns computation time, constraint violations, and smoothness. It shows that after model identification, order reduction, and validation on the real robot, parallel integrators with compensation for input delays exhibit the best compromise between accuracy and computational complexity. The model predictive controller can successfully approach a moving target configuration without prior knowledge of the reference motion. The results show that pure hard constraints are not sufficient and lead to nonsmooth controls. In combination with soft constraints, which evaluate the proximity of obstacles, smooth and safe trajectories are planned.     

Is Use of BMP-2 Associated with Tumor Growth and Osteoblastic Differentiation in Murine Models of Osteosarcoma?

BackgroundThe putative benefit of rhBMP-2 is in the setting of limb reconstruction using structural allografts, whether it be allograft-prosthetic composites, osteoarticular allografts, or intercalary segmental grafts. There are also potential advantages in augmenting osseointegration of uncemented endoprosthetics and in reducing infection. Recombinant human BMP-2 might mitigate nonunion in structural allograft augmented osteosarcoma limb salvage surgery; however, its use is limited because of concerns about the prooncogenic effects of the agent.Questions/purposes(1) To assess if BMP-2 signaling influences osteosarcoma cell line growth. (2) To characterize degree of osteosarcoma cell line osteoblastic differentiation in response to BMP-2. (3) To assess if BMP-2 signaling has a consistent effect on local or systemic tumor burden in various orthotopic murine models of osteosarcoma.MethodsIn this study, 143b, SaOS-2 and DLM8-M1 osteosarcoma cell lines were transfected with BMP-2 cDNA controlled by a constitutive promoter (experimental) or an empty vector (control) using a PiggyBac transposon system. Cellular proliferation was assessed using a quantitative MTT colorimetric assay. Osteoblastic differentiation was compared between control and experimental cell lines using quantitative real-time polymerase chain reaction of the osteoblastic markers connective tissue growth factor, Runx-2, Osterix, alkaline phosphatase and osteocalcin. Experimental and control cell lines were injected into the proximal tibia of either NOD-SCID (143b and SaOS-2 xenograft model), or C3H (DLM8-M1 syngeneic model) mice. Local tumor burden was quantitatively assessed using tumor volume caliper measurements and bioluminescence, and qualitatively assessed using post-mortem ex vivo microCT. Lung metastasis was qualitatively assessed by the presence of bioluminescence, and incidence was confirmed using histology. rhBMP-2 soaked absorbable collagen sponges (experimental) and sterile-H₂O soaked absorbable collagen sponges (control) were implanted adjacent to 143b proximal tibial cell line injections to compare the effects of exogenous BMP-2 application with endogenous upregulation.ResultsConstitutive expression of BMP-2 increased the in vitro proliferation of 143b cells (absorbance values 1.2 ± 0.1 versus 0.89 ± 0.1, mean difference 0.36 [95% CI 0.12 to 0.6]; p = 0.01), but had no effect on SaOS-2 and DLM8-M1 cell proliferation. In response to constitutive BMP-2 expression, 143b cells had no differences in osteoblastic differentiation, while DLM8-M1 cells downregulated the early marker connective tissue growth factor (mean ΔCt 0.2 ± 0.1 versus 0.6 ± 0.1; p = 0.002) and upregulated the early-mid range marker Runx-2 (mean ΔCt -0.8 ± 0.1 versus -1.1 ± 0.1; p = 0.002), and SaOS-2 cells upregulated the mid-range marker Osterix (mean ΔCt -2.1 ± 0.6 versus -3.9 ± 0.6; p = 0.002). Constitutive expression of BMP-2 resulted in greater 143b and DLM8-M1 local tumor volume (143b: 307.2 ± 106.8 mm³ versus 1316 ± 387.4 mm³, mean difference 1009 mm³ [95% CI 674.5 to 1343]; p < 0.001, DLM8-M1 week four: 0 mm³ versus 326.1 ± 72.8 mm³, mean difference 326.1 mm³ [95% CI 121.2 to 531]; p = 0.009), but modestly reduced local tumor growth in SaOS-2 (9.5 x 10⁸ ± 8.3x10⁸ photons/s versus 9.3 x 10⁷ ± 1.5 x 10⁸ photons/s, mean difference 8.6 x 10⁸ photons/s [95% CI 5.1 x 10⁸ to 1.2 x 10⁹]; p < 0.001). Application of exogenous rhBMP-2 also increased 143b local tumor volume (495 ± 91.9 mm³ versus 1335 ± 102.7 mm³, mean difference 840.3 mm³ [95% CI 671.7 to 1009]; p < 0.001). Incidence of lung metastases was not different between experimental or control groups for all experimental conditions.ConclusionsAs demonstrated by others, ectopic BMP-2 signaling has unpredictable effects on local tumor proliferation in murine models of osteosarcoma and does not consistently result in osteosarcoma cell line differentiation. Further investigations into other methods of safe bone and soft tissue healing augmentation and the use of differentiation therapies is warranted.Clinical RelevanceOur results indicate that BMP-2 has the potential to stimulate the growth of osteosarcoma cells that are poorly responsive to BMP-2 mediated osteoblastic differentiation. As this differentiation potential is unpredictable in the clinical setting, BMP-2 may promote the growth of microscopic residual tumor burden after resection. Our study provides further support for the recommendation to avoid the use of BMP-2 after limb-salvage surgery in patients with osteosarcoma.     

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European Spine Journal - Depression, anxiety, catastrophising, and fear-avoidance beliefs are key "yellow flags" (YFs) that predict a poor outcome in back patients. Most surgeons...     

Long-term,prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m² at 6 months and 52.5 ± 23.0 ml/min/1.73 m² at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.     

Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant – a historical prospective study

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X-rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO₂/FiO₂ ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized.