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Purpose: The purpose of the present study was to investigate the mid-term outcomes of a single-stage cell-based procedure in patients with knee focal symptomatic cartilage defects using matrix-induced culture-expanded autologous AD-MSCs. It was hypothesised that the increased number of autologous AD-MSCs after culture expansion is a safe and efficient cartilage repair procedure, which improves overtime chondrogenesis in cartilage lesions METHODS: Twenty-five consecutive patients treated for a symptomatic cartilage defect were prospectively followed for 3 years. The median age of patients was 30.5 (range 16-43) with a median BMI of 23.6 kg/m 2 (range 19-29) and an average size of the lesion of 3.5 cm 2 (range 2-6). All patients underwent a single-stage procedure consisting in filling each defect with autologous culture-expanded mesenchymal stem cells embedded in a trimmed-to-fit commercially available biodegradable matrix. Pre-operative and post-operative evaluation included knee-related clinical and functional evaluation based on objective and subjective scores at 6, 12, 24 and 36 months and MRI evaluation of the repair tissue using the MOCART score at 12 and 24 months., Results: Clinical outcomes recorded significant improvements (p < 0.05) at the final follow-up compared with baseline as following: all subcategories of KOOS Score, the IKDC subjective from 40.9 (range 20.7-65.6) to 76.9 (range 42-90.3), Tegner Activity Score from 3 (range 2-4) to 4 (range 3-4), VAS for pain from 6 (range 4-8) to 1 (range 0-3). All patients improve significantly their IKDC objective scores. The MRI findings showed complete filling of the defect and integration to the border zone for 65% of the patients. Two patients underwent post-operative biopsies and the histological analysis demonstrated the presence of hyaline-like tissue., Conclusions: Adipose-derived culture-expanded mesenchymal stem cells were shown to be an efficient and safe single-stage cell-based procedure for symptomatic, full-thickness knee chondral lesions. The findings of the present study demonstrate that all patients presented significant mid-term clinical, functional and radiological improvement., Level of Evidence: IV.

The purpose of this study was to evaluate and describe the clinical results of complete arthroscopic synovectomy through the four arthroscopic portals in the knees affected by diffuse pigmented villonodular synovitis (DPVNS). Between 2009 and 2012, 21 patients (15 men and 6 women) with the diffuse form of PVNS of the knee were enrolled in the study after qualification. The clinical diagnosis was confirmed by magnetic resonance imaging and postsurgical pathologic examination. All patients underwent complete synovectomy through posteromedial, posterolateral, anteromedial, and anterolateral portals. Each patient was evaluated before treatment and followed up for a minimum of 5 years (range: 60-79 months) using the Lysholm score and International Knee Documentation Committee (IKDC) score. Both Lysholm score and IKDC scores were significantly improved in all study participants. No cases of clinical recurrence, infection, joint stiffness, or neurovascular lesions were observed. This study showed that an attentive arthroscopic synovectomy is a safer alternative with better clinical outcomes, with no clinical recurrences., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen-hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions., Methods: In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness., Results: A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups., Conclusions: This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions., Level of Evidence: I.

Total knee replacement is an accepted standard of care for the treatment of advanced knee osteoarthritis with good results in the vast majority of older patients. The use in younger and more active populations, however, remains controversial due to concerns over activity restrictions, implant survival, and patient satisfaction with the procedure. It is in these younger patient populations that alternatives to arthroplasty are increasingly being explored. Historically, osteotomy was utilized to address unicompartmental pain from degeneration and overload, for example, after meniscectomy. Utilization rates of osteotomy have fallen in recent years due to the increasing popularity of partial and total knee arthroplasty. This article explores the indications and outcomes of traditional unloading osteotomy, as well as newer options that are less invasive and offer faster return to function.

Conflicting clinical outcomes have been reported recently with the use of an osteochondral scaffold plugs for cartilage repair in the knee. In this study, twenty patients were consecutively treated for their cartilage lesions with the synthetic plug technique. These patients were prospectively clinically evaluated with a mean follow-up of 34.15 months. Magnetic resonance imaging (MRI) was used for morphologic analysis of the cartilage repair. The patients included in this study showed a significant gradual clinical improvement after the osteochondral scaffold plug. However, this clinical improvement was not confirmed by the MRI findings of this cohort study. Subchondral bone changes were seen in all patients on MRI and deficient filling of the defect was noticed in in 30.7% of the cases at 24 months of follow-up. There was no evidence found to support osteoconductive bone ingrowth. Therefore, the use of this type of osteochondral scaffold plug in osteochondral repair is questionable. Level of evidence: IV.

