MiR-217 Regulates SIRT1 Expression and Promotes Inflammatory and Apoptotic Responses in Osteoarthritis.

Previous studies have reported miR-217 uregulation in age-related pathologies. We investigated the impact of miR-217-5p on sirtuin 1 (SIRT1) regulation in human osteoarthritic (OA) chondrocytes. MiR-217 target enrichment analyses were performed using three public databases, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. MiR-217-5p expression levels were quantified in normal and OA chondrocytes. SIRT1 expression levels, nuclear factor kappa-B p65 subunit (NF-κBp65) and p53 acetylation levels, and expression levels of OA-related pro-inflammatory markers [tumor necrosis factor α (TNFα), interleukin 1ß (IL-1ß), IL-6], pro-apoptotic markers [Bax, pro-caspase 3, cleaved caspase 3] and matrix regulators [matrix metalloproteinase (MMP)-1, MMP-13, MMP-9, Collagen 2 (COL2A1), Aggrecan (ACAN)] were evaluated in miR-217 mimic-treated and/or miR-217 inhibitor-treated OA chondrocytes, with/without subsequent treatment with siRNA against SIRT1 (siSIRT1). MiR-217-5p was upregulated in OA chondrocytes, while target prediction/enrichment analyses revealed SIRT1 as miR-217 target-gene. Deacetylation of NF-κBp65 and p53 in miR-217 inhibitor-treated OA chondrocytes was reversed by siSIRT1 treatment. MiR-217 inhibitor-treated OA chondrocytes showed increased COL2A1, ACAN and decreased IL-1ß, IL-6, TNFα, Bax, cleaved caspase 3 and MMPs expression levels, which were reversed following miR-217 inhibitor/siSIRT1 treatment. Our findings highlight the impact of miR-217-5p on SIRT1 downregulation contributing to OA pathogenesis.

An observational study of complications in patients with established multiple compartments syndrome of the leg.

INTRODUCTION: Established multiple compartments syndrome of the leg (EMCSL) is defined as permanent ischemic lesions of muscles and nerves of the compartment, leading to multiple muscle contractions, muscle weakness and wasting and reduced limb sensation. The leg is seriously affected and the patient is unable to return to prior activities. The objective of this research is to quantify long-term consequences, morbidity and socioeconomic impact of established multiple compartments syndrome of the leg MATERIALS AND METHODS: 28 patients suffering from complications from EMCSL were referred to our clinic for secondary management between January 2012 and April 2016 and were followed for mean 41.4 months. Reconstructive procedures to address multiple conditions following established tibia compartment syndrome were performed. The number of reconstructive procedures, days of hospitalization, relationship, educational and employment status per patient were recorded. Preop and postop SF-12 score at final follow-up was documented for the 21 patients who were operated on. RESULTS: A median of three reconstructive procedures was performed per patient for 21 patients. The hospitalization period ranged from 6 to 365 days, with a mean period of 47.5 days (SD 71.4). At the final follow-up, 19 patients had lost their occupation, 3 patients had returned to lighter manual labor, 5 patients had lost two school years, and 1 patient had abandoned school. At the time of injury, 24 patients were single. At final follow-up, 19 of these patients, with a mean age of 38.5 years, were still single. Preoperative and postoperative (at final follow-up) physical and mental components of the SF-12 score had a statistically significant difference (p < 0.001), but final values were not normal. CONCLUSIONS: Despite advancements in surgical reconstructive intervention, patients with established compartment tibia syndrome experience permanent grave residual disability with personal and social implications.

Better knee function after surgical repair of acute quadriceps tendon rupture in comparison to acute patellar tendon rupture.

INTRODUCTION: The purpose of this study was to determine if there is a difference in knee function between patients with quadriceps tendon rupture and patellar tendon rupture after acute surgical repair. Our hypothesis was that knee function would be similar between the two groups. METHODS: The study population included 24 patients; 13 patients suffered from quadriceps tendon rupture and 11 patients from patellar tendon rupture. All patients underwent acute surgical repair using heavy non-absorbable trans-osseous sutures; another non-absorbable suture, passed through both retinaculum and around the repaired tendon to augment the repair. Clinical evaluation was performed using the Lysholm, Kujala, and VAS scoring systems. In addition, radiographic evaluation to evaluate patellar height and patello-femoral joint arthritis using Iwano's classification was performed. RESULTS: The average follow-up time was 70.5 months. All patients in the quadriceps tendon group had full range of knee motion while 3 patients (27%) in the patellar tendon group had reduced knee flexion. Patients in the quadriceps tendon group had a significantly higher Kujala score in comparison to the patellar tendon group (88 vs. 73 p=0.033). No significant differences were identified between the two groups according to the Lysholm scoring system. Patients in the quadriceps tendon group had significantly less pain according to VAS scale (1.2 vs. 3.5 p=0.012). Radiographic evaluation revealed that two patients from each group showed signs of grade II patello-femoral joint arthritis according to Iwano's classification. CONCLUSION: Acute surgical repair of quadriceps tendon ruptures provides better knee function, in comparison to the surgical restoration of patellar tendon rupture. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

A M. avium complex spondylodiscitis in a middle-aged woman with diabetes.

