Cartilage MRI relaxation times after arthroscopic partial medial meniscectomy reveal localized degeneration.

PURPOSE: Little is known about the early changes in cartilage composition and tibiofemoral kinematics following partial meniscectomy. The purpose of this study was to determine the effects of partial meniscectomy on cartilage compositional properties using T1ρ and T2 relaxation time mapping and to assess changes in tibiofemoral kinematics. It is hypothesize that abnormal tibiofemoral kinematics and relaxation time elevation (a reflection of changes in cartilage biochemical composition) in the weight-bearing regions of the knees following meniscectomy will be observed. METHODS: Nine patients (7 males and 2 females; mean age, 48.6 ± 10.8 years; BMI = 27.3 ± 3.8 kg/m(2)) with tears of the posterior horn of the medial meniscus underwent arthroscopic partial meniscectomy. Pre-surgical and 6 months post-surgical MRIs were obtained in all subjects to evaluate cartilage relaxation times and tibiofemoral kinematics. Paired t tests were performed to determine significant changes in cartilage relaxation times from baseline. RESULTS: T1ρ relaxation time in the region of the medial femoral condyle directly adjacent to the resection showed an increase of 7.4% at 6 months (p = 0.02). T2 relaxation times in both the medial and lateral tibial plateaus showed significant elevation at 6 months. Consistent kinematic trends were not found in post-meniscectomized knees. CONCLUSIONS: These results suggest that arthroscopic partial meniscectomy affects the biochemical composition of articular cartilage in the knee in as early as 6 months. The largest responses were observed in the weight-bearing regions and the cartilage immediately adjacent to the resection. This suggests that the loading environment has been altered enough to result in cartilage compositional changes in a very brief period of time following meniscectomy. LEVEL OF EVIDENCE: IV.

Pain as Initial Presenting Symptom Is Associated With Delay to Seeking Medical Attention, Higher Risk of Relapse, and Shorter Survival in Patients With Early-Stage Extremity or Trunk Synovial Sarcoma.

BackgroundWhether the presenting symptom of pain vs mass impacts survival of early-stage synovial sarcoma is not known. Patients and MethodsThe authors investigated patients with early-stage extremity/trunk synovial sarcoma diagnosed from 2005 to 2017 at Kaiser Permanente Northern California for associations between the presenting symptom and survival. ResultsAmong 56 patients with early-stage extremity/trunk synovial sarcoma, median disease-free survival (DFS) was 20.3 months for the pain-only group (n = 19) vs 50.5 months for the mass ± pain group (n = 37) (p = 0.004), and median overall survival (OS) was 35.7 months vs 53.9 months (p = 0.009), respectively. Median DFS was 26.9 months for the pain ± mass group (n = 32) vs 48.6 months for the mass-only group (n = 24) (p = 0.047), whereas OS was not significantly different (49.6 vs. 53.6 months, p = 0.282). Pain at presentation was associated with a higher incidence of deep tumors and a higher risk of relapse. Cox regression model adjusting for age, sex, race, tumor location, tumor size, and wait-time to seek medical attention showed that pain at presentation was associated with 3-fold worse DFS and OS. ConclusionPain at presentation was an adverse risk factor for patients with early-stage extremity/trunk synovial sarcoma.

Magnetic resonance imaging evaluation of knee kinematics after anterior cruciate ligament reconstruction with anteromedial and transtibial femoral tunnel drilling techniques.

