Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE®: a phase I/II, randomized, active-control, single-blind, multiple-center clinical trial.

OBJECTIVE: To evaluate the safety and efficacy of intra-articular (IA) injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE® for knee osteoarthritis. METHODS: This was a patient-blind, randomized, active-control trial consisted of 4 arms including hyaluronic acid (HA) control and 3 ELIXCYTE® doses. A total of 64 subjects were screened, and 57 subjects were randomized. The primary endpoints included the changes from baseline to post-treatment visit of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at Week 24 and the incidence of adverse events (AEs) and serious adverse events (SAEs). RESULTS: No ELIXCYTE®-related serious adverse events were reported during 96 weeks of follow-up and no suspected unexpected serious adverse reaction (SUSAR) or death was reported. The changes of the primary endpoint, WOMAC pain score at Week 24, showed significant differences in all ELIXCYTE® groups, as well as in HA groups between post-treatment visit and baseline. The ELIXCYTE® groups revealed significant decreases at Week 4 compared to HA group in WOMAC total scores, stiffness scores, functional limitation scores suggested the potential of ELIXCYTE® in earlier onset compared to those from HA. The significant differences of visual analog scale (VAS) pain score and Knee Society Clinical Rating System (KSCRS) functional activities score at Week 48 after ELIXCYTE® administration suggested the potential of ELIXCYTE® in the longer duration of the effectiveness compared to HA group. CONCLUSIONS: ELIXCYTE® for knee osteoarthritis treatment was effective, safe, and well-tolerated. The efficacy results were showed that ELIXCYTE® conferred the earlier onset of reductions in pain scores and improvements in functional scores than HA group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02784964. Registered 16 May, 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02784964.

Improvement in High-Grade Osteosarcoma Survival: Results from 202 Patients Treated at a Single Institution in Taiwan.

The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995-2003 vs 2004-2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%-16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients.

Magnetic resonance imaging guided biopsy of musculoskeletal lesions.

BACKGROUND: Minimally invasive interventional biopsy procedures have the advantages of accurate localization, small incisions, and rapid recovery. The purpose of this study was to clinically test and evaluate the efficacy of the magnetic resonance imaging (MRI)-guidance techniques for obtaining musculoskeletal biopsies using the appropriate imaging modalities and instruments. METHODS: We used MRI-compatible biopsy needles from the Invivo Bone Biopsy Set (Daum, Germany), and a 1.5-T closed-magnet MRI scanner was used to perform the MRI-guided biopsy. The pulse sequences included fast spin echo T1- and T2-weighted imaging and gradient echo imaging. The inclusion criteria included the presence of bone or soft tissue masses, infectious disease, and other nonspecific lesions that required tissue confirmation. Lesions that could not be visualized by computed tomography (CT) or other imaging modalities were preferred. RESULTS: From January 2005 through December 2009, 23 patients (12 males and 11 females, aged 11-82 years) underwent musculoskeletal MRI-guided biopsy. The biopsy locations were as follow: spine (n = 12), tibia (n = 3), pelvis (n = 1), femur (n = 2), scapula (n = 1), humerus (n = 1), ulna (n = 1), scapula (n = 1), and soft tissue mass of the shoulder (n = 1). The final diagnoses included bone metastasis (n = 7), spinal osteomyelitis and discitis (n = 5), osteonecrosis after chemotherapy (n = 4), bone marrow change or benign lesion without malignancy (n = 3), insufficiency fracture (n = 1), long bone osteomyelitis (n = 1), soft tissue metastasis (n = 1), and perineural ganglion cyst (n = 1). In 10 of the 23 cases, the lesions were barely visualized or invisible on CT guidance. Pathologic analysis and laboratory culturing revealed that the lesions were successfully accessed by MRI-guided biopsy in 100% (23/23) of cases. No obvious complications developed during or after the procedures. CONCLUSION: Biopsy under MRI guidance is especially valuable for the localization of bone marrow lesions, viable tumors (after chemotherapy or radiation), and lesions that cannot be visualized using CT. It is both accurate and safe, is a good alternative biopsy method, and may be a good adjunctive technique for the localization of bone lesions for radiofrequency ablation or other interventional procedures.

