The hallmark of human cancer is heterogeneity, reflecting the complexity and variability of the vast array of somatic mutations acquired during oncogenesis. An ability to dissect this heterogeneity, to identify subgroups that represent common mechanisms of disease, will be critical to understanding the complexities of genetic alterations and to provide a framework to develop rational therapeutic strategies. Here, we describe a classification scheme for human breast cancer making use of patterns of pathway activity to build on previous subtype characterizations using intrinsic gene expression signatures, to provide a functional interpretation of the gene expression data that can be linked to therapeutic options. We show that the identified subgroups provide a robust mechanism for classifying independent samples, identifying tumors that share patterns of pathway activity and exhibit similar clinical and biological properties, including distinct patterns of chromosomal alterations that were not evident in the heterogeneous total population of tumors. We propose that this classification scheme provides a basis for understanding the complex mechanisms of oncogenesis that give rise to these tumors and to identify rational opportunities for combination therapies.

Background: Impaction fractures of the posterolateral tibial plateau commonly occur in the setting of anterior cruciate ligament (ACL) tears, with considerable variability found in fracture size and morphologic features. Purpose: The primary objective was to characterize different morphologic variants of posterolateral tibial plateau impaction fractures. The secondary objective was to investigate the association between these impaction fracture variants and concomitant meniscal and ligamentous injuries. Study Design: Cross-sectional study; Level of evidence 3. Methods: Patients treated for primary ACL tears and having magnetic resonance imaging available were included in this study, and magnetic resonance images were reviewed with denotation of displaced posterolateral tibial impaction fractures. A classification system was created based on morphologic variants of impaction fractures; associations were evaluated through use of independent chi-square testing. Results: There were 825 knees meeting the inclusion criteria, with displaced posterolateral tibial plateau impaction fractures present in 407 knees (49.3%). We observed 3 distinct morphologic variants of lateral tibial plateau impaction fractures: (I) posterior cortical buckle not involving the articular surface; (II) posterior impaction fracture involving the articular surface, with subtypes based on (A) tibial plateau depth bone loss <10% and (B) bone loss >10%; and (III) displaced osteochondral fragment, with subtypes for (A) shear or (B) depressed fragment. Type IIIA impaction fractures were associated with an increased incidence of lateral meniscus posterior root tears (33.3% vs 12.4%; P = .009) and an increased incidence of lateral meniscal tears (83.3% vs 56.7%; P = .024) compared with all knees without type IIIA impaction fracture. An increased incidence of medial collateral ligament (MCL) tears was noted in patients with type IIIA impaction fractures compared with those who had no fracture or had another fracture type (61.1% vs 20.1%; P < .001). Type IIIB impaction fractures were associated with an increased incidence of lateral meniscal tears (80.0% vs 56.2%; P = .005). Conclusion: A high prevalence of displaced posterolateral tibial plateau impaction fractures occur in the setting of ACL tears, and they can be classified into distinct morphologic subtypes. Posterolateral tibial plateau impaction fractures with displaced depressed or shear fragments were both associated with an increased incidence of lateral meniscal tears, whereas impaction fractures with a shear fragment were associated with an increased incidence of lateral meniscus posterior root tears and MCL tears.

