Can platelet-rich plasma be an alternative to surgery for resistant chronic patellar tendinopathy in sportive people? Poor clinical results at 1-year follow-up.

INTRODUCTION AND PURPOSE: Patellar tendinopathy is a disease affecting particularly athletes. Platelet-rich plasma (PRP) injections have gained increasing interest for their potential benefits. Anyway, a tendon disease longer than 6 months should be considered as an indication for surgery. The aim of our study was to evaluate the efficacy of PRP in athletes with a severe chronic patellar tendinopathy longer than 6 months when surgery should be chosen. METHODS: We enrolled 17 sport practitioners (19 patellar tendons) who did not want to undergo surgery and who are nonresponders to other conservative treatments. We treated them with PRP and calculated the results using the visual analog scale (VAS), the Victorian Institute of Sport Assessment-Patellar (VISA-P) score, and Tegner Activity Scale. Every test has been conducted at T0, T1 (4 months), and T2 (12 months). RESULTS: We found a poor improvement at T1 and a clinical worsening at T2 through VAS. VISA-P showed a medium improvement both at T1 and T2. Tegner scale did not show improvements. CONCLUSIONS: Our study was not able to remove the doubts about the benefits of PRP in patellar tendinopathy, confirming ambiguous certainties. Further investigations are needed to assess its effectiveness.

Erratum to: Relationship between Clinical, MRI, and Arthroscopic Findings: A Guide to Correct Diagnosis of Meniscal Tears.

[This corrects the article DOI: 10.1055/s-0037-1605583.].

Relationship between Clinical, MRI, and Arthroscopic Findings: A Guide to Correct Diagnosis of Meniscal Tears.

Purpose The aim of this prospective study was to compare and correlate clinical, MRI, and arthroscopic findings in cases of suspected meniscal tears. Using arthroscopic findings as the gold standard, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of clinical investigation and MRI were evaluated to determine if is possible, after a careful examination, to bypass MRI and perform directly arthroscopy in suspected cases. Methods A total of 80 patients with a history of knee trauma, preoperative RX, and MRI underwent arthroscopy over an 8-month period at our department. All patients had a clinical examination performed by an experienced knee surgeon. These examiners evaluated and recorded the results of three tests: medial and lateral joint line tenderness test, McMurray's test, and Apley's test. The injury was classified as a meniscal tear if there were at least two positive tests. Finally, using the arthroscopic findings as the gold standard, sensibility, specificity, accuracy, positive and negative predictive values of clinical examination, and MRI were evaluated and compared. Results Clinical examination performed by an experienced knee surgeon reported better sensitivity (91 vs. 85%), specificity (87 vs. 75%), accuracy (90 vs. 82%), positive predictive value (94 vs. 88%), and negative predictive value (81 vs. 71%) than MRI for medial meniscal tears. These parameters showed minimal differences for lateral meniscal tears. Conclusion Clinical examination performed by an experienced knee surgeon provided equal or better results to diagnose meniscal injuries in comparison to MRI. MRI is not necessary to confirm these lesions and should not be used as the primary diagnostic tool. Level of Evidence Level II, prospective study.

A Fatal Sepsis Caused by Hyaluronate Knee Injection: How Much the Medical History and the Informed Consent Might Be Important?

The incidence of Osteoarthritis (OA) is gradually increasing worldwide due to two main reasons: longer life expectation and increased functional demand. Several treatment options have been proposed for this disease. Conservative treatment has the goal to improve the quality of life, reduce pain, and prevent the progression of the disease. Hyaluronate viscosupplementation is one of the most used infiltrative treatments for OA, but, despite its common use, clinical efficacy is still under question. Though adverse reactions for this medical option are actually rare, septic arthritis is a very scaring complication. We present a case report of a 59-year-old man who has been submitted to only one knee hyaluronate injection and consequently reported a severe septic arthritis and systemic sepsis, which lead to the death of the patient. We recommend producing correct guidelines for a clean aseptic procedure of injection to obtain proper consensus from the patient and to pay attention to his clinical history and comorbidities before acting any kind of invasive treatment, including joint injection.

Serologic and radiographic outcome of total hip arthroplasty with CoCr modular neck at mid-term follow-up.

PURPOSE: The aim of this study is a radiographic evaluation and to determine serologic values of chromium and cobalt in the blood and urine of patients who have been implanted with a Stryker® ABG II Modular Neck and see if there is correlation with the features of prosthesis and patients. METHODS: The study involves the collection of data from patients operated on for total hip model with the ABG II Modular Neck with a minimum follow-up of 1 year. RESULTS: We evaluated 22 patients who underwent implantation of a hip prosthesis with modular neck in CoCr. Of these, the average Cr in the blood was 0.63 µgL-1 (range 0.1-2.15 µgL-1), the average of Co in the blood was 3.50 µgL-1 (range 0.62-7.78 µgL-1), the average Cr in the urine was 1.24 µgL-1 (range 0.48-2.21 µgL-1), and the average Co in urine was 14.22 µgL-1 (range 3.3-31.2 µgL-1). None of these patients had undergone revision surgery. CONCLUSIONS: Our study seems to indicate that the restoration of offset and age are correlated with the release of metal ions, although the correlation is weak and needs better methodological studies and a greater number of patients to confirm this hypothesis. STUDY TYPE: Case series Level of Evidence 4.

