Miroslav Hašpl

Characterized Chondrocyte Implantation Results in Better Structural Repair When Treating Symptomatic Cartilage Defects of the Knee in a Randomized Controlled Trial Versus Microfracture

Background As the natural healing capacity of damaged articular cartilage is poor, joint surface injuries are a prime target for regenerative medicine. Characterized chondrocyte implantation uses an autologous cartilage cell therapy product that has been optimized for its biological potency to form stable cartilage tissue in vivo. Purpose To determine whether, in symptomatic cartilage defects of the femoral condyle, structural regeneration with characterized chondrocyte implantation is superior to repair with microfracture. Study Design Randomized controlled trial; Level of evidence, 1. Methods Characterized chondrocyte implantation was compared with microfracture in patients with single grade III to IV symptomatic cartilage defects of the femoral condyles in a multicenter trial. Patients aged 18 to 50 years were randomized to characterized chondrocyte implantation (n = 57) or microfracture (n = 61). Structural repair was blindly assessed in biopsy specimens taken at 1 year using (1) computerized histomorphometry and (2) evaluation of overall histological components of structural repair. Clinical outcome was measured using the self administered Knee injury and Osteoarthritis Outcome Score. Adverse events were recorded throughout the study. Results Characterized chondrocyte implantation resulted in better structural repair, as assessed by histomorphometry (P = .003) and overall histologic evaluation (P = .012). Aspects of structural repair relating to chondrocyte phenotype and tissue structure were superior with characterized chondrocyte implantation. Clinical outcome as measured by the Knee injury and Osteoarthritis Outcome Score at 12 to 18 months after characterized chondrocyte implantation was comparable with microfracture at this stage. Both treatment groups had a similar mean baseline overall Knee injury and Osteoarthritis Outcome Score (56.30 ± 13.61 and 59.53 ± 14.95 for microfracture and characterized chondrocyte implantation, respectively), which increased in both groups to 70.56 ± 12.39 and 72.63 ± 15.55 at 6 months, 73.26 ± 14.66 and 73.10 ± 16.01 at 12 months, and 74.73 ± 17.01 and 75.04 ± 14.50 at 18 months, respectively. Both techniques were generally well tolerated; the incidence of adverse events after characterized chondrocyte implantation was not markedly increased compared with that for microfracture. Conclusion One year after treatment, characterized chondrocyte implantation was associated with a tissue regenerate that was superior to that after microfracture. Short-term clinical outcome was similar for both treatments. The superior structural outcome may result in improved long-term clinical benefit with characterized chondrocyte implantation. Long-term follow-up is needed to confirm these findings.

The incidence of injuries in elite junior figure skaters.

Background There has been rapid growth in the technical and physiologic demands made on skaters who perform more and more difficult jumps, spins, lifts, throws, and free skating movements. Purpose To investigate the frequency of injuries and overuse syndromes in elite junior skaters. Study Design Questionnaire. Methods During four consecutive Junior World Figure Skating Championships and the Croatia Cup, we interviewed 236 female and 233 male skaters by questionnaire to determine the frequency of injuries and overuse syndromes. Results Fifty-nine of the female skaters (25%) and 65 of the male skaters (27.9%) reported sustaining acute injuries; 101 female (42.8%) and 106 male (45.5%) skaters reported overuse syndromes. Low back pain was reported by 19 female and 23 male skaters. The most frequent acute injury was ankle sprain. In singles female skaters, the most frequent overuse injury was stress fracture (19.8%), followed by jumpers knee (14.9%). In singles male skaters, jumpers knee (16.1%) was the most frequent injury, followed by Osgood-Schlatter disease (14.2%). More than 50% of injuries in young singles figure skaters involved overuse syndromes. Pairs skaters and ice dance skaters had a higher risk of acute injury than overuse syndrome because of falls from lifts and throw jumps. Conclusions Programs to improve postural alignment, flexibility, and strength, especially during the asynchronous period of bone and soft tissue development, should be instituted to prevent and reduce overuse syndromes.

