Utilizing Nonequilibrium Isotope Enrichments to Dramatically Increase Turnover Measurement Ranges in Single Biopsy Samples from Humans.

The synthesis of new proteins and the degradation of old proteins in vivo can be quantified in serial samples using metabolic isotope labeling to measure turnover. Because serial biopsies in humans are impractical, we set out to develop a method to calculate the turnover rates of proteins from single human biopsies. This method involved a new metabolic labeling approach and adjustments to the calculations used in previous work to calculate protein turnover. We demonstrate that using a nonequilibrium isotope enrichment strategy avoids the time dependent bias caused by variable lag in label delivery to different tissues observed in traditional metabolic labeling methods. Turnover rates are consistent for the same subject in biopsies from different labeling periods, and turnover rates calculated in this study are consistent with previously reported values. We also demonstrate that by measuring protein turnover we can determine where proteins are synthesized. In human subjects a significant difference in turnover rates differentiated proteins synthesized in the salivary glands versus those imported from the serum. We also provide a data analysis tool, DeuteRater-H, to calculate protein turnover using this nonequilibrium metabolic 2H2O method.

Descriptive Epidemiology From the Research in Osteochondritis Dissecans of the Knee (ROCK) Prospective Cohort.

BACKGROUND: Osteochondritis dissecans (OCD) occurs most commonly in the knees of young individuals. This condition is known to cause pain and discomfort in the knee and can lead to disability and early knee osteoarthritis. The cause is not well understood, and treatment plans are not well delineated. The Research in Osteochondritis Dissecans of the Knee (ROCK) group established a multicenter, prospective cohort to better understand this disease. PURPOSE: To provide a baseline report of the ROCK multicenter prospective cohort and present a descriptive analysis of baseline data for patient characteristics, lesion characteristics, and clinical findings of the first 1000 cases enrolled into the prospective cohort. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients were recruited from centers throughout the United States. Baseline data were obtained for patient characteristics, sports participation, patient-reported measures of functional capabilities and limitations, physical examination, diagnostic imaging results, and initial treatment plan. Descriptive statistics were completed for all outcomes of interest. RESULTS: As of November 2020, a total of 27 orthopaedic surgeons from 17 institutions had enrolled 1004 knees with OCD, representing 903 patients (68.9% males; median age, 13.1 years; range, 6.3-25.4 years), into the prospective cohort. Lesions were located on the medial femoral condyle (66.2%), lateral femoral condyle (18.1%), trochlea (9.5%), patella (6.0%), and tibial plateau (0.2%). Most cases involved multisport athletes (68.1%), with the most common primary sport being basketball for males (27.3% of cases) and soccer for females (27.6% of cases). The median Pediatric International Knee Documentation Committee (Pedi-IKCD) score was 59.9 (IQR, 45.6-73.9), and the median Pediatric Functional Activity Brief Scale (Pedi-FABS) score was 21.0 (IQR, 5.0-28.0). Initial treatments were surgical intervention (55.4%) and activity restriction (44.0%). When surgery was performed, surgeons deemed the lesion to be stable at intraoperative assessment in 48.1% of cases. CONCLUSION: The multicenter ROCK group has been able to enroll the largest knee OCD cohort to date. This information is being used to further understand the pathology of OCD, including its cause, associated comorbidities, and initial presentation and symptoms. The cohort having been established is now being followed longitudinally to better define and elucidate the best treatment algorithms based on these presenting signs and symptoms.

Early Operative Versus Delayed Operative Versus Nonoperative Treatment of Pediatric and Adolescent Anterior Cruciate Ligament Injuries: A Systematic Review and Meta-analysis.