ENOX2 (or tNOX): a new and old molecule with cancer activity involved in tumor prevention and therapy.

Cancer includes a number of related diseases due to abnormal cell proliferation that spreads to nearby tissues. Many compounds (physical, chemical and biological) have been used to try to halt this abnormal proliferation, but the therapeutic results are poor, due also to the side effects. It has been reported that ecto-nicotinamide adenine dinucleotide oxidase di-sulfide-thiol exchanger 2 (ENOX2), also known as tumor-associated nicotinamide adenine dinucleotide oxidase (tNOX), was found to be located on the cancer cell surface, essential for cancer cell growth. Capsaicin and other anti-oxidants are capable of inhibiting tNOX, causing apoptosis of cells, exerting anti-tumor activity. It is interesting that some authors reported that ENOX2 is present in the serum of cancer patients several years before the clinical symptoms of the tumor. However, this result has to be confirmed. In this article we discuss ENOX2 and its inhibition as a hope of improving cancer therapy.

Endocrinology of the skin: intradermal neuroimmune network, a new frontier.

Endocrinology systems exert an important effect on vascular function and have direct actions on blood vessels. Estrogens provoke an increase in skin elasticity, epidermal hydration, skin thickness, reduce skin wrinkles and augment the content of collagen and the level of vascularisation. Therefore, there is an intricate cross-talk between skin conditions and stress. In stress, ß2--adrenoreceptor (ß2AR) pathway, cortisol, epinephrine and norepinephrine increase DNA damage and interfere with the regulation of the cell cycle, contributing to aging and skin diseases. Substance P is a neuropeptide released in the skin from the peripheral nerve and is related to stress and inflammation. SP provokes infiltration of inflammatory cells in the skin and induces a variety of cytokines/chemokines. Corticotropin-releasing hormone (CRH), produced by mast cells, is a neuropeptide also expressed in skin and responds to stress. CRH initiates diverse intracellular signaling pathways, including cAMP, protein kinase C, and mitogen-activated protein kinases (MAPK). Under stress, CRH, glucocorticoids, epinephrine and cytokines are generated. Moreover, the release of ACTH binds the receptor MC2-R and stimulates the generation of glucocorticoids such as corticosterone and cortisol, which interact with the transcription factors AP-1 and NF-kB. In skin keratinocytes, ACTH promotes the generation of pro-inflammatory cytokines, which enhances T-cell activity. Cortisol is immunosuppressive by inhibiting Th1 and Th2 cell response, antigen presentation, antibody and cytokine/chemokine production. However, glucocorticoids are certainly helpful in Th1-mediated autoimmune disorders. On the other hand, cytokines, such as TNF, IL-1 and IL-6, stimulate the generation of CRH and activate HPA axis in inflammatory states. Here, we describe for the first time a cross-talk between endocrinology and skin, including pro-inflammatory cytokines and neurogenic inflammatory pathways.

Is vitamin E an anti-allergic compound?

Vitamin E is found in eight forms in nature which include four tocopherols (alpha, beta, gamma and delta) and four tocotrianols (alpha, beta, gamma and delta). The classic effect of vitamin E is to reduce and prevent oxygen damage to the tissue and is useful for the treatment of pain, inflammation and allergic reactions. In addition to antioxidant activity, vitamin E also has a number of different and related functions. It protects against cancer, improves immune response, lowers the incidence of infectious diseases, cardiovascular diseases and is protective in allergy and asthma risk, and other disorders. Vitamin E increases n-6 polyunsaturated fatty acid (PUFA) and decreases n-3 PUFA, an effect that diminishes asthma and allergic diseases. Moreover, vitamin E regulates vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration through its oxidant and non-antioxidant effect. Furthermore, vitamin E modulates the endothelial function by altering VCAM-1-induced oxidative activation of endothelial cell PKCα. However, vitamin E is not consistently associated with asthma and/or allergy, and in some cases there are conflicting results on allergy and inflammatory diseases. The association of vitamin E and allergy appears to be very complex, and further study needs to clarify this dilemma.

IMMUNOMODULATORY EFFECTS OF VITAMIN D ON SKIN INFLAMMATION.

