Terminology and Classification of Muscle Injuries in Sport: The Munich Consensus Statement

Objective: To provide a clear terminology and classification of muscle injuries in order to facilitate effective communication among medical practitioners and development of systematic treatment strategies. Methods: Thirty native English-speaking scientists and team doctors of national and first division professional sports teams were asked to complete a questionnaire on muscle injuries to evaluate the currently used terminology of athletic muscle injury. In addition, a consensus meeting of international sports medicine experts was established to develop practical and scientific definitions of muscle injuries as well as a new and comprehensive classification system. Results: The response rate of the survey was 63%. The responses confirmed the marked variability in the use of the terminology relating to muscle injury, with the most obvious inconsistencies for the term strain. In the consensus meeting, practical and systematic terms were defined and established. In addition, a new comprehensive classification system was developed, which differentiates between four types: functional muscle disorders (type 1: overexertion-related and type 2: neuromuscular muscle disorders) describing disorders without macroscopic evidence of fibre tear and structural muscle injuries (type 3: partial tears and type 4: (sub)total tears/tendinous avulsions) with macroscopic evidence of fibre tear, that is, structural damage. Subclassifications are presented for each type. Conclusions: A consistent English terminology as well as a comprehensive classification system for athletic muscle injuries which is proven in the daily practice are presented. This will help to improve clarity of communication for diagnostic and therapeutic purposes and can serve as the basis for future comparative studies to address the continued lack of systematic information on muscle injuries in the literature. What are the new things: Consensus definitions of the terminology which is used in the field of muscle injuries as well as a new comprehensive classification system which clearly defines types of athletic muscle injuries

Gene-therapeutic approach for the expression of heterologous receptors in the heart

Vorliegende Arbeit untersucht die Grundlagen und die Durchführbarkeit für einen neuen, möglichen Ansatz zur Therapie der Herzinsuffizienz auf molekularer Ebene. Hierzu wurde der im Herzen heterologe, G-Protein-gekoppelte, PTH/PTHrP1-Rezeptor in Kardiomyoblasten und Kardiomyozyten zur Expression gebracht. Da in der Herzinsuffizienz im Myokard dehnungsabhängig PTHrP ausgeschüttet wird, könnte so über die Expression des heterologen Rezeptors und cAMP-Bildung über das Gs-Adenylatzyklase-System ein parakriner Loop geschlossen und damit eine Steigerung der Kontraktilität rezeptorbesetzter Zellen, d.h. ein positiv inotroper Effekt erreicht werden. Als Gen-Vektoren untersuchten wir zum einen Adenoviren, zum anderen Adeno-assoziierte Viren, die beide mittels Markergenen auf ihre Effektivität, Fremd-DNA in Herzzellen einzuschleusen, getestet wurden. Alle Virus-Proplasmide, in die das Gen für den PTH/PTHrP1-Rezeptor einkloniert worden war, wurden funktionell gemessen. Die Arbeit zeigt, daß es prinzipiell möglich ist, fremde Gene, insbesondere das Gen für den PTH/PTHrP1-Rezeptor, mit guter Effizienz sowohl in vitro in Kardiomyoblasten und in isolierten Kardiomyozyten als auch in vivo im Myokard zur Expression zu bringen. Alle Gene behielten nach Umklonierung und heterologer Expression in den verschiedenen Zellen ihre Funktion.The present study investigates the feasibility of a novel, molecular approach to therapy congestive heart failure. For this, we overexpressed the heterologous, G-Protein-coupled, PTH/PTHrP1-Receptor in cardiomyoblasts and cardiomyocytes. Because PTHrP is released in a stretch-responsive manner from the myocard in congestive heart failure, overexpression of the heterologous receptor and cAMP formation via the Gs/adenylyl cyclase system could result in a positive inotropic paracrine loop through an increased contractility of PTH/PTHrP1-expressing cells. As gene-vectors we investigated on the one hand adenoviruses, on the other hand adeno-associated viruses. Both were tested with reportergenes for their ability to transfer foreign DNA into heartcells. All virus-proplasmides, encoding the PTH/PTHrP1-receptor, were functionally tested. The investigations show, that it is possible to express with a good efficiency heterologous genes, especially the PTH/PTHrP1-gene, as well in vitro in cardiomyoblasts and in cardiomyocytes as in vivo in the myocard. All genes maintained after cloning and heterologous expression in the different cells their function

Should we avoid shoulder surgery in wheelchair users? A systematic review of outcomes and complications

Introduction: The prevalence of shoulder pathology in wheelchair dependent patients is high. The shoulder joint is critical for maintaining independence but traditionally there has been reluctance to offer surgical intervention in view of perceived poor outcomes. The aim of this study was to provide patients and surgeons with a realistic overview of outcomes following surgical intervention for shoulder pathology. Methods: A systematic review of the online databases Medline and EMBASE was performed in September 2017. Studies reporting functional outcomes, complications or rate of revision surgery after shoulder surgery in patients’ dependent on wheelchair for mobility were included. A narrative synthesis of the studies and appraisal using the MINORS tool was performed. Results: The search strategy identified 11 eligible studies; 7 assessed rotator cuff repair and 4 shoulder arthroplasty. Six of the seven studies reporting on rotator cuff repairs demonstrated improvement in pain, range of motion and functional outcomes with a re-tear rate between 12% and 39%. Although total shoulder arthroplasty and hemiarthroplasty reportedly improved pain and function, the subsequent risk of rotator cuff failure was reported up to 100%. The two studies assessing reverse arthroplasty demonstrated significant improvement in function and pain with the largest series reporting a 15.8% failure rate. Conclusion: Rotator cuff repairs and reverse shoulder arthroplasties performed in wheelchair users are associated with significant functional improvement and a slightly higher complication profile to those performed in ambulatory patients. This review provides a resource to aid surgeons and patients in holding realistic expectations following shoulder surgery in wheelchair users

MR imaging of osteochondral grafts and autologous chondrocyte implantation

Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible

Inducible nonviral gene expression in the treatment of osteochondral defects.

