A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast‐like cells

Neurofibromatosis type 1 (NF1) is a common genetic condition caused by mutations in the NF1 gene. Patients often suffer from tissue‐specific lesions associated with local double‐inactivation of NF1. In this study, we generated a novel fracture model to investigate the mechanism underlying congenital pseudarthrosis of the tibia (CPT) associated with NF1. We used a Cre‐expressing adenovirus (AdCre) to inactivate Nf1 in vitro in cultured osteoprogenitors and osteoblasts, and in vivo in the fracture callus of Nf1^flox/flox and Nf1^flox/? mice. The effects of the presence of Nf1^null cells were extensively examined. Cultured Nf1^null‐committed osteoprogenitors from neonatal calvaria failed to differentiate and express mature osteoblastic markers, even with recombinant bone morphogenetic protein‐2 (rhBMP‐2) treatment. Similarly, Nf1^null‐inducible osteoprogenitors obtained from Nf1 mouse muscle were also unresponsive to rhBMP‐2. In both closed and open fracture models in Nf1^flox/flox and Nf1^flox/? mice, local AdCre injection significantly impaired bone healing, with fracture union being <50% that of wild type controls. No significant difference was seen between Nf1^flox/flox and Nf1^flox/? mice. Histological analyses showed invasion of the Nf1^null fractures by fibrous and highly proliferative tissue. Mean amounts of fibrous tissue were increased upward of 10‐fold in Nf1^null fractures and bromodeoxyuridine (BrdU) staining in closed fractures showed increased numbers of proliferating cells. In Nf1^null fractures, tartrate‐resistant acid phosphatase–positive (TRAP+) cells were frequently observed within the fibrous tissue, not lining a bone surface. In summary, we report that local Nf1 deletion in a fracture callus is sufficient to impair bony union and recapitulate histological features of clinical CPT. Cell culture findings support the concept that Nf1 double inactivation impairs early osteoblastic differentiation. This model provides valuable insight into the pathobiology of the disease, and will be helpful for trialing therapeutic compounds. © 2012 American Society for Bone and Mineral Research     

Incidence and predictors of post-reperfusion syndrome in living donor liver transplantation

A characteristic pattern of hemodynamic changes that may occur in reperfusion phase of liver transplantation (LT) is known as post-reperfusion syndrome (PRS). In this study, we determined the frequency of PRS and evaluated possible predictors of PRS. The medical records of 152 patients who underwent living donor LT were reviewed. PRS was defined as a decrease in mean arterial pressure of more than 30% from the baseline value for more than one min during the first five min after reperfusion. The frequency of PRS was determined, and patients were divided into two groups: PRS group and non-PRS group. Donor factors, preoperative and intraoperative recipient factors, and postoperative outcomes were compared between the two groups. PRS occurred in 58 recipients (34.2%). Preoperative model for end-stage liver disease scores of recipients and percentage of graft steatotic changes were higher in PRS group. PRS group showed higher heart rates and lower hemoglobin values preoperatively. Before reperfusion, PRS group received more transfusion and their urine output was less than that of non-PRS group. Postoperatively, peak bilirubin during the first five d after LT was higher in PRS group. In conclusion, both severity of liver disease and graft steatosis may increase risk for PRS in LT. Further prospective studies of PRS in its relationship to outcome are indicated.     

Patient perspective survey of total hip vs total knee arthroplasty surgery

A 42-item survey was developed and administered to determine patient perception of and satisfaction with total hip arthroplasty (THA) vs total knee arthroplasty (TKA). A total of 153 patients who had both primary THA and TKA for osteoarthritis with 1-year follow-up were identified. Survey response rate was 72%. Patients were more satisfied with THA meeting expectations for improvement in function and quality of life (P < .05), whereas pain relief expectations were equivalent. Most patients (70.9%) reported that TKA required more physiotherapy. One-year Oxford score and improvement in Oxford score from preoperative to 1 year were superior for THAs (P = .000). Despite equivalent pain relief, THAs trend toward higher satisfaction compared with TKAs. THA is more likely to "feel normal" with greater improvement in Oxford score. Recovery from TKA requires more physiotherapy and a longer time to achieve a satisfactory recovery status. Patients should be counseled accordingly.     

The timing of drain removal—empiricism or science?

Surgical drains are commonly used in plastic surgery. Drains are subsequently removed at arbitrary volumes depending on local protocols. The rational for when to remove a drain has not been scientifically determined. We compared removal of drains at ≤30?ml/24?h vs. ≤50?ml/24?h for 158 wounds, in 90 patients. Postoperative complications, length of hospital stay and resulting cost–benefit were considered. Prospective data were collected for two consecutive similar cohorts of patients undergoing abdominoplasty, bilateral breast reduction and breast augmentation. In the first cohort, drains were removed when drainage was ≤30?ml/24?h and the second cohort when ≤50?ml/24?h. Demographics, days of drainage, surgeon grade and duration of postoperative hospital stay were recorded. Patient records were then analysed and complications recorded, including haematoma, infection, seroma, wound breakdown and fat necrosis. The median postoperative stay for all three operations for both drainage cohorts was similar with no statistically significant difference; however, the drainage time in breast augmentation was significantly less in the <50?ml/24?h group. There were no significant differences in outcome measures between the patients undergoing abdominoplasty, breast reduction or breast augmentation. Drain removal at ≤50 vs. ≤30?ml/24?h did not result in an increase in postoperative morbidity or adverse outcome in any of the three different operation types.     

A comparison of keratinocyte cell sprays with and without fibrin glue

Fibrin glue is an excellent template for cellular migration and has been shown to be an effective delivery system for cultured autologous keratinocytes. We have investigated whether fibrin glue has any benefit on the percentage of epithelial cover when cultured autologous keratinocytes are sprayed onto a freshly debrided wound bed.Three pigs were used for this study. This provided a total of 18 full thickness, vertically orientated wounds, each 4cm in diameter and isolated in PTFE chambers to prevent re-epithelialisation from the wound margins. Eight wounds were sprayed with cultured autologous keratinocytes suspended in 2ml culture medium and eight wounds were sprayed with cultured autologous keratinocytes suspended in 1ml of the fibrin/aprotinin component of Tisseel fibrin glue (Baxter) mixed with 1ml of culture medium. In the latter group the thrombin component of the fibrin glue kit was applied to the wound bed immediately prior to grafting. The remaining two wounds were used as controls and sprayed with either culture medium or fibrin glue without cells. Epithelial cover was calculated in whole-wound biopsies at 3 weeks using image analysis, histology and immunohistochemistry.The cell suspension in fibrin glue appeared to spread more evenly over the wound surface, with no pooling in the inferior aspect of the wound. However, mean epithelial area at 3 weeks in the fibrin group was 1.6cm(2) per wound compared with 1.8cm(2) for the non-fibrin group, as measured by image analysis of digital photographs. There was no statistically significant difference between the two groups (P=0.802). This surprising result was confirmed by histological analysis of the wound biopsies, with a good correlation between histological and image analysis data (R=0.967). There was no observable difference in the quality of the epithelium on histological and immunohistological analysis of either group.