Faculty Bibliography

BACKGROUND: Hip fractures in the elderly are associated with high 1-year mortality rates, but whether patients with other lower extremity fractures are exposed to a similar mortality risk is not clear. QUESTIONS/PURPOSES: We evaluated the mortality of elderly patients after distal femur fractures; determined predictors for mortality; analyzed the effect of surgical delay; and compared survivorship of elderly patients with distal femur fractures with subjects in a matched hip fracture group. PATIENTS AND METHODS: We included 92 consecutive patients older than 60 years with low-energy supracondylar femur fractures treated between 1999 and 2009. Patient, fracture, and treatment characteristics were extracted from operative records, charts, and radiographs. Data regarding mortality were obtained from the Social Security Death Index. RESULTS: Age-adjusted Charlson Comorbidity Index and a previous TKA were independent predictors for decreased survival. Congestive heart failure, dementia, renal disease, and history of malignant tumor led to shorter survival times. Patients who underwent surgery more than 4 days versus 48 hours after admission had greater 6-month and 1-year mortality risks. No differences in mortality were found comparing patients with native distal femur fractures with patients in a hip fracture control group. CONCLUSIONS: Periprosthetic fractures and fractures in patients with dementia, heart failure, advanced renal disease, and metastasis lead to reduced survival. The age-adjusted Charlson Comorbidity Index may serve as a useful tool to predict survival after distal femur fractures. Surgical delay greater than 4 days increases the 6-month and 1-year mortality risks. Mortality after native fractures of the distal femur in the geriatric population is high and similar to mortality after hip fractures. LEVEL OF EVIDENCE: Level II, prognostic study. See the guidelines online for a complete description of evidence.

BACKGROUND: The posterior interosseous nerve is at risk for iatrogenic injury during surgery involving the proximal aspect of the radius. Anatomic relationships of this nerve in skeletally intact cadavers have been defined, but variations associated with osseous and soft-tissue trauma have not been examined. This study quantifies the effect of a simulated diaphyseal fracture of the proximal aspect of the radius and of a radial neck fracture with an Essex-Lopresti injury on the posterior interosseous nerve. METHODS: In twenty unembalmed cadaveric upper extremities, the distance from the radiocapitellar joint to the point where the posterior interosseous nerve crosses the midpoint of the axis of the radius (Thompson approach) was recorded in three forearm positions (supination, neutral, and pronation). Specimens were then treated with either proximal diaphyseal osteotomy (n = 10) or radial head excision with simulated Essex-Lopresti injury (n = 10), and the position of the nerve in each forearm position was remeasured. We evaluated the effect of the simulated trauma on nerve position and correlated baseline measurements with radial length. RESULTS: In neutral rotation, the posterior interosseous nerve crossed the radius at a mean of 4.2 cm (range, 2.5 to 6.2 cm) distal to the radiocapitellar joint. In pronation, the distance increased to 5.6 cm (range, 3.1 to 7.4 cm) (p < 0.01). Supination decreased that distance to 3.2 cm (range, 1.7 to 4.5 cm) (p < 0.01). Radial length correlated with each of these measurements (r > 0.50, p = 0.01). Diaphyseal osteotomy of the radius markedly decreased the effect of forearm rotation, as the change in nerve position from supination to pronation decreased from 2.13 +/- 0.8 cm to 0.24 +/- 0.2 cm (p = 0.001). Proximal migration of the radius following radial head excision was accompanied by similar magnitudes of proximal nerve migration in all forearm positions. CONCLUSIONS: Forearm pronation has minimal effect on posterior interosseous nerve position within the surgical window following a displaced diaphyseal osteotomy of the proximal aspect of the radius. The nerve migrates proximally toward the capitellum with proximal migration of the radius in all forearm positions following a simulated Essex-Lopresti lesion. Visualization and protection of the posterior interosseous nerve is recommended when operatively exposing the traumatized proximal aspect of the radius.

