MicroRNA as Possible Mediators of the Synergistic Effect of Celecoxib and Glucosamine Sulfate in Human Osteoarthritic Chondrocyte Exposed to IL-1ß.

This study investigated the role of a pattern of microRNA (miRNA) as possible mediators of celecoxib and prescription-grade glucosamine sulfate (GS) effects in human osteoarthritis (OA) chondrocytes. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination, for 24 h, with or without interleukin (IL)-1ß (10 ng/mL). Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis and reactive oxygen species (ROS) by cytometry, nitric oxide (NO) by Griess method. Gene levels of miRNA, antioxidant enzymes, nuclear factor erythroid (NRF)2, and B-cell lymphoma (BCL)2 expressions were analyzed by quantitative real time polymerase chain reaction (real time PCR). Protein expression of NRF2 and BCL2 was also detected at immunofluorescence and western blot. Celecoxib and GS, alone or in combination, significantly increased viability, reduced apoptosis, ROS and NO production and the gene expression of miR-34a, -146a, -181a, -210, in comparison to baseline and to IL-1ß. The transfection with miRNA specific inhibitors significantly counteracted the IL-1ß activity and potentiated the properties of celecoxib and GS on viability, apoptosis and oxidant system, through nuclear factor (NF)-κB regulation. The observed effects were enhanced when the drugs were tested in combination. Our data confirmed the synergistic anti-inflammatory and chondroprotective properties of celecoxib and GS, suggesting microRNA as possible mediators.

Short time effects of a low-frequency, high intensity magnetic field in the treatment of chronic neck and low back pain.

Introduction: Neck and back pain afflicts millions of people. Magnetotherapy has shown to have anti-inflammatory effects that could act on pain generation, but the literature lacks provide a precise therapeutic protocol. Methods: A high-intensity electromagnetic field with a dedicated applicator was administered to 38 patients with low-back pain and 30 patients with neck pain. The device provides 60 mT and a frequency of 50 Hz for 30 minutes, the session was repeated 4 times. Results: The mean VAS of the low-back pain group decreased from 6.56 to 4.54, with a significant reduction of 30.8%. The mean VAS of the neck pain group decreased from 6.51 to 1.96, with a significant reduction of 69.9%. Discussion: The treatment used showed good results in both groups of the patient, without side effects. The therapeutic protocol adopted is safe, provide rapid relief from the pain and is not time demanding. This treatment could represent an effective non-pharmacologic physical therapy option in the treatment of low-back pain and cervical pain.

Single-Dose Intra-Articular Administration of a Hybrid Cooperative Complex of Sodium Hyaluronate and Sodium Chondroitin in the Treatment of Symptomatic Hip Osteoarthritis: A Single-Arm, Open-Label, Pilot Study.

INTRODUCTION: Intra-articular (i.a.) hyaluronic acid is an accepted conservative therapy for knee osteoarthritis (OA). This study evaluated the safety and efficacy of a single i.a. injection of an innovative formulation of sodium hyaluronate 2.4% plus sodium chondroitin non-sulphated 1.6% of biotechnological origin (HA-SC) for the treatment of patients with radiographically confirmed symptomatic hip OA and moderate-to-severe pain. METHODS: In this prospective, multicenter, open-label, pilot study, HA-SC was administered using a standard ultrasound-guided procedure. Adverse events, global/local evaluation of tolerability, and use of rescue analgesics were recorded. Efficacy endpoints included visual analogue scale (VAS) measurement of hip pain, changes in Lequesne's algofunctional Index, and assessment of global status. RESULTS: Treatment was well tolerated; adverse device events of moderate-to-severe intensity, most commonly, injection site pain/localized arthralgia occurred in 20.8% of subjects. Global evaluation of tolerability was rated as excellent or good (75.0%), fair (16.7%), and poor (8.3%) by subjects and 77.1, 14.6, and 8.3%, respectively, by investigators. There was a rapid and significant decrease in hip pain after a single injection; VAS pain score decreased from a mean of 67.5 mm at baseline to 29.3 mm by day 7, with the effects sustained during 6 months of follow-up (P < 0.0001). There were significant improvements in Lequesne's Index for hip OA total scores at all time points during follow-up (P < 0.0001). The majority of subjects reported 'Very much improved' or 'Slightly improved' global improvement at any time point. Use of rescue paracetamol was generally low. CONCLUSIONS: A single i.a. injection of an innovative HA-SC formulation was well tolerated, safe, and effective in the treatment of symptomatic hip OA.