The risk of stroke after percutaneous vertebroplasty for osteoporosis: a population-based cohort study.

PURPOSE: To investigate the incidence and risk of stroke after percutaneous vertebroplasty in patients with osteoporosis. METHODS: A group of 334 patients with osteoporosis, and who underwent percutaneous vertebroplasty during the study period, was compared to 1,655 age-, sex- and propensity score-matched patients who did not undergo vertebroplasty. All demographic covariates and co-morbidities were deliberately matched between the two groups to avoid selection bias. Every subject was followed-up for up to five years for stroke. Adjustments using a Cox regression model and Kaplan-Meier analyses were conducted. RESULTS: A total of 1,989 osteoporotic patients were followed up for 3,760.13 person-years. Overall, the incidence rates of any stroke, hemorrhagic stroke and ischemic stroke were 22.6, 4.2 and 19.6 per 1,000 person-years, respectively. Patients who underwent vertebroplasty were not more likely to have any stroke (crude hazard ratio = 1.13, p = 0.693), hemorrhagic stroke (HR = 2.21, p = 0.170), or ischemic stroke (HR = 0.96, p = 0.90). After adjusting for demographics, co-morbidities and medications, the vertebroplasty group had no significant difference with the comparison group in terms of any, hemorrhagic and ischemic strokes (adjusted HR = 1.22, 3.17, and 0.96, p = 0.518, 0.055, and 0.91, respectively). CONCLUSIONS: Osteoporotic patients who undergo percutaneous vertebroplasty are not at higher risk of any stroke in the next five years after the procedure.

Clinical outcome and imaging of arthroscopic single-row and double-row rotator cuff repair: a prospective randomized trial.

PURPOSE: The purpose of this study was to compare the clinical and imaging outcomes of single-row and double-row suture anchor fixation in arthroscopic rotator cuff repair with emphasis on analysis of the effect of various tear size on repair integrity. METHODS: Fifty-three patents were randomized to either single-row or double-row rotator cuff repair at the time of surgical intervention. The clinical results were evaluated by applying the UCLA score and the ASES index and assessing muscle strength in abduction and external rotation with a minimum 2-year follow-up. The postoperative rotator cuff integrity was evaluated by magnetic resonance arthrography at 6-month and minimum 2-year follow-up. RESULTS: We enrolled 27 patients in the single-row group and 26 patients in the double-row group. Statistically, the UCLA score; the ASES index; and muscle strength were significantly increased in both groups after surgery, but there was no significant difference between the 2 groups. At minimum 2-year follow-up, intact rotator cuffs were found in 17 patients in the single-row group and 20 in the double-row group, based on magnetic resonance arthrography results. Overall, there was no significant difference in postoperative structural integrity between the 2 groups at 6-month and 2-year follow-up. In patients with tear size larger than 3 cm, the muscle strength of the shoulder was significantly better in the double-row group. For the final imaging results, regardless of the tear size, there was no difference between the single-row and double-row groups. CONCLUSIONS: Arthroscopic rotator cuff repair with double-row fixation showed better shoulder strength in patients with larger tear size (>3 cm) in comparison with single-row fixation. However, the imaging results showed no significant difference in cuff integrity in both groups in patients with any tear size at 6-month and minimum 2-year follow-up. LEVEL OF EVIDENCE: Level II, lesser-quality randomized control trial.

Polymethylmethacrylate augmentation of the pedicle screw: the cement distribution in the vertebral body.