BACKGROUND: Treatment options for pediatric and adolescent anterior cruciate ligament (ACL) injuries include early operative, delayed operative, and nonoperative management. Currently, there is a lack of consensus regarding the optimal treatment for these injuries. PURPOSE/HYPOTHESIS: The purpose was to determine the optimal treatment strategy for ACL injuries in pediatric and adolescent patients. We hypothesized that (1) early ACL reconstruction results in fewer meniscal tears than delayed reconstruction but yields no difference in knee stability and (2) when compared with nonoperative management, any operative management results in fewer meniscal tears and cartilage injuries, greater knee stability, and higher return-to-sport rates. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: A systematic search of databases was performed including PubMed, Embase, and Cochrane Library using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were a pediatric and adolescent patient population (≤19 years old at surgery), the reporting of clinical outcomes after treatment of primary ACL injury, and original scientific research article. Exclusion criteria were revision ACL reconstruction, tibial spine avulsion fracture, case report or small case series (<5 patients), non-English language manuscripts, multiligamentous injuries, and nonclinical studies. RESULTS: A total of 30 studies containing 50 cohorts and representing 1176 patients met our criteria. With respect to nonoperative treatment, knee instability was observed in 20% to 100%, and return to preinjury level of sports ranged from 6% to 50% at final follow-up. Regarding operative treatment, meta-analysis results favored early ACL reconstruction over delayed reconstruction (>12 weeks) for the presence of any meniscal tear (odds ratio, 0.23; P = .006) and irreparable meniscal tear (odds ratio, 0.31; P = .001). Comparison of any side-to-side differences in KT-1000 arthrometer testing did not favor early or delayed ACL reconstruction in either continuous mean differences (P = .413) or proportion with difference ≥3 mm (P = .181). Return to preinjury level of competition rates for early and delayed ACL reconstruction ranged from 57% to 100%. CONCLUSION: Delaying ACL reconstruction in pediatric or adolescent patients for >12 weeks significantly increased the risk of meniscal injuries and irreparable meniscal tears; however, early and delayed operative treatment achieved satisfactory knee stability. Nonoperative management resulted in high rates of residual knee instability, increased risk of meniscal tears, and comparatively low rates of return to sports.

Management of the Anterior Cruciate Ligament-Injured Knee in the Skeletally Immature Athlete.

Intrasubstance tears of the anterior cruciate ligament (ACL) are being diagnosed with increasing frequency in the skeletally immature. Management options include nonoperative/ early surgical, or delayed surgical reconstruction. Nonoperative/delayed reconstruction results in worse functional outcomes than early reconstruction. Physicians are faced with a treatment dilemma; clinical and basic science studies have demonstrated risk of limb-length discrepancy and angular deformity with ACL reconstruction. Vertical drill tunnels decrease physeal damage and minimize growth deformity; however, this technique results in nonanatomic ACL graft placement. All-epiphyseal reconstruction avoids damage to the growth plate. These techniques are biomechanically superior to extraarticular and modified physeal-sparing procedures.

Iliopsoas: Pathology, Diagnosis, and Treatment.

Disorders of the iliopsoas can be a significant source of groin pain in the athletic population. Commonly described pathologic conditions include iliopsoas bursitis, tendonitis, impingement, and snapping. The first-line treatment for iliopsoas disorders is typically conservative, including activity modification, physical therapy, nonsteroidal anti-inflammatory drugs, and corticosteroid injections. Surgical treatment can be considered if the patient fails conservative measures and typically involves arthroscopic lengthening of the musculotendinous unit and treatment of concomitant intra-articular abnormality. Tendon release has been described: in the central compartment, in the peripheral compartment, and at the lesser trochanter, with similar outcomes observed between the techniques.

Femoral Neck Stress Fractures and Imaging Features of Femoroacetabular Impingement.