PURPOSE: The purpose of this study was to use magnetic resonance (MR) imaging to evaluate the translational and rotational kinematics of anterior cruciate ligament (ACL) reconstructed knees with transtibial (TT) and anteromedial (AM) femoral tunnel drilling. METHODS: ACL reconstruction was performed in 21 subjects: 12 with AM drilling (5 men and 7 women; mean age, 33 ± 9 years; imaged 18 ± 5 months after surgery) and 9 with TT drilling (5 men and 4 women; mean age, 32 ± 9 years; imaged 12 ± 8 months after surgery). Three-tesla MR imaging was obtained bilaterally at extension and 30° to 40° of flexion under simulated loading (125 N). MR images were segmented and kinematic calculations done with in-house MATLAB software (The MathWorks, Natick, MA). Translation and rotation of the tibia and the tibiofemoral contact area were measured. Statistical analysis treated reconstructed and contralateral knees as independent groups. Reconstructed groups were compared with analysis of covariance using contralateral knees as baseline. P < .05 indicated significance. RESULTS: All kinematic measures in the AM group were similar to contralateral knees. The TT group showed significantly more total tibial rotation than contralateral knees (TT, 8.4° ± 3.9°; contralateral, 2.9° ± 6.8°) (P = .03), whereas the AM group did not (AM, 3.1° ± 5.6°; contralateral, 2.3° ± 5.4°) (P = .36). At knee extension, the tibia was more externally rotated in the TT group than in controls. Medial tibial translation was greater in the TT group than in controls. The AM group showed increased contact area in the lateral compartment compared with controls; no differences were seen in the TT group. CONCLUSIONS: Using an MR-based approach, we found that knee kinematics were better restored with the AM femoral tunnel drilling ACL reconstruction than with the TT femoral tunnel drilling approach, which resulted in increased knee laxity. Our in vivo results support previous cadaveric and clinical studies that have found AM ACL reconstruction to restore anatomy and stability better than the TT approach. However, the clinical significance of increased contact area in the AM group remains unclear. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Complete Regression of Rhabdomyosarcoma in an Adult Secondary to Postoperative Wound Infection Following Limb Salvage Surgery: A Case Report.

CASE PRESENTATION: A 33-year old man presented with a 25-cm lower extremity embryonal rhabdomyosarcoma with presumed extensive nodal metastasis on positron emission topography scan. Neoadjuvant chemotherapy and radiation provided minimal response. Following limb salvage resection and flap coverage, a prolonged postoperative infection occurred requiring intravenous antibiotics and wound care over 5 months. Given the infection, no postoperative radiation or chemotherapy was administered. Eight months following surgery, positron emission topography scan showed complete regression of local and nodal disease. The patient has remained in complete remission for more than 4 years. CONCLUSION: Postoperative wound infection leading to complete regression of embryonal rhabdomyosarcoma has not been reported. Stimulation of the innate and adaptive immune system through infectious elements is an area of ongoing immunotherapy research to improve sarcoma treatment outcomes.

Feasibility and Value of Establishing a Community-Based Virtual Multidisciplinary Sarcoma Case Conference.

PURPOSE: Management of soft tissue and bone sarcoma presents many challenges, both diagnostically and therapeutically, and requires multidisciplinary collaboration; however, such collaboration is often challenging to establish, especially in the community setting. We share our experiences of a virtual multidisciplinary sarcoma case conference (VMSCC). METHODS: We conducted retrospective review of the VMSCC data-initially via Webex, now Microsoft Teams-and the surveys of referring physicians to understand the feasibility and value of the VMSCC. RESULTS: The VMSCC was established in March 2013 in Kaiser Permanente Northern California with consistent participation of the Departments of Musculoskeletal Oncology (orthopedic oncology), Musculoskeletal Radiology, Pathology, Medical Oncology, Radiation Oncology, Nuclear Medicine, Surgical Oncology, and Genetics. Pediatric Oncology participated ad hoc when pediatric sarcoma cases were presented. Referrals were from multiple specialties and regions, including the Kaiser Permanente Mid-Atlantic and Hawaii regions. From March 2013 to December 2019, 1,585 cases were reviewed encompassing 36 histologic types. More than 300 cases were reviewed per year from 2017 to 2019. Survey results of referring physicians demonstrate that the VMSCC enhanced the confidence of treating physicians, and its recommendations frequently led to treatment changes. CONCLUSION: Establishing a valuable community-based VMSCC is feasible. VMSCC recommendations frequently led to treatment changes and improved the confidence of treating physicians.

Feasibility and Value of Establishing a Community-Based Virtual Multidisciplinary Sarcoma Case Conference.

PURPOSE: Management of soft tissue and bone sarcoma presents many challenges, both diagnostically and therapeutically, and requires multidisciplinary collaboration; however, such collaboration is often challenging to establish, especially in the community setting. We share our experiences of a virtual multidisciplinary sarcoma case conference (VMSCC). METHODS: We conducted retrospective review of the VMSCC data-initially via Webex, now Microsoft Teams-and the surveys of referring physicians to understand the feasibility and value of the VMSCC. RESULTS: The VMSCC was established in March 2013 in Kaiser Permanente Northern California with consistent participation of the Departments of Musculoskeletal Oncology (orthopedic oncology), Musculoskeletal Radiology, Pathology, Medical Oncology, Radiation Oncology, Nuclear Medicine, Surgical Oncology, and Genetics. Pediatric Oncology participated ad hoc when pediatric sarcoma cases were presented. Referrals were from multiple specialties and regions, including the Kaiser Permanente Mid-Atlantic and Hawaii regions. From March 2013 to December 2019, 1,585 cases were reviewed encompassing 36 histologic types. More than 300 cases were reviewed per year from 2017 to 2019. Survey results of referring physicians demonstrate that the VMSCC enhanced the confidence of treating physicians, and its recommendations frequently led to treatment changes. CONCLUSION: Establishing a valuable community-based VMSCC is feasible. VMSCC recommendations frequently led to treatment changes and improved the confidence of treating physicians.

