A simple bone cyst (SBC) is a benign bone lesion of unknown etiology. It can be differentiated from an aneurysmal bone cyst (ABC) by radiologic and histopathologic features, as well as by the absence ...of fusions of the USP6 gene characteristic of an ABC. In an attempt to differentiate between ABC and SBC in a recurrent bone cyst, we performed targeted RNA sequencing and found an EWSR1-NFATC2 fusion and no fusion of the USP6 gene. We subsequently analyzed additional 10 cysts, consistent with SBCs after radiologic-pathologic correlation, for the presence of an NFATC2 gene fusion, by targeted RNA sequencing, reverse-transcription polymerase chain reaction (RT-PCR) and Sanger sequencing, and fluorescent in situ hybridization. Targeted RNA sequencing showed a FUS-NFATC2 fusion in 4 of 11 SBCs and an EWSR1-NFATC2 fusion in 2 of 11 SBCs. No fusion was identified in 3 SBCs and the analysis was not successful in 2 SBCs because of the low quantity or poor quality of isolated RNA. All the 6 fusions detected by targeted RNA sequencing were confirmed by RT-PCR and Sanger sequencing, and 5 of the 6 fusions by fluorescent in situ hybridization. An additional FUS-NFATC2 fusion was identified by RT-PCR, Sanger sequencing, and fluorescent in situ hybridization in 1 of the 3 cases negative for fusions by targeted RNA sequencing. At least a large subset of SBCs represents cystic neoplasms characterized by FUS-NFATC2 or EWSR1-NFATC2 fusions, which also define a group of distinct, rare "Ewing-like" sarcomas that predominantly arise in long bones. Our results provide additional evidence of the existence of benign lesions with FUS-NFATC2 or EWSR1-NFATC2 fusions. Although they can recur locally in a nondestructive manner, their clinical course and possible relation to sarcoma with EWSR1-NFATC2 or FUS-NFATC2 fusion remains to be elucidated.
Purpose
To evaluate predicting factors for patient-reported outcomes and revision interventions following surgical treatment of patients with patellofemoral instability.
Methods
From a prospective ...database at the university Orthopedic Department, 138 knees from 116 patients who underwent patellofemoral instability surgery (2012–2019) were enrolled in a retrospective analysis: 34 cases of isolated MPFLrec; 92 cases of MPFLrec plus tibial tuberosity transfer; and 12 cases of MPFLrec plus trochleoplasty. Patient-reported outcome measures were recorded for knee-specific function (KOOS), general quality of life (EQ-5D), and activity level (Tegner scale). Post-operative revision interventions were also actively recorded. As potential predicting factors, patient demographic (gender, age, BMI) and radiographic (pre-operative: patellar height and tilt, tibial tuberosity–trochlear groove distance, trochlear dysplasia, knee osteoarthritis; post-operative: MPFL insertion point; intra-operative: isolated vs. combined procedures, chondropenia severity score) parameters were analyzed using multivariate linear regression models.
Results
With median follow-up of 4.4 (1.0–8.9) years, all patient-reported outcome measures had significantly improved from pre-operative levels: KOOS cumulative, from 71 (15) to 78 (16); EQ-5D, from 0.68 (0.20) to 0.78 (0.21); and Tegner activity scale, from 3 (0–10) to 4 (0–10). No patellofemoral instability revision procedures were performed. One-fifth (27/138) of the operated knees required second surgical interventions, predominately due to hardware or arthrofibrosis. Patients who required post-operative knee manipulation under anesthesia or arthroscopic debridement showed lower post-operative improvement for KOOS cumulative and EQ-5D. Age, BMI, patellofemoral knee osteoarthritis, and shorter follow-up time revealed significant negative correlations to some of the post-operative KOOS subscales. Age was negatively correlated to post-operative EQ-5D, while post-operative Tegner activity scale was negatively correlated to female gender and patellofemoral chondropenia severity score. Femoral MPFL insertion point revealed no association with any outcome measures.
Conclusion
Patellofemoral instability surgery for isolated or combined MPFLrec is safe and substantially improves knee function and patient quality of life and activity levels. Serious adverse events are rare, with no recurrent patellofemoral instability. Patients who required post-operative knee manipulation or arthroscopic debridement showed less improvement in subjective measures of treatment outcomes. Older age, higher BMI, worse pre-operative patellofemoral cartilage status, and female gender had negative effects on outcome.