BACKGROUND: Prior literature has suggested an association between the radiographic signs of femoroacetabular impingement (FAI) and femoral neck stress fractures (FNSF) or femoral neck stress reactions (FNSR). At the time of the writing of this article, no study has described the association of FAI and FNSF/FNSR along with the need for surgical intervention and outcomes. OBJECTIVE: To determine the prevalence of radiographic features of FAI in patients diagnosed with FNSF. DESIGN: Retrospective case series. SETTING: Tertiary care, institutional setting. PATIENTS: A medical records search program (Stanford Translational Research Integrated Database Environment, Stanford University, California) was used to retrospectively search for patients 18-40 years old with a history of FNSF or FNSR. The records were obtained from the period July 25, 2003, to September 23, 2011. METHODS: For assessment of risk factors, plain radiographs and magnetic resonance imaging studies were reviewed for features of cam or pincer FAI. Medical records were reviewed to determine whether patients required operative intervention. MAIN OUTCOME MEASURES: Incidence of abnormal alpha (α) angle, abnormal anterior offset ratio, abnormal femoral head-neck junction, coxa profunda, positive crossover sign, and abnormal lateral center-to-edge angle. RESULTS: Twenty-one female and 3 male participants (mean age 27 years, range 19-39 years) were identified with magnetic resonance imaging evidence of femoral neck stress injury. Cam morphology was seen in 10 patients (42%). Pincer morphology could be assessed in 18 patients, with coxa profunda in 14 (78%) and acetabular retroversion in 6 (14%). Features of combined pincer and cam impingement were observed in 4 patients (17%). Seven patients (29%) had operative intervention, with 3 (12%) requiring internal fixation of their femoral neck fractures, and all had radiographic evidence of fracture union after surgery. Four patients (17%) had persistent symptoms after healing of their FNSF with conservative treatment and eventually required surgery for FAI, 3 had no pain at final follow-up 1 year post-surgery, and one patient was lost to follow-up. CONCLUSION: The results of the current study suggest that patients in the general population with femoral neck stress injuries have a higher incidence of bony abnormalities associated with pincer impingement, including coxa profunda and acetabular retroversion, although it is unclear whether pincer FAI is a true risk factor in the development of FNSF.

Correlation of meniscal and articular cartilage injuries in children and adolescents with timing of anterior cruciate ligament reconstruction.

BACKGROUND: In pediatric patients, anterior cruciate ligament (ACL) reconstruction is controversial; however, delaying surgery until skeletal maturity is complete may increase the risk of secondary meniscal and articular cartilage injury. PURPOSE: To assess the risk of meniscal and chondral injuries with delay of ACL reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Records were reviewed in patients younger than 17 years (median age, 14 years) who had ACL reconstruction. Patients were consecutively enrolled and assigned to 1 of 3 surgical groups based on timing of surgery: acute (<6 weeks after surgery), subacute (6-12 weeks), or chronic (>3 months). The type and grade of meniscal injuries was documented according to the International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) meniscal classification criteria. International Cartilage Repair Society (ICRS) criteria were used to document location and grade of chondral injuries. Associations between patient characteristics and meniscal injury were tested using rank sum and chi-square tests. Regression analyses were conducted to model incidence and severity of lateral and medial meniscal tears. There were 130 patients who had 135 ACL reconstructions between the years of 2000 and 2012. RESULTS: Sixty-two ACL injuries were treated acutely, 37 were subacute, and 36 were chronic. Meniscal injuries (n = 112) included 70 lateral and 42 medial tears. Time to surgery had bivariate association with lateral and medial meniscal tears (P = .016 and .007, respectively). Independent risk factors for incidence of lateral meniscal tears were younger age (P = .028) and return to sports activities before surgery (P = .007). Patients with 1 episode of instability had 3-fold higher odds of higher grade lateral meniscal tear (95% CI, 1.30-7.60). Compared with acute reconstruction, subacute and chronic reconstruction patients had 1.45 and 2.82 times higher odds, respectively, of lateral meniscal tear severity (P = .12). Independent risk factors for incidence of medial meniscal tears were female sex (P = .03), older age (P = .01), and any episode of instability (P = .01). Adjusted odds ratio for medial meniscal tear was 4.7 for an instability episode (vs no episode; P = .01). Adjusted odds ratio for increased severity of medial meniscal tears included any instability episode, 5.6 (P < .01); playing sports before reconstruction, 15.2 (P < .01); and time to surgery greater than 3 months, 4.3 (P = .046). Seventeen patients had 23 chondral injuries. The risk factors for chondral injury included increased time to surgery (P = .005) and any instability episode (P = .001). For increased grade of chondral injury, risk factors were time to surgery (P ≤ .001) and any instability episode (P = .003). CONCLUSION: Delayed ACL reconstruction increased the risks of secondary meniscal and chondral injuries in this population of pediatric patients.