Articular cartilage repair by genetically modified bone marrow aspirate in sheep

Bone marrow presents an attractive option for the treatment of articular cartilage defects as it is readily accessible, it contains mesenchymal progenitor cells that can undergo chondrogenic differentiation and, once coagulated, it provides a natural scaffold that contains the cells within the defect. This study was performed to test whether an abbreviated ex vivo protocol using vector-laden, coagulated bone marrow aspirates for gene delivery to cartilage defects may be feasible for clinical application. Ovine autologous bone marrow was transduced with adenoviral vectors containing cDNA for green fluorescent protein or transforming growth factor (TGF)-β1. The marrow was allowed to clot forming a gene plug and implanted into partial-thickness defects created on the medial condyle. At 6 months, the quality of articular cartilage repair was evaluated using histological, biochemical and biomechanical parameters. Assessment of repair showed that the groups treated with constructs transplantation contained more cartilage-like tissue than untreated controls. Improved cartilage repair was observed in groups treated with unmodified bone marrow plugs and Ad.TGF-β1-transduced plugs, but the repaired tissue from TGF-treated defects showed significantly higher amounts of collagen II (P<0.001). The results confirmed that the proposed method is fairly straightforward technique for application in clinical settings. Genetically modified bone marrow clots are sufficient to facilitate articular cartilage repair of partial-thickness defects in vivo. Further studies should focus on selection of transgene combinations that promote more natural healing.

Articular cartilage repair: the role of bone morphogenetic proteins.

Joint surface repair is still a major challenge in modernmedicine because the factors initiating cartilage forma-tion, maturation, and repair are poorly understood. Spe-cific biological challenges include the variable qualityand quantity of the cartilage produced, decreasing re-sponsiveness with age, bonding to the adjacent cartilage,and restoration of the subchondral bone [36]. Injury tocartilage initiates a specific reparative response. In le-sions of the articular cartilage with no collagen damage aloss of non-collagenous matrix occurs, leading eventual-ly to complete repair of the damaged matrix [6]. In moresevere cases, where there is a damage of the fibrillar net-work and cell death, the articular cartilage does not heal[33, 44].Over the past several decades in clinical orthopaedicwork, techniques to treat chondral defects included abra-sion, drilling, micro-fracturing of the underlying bone,tissue autografts, allografts, and cell transplantation [1,3, 15, 16, 21, 26, 27, 28, 34, 40, 41, 51]. In recent yearsmore has been learned about various growth factors thatstimulate chondrocyte differentiation and cartilage ma-trix production, but to date no procedure has been fullysuccessful in achieving properly structured regenerativearticular cartilage.

Repair of a resistant tibial non-union with a recombinant bone morphogenetic protein-7 (rh-BMP-7)

Article presents a very rare patient with a pre-amputation non-union of the distal tibia who was healed with rh-BMP-7 and external fixator by Ilizarov after 14 years of unsuccessful treatment.

Plasma cytokines as markers of aseptic prosthesis loosening

The proinflammatory cytokines IL-1β, IL-8, and TNF-α play a major role in the process of bone resorption during aseptic loosening of large joint prostheses. These cytokines secreted locally during bone resorption in aseptic loosening may enter peripheral circulation. Increased concentration of IL-1β, IL-8, and TNF-α in peripheral circulation may indicate aseptic loosening. We determined whether bone resorption could be verified by cytokine presence in plasma. We recruited 50 patients with aseptic prosthesis loosening, 50 with stable prostheses, 50 with osteoarthritis, and 50 healthy individuals. Cytokine levels were determined in plasma by ELISA tests. Patients with prosthesis loosening had higher plasma levels (IL-1β, 3.7 ± 5.5 pg/mL; IL-8, 14.7 ± 9 pg/mL; TNF-α, 32.7 ± 32.4 pg/mL) than patients with stable prostheses (IL-1β, 1.5 ± 2 pg/mL; IL-8, 8.1 ± 4.7 pg/mL; TNF-α,22.9 ± 18.7 pg/mL), patients with osteoarthritis (IL-1β,0.7 ± 1.1 pg/mL; IL-8, 5.8 ± 3.8 pg/mL; TNF-α, 9.8 ± 7.7 pg/mL) and healthy individuals (IL-1β, 0.7 ± 1.1 pg/mL; IL-8, 4.2 ± 1.3 pg/mL; TNF-α, 3.9 ± 3.9 pg/mL). Our data suggest elevated plasma levels of proinflammatory cytokines may be useful as markers of bone resorption in the laboratory diagnosis of prosthesis loosening.Level of Evidence: Level IV, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Assessment of femoral neck-shaft and antetorsion angles