Spondylodiscitis, the inflammation of the vertebral bodies and the intervertebral disk space, is the reason for low back pain in a minority of cases. This is caused by various pathogens. Mycobacterium tuberculosis is responsible for 17-39% of all the cases of spondylodiscitis. On the contrast, spondylodiscitis from non tuberculous mycobacteria is extremely rare in literature. We describe a 68 -year old diabetic woman which is the first case of bone marrow involvement by M. intracellulare (member of M avium complex)with spondylodiscitis.

Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7.

AIM: To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7 (rhBMP-7) for the treatment of nonunions. METHODS: Bone morphogenetic proteins (BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients (80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent joints were also carried out. Factors related to the patient (age, gender), the nonunion (location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure (graft and fixation type, amount of rhBMP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ 2 test was performed. RESULTS: Eighty point nine percent of the nonunions treated with rhBMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients (17.8%) and it was apparent in the routine radiological evaluation of the nonunion site, in a mean time of 5.5 mo after the rhBMP-7 application (range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhBMP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient's gender was the only important factor for the development of heterotopic ossification (P = 0.007). CONCLUSION: Heterotopic ossification after the use of rhBMP-7 in nonunions was common but it did not compromise the final clinical outcome in most cases, and affected only male patients.

Quadratus femoris tear as an unusual cause of hip pain: a case report.

PURPOSE: To show that quadratus femoris muscle partial or complete tear is an extremely rare if not underdiagnosed cause of hip pain. METHODS: We present the case of a 75-year-old Caucasian woman with spontaneous non-traumatic quadratus femoris tear. RESULTS: Computed Tomography showed quadratus femoris tear with occult underlying ischiofemoral impingement pathology. CONCLUSIONS: Quadratus femoris muscle is a hip external rotator and adductor and is situated along the posterior aspect of the hip joint and its proximity of anatomy with other external rotators leads to diagnostic pitfalls for radiologists. Identification of the exact muscle tear will establish the diagnosis, guide the proper physical therapy and reliably inform the patient what to expect after treatment.

Myxoid liposarcoma with cartilaginous differentiation: A case study with fish analysis and review of the literature.

Cartilaginous differentiation is rarely encountered in myxoid liposarcomas. To date, a small number of such cases have been described, and molecular or cytogenetic analysis was performed only in few of them. In the present study, we describe a primary myxoid liposarcoma with cartilaginous differentiation which arised in the left thigh of a 37-year-old man. Miscroscopically, the tumor consisted of areas with typical myxoid liposarcoma morphology and areas of sharply demarcated hyaline cartilage nodules. Here, we present the results of Fluorescence In Situ Hybridization (FISH) analysis that revealed the presence of FUS and DDIT3 gene rearrangements in both the liposarcomatous and cartilaginous components of the tumor. These findings confirm the neoplastic nature of the cartilage component in this rare tumor.

Effect of interscalene brachial plexus block on heart rate variability.

BACKGROUND: Interscalene brachial plexus block (ISB) may be followed by cardiovascular instability. Until date, there is no clear picture available about the underlying mechanisms of ISB. In this study, we aimed to determine the changes in heart rate variability (HRV) parameters after ISB and the differences between right- and left-sided ISBs. METHODS: We prospectively studied 24 patients operated for shoulder surgery in sitting position and divided them into two respective groups: R (right-sided block = 14 pts) and L (left-sided block = 10 pts). HRV data were taken before and 30 min after the block. Ropivacaine without ephedrine was used for the ISB through an insulated block needle connected to a nerve stimulator. Statistical analysis implemented chi-square, Student's and t-paired tests. Skewed distributions were analyzed after logarithmic transformation. RESULTS: All the studied patients had successful blocks. Horner's syndrome signs were observed in 33.3% of the patients (R = 5/14, L = 3/10; [P = 0.769]). There were no significant differences in pre-block HRV between the groups. The application of ISB had differential effect on HRV variables: R-blocks increased QRS and QTc durations and InPNN50, while a statistical decrease was seen in InLF. L-blocks did not show any significant changes. These changes indicate a reduced sympathetic and an increased parasympathetic influence on the heart's autonomic flow after R-block. CONCLUSIONS: Based on the obtained results we conclude that ISB, possibly through extension of block to the ipsilateral stellate ganglion, alters the autonomic outflow to the central circulatory system in a way depending on the block's side.