ALDI (Anterior Lateral Decubitus Intermuscular) approach to the hip: Comprehensive description of the surgical technique with operative video.

The direct anterior approach to the hip is judged to be difficult and even after many solutions, such as special operating tables, have been proposed to perform it, in some reports the complication rate remains high. The complications reported are nerve lesions, dislocation, muscles damages, intraoperative fractures. We describe a modification of the anterior approach, undertaken keeping the patient in lateral decubitus, in order to gain a better range of leg movement and a significant reduction of the force applied to the retractors, the technique was named ALDI (anterior lateral decubitus intermuscular) approach. The surgeon starts behind the patient as in all the other traditional approaches, to maintain unchanged the acetabular view and the dexterity in cup implantation. For the femoral preparation, he moves in front of the patient to have a better visualization. In a series of 150 patients, with a mean operative time of 51.38minutes (range, 40-112), we had no intraoperative fractures, one (0.6%) lateral femoral cutaneous nerve temporary neurapraxia, one (0.8%) posttraumatic dislocation four years after the operation and, no revisions for aseptic loosening or infection. At the 5 years follow-up, the mean Oxford Hip score was 45.2 (range, 38-48; SD 2.6), the mean Harris Hip Score was 96,7 (range, 76-100; SD 2.8), and the mean UCLA score was 7 (range, 5-10; SD 1.4). The possibility to always obtain the optimal position of the surgical window with reduced tension on the muscles, and the unchanged initial surgeon position, could make the ALDI approach the ideal technique for the surgeons that decide to perform an anterior approach.

Jockey injuries during the Siena "Palio". A 72-year analysis of the oldest horse race in Italy.

INTRODUCTION: Horse racing is a hazardous sport. We analyzed the incidence and characteristics of jockey injuries in a typical horse race. METHODS: We analyzed all injuries sustained by 224 jockeys in the last 72 years. RESULTS: It was found that in 96.1% of the races there was at least one fall and in 28.6% of the races 50% or more of the jockeys fell. In 43.4% of the falls, the jockey was taken to the emergency room. Comparing the Palio with traditional races in other countries, a higher injury incidence rate was observed for every 100 falls (109.884 vs 27-59) and a lower concussion rate/100 falls (0.97 vs 1.8-7.4). CONCLUSION: The Palio is one of the most threatening races that continues today. Jockeys are at greater risk for a fall than any other race in the world.

Differentiating overlapping symptoms of vulvodynia and pudendal neuralgia.

CONTEXT: Vulvodynia is defined as a chronic vulvar pain non-associated with infectious, inflammatory, neoplastic or hormonal disorders. OBJECTIVES: To present a case demonstrating the difficulty in assessing concomitant disease in vulvodynia. METHODS: A 26-year-old woman, presented with persistent vulvodynia. She received oral and topical medications and behavioural interventions to lessen sexual pain and restore sexuality. As sexual pain decreased, the patient reported symptoms previously not mentioned: continuous, intense periclitoral pain and numbness at the perineum when sitting for a long time. These new symptoms suggest the involvement of the peripheral neural system. The physical evaluation confirmed right-side pelvic distortion, and pathological increase in lumbar lordosis, which caused neuralgia radiating to the external genitalia and perineum, and overlapping with sexual pain. After diagnosing pudendal neuralgia according to the Nantes criteria, physical treatment and relaxation exercises to de-contract the spine were added to the vulvodynia regimen. RESULTS: During treatment, vulvodynia was sometimes present but never unbearable, allowing satisfactory sex. With physical therapy, the symptoms of pudendal neuralgia decreased. CONCLUSION: Differentiating the presence of two conditions with overlapping symptoms is difficult because the vestibular pain had shadowed pudendal neuralgia symptoms at initial assessment. Syndromes of chronic pain tend to associate with each other and one syndrome may shadow symptoms of the concomitant condition affecting adjacent anatomical areas. Only the accurate identification of all the syndromes involved allows adopting the correct treatment.