Level of evidence
III.
Seven different autologous chondrocyte implantation (ACI) grafts were used consecutively over a period of 18 years for the treatment of cartilage lesions in the knees. The aim was to evaluate this ...entire ACI patient series for graft-related or unrelated serious adverse events (SAE), graft failures, and to reveal potential risk factors for these incidents. The study group comprised 151 operated patients: classical periosteum-ACI (n = 45); ACI-seeded fibrin-collagen patch, fixed by either periosteum (n = 59), collagen membrane (n = 15), or fibrin glue (n = 6); ACI seeded alginate-agarose hydrogel (n = 14); and biomimetic collagen-hydroxyapatite scaffold injected with the ACI suspension (n = 12). The covariates analyzed as possible predicting factors were: age, gender, BMI, lesion depth, lesion size, lesion location, previous surgeries, and concomitant procedures. The Kaplan–Meier method for estimating survival curves, and Cox’s proportional hazards model to test for covariates, were used in the statistical analysis. The patients in this series, follow-up 10.1 (2.1–18.3) years, encountered 11% of graft-related SAE (risk factors: previous cartilage surgery, age over 40 years, BMI over 25 kg/m2, and meniscus surgery) and 10% of graft unrelated SAE (risk factors: meniscus surgery and osteotomy). None of these factors was a risk for definitive graft failure. The 10-year graft survival rate was 86%. Females had 2.8 times higher incidence of graft failures than males. There was a tendency toward higher graft failures after a previous cartilage surgery. Different ACI graft types offered safe and durable cartilage repair. Female gender, age over 40 years, increased weight, previous cartilage surgery, and meniscus loss showed increased risk for revision surgery or graft failures.
Aneurysmal bone cyst (ABC) is a benign but locally aggressive neoplasm, with a tendency for local recurrence. In contrast to other bone tumors with secondary cystic change, ABC is characterized by ...USP6 gene rearrangement. There is a growing list of known USP6 fusion partners, characterization of which has been enabled with the advent of next‐generation sequencing (NGS). The list of known fusion partners includes CDH11, CNBP, COL1A1, CTNNB1, EIF1, FOSL2, OMD, PAFAH1B1, RUNX2, SEC31A, SPARC, STAT3, THRAP3, and USP9X. Using NGS, we analyzed a series of 11 consecutive ABCs and identified USP6 fusions in all cases, providing further evidence that USP6 fusions are universally present in primary ABCs. We identified four novel fusion partners in five ABCs and confirmed them by RT‐PCR and Sanger sequencing, ASAP1, FAT1, SAR1A, and TNC (in two cases). Because of high sensitivity and specificity, detection of a USP6 fusion by NGS may assist in differentiating between ABC and its mimics, especially in small biopsy samples when a definite diagnosis cannot be achieved on morphological grounds alone. Further studies with a large number of cases and follow‐up are needed to determine whether different fusion partners are associated with specific clinical and pathologic features of ABCs.
Purpose
To document clinical, radiologic, and cellular data of a prospective patient series treated by a tri-layer collagen-hydroxyapatite biomimetic osteochondral scaffold (CHAS) intra-operatively ...seeded with cultivated autologous chondrocytes (AC) or with filtered bone marrow stem/stromal cells (fBMSC) to address chronic osteochondral knee lesions.
Methods
Thirty-six consecutive patients (15 to 59 years) with chronic osteochondral lesions (1.8–10 cm
2
) in the condylar or patellofemoral knee surfaces were enrolled. Lesions were covered with CHAS fixed with a fibrin glue. The superficial layer of CHAS was intra-operatively injected with active cells: in initial five patients, ACs were put directly onto dry CHAS (dry-AC); next, eight AC patients had CHAS moistened with cell culture media (media-AC), while the tourniquet was released allowing blood soaking of CHAS in the rest (14 blood-AC, 9 blood-fBMSC). Seventeen (50%) patients required different concomitant procedures. All patients were followed for serious adverse events (SAE) or graft failures; clinical, radiographic, and MRI evaluation was conducted. Cellular data on the injected cells were assessed.