Factors affecting the quality of life after total knee arthroplasties: a prospective study.

BACKGROUND: The purpose of the study is to evaluate the self-reported outcomes in the first year after primary total knee arthroplasty (TKA), and to determine factors influencing the quality of life (QoL) 6 weeks, 3, 6, and 12 months after TKA. METHODS: A cohort of patients with knee osteoarthritis undergoing primary TKA at two hospitals (a regional university hospital and a capital's metropolitan hospital) was prospectively followed for 12 months. Patients were assessed preoperatively and at 4 postoperative time-points, with the use of self-reported measurements for pain, physical function and depression with the following evaluation tools: Western Ontario and McMaster Osteoarthritis Index [WOMAC], Knee Society Scoring system [KSS], Centre for Epidemiological Studies Depression Scale, [CES-D10] and visual analog scale [VAS] for pain). General linear modelling for repeated measures was used to evaluate the effect of each independent variable including clinical and sociodemographic data. Differences between groups at different time points were tested by the independent samples t-test. RESULTS: Of the 224 eligible patients, 204 (162 females, mean age 69.2) were included in the analysis. Response rate at one year was 90%. At 6 weeks after surgery, despite improvement in pain and alleviation of the depressive mood, the physical function remained less satisfactory. Females presented lower scores in terms of quality of life, both preoperatively and 6 weeks after TKA. Significant improvement was already experienced at 3 months postoperatively. According to WOMAC, KSS, CES-D10 and pain VAS scores the Qol was significantly improved 12 months after TKA (P < 0.001). CES-D10 score was positively correlated with WOMAC and pain VAS scores at all the time points assessed (P < 0.001). Age, body mass index (BMI), place of residence, level of education and social support were not significant predictors of QoL after TKA. CONCLUSIONS: Patients experienced great improvement in their QoL after TKA in spite of a less satisfactory physical function in the first 6 weeks after surgery, with noticeable differences in the QoL among genders in the same time period. After that period all patients experienced significant improvement for all the measured parameters, until the third postoperative month with smaller changes thereafter.

Outcome after tantalum rod implantation for treatment of femoral head osteonecrosis: 26 hips followed for an average of 3 years.

BACKGROUND AND PURPOSE: Tantalum rod implantation has recently been proposed for treatment of early stages of femoral head osteonecrosis.The purpose of our study was to report the early results of its use in pre- and post-collapse stages of the disease. METHODS: We studied prospectively 27 patients who underwent tantalum rod implantation for treatment of nontraumatic femoral head osteonecrosis between December 2000 and September 2005. Patients were evaluated radiologically and clinically using the Steinberg classification and the Harris hip score (HHS). Disease stage varied between stages II and IV. Mean follow-up time was 38 (15-71) months. RESULTS: 1 patient (1 hip) died 15 months after surgery for reasons unrelated to it. 13 of 26 hips remained at the same radiographic stage, and 13 deteriorated. Mean HHS improved from 49 to 85. 6 patients required conversion to total hip arthroplasty. When the procedure was used for stages III and IV, both radiological outcome and revision rates were worse than for the stage II hips. There was, however, no difference in postoperative HHS between patients at pre- and post-collapse stages at the time of initial evaluation. Survivorship, with revision to THA as the endpoint,was 70% at 6 years. INTERPRETATION: The disease process does not appear to be interrupted,but there was a significant improvement in hip function initially in most hips. Tantalum rod implantation is a safe "buy-time" technique, especially when other joint salvage procedures are not an option. Appropriate patient selection and careful rod insertion are needed for favorable results.

Acute non-traumatic marrow edema syndrome in the knee: MRI findings at presentation, correlation with spinal DEXA and outcome.