WITHDRAWN: Jockey injuries during the Siena "Palio". A 72-year analysis of the oldest horse race in Italy.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Injury, 50(2) 2019 365­368, https://doi.org/10.1016/j.injury.2018.12.014. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

The Challenges of the Femoral Bone Loss in the Management of the Floating Knee IIB According Fraser: A Case Report.

INTRODUCTION: This case report describes the management and the possible therapeutic solutions for the treatment of femoral bone loss associated with an open fracture IIIB Gustilo Andersonin a polytrauma that includes floating knee (GF) Fraser IIB from damage control orthopedics to final treatment. CASE REPORT: The patient was treated with an external fixator femorotibial bridge after extensive cleaning and debridement of open fractures. After 17-day post-trauma, we substitute the fixator with a less invasive stabilization system plate and screws with contralateral allograft bone strut.3months after the first surgery, the patient underwent surgery for the intramedullary nailing of the tibia. The follow-up was clinical using the knee injury and osteoarthritis outcome score (KOOS), short form 12 health survey (SF-12) for quality of life, and radiological at 1-3-6-12-18-24-36 months. The patient walked with partial load up until the 6months after injury and then began a progression to a total load. At 24-months post surgery, the patient had both the KOOS and SF-12 at 100 points. CONCLUSION: Not all Fraser IIB are equal, the timing of treatment should be discussed case by case. The surgical sequence should be respected: First, the fixation of the femur, and then, the stabilization of the tibia, taking into account the condition of the skin, eventual exposure or the eventual level of sub-amputation of the limb. The clinical and radiographic results show how efficient damage can lay the foundations for an excellent definitive treatment.

Analysis of Injuries and Risk Factors in Taekwondo during the 2014 Italian University Championship.

Purpose This study aims to analyze the risk factors and type of injuries occurring in Taekwondo athletes participating in a national competition. Methods Out of the 127 competitors, 18 athletes got injured during a Taekwondo championship who were analyzed for the following parameters: modality of training; age, weight; belt color; and the type of injury. Results Around 89% of the injuries were due to bruising and were found mainly on the lower limbs (61%) during the elimination rounds and during the first match of the day. The higher probability of injury was in the second round (56%), and during the first match of the day (72%). Nearly all the athletes were able to complete the game in which they were injured (83%). Comparing the average age of the athletes suffering an injury (23.6 ± 2.06 years) with their average years of training (8.4 ± 7.05 years) it can be noted that these athletes began this discipline rather late. The more is the training age and the weekly hours of training, the more are the numbers of matches completed, even as injured. Beginners with a low-level belt suffered more injuries than the experienced subjects did. Conclusion The following risk factors for injury were found: starting to practice in late age, weekly training sessions with a few number of hours, male sex, low-level belt, elimination rounds, the first match of the day, and second round. Level of Evidence Level III, observational analytic study without a control group.

Hydrostatic Pressure Regulates MicroRNA Expression Levels in Osteoarthritic Chondrocyte Cultures via the Wnt/ß-Catenin Pathway.