Hip-femoral acetabular impingement.

Magnetic resonance imaging (MRI) has become a valuable technology for the diagnosis and treatment of femoroacetabular impingement (FAI). This article reviews the basic pathophysiology of FAI, as well as the techniques and indications for MRI and magnetic resonance arthrography. Normal MRI anatomy of the hip and pathologic MRI anatomy associated with FAI are also discussed. Several case examples are presented demonstrating the diagnosis and treatment of FAI.

Biomechanical evaluation of physeal-sparing fixation methods in tibial eminence fractures.

BACKGROUND: Tibial eminence fractures occur most commonly in skeletally immature children. Several techniques using physeal-sparing fracture fixation have been described, but their structural properties have not been evaluated. PURPOSE: To determine the strength and resistance to displacement of physeal-sparing techniques used to fix tibial eminence fractures. STUDY DESIGN: Controlled laboratory study. METHODS: Skeletally immature porcine knees were randomized into 4 treatment groups: (1) ultra-high molecular weight polyethylene suture-suture button (UHMWPE/SB), (2) suture anchor, (3) polydioxanone suture-suture button (PDS/SB), and (4) screw fixation. A prospective analysis of bone mineral density using dual-energy x-ray absorptiometry was performed on all specimens. Fracture fragments were created in a standardized manner and measured for size comparison. After fracture fixation, biomechanical testing was performed with cyclical and load-to-failure protocols by loading the tibia with an anterior shear force. RESULTS: In load-to-failure testing, screw fixation had a significantly lower median peak failure load (186.4 N; lower quartile [LQ], 158.4 N; upper quartile [UQ], 232.6 N) than did UHMWPE/SB (465.8 N; LQ, 397.8 N; UQ, 527.8 N), suture anchors (440.5 N; LQ, 323.0 N; UQ, 562.3 N), and PDS/SB (404.3 N; LQ, 385.9 N; UQ, 415.6 N). UHMWPE/SB demonstrated a significantly higher median yield load (465.8 N; LQ, 397.8 N; UQ, 527.8 N) than did PDS/SB (306.7 N; LQ, 271.4, N; UQ, 405.7 N) and screw fixation (179.0 N; LQ, 120.2 N; UQ, 232.5 N). During cyclical testing, screw fixation demonstrated significantly lower percentage survival of specimens (0%) compared with the other groups (UHMWPE/SB, 100%; suture anchor, 78%; PDS/SB, 78%). After 1000 cycles of loading, PDS/SB fixation had significantly more median creep (6.76 mm; LQ, 6.34 mm; UQ, 8.28 mm) than did UHMWPE/SB (4.43 mm; LQ, 3.80 mm; UQ, 4.73 mm) and suture anchor fixation (3.06 mm; LQ, 2.59 mm; UQ, 4.28 mm). The lowest median stiffness was observed in the PDS/SB group (48.6 N/mm; LQ, 45.3 N/mm; UQ, 54.2 N/mm). UHMWPE/SB fixation demonstrated a significantly higher median peak failure load after cyclic testing (469.0 N; LQ, 380.6 N; UQ, 507.2 N) than did PDS/SB (237.7 N; LQ, 197.3 N; UQ, 298.3 N) and screw fixation (132.4 N; LQ, 123.7 N; UQ, 180.9 N). Suture anchor fixation had significantly more variance, as demonstrated by width of interquartile range, in peak failure load, yield load, and creep than did other techniques. CONCLUSION: Physeal-sparing fixation of tibial eminence fractures with UHMWPE suture-suture button is biomechanically superior to both PDS suture-suture button and a single screw at the time of surgery and provides more consistent fixation than do suture anchors. CLINICAL RELEVANCE: Suture anchors provide inconsistent fixation for tibial eminence fractures.