Many studies have proven that the polymethylmethacrylate (PMMA) augmentation of the pedicle screw can significantly increase stiffness and strength of spinal fixation. Some major complications have also been reported. However, there are no reports discussing cement distribution and its morphology in the osteoporotic vertebral body, which is critical in the analysis of the biomechanical strength of the pedicle screw and the risk of cement leakage after pedicle screw augmentation. In this study, we used computed tomography (CT) to evaluate the cement distribution in the osteoporotic vertebral body after PMMA augmentation of a pedicle screw and to analyze the factors leading to cement leakage. Two groups of patients were studied. Group A consisted 25 osteoporotic patients (mean age of 73 years) with spinal instrumentation who had a total of 145 pedicle screws and cement augmentation with biopsy needles. Group B consisted of 23 osteoporotic patients (mean age of 74.6 years) with spinal instrumentation who had a total of 125 cannulated pedicle screws with cement augmentation. All patients had CT evaluation of the cement distribution in the vertebral body after the surgery. The cement distribution in the vertebrae was divided into four zones in the axial CT view: anterior one-third, middle third, and posterior third of vertebral body, and the pedicle. The morphology of the cement distribution around the pedicle screw was defined as scattered type or concentrate type. The leakage pattern was divided to anterior-lateral, posterior-lateral, and canal leakage. The correlations among bone mineral density (BMD), the cement leakage rate, and cement distribution morphology were also analyzed. The results showed that most augmented pedicle screws had cement extension into three of the four zones of the vertebral body (66.3%), followed by two zones (20%), all four zones (11.5%), and only one zone (2.2%). Overall, 123 screws (84.8%) in Group A and 108 screws (86.4%) in Group B had cement concentrate type distribution. The cement leakage rate in Group A is 18.3% and 13.6% in Group B. Patients with a BMD <0.6 g/cm(2) had significantly higher rates of cement leakage and tended toward a scattered cement distribution. There was only one patient who had a symptomatic leakage (sciatica) in Group B. We concluded that the cement distribution after pedicle screw augmentation with biopsy needle or cannulated screw technique was mostly localized in three zones of the vertebral body, and patients with lower BMD had a higher risk of cement leakage and scattered cement distribution.

Different and identical features of chondroblastic osteosarcoma and chondrosarcoma: highlights on radiography and magnetic resonance imaging.

BACKGROUND: To identify the different and identical features of 2 tumors with similar pathologic findings, chondroblastic osteosarcoma (OGS) and chondrosarcoma (CSA), with highlights on radiography and magnetic resonance imaging (MRI). METHODS: Ten patients with chondroblastic OGS and 10 patients with CSA were enrolled. After recording the tumor location, tumor morphology was evaluated for patterns of bony destruction, visible tumor matrix, and aggressive periosteal reactions, endosteal scalloping, cortical expansion, cortical breakthrough and pathologic fracture by radiographic analysis. Signal intensity changes, enhancement pattern, and tumor extensions were evaluated by MRI. RESULTS: The mean patient ages were 24.7 and 56.7 years in patients with chondroblastic OGS and CSA, respectively (p = 0.001). Tumor occurrence was detected in the appendicular bones in 8 chondroblastic OGS and 3 CSA. Three chondroblastic OGS occurred around the knee (p = 0.003). In addition, there were 6 tumors arising from the metaphysis and 2 arising from the diaphysis in chondroblastic OGS patients. In CSA patients, 1 tumor arose in the metaphysis, 1 in the diaphysis, and 1 in the epiphysis (p = 0.039). On radiographs, visible bone-forming tumor matrix was present in 8 chondroblastic OGS, and coexistence of bone- and cartilage-forming patterns were detected in 2. Visible cartilage-forming tumor matrix was present in 7 CSA, and atypical radiodensity patterns were detected in 2 (p < 0.001). Aggressive periosteal reaction was present in 7 chondroblastic OGS, and non-aggressive periosteal reaction was found in 1 CSA (p = 0.008). MRI revealed the presence of a lobular structure of high signal intensity on T2-weighted images, and peripheral rim and septal enhancement pattern was noted in 2 chondroblastic OGS and 10 CSA patients. Inhomogeneous and marginal enhancement patterns were noted in 6 and 2 chondroblastic OGS, respectively (p = 0.001). CONCLUSION: Metaphysis origin, bone-forming tumor matrix, aggressive periosteal reaction, and young patient age favored chondroblastic OGS. Some chondroblastic OGS showed radiologic and MRI appearances that were typical of CSA.

Tuberculous spondylitis and pyogenic spondylitis: comparative magnetic resonance imaging features.