Mechanical loading and hydrostatic pressure (HP) regulate chondrocytes' metabolism; however, how mechanical stimulation acts remain unclear. MicroRNAs (miRNAs) play an important role in cartilage homeostasis, mechanotransduction, and in the pathogenesis of osteoarthritis (OA). This study investigated the effects of a cyclic HP (1-5 MPa), in both normal and OA human chondrocytes, on the expression of miR-27a/b, miR-140, miR-146a/b, and miR-365, and of their target genes (MMP-13, ADAMTS-5, IGFBP-5, and HDAC-4). Furthermore, we assessed the possible involvement of Wnt/ß-catenin pathway in response to HP. Chondrocytes were exposed to HP for 3h and the evaluations were performed immediately after pressurization, and following 12, 24, and 48 h. Total RNA was extracted and used for real-time PCR. ß-catenin was detected by Western blotting analysis and immunofluorescence. In OA chondrocytes, HP induced a significant increase (p < 0.01) of the expression levels of miR-27a/b, miR-140, and miR-146a, and a significant reduction (p < 0.01) of miR-365 at all analyzed time points. MMP-13, ADAMTS-5, and HDAC-4 were significantly downregulated following HP, while no significant modification was found for IGFBP-5. ß-catenin levels were significantly increased (p < 0.001) in OA chondrocytes at basal conditions and significantly reduced (p < 0.01) by HP. Pressurization did not cause any significant modification in normal cells. In conclusion, in OA chondrocytes, HP restores the expression levels of some miRNAs, downregulates MMP-13, ADAMTS-5, and HDAC-4, and modulates the Wnt/ß-catenin pathway activation.

Dynamic corset versus three-point brace in the treatment of osteoporotic compression fractures of the thoracic and lumbar spine: a prospective, comparative study.

BACKGROUND: The three-point orthosis is the most commonly used brace in the conservative treatment of osteoporotic vertebral fractures. The Spinomed® dynamic orthosis represents an alternative. AIMS: We compared efficacy and safety of these two types of brace in treating osteoporotic vertebral fractures. METHODS: One hundred forty patients, aged 65-93 years, sustaining osteoporotic vertebral fracture were consecutively recruited and divided into two groups, and treated with either three-point orthosis or dynamic corset. Patients were evaluated with Visual Analogue Scale, Oswestry Low Back Pain Disability Questionnaire, and measurement of forced expiratory volume in the first second. Regional kyphosis angle, Delmas Index, and height of the fractured vertebral body were also measured on full-spine X-rays. Follow-up intervals were 1, 3, and 6 months after trauma. The complications encountered during the 6-month follow-up were recorded. RESULTS: At the 3- and 6-month follow-ups, there was a significant difference (p < 0.05) in pain, disability, and respiration in favor of the dynamic orthosis group. At 6-month follow-up, there was no significant difference (p > 0.05) in all the radiological parameters between groups. Complications were reported for 28 patients in the three-point orthosis group, and for eight patients in the dynamic corset group (p < 0.05). DISCUSSION: Biofeedback activation of back muscles is probably a key factor in improving functional outcome with dynamic orthosis. CONCLUSIONS: Compared to three-point orthosis, patients treated with dynamic orthosis had a greater reduction in pain and a greater improvement in quality of life and respiratory function, with equal effectiveness in stabilizing the fracture, and fewer complications.

The Biological Metallic versus Metallic Solution in Treating Periprosthetic Femoral Fractures: Outcome Assessment.

Introduction. The periprosthetic fracture of the femur is, in order of frequency, the fourth leading cause (5.9%) of surgical revision. Our study aims to demonstrate how the grafting of bone splint betters the outcomes. Materials. We treated 15 periprosthetic femoral fractures divided into two groups: PS composed of 8 patients treated with plates and splints and PSS involving 7 patients treated only with plates. The evaluation criteria for the two groups during the clinical and radiological follow-up were the quality of life measured by the Short Form (36) Health Survey (SF-36), Harris Hip Score (HHS), Modified Cincinnati Rating System Questionnaire (MCRSQ), bone healing measured by the Radiographic Union Score (RUS), postoperative complications, and mortality. The evaluation endpoint was set at 24 months for both groups (p < 0.05). Results. The surgery lasted an average of 124.5 minutes for the PS group and 112.6 minutes for the PSS. At 24 months all clinical and radiographic scores were p < 0.05 for the PS group. During follow-up 4 patients (2 in each group) died of causes not related to surgery. Conclusions. The use of the metal plate as opposed to cortical allogenic splint should be taken into consideration as a noteworthy point for periprosthetic femoral fractures.

