In Vitro Characterization of the Human Skeletal Stem Cell-like Properties of Primary Bone-Derived Mesenchymal Stem/Stromal Cells in Patients with Late and Early Hip Osteoarthritis.

Human skeletal stem cells (hSSCs) were recently identified as podoplanin (PDPN)/CD73/CD164-positive and CD146-negative cells that decline with age, and play a role in the pathogenesis of osteoarthritis (OA). The aim of this study was to identify the hSSC-like properties of bone-derived mesenchymal stem/stromal cells (MSCs) of patients with late and early OA. Methods: First, we performed gene expression profiling for the hSSC markers in 32 patients with late and early OA, and donors without OA. Having identified the low expression of hSSC markers in late OA patients, we further performed trilineage differentiation and immunophenotyping for hSSC makers in the selected subsets from each donor group. Results: Our results show no differences in osteogenesis, chondrogenesis, and adipogenesis between the MSCs from the three groups. However, the immunophenotyping shows lower CD164 in MSCs from early OA patients in comparison with late and no OA subjects (p = 0.002 and p = 0.017). Conclusions: Our study shows that the in vitro hSSC-like properties of bone-derived MSCs are similar in patients with early and late OA, and in donors without OA. However, the lower percentage of CD164-positive MSCs in early OA patients indicates the potential of CD164 as a marker of the onset of OA.

A prospective, single-center study following operative treatment for osteochondral lesions of the talus.

BACKGROUND: (1) To evaluate patient-reported outcomes and revision surgeries after various operative interventions for osteochondral lesions of the talus (OLT) in a prospective single center series over 10 years, and (2) to identify predicting factors related to subjective ankle status and quality of life pre- and postoperatively. METHODS: Ninety-nine patients underwent operative treatment due to primary or recurrent OLT, with an average follow up 3.5 (1.8) years. Treatment outcome was followed clinically (FAOS, EQ-5D, Tegner activity scale) and by pursuing any serious adverse events or graft failures. RESULTS: There were 80 responding patients (81%) for the study. The mean lesion size was 2.0 (1.1) cm2. All FAOS values increased from preoperative to final follow-up values (Symptoms 60-68, Pain 58-69, ADL 71-80, Sport 36-54, QoL 30-45). EQ-5D increased from 0.49 to 0.62, while Tegner activity scale change from 3.2 to 3.4. There were 19 (24%) serious adverse events recorded; 13 (16%) of them were graft-related. Graft survival rates were 100% at 1 year, 94% (males)/93% (females) at 2 years, and 77% (males)/47% (females) at 5 years. Female gender, higher BMI, and higher Kellgren-Lawrence ankle OA score were negative predictors for preoperative patient-reported ankle joint status. The foremost improvement after operative intervention was observed in patients with large osteochondral lesions without postoperative adverse events. CONCLUSION: Various operative interventions for OLT significantly improved patients' ankle status and quality of life. High graft survival rates were demonstrated over first two years, but notable decline was confirmed thereafter, especially in female patients.

Age-related alterations and senescence of mesenchymal stromal cells: Implications for regenerative treatments of bones and joints.

The most common clinical manifestations of age-related musculoskeletal degeneration are osteoarthritis and osteoporosis, and these represent an enormous burden on modern society. Mesenchymal stromal cells (MSCs) have pivotal roles in musculoskeletal tissue development. In adult organisms, MSCs retain their ability to regenerate tissues following bone fractures, articular cartilage injuries, and other traumatic injuries of connective tissue. However, their remarkable regenerative ability appears to be impaired through aging, and in particular in age-related diseases of bones and joints. Here, we review age-related alterations of MSCs in musculoskeletal tissues, and address the underlying mechanisms of aging and senescence of MSCs. Furthermore, we focus on the properties of MSCs in osteoarthritis and osteoporosis, and how their changes contribute to onset and progression of these disorders. Finally, we consider current treatments that exploit the enormous potential of MSCs for tissue regeneration, as well as for innovative cell-free extracellular-vesicle-based and anti-aging treatment approaches.

Intraarticular nodular fasciitis-detection of USP6 gene fusions in three cases by targeted RNA sequencing.

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.

Computer assistance in hip preservation surgery-current status and introduction of our system.