Vitamin D has a major role in calcium absorption and maintenance of healthy bones. Vitamin D is also involved in cancer, cardiovascular system, allergic diseases, immune regulation and immune disor¬ders. Irradiation of food as well as animals produces vitamin D and more than 90% of previtamin D3 synthesis in the skin occurs in the epidermis. Vitamin D receptor has been found in many cells including T and B lymphocytes, macrophages, mast cells, NK cells and Tregs, and it selectively binds with high affinity to its ligand. Vitamin D binds its receptor VDR, resulting in transcription of a number of genes playing a role in inhibition of MAPK. Its effect may be also mediated by the direct activation of PKC. Vitamin D has the ability to suppress inflammatory cytokines such as TNF, IL-1, IFN-gamma and IL-2; while it increases the generation of anti-inflammatory cytokines IL-4 and IL-10. In B cells, vitamin D3 have also been shown to suppress IgE antibody class switch partly through the inhibition of NF-kB. Here we discuss the relationship between vitamin D, immunity and skin disorders.

CROSSTALK BETWEEN VITAMIN B AND IMMUNITY.

Vitamin B1 (thiamin) is considered to be the oldest vitamin and in 1936 R.R. Williams and colleagues determined its chemical structure and were able to synthesize this vitamin. Vitamin B1 influences pro-apoptotic proteins, mitochondrial membrane potential, cytochrome C release, protein kinases, p38-MAPK, suppresses oxidative stress-induced NF-kappaB and has anti-inflammatory properties. Deficiency of vitamin B1 may cause beriberi, dysfunction of the nervous system, neuroinflammation, T cell infiltration, chemokine CCL2 activation, over expression of proinflammatory cytokines, such as IL-1, TNF, IL-6, and arachidonic acid products, and induces expression of CD40 by the microglia and CD40L by astrocytes which provoke the death of neurons. Here we report the relationship between vitamin B complex and immunity.

Can vitamin a mediate immunity and inflammation?

Vitamins are natural components of foods and are organic compounds distinct from fat, carbohydrates and proteins. Vitamin A is the generic descriptor for compounds with the qualitative biological activity of retinol. Unlike beta-carotene, vitamin A is not an antioxidant and its benefit is related to possible boosting of immune reactions. The effect of vitamin A on immune function is wide-reaching and its deficiency appears to affect immunity in several ways. Innate and adaptive immune responses are affected in some way by lack of vitamin A. Retinoids seem to act on differentiation of lymphocytes, antibody production, phagocytosis of macrophages, NK, Treg, and T helper cell activity. In addition, in humans, signs of a vitamin A deficiency also include the dysregulation of cytokine/chemokine generation and release. However, excess of vitamin A has been demonstrated to have toxic effects in most species studied. Here we summarize some important effects of vitamin A in immunity and inflammation.

Role of TNF in mast cell neuroinflammation and pain.

Inflammatory mediators, such as cytokines, chemokines and arachidonic acid compounds, lead to vascular permeability and dilation and increase sensitization and pain receptors. Proinflammatory cytokines, including tumor necrosis factor, are involved in the etiology of clinical neurological disorders. These cytokines activate nuclear factor-κB (NF-κB) which leads to the activation of different inflammatory genes. TNF implicated in neurological disorders has an important role in the activation of microglia and astrocytes. The inhibition of TNF may lead to the decrease of microglia activation and can be useful for therapeutic intervention. TNF, at the site of nerve injury may activate mast cells (MCs) which mediate pathologic events such as headache and pain. TNF is the only cytokine stored in mast cells and can be rapidly released along with biogenic amines after MC stimulation. Activation of MCs leads to NF-κB and AP1 generation with release of many cytokines including TNF, IL-33 and IL-1. In this paper we discuss the role of TNF in MC activation, mediating pain and neurological disorders.

Anatomy of the Medial Patello-Femoral Ligament: a systematic review of the last 20 years literature.

BACKGROUND: Although many studies have investigated the anatomy of the Medial Patello-Femoral Ligament (MPFL), some studies have even questioned its existence. In the last 20 years, there is a renewed interest on the role of the MPFL in patello-femoral instability. As a result, several studies have been published that describe the anatomy, function and possible surgical reconstruction of the MPFL. Despite the large amount of literature produced, there is still a lack of consensus on what is its real anatomy as there are currently no systematic reviews on this topic. PURPOSES: Thus, the aim of this review is to systematically report the results in literature regarding in anatomical papers, the existence, size, insertion sites and relationships of this ligament with the other medial structures of the knee. METHODS: We have systematically analyzed anatomical studies currently available in literature between 1980 and December 2012. The search was carried out on Medline, Embase, Cochrane Library and Google Scholar. We checked reference lists of articles, reviews and textbooks identified by the search strategy for other possible relevant studies. RESULTS: The outcomes examined are the presence of the ligament, its size (length, width, thickness), and its patellar and femoral insertions. A total of 312 cadaveric knees were included in the 17 studies; the MPFL was identified in 99% of cases (309). CONCLUSIONS: The consensus is that the MPFL is almost always present in the dissected knees. The size and insertions of the ligament demonstrate great variation between cadavers. LEVEL OF EVIDENCE: Systematic review of anatomical study, Level 1.