The treatment of osteochondral lesions is of great interest to orthopaedic surgeons because most lesions do not heal spontaneously. We present the short-term clinical outcome and MRI findings of a cell-free scaffold used for the treatment of these lesions in the knee. A total of 38 patients were prospectively evaluated clinically for two years following treatment with an osteochondral nanostructured biomimetic scaffold. There were 23 men and 15 women; the mean age of the patients was 30.5 years (15 to 64). Clinical outcome was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Tegner activity scale and a Visual Analgue scale for pain. MRI data were analysed based on the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system at three, 12 and 24 months post-operatively. There was a continuous significant clinical improvement after surgery. In two patients, the scaffold treatment failed (5.3%) There was a statistically significant improvement in the MOCART precentage scores. The repair tissue filled most of the defect sufficiently. We found subchondral laminar changes in all patients. Intralesional osteophytes were found in two patients (5.3%). We conclude that this one-step scaffold-based technique can be used for osteochondral repair. The surgical technique is straightforward, and the clinical results are promising. The MRI aspects of the repair tissue continue to evolve during the first two years after surgery. However, the subchondral laminar and bone changes are a concern., (©2015 The British Editorial Society of Bone & Joint Surgery.)

Meniscal allograft transplantation has emerged as a useful treatment for carefully selected patients. The aim of this review of meniscal allograft transplantation is to put this procedure into a clinical perspective. Since there still is a lack of consensus on how the success of meniscal transplantation should be evaluated it is difficult to compare study outcomes. Nevertheless, almost all studies report an increase in patient satisfaction and improvement in pain and function. Clinical and functional outcome is improved in the majority of patients. Progression of cartilage degeneration according to MRI and radiological criteria was halted in a number of patients, indicating a chondroprotective effect. Joint space narrowing is only significantly progressive at long-term follow-up. On magnetic resonance imaging, shrinkage is seen after some years, but more in lyophilized allografts. Second-look arthroscopy usually shows good healing to the capsule. Overall, the clinical results of this type of surgery are encouraging and long-lasting in a well selected patient population who suffered a total meniscectomy. Meniscal allografting appears to becoming the golden standard therapy for these type of patients., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this short-term pilot study was to determine the clinical and MRI outcome of a combination of microfracture with a cell-free polymer-based matrix for the treatment of cartilage defects in the knee., Methods: The technique was used for treatment of symptomatic cartilage defects in the knee. Five patients were prospectively evaluated during 2 years with use of the Knee injury and Osteoarthritis Outcome Score (KOOS), the Tegner activity scale and the visual analog scale (VAS). MRI data were analyzed based on the original and modified MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) scoring system at 6, 12 and 24 months of follow-up., Results: A gradual clinical improvement was observed during the follow-up. Adverse reactions to the matrix were not observed. The scaffold was firmly fixed with the use of bioresorbable pins. Both MOCART scoring systems revealed no significant deterioration or improvement in the repair tissue during the follow-up period. However, the majority of the patients exhibited subchondral lamina and bone changes. The formation of an intralesional osteophyte was observed in one case., Conclusions: The key finding in this study was that this procedure is safe for the treatment of cartilage defects in the knee. The patients showed a gradual clinical improvement postoperatively. Sixty percent (3/5) of the defects were adequately (complete or hypertrophic) filled with repair tissue at 2 years of follow-up., Level of Evidence: IV.

Long after the first reports on human autologous chondrocyte implantation (ACI) by Brittberg in 1994, the development of a so-called optimal technology for osteochondral tissue regeneration is still one of the most challenging issues in knee surgery. Although the short- and intermediate-term results of ACI appear to be favorable, resources are being directed toward scaffold research to improve the technology. Scaffolds used for osteochondral repair may be either cell or noncell-based before its implantation in the knee. The characteristics that make scaffolds optimal for clinical use are that they be biocompatible, biodegradable, permeable, reproducible, mechanically stable, noncytotoxic, and capable of serving as a temporary support for the cells while allowing for eventual replacement by matrix components synthesized by the implanted cells. There is a growing interest in noncell and last-minute cell seeding technologies since they allow for a one-step surgery eliminating the morbidity and necessity of a previous chondral biopsy. Although clinical and histological results from many, already clinically available scaffolds seem to be promising, improvements throughout these technologies and the developments of new ones are still necessary to obtain a more efficient biological response as well as to improve the implant's stability. Moreover, as the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention should be directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only.

