The Incidence and Clinical Relevance of Graft Hypertrophy After Matrix-Based Autologous Chondrocyte Implantation

Background: Graft hypertrophy is the most common complication of periosteal autologous chondrocyte implantation (p-ACI). Purpose: The aim of this prospective study was to analyze the development, the incidence rate, and the persistence of graft hypertrophy after matrix-based autologous chondrocyte implantation (mb-ACI) in the knee joint within a 2-year postoperative course. Study Design: Case series; Level of evidence, 4. Methods: Between 2004 and 2007, a total of 41 patients with 44 isolated cartilage defects of the knee were treated with the mb-ACI technique. The mean age of the patients was 35.8 years (standard deviation [SD], 11.3 years), and the mean body mass index was 25.9 (SD, 4.2; range, 19-35.3). The cartilage defects were arthroscopically classified as Outerbridge grades III and IV. The mean area of the cartilage defect measured 6.14 cm2 (SD, 2.3 cm2). Postoperative clinical and magnetic resonance imaging (MRI) examinations were conducted at 3, 6, 12, and 24 months to analyze the incidence and course of the graft. Results: Graft hypertrophy developed in 25% of the patients treated with mb-ACI within a postoperative course of 1 year; 16% of the patients developed hypertrophy grade 2, and 9% developed hypertrophy grade 1. Graft hypertrophy occurred primarily in the first 12 months and regressed in most cases within 2 years. The International Knee Documentation Committee (IKDC) and visual analog scale (VAS) scores improved during the postoperative follow-up time of 2 years. There was no difference between the clinical results regarding the IKDC and VAS pain scores and the presence of graft hypertrophy. Conclusion: The mb-ACI technique does not lead to graft hypertrophy requiring treatment as opposed to classic p-ACI. The frequency of occurrence of graft hypertrophy after p-ACI and mb-ACI is comparable. Graft hypertrophy can be considered as a temporary excessive growth of regenerative cartilage tissue rather than a true graft hypertrophy. It is therefore usually not a persistent or systematic complication in the treatment of circumscribed cartilage defects with mb-ACI

Effect of the defect localization and size on the success of third-generation autologous chondrocyte implantation in the knee joint

Introduction. Femoral and patellar cartilage defects with a defect size > 2.5 cm2 are a potential indication for an autologous chondrocyte implantation (ACI). However, the influence of the localization and the absolute and relative defect size on the clinical outcome has not yet been determined. The purpose of this study is to analyze the influence of the localization and the absolute and relative defect size on the clinical outcome after third-generation autologous chondrocyte implantation. Methods. A total of 50 patients with cartilage defects of the knee were treated with third-generation autologous chondrocyte implantation (Novocart® 3D). A match paired analysis was performed of 25 treated femoral and 25 treated patella defects with a follow-up of three years. MRI data was used to do the manual segmentation of the cartilage layer throughout the knee joint. The defect size was determined by taking the defect size measured in the MRI in relation to the whole cartilage area. The clinical outcome was measured by the IKDC score and VAS pre-operatively and after six, 12, 24, and 36 months post-operatively. Results. IKDC and VAS scores showed a significant improvement from the baseline in both groups. Femoral cartilage defects showed significantly superior clinical results in the analyzed scores compared to patellar defects. The femoral group improved IKDC from 33.9 (SD 18.1) pre-operatively to 71.5 (SD 17.4) after three years and the VAS from 6.9 (SD 2.9) pre-operatively to 2.4 (SD 2.5) after three years. In the patellar group, IKDC improved from 36.1 (SD 12.6) pre-operatively to 54.7 (SD 20.3) after three years and the VAS improved from 6.7 (SD 2.8) pre-operatively to 3.4 (SD 2.) after three years. Regarding the defect size, results showed that the same absolute defect size at med FC (4.8, range 2–15) and patella (4.6, range 2–12) has a significantly different share of the total cartilaginous size of the joint compartment (med FC: 6.7, range 1.2–13.9; pat: 18.9, range 4.0–47.0). However, there was no significant influence of the relative defect size on the clinical outcome in either patellar or femoral localization. Conclusion. Third-generation autologous chondrocyte implantation in ACI-treated femoral cartilage defects leads to a superior clinical outcome in a follow-up of three years compared with patellar defects. No significant influence of the defect size was found in either femoral or patellar cartilage defects

Increase in the Tibial Slope Reduces Wear after Medial Unicompartmental Fixed-Bearing Arthroplasty of the Knee

