Safety and tolerability of intra-articular hyaluronic acid (Sinovial®/GELSYN-3tm) injections in the treatment of knee osteoarthritis.

Osteoarthritis (OA) is a progressively degenerative joint disease, with a very high prevalence rate that is expected to increase worldwide with the ageing of the population. Considering that OA requires long-term treatment, therapies with minimal side effects and which can be repeated as needed are warranted. Hyaluronic acid (HA), a natural glycosaminoglycan with viscoelastic properties, is a major component of synovial fluid and the extracellular matrix of the joint cartilage, and plays key roles in maintaining synovial fluid viscosity and the bio-mechanical integrity of healthy cartilage. Intra-articular administration of exogenous HA has therefore been used to successfully improve the viscoelastic properties of the joint to improve lubrication, modulate inflammation and modify the catabolic micro-environment. Sinovial®/GELSYN-3TM is a sterile, non-pyrogenic formulation of highly purified, chemically unmodified HA of bio-fermentative origin, which has been introduced in several different concentrations in clinical use within the European market. This expert opinion reports on the published data regarding the efficacy and tolerability of first and multiple injection series of Sinovial®-based product formulations. The data regarding the tolerability of Sinovial® in patients with knee osteoarthritis were analyzed, showing that this formulation, beside favourable therapeutic effects, has a very good tolerability profile, with only mild, transient, and easily managed, local injection-site reactions and absence of systemic reactions. In particular, repetitive cycles of HA have been shown to yield positive results in terms of both efficacy and safety and therefore should be offered to patients who had undergone a successful first course of therapy when their symptoms reoccur.

The effect of hydroxyapatite coated screw in the lateral fragility fractures of the femur. A prospective randomized clinical study.

Due to a growing numbers of lateral fragility fractures of the femur and their high social costs the need to work out an effective strategy in order to find a better solution for these patients is warranted. From January 2010 to July 2011, we carried out a prospective randomized clinical study comparing the results of patients with femoral lateral fractures treated by nail and cephalic hydroxyapatite coated screws (study group including 27 patients) compared to the patients with the same fractures treated with nail and head standard screws (control group including 27 patients). We defined the two parts of the femoral neck as ROI 1 (under the head screw) and ROI 2 (above the femoral screw) on the AP view. The bone density of the two areas was calculated using DEXA at T0 (1st day post-surgery), at T1 (40th day post-surgery), at T2 (3 months later), at T3 (1 year later). The clinical-radiography evaluations were based on the Harris Hip Score (HHS), ADL test and x-ray views of the hip. As far as the bone mineral density average of ROI 1 and ROI 2 is concerned, we found a significant statistical increase at T1 and T3 in the study group, while it was not significant in the control group. We could account for this data through the higher mechanical stability of hydroxyapatite coated screws than standard screws. In fact, this material was responsible for improved implant osteointegration. Thanks to a 1 year follow-up we were able to demonstrate the implant utility associated with augmentation and the importance of densitometry exams such as easily repeatable and low cost diagnostics to prevent the onset of complications linked to screw loosening.

Transtibial versus anteromedial transportal femoral tunnel in single-bundle anterior cruciate ligament reconstruction: a systematic review and meta-analysis of prospective randomized controlled trials.