Results
At a follow-up of 39 months (16–81), 17 patients required an additional surgical intervention: seven graft-related SAE (early post-operative synovitis and/or arthrofibrosis) were registered (3 dry-AC, 3 media-AC, 1 blood-fBMSC). There were two graft failures (1 dry-AC, 1 blood-fBMSC) for secondary reasons. All clinical scores significantly improved from pre- to post-operative values: IKCD subjective 44 to 65; IKDC examination (9/17/5/5) to (20/10/5/1); KOOS (P61/S59/ADL67/Sp32/QoL31) to (P79/S75/ADL84/Sp55/QoL51); Tegner activity scale 3.3 to 4.4. There was evidence of radiographic osteoarthritis progression—Kellgren-Lawrence 1.0 to 1.5. MOCART scores at the final follow-up averaged 71 (10 to 95). Graft-type analysis demonstrated an increased rate of graft-related SAE in dry-AC and media-AC, but their final outcomes were equivalent. Cellular data of AC at the implantation were as follows: cells in suspension 9.2 × 10
6
, viability 95%. In blood-fBMSC group, a cell suspension with 87% viability was injected, which contained 1156 CFU-Fs.
Conclusion
CHAS with intra-operative seeding of active cells, either AC or fBMSC, led to an overall successful outcome for the treatment of chronic osteochondral lesions in the knee. Blood soaking of CHAS in situ before cell seeding significantly decreased early post-operative adverse events, such as synovitis and arthrofibrosis.
Effects of low‐load blood flow restricted (LL‐BFR) training remain unexplored in patients with ACL rupture. Our hypothesis was that LL‐BFR training triggers augmented gains in knee muscle strength ...and size, which are paralleled with transcriptional responses of hypoxia‐regulated genes and myokines. Eighteen volunteers (age 37.5 ± 9 years) planned for ACL reconstruction, participated in the study. Twelve were divided between BFR group, performing 9 sessions of LL‐BFR exercise, and SHAM‐BFR group performing equal training with sham vascular occlusion. Six subjects served as a control for muscle biopsy analysis. Cross‐sectional area (CSA) and isokinetic strength of knee muscles were assessed before and after the training. Change in CSAquad was significantly (p < 0.01) larger in BFR (4.9%) compared with SHAM‐BFR (1.3%). Similarly, change in peak torque of knee extensors was significantly (p < 0.05) larger in BFR (14%) compared with SHAM‐BFR (−1%). The decrease in fatigue index of knee extensors (6%) was larger (p < 0.01) in BFR than in SHAM‐BFR (2%). mRNA expression of HIF‐1α in the vastus lateralis was reduced (p < 0.05) in SHAM‐BFR, while VEGF‐A mRNA tended to be higher in BFR. The mRNA expression of myostatin and its receptor were reduced (p < 0.05) in the semitendinosus after both types of training. Expression of IL‐6, its receptors IL‐6Rα and gp130, as well as musclin were similar in control and training groups. In conclusion, our results show augmented strength and endurance of knee extensors but less of the flexors. LL‐BFR training is especially effective for conditioning of knee extensors in this population.
Purpose
This prospective study assessed the 10-year clinical outcomes of periosteum autologous chondrocyte implantation (ACI) due to cartilage lesions of the femoral condyles.
Methods
Thirty-three of ...45 patients (3 failures, 7 non-responders, 2 others) were available for clinical and radiographic evaluation at 2, 5, and 10 years. Patients were categorized into groups with focal cartilage lesions, osteochondritis dissecans (OCD), and cartilage lesions with simultaneous ACL reconstruction (ACL). Seven patients in the overall series required an arthroscopic re-intervention (3 ACI related, 4 ACI unrelated).
Results
Subjective knee scores and activity scores were significantly improved at 2 years toward their pre-operative levels and then remained stable up to 10 years; however, patients did not reach their pre-injury activity levels. Upon 10-year examination, using the IKDC knee examination form, there were 15 normal, 11 nearly normal, 5 abnormal, and 2 severely abnormal knees. Radiographic evidence of osteoarthritis was found in 45 % of patients (5 focal lesions, 2 OCD, and 8 ACL).
Conclusions
ACI provided safe and stable performance of operated knees over 10 years with a significant improvement toward pre-operative levels. Patients restrained from high-impact knee joint activities, post-surgery, and their knee radiographs demonstrated a high incidence of knee OA in trauma-related lesions. Optimal long-term performance is expected in localized, low-impact cartilage lesions of young patients.