INTRODUCTION: Preservation surgery of the hip with open or arthroscopic approach has always been challenging as complex 3-D anatomy and limited surgical access make intraoperative evaluation difficult. Recent advances in computer technology offer a wide range of innovative solutions with a goal to improve accuracy and safety of corrective procedures on human joints. METHOD: The author critically reviews currently available literature in the field of computer assistance in hip preservation surgery. Basic features of unique planning software and navigation surgical system used in treatment of femoroacetabular impingement and hip dysplasia are introduced. RESULTS: Currently available software provides preoperative identification of hip deformity on CT-based 3-D model and planning of the surgical correction using kinematic protocols. Real-time intraoperative 3-D orientation is possible, and execution of surgical correction can be performed either with navigation of surgical tools or with printed templates. Computer assistance in hip preservation surgery is in the developing phase. First clinical experiences of its use in treatment of femoroacetabular impingement, hip dysplasia, hip tumors, and avascular necrosis of the femoral head are promising. CONCLUSION: Computer assistance has been applied for treatment of several hip disorders. Technical advances are suggested and quality basic studies and clinical trials are encouraged for the novel technology to become more user friendly and widely accepted.

Patient-reported joint status and quality of life in sports-related ankle disorders and osteoarthritis.

PURPOSE: To compare self-reported joint status, quality of life, level of activity and pain management in patients scheduled for surgical treatment of seven common ankle disorders: osteoarthritis (OA), primary osteochondral lesion of talus (P-OLT), recurrent osteochondral lesion of talus (R-OLT), lateral ankle instability (INST) and anterior (ANT-IMP), posterior (POST-IMP) and combined (COMB-IMP) ankle impingements. METHODS: The cross-sectional study design was implemented. Hospital records of 610 patients that were admitted for surgical intervention on the ankle joint over a seven year period were reviewed. Patient selection (over 18 years, no systemic musculoskeletal illnesses, only one isolated ankle pathology) resulted in 123 eligible patients for current study (OA 22, P-OLT 19, R-OLT 18, INST 15, ANT-IMP 20, POST-IMP 13, COMB-IMP 16). Foot and Ankle Outcome Score (FAOS), European quality of life in a visual analogue and in five dimensions (EQ-VAS, EQ-5D-3L), Tegner activity scale (TAS) and pain medication usage were recorded at the admission and compared across these seven groups. RESULTS: All evaluated ankle disorders induced the following: (a) subjective joint-specific dysfunction - FAOS cumulative: 42 (OA), 50 (R-OLT), 65 (P-OLT), 65 (INST), 63 (ANT-IMP), 61 (POST-IMP), 60 (COMB-IMP); (b) decreased quality of life - EQ-5D-3L: 0.41 (OA), 0.44 (R-OLT), 0.56 (P-OLT), 0.62 (INST), 0.64 (ANT-IMP), 0.56 (POST-IMP), 0.60 (COMB-IMP) and (c) decreased activity level - TAS: 2.1 (OA), 2.7 (R-OLT), 3.7 (P-OLT), 4.0 (INST), 4.7 (ANT-IMP), 4.4 (POST-IMP), 5.1 (COMB-IMP). FAOS subscales, EQ-5D-3L and TAS were significantly lower in OA and R-OLT patients. Between 31% (POST-IMP) and 68% (OA and R-OLT) of patients required pain medication over one month prior to the assessment. CONCLUSION: All analysed ankle disorders in patients amenable for surgical treatment induced a considerable decline in patients` perceived ankle function, quality of life and activity level. The worst subjective ankle status was reported equally by OA and R-OLT patients, while patients with the other five disorders reported comparable values.

Synovium-Derived Mesenchymal Stem/Stromal Cells and their Promise for Cartilage Regeneration.

Adult tissues are reservoirs of rare populations of cells known as mesenchymal stem/stromal cells (MSCs) that have tissue-regenerating features retained from embryonic development. As well as building up the musculoskeletal system in early life, MSCs also replenish and repair tissues in adult life, such as bone, cartilage, muscle, and adipose tissue. Cells that show regenerative features at least in vitro have been identified from several connective tissues. Bone marrow and adipose tissue are the most well recognized sources of MSCs that are already used widely in clinical practice. Regenerative medicine aims to exploit MSCs and their tissue regeneration even though the underlying mechanisms for their beneficial effects are largely unknown. Despite many studies that have used various tissue-derived MSCs, the most effective tissue source for orthopedic procedures still remains to be identified. Another question that needs to be addressed is how to evaluate autologous MSCs (i.e., patient derived). Previous studies have suggested the features of bone-marrow-derived MSCs can differ widely between individuals, and can be changed in particular in patients suffering from some forms of degenerative disorder, such as osteoarthritis. The synovium is a thin membrane that protects the synovial joints, and it is a rich source of MSCs that show great potential for regenerative medicine. Here, we review synovium-derived MSCs from reports on basic and clinical studies. We discuss their potential to treat cartilage defects caused by either degeneration or trauma, and what needs to be done in further research toward their better exploitation for joint regeneration.

