Matthias Brem

Chondromodulin 1 stabilizes the chondrocyte phenotype and inhibits endochondral ossification of porcine cartilage repair tissue

OBJECTIVE To investigate the effect of chondromodulin 1 on the phenotype of osteochondral progenitor cells in cartilage repair tissue. METHODS Self-complementary adeno-associated virus (AAV) vectors carrying chondromodulin 1 complementary DNA (AAV-Chm-1) were applied to cartilage lesions in the knee joints of miniature pigs that were treated by the microfracture technique. Alternatively, isolated porcine osteochondral progenitor cells were infected with AAV-Chm-1 or with AAV-GFP control vectors ex vivo prior to being transplanted into cartilage lesions in which the subchondral bone plate was left intact. The quality of the repair tissue and the degree of endochondral ossification were assessed by histochemical and immunohistochemical methods. The effects of chondromodulin 1 overexpression were also analyzed by angiogenesis assays and quantitative reverse transcriptase-polymerase chain reaction. RESULTS AAV-Chm-1-infected cells efficiently produced chondromodulin 1, which had strong antiangiogenic effects, as verified by the inhibition of tube formation of endothelial cells. Gene expression analyses in vitro revealed the cell cycle inhibitor p21WAF1/Cip1 as one target up-regulated by AAV-Chm-1. Direct application of AAV-Chm-1 vectors into microfractured porcine cartilage lesions stimulated chondrogenic differentiation of ingrowing progenitor cells, but significantly inhibited terminal chondrocyte hypertrophy, the invasion of vessel structures, and excessive endochondral ossification, which were otherwise observed in untreated lesions. Indirect gene transfer, with infection of porcine osteochondral progenitor cells by AAV-Chm-1 ex vivo, also supported chondrogenic differentiation of these transplanted cells. AAV-Chm-1-infected cells maintained a chondrocyte-like phenotype and formed a hyaline-like matrix that was superior to that formed by uninfected or AAV-GFP-infected cells. CONCLUSION Our findings indicate that the antiangiogenic factor chondromodulin 1 stabilizes the chondrocyte phenotype by supporting chondrogenesis but inhibiting chondrocyte hypertrophy and endochondral ossification.

Atrial and Ventricular Functional and Structural Adaptations of the Heart in Elite Triathletes Assessed with Cardiac MR Imaging

PURPOSE To assess cardiac morphologic and functional adaptations in elite triathletes with magnetic resonance (MR) imaging and to compare findings to those in recreationally active control subjects. MATERIALS AND METHODS The institutional review board approved the study, and written informed consent was obtained from all subjects. Twenty-six male triathletes (mean age ± standard deviation, 27.9 years ± 3.5; age range, 18-35 years) and 27 nonathletic male control subjects (mean age, 27.3 years ± 3.7; age range, 20-34 years) underwent cardiac MR imaging. Electrocardiographically gated steady-state free-precession cine MR imaging was used to measure indexed left ventricular (LV) and right ventricular (RV) myocardial mass, end-diastolic and end-systolic volumes, stroke volume, ejection fraction (EF), and cardiac index at rest. The ventricular remodeling index, which is indicative of the pattern of cardiac hypertrophy, was calculated. The maximum left atrial (LA) volume was calculated according to the biplane area-length method. Differences between means of athletes and control subjects were assessed by using the Student t test for independent samples. RESULTS The atrial and ventricular volume and mass indexes in triathletes were significantly greater than those in control subjects (P < .001). In 25 of the 26 athletes, the LV and RV end-diastolic volumes were greater than the normal ranges reported in the literature for healthy, male, nonathletic control subjects (47-92 mL/m(2) and 55-105 mL/m(2), respectively). There was a strong positive correlation between end-diastolic volume and myocardial mass (P < .01). The mean LV and RV remodeling indexes of the athletes (0.73 g/mL ± 0.1 and 0.22 g/mL ± 0.01, respectively) were similar to those of the control subjects (0.71 g/mL ± 0.1 [P = .290] and 0.22 g/mL ± 0.01 [P = .614], respectively). There was a negative correlation between LA end-systolic volume and heart rate (P < .01). CONCLUSION Changes in cardiac morphologic characteristics and function in elite triathletes, as measured with cardiac MR imaging, reflect a combination of eccentric and concentric remodeling with regulative enlargement of atrial and ventricular chambers. These findings are different from what has been observed in previous studies in other types of elite athletes.