Purpose: To present our short-term experience with an osteochondral scaffold plug (TruFit plug; Smith & Nephew, Andover, MA) for cartilage repair in the knee and, more importantly, to discuss our approach to treat early clinical failures., Methods: Twenty patients were consecutively treated for their cartilage lesions with the plug technique. These patients were prospectively clinically evaluated at 6 and 12 months of follow-up. Magnetic resonance imaging (MRI) was used for morphologic analysis of the cartilage repair. Biopsy samples were taken from 3 cases during revision surgery, allowing histologic assessment of the repair tissue., Results: The short-term clinical and MRI outcome of this pilot study are modest. No signs of deterioration of the repair tissue were observed. Of the 15 patients followed up during 1 year, 3 (20.0%) showed persistent clinical symptoms or even more clinical symptoms after insertion of the plug. These patients were considered as failures and therefore eligible for revision surgery. During revision surgery, the repair tissue was carefully removed. The remaining osteochondral defect was filled with autologous bone grafts. Immediate and persistent relief of symptoms was observed in all 3 patients. Histologic assessment of biopsy specimens taken during revision surgery showed fibrous vascularized repair tissue with the presence of foreign-body giant cells., Conclusions: The overall short-term clinical and MRI outcome of the osteochondral scaffold plug for cartilage repair in the knee is modest. In this pilot study a modest clinical improvement became apparent at 12 months of follow-up. MRI data showed no deterioration of the repair tissue. Of the 15 patients, 3 (20%) had persistent clinical symptoms after surgery. These patients were successfully treated with removal of the osteochondral plug remnants and the application of autologous bone grafts., Level of Evidence: Level IV, therapeutic case series., (Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

The meniscus plays an important role in the proprioceptive ability of the knee joint. The aim of this prospective study was to assess the short-term influence of a meniscus replacement on the proprioception of the knee. Fourteen patients who had undergone a fresh meniscal allograft transplantation between May 2001 and June 2003 were tested pre-operatively and 6 months post-operatively. Disability regarding pain, stiffness and functionality of the affected knee during daily activities was measured by the Western Ontario and McMaster Universities Arthritis (WOMAC) scale. The knee joint position sense was assessed using the Biodex System 3 isokinetic dynamometer. The results of the WOMAC scale showed no significant differences concerning pain, stiffness or knee function between the pre- and post-operative condition of the knee. Assessment of the knee joint position sense at a reference point of 70 degrees of knee flexion revealed a significant improvement of the proprioception of the operated knee at 6 months after surgery compared with the pre-operative condition. The results of this study suggest that although no significant improvement of pain and functionality of the operated knee occurred at this short-term follow-up period, a meniscal allograft transplantation seems to have a significant positive effect on the joint position sense of the previously meniscectomised knee.

Long-term data on the clinical outcome and the fate of the meniscus allograft after transplantation are scarce. In this study we present the clinical, radiological and MRI outcome of the meniscus graft and the articular cartilage after 42 meniscus allograft transplantations in 41 patients with a minimum follow-up of 10 years. A total of 27 medial and 15 lateral meniscal allografts were transplanted. Eleven of the medial allograft procedures were associated with a high tibial osteotomy. The patients were evaluated clinically at the time of transplantation and at the final follow-up using the modified HSS scoring system. The knee injury and osteoarthritis outcome score (KOOS) was used as an evaluation tool for patient-related outcome at the final follow-up. Joint space width narrowing and Fairbank changes were radiological outcome parameters, which were available for 32 patients. Femoral and tibial cartilage degeneration, graft extrusion and signal intensity were scored on MRI scans obtained in 17 patients approximately 1 year after transplantation and at the final follow-up (>10 years). For statistical analysis the patients were divided into three groups: lateral meniscal allograft (LMT), medial meniscal allograft transplantation with a high tibial osteotomy (MMT+HTO) and without (MMT). The modified HSS score revealed a significant improvement in pain and function at the final follow-up for all groups. Further analysis also revealed that an MMT+HTO procedure resulted in a greater improvement at the final follow-up when compared to MMT. Nonetheless, the KOOS scores obtained at the final follow-up revealed the presence of substantial disability and symptoms, in addition to a reduced quality of life. Radiographical analysis revealed no further joint space narrowing in 13/32 knees (41%). Fairbank changes remained stable in 9/32 knees (28%). MRI analysis showed no progression of cartilage degeneration in 6/17 knees (35%). An increased signal intensity of the allograft was present, as was partial graft extrusion in the majority of patients at the final follow-up. Seven cases had to be converted to a total knee arthroplasty during the follow-up; the overall failure rate was 18%. Long-term results after viable meniscus allograft transplantation are encouraging in terms of pain relief and improvement of function. Despite this significant improvement, substantial disability and symptoms were present in all investigated subgroups. Progression of further cartilage degeneration or joint space narrowing was absent in a considerable number of cases, indicating a potential chondroprotective effect. Level of evidence is therapeutic study, Level IV and retrospective analysis of prospectively collected data.