OBJECTIVE: The repair of osteochondral defects with chondrocytes genetically modified to express desired growth factors promises great potential in orthopaedic therapy. Controlled expression of the transgenes is required in many instances. The objective of the present study was to demonstrate the inducibility of tetracycline-responsive transgene expression in osteochondral defects in the knee joint filled with genetically modified chondrocyte implants. METHODS: An expression plasmid containing the lacZ gene under the control of the minimal CMV promoter fused to the Tet-responsible element (TRE) as well as the reverse transactivator (rtTA2s-M2) was constructed and used to transfect isolated articular chondrocytes from New Zealand white rabbits. rtTA2s-M2 binds to the TRE in the presence of tetracycline and leads to the transcription of the transgene. Different concentrations of DNA and various DNA:lipid ratios were tested to determine best transfection conditions. Transfection efficiency and inducibility were analysed by histochemical analysis and flow-cytometry. To evaluate the system in vivo, collagen-sponges were seeded with transfected autologous chondrocytes and implanted in osteochondral defects in the knees of NZW-rabbits. Gene expression was induced by doxycycline and 3 weeks later, LacZ-expression in isolated knee joints was evaluated in histological sections by X-gal staining. RESULTS: In vitro 13.5% (+/-1.32) of induced primary chondrocytes were LacZ-positive, while non-induced controls showed a background-staining in 0.6% (+/-0.2). In vivo, upon doxycycline treatment, induction of lacZ-gene-expression could be demonstrated in chondrocytes in 3-week-old, well-integrated implants. CONCLUSION: For the first time, tetracycline-inducible gene expression is demonstrated to work in the treatment of osteochondral defects. This demonstrates the feasibility for a gene therapy-assisted approach using controlled expression of therapeutic growth factors from transplanted genetically modified chondrocytes

Retrograde cartilage transplantation on the proximal and distal tibia.

The authors, with experience with more than 400 osteochondral autograft transplantation (OATS) cases since 1996, report a new technique of a retrograde osteochondral autograft transplantation for the treatment of isolated osteochondral lesions of the proximal and the distal tibia started in 1999. We treated 5 patients, 3 who presented with painful traumatic chondral defects in the central weight-bearing portion of the tibial plateau (1 in the medial and 2 in the lateral compartment), and 2 who presented with painful chondral lesions on the distal tibia. An anterior cruciate ligament (ACL) drill guide positioned in the center of the defect was used to accurately prepare the cartilage surface, in one case arthroscopically and in 4 cases through an open incision. A guide-wire was introduced and drilled through the tibia, and a cannulated reamer equal to the diameter of the defect was advanced. An osteochondral cylinder was harvested from the non-weight-bearing zone of the femoral trochlea at the angle that corresponded to the angle on the ACL drill guide. The autograft was inserted in a retrograde fashion from the cortical window into the tibial tunnel to be flush with the articular surface in press-fit technique. The remaining tunnel defect between the cortical window on the tibia and the distal aspect of the autograft was filled with a cancellous bony cylinder and secured with a diagonal bioabsorbable screw. A concomitant varus deformity with the lesion on the medial tibial plateau was corrected in the same surgery using a high tibial osteotomy to relieve stress on the graft. Patients were followed up for 6 to 35 months. A complete healing of the grafts was seen in control magnetic resonance images (MRIs). All patients were satisfied with the surgery. Control arthroscopies showed the osteochondral cylinders well integrated and flush with the articular surface

In vivo analysis of retroviral gene transfer to chondrocytes within collagen scaffolds for the treatment of osteochondral defects.

To examine a retroviral gene transfer to chondrocytes in vitro and in vivo in tissue-engineered cell-collagen constructs articular chondrocytes from rabbits and humans were isolated and transduced with VSV.G pseudotyped murine leukemia virus-derived retroviral vectors. Viral supernatants were generated by transient transfection of 293T cells using the pBullet retroviral vector carrying the nlslacZ gene, a Moloney murine leukemia virus gag/pol plasmid and a VSV.G coding plasmid. Transduction efficiency was analyzed by fluorescence-activated-cell-sorter analysis and transduced autologous chondrocytes from rabbits were seeded on collagen-scaffolds and implanted into osteochondral defects in the patellar groove of the rabbit's femur (n=10). LacZ-expression was analyzed by X-gal staining on total knee explants and histological sections. Retroviral transduction efficiency exceeded 92.3% (SEM+/-3.5%) in rabbit articular chondrocytes, 74.7% (SEM+/-1.8%) in human articular chondrocytes and 52.7% (SEM+/-5.8%) in osteoarthritic human chondrocytes. Reporter gene expression remained high after 15 weeks in 75.7% (SEM+/-8.2%) of transduced rabbit articular chondrocytes. In vivo, intraarticular beta-galactosidase activity could be determined in the majority of implanted chondrocytes in the osteochondral defects after 4 weeks