Background: Labral reconstruction has been shown to result in improved patient-reported outcomes (PROs) at mid-term follow-up in patients with a deficient labrum. The purpose of this study was to determine survivorship and PROs at a minimum 10-year follow-up. Methods: A retrospective evaluation of a prospectively collected single-surgeon database included 91 hips (89 patients) that underwent arthroscopic labral reconstruction with iliotibial band autograft between 2006 and 2008. The primary PRO was the Hip Outcome Score (HOS)-activities of daily living (ADL). The modified Harris hip score (mHHS), HOS-sports, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and patient satisfaction (on a scale of 1 to 10) were also collected at a 10-year minimum follow-up. Survivorship analysis curves were evaluated. Results: Eighty-two hips were evaluated at a 10-year minimum follow-up. Overall survivorship, with revision hip arthroscopy or total hip arthroplasty (THA) as the end point, was 70% at 5 years and 61% at 10 years, and the mean survival time was 9 years (95% confidence interval = 7.6 to 10 years). For the patients who did not undergo subsequent surgery, on average the mHHS increased from 60 preoperatively to 82 at the 10-year follow-up (p = 0.001), the HOS-ADL improved from 69 to 90 (p = 0.004), the HOS-sports improved from 43 to 76 (p = 0.001), and the median patient satisfaction was 10 of 10. Eighty percent of the patients achieved the minimal clinically important difference (MCID) in the HOS-ADL, and 87% obtained a patient acceptable symptom state (PASS). Conclusions: Following arthroscopic labral reconstruction with iliotibial band autograft, 9% of the hips underwent revision arthroscopy and 27% underwent THA. At 10 years, the survival rate, with revision hip arthroscopy or THA as the end point, was 61%; however, for those with >2 mm of joint space, the current indication for labral reconstruction, the 10-year survival rate was 90%. Excellent PROs and patient satisfaction were reported by those who did not require revision or THA. With appropriate patient selection and prevention of postoperative adhesions, labral reconstruction results in excellent outcomes and high patient satisfaction that is sustained at a minimum 10-year follow-up. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background: Bone bruising of the posterolateral tibial plateau and the lateral femoral condyle sulcus terminalis has a well-established association with anterior cruciate ligament (ACL) tears. Impaction fractures of the femur and tibia may occur in these locations; however, there is a paucity of literature describing these fractures. Purpose: The primary objective was to quantify the incidence, size, and location of impaction fractures of the posterolateral tibial plateau and lateral femoral condyle in patients with primary ACL tears. The secondary objective was to investigate the association between impaction fractures and concomitant meniscal and ligamentous injuries. Study Design: Case series; Level of evidence 4. Methods: Patients with available magnetic resonance imaging (MRI) scans who were treated for primary ACL tear by a single surgeon were identified. MRI scans were reviewed with denotation of posterolateral tibial and femoral condylar contusions and displaced impaction fractures. Measurements of the lateral tibial plateau were taken in all patients with displaced lateral tibial plateau fractures and in a subset of control patients without tibial plateau fracture present to characterize the size and location of the bony lesion. Associations of impaction fractures with concomitant meniscal or ligamentous injuries were evaluated through use of chi-square testing. Results: There were 825 knees identified with available MRI scans. Lateral tibial plateau bone bruising was present in 634 knees (76.8%), and lateral femoral condyle bone bruising was present in 407 knees (49.3%). Posterolateral tibial plateau impaction fractures were present in 407 knees (49.3%), and lateral femoral condylar impaction fractures were present in 214 knees (25.9%). Patients with posterolateral tibial plateau impaction fractures were older than patients without these fractures (42.6 vs 32.7 years; P < .001), whereas patients with lateral femoral condylar impaction fractures were younger (23.8 vs 32.7 years; P < .001). There were 71 knees (8.6%) with a posterolateral tibial plateau impaction fracture with greater than 10% loss of lateral tibial plateau depth, and this group had an increased incidence of lateral meniscus posterior root tears (22.1% vs 12.0%; P = .02). Conclusion: Posterolateral tibial plateau impaction fractures occurred with a high incidence (49.3%) in patients with primary ACL tears and demonstrated an increased association with lateral meniscus posterior horn root tears as their size increased. Lateral femoral condylar impaction fractures occurred in 25.9% of patients with primary ACL tears and entailed an increased incidence of lateral meniscal tears and medial meniscal ramp lesions.

Background: Meniscal vascular supply is an important determinant of its healing potential. It has been reported that only the peripheral 30% of the meniscus is vascularized in cadavers aged 53 to 94 years; however, the vascularity in young patients, in whom meniscal repair is more often performed, is unknown. Purpose: The primary objective was to analyze and measure the microvascular anatomy of the meniscus in adult cadaveric specimens <35 years old. The secondary objective was to assess angiogenic potential by quantifying regional gene expression in a meniscal allograft cohort <45 years old. Study Design: Descriptive laboratory study. Methods: In part 1 of this study, 13 fresh-frozen cadaveric knees (age range, 22-34 years; mean, 28.5 years) underwent popliteal artery India ink injection and tissue clearing using a Spalteholz technique, followed by microvascular vascular measurement. In part 2, mRNA was isolated from 13 meniscal allografts (age range, 17-43 years; mean, 27.2 years), and expression of angiogenic genes, vascular endothelial growth factor ( VEGF), and vascular endothelial growth factor receptor 1 ( FLT1) was quantified using real-time polymerase chain reaction. Results: The maximal depth of vascular penetration into the periphery of the medial and lateral menisci ranged from 0% to 42% and 0% to 48%, respectively. There was variation in the degree of vascular penetration within the medial meniscus, with the posterior horn having a significantly smaller depth of penetration (median, 8.7%) than that of the anterior horn (median, 17.4%; P < .0001) or midbody (median, 17.5%; P = .0003). There were no differences in angiogenesis gene expression ( VEGF/ FLT1) based on circumferential or radial meniscal locations. Conclusion: The vascular supply of the medial and lateral menisci in specimens from adults <35 years of age extended farther than what was reported in specimens from older individuals; however, median values remained consistent. Gene expression of the angiogenic marker VEGF was low throughout all regions of uninjured menisci from young adults, which is consistent with reports in older specimens. Clinical Relevance: Improved understanding of meniscal vascular supply in young adults is critical to informing clinical treatment decisions.