Background: Few medium-term or long-term reports on meniscal allograft transplantations are available. In this study, we present the results of a survival analysis of the clinical outcomes of our first 100 procedures involving transplantation of viable medial and lateral meniscal allografts performed in ninety-six patients., Methods: Thirty-nine medial and sixty-one lateral meniscal allografts were evaluated after a mean of 7.2 years. Survival analysis was based on specific clinical end points, with failure of the allograft defined as moderate occasional or persistent pain or as poor function. An additional survival analysis was performed to assess the results of the sixty-nine procedures that involved isolated use of a viable allograft (twenty of the thirty-nine medial allograft procedures and forty-nine of the sixty-one lateral allograft procedures) and of the thirteen viable medial meniscal allografts that were implanted in combination with a high tibial osteotomy in patients with initial varus malalignment of the lower limb., Results: Overall, eleven (28%) of the thirty-nine medial allografts and ten (16%) of the sixty-one lateral allografts failed. The mean cumulative survival time (11.6 years) was identical for the medial and lateral allografts. The cumulative survival rates for the medial and lateral allografts at ten years were 74.2% and 69.8%, respectively. The mean cumulative survival time and the cumulative survival rate for the medial allografts used in combination with a high tibial osteotomy were 13.0 years and 83.3% at ten years, respectively., Conclusions: Transplantation of a viable meniscal allograft can significantly relieve pain and improve function of the knee joint. Survival analysis showed that this beneficial effect remained in approximately 70% of the patients at ten years. This study identified the need for a prospective study comparing patients with similar symptoms and clinical findings treated with and without a meniscal allograft and followed for a longer period with use of clinical evaluation as well as more objective documentation tools regarding the actual fate of the allograft itself and the articular cartilage.

In patients complaining of recurrent patellar dislocations or persistent retropatellar pain due to a dysplastic femoral trochlea, we perform a Henri Dejour trochleoplasty. In this technique the femoral trochlea is deepened by removing the subchondral trochlear bone followed by incision, impaction and fixation of the cartilage flange along the trochlear groove. Between 1996 and 1999, 13 procedures were performed in 12 patients. Strictly lateral X-rays showed dysplasia of the trochlea, as defined by the "crossing sign", whether or not in combination with patella alta. Patients were assessed using the Larsen-Lauridsen score considering pain, stiffness, osteopatellar crepitus, flexion and loss of function. Although the majority of patients scored fair and poor on an objective scoring system, we achieved 77% good to very good subjective results. Although the result was not perfect, the patients were satisfied with the procedure. This technique might be a valuable alternative in cases of frank trochlear dysplasia associated with persistent retropatellar pain or recurrent patellar dislocations.

Objective: Studies on the biology of the human meniscus cell are scarce. The objective of our studies was to assess survival/proliferation of human meniscus cells in different culture conditions and to characterize the extracellular matrix (ECM) produced by these cells in these artificial environments. The composition of this ECM offers a variable to define the distinct meniscus cell phenotype., Materials and Methods: Human meniscus cells were isolated enzymatically from visually intact lateral and medial knee menisci. Cells were cultured in monolayer conditions or in alginate gel. The composition of the cell-associated matrix (CAM) accumulated by the isolated cells during culture was investigated and compared to the CAM of articular chondrocytes cultured in alginate using flow cytometry with fluorescein isothiocyanate-conjugated monoclonal antibodies against type I collagen, type II collagen and aggrecan. Additional cell membrane markers analysis was performed to further identify the different meniscus cell populations in the alginate culture conditions and meniscus tissue sections. Proliferation was analyzed using the Hoechst 33258 dye method. In some experiments, the effect of TGFbeta1 on some of these variables was investigated., Results: The CAM of monolayer cultured meniscus cells is composed of high amounts of type I and II collagen and low amounts of aggrecan. A major population of alginate cultured meniscus cells on the other hand synthesized a CAM containing high amounts of type I collagen, low amounts of type II collagen and high amounts of aggrecan. This population is CD44+CD105+CD34-CD31-. In contrast, a minor cell population in the alginate culture did not accumulate ECM and was mainly CD34+. The CAM of alginate cultured articular chondrocytes is composed of low amounts of type I collagen, high amounts of type II collagen and aggrecan. The expression of aggrecan and of type II collagen was increased by the addition of TGFbeta1 to the culture medium. The proliferation of meniscus cells is increased in the monolayer culture conditions. Cell numbers decrease slightly in the alginate culture, but can be increased after the addition of TGFbeta1., Conclusion: These results demonstrate that the human meniscus is populated by different cell types which can be identified by a distinct CAM composition and membrane marker expression. Unlike the monolayer culture conditions, the alginate culture conditions appear to favor a more fibrochondrocyte-like cell accumulating a CAM resembling the native tissue composition. This CAM composition is distinctly different from the CAM composition of phenotypically stable articular cartilage chondrocytes cultured in the same alginate matrix.