Cardiac magnetic resonance assessment of left and right ventricular morphologic and functional adaptations in professional soccer players

BACKGROUND Professional, long-term physical training is associated with cardiac morphologic and functional changes that depend on the type of exercise performed. So far, the specific effect of soccer training on cardiac morphology has not been investigated with cardiac magnetic resonance imaging (CMRI). We sought to use CMRI to study left ventricular (LV) and right ventricular (RV) morphologic and functional adaptations in professional soccer players. METHODS Twenty-nine male professional soccer players (mean age 24.6 +/- 3.9 years, range 18-31 years) in different playing positions and 29 nonathlete male controls (27.0 +/- 3.7 years, 21-34 years) underwent CMRI. Electrocardiographic-gated steady-state free-precession cine CMRI was used to measure myocardial mass (MM), end-diastolic volume (EDV) and end-systolic volume, stroke volume (SV), ejection fraction, and cardiac index at rest. We calculated the ventricular remodeling index (RI) to describe the pattern of cardiac hypertrophy. RESULTS Ventricular volume and mass indices were significantly (P < .001) higher in athletes. LVEDV and RVEDV on MRI was above normal in 27/29 athletes. There was a strong positive correlation between EDV and myocardial mass (P < .01). The LVRI and RVRI were similar (0.73 +/- 0.1 g/mL; 0.22 +/- 0.01 g/mL) to that of controls (0.71 +/- 0.1 g/mL; 0.22 +/- 0.01 g/mL). No significant differences were observed for LV ejection fraction and cardiac index. Neither the comparison of athletes in different playing positions nor the comparison of younger and older players revealed statistically significant differences. CONCLUSION Cardiac magnetic resonance imaging measurements enable studying the mechanisms of LV and RV adaptation in professional soccer players and reflect the ventricular response to combined endurance and strength based training.

Paracrine effect of transplanted rib chondrocyte spheroids supports formation of secondary cartilage repair tissue

The studys objective was to investigate if transplanted chondrocyte or periosteal cell spheroids have influence on ingrowing bone marrow‐derived cells in a novel cartilage repair approach in miniature pigs. Autologous rib chondrocytes or periosteal cells were cultured as spheroids and press‐fitted into cavities that were milled into large, superficial chondral lesions of the patellar joint surface. Within the milled cavities, the subchondral bone plate was either penetrated or left intact (full‐thickness or partial‐thickness cavities). The transplantation of chondrocyte spheroids into full‐thickness cavities induced the formation of additional secondary repair cartilage that exceeded the original volume of the transplanted spheroids. The resulting continuous tissue was rich in proteoglycans and stained positive for type II collagen. Cell labeling revealed that secondarily invading repair cells did not originate from transplanted spheroids, but rather from arroded bone marrow. However, secondary invasion of repair cells was less pronounced following transplantation of periosteal cells and absent in partial‐thickness cavities. According to in vitro analyses, these observations could be ascribed to the ability of chondrocyte spheroids to secrete relevant amounts of bone morphogenetic protein‐2, which was not detected for periosteal cells. Transplanted chondrocyte spheroids exert a dual function: they provide cells for the repair tissue and have a stimulatory paracrine activity, which promotes ingrowth and chondrogenesis of bone marrow‐derived cells.

[The vacuum-assisted closure (V.A.C.) and instillation dressing: limb salvage after 3 degrees open fracture with massive bone and soft tissue defect and superinfection].

We report the case of a 17-year-old boy who was hit by a high velocity train. The polytraumatized patient suffered a 3 degrees open femur defect fracture with a substantial loss of the lateral femoral muscles and significant disruption of the soft tissue of the lower leg. The enormous wound areas on the thigh and the lower leg were infected by Pseudomonas aeruginosa, Enterobacter cloacae, and Stenotrophomonas maltophilia. The enormous tissue defects and the superinfection did not leave any hope for saving the limb from amputation. After rapid aggressive debridement and pulsatile lavage, we covered the wounds as a last resort with a new technique of vacuum-assisted closure (V.A.C) and instillation (V.A.C. Instill(R)) dressings. In sequences of 1 min we instilled Lavasept, kept it for 20 min on the wound surface, and exhausted the liquid. We repeated this for 6 consecutive days and then changed the dressing. In the follow-up examinations the number of germs was significantly reduced. During follow-up care we used the V.A.C. treatment without instillation and finally we transplanted skin onto the clean wound surface and were able to save the leg of this young patient. We discharged him with a good function of his lower leg. This technique of V.A.C. Instill seems to offer great possibilities in critically infected wound situations.

Der „Vacuum-assisted closure and instillation-“ (VAC™-Instill-)Verband

We report the case of a 17-year-old boy who was hit by a high velocity train. The polytraumatized patient suffered a 3 degrees open femur defect fracture with a substantial loss of the lateral femoral muscles and significant disruption of the soft tissue of the lower leg. The enormous wound areas on the thigh and the lower leg were infected by Pseudomonas aeruginosa, Enterobacter cloacae, and Stenotrophomonas maltophilia. The enormous tissue defects and the superinfection did not leave any hope for saving the limb from amputation. After rapid aggressive debridement and pulsatile lavage, we covered the wounds as a last resort with a new technique of vacuum-assisted closure (V.A.C) and instillation (V.A.C. Instill(R)) dressings. In sequences of 1 min we instilled Lavasept, kept it for 20 min on the wound surface, and exhausted the liquid. We repeated this for 6 consecutive days and then changed the dressing. In the follow-up examinations the number of germs was significantly reduced. During follow-up care we used the V.A.C. treatment without instillation and finally we transplanted skin onto the clean wound surface and were able to save the leg of this young patient. We discharged him with a good function of his lower leg. This technique of V.A.C. Instill seems to offer great possibilities in critically infected wound situations.