Summary.  The biplanar (Rippstein/Dunlop) technique is commonly used to radiographically determine the neck-shaft and anteversion angles of the hip. This method is unsuitable for certain groups of patients, such as those with fixed contracture of the hip joint. In these patients we have found the ‘sinus wave’ method to be preferable. We compared the neck shaft and anteversion angles of 30 hips determined by these two methods. Correlation was good for both the neck shaft (r = 0.972) and anteversion angles (0.69). We also used ultrasound to measure the anteversion but this correlated poorly with the Rippstein/Dunlop technique (r = 0.56). We believe that the sound wave technique is an accurate and practical way to determine the anteversion and neck-shaft angles of the hip.Résumé . Nous avons effectué une recherche sur 30 malades (30 hanches) en mesurant l’angle cervico diaphysare (CCD) et l’angle d’antétorsion (AT) par la méthode Rippstein/Dunlop (RD) et la méthode de »l’onde sinusoïdale« (OS), l’angle AT ayant étéégalement mesuré par la méthode aux ultrasons (US). En comparant la méthode RD avec celle de OS, nous avons trouvé une assez bonne corrélation dans la mesure de l’angle CCD (r = 0.97272) avec un petit écart de moyennes arythmétiques de 1.33 degrés et un écart de déviations standard de 4.62 degrés. Une moindre corrélation existe dans la mesure de l’angle AT, (r = 0.68710), avec un écart de moyennes arythmétiques de 9.37 degrés et un écart de déviations standard de 13.68 degrés, ce qui est logique eu égard à l’utilisation de différents axes du col. Par la comparaison de l’angle AT mesuréà l’aide des méthodes RD et US, il a été constaté la moindre corrélation r = 0.56480 avec un écart des moyennes arythmétiques de 8.83 degrés un écart de déviations standard de 13.98 dégrés. Ici également il faut tenir compte des différents axes du col du fémur. Les méthodes RD et US satisfont entièrement à un emploi clinique quotidien. L’inconvénient de la methode RD réside dans le fait que la radiographie n’est pas réalisable en cas d’ankylose ou de raideur de la hanche, et qu’elle est plus difficile à réaliser en présence des douleurs de la hanche, chez les malades agés moins mobiles et chez les enfants agités. La plupart de ces inconvénients peuvent être évités par l’application de la méthode OV. La méthode US est utile pour une orientation de la position du fémur proximal dans le sens de l’antétorsion.

Arthroscopic retrieval of metal foreign bodies from the knee joint after war wounds

From 1991 to 1995 metal bodies were removed from 16 knee joints (in 16 patients) using arthroscopic procedures. In 14 patients the wound resulted from explosive devices and in two from rifle bullets. Nine patients had more than one wound. Arthroscopy was performed on average 8.23 months after the injury took place (ranging from 14 days to 4 years). One metal foreign body was retrieved from 13 patients, two from two and four from one patient. The size of the metal foreign bodies varied from 2 to 24 mm, with an average of 8.61 mm. Different degrees of joint damage were present in all but one patient. The metal bodies were found in the posterolateral angle by the popliteus tendon in four patients, in three of whom the metal bodies went into this position during arthroscopy.

BMPs in articular cartilage repair

Over the past several decades, in clinical orthopedic work, from open Magnusson “housecleaning” arthroplasty to the autologous chondrocyte implantation, much has been learned about articular cartilage and its physiological capacity to restore itself. To date, no technique has been completely successful in restoring normal regenerative articular cartilage. Techniques to treat chondral defects include abrasion, drilling, microfracture technique, tissue autografts, allografts, and cell transplantation [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12]. Bone marrow stimulation techniques such as abrasion, drilling, and microfractures produce only fibrocartilage and therefore do not offer a longterm cure. Subchondral bone plate microfracture (abrasion or drilling) has shown to enhance chondral resurfacing by providing a suitable environment for tissue regeneration and taking advantage of the body’s own healing potential. The formation of a fibrin clot (“super clot”) containing desired pluripotential stem cells is stimulated [10]. This clot then differentiates and remodels, resulting in a durable fibrocartilage repair tissue [1]. Perichondral and periostal interposition grafts produce repair tissue that is similar to hyaline cartilage but also lack the mechanical durability. Like bone marrow stimulation techniques, interposition grafts introduce precursor cells, which have a tendency to differentiate along lines other than cartilage [7]. Autologous osteochondral transplant systems have shown encouraging results, but graft matching and contouring to the recipient articular surface proved to be difficult.

The Role of Ultrasonographic Monitoring for Hip Joint Changes in Patients with Chronic Renal Failure

Damir Matokovic, Miroslav Haspl, Petar Petric, Sanja Skorvaga,Vlado Drkulec and Goran Santak Department of Orthopaedics, General County Hospital Pozega Special Hospital for Orthopaedics and Traumatology of the Bone and Joint System Akromion, Krapinske Toplice Department of Internal Medicine, General County Hospital Pozega Department of Clinical Biochemistry, General County Hospital Pozega Department of Pediatrics, General County Hospital Pozega Department of Surgery, General County Hospital Pozega Croatia