A pathway-based classification of human breast cancer.

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.

New-onset synovial chondromatosis after total knee arthroplasty.

Total joint arthroplasty is commonly recommended as a definitive treatment for synovial chondromatosis refractory to other treatment. We describe a unique case of synovial chondromatosis developing after total joint arthroplasty in a patient presenting 5 years after total knee arthroplasty for osteoarthritis. This case illustrates that the diagnosis of synovial chondromatosis cannot be excluded in a patient with chronic, painful swelling of a joint, even after total joint arthroplasty.

Incidence of Injury for Professional Soccer Players in the United States: A 6-Year Prospective Study of Major League Soccer.

Background: Despite an abundance of injury research focusing on European professional soccer athletes, there are limited injury data on professional soccer players in the United States. Purpose: To describe the epidemiology of injury across multiple years in Major League Soccer (MLS) players. Study Design: Descriptive epidemiology study. Methods: A web-based health management platform was used to prospectively collect injury data from all MLS teams between 2014 and 2019. An injury was defined as an incident that required medical attention and was recorded into the health management platform anytime over the course of the 2014-2019 seasons. Injuries and exposure data were recorded in training and match settings to calculate injury incidence. Results: A total of 9713 injuries were recorded between 2014 and 2019. A mean 1.1 injuries per year per player were identified, with midfielders sustaining the largest number of injuries. The most common injuries were hamstring strains (12.3%), ankle sprains (8.5%), and adductor strains (7.6%). The mean time missed per injury was 15.8 days, with 44.2% of injuries resulting in no days missed. Overall injury incidence was 8.7 per 1000 hours of exposure, declining over the course of the investigation, with a 4.1-times greater mean incidence during matches (14.0/1000 h) than training (3.4/1000 h). Conclusion: Between 2014 and 2019, the most commonly reported injuries in MLS players were hamstring strains, ankle sprains, and adductor strains. Injury incidence during matches was 4.1 times greater when compared with training, while overall injury incidence was found to decline during the course of the study period.

Acetabular Labral Reconstruction with Iliotibial Band Autograft: Outcome and Survivorship at a Minimum 10-Year Follow-up.

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.

Microvascular Anatomy and Intrinsic Gene Expression of Menisci From Young Adults.

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.

Clinical Presentation and Outcomes Associated With Fabellectomy in the Setting of Fabella Syndrome.

BACKGROUND: Clinical outcomes pertaining to isolated lateral fabellectomy in the setting of fabella syndrome are limited to small case reports at this time. PURPOSE: To assess the most common presenting symptoms, clinical outcomes, and satisfaction after fabella excision in the setting of fabella syndrome. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Consecutive patients with a minimum of 21-month follow-up after isolated fabellectomy for fabella syndrome were reviewed retrospectively. Clinical outcome scores of the following domains were collected: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and Lysholm knee survey, along with a simple numeric patient satisfaction score (range, 1-10; 10 = "very satisfied"). Statistical analysis was performed using paired t tests for all clinical outcome data. RESULTS: A total of 11 isolated fabella excisions were included in 10 patients with isolated lateral-sided knee pain in the setting of fabella syndrome (8 males, 2 females), with a mean age of 36.9 years (range, 23-58 years) and a mean follow-up of 2.4 years (range, 21-47 months). A total of 8 patients (80%) were able to return to full desired activities, including sports. Only 5 of 11 (45%) excisions had concomitant lateral femoral condyle cartilage pathology. There were significant improvements across multiple WOMAC domains, and the WOMAC total score improved from 28.5 ± 17.6 preoperatively to 11.6 ± 10.2 postoperatively (P < .05). Lysholm scores significantly improved from 66.6 ± 23.1 preoperatively to 80.2 ± 13.9 postoperatively (P = .044). Overall patient-reported satisfaction was 8.8 ± 1.6. CONCLUSION: Fabella excision in the setting of fabella syndrome demonstrated improvements in clinical outcome scores, high rate of returning to preinjury level of activities, and low risk of complications or need for additional surgical procedures.

Incidence of Displaced Posterolateral Tibial Plateau and Lateral Femoral Condyle Impaction Fractures in the Setting of Primary Anterior Cruciate Ligament Tear.

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.

Morphologic Variants of Posterolateral Tibial Plateau Impaction Fractures in the Setting of Primary Anterior Cruciate Ligament Tear.

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.

Combined Anterior Cruciate Ligament Reconstruction and Lateral Extra-Articular Tenodesis.

Anterolateral rotational instability may persist after anterior cruciate ligament (ACL) reconstruction for a variety of reasons including damage to lateral or posterolateral structures, injury to the meniscus, disruption of anterolateral soft tissue structures, or increased tibial slope. In the setting of revision or primary ACL reconstruction with persistent anterolateral laxity, despite repair or reconstruction of other injured structures or in the setting of increased tibial slope, a lateral extra-articular tenodesis procedure can be used to augment an ACL reconstruction to aid in restoring anterolateral rotational stability and to upload the ACL reconstruction graft. This article details our technique for performing a modified Lemaire lateral extra-articular tenodesis using iliotibial band autograft as an adjunct to ACL reconstruction.