Arthroscopic removal of osteoid osteoma with gamma probe assistance in the hip joint.

AIM: The aim was to present the surgical technique and clinical outcome in a series of patients treated with gamma-probe-assisted arthroscopic removal of osteoid osteoma in the hip joint. METHODS: The case series consisted of 10 patients diagnosed with osteoid osteoma of the hip, who were treated by arthroscopic nidus removal. An endoscopic gamma probe was used intraoperatively to locate the nidus and to control the extent of its removal. Residual osteoma cavities were additionally treated with an arthroscopic radiofrequency ablator. Microfracturing was performed when the osteochondral defect was in the weight-bearing area and osteochondroplasty was done in cases of concomitant cam deformity. Nonarthritic Hip Score (NAHS), Tegner activity score, quality of life questionnaire (EQ-5D) and postoperative magnetic resonance imaging (MRI) were used for evaluation before and post-surgery, with a minimum follow-up of 2 years. RESULTS: The relative reduction of the gamma irradiation count immediately after removal of the nidus was 44.9% (range 33.3-54.5%). Postoperatively, all patients experienced prompt pain relief and a significant improvement according to all patient reported outcomes. Control MRI revealed fibro-cartilaginous tissue repair of post-osteoma osteochondral defects in the weight-bearing area; 1 patient showed signs of early degeneration. CONCLUSIONS: The results of this case series demonstrated the safety and high efficacy of gamma-probe-assisted arthroscopic removal of the osteoid osteoma from the hip joint. Endoscopic gamma probe was recognised as a very useful device for locating the nidus of the osteoid osteoma exactly and preventing incomplete or excessive removal of the bone.

Short-Term Preconditioning With Blood Flow Restricted Exercise Preserves Quadriceps Muscle Endurance in Patients After Anterior Cruciate Ligament Reconstruction.

Surgical ACL reconstruction performed with a tourniquet induces compression and ischemic stress of the quadriceps femoris (QF) muscle which can accelerate postoperative weakness. Given that low-load blood flow restricted (BFR) exercise is potent in enhancing muscle oxygenation and vascular function, we hypothesized that short-term preconditioning with low-load BFR exercise can attenuate QF muscle endurance deterioration in the postoperative period. Twenty subjects undergoing arthroscopic ACL reconstruction performed 5 exercise sessions in the last 8 days prior to surgery. They were assigned into either BFR group, performing low-load BFR knee-extension exercise, or SHAM-BFR group, replicating equal training volume with sham occlusion. Blood flow (near-infrared spectroscopy) and surface EMG of QF muscle during sustained isometric contraction at 30% of maximal voluntary isometric contraction (MVIC) torque performed to volitional failure were measured prior to the intervention and again 4 and 12 weeks after surgery. There was an overall decrease (p = 0.033) in MVIC torque over time, however, no significant time-group interaction was found. The time of sustained QF contraction shortened (p = 0.002) in SHAM-BFR group by 97 ± 85 s at week 4 and returned to preoperative values at week 12. No change in the time of sustained contraction was detected in BFR group at any time point after surgery. RMS EMG amplitude increased (p = 0.009) by 54 ± 58% at week 4 after surgery in BFR group only. BFm increased (p = 0.004) by 52 ± 47% in BFR group, and decreased (p = 0.023) by 32 ± 19% in SHAM-BFR group at week 4 after surgery. Multivariate regression models of postoperative changes in time of sustained QF contraction revealed its high correlation (R2 = 0.838; p < 0.001) with changes in BFm and RMS EMG in the SHAM-BFR group, whereas no such association was found in the BFR group. In conclusion, enhanced endurance of QF muscle was triggered by combination of augmented muscle fiber recruitment and enhanced muscle perfusion. The latter alludes to a preserving effect of preconditioning with BFR exercise on density and function of QF muscle microcirculation within the first 4 weeks after ACL reconstruction.

A descriptive study of potential effect of anterior tibial translation, femoral tunnel and anterior cruciate ligament graft inclination on clinical outcome and degenerative changes.