The purpose of this study was to systematically review and meta-analyze randomized controlled trials (RCTs) reporting the comparative clinical and functional outcomes, postoperative complications, and radiological outcomes of single-bundle anterior cruciate ligament reconstruction (ACLR) performed using the transtibial (TT) approach or anteromedial (AM) technique. A systematic review of the literature was performed according to Cochrane and PRISMA guidelines. RCTs comparing TT and AM techniques were considered only. The quality of the studies was defined using the GRADE system, and the risk of bias was assessed with the RoB 2 tool. The primary endpoint was to systematically review and meta-analyze the clinical outcomes, residual laxity and failure rate of both AM and TT techniques. In the current meta-analysis 13 RCTs involving 989 patients who underwent arthroscopic single-bundle ACLR (486 TT and 503 AM) were included. Patients undergoing AM technique resulted in higher objective-IKDC (p < 0.001) and Lysholm scores (p = 0.002), despite a lower incidence of pathological anterior tibial translation (p < 0.001) and positive pivot-shift test (p < 0.001). No differences were detected in IKDC subjective score (p = 0.26), Tegner activity scale (p = 0.18) and graft failure (p = 0.07). ACL reconstruction through AM portal technique provides better clinical outcomes and lower incidence of residual rotational and anteroposterior laxity in comparison with the TT technique. No statistically significant difference in subjective outcomes and graft failure was reported.

First case report of vanadium metallosis after ceramic-on-ceramic total hip arthroplasty.

The development of metallosis as a complication following rupture of a hip replacement is known to occur as a result of contact with metal components of the prosthesis (1).In such cases, high cobalt (Co), chromium (Cr) and molybdenum (Mo) levels in the blood have been reported by several Authors (2).Recently, it has been stressed that the clinical investigation should focus on general reactions to high circulating metal levels, such as toxicity for the central nervous system (CNS) and the immune system (3).Despite the increasing interest of literature in ceramic-on-ceramic hip arthroplasty (4),little is known about these complications, and in particular of metallosis. To our knowledge this is the first description of a condition of extensive metallosis and radiographic signs presenting as a result of wear of a ceramic-on-ceramic prosthesis.

A modified Frosch approach for posterior tibial plateau fractures: Technical note and case series.

Achieving the best possible articular congruity following a tibial plateau (TP) fracture is associated with better long-term functional outcomes; TP has an essential role in the movements of the knee joint and is well established that a not optimal reduction leads to articular instability and early osteoarthritis. In recent times, 3D reconstruction from CT scan has greatly contributed to improve the surgical treatment of these fractures since an accurate preoperative plan gives the possibility to decide the best interventional strategy before the surgical incision. Reduction of the posterior part of tibial plateau is not easily achievable with standard surgical access. Several posterolateral approaches, proposed by authors such as Frosch and Lobenhoffer, have been described over the years; these approaches can be divided into 2 groups: with or without osteotomy of the fibula. Main disadvantages of these techniques are the large skin incision, the difficulty of exposing the lateral part of the tibia, the high frequency of damages of the posterolateral TP corner, and in some cases the necessity of performing fibular head osteotomy. The surgical approach presented in this paper is a simple innovation of the well-known Frosch approach: skin incision is about 12 centimeters in length and runs in a "S" shape with the center positioned over the head of the fibula. It starts 2 centimeters laterally to the tibial crest 6 centimeters below the tibial tuberosity and is directed proximally, curving posteriorly at the level of fibular head and returning straight in the most proximal part; it terminates 4 centimeters posteriorly the lateral femoral condyle. This innovative approach allows the trauma surgeon to achieve an optimal exposure and control of posterior tibial plateau fractures, with the great advantage of being able to treat the lateral tibial plateau with the same surgical incision.

Platelet rich plasma in tendinopathies: how to explain the failure.

Tendinopathies are very common in athletes and in people practicing sport activities. The experimental evidence that growth factors (GFs), present in platelets, enhance the recruitment, proliferation and differentiation of cells involved in tissue regeneration, has prompted the use of platelet rich plasma (PRP) preparations in the treatment of these diseases. However, at present, a sound demonstration of the clinical efficacy of PRP is still lacking. Several theoretical and practical reasons can explain the failure of the treatment: a) animal experiments have been carried out on normal tendons submitted to surgical lesions, and it is questionable whether these models may best mimic human pathology; b) the pathway of chronic tendinopathies is very complex, involving, besides GFs, many other pathogenetic factors, which operate at different stages of the disease; c) several methods have been used to produce PRP, which can result in a large variation in GF content, and in kinetics of release. Therefore, further research is desirable. As a preliminary step, it is necessary to standardize PRP preparation, and to establish the modalities of its activation and administration. Secondly, prospective, randomized, double-blind studies are needed, selecting subjects with homogenous forms of tendinopathies: load-bearing and non-load-bearing tendons, midportion and insertional tendinopathies, with or without neovascularization. Finally, new strategies in PRP use should be exploited: among them, the association of PRP with autologous stem cells or the administration of selective GFs (fibroblast growth factor, vascular endothelial growth factor, or anti-angiogenic factors), which could be better options in specific situations.