Introduction. Unicompartmental arthroplasty of the knee in patients with isolated medial osteoarthritis gives good results, but survival is inferior to that of total knee prosthesis. Knees may fail because positioning of the prosthesis has been suboptimal. The aim of this study was to investigate the influence of the tibial slope on the rate of wear of amedial fixed-bearing unicompartmental knee arthroplasty. Materials and Methods. We simulated wear on a medial fixed-bearing unicompartmental knee prosthesis (Univation) in vitro with a customised, four-station, and servohydraulic knee wear simulator, which exactly reproduced the walking cycle (International Organisation for Standardisation (ISO) 14243-1: 2002(E)). The medial prostheses were inserted with 3 different posterior tibial slopes: 0 degrees, 4 degrees, and 8 degrees (n = 3 in each group). Results. The wear rate decreased significantly between 0 degrees and 4 degrees slope from 10.4 (SD 0.62) mg/million cycles to 3.22 (SD 1.71) mg/million cycles. Increasing the tibial slope to 8 degrees did not significantly change the wear rate. Discussion. As an increase in the tibial slope reduced the wear rate in a fixed-bearing prosthesis, a higher tibial slope should be recommended. However, other factors that are influenced by the tibial slope (e.g.,the tension of the ligament) must also be considered

Increase in the Tibial Slope Reduces Wear after Medial Unicompartmental Fixed-Bearing Arthroplasty of the Knee

Introduction. Unicompartmental arthroplasty of the knee in patients with isolated medial osteoarthritis gives good results, but survival is inferior to that of total knee prosthesis. Knees may fail because positioning of the prosthesis has been suboptimal. The aim of this study was to investigate the influence of the tibial slope on the rate of wear of amedial fixed-bearing unicompartmental knee arthroplasty. Materials and Methods. We simulated wear on a medial fixed-bearing unicompartmental knee prosthesis (Univation) in vitro with a customised, four-station, and servohydraulic knee wear simulator, which exactly reproduced the walking cycle (International Organisation for Standardisation (ISO) 14243-1: 2002(E)). The medial prostheses were inserted with 3 different posterior tibial slopes: 0 degrees, 4 degrees, and 8 degrees (n = 3 in each group). Results. The wear rate decreased significantly between 0 degrees and 4 degrees slope from 10.4 (SD 0.62) mg/million cycles to 3.22 (SD 1.71) mg/million cycles. Increasing the tibial slope to 8 degrees did not significantly change the wear rate. Discussion. As an increase in the tibial slope reduced the wear rate in a fixed-bearing prosthesis, a higher tibial slope should be recommended. However, other factors that are influenced by the tibial slope (e.g.,the tension of the ligament) must also be considered

Graft Hypertrophy After Third-Generation Autologous Chondrocyte Implantation Has No Correlation With Reduced Cartilage Quality: Matched-Pair Analysis Using T2-Weighted Mapping

Background: Graft hypertrophy is common after matrix-based autologous chondrocyte implantation (ACI) in the knee joint. However, it is not clear whether graft hypertrophy is a complication or an adjustment reaction in the cartilage regeneration after ACI. Purpose: To analyze the cartilage quality of the ACI regeneration with graft hypertrophy using T2-weighted mapping. Study Design: Cohort study;Level of evidence, 2. Methods: A total of 91 patients with isolated cartilage defects (International Cartilage Repair Society [ICRS] grade III-IV) of the knee were treated with Novocart 3D, a third-generation, matrix-based, ACI procedure in the knee joint. All patients were evaluated with a standardized magnetic resonance imaging protocol after 3, 6, 12, 24, 36, and 48 months postoperatively. For morphological and biochemical assessment, the T2-weighted relaxation times of the ACI grafts as well as the healthy surrounding cartilage were determined. The results of the 20 patients with graft hypertrophy (hypertrophic group) were compared with the results of 21 matched patients without graft hypertrophy (nonhypertrophic group) after ACI. Match-paired analysis was performed by comparison of age, defect size, and body mass index. Results: The T2-weighted relaxation times of the ACI graft showed significant improvement, with values decreasing from 52.1 milliseconds to 33.3 milliseconds after 48 months. After 12 months, the T2-weighted relaxation times were constant and comparable with the healthy surrounding cartilage. Graft hypertrophy was seen in 22% (n = 20) of the patients who underwent ACI. A significant difference in T2-weighted relaxation times between the hypertrophic and nonhypertrophic ACI grafts could not be found except after 36 months (hypertrophic T2-weighted relaxation time/nonhypertrophic T2-weighted relaxation time: 3 months, 48.0/56.4 ms, P = .666;6 months, 45.6/42.5 ms, P = .280;12 months, 39.3/34.7 ms, P = .850;24 months, 34.8/32.2 ms, P =.742;36 months, 34.6/38.2 ms, P = .030;48 months, 34.2/32.3 ms, P = .693). Conclusion: The T2-weighted relaxation time of the ACI graft cartilage showed significant improvements over the observation period of 4 years postoperatively. After 2 years, graft maturation was completed. Graft hypertrophy after ACI was seen in 22% of the patients. Reduced cartilage quality could not be found in patients with graft hypertrophy after ACI

The influence of different footprint preparation techniques on tissue regeneration in rotator cuff repair in an animal model