INTRODUCTION: There is no evidence that anatomically correct anterior cruciate ligament reconstruction (ACLR) offers lower rate of degenerative changes development or that it would lead to a better outcome. The significance and understanding of the abnormal anterior tibial translation (ATT) in ACLR patients is yet to be established. METHODS: Sixty subjects (40 patients at 5.9 years after ACLR, 20 healthy controls) underwent 3 T MRI. Quantitative cartilage T2 mapping and morphological whole organ magnetic resonance imaging score (WORMS) evaluation was performed. Self-reported questionnaires were used for subjective clinical evaluation. Correlations were calculated with the following MRI measurements; femoral tunnel inclination, ACL graft inclination, lateral and medial compartment ATT. RESULTS: In the ACLR group positive correlation was found between the patellar cartilage T2 values and sagittal ACL graft inclination. In the ACLR group lateral compartment ATT showed negative correlation with ACL graft inclination and subjective clinical evaluation, and positive correlation with morphological degenerative changes. Femoral tunnel showed positive correlation with ACL graft inclination in the same plane. CONCLUSIONS: Increased ATT offers worse clinical outcome and increased rate of degenerative changes. Furthermore, ATT is affected by the ACL inclination. Inclination of the drilling tunnel affects ACL graft inclination; thereby independent drilling techniques provide superior results of anatomical ACL graft positioning.

The effects of preconditioning with ischemic exercise on quadriceps femoris muscle atrophy following anterior cruciate ligament reconstruction: a quasi-randomized controlled trial.

BACKGROUND: The degree of quadriceps femoris muscle (QF) atrophy is recognized as one of the key factors of poor knee function and patient's outcome, despite successful reconstruction of anterior cruciate ligament (ACL). AIM: The study assessed whether muscle preconditioning with ischemic exercise can attenuate loss of QF volume, strength, and function after ACL reconstruction. DESIGN: Prospective, single-centre, quasi-randomized, controlled trial with sham intervention. SETTING: University Medical Centre and Laboratory of Physiotherapy Research. POPULATION: Patients with total ACL rupture elected for reconstructive surgery. METHODS: Twenty subjects undergoing ACL reconstruction performed 5 exercise sessions during the last 10 days before surgery. They were assigned into two groups performing either low-load ischemic knee-extension exercise (ISHEMIC group), or standard knee-extension exercise (SHAM group). QF volume, maximal voluntary isometric contraction torque and single-leg anterior reach distance were assessed prior to preconditioning and at 4 and 12 weeks postsurgery. RESULTS: There were no significant differences between the groups in any of the variables prior to, or after surgery. The deficit in QF vastii volume increased (P<0.001) to 20±5 % in ISCHEMIC and 23±10 % in SHAM group at 4 weeks and persisted (P<0.001) at 16±4 % in ISCHEMIC and 20±11 % in SHAM group at 12 weeks postsurgery. Deficit in QF maximal isometric torque persisted (P<0.05) at 15±15 % in ISCHEMIC and 22±16 % in SHAM group at 12 weeks postsurgery. There were no significant differences in single-leg anterior reach distance between the groups at any time point. CONCLUSIONS: Short-term preconditioning with low-load ischemic exercise exhibited no different effect on QF muscle mass, isometric strength, or knee functional loss than comparable standard exercise in patients undergoing ACL reconstruction. CLINICAL REHABILITATION IMPACT: Preconditioning with ischemic exercise of five training sessions or shorter does not have any clinically important effect on preservation of quadriceps femoris muscle mass and function in patients after arthroscopic ACL reconstruction.

[Hip arthroscopy]. / Artroskopija kuka.

In the last ten years, hip arthroscopy has been developing intensively and it is rapidly gaining primacy in the treatment of various injuries and damages to the hip itself and its immediate vicinity. The basic advantage of hip arthroscopy surgery versus classic open surgery is avoiding an open dislocation of the hip and, thus, reducing patient's morbidity and accelerating his/her rehabilitation, which leads to a quicker return to everyday activities. The success of arthroscopic surgery depends on the correct indication for the surgery and on the experience and the skill of the operator. It also depends on the properly conducted rehabilitation and the patient's compliance, as well as on the patient's realistic expectations. Indications for hip arthroscopy today are the following: injury and damage to acetabular labrum and/or articular cartilage, femoroacetabular impingement syndrome, injuries and damages to the ligament of the femoral head, loose and foreign joint bodies as well as different conditions of synovial membrane (synovial chondromatosis, pigmented villonodular synovitis and other inflammatory arthropathy such as rheumatoid arthritis). In this article we describe the indications, technique, complications and the prospect of hip arthroscopy, with a detailed overview of contemporary literature data.

