Nir Cohen

Fibroblast growth factor receptor-3 as a marker for precartilaginous stem cells.

The epiphyseal organ contains two kinds of cartilage, articular and growth plate. Both enlarge during the growth phase of life. However, mitosis is not apparent in these tissues. In the current study, a search to trace the reservoirs of stem cells needed for the growth of these cartilages is done. A disorder in which the stem cells responsible for bone growth are mutated is achondroplasia; the mutation resides in the fibroblast growth factor receptor-3. Epiphyses stained with antifibroblast growth factor 3 antibodies reveal clusters of positively stained cells residing in the perichondrial mesenchyme, known as the ring of La Croix. Removal of the ring of La Croix causes a drastic growth arrest in the limbs of rat neonates. Cell cultures derived of the ring of La Croix biopsy specimens show high rates of cell proliferation and cell migration in vitro, in contrast to articular or growth plate derived chondrocytes. These cells stain intensely by antifibroblast growth factor receptor-3 antibodies and antiproliferative cells nuclear antigen, in contrast with articular and epiphyseal chondrocytes. Transfection of cells from the ring La Croix by an adenovirus vector containing the gene encoding for Escherichia coli beta-galactosidase (lacZ), allows tracing of these cells in tissues. Local injections were performed either to the ring of La Croix or to the joint cavity in a guinea pig model. A characteristic distribution was seen after injection. The transfected cells migrated to areas of bone and cartilage formation in the subchondral bone plate and on either side of the growth plate. This labeling and distribution is maintained for as many as 3 months after injection. The cells from the ring of La Croix appear to be responsible for bone growth. Furthermore, perichondrial cells and other precartilaginous cells expressing fibroblast growth factor-3 have been shown to be good cells for implantation to correct defects of articular cartilage.

Vacuum-assisted wound closure after resection of musculoskeletal tumors.

Resection of musculoskeletal tumors may result in large soft tissue defects that cannot be closed primarily and require prolonged dressing changes and complex surgical interventions for wound coverage. We retrospectively reviewed 23 patients with such defects treated with a vacuum-assisted wound closure system and compared the outcome of these patients with a control group. The study group included 15 women and eight men who had their wounds located at the back (two), pelvic girdle (11), thigh (eight), and leg (two). Treatment included sealed wound coverage with polyurethane foam and overlying tape connected to a vacuum pump. This system was disconnected and changed every 48 hours for 7 to 19 days, after which all defects were reduced in size by an average of 25% and covered with a viable granulation tissue. This allowed primary closure in seven patients, primary closure with skin grafting in 14 patients, and healing by secondary intention in two patients. Compared with the control group, patients in the study group had shorter hospital stays and number of surgical interventions and greater rates of primary wound closure. The use of vacuum-assisted wound closure facilitates wound healing and primary wound closure in patients who have a large soft tissue defect after resection of a musculoskeletal tumor. Level of Evidence: Therapeutic study, Level III (retrospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.

The use of dynamic CT surview for cervical spine clearance in comatose trauma patients : A pilot prospective study

BACKGROUND Bedside flexion and extension fluoroscopy was proposed for detecting occult ligamentous instability in comatose trauma patients. Nevertheless, a recent study showed that the C7-T1 motion segment is rarely visualised by this technique. We propose a new method for clearing the cervical spine in comatose patients. METHODS We conducted a prospective clinical pilot study on 31 consecutive comatose trauma patients to evaluate a new dynamic imaging technique for cervical spine clearance in comatose trauma patients. All patients were examined by a fine-cut helical CT scan of the entire cervical spine (C-spine) and by four-stage flexion-extension examination using the surview function of the CT scanner. The mean range of motion between extension and full flexion, the lowest visualised vertebrae, complications, positive findings, and the time from arrival to clearance was recorded. RESULTS The mean range of motion of the subaxial cervical spine was 39 degrees . The C7-T1 segment was fully visualised at the CT surview in 15 patients. The C6-C7 segment was visualised in all patients. No complication directly related to the study protocol was observed. C-spine clearance was completed in less than 6h from arrival in 26 patients. CONCLUSION The CT surview allows better visualisation of the C6-C7 and cervicothoracic junctions during flexion and extension. A short series of CT cuts can be used when visualisation is inadequate. Further studies are needed to assess the risks and benefits of the suggested protocol.

The value of 18-FDG PET/CT in the diagnosis and management of implant-related infections of the tibia: A case series

