Y-27632 acts beyond ROCK inhibition to maintain epidermal stem-like cells in culture.

Conditional reprogramming is a cell culture technique that effectively immortalizes epithelial cells with normal genotypes by renewing epidermal stem cells. Y-27632, a compound that promotes conditional reprogramming through an unknown mechanism, was developed to inhibit the two Rho-associated kinase (ROCK) isoforms. We used human foreskin keratinocytes (HFKs) to study the role of Y-27632 in conditional reprogramming and learn how ROCKs control epidermal stem cell renewal. In conditional reprogramming, Y-27632 increased HFK adherence to culture dishes, progression through S, G2 and M phases of the cell cycle, and epidermal stem cell marker levels. Although this correlated with ROCK inhibition by Y-27632, we generated CRISPR-Cas9-mediated HFK ROCK knockouts to test the direct role of ROCK inhibition. Knockout of single ROCK isoforms was insufficient to disrupt ROCK activity or promote HFK propagation without Y-27632. Although ROCK activity was reduced, HFKs with double knockout of ROCK1 and ROCK2 still required Y-27632 to propagate. Y-27632 was the most effective among the ROCK inhibitors we tested at promoting HFK proliferation and epidermal stem cell marker expression. Thus, the ability of Y-27632 to promote an epidermal stem cell state in conditional reprogramming not only depends upon ROCK inhibition but also acts via as-yet-unidentified mechanisms. Epidermal stem cell renewal might in part be regulated by ROCKs, but also involves additional pathways.

Major complications after distal biceps tendon repairs: retrospective cohort analysis of 970 cases.

BACKGROUND: The major complication and reoperation rates after distal biceps repair are poorly defined. The purpose of this large retrospective cohort study of distal biceps repairs performed by multiple surgeons within a large orthopedic group was to more clearly define the rates and risk factors of clinically impactful major complications and reoperations. METHODS: All distal biceps tendon repairs performed from January 2005 through April 2017 with a minimum 2-month follow-up were identified using Current Procedural Terminology code 24342. We included 970 patients. The primary outcome measure was the total major complication rate. Reoperations, minor complications, and risk factors were also tracked. RESULTS: Repairs were performed via a single anterior incision in 652 cases and a 2-incision exposure in 318 cases. A 7.5% major complication rate and 4.5% reoperation rate were observed overall. Major complications occurred at the following rates: proximal radioulnar synostosis, 1.0%; heterotopic ossification or loss of range of motion with reoperation, 0.9%; tendon rerupture, 1.6%; deep infection, 0.5%; posterior interosseous nerve palsy, 1.9%; and complex regional pain syndrome, 0.6%. The 2-incision exposure was identified as a significant risk factor for the development of proximal radioulnar synostosis when compared with single-incision repair techniques (P = .0003; odds ratio, 19), occurring in 2.8% of 2-incision exposure cases. Lateral antebrachial cutaneous nerve neuritis or numbness and radial sensory nerve neuritis or numbness were documented more frequently in the postoperative period among patients treated with a single-incision exposure (P < .0001 and P = .034, respectively). CONCLUSIONS: Distal biceps repair is associated with a 7.5% major complication rate and 4.5% reoperation rate. The use of a 2-incision technique for repair increases the risk of radioulnar synostosis.

Variability in Patellofemoral Alignment Measurements on MRI: Influence of Knee Position.

OBJECTIVE: The purpose of this study was to determine the variability of distances between four distinct anatomic landmarks used for the evaluation of patellofemoral alignment while implementing controlled changes in patient positioning during MRI. MATERIALS AND METHODS: Limited MRI was performed of 12 knees in healthy volunteers (10 men, two women; mean age, 28 years) with the knees in four different positions. The four landmarks used were TT (the most anterior point of the osseous tibial tubercle), TG (the nadir of the cartilaginous trochlear groove), PT (the center of the patellar tendon insertion on the tibia), and PCL (the medial border of the posterior cruciate ligament at its insertion along the posterior tibia). TT-TG, PT-TG, TT-PCL, and PT-PCL distances were measured on the MR images. Each distance was measured with the knee at maximum patient comfort (rest), full extension, 15° of flexion, and 30° of flexion. Linear mixed models with random intercepts were implemented to determine variability between measurements and knee position. RESULTS: In general, measurements based on anatomic landmark and knee position varied greatly. The greatest variability in different knee positions was seen in mean TT-TG and PT-TG distances ± SD (TT-TG: rest, 18.1 ± 7.9 mm; full extension, 17.3 ± 5.3 mm; 15° of flexion, 11.4 ± 5.7 mm; 30° of flexion, 11.7 ± 6.0 mm; intraclass correlation coefficient [ICC] = 0.539; PT-TG: rest, 18.1 ± 6.3 mm; full extension, 17.9 ± 4.7 mm; 15° of flexion, 13.2 ± 5.2 mm; 30° of flexion, 11.8 ± 4.3 mm; ICC = 0.633). In contrast, knee position did not significantly affect distances for TT-PCL and PT-PCL (TT-PCL: rest, 23.5 ± 6.8 mm; full extension, 20.5 ± 5.5 mm; 15° of flexion, 22.8 ± 6.2 mm; 30° of flexion, 22.8 ± 6.7 mm; ICC = 0.484; PTPCL: rest, 23.4 ± 5.3 mm; full extension, 21.5 ± 4.5 mm; 15° of flexion, 22.3 ± 4.3 mm; 30° of flexion, 23.1 ± 4.8 mm; ICC = 0.509). CONCLUSION: On MRI, TT-PCL and PT-PCL measurements have significantly less variability compared with TT-TG and PT-TG measurements, regardless of knee position. Although further studies are warranted, the use of TT-PCL and PT-PCL measurements may offer more reliable assessment of tibial tubercle lateralization and patellofemoral alignment.