STUDY DESIGN: We retrospectively compared magnetic resonance images (MRIs) of tuberculous (TB) spondylitis and pyogenic spondylitis. OBJECTIVE: To identify differences between the diseases. SUMMARY OF BACKGROUND DATA: Clinical and imaging findings of the 2 diseases are hard to distinguish. MRI may show important differences and aid in early diagnosis and treatment. METHODS: We compared 22 MRI parameters in 33 patients with TB spondylitis (average age, 66 years) and in 33 patients with pyogenic spondylitis (average age, 65 years). RESULTS: Seventeen parameters significantly differed between the groups. The most important were local and heterogeneous enhancement of the vertebral body in all patients with TB spondylitis, diffuse and homogeneous enhancement of the vertebral body in 94% of patients with pyogenic spondylitis, vertebral intraosseous abscess with rim enhancement (TB vs. pyogenic, 79% vs. 0%), disc abscess with rim enhancement (9% vs. 64%), and well-defined paraspinal abnormal signal intensity (82% vs. 18%). CONCLUSIONS: Most parameters occurred in both diseases. Distinctive findings were a pattern of bone destruction with relative disc preservation and heterogeneous enhancement for TB spondylitis and a diskitis pattern (disc destruction) with peridiscal bone destruction and homogeneous enhancement for pyogenic spondylitis. These MRI parameters may facilitate the differential diagnosis of these diseases.

Edematous Schmorl's nodes on thoracolumbar MR imaging: characteristic patterns and changes over time.

OBJECTIVE: To describe the patterns and note the evolution of edematous Schmorl's nodes. MATERIALS AND METHODS: In 47 patients (M:F=26:21, 24-86 years, average 60), 84 Schmorls nodes with T2 hyperintensity with serial MR exams were evaluated. Interval between MR exams was 2-72 months (average 17). Two observers noted size, location, margins, internal and surrounding T1/T2 signal, adjacent disc herniation or bulge, concentric ring, underlying fracture, malignancy, infection, or prior disc surgery, and serial MR changes in these characteristics over time. RESULTS: Node size averaged 7x9 mm. Most were located at L3 (29%, 24/84), L4 (19%, 16/84) and L2 (13%, 11/84), at the central (39%, 33/84) or outer (30%, 25/84) third of the endplate. 55% (39/71) had a bulging disc, 7% (5/71) had disc herniation. 10% (8/84) had evidence of associated fracture, 17% (14/84) tumor, 7% (6/84) infection. Most nodes had well-defined margins (82%, 69/84). The most common node internal signal was isointense to adjacent disc on T1/T2 (33%, 28/84); surrounding marrow was most commonly hypointense on T1 and hyperintense on T2 (54%, 38/71). A common finding was concentric rings (38%, 32/84) in the marrow surrounding the node, a finding which had 72% negative predictive value for absence of infection, tumor and fracture. On follow-up, there was no interval change in node size in 46%(39/84) of Schmorl's nodes. 26% (22/84) had increased size. Most (60%, 50/84) showed no temporal change in internal T2 signal. 21% (18/84) of nodes showed decreased internal T2 signal, 13% (11/84) showed increased T2 signal. Regarding the surrounding marrow, most (58%, 49/84) showed no temporal change in T2 signal; 21%(18/84) showed decreased T2 signal, 13% (11/84) showed increased T2 signal. In 13 Schmorl's nodes with intranodal enhancement, eight (62%) showed no interval change; among eight with enhancement in surrounding marrow, five (63%) showed no change on follow-up. CONCLUSION: Although most remain unchanged, a relatively large minority of edematous Schmorl's nodes evolve in size and signal over a relatively short time. Some evolve to form well-defined concentric rings in the surrounding marrow that appear to be analogous to degenerative changes of endplates. Concentric ring formation has a high negative predictive value for "idiopathic" Schmorl's nodes without underlying fracture, infection, or malignancy.

Is epidural fat associated with body habitus?