Incisional negative pressure wound therapy after hemiarthroplasty for femoral neck fractures – reduction of wound complications

The aim of the study was to evaluate the use of incisional negative pressure wound therapy (iNPWT) in wound healing after femoral neck fracture (FNF) treated with hip hemiarthroplasty (HA) and its influence on postoperative seromas, wound secretion, as well as time and material consumption for dressing changes. The study is a prospective randomised evaluation of iNPWT in patients with large surgical wounds after FNF. Patients were randomised either to be treated by iNPWT (group A) or a standard wound dressing (group B). Follow‐up included ultrasound measurements of seroma volumes on postoperative days 5 and 10, duration of wound secretion, and time and material spent for wound dressing changes. For comparison of the means, we used the t‐test for independent samples, P > 0·05 was considered significant. There were 21 patients randomised in this study. Group A (11 patients, 81·6 ± 5·2 years of age) developed a seroma of 0·257 ± 0·75 cm3 after 5 days and had a secretion of 0·9 ± 1·0 days, and the total time for dressing changes was 14·8 ± 3·9 minutes, whereas group B (ten patients, 82·6 ± 8·6 years of age) developed a seroma of 3·995 ± 5·01 cm3 after 5 days and had a secretion of 4·3 ± 2·45 days, and the total time for dressing changes was 42·9 ± 11·0 minutes. All mentioned differences were significant. iNPWT has been used on many different types of traumatic and non‐traumatic wounds. This prospective, randomised study has demonstrated decreased development of postoperative seromas, reduction of total wound secretion days and reduction of needed time for dressing changes.

Negative pressure wound therapy for seroma prevention and surgical incision treatment in spinal fracture care

To evaluate the clinical use and economic aspects of negative pressure wound therapy (NPWT) after dorsal stabilisation of spinal fractures. This study is a prospective randomised evaluation of NPWT in patients with large surgical wounds after surgical stabilisation of spinal fractures by internal fixation. Patients were randomised to either standard wound dressing treatment (group A) or NPWT (group B). The wound area was examined by ultrasound to measure seroma volumes in both groups on the 5th and 10th day after surgery. Furthermore, data on economic aspects such as nursing time for wound care and material used for wound dressing were evaluated. A total of 20 patients (10 in each group) were enrolled. Throughout the whole study, mean seroma volume was significantly higher in group A than that in group B (day 5: 1·9 ml versus 0 ml; P = 0·0007; day 10: 1·6 ml versus 0·5 ml; P <0·024). Furthermore, patients of group A required more wound care time (group A: 31 ± 10 minutes; group B 13·8 ± 6 minutes; P = 0·0005) and more number of compresses (total number; group A 35 ± 15; group B 11 ± 3; P = 0·0376). NPWT reduced the development of postoperative seroma, reduced nursing time and reduced material required for wound care.

Value of incisional negative pressure wound therapy in orthopaedic surgery

Soft tissue and wound treatment after orthopaedic interventions (especially after trauma) is still an enormously challenging situation for every surgeon. Since development of negative pressure wound therapy (NPWT), new indications have been consistently added to the original field of application. Recently, NPWT has been applied directly over high‐risk closed surgical incisions. Review of the literature indicates that this therapy has shown positive effects on incisions after total ankle replacement or calcaneal fractures, preventing haematoma and wound dehiscence. In those cases reduced swelling, decreased pain and healing time of the wound were seen. Additionally, NPWT applied on incisions after acetabular fractures showed a decreased rate of infection and wound healing problems compared with published infection rates. Even after total hip arthroplasty, incisional NPWT reduced incidence of postoperative seroma and improved wound healing. In patients with tibial plateau, pilon or calcaneus fractures requiring surgical stabilisation after blunt trauma, reduced risk of developing acute and chronic wound dehiscence and infection was observed when using incisional NPWT. To conclude, incisional NPWT can help to reduce risk of delayed wound healing and infection after severe trauma and orthopaedic interventions.

The accelerating effect of negative pressure wound therapy with Prevena™ on the healing of a closed wound with persistent serous secretion

Negative pressure wound therapy has been lately used on closed incisions in the immediate postoperative period to accelerate wound healing. However, there are no data in the literature regarding the use of this type of therapy for wounds with persistent secretion in the early postoperative care. We present the first report of persistent postoperative serous wound secretion in a patient after femoral nailing treated successfully with Prevena™ (KCI), a closed incision negative pressure management system (CINPWT).