Endothelial cells, cholesterol, cytokines, and aging.

It has been reported that high levels of cholesterol and triglycerides are associated with increased risk of developing atherosclerosis and shorter life. In fact, vascular endothelial dysfunction occurs during the human aging process. Accumulation of lipids in vascular endothelium activates leukocytes to produce cytokines and chemokines which recruit macrophages. On the other hand, macrophages augment inflammatory response and secrete vascular endothelial growth factor, a key cytokine that mediates angiogenesis and inflammatory response. In addition, hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Here, we review the interrelationship between endothelial cells, high level of cholesterol, and aging.

Nutrition and cancer prevention.

Cancer cells invade surrounding tissues and metastasize to distant sites. Diet high in fat is a strong link to, and perhaps causes, a high incidence of tumours. Trans-fatty acid might impair the function and it could be involved in the development of cancer. Cholesterol is also strongly suspected to be involved in the development of tumours, therefore it is important for everyone to eat well, especially for people with cancer to prevent the body tissues from breaking down and helping to rebuild the normal tissue that may have been affected by the treatments. Factors secreted by adipocytes and macrophages such as TNF-alpha and other inflammatory proteins are involved in inflammation in cancer. In addition, MCSF which up-regulates adipocyte tissue is also important for the stimulation of fat cell proliferation and is expressed by human adipocytes. Many cytokines, such as IL-1, IL-6, IL-8, IL-32, IL-33 and MCP-1, are biomarkers for cancer and chronic diseases along with transcription factors NFκB and AP-1; these last two factors are important bioactive substances on the molecular mechanism of the control of genes which in turn affect cellular metabolism. In this paper we revisit the interrelationship between cancer and metabolism.

IL-36 a new member of the IL-1 family cytokines.

Interleukin-36 (IL-36) is a pro-inflammatory cytokine which plays an important role in innate and adaptive immunity. IL-36 activates MAPK and NF-kB pathways and is produced by many different cells. This cytokine is a family member of interleukin-1 (IL-1) and plays an important role in the pathophysiology of several diseases. Here we summarise and review the new aspects of this important pro-inflammatory cytokine.

Role of mast cells in innate and adaptive immunity.

Mast cells play a central role in inflammatory and immediate allergic reactions and are necessary for allergic reactions. Mast cells play a role in the pathophysiology of autoimmune diseases and appear to be especially important in inflamed tissues, because they infiltrate tissues and produce a variety of cytokines. Mast cells are important for both innate and adaptive immunity in tissues that are in close contact with the environment, i.e. the skin, the airways and the lung, and the lining of the intestine. However, there are still many unsolved issues of mast cell functions, including their regulatory mechanism on cell differentiation in bone marrow; for example, the cytokines and transcription factors necessary for their differentiation and expansion, as well as the molecular mechanism underlying basophil migration from the bloodstream to peripheral tissues such as lymph nodes still need to be clarified.

Interleukin-9 and mast cells.