OBJECTIVES: To evaluate the variability of the ideal trochanteric starting point as a possible cause for malreduction of subtrochanteric fractures and to analyze the accuracy of contralateral templating to predict correct entry site. METHODS: Standardized anteroposterior pelvis radiographs of 50 patients were evaluated by two independent reviewers. Patients with advanced osteoarthritis, severe hip deformity, and radiographs with asymmetric hip rotation were excluded. Ideal nail entry site was established using a template for a trochanteric nail with a 6 degrees proximal bend. The distance from the greater trochanteric tip to the ideal nail entry site was measured. Additionally, offset of the greater trochanter tip from the femoral longitudinal axis was measured. Interobserver reliability and accuracy of contralateral templating were evaluated. RESULTS: The ideal entry point ranged from 16 mm medial to 8 mm lateral to the trochanteric tip (mean, 3 mm medial; standard deviation, 5 mm). In 70% of patients, the ideal entry point was medial to and in 23% lateral to the tip of the greater trochanter. Ideal entry points were located within 2 mm of the trochanteric tip in 29% and within 4 mm in 44% of patients. The location of the ideal entry point relative to the trochanteric tip had a weak correlation with patient height and neck shaft angle (r: -0.23 and r: -0.35, respectively). Interobserver reliability and agreement between left and right side measurements were strong (intraclass correlation coefficient: >0.94 and >0.88, P < 0.001, respectively). The mean measurement differences between sides was 0 mm (95% confidence interval: -1 to 1). Greater trochanter offset averaged 15 mm (range, 5-26 mm; standard deviation: 5) on the right and 15 mm (range, 5-25 mm; standard deviation: 5.1) on the left (P = 0.95). CONCLUSION: A high degree of variability exists for the ideal trochanteric entry site. The trochanteric tip represents the ideal starting point in only the minority of cases. Preoperative contralateral templating provides an accurate means for establishing a patient-specific entry point to minimize fracture malreduction.

BACKGROUND: The mechanisms underlying the interaction between the local mechanical environment and fracture healing are not known. We developed a mouse femoral fracture model with implants of different stiffness, and hypothesized that differential fracture healing would result. METHODS: Femoral shaft fractures were created in 70 mice, and were treated with an intramedullary nail made of either tungsten (Young's modulus = 410 GPa) or aluminium (Young's modulus = 70 GPa). Mice were then sacrificed at 2 or 5 weeks. Fracture calluses were analyzed using standard microCT, histological, and biomechanical methods. RESULTS: At 2 weeks, callus volume was significantly greater in the aluminium group than in the tungsten group (61.2 vs. 40.5 mm(3), p = 0.016), yet bone volume within the calluses was no different between the groups (13.2 vs. 12.3 mm(3)). Calluses from the tungsten group were stiffer on mechanical testing (18.7 vs. 9.7 N/mm, p = 0.01). The percent cartilage in the callus was 31.6% in the aluminium group and 22.9% in the tungsten group (p = 0.40). At 5 weeks, there were no differences between any of the healed femora. CONCLUSIONS: In this study, fracture implants of different stiffness led to different fracture healing in this mouse fracture model. Fractures treated with a stiffer implant had more advanced healing at 2 weeks, but still healed by callus formation. Although this concept has been well documented previously, this particular model could be a valuable research tool to study the healing consequences of altered fixation stiffness, which may provide insight into the pathogenesis and ideal treatment of fractures and non-unions.