Combined Posterior Cruciate Ligament and Superficial Medial Collateral Ligament Knee Reconstruction: Avoiding Tunnel Convergence.

Combined posterior cruciate ligament (PCL) and medial collateral ligament (MCL) injuries represent a complex pathology that requires a thorough clinical and radiographic examination to diagnose and identify all injured structures. Anatomic reconstruction of the injured ligaments is recommended, including double-bundle PCL reconstruction and superficial MCL augmentation. In the setting of this complex reconstruction, several technical aspects require consideration and preoperative planning, including the risk of femoral tunnel convergence on the medial aspect of the femoral condyle. This article details our technique for combined anatomic double-bundle PCL reconstruction and superficial MCL augmentation to avoid tunnel convergence. Level I (knee); level II (PCL).

Injury Surveillance in Major League Soccer: A 4-Year Comparison of Injury on Natural Grass Versus Artificial Turf Field.

BACKGROUND: Artificial playing surfaces are becoming more common due to decreased cost of maintenance and increased field usability across different environmental conditions. The Fédération Internationale de Football Association (FIFA) has approved newer generation artificial turf for soccer competition at the elite level, but many elite-level athletes prefer to play on natural grass surfaces due to a perceived increase in injury rate, discomfort, and fatigability on artificial turf. HYPOTHESIS: Injury rates and rates of individually categorized types of injury experienced on artificial turf are noninferior to rates of injury on the standard comparator, natural grass, in elite-level Major League Soccer athletes. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Over the course of 4 Major League Soccer seasons (2013-2016), athlete injury data were recorded electronically. Injury data recorded in matches between 2 Major League Soccer teams were then analyzed. Playing surface was known for each venue, and all artificial turf surfaces were rated as 2-star according to FIFA criteria. Incidence rate ratios (Artificial Turf ÷ Natural Grass) were calculated with a 95% CI (α = .05) for both overall injury incidence and individual injury subgroups. A noninferiority margin (δ) of 0.15 was used to determine noninferiority of injury incidence rates. RESULTS: A total of 2174 in-game injuries were recorded during the study period, with 1.54 injuries per game on artificial turf and 1.49 injuries per game on natural grass (incidence rate ratio, 1.033; 95% CI, 0.937-1.139). Within injury subgroups, overall ankle injury, Achilles injury, and ankle fracture were found to have a statistically higher incidence on artificial turf. Artificial turf was found to be noninferior to natural grass for overall foot injury and forefoot injury. No statistically significant differences were found in knee injuries between the 2 surfaces. CONCLUSION: The overall rate of injury on artificial turf was noninferior to that on natural grass. Within individual injury categories, a higher rate of ankle injury was found on artificial turf. No other injury subgroup demonstrated statistically significant differences between surfaces. CLINICAL RELEVANCE: FIFA 2-star rated artificial turf is a viable alternative to natural grass in elite-level soccer competition. Innovative research methods for comparing artificial turf versus natural grass may elucidate relative advantages with respect to player safety.

Surgical Management and Treatment of the Anterior Cruciate Ligament-Deficient Knee with Malalignment.

Varus malalignment and an increased tibial slope can result in instability in an anterior cruciate ligament (ACL)-deficient knee. Malalignment can also be a cause of recurrent instability following ACL reconstruction. Varus malalignment can contribute to loosening or failure of primary ACL reconstruction and contribute to progressive medial compartment arthritis. High tibial osteotomies performed in conjunction with ACL reconstruction can improve alignment, restore anterior knee stability, and help reduce the advancement of arthritis.

Massive gas gangrene secondary to occult colon carcinoma.

Gas gangrene is a rare but often fatal soft-tissue infection. Because it is uncommon and the classic symptom of crepitus does not appear until the infection is advanced, prompt diagnosis requires a high index of suspicion. We present a case report of a middle-aged man who presented with acute onset lower-extremity pain that was initially thought to be due to deep vein thrombosis. After undergoing workup for pulmonary embolism, he was found to have massive gas gangrene of the lower extremity secondary to an occult colon adenocarcinoma and died within hours of presentation from multisystem organ failure.

Iatrogenic hallux varus treatment algorithm.

Iatrogenic hallux varus is a relatively rare complication of corrective hallux valgus surgery that has multiple pathologic facets. It requires a comprehensive assessment that focuses on joint flexibility, joint integrity, soft tissue balance, and bony deformity. A step-wise treatment approach is used to address all elements of the deformity. The literature on hallux varus treatments consists mainly of retrospective case series, with several proposed procedures addressing various degrees of deformity. Comparison of these procedures is a challenging endeavor and each case should be considered on an individual basis.