PURPOSE: The aim of the study was to present the MRI findings of non-traumatic edema-like lesions presented acutely in the adult knee and to correlate them with the 3-year outcome and the bone mineral density (BMD) in the spine. MATERIALS AND METHODS: Ninety-eight patients (40 men, 58 women, mean age 60.1+/-11 years, age range 27-82 years), were followed up clinically as well as with MR imaging, when indicated, for at least 3 years. Patients were classified according to presentation in 3 groups (A: bone marrow edema (BME), B: BME and subchondral fracture, C: BME and articular collapse) and according to outcome in 2 groups (A: reversible BME, B: articular collapse). BMD measurements of the spine were carried out in males over 70 and females over 60 years old using DEXA. RESULTS: The isolated BME pattern was observed in 64.3% (Group A), subchondral fractures without articular collapse in 11.2% (Group B) and articular collapse in 24.5% (Group C). Significant differences were found among the 3 groups at presentation, regarding the age, sex, BMD, affected area and duration of symptoms prior to imaging (p<0.05). Localization of the lesions in the weight-bearing areas of the knee was shown in 100% of C, in 90.9% of B and in 50.8% of A. The duration of symptoms prior to imaging was longer in C (7.6+/-2.8m) than in A (2.5+/-1.7m) and B (4.0+/-3.2m) (p<0.05). Group B progressed to articular collapse in 45.5%, the rest demonstrating a favourable outcome. Group C showed clinical improvement in 75% and persistent symptoms that required knee arthroplasty in 25% of cases. Articular collapse was the final outcome in 29.6% and transient BME in 70.4% of patients. These two groups showed significant differences regarding the age (p approximately 0), sex (p=0.002), low BMD (p=0.004), affected area (p approximately 0), presence of subchondral sparing (p approximately 0), duration of symptoms prior to imaging (p approximately 0), time from onset of symptoms to the final outcome (p approximately 0) and need for arthroplasty (p=0.001). None of the patients with transient BME syndrome eventually progressed to articular collapse. CONCLUSION: In the context of acute non-traumatic knee BME, the age and sex of the patient, the duration of symptoms before imaging, the pattern of BME, and the BMD appear to correlate with the final outcome.

Total knee arthroplasty in patients with pre-existing fracture deformity.

Pre-existing femoral or tibial extra-articular fracture deformity may adversely affect the results of total knee arthroplasty (TKA). This deformity can be addressed with asymmetrical intra-articular resection or with correctional osteotomy performed prior to or at the time of primary TKA. Careful preoperative planning obviates many potential problems that can occur at the time of surgery with correction of many complex deformities.

Arthroscopic meniscal repair: a comparative study between three different surgical techniques.

The purpose of this prospective study was to evaluate and compare the results of arthroscopic meniscal repair using three different techniques. Between January 2002 and March 2004, 57 patients who met the inclusion criteria underwent an arthroscopic meniscal repair. The outside-in technique was used in 17 patients (group A), the inside-out in 20 patients (group B), while the rest of the 20 patients (group C) were managed by the all-inside technique using the Mitek RapidLoc soft tissue anchor (Mitek Surgical Products, Westwood, MA, USA). Anterior cruciate ligament (ACL) reconstruction was performed in 29 patients (51%). The criteria for clinical success included absence of joint line tenderness, locking, swelling, and a negative McMurray test. The minimum follow-up was one year for all groups. The mean follow-up was 23 months for group A, 22 months for group B, and 22 months for group C. All meniscal repairs were considered healed according to our criteria in group A, while 19 out of 20 repairs (95%) healed in group B. Finally 7 of 20 repairs (35%) were considered failures in group C and this difference was statistically significant in comparison with other groups. The time required for meniscal repair averaged 38.5 min for group A, 18.1 min for group B, and 13.6 min for group C. Operation time for meniscal repair in group A was statistically longer in comparison with other groups. There were no significant differences among the three groups concerning complications. According to our results, arhtroscopic meniscal repair with the inside-out technique seems to be superior in comparison with the other methods because it offers a high rate of meniscus healing without prolonged operation time.

Absence of linkage to chromosomes 6q and 16p in a Greek population with knee osteoarthritis.

Osteoarthritis (OA) is a common age-related debilitating disease of the joints characterized by degeneration of the articular cartilage which leads to joint pain, discomfort, and immobility. Several risk factors have been associated with OA including a genetic predisposition. Specific chromosomal regions have thus far been associated with susceptibility to OA, the strongest being on chromosomes 2, 6, and 16. We hereby report our data on 34 Central Greek knee OA families that were investigated for linkage to the chromosome 6q and 16p susceptibility regions. All affected members had undergone total knee replacement surgery (TKR) at a single large Orthopedics Unit in Central Greece. Nineteen microsatellite markers were selected, 15 for chromosome 6q and 4 for chromosome 16p at a distance of approximately 7 cm. Allele fragment sizes were determined by an automated DNA sequencer using the Fragment Analysis Software. Our results revealed a statistically significant difference in the ratio of affected females to males with knee OA and also showed that there is no evidence of linkage to regions 6q and 16p in a cohort of Central Greek pedigrees with knee OA.