Non-Radiographic Risk Factors Differentiating Atypical Lipomatous Tumors from Lipomas.

PURPOSE: To determine non-radiographic risk factors differentiating atypical lipomatous tumors (ALTs) from lipomas. METHODS: All patients with deep-seated lipomatous tumors of the extremities treated from January 2000 to October 2010 were retrospectively reviewed. Factors reviewed included age, gender, tumor location, size, histology, local recurrence, dedifferentiation, and metastasis. Multivariate logistic regression models were used to evaluate the effects of patient characteristics on ALT status. RESULTS: Ninety-four lipomas and 46 ALTs were included. Patients with an ALT were older (median: 60.5 vs. 55 years). Lipomas were evenly distributed between upper (48.9%) and lower extremities (51.1%), whereas ALTs predominately involved the lower extremities (91.3%). Median ALT size (22 cm) was greater than lipomas (10 cm), p < 0.0001. One lipoma (1.04%) recurred at 77 months and five ALTs (10.9%) recurred at an average of 39 months (19-64 months). Two ALTs originally treated with wide resection recurred with a dedifferentiated component and were treated with wide re-excision and chemotherapy. No metastases or tumor-related deaths occurred in either group at the time of last follow-up. Patients older than 60 years, tumors greater than 10 cm, or thigh location, were more likely to be diagnosed with an ALT (p < 0.05). CONCLUSION: Lipomatous tumors were more likely to be ALTs when the tumor was at least 10 cm in size, located in the thigh, or found in patients that were 60 years of age or older. These risk factors may be used to guide management and surveillance strategies, when lipomatous tumors do not display characteristic radiographic features.

FDA-preapproved drugs targeted to the translational regulation and processing of the amyloid precursor protein.

The 5' untranslated region (5'UTR) of the transcript encoding the Alzheimer's amyloid precursor protein (APP) is a key regulatory sequence that determines the amount of intracellular APP holoprotein present in brain derived cells. Using neuroblastoma cells (SY5Y) we developed a transfection based screen of a library of FDA drugs to identify compounds that limited APP luciferase reporter expression translated from the APP 5'UTR. Paroxetine (Paxil trade mark ), dimercaptopropanol, phenserine, desferrioxamine, tetrathiolmobdylate, and azithromycin were six leads that were subsequently found to also suppress APP holoprotein levels or to alter APP cleavage (azithromycin). Since APP holoprotein levels are proportionate to Abeta peptide output in many systems we tested the efficacy of paroxetine and dimercaptopropanol to limit Abeta secretion as measured by ELISA assays. Paroxetine and dimercaptopropanol limited Abeta peptide secretion from lens epithelial cells (B3 cells). Interestingly, paroxetine changed the steady-state levels of transferrin receptor mRNAs. These data suggested that this serotonin reuptake inhibitor (SSRI) provided extra pharmacological action to chelate interacellular iron or change the intracellular iron distribution. An altered iron distribution would be predicted to indirectly limit APP holoprotein expression and Abeta peptide secretion.

Alterations in T2 relaxation magnetic resonance imaging of the ovine intervertebral disc due to nonenzymatic glycation.