Mast cells are granulated hematopoietic cells derived from stem cells that reside in nearly all tissues and are involved in protection of a host from bacterial infection with a protective and pathogenic activity. Mast cells are important for both innate and adaptive immunity in tissues which are in close contact with the environment. These cells express proinflammatory cytokines such as IL-1, IL-6, IL-8 and tumor necrosis factor which are necessary for innate immunity. Mast cells also produce interleukin-9 and enhance mast cell expression of several cytokines including IL-1beta, IL-5, IL-6, IL-9 and IL-13. In addition, IL-9 can induce mast cell production of TGF-beta which can have proinflammatory downstream effects. IL-9 can function as either a positive or a negative regulator of immune responses and can have a detrimental role in allergy and autoimmunity. Furthermore, IL-9 contributes to disease by promoting mast cell expansion and production of IL-13 which in turn contributes to airway hyperresponsiveness. Here, in this editorial we review the interrelationship between IL-9 and mast cells.

Management of prosthetic joint infections: a guidelines comparison.

BACKGROUND: In the last decade, the number of prosthetic joint replacements has been rising each year and this growing trend is related to the increased number of prosthetic joint infections (PJI). As PJI represent a devastating condition for the patient, physicians must identify the best treatment option for each case. Guidelines are not always clear regarding the most appropriate therapy pathway as they differ in many parameters. MATERIALS AND METHODS: Aim of this article is to compare the different indications as reported by four major Academic Societies: the Infectious Disease Society of America, the American Academy of Orthopaedic Surgeons, and the Musculoskeletal Infection Society (MSIS) which published the guideline in partnership with the European Bone And Joint Infection Society. CONCLUSIONS: PJI Guidelines differ in many parameters, therefore the choice of treatment for each case does not appear immediate; it would be desirable that, in the next few years, new scientific evidence will help clarify the indications of the most effective therapeutic protocols for PJI to determine the ultimate surgical strategy for every single patient.

Percutaneous steroidal treatment in relapses of chronic tendinopathies: a pilot study.

Relapses are frequently observed in subjects with chronic tendinopathies. Corticosteroid injections are usually performed with positive results, but are uncomfortable for the patient and not free from side effects. The aim of this pilot study is to evaluate the short-term efficacy and tolerability of an occlusive Betamethasone Valerate medicated Plaster (BMVP). Fifteen subjects with relapses of chronic tendinopathies (clinical and ultrasound diagnosis) were enrolled, and treated according to RICE (Rest - Ice - Compression - Elevation) protocol. An BMVP plaster was also applied on the affected tendon. Clinical examination, at baseline and after 7, 14, 21 and 28 days, included pain (VAS at rest and during activities) and functional evaluation. Local side effects on the area and drop-outs were also recorded. Pain, both at rest and during activities, significantly decreased at 28 days (from 3.7 ± 2.7 to 1.1 ± 1.7 p < 0.01, and from 7.3 ± 1.7 to 3.3 ± 1.4 p < 0.0000, respectively). Moreover, the patients reported a significant improvement in the functional limitation. Five subjects dropped out of the study. No side effects were reported. The release of the steroid in pharmacologically-active concentrations over 12 - 24 hours and the good penetration of the drug in subcutaneous tissues explain the positive results. BMVP application may be considered a reliable first therapeutic approach in relapses of chronic tendinopathies.

Diagnostic failure of ciprofloxacin-induced spontaneous bilateral Achilles tendon rupture: case-report and medical-legal considerations.

Rare side-effects of fluoroquinolone therapy are tendinitis and tendon rupture. Many reports have demonstrated that the concomitant use of corticosteroids, in patients aged 60 years or older, increase the risk substantially. We present a case of spontaneous bilateral Achilles tendon rupture induced by ciprofloxacin and methylprednisolone. A 61-year-old woman was diagnosed with Bronchiolitis Obliterans with Organizing Pneumonia (BOOP) and was started on oral ciprofloxacin 500 mg twice daily for 3 weeks and on oral methylprednisolone 16 mg twice daily for 2 weeks. The diagnosis was made after doctors, rather than stop drug therapy and advise complete rest, had mistakenly prescribed for the woman to undergo physiotherapy and local NSAIDs, thus favoring the onset of tendon ruptures and resulting in surgical and legal implications. Inspired by this case, we also submit a brief review on professional liability in Orthopaedics.