Adaptive changes in the dominant shoulders of female professional overhead athletes: mutual association and relation to shoulder injury.

The aim of our study was to evaluate adaptive changes in the dominant shoulders of female professional overhead athletes, their mutual association, and relation between adaptive changes and shoulder injury. Thirty-six female professional volleyball and handball players were divided into two groups: 14 athletes were included in the symptomatic group (positive shoulder injury history and specific shoulder tests) and 22 athletes were included in the asymptomatic group (negative shoulder injury history and specific shoulder tests). Clinical examinations with specific shoulder tests, evaluation of rotational mobility, and symptoms of malposition and dyskinesis of the dominant scapula (SICK scapula syndrome) were performed. Glenohumeral rotators were isokinetically tested at 60 and 150°/s, with evaluation of stability ratios and rotator fatigability. On average, the participants had decreased internal rotation (P<0.001) and increased external rotation (P<0.001), lower spiking (P<0.01 at 60 and 150°/s) and conventional ratios (P≤0.01 at 60 and 150°/s), lower eccentric external rotator peak torques (eER) (P≤0.05 at 60 and 150°/s), and marginally lower eccentric internal rotator peak torques at 60°/s (P=0.061) on the dominant side compared with the nondominant side. The symptomatic group showed decreased ER (P=0.021), higher deficit of dominant eER at 60°/s (P=0.049), and higher fatigability of internal (P=0.013) and external rotators (P=0.028). The athletes with increased ER had more scapular lateralization (ρ=0.340, P=0.042), higher spiking ratios at 60°/s (ρ=0.349, P=0.037) and 150°/s (ρ=0.330, P=0.049), and lower cocking ratios at 60°/s (ρ=-0.477, P=0.003). Decreased dominant ER, higher deficit of dominant eccentric ER peak torques, and higher dominant rotator fatigability correlate with previous shoulder pain/injury. Different adaptive changes (rotational mobility, SICK scapula signs, and glenohumeral muscular imbalance) are inter-related. As a form of both prevention and rehabilitation for the athletes at risk, we recommend individually adjusted shoulder training on the basis of clinical and isokinetic testing.

Intraarticular nodular fasciitis of the hip.

Intraarticular nodular fasciitis is a rare lesion that has only recently been recognised. We present a case of intraarticular nodular fasciitis of the hip joint in a 25-year-old woman, who presented with a 9-month-history of right groin pain and a decreased range of right hip motion. A polypoid mass, composed of five nodules attached to the synovial membrane of the distal peripheral compartment of the hip was removed arthroscopically, together with two detached nodules. Histopathological examination revealed a myofibroblastic proliferation typical of nodular fasciitis. Complete resolution of symptoms and restoration of function was achieved, without recurrence 2 years after removal of the lesion. To the best of our knowledge, this is the first case of intraarticular nodular fasciitis of the hip, presenting a new indication for arthroscopic treatment.

Arthroscopic removal of juxtaarticular osteoid osteoma of the elbow.

A case of a 42-year-old male patient with symptomatic juxtaarticular osteoid osteoma of the capitulum humeri is presented. After the clinical diagnosis was confirmed with plain radiographs, bone scan, computer tomography and magnetic resonance imaging, the patient underwent arthroscopic removal of the lesion. A partial synoviectomy was performed first and then the center of the lesion was marked with Kirschner wire using the X-ray monitoring. The marked lesion was transarticularly removed with a motorized shaver device. Post-operatively, the patient reported prompt relief of pain that had not reoccurred during 1 year of follow up. To the authors' knowledge, this is the first report of the arthroscopic removal of juxtaarticular osteoid osteoma of the humeral capitulum which promises to be an effective and less invasive alternative to the existing treatment options.

Biological impact of polyacetal particles on loosening of isoelastic stems.

The aim of our study was to identify biological factors responsible for premature loosening of polyacetal hip stems. The results of histological analyses of the tissue around 11 total hip prostheses with loosened polyacetal femoral stems were compared to those obtained in a group of 11 total hip prostheses with loosened metal (CoCr) femoral components. A higher number of polymer wear particles surrounded by giant cells, more bone chips, and a more extensive necrosis were found around loosened polyacetal stems. Histomorphological characteristics of polyacetal wear particles containing BaSO(4) granules in the tissue around loosened polyacetal stems were described. Radiological evaluation of the wear of polyethylene cups suggested that elastic modulus of the stem had no influence on the wear of polyethylene cups. This study indicates that polyacetal wear particles have a great biological potential accelerating the process of loosening.