Diagnostic accuracy of ultrasound, conventional radiography and synovial fluid analysis in the diagnosis of calcium pyrophosphate dihydrate crystal deposition disease.

OBJECTIVES: To assess the diagnostic performance of ultrasound (US), x-rays, and microscopic analysis of synovial fluid (SF) for calcium pyrophosphate dihydrate crystal deposition disease (CPPD) using histology as a reference standard. METHODS: We enrolled consecutive patients with osteoarthritis waiting to undergo knee replacement surgery. Each patient underwent US of the knee, focusing on menisci and the hyaline cartilage, the day before surgery. During surgery, SF, menisci and condyles were retrieved and examined microscopically. For the meniscus and cartilage microscopic analysis, 8 samples were collected from each specimen and knee radiographs, performed up to 3 months before surgery, were also assessed. A dichotomous score was given for the presence/absence of CPP for each method. Microscopic findings of the specimens were considered the reference standard. All the procedures followed were in accordance with the ethical standards of the local responsible committee. RESULTS: 42 patients (14 males) were enrolled. All patients underwent US, 34 had eligible radiographs and 32 had SF analysis. 25 patients (59.5%) were positive for CPP at US, 15 (44.1%) at X-ray and 14 (43.7%) at SF. Sensitivity and specificity values were 96% and 87% for US, 75% and 93% for radiography and 77% and 100% for SF respectively. There were no statistically significant differences between the diagnostic performance across single tests. CONCLUSIONS: US proved to be at least as accurate as SF analysis for the diagnosis of CPPD. US, which is feasible and harmless, could be considered the first exam of choice for CPPD diagnosis.

Serum C-reactive protein and procalcitonin kinetics in patients undergoing elective total hip arthroplasty.

BACKGROUND: The sensitivity and the specificity of different methods to detect periprosthetic infection have been questioned. The current study aimed to investigate the kinetics of C-reactive protein (CRP) and procalcitonin (PCT) in patients undergoing uncomplicated elective total hip arthroplasty (THA), to provide a better interpretation of their levels in noninfectious inflammatory reaction. METHODS: A total of 51 patients were included. Serum CRP and PCT concentrations were obtained before surgery, on the 1st, 3rd, and 7th postoperative days and after discharge on the 14th and 30th days and at 2 years. RESULTS: Both markers were confirmed to increase after surgery. The serum CRP showed a marked increase on the 3rd postoperative day while the peak of serum PCT was earlier, even if much lower, on the first day. Then, they declined slowly approaching the baseline values by the second postoperative week. PCT mean values never exceed concentrations typically related to bacterial infections. CONCLUSIONS: CRP is very sensitive to inflammation. It could be the routine screening test in the follow-up of THA orthopaedic patients, but it should be complemented by PCT when there is the clinical suspicion of periprosthetic infection.

Proteomics of human primary osteoarthritic chondrocytes exposed to extremely low-frequency electromagnetic fields (ELF EMFs) and to therapeutic application of musically modulated electromagnetic fields (TAMMEF).