STUDY DESIGN: An in vitro study using ovine intervertebral discs to correlate the effects of increasing advanced glycation end-products (AGEs) with disc hydration evaluated by magnetic resonance imaging (MRI). OBJECTIVE: To determine the relationship between the level of AGEs and tissue water content in intervertebral discs using T2 relaxation MRI. SUMMARY OF BACKGROUND DATA: AGEs result from nonenzymatic glycation, and AGEs have been shown to accumulate in the intervertebral disc tissue with aging and degeneration. AGEs can alter biochemical properties, including the hydrophobicity of the extracellular matrix. Because one of the degenerative signs of the intervertebral disc (IVD) is reduced hydration, we hypothesized that increased levels of tissue AGEs contribute to disc hydration. T2 relaxation MRI has been shown to be sensitive to the hydration status of the disc and may be valuable in detecting the changes in the IVD mediated by the increase of AGEs. METHODS: Thirty-eight IVDs were obtained from 4 ovine spines, and the annulus fibrosis (AF) and nucleus pulposus (NP) tissues were isolated from these discs. The tissues were incubated in either a ribosylation or control solution for up to 8 days to induce the formation of AGEs. T2 relaxation times were obtained from these tissues after ribosylation. These tissues were subsequently analyzed for hydration, proteoglycan, collagen, and AGEs content. RESULTS: In vitro ribosylation led to the increased accumulation of AGEs and reduced water content in both the AF and NP in a dose-dependent manner, but did not affect the proteoglycan and collagen composition. When analyzed by MRI, ribosylation significantly altered the mean T2 relaxation times in the NP (P = 0.001), but not in the AF (P = 0.912). Furthermore, the mean T2 values in the NP significantly decreased with increasing periods of incubation time (P < 0.001). CONCLUSION: This study demonstrates that levels of AGEs in the IVD may affect the tissue water content. Moreover, these ribosylation-mediated changes in tissue hydration were detectable using T2 relaxation MRI. T2 relaxation MRI may provide a noninvasive tool to measure in vivo changes in disc hydration that are negatively correlated with the accumulation of AGEs.

Culture and ethnicity influence outcomes of the Scoliosis Research Society Instrument in adolescent idiopathic scoliosis.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To report preoperative differences in the Scoliosis Research Society Outcomes Instrument (SRS-30) between multiple US ethnicities and native Japanese and Korean children with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: The SRS-24 was developed in a US cohort with AIS. Comparative studies using the SRS-24 between US and Japanese patients showed differences, suggesting that culture might affect functional outcome. METHODS: Preoperative SRS-30 outcomes were collected from 1853 children with AIS from 6 different ethnic groups: US white (1234), black (213), Hispanic (78), and Asian (29), as well as native Japanese (192) and Koreans (107). Analysis of covariance of 4 SRS-30 domains (pain, appearance, activity, and mental) was compared between groups adjusting for differences in age, sex, major curve magnitude, and body mass index. Pairwise comparisons of the 4 SRS-30 domains were adjusted for multiple comparisons, using Bonferroni correction. A P value of less than 0.05 was considered significant. RESULTS: Significant differences between ethnicities were found in all domains (P < 0.001). Whites reported more pain than Japanese or Koreans (Japanese = 4.52, Korean = 4.47, white = 4.04). Korean and Japanese patients had the lowest appearance scores (Japanese = 2.89, Korean = 2.73, US Asian = 3.55, Hispanic = 3.11, black = 3.47, white = 3.29). Koreans also had the lowest activity (Korean = 3.64, Japanese = 4.24, US Asian = 4.07, Hispanic = 4.02, black = 4.06, white = 4.16), mental (Korean = 3.70, Japanese = 4.23, US Asian = 4.05, Hispanic = 3.75, black = 4.03, white = 3.94), and total scores (Korean = 3.63, Japanese = 3.92, US Asian = 4.02, Hispanic = 3.75, black = 3.92, and white = 3.84). CONCLUSION: Culture and ethnicity influence SRS-30 outcomes in AIS. Whites reported more pain than Japanese and Koreans. Japanese and Koreans had the lowest appearance scores. Koreans additionally were distinguished by the lowest activity, mental, and total scores. These cultural and ethnic differences must be taken into account when counseling patients with AIS and studying functional outcomes.

Effects of a verbenachalcone derivative on neurite outgrowth, inhibition of caspase induction and gene expression.

A verbenachalcone derivative was synthesized and shown to protect N2a cells from caspase induction caused by serum starvation and to enhance the effect of NGF on neurite outgrowth in PC12 cells. As an initial investigation of the compound's mechanism(s) of action, we performed differential gene expression profiling in PC12 cells using oligonucleotide ( approximately 10,000 gene probes) microarrays. Gene expression patterns were compared in the presence of NGF (2 and 50 ng/mL) and NGF (2 ng/mL) plus the verbenachalcone derivative. Ten genes were significantly (2-fold; p0.05) up-regulated and seven genes were significantly down-regulated in the presence of the compound. These results were independently validated by quantitative real-time PCR for a subset of genes (cathepsin L, sigma-1 receptor and protein tyrosine phosphatase receptor type R). These genes or their protein products may represent useful therapeutic targets for treating neurodegeneration, such as Alzheimer's disease.