Introduction: Rotator cuff tears are common diseases of the upper extremity. There are no recommendations to the surgeon on how to prepare the footprint to ensure optimal tendon-to-bone healing. However, biologic augmentation using stem cells and growth factors is considered to encourage the healing process of the tendon. The aim of the study was to investigate the biomechanical and histological outcome of different footprint preparations in rotator cuff repair. Material and methods: One hundred and eighty-nine Sprague-Dawley rats were randomly assigned to either spongialization, radiofrequency ablation or an untreated control group. Rats were killed after 1 or 7 weeks for histological evaluation or after 7 weeks for biomechanical testing. Results: Histological evaluation showed better tissue organization in the control and spongialization group compared to the radiofrequency ablation group. The highest collagen I to collagen III quotient was found in the control group, followed closely by the spongialization group. Measured quotients showed a decrease in the values after 1 week compared to the values after 7 weeks, except in the radiofrequency ablation group, where an increase was detected. A significant difference was found in the load to failure test comparing the radiofrequency ablation group to the spongialization group (p = 0.0409) and control group (p = 0.014), but not comparing the spongialization group to the control group (p = 0.2456). Conclusions: The results of this study suggest that spongialization of the footprint before attaching the torn supraspinatus tendon can lead to better structural properties and higher quality of tendon-to-bone restoration at the insertion area when compared with radiofrequency ablation

Reference Values of Flexion and Supination in the Elbow Joint of a Cohort without Shoulder Pathologies

Background After surgery of the long head of the biceps tendon, the examination of the biceps brachii muscle function and strength is common clinical practice. The muscle strength is usually compared with the uninjured contralateral side or with a matched pair group assuming that the uninjured side can be used as an appropriate reference. Hypothesis/Purpose The purpose of this study was to define reference values of the supination and flexion strength in the elbow joint and to investigate the influence of the arm positions and various anthropometric factors. Methods 105 participants without any shoulder pathologies were enrolled. A full medical history was obtained and a physical examination was performed. The bilateral isometric testing included the supination torque in various forearm positions and elbow flexion strength with a custom engineered dynamometer. Multiple linear regression analysis was used to investigate the correlation of the strength and anthropometric factors. Results Only age and gender were significant supination and flexion strength predictors of the elbow. Hence, it was possible to calculate a gender-specific regression line for each forearm position to predict the age-dependent supination torque. The supination strength was greatest with the arm in 90° elbow flexion and the upper arm in full pronation

Infraglenoidal scapular notching in reverse total shoulder replacement: a prospective series of 60 cases and systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>The impact of infraglenoidal scapular notching in reversed total shoulder arthroplasty (RTSA) is still controversially discussed. Our goal was to evaluate its potential influence on subjective shoulder stability and clinical outcome. We hypothesized that subjective instability and clinical outcome after implantation of RTSA correlates with objective scapular notching.</p> <p>Methods</p> <p>Sixty shoulders were assessed preoperatively and at minimum 2-year follow-up for active range of motion and by use of the Oxford instability score, Rowe score for instability, Constant score for pain, Constant shoulder score, DASH score. All shoulders were evaluated on anterior-posterior and axillary lateral radiographic views. These X-ray scans were classified twice by two orthopaedic surgeons with respect to infraglenoidal scapular notching according to the classification of Nerot. Notching was tested for correlation with clinical outcome scores to the evaluated notching.</p> <p>Results</p> <p>We found no significant correlation between infraglenoidal scapular notching and clinical outcomes after a mid-term follow-up from 24 to 60 months, but at the final follow-up of 60 months and more, we did see statistically significant, positive correlations between infraglenoidal scapular notching and the Constant pain score as well as active range of motion. At mean follow-up of 42 months (range from 24 to 96 months) we found no significant correlation between subjective instability and infraglenoidal scapular notching.</p> <p>Conclusions</p> <p>We conclude that patients' subjective impression on their shoulders' stability is not correlating with radiological signs of infraglenoidal scapular notching. Nevertheless clinical parameters are affected by infraglenoidal scapular notching, at least in the long term</p

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

Data driven gradient flows

We present a framework enabling variational data assimilation for gradient flows in general metric spaces, based on the minimizing movement (or Jordan-Kinderlehrer-Otto) approximation scheme. After discussing stability properties in the most general case, we specialise to the space of probability measures endowed with the Wasserstein distance. This setting covers many non-linear partial differential equations (PDEs), such as the porous medium equation or general drift-diffusion-aggregation equations, which can be treated by our methods independent of their respective properties (such as finite speed of propagation or blow-up). We then focus on the numerical implementation of our approach using an primal-dual algorithm. The strength of our approach lies in the fact that by simply changing the driving functional, a wide range of PDEs can be treated without the need to adopt the numerical scheme. We conclude by presenting detailed numerical examples