Osteoarthritis (OA) is the most frequent joint disease, characterized by degradation of extracellular matrix and alterations in chondrocyte metabolism. Some authors reported that electromagnetic fields (EMFs) can positively interfere with patients affected by OA, even though the nature of the interaction is still debated. Human primary osteoarthritic chondrocytes isolated from the femoral heads of OA-patients undergoing to total hip replacement, were cultured in vitro and exposed 30 min/day for two weeks to extremely-low-frequency electromagnetic field (ELF) with fixed frequency (100 Hz) and to therapeutic application of musically modulated electromagnetic fields (TAMMEF) with variable frequencies, intensities and waveforms. Sham-exposed (S.E.) cells served as control group. Cell viability was measured at days 2, 7 and 14. After two weeks, cell lysates were processed using a proteomic approach. Chondrocyte exposed to ELF and TAMMEF system demonstrated different viability compared to untreated chondrocytes (S.E.). Proteome analysis of 2D-Electrophoresis and protein identification by mass spectrometry showed different expression of proteins derived from nucleus, cytoplasm and organelles. Function analysis of the identified proteins showed changes in related-proteins metabolism (glyceraldeyde-3-phosphate-dehydrogenase), stress response (Mn-superoxide-dismutase, heat-shock proteins), cytoskeletal regulation (actin), proteinase inhibition (cystatin-B) and inflammation regulatory functions (S100-A10, S100-A11) among the experimental groups (ELF, TAMMEF and S.E.). In conclusion, EMFs do not cause damage to chondrocytes, besides stimulate safely OA-chondrocytes and are responsible of different protein expression among the three groups. Furthermore, protein analysis of OA-chondrocytes treated with ELF and the new TAMMEF systems could be useful to clarify the pathogenetic mechanisms of OA by identifying biomarkers of the disease.

Painful hip arthroplasty: definition.

Total hip arthroplasty (THA) has been indicated as the surgical intervention with greatest improvement in pain and physical function. However some patients continue to experience hip pain after elective surgery. We investigate prognostic factors that negatively affect treatment effectiveness and the patient outcome. The "hip region" constitutes the groin, buttock, upper lateral thigh, greater trochanteric area, and the iliac crest. Pain originating from various sources and not directly linked to prosthesis may be perceived here and includes the lumbosacral spine, referred pain from abdominal organs and soft tissue sources such as trochanteric bursitis, tendinitis, hip abductor dysfunction, and inguinal hernia. An accurate assessment of the pain cause is extremely difficult to construct and a complete differential diagnosis is fundamental. We assess all the possible causes of hip pain after THA and we divide them depending on the presence or absence of radiographic signs.

Retroperitoneal hematoma due to spontaneous lumbar artery rupture during fondaparinux treatment. Case report and review of the literature.

We present the case of a 78 year-old man who developed a spontaneous rupture of the lumbar artery leading to a retroperitoneal hematoma while receiving fondaparinux therapy after a total hip replacement. A selective angiographic embolization stopped the bleeding. Fondaparinux was discontinuated and the patient presented a complete resolution of his medical status. Spontaneous hematomas has been well described during low molecular weight heparin (LMWH) treatment, expecially in elderly patients, but there are no previous reports of hematomas induced by fondaparinux. We reviewed the literature to identify the possible risk-factors of bleeding. Our review shows that even if many works suggest that fondaparinux is a safe and effective alternative to LMWH in the prevention of venous thromboembolism following major orthopaedic surgery, it should carefully be used in elderly people and patients with renal disfunction.

Recovery of physical function and patient's satisfaction after total hip replacement (THR) surgery supported by a tailored guide-book.

BACKGROUND AND AIM OF THE WORK: The purpose of this prospective study was to give a customized guide, describing the hospitalization period and the postoperative exercise program, to patients scheduled for total hip arthroplasty (THA) and to show its effectiveness on functional recovery and on patient's satisfaction with the rehabilitation care and with the in-hospital discharge planning after surgery. METHODS: This trial included 365 consecutive subjects with osteoarthritis who underwent THA at the Orthopaedic and Traumatology Clinic of Siena (Italy). The Harris Hip Score (HHS), a disease specific measure, was determined before and after surgery. Postoperative evaluations, associated with a Satisfaction Questionnaire, were carried out at the time of discharge and after 3 months. RESULTS: The overall satisfaction level was very high, both at discharge (81+/-28) and at follow-up (90+/-17). The HHS results showed a significant (p< or =0.05) improvement over time in patients with higher scores 3 months after surgery in comparison with baseline. CONCLUSIONS: Patients reported high levels of satisfaction at the 3 month postoperative follow-up and good levels at discharge. After surgery, the highest improvements were shown in bodly pain and physical function scores. The current study showed that a customized guide was well accepted by patients with THA and satisfie their need of information. It was also effective in improving patient's satisfaction and early recovery of physical function after surgery.