Evaluation of meniscal repair with serial magnetic resonance imaging: a comparative study between conventional MRI and indirect MR arthrography.

OBJECTIVE: To prospectively investigate the healing process of meniscal repair with plain magnetic resonance imaging (MRI) and indirect MR arthrography and to compare the two methods. MATERIALS AND METHODS: Twenty patients with an arthroscopic meniscal repair without clinical symptoms underwent conventional and indirect MR arthrography of the affected knee, 3, 6 and 12 months after the index operation applying a T1-w Spin Echo sequence in three planes. The size of the tear gap was measured on transverse images. The signal-to-noise ratio and the configuration of the abnormal signal were evaluated in the coronal images. RESULTS: All patients demonstrated abnormal signal intensity at the side of the meniscal repair. The size of the gap at the previous tear side, reduced significantly by 45 and 40% on conventional MRI and indirect MR arthrography respectively, from 3 months to 1 year (P < 0.05). The signal-to-noise ratio of the intrameniscal abnormal signal reduced significantly and approximately 50% from 3 to 6 months, and from 6 to 12 months postoperatively, as demonstrated with indirect MR arthrography. However, as opposed to normal meniscus, the signal-to-noise ratio of the abnormal area remains 5.5 times higher 12 months postoperatively. In contrast, the reduction of signal-to-noise ratio of the abnormal area at conventional MRI was not significant even from 3 to 12 months. In 90% of the cases, the indirect MR arthrography showed the intrameniscal abnormal signal on plain MRI, to extend to the articular surface as opposed to 25% on plain MRI. CONCLUSION: With indirect MR arthrography, the natural process of meniscal healing can be evaluated. Significant reduction of the size of the tear gap and significant reduction of the signal-to-noise ratio of the abnormal signal as well as its configuration are the main parameters interpretating the normal healing process.

MR imaging findings in transient osteoporosis of the hip.

PURPOSE: The authors sought to describe the magnetic resonance (MR) imaging findings including perfusion imaging, in association with the course of acute bone marrow oedema syndrome (aBMEs), in a group of patients with acute hip pain and a final diagnosis of transient osteoporosis of the hip (TOH). MATERIALS AND METHODS: From 217 patients referred with a probable diagnosis of avascular necrosis (AVN) of the femoral head, we identified 42 patients who had clinical and radiographic findings not relevant to AVN. MR imaging examinations were performed on a 1.0T scanner. Perfusion imaging was performed in 20 patients. The bone marrow oedema (BME) was classified in four stages. In addition, the presence or absence of oedema in the subchondral area and the presence of other subchondral lesions were recorded. Acetabular bone marrow was also assessed for the presence of oedema. The quantitative measurements included: maximum size of the effusion, percentage of enhancement (PE) and time of peak enhancement of abnormal marrow compared to the first pass, on the perfusion images. RESULTS: Osteopenia was present on plain radiographs in 87% of cases. The most common pattern of BME was extending to the femoral head and neck. Acetabulum was involved in 16.6%. In 22.6% the BME spared the subchondral region of the femoral head. There were two cases (4.7%) with subchondral changes. A joint effusion was noted in 33 of the 42 patients. On perfusion imaging, a delayed peak enhancement was noted in 20 patients between 40 and 65 s after the first pass of contrast. No patient had any evidence of femoral head collapse or change in sphericity on follow-up MRI. None of the patients developed avascular necrosis in a time frame of 18 months from the onset of the acute hip pain. CONCLUSION: The aBMEs MR imaging pattern varies and is most commonly appearing on X-rays as osteopenia. Absence of subcondral lesions, delayed peak enhancement of the abnormal marrow on perfusion images, and sparing of subchondral zone from marrow oedema are MR imaging findings highly correlated to TOH.

Idiopathic osteoarthritis of the hip: incidence, classification, and natural history of 272 cases.

Long-term clinical and radiographic data of 210 patients (272 hips) with idiopathic hip osteoarthritis were reviewed. Of the 272 hips, 218 (80%) were eccentric and 54 (20%) were concentric. In eccentric hips, the femoral head migrated superolaterally or superomedially, because of the eccentric development of the degenerative changes, which had deteriorated rapidly. Hips with eccentric idiopathic osteoarthritis underwent total hip arthroplasty (THA) at an average of 4 years after symptom onset. In concentric hips, the femoral head migrated medially, causing progressive thinning of the medial wall of the acetabulum, and degenerative changes progressed slowly. Hips with concentric idiopathic osteoarthritis underwent THA at an average of 10 years after symptom onset.