Bone grafts and bone graft substitutes in prosthetic hip surgery replacement.

The need for bone grafting procedures to replace skeletal defects has become more considerable because of increased opportunities to save major bone loss. We report our experience and a critical analysis about the role of bone grafts and bone graft substitutes in prosthetic hip surgery replacement.

Cholesterol, cytokines and diseases.

A high level of cholesterol is associated with obesity, cardiovascular diseases and atherosclerosis. Immune response in atherosclerosis is mediated by chemokines which attract monocytes, leading to the innate immune response characterised by the production of cytokines. The immunoregulatory cytokines are an important bridge between innate and adductive immunity. TH1 cytokines are involved as effector T cells in inflammatory response, while TH2 cytokines can be anti-inflammatory such as IL-10 and IL-4. It is well known that statins enhance the production of TH2 cytokines whereas the secretion of TH1 cytokines is suppressed. For this purpose, we studied the significance of anti-inflammatory effect and suppression of inflammation by statins. In this paper we revisited the role of cholesterol and cytokines IL-18, IL-10, IL-12, TNF-α, interferon-γ, and chemokines in inflammatory diseases.

Atherosclerosis: a classic inflammatory disease.

Atherosclerosis is an inflammatory disease due to a diet high in saturated fat, hypercholesterolemia, obesity, hypoglycemia, etc. mainly mediated by the infiltration of macrophage and T cells into the vascular wall. Once the endothelial is damaged monocytes penetrate the tissue and are transformed in scavenger cells. Upon stimulation of Th1 cells, a group of cytokines is released and contributes to the inflammatory response of atherosclerotic tissue. When macrophages proliferate they amplify inflammatory response through the secretion of growth factors and cytokines such as TNF and IL-1. In addition, chemokines such as RANTES and other C-C chemokines are generated, and matrix metalloprotinease 9 (MMP-9) are produced by activated monocytes. However, the immune system in atherosclerosis still remains unclear. Here, in this study we revisited the inter-relationship between atherosclerosis and inflammation.

Psychological stress and vitamins.

Conditions of stress and anxiety have complex interactions with insufficient vitamin intake and malnutrition. This study, based on literature research in Medline, analyzes the inter-relationship between vitamins and stress. This report concerns a number of vitamins that have been receiving much attention in earlier reviews of the literature, for their potential to protect against stress-related events, and focus is placed upon recent findings.

Cholesterol and vitamins: revisited study.

The link between low density lipoprotein and coronary heart disease has been widely studied. Oxidized LDL damages the artery wall, and a diet rich in vitamins and low in saturated fat and cholesterol may reduce this risk. Not only hypercholesterolemia but also low levels of high density lipoprotein cholesterol are critical risk factors for atherosclerosis and related diseases. It has been reported that high doses of B complex vitamin may be useful in lowering blood cholesterol and triglyceride levels in the body, however the use of this compound has been limited by an annoying flush and concern for toxicity. Niacin is a B-complex vitamin with anti-atherosclerotic properties and is an effective medication for raising high density lipoprotein. The combination of niacin with other lipid-lowering drugs, such as statins, reduces the dynamic of atherosclerosis disease. In addition, vitamin E is one of the most important lipid soluble anti-oxidants in humans, and reduces atherosclerosis plaque, coronary artery diseases and myocardial infarction. Vitamin E protects the integrity of membranes by inhibiting lipid peroxidation. In this study we revisited the interrelationship between cholesterol, low density lipoproteins and vitamins.

Impact of IL-18 on inflammation.

IL-18 is produced by many cell types, such as Kupffer cells, keratinocytes, macrophages, dendritic cells, and activated T cells stimulated by LPS. It is an important regulator of both innate and acquired immune responses. IL-18 plays a central role in rheumatoid arthritis since the T cells and macrophages that invade the synovial. These finding support a role for IL-18 in inflammation, allergy and immune diseases.