BACKGROUND Positron emission tomography (PET) combined with Computerised Tomography (CT) is gaining ground in clinical settings due to its added value of combined metabolic and anatomical imaging. PET/CT has shown promising results in diagnosing both acute and chronic infection of the axial and appendicular skeleton. PET imaging has an advantage in patients with metallic implants because FDG uptake, in contrast to magnetic resonance imaging (MRI) and standard computed tomography (CT), is not hampered by metallic artifacts. The role of PET/CT in the evaluation of implant-related infections involving the tibia in particular has not been thoroughly studied. PURPOSE To investigate the usefulness of 18-FDG PET/CT in the diagnosis and treatment of implant-related infections of the tibia following osteosynthesis. METHODS We reviewed 10 patients who underwent internal fixation to the tibia following trauma (4 open fractures, 6 closed fractures) and presented later with clinical signs of a possible implant-related infection. In evaluating the patients we used standard work-up methods (standard radiographs, lab tests) as well as advanced imaging techniques (PET/CT) in order to confirm the diagnosis and decide upon the preferred treatment. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were then calculated for PET/CTs ability to predict presence of infection using intraoperative cultures as the gold standard. RESULTS PET/CT validated our working diagnosis 9 out of 10 patients. In particular, it helped distinguish between: infected nonunion (n=4), aseptic nonunion (n=1), soft tissue infection (n=2) and chronic osteomyelitis (n=3). The overall sensitivity and specificity of PET/CT for identifying an osseous infection were 85.7% and 100%, respectively. The PPV and NPV were 100% and 75%, respectively. CONCLUSION PET/CT is a promising imaging modality that can aid in the work up of patients with suspected implant-related infections of the tibia following osteosynthesis, and may be used as a supportive measure in clinical decision making.

Storing live embryonic and adult human cartilage grafts for transplantation using a joint simulating device

OBJECTIVES Cartilage transplantation as a means to replace damaged articular surfaces is of interest. A major obstacle is the long-term preservation of cartilage grafts. The commonly used technique of freezing the grafts inevitably leads to cellular death. The current study compares the technique to an innovative approach using a pulsed-pressure perfusion system termed a joint simulating device (JSD), intended to simulate intra-articular mechanical forces. METHODS Human articular cartilage explants were harvested from both embryonic epiphyseal tissue and femoral heads of elderly women (over 70 years of age) undergoing a partial joint replacement (hemi-arthroplasty) and were divided in two groups: half of the samples were incubated in the JSD while the remaining half were grown in static culture within tissue culture plates. After 10 days all samples were evaluated for: (a) cell vitality as assessed by image analysis and XTT assay; (b) biosynthetic activity as expressed by radioactive sulfate incorporation into glycosaminoglycans (GAGs); and (c) proteoglycan content as assessed by alcian blue staining intensity. RESULTS A 10-fold increase in sulfate incorporation in samples held in the JSD compared to the static culture group was observed in embryonic cartilage. In adult cartilage culture in the JSD elevated sulfate incorporation by threefold as compared to static culture. Central necrosis was observed in specimens grown in the static culture plates, while it did not occur in the samples held in the JSD. Cell vitality as assessed by XTT assay was significantly better in the JSD group as compared to static culture. The difference was more pronounced in the embryonic specimens as compared to adult cartilage. The specimens cultured within the JSD retained proteoglycans significantly better than those cultured in static culture. CONCLUSIONS Maintenance of cartilage specimens in a JSD was highly effective in keeping the vitality of cartilage explants in vitro over a 10-day period. A possible future application may be a long-term preservation of chondral grafts, without freezing. Avoidance of freezing of cartilage grafts, might prevent the cartilage degeneration often observed in frozen osteochondral grafts.

Reduced NO accumulation in arthrotic cartilage by exposure to methylene blue

Nitric oxide (NO) appears to be a final common inflammation mediator of cartilage degradation. Halting the pathological formation of excessive NO, by suppressing the inducible NO synthase (iNOS) activity, may help to preserve cartilage integrity. We used fresh ex-vivo human articular cartilage explants from normal and arthrotic joints for assessment of NO levels, as determined by its nitrite degradation products and nitric oxide synthase expression. We measured matrix proteoglycan content, assessed by image analysis of alcian blue staining, and proteoglycan synthesis, assessed by sulfate incorporation into proteoglycans. The effect of methylene blue, a nitric oxide synthase inhibitor, on matrix preservation was evaluated. Cartilage discs in vitro, derived from normal appearing joints, secreted about one tenth as much NO compared to discs derived from arthrotic cartilage. Cartilage explants showed a time-dependent reduction in the amount of aggrecan within the cartilaginous matrix. Addition of methylene blue to the growth medium lowered nitric oxide accumulation and prevented matrix degradation in the cultured cartilage discs. The cartilage matrix preservation effect was mediated through downregulation of all three isoforms of NOS, i.e., the neuronal NOS, endothelial NOS and inducible NOS and upregulation of TGF beta receptor in the chondrocytes. Our findings indicate that inhibition of NOS activity preserves cartilage matrix in vitro.

Plastic cylindrical cement mold in the treatment of long bone metastatic fractures

Presented here is a simple and practical surgical technique for creating a cement spacer in the cement–metal composite fixation of pathological fractures. This technique has been effectively used in several of our patients for fixation of pathological fractures due to metastatic disease of long bones.

Extended Paratricipital Approach for Intra-articular Fractures of the Distal Humerus.

This article describes an extensile surgical exposure to the distal humerus that is suitable for complex fractures involving the articular surface and extending into the humeral diaphysis proximal to the radial nerve. This method combines 2 approaches: olecranon osteotomy and the lateral paratricipital approach. This combination allows an appropriate exposure of both the articular surface and the humeral diaphysis up to the level of the deltoid tuberosity, while maintaining the extensor mechanism unharmed.