OBJECTIVE: To evaluate, in the spine, the relationship between the amount of epidural fat to body weight, height, body mass index (BMI), presence of obesity, depth of posterior subcutaneous fat, as well as gender and age. METHODS: At 1.5 T, 101 random patients were analyzed. In the lumbar spine, we calculated the depth of the anterior and posterior epidural fat, as well as posterior subcutaneous fat, separately at the L3-4, L4-5, and L5-S1 levels. Obtained via questionnaire was patient's age, gender, body weight, height, with a calculated BMI (body weight/height, kg/m). Statistical analysis was performed to assess the correlation between epidural and subcutaneous fat with age and gender, weight, height, BMI, and presence of obesity (BMI > 27.5 kg/m). RESULTS: There were 66 men and 45 women, age ranged 14-83 years old (mean 43). The weight range was 47.6-135.4 (mean 79.5 kg); height range was 124.5-208.3 (mean 169.7 cm); BMI range was 16.9-42.8 (mean 27.8). Female gender correlated only with subcutaneous fat depth (sum, r=-0.31, P=0.002). Younger patients had more anterior epidural fat (sum, r=-0.22, P=0.024) but not posterior epidural fat (sum, r=0.01, P=0.954) or subcutaneous fat (sum, r=0.09, P=0.0357). Weight correlated with posterior epidural fat (sum, r=0.21, P=0.037) and subcutaneous fat (sum, r=0.51, P <0.0001). Height showed correlation negatively with posterior subcutaneous fat thickness (sum, r=-0.25, P=0.014), but had no significant correlation with epidural fat. BMI showed a correlation with posterior subcutaneous fat (r=0.71, P <0.0001 for sum). Somewhat unexpectedly, BMI had no correlation with either posterior (r=0.12, P=0.221 for sum) or anterior epidural fat (r=0.11, P=0.271 for sum), and most importantly the presence of obesity was associated only with subcutaneous fat (P <0.0001), but not with any specific or summated epidural fat measurement (P=0.0801-0.7692). CONCLUSION: Weight but not body habitus is associated with specific, usually posterior, patterns of epidural fat deposition. Overall obesity is unrelated to epidural fat.

Potential MR signs of recurrent carpal tunnel syndrome: initial experience.

OBJECTIVE: In nonoperated patients, the MR diagnosis of carpal tunnel syndrome (CTS) is difficult. In the postoperative patient this difficulty is compounded. Consequently, we sought to evaluate for potential MR signs of postoperative CTS. METHODS: At 1.5 T, 41 wrists in 37 patients with previous CTS release were evaluated by two observers for 1) flexor retinacular regrowth; 2) median nerve: a) high T2 signal, b) proximal enlargement, c) fibrous fixation, d) neuroma, and e) entrapment; 3) flexor tenosynovitis; 4) mass, bursitis, accessory muscle, distal belly progression, or excessive deep fat; 5) hamate fracture; and 6) volar nerve migration. Electromyography (EMG), operative findings, and clinical follow-up were used to determine the presence of recurrent CTS. RESULTS: Fifteen of 41 wrists had recurrent CTS. Retinacular regrowth was seen in 4/15 (27%) with and 7/26 (27%) without recurrent CTS (P=0.7). Excessive fat was seen in 1/15 (7%) with and 2/26 (8%) without CTS (P=0.19). No patient had incomplete resection of flexor retinaculum, scarring, neuroma of nerve, or tendon laceration; bursitis, accessory or distal muscle progression of muscle belly, or hamate fracture. Nerve edema with high T2 signal was seen in 4/15 (27%) with and 3/26 (12%) without CTS (P=0.16); proximal enlargement was seen in 6/15 (40%) with CTS and 2/26 (8%) without CTS (P=0.007). Also, 1 patient with recurrent disease demonstrated a mass and 1 other patient without CTS had nerve entrapment. Tenosynovitis was seen in 9/15 (60%) with and 9/26 (35%) without recurrent CTS (P=0.02). Counterintuitively, the nerve was more palmar with recurrent CTS than without (mean 6.9/8.9 mm). CONCLUSION: Only proximal enlargement, tenosynovitis, and the rare mass may help to diagnose recurrent CTS by MR. However, there appears to be a subgroup of patients with recurrent neuropathy related to an excessively superficial median nerve.