OBJECTIVE: To evaluate the prevalence and magnitude of sagittal plane deformity in bicondylar tibial plateau fractures. DESIGN: Retrospective radiographic review. SETTING: Two Level I trauma centers. MAIN OUTCOME MEASUREMENT: Sagittal inclination of the medial and lateral plateau measured in relation to the longitudinal axis of the tibia using computed tomographic reconstruction images. PATIENTS: Seventy-four patients (mean age, 49 years; range, 16-82 years; 64% male) with acute bicondylar tibial plateau fractures (Orthopaedic Trauma Association 41C, Schatzker VI) treated from October 2006 to July 2009. RESULTS: The average sagittal plane angulation of the lateral plateau was 9.8 degrees posteriorly (range, 17 degrees anteriorly to 37 degrees posteriorly). The medial plateau was angulated 4.1 degrees posteriorly on average (range, 16 degrees anteriorly to 31 degrees posteriorly). Forty-two lateral plateaus were angulated more than 5 degrees from the "normal" anatomic slope (defined as 5 degrees of posterior tibial slope). Of these, 76% were angulated posteriorly. Forty-three (58%) of the medial plateaus were angulated greater than 5 degrees from normal, of which only 47% were inclined posteriorly (P = 0.019 compared with lateral plateaus). In 68% of patients, the difference between medial and lateral plateaus was greater than 5 degrees ; the average intercondylar slope difference was 9 degrees (range, 0 degrees -31 degrees ; P < 0.001). Spanning external fixation did not affect the slope of either the medial or lateral tibial plateau. Intraobserver and interobserver correlations were high for both the medial and lateral plateaus (r > 0.81, P < 0.01). CONCLUSIONS: Considerable sagittal plane deformity exists in the majority of bicondylar tibial plateau fractures. The lateral plateau has a higher propensity for sagittal angulation and tends to have increased posterior slope. Most patients have a substantial difference between the lateral and medial plateau slopes. The identification of this deformity allows for accurate preoperative planning and specific reduction maneuvers to restore anatomic alignment.

Recent studies suggest that innate immune responses by natural killer (NK) cells play a significant role in restricting human immunodeficiency virus type-1 (HIV-1) pathogenesis. Our aim was to characterize changes in NK cells associated with HIV-1 clade C disease progression. Here we used multiparametric flow cytometry (LSRII) to quantify phenotype and function of NK cells in a cross-sectional analysis of cryopreserved blood samples from a cohort of 41 chronically HIV-1-infected, treatment-naive adult South Africans. These individuals ranged in disease severity from early (CD4 count >500) to advanced HIV-1 disease (CD4 count <50). We found that the frequency of NK cells expressing KIR2DL1, an inhibitory receptor, and/or KIR2DS1, an activating receptor, tended to decrease with increasing HIV-1 viral load. We also discovered a significant increase (p < 0.05) in overall NK cell degranulation with disease progression. We found that acutely activated NK cells (CD69(pos)) were deficient in NKp46 expression ex vivo. In conclusion, we observed that with viremia and advanced HIV-1 disease, activated NK cells lack NKp46 expression, and KIR2DS1(pos) and/ or KIR2DL1(pos) NK cells are reduced in frequency. These findings suggest that modulation of receptor expression on NK cells may play a role in HIV-1 pathogenesis, and provide new insights on immunological changes in advanced HIV-1 disease.

The exceptional value of gene targeting technology to generate mouse models of human disease exists under the shadow of potential genetic errors. We previously observed an unexpected brain-behavior phenotype that resulted from a gene-targeting experiment designed to delete the Zfa gene. Given that the transcription of Zfa is restricted to the germ cell lineage of adult testis, it was both a surprise and a concern when the resulting mice had a phenotype present in both sexes that included abnormal brains and violent behavior. We hypothesized that an unrelated mutation may have been responsible for the unexpected phenotype. Here we show that the single gene mutation, Nr2e1(frc) (fierce), which was responsible for the brain-behavior phenotype, existed in the embryonic stem (ES) cell even before the derivation of the Zfa knockout mice. Our work thus highlights a concern in gene targeting, namely, that ES cells can harbor unexpected mutations, which can lead to genotype-phenotype misattribution. Based on our findings, we caution the gene-targeting community to use low-passage ES cells, to characterize mice derived from more than one independently targeted ES cell clone, and to backcross mice to allow for segregation of distant but linked mutations.