Level of evidence
Case series, Level IV.
Intraarticular nodular fasciitis arising in the joint synovium is an uncommon lesion. Most cases have been reported in the knee and rarely in other joints. A
USP6
gene fusion has so far been ...documented in only four cases of intraarticular nodular fasciitis, three were located in the knee and one in the proximal interphalangeal joint. In all three cases located in the knee,
MYH9
was detected as a
USP6
fusion partner. We analysed three cases of intraarticular nodular fasciitis for the presence of
USP6
fusion by targeted RNA sequencing. Two cases were located in the hip (a 25-year-old female and 48-year-old male) and one in the shoulder (a 38-year-old male). We detected a
MYH9-USP6
fusion in the two hip cases and a
COL1A1-USP6
fusion in the shoulder case. Our findings provide additional evidence that intraarticular nodular fasciitis is a form of nodular fasciitis arising in the joint synovium, harbouring a
USP6
fusion. Although a
MYH9-USP6
fusion seems to predominate in intraarticular nodular fasciitis, other fusion partners of the
USP6
gene may also be involved. Detection of a
USP6
fusion by targeted RNA sequencing may assist in confirming the diagnosis in selected cases.
Minimum cement volume for vertebroplasty Martinčič, David; Brojan, Miha; Kosel, Franc ...
International orthopaedics,
04/2015, Letnik:
39, Številka:
4
Journal Article
Recenzirano
Purpose
Percutaneous vertebroplasty is a widely used vertebral augmentation technique. It is a minimally invasive and low-risk procedure, but has some disadvantages with a relatively high number of ...bone cement leaks and adjacent vertebral fractures. The aim of this cadaveric study was to determine the minimum percentage of cement fill volume in vertebroplasty needed to restore vertebral stiffness and adjacent intradiscal pressure.
Methods
Thirteen thoracolumbar spine mobile segments were loaded to induce a vertebral fracture. After fracture vertebroplasty was performed, four times in the same fractured vertebra. The injected cement volume was 5 % of the fractured vertebral volume to reach 5, 10, 15 and 20 % of cement fill. Biomechanical testing was performed before the fracture, after the fracture and after each cement injection.
Results
After vertebral fracture compressive stiffness was reduced to 47 % of the pre-fracture value and was partially restored to 61 % after 10 % cement fill. With vertebroplasty intradiscal pressure gradually increased, depending on specimen position, from 48 to a total of 71 % at 15 % of cement fill.
Conclusions
Compressive stiffness and intradiscal pressure increase with the percentage of cement fill. Fifteen per cent of cement fill was the limit beyond which no substantial increase in compressive stiffness or intradiscal pressure could be detected and is the minimum volume of cement we recommend for vertebroplasty. In the average thoracolumbar vertebra this means 4–6 ml of cement.
Purpose
To retrospectively analyze the entire cohort of patients in the Republic of Slovenia diagnosed with bone sarcomas in the long bones or pelvis/sacrum/coccyx from January 1, 2009, to December ...31, 2018, with an observational nationwide study, whereby all patients were evaluated by one single tumor board in the country. We evaluated surgical outcomes and tested whether survival of bone sarcoma patients depended on age, gender, histological diagnosis.
Materials and methods
Cancer Registry of the Republic of Slovenia was screened for all ICD-10 diagnoses from C40.0 to C40.9 and C41.4 in the designated time frame, and the patients were then clinically followed up until the end of the observation period on June 1, 2019.
Results
The cohort of 160 patients was treated surgically in 141 cases, 29 patients required subsequent revision(s) and cumulative endoprosthetic infection rate was 12.5%. In the follow-up, 54 patients died and the 2 patients were missing. Cumulative proportion of survival at 5/10 years was 61%/54%, respectively. After adjustment for age, gender and diagnosis, higher age (odds ratio 1.06 for each additional year), osteosarcoma (odds ratio 4.07) and Ewing sarcoma (odds ratio 11.68) were the significant risk factors of shorter oncological survival.
Conclusion
This is the first Slovenian nationwide cohort study of bone sarcoma patients, unique in its circumscribed geographic area and evaluation/treatment at a single center by a single tumor board. Although comparable to other countries, results show a grim picture and the lack of improvement in bone sarcoma survival within the last 20 years.
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