There have been numerous reports about the use of knee braces to prevent traumatic knee injuries. Despite the frequent use of braces, very few prospective studies have been performed to study the effect of knee braces for preventing anterior knee pain syndrome (AKPS). The purpose of this study was to assess the effectiveness of a dynamic patellofemoral brace (On-Track System, dj Orthopedics) in the prevention of AKPS. 167 military recruits without history of knee pain were randomized into two groups prior to the start of their 6-week basic military training (BMT) program. The first group (brace group) consisted of 54 recruits who wore the braces for all physical activities during these 6 weeks. 113 recruits served as a control group, and followed the same 6-week strenuous training program. Chi square statistics (Fisher exact test) were used to compare the number of AKPS patients in the brace group and in the non-brace group. Our results indicated that recruits in the brace group appeared to develop significantly less anterior knee pain compared to the recruits in the control group (p=0.020). Out of the 54 recruits in the brace group, ten (18.5%) developed anterior knee pain during this study. In the control group (n=113), 42 recruits (37%) developed anterior knee pain. We conclude that the result of the present study suggests that the use of a dynamic patellofemoral brace is an effective way to prevent the development of anterior knee pain in persons undergoing a strenuous training program.

Nocardia is a gram positive, aerobic branched actinomycete; it is an ubiquitous soil saprophyte. As an infecting agent it has been increasingly identified in humans, especially in immuno-suppressed hosts. Nocardia as a cause of septic arthritis is very unusual. The described genus was Nocardia asteroides in nearly all previously reported cases. We report an unusual case of spontaneous Nocardia farcinica septic arthritis of the left knee in a 68-year-old man, who was under systemic corticosteroids for chronic obstructive pulmonary disease. The diagnosis was rapidly made by Gram and acid-fast stains and later confirmed by culture. PCR was used to identify the subtype. The patient was treated successfully with sulphametaxazole-trimethoprim for six months. Our case re-emphasises, especially in the immuno-compromised patient, the importance of performing fungal and acid-fast bacilli cultures, besides the most common bacterial cultures for aerobic and anaerobic organisms, in order to identify less common organisms and to initiate early and adequate treatment.

The purpose of this prospective randomized intervention study was to evaluate the effect of two exercise protocols on reflex response time of vastus medialis obliquus (VMO), vastus lateralis (VL), in patients with anterior knee pain. Sixty patients were randomized into a 5-week treatment program, which consisted of only open kinetic chain tonification exercises (group I) (n = 30), or only closed kinetic chain tonification exercises (group II) (n = 30). Assessment of an aspect of neuromotor control was obtained by measuring the reflex response times of VMO and VL at the time of initial clinical examination, at the end of the exercise period (five weeks), and three months after the completion of the exercise period. At these evaluation occasions, the intensity and the number of times that the patients experienced anterior knee pain during daily life was recorded on a Visual Analog Scale (VAS). No alterations in reflex response times of VMO and VL were observed in either group. Changes of anterior knee pain over time were statistically significant in both groups. Only small and not statistically supported differences in anterior knee pain were found between the two groups. These results suggest that the reflex response times of the two vasti muscles can not be altered after a five week open or closed kinetic chain exercise program. In contrast, knee pain decreased significantly in both groups.

The aims of a meniscal replacement are: 1) to reduce the pain experienced by some patients following meniscus resection; 2) to prevent the degenerative changes of cartilage and the changes in subchondral bone following meniscus resection; 3) to avoid or reduce the risk of osteoarthritis following meniscus resection; 4) to restore optimally the mechanical properties of the knee joint after meniscal resection. The results of meniscus transplantation have been studied in animals. There is no proof from these experiments that replacement of a meniscus can reduce the risk of arthritis, but there are indications that it can decrease the development of cartilage degeneration. In humans, the results of meniscus transplantation have been reported in several series of patients, operated with different techniques. There are no controlled studies of meniscus replacement in humans. In case of meniscal allograft implantation surgery should be minimally invasive, not sacrificing the original meniscal insertion points. It appears preferable to use an open technique in medial transplantation, whereas the arthroscopic approach appears to allow for easier lateral implantation.