Arthroscopic hip labral repair: the iberian suture technique.

Arthroscopic hip labral repair has beneficial short-term outcomes; however, debate exists regarding ideal surgical labral repair technique. This technical note presents an arthroscopic repair technique that uses intrasubstance labral suture passage to restore the chondrolabral interface. This "Iberian suture technique" allows for an anatomic repair while posing minimal risk of damage to the labral and chondral tissues.

Reliability, validity, and responsiveness of a modified International Knee Documentation Committee Subjective Knee Form (Pedi-IKDC) in children with knee disorders.

BACKGROUND: The International Knee Documentation Committee (IKDC) Subjective Knee Form is a knee-specific measure of symptoms, function, and sports activity. A modified IKDC Subjective Knee Form (pedi-IKDC) has been developed for use in children and adolescents. The purpose of this study was to determine the psychometric characteristics of the pedi-IKDC in children and adolescents with knee disorders. HYPOTHESIS: The pedi-IKDC is a reliable, valid, and responsive patient-administered outcome instrument in the pediatric population with knee disorders. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Test-retest reliability, content validity, criterion validity, construct validity, and responsiveness to change were determined for the pedi-IKDC in patients aged 10 to 18 years with a variety of knee disorders. Test-retest reliability was measured in a group of 72 patients with a stable knee disorder. Validity was measured in a group of 589 patients with the Child Health Questionnaire to determine criterion validity. Responsiveness was measured in a group of 98 patients undergoing a variety of knee surgical procedures. RESULTS: The overall pedi-IKDC had acceptable test-retest reliability (intraclass correlation coefficient, .91) and excellent internal consistency (Cronbach alpha, .91). The form also demonstrated acceptable floor (0%) and ceiling (6%) effects. There was acceptable criterion validity with significant (P < .01) correlation between the overall pedi-IKDC and 9 relevant domains of the Child Health Questionnaire. Construct validity was acceptable, with all 11 hypotheses demonstrating significance (P < .0001). Responsiveness to change was acceptable (effect size, 1.39; standardized response mean, 1.35). CONCLUSION: The pedi-IKDC demonstrated overall acceptable psychometric performance for outcome assessment of children and adolescents with various disorders of the knee.

Fixation of juvenile osteochondritis dissecans lesions of the knee using poly 96L/4D-lactide copolymer bioabsorbable implants.

BACKGROUND: The fixation of juvenile osteochondritis dissecans (OCD) lesions has been described using metal implants, staples, bone pegs, and bioabsorbable implants. Bioabsorbable fixation has potential benefits including not requiring a second surgery for implant removal, no interference on postoperative magnetic resonance imaging (MRI) scans, and a potentially lower incidence of prominent hardware. The possible complications of bioabsorbable fixation include synovitis, loss of fixation owing to noncompressive properties, and sterile abscess formation. The results of bioabsorbable fixation of juvenile OCD lesions of the knee have not been well studied. The purpose of this study was to evaluate the efficacy and safety of a bioabsorbable copolymer fixation in the management of unstable OCD lesions of the knee in adolescents. METHODS: This is a retrospective case series of patients with unstable OCD lesions of the knee that were treated with poly 96L/4D-lactide copolymer bioabsorable implants. Information was gathered through 3 standardized and validated knee-function questionnaires, participants' medical records, plain films, MRIs, and pain level and satisfaction scale questionnaires. RESULTS: Twenty-four knees in 24 patients were evaluated. The mean age at the time of surgery was 14.4 years. The mean follow-up was 39.6 months. The mean International Knee Documentation Committee score at follow-up was 84.9, the mean Lysholm score was 88.0, and the mean Tegner score was 7.9. Plain films at an average of 19.2 months postoperatively revealed interval healing in 9 patients, no significant change in 1 patient, complete healing in 13 patients, and loose bodies with no interval healing in 1 patient. MRIs were obtained postoperatively in 17 knees, with a mean follow-up of 22.4 months. Interval healing was present in 16 of 17 MRIs, consistent with the plain film findings. Twenty-two of 24 patients had good-to-excellent outcomes. CONCLUSION: Poly 96L/4D-lactide copolymer bioabsorable implants seem to be safe and effective for the management of unstable juvenile OCD lesions of the knee. They offer stability for the healing OCD lesions, with minimal reaction from degradation products.

Prediction of spatial orientation and morphology of calcaneonavicular coalitions.