Operative Fixation of Chondral Loose Bodies in Osteochondritis Dissecans in the Knee: A Report of 5 Cases.

BACKGROUND: Osteochondritis dissecans (OCD) can progress to loose body formation, with or without subchondral bone attachment to the lesion. The efficacy of internal fixation of chondral loose bodies has not been determined. HYPOTHESIS: Operative fixation of cartilaginous loose bodies would result in (1) healed OCD at second-look arthroscopy, (2) restored cartilage appearance on magnetic resonance imaging (MRI), and (3) nearly normal knee function, as determined by patient-reported outcome scores. STUDY DESIGN: Retrospective case series; Level of evidence, 4. METHODS: Five patients who underwent cartilaginous loose body fixation were identified. Lesions were located on the lateral trochlea (n = 2) and medial femoral condyle (n = 3) (mean size, 2.5 cm(2)). Loose bodies were reattached with compression screws through mini-arthrotomy or arthroscopy. Patients were nonweightbearing for 12 weeks postoperatively. After 12 weeks, screws were removed arthroscopically, and OCD stability was evaluated. Three patients underwent MRI to determine articular cartilage status. Images were evaluated using the magnetic resonance observation of cartilage repair tissue (MOCART) score. Patients were interviewed and completed the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire. RESULTS: Four patients had stable lesions at 12 weeks after surgery. One patient had slight motion to one-third of the lesion and stability to the remaining two-thirds. Three patients underwent an MRI. The mean time from surgery to MRI was 3.1 years. Mean MOCART score was 72.0 ± 10.4. One patient required repeat arthroscopy 1 year after initial fixation for debridement and arthroscopic drilling of an incompletely healed area of the lesion. Four patients completed the KOOS questionnaire. The mean time to KOOS completion was 4.6 years. Mean KOOS subscales for knee pain (91.0 ± 8.9), knee symptoms (83.0 ± 7.9), and function in activities of daily living (91.9 ± 10.6) were similar to published age-matched controls; however, scores for sports and recreation function (70.0 ± 17.8) and knee-related quality of life (67.2 ± 12.9) were lower. CONCLUSION: Operative fixation of chondral loose bodies, without macroscopically visible subchondral bone attachment, resulted in lesion stability at second-look arthroscopy. At final follow-up, patients had no substantial pain and normal function in activities of daily life compared with controls; however, knee-related quality of life and sport and recreation function were reduced, and 1 patient required reoperation for an unhealed portion of the lesion.

Radiographic measurements of the intercondylar notch: are they accurate?

PURPOSE: The purpose of this study was to evaluate the accuracy of radiographic measurements of the intercondylar notch. METHODS: Radiographs of 10 cadaveric knees were obtained via the 3 methods reported in the literature (Holmblad 45 degree, Holmblad 70 degree, and Rosenberg views), after removal of the patella and surrounding soft tissues. The anterior outlet of the intercondylar notch of each knee was then outlined with barium paste, and radiography was repeated. A total of 1,770 radiographs were obtained for the 10 knees. Six measurements of the anterior outlet of the intercondylar notch were made from each radiograph and corrected for magnification. Finally, the notch width index was calculated. Caliper measurements were subsequently made of each knee to compare the size of the anterior outlet of the notch with the radiographic measurements with and without barium. RESULTS: There were statistically significant differences in caliper measurements compared with all but one radiographic measurement obtained from the Holmblad 45 degree, Holmblad 70 degree, and Rosenberg views. The radiographs taken with barium outlining the intercondylar notch clearly showed the inability to accurately identify the anterior outlet on radiographs. CONCLUSIONS: Even under optimal conditions, correcting for technique, projection, and magnification, most of the radiographic measurements of the anterior outlet of the intercondylar notch were inaccurate. The notch width index calculated from the Holmblad 70 degree view appears to be the only accurate radiographic measurement. CLINICAL RELEVANCE: This controlled laboratory study shows that clinicians should use caution when basing conclusions on radiographic measurements of the intercondylar notch.