BACKGROUND: Calcaneonavicular coalitions (CNC) have been reported to be associated with anatomical aberrations of either the calcaneus and/or navicular bones. These morphological abnormalities may complicate accurate surgical resection. Three-dimensional analysis of spatial orientation and morphological characteristics may help in preoperative planning of resection. MATERIALS AND METHODS: Sixteen feet with a diagnosis of CNC were evaluated by means of 3-D CT modeling. Three angles were defined that were expressed in relation to one reproducible landmark (lateral border of the calcaneus): the dorsoplantar inclination, anteroposterior inclination, and socket angle. The depth and width of the coalitions were measured and calculated to obtain the estimated contact surface. Three-dimensional reconstructions of the calcanei served to evaluate the presence, distortion or absence of the anterior calcaneal facet and presence of a navicular beak. The interrater correlations were assessed in order to obtain values for the accuracy of the measurement methods. Sixteen normal feet were used as controls for comparison of the socket angle; anatomy of the anterior calcaneal facet and navicular beak as well. RESULTS: The dorsoplantar inclination angle averaged 50 degrees (+/-17), the anteroposterior inclination angle 64 degrees (+/-15), and the pathologic socket angle 98 degrees (+/-11). The average contact area was 156 mm(2). Ninety-four percent of all patients in the CNC group revealed a plantar navicular beak. In 50% of those patients the anterior calcaneal facet was replaced by the navicular portion and in 44% the facet was totally missing. In contrast, the socket angle in the control group averaged 77 degrees (+/-18), which was found to be statistically different than the CNC group (p = 0.0004). Only 25% of the patients in the control group had a plantar navicular beak. High, statistically significant interrater correlations were found for all measured angles. CONCLUSION: Computer-aided CT analysis and reconstructions help to determine the spatial orientations of CNC in space and provide useful information in order to anticipate morphological abnormalities of the calcaneus and navicular.

Surgical treatment of unresolved Osgood-Schlatter disease: ossicle resection with tibial tubercleplasty.

UNLABELLED: The mainstay of treatment of Osgood-Schlatter apophysitis is nonoperative. Surgical treatment has been described for patients who have failed nonoperative management of Osgood-Schlatter disease. The purpose of this study is to evaluate the functional outcome of ossicle excision and tibial tubercleplasty for unresolved Osgood-Schlatter disease that has failed nonoperative treatment. METHODS: A retrospective review was performed on 16 knees in 15 patients who underwent ossicle excision and tibial tubercleplasty for unresolved Osgood-Schlatter disease. Functional outcome was assessed using the International Knee Documentation Committee, the Lysholm Knee Scale, and Tegner Activity Score. RESULTS: Twelve patients (75%) returned to preoperative activities and sports, 2 patients (12.5%) partially returned, and 1 patient (6%) did not return. The mean postoperative Lysholm knee score was 76.5. Patients' individual scores ranged from 40 to 100. The mean International Knee Documentation Committee knee score was 75, ranging from 40 to 100. The mean Tegner activity level was 6.8 (range, 3-10). CONCLUSIONS: It is our recommendation that when patients fail extensive nonoperative management, surgery to remove the symptomatic ossicle should be offered after skeletal maturity. When this is the case, the addition of tubercleplasty should be performed.

Internal fixation of juvenile osteochondritis dissecans lesions of the knee.

BACKGROUND: Operative techniques for the management of juvenile osteochondritis dissecans lesions of the knee include drilling, internal fixation, fragment removal, and chondral resurfacing. PURPOSE: To evaluate the functional and radiographic outcome of internal fixation of juvenile osteochondritis dissecans lesions of the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The study design was a retrospective case series. Twenty-six knees in 24 skeletally immature patients underwent internal fixation of osteochondritis dissecans lesions. Mean follow-up was 4.25 years (range, 2-14.75 years). Mean patient age was 14.7 years (range, 11-16 years). There were 13 boys and 11 girls. Lesions were graded per the Ewing and Voto classification, with 9 stage II lesions (fissured), 11 stage III lesions (partially attached), and 6 stage IV lesions (detached). Methods of internal fixation included variable pitch screws (n = 11), bioabsorbable tacks (n = 10), partially threaded cannulated screws (n = 3), and bioabsorbable pins (n = 3). Mean follow-up was 4.25 years (range, 2.0-14.75 years). RESULTS: Healing occurred in 22 of 26 lesions (healing rate, 84.6%). There was no significant difference in healing rate for lesion location, fixation method, or lesion grade. In fact, all 6 stage IV (detached) lesions healed. The mean postoperative Lysholm score was 85.8, mean postoperative International Knee Documentation Committee score was 82.6, and mean postoperative Tegner activity level was 7.4. Mean time to healing was 6 months. Eight patients underwent additional procedures: 4 for nonunion, 1 for hemarthrosis, and 3 for elective screw removal. CONCLUSION: Given the relatively high healing rate, good functional outcome, and low complication rate, the authors advocate internal fixation of unstable juvenile osteochondritis dissecans lesions of the knee, even for detached lesions and in patients with a history of surgery for the osteochondritis dissecans lesion.