Relationship between serotonin and mast cells: inhibitory effect of anti-serotonin.

Serotonin (5-HT) is an important neurotransmitter that acts in both central and peripheral nervous system, and has an impact on cell proliferation, migration and apoptosis. 5HT exerts its effects via several receptors. Treatment with anti-5-HT receptors diminish the severity of contact allergy in experimental animals, an effect mediated by mast cells; while an agonist reduces the stress level and relieves pruritus in patients with atopic dermatitis. Mast cells are important for both innate and adaptive immunity and they are activated by cross-linking of FceRI molecules, which are involved in the binding of multivalent antigens to the attached IgE molecules, resulting in a variety of responses including the immediate release of potent inflammatory mediators. Serotonin is present in murine mucosal mast cells and some authors reported that human mast cells may also contain serotonin, especially in subjects with mastocytosis. Here we report the interrelationship between mast cells, serotonin and its receptor inhibitor.

Impact of mast cells on multiple sclerosis: inhibitory effect of natalizumab.

Mast cells (MCs) derive from a distinct precursor in the bone marrow and are predominantly found in tissues at the interface between the host and the external environment where they can secrete mediators without overt degranulation. Mast cells mature under local tissue microenvironmental factors and are necessary for the development of allergic reactions, through crosslinking of their surface receptors for IgE (FcεRI), leading to degranulation and the release of vasoactive, pro-inflammatory and nociceptive mediators that include histamine, pro-inflammatory and anti-inflammatory cytokines and proteolytic enzymes. Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demylination within the central nervous system. MCs are involved in the pathogenesis of MS by generating various vasoactive mediators and cytokines and participate in the destruction of the myelin sheath and the neuronal cells. The process of the development of demyelinating plaques in MS is probably linked with the rupture of the blood-brain barrier by MC products. The effects of natalizumab, which is a very effective drug in reducing the annualized relapse rate and other relapse-based endpoints, are discussed. Here, we report the relationship between MCs and MS.

Corticotropin-releasing hormone, microglia and mental disorders.

Microglia derive from mononuclear myeloid progenitors and are a major glial complement of the central nervous system. When microglia are activated they secrete inflammatory cytokines and toxic mediators which amplify the inflammatory response. In addition, the microglia inflammatory products are implicated in the neuronal destruction usually observed in various neurodegenerative diseases. Microglia cells express corticotropin releasing hormone (CRH) receptors, and activation of microglia by CRH releases bioactive molecules which have a biological effect in the brain and regulate several neurological diseases. CRH plays a pivotal role in stress responses and is a key mediator of the hypothalamic-pituitary-adrenocortical system. CRH is expressed in human mast cells, leading to autocrine effects and participates in inflammatory response together with neuropeptides, and stimulates mast cells. IL-33-activated mast cells release vascular endothelial growth factor in response to CRH and act synergistically to increase vascular permeability. CRH also up-regulates IL-18 expression by increasing intracellular reactive oxygen in microglia cells. Here we report the relationship between CRH, microglia and mental disorders.

Neuropeptide NGF mediates neuro-immune response and inflammation through mast cell activation.

Human mast cells (first described in 1879 by Paul Ehrlich) develop from committed precursors in the bone marrow expressing the differentiation marker CD34+ and distinct from the three other myeloid cells. Mast cells are present in various tissues especially near blood vessels, epithelia and nerves and they are activated by cross-linking of FcεRI, but also by a number of neuropeptides. NGF mediates a number of inflammatory and autoimmune states in conjunction with an increased accumulation of mast cells which appear to be involved in neuroimmune interactions and tissue inflammation. Here we report some relationships between mast cells and nerve growth factor (NGF).

Interrelationship between IL-3 and mast cells.

It is well established that mast cells, which are found in the tissues in the proximity of small blood vessels and post-capillary venules, play a key role in the early phase of IgE-mediated allergic reactions. A greatly expanded understanding of the biology of IL-3 has emerged since the early 1980s. IL-3 is a specific factor that stimulates the growth of hematopoietic stem and progenitor cells of a variety of lineages and can promote the proliferation of certain classes of lymphocytes distinct from those that are dependent on IL-2. IL-3 has been identified among the most important cytokines for regulation of mast cell growth and differentiation, migration and effector function activities of many hematopoietic cells. IL-3 termed multi colony-stimulating-factor (multi-CSF) or mast cell growth factor (MCGF) is a haematopoietic growth factor which stimulates the formation of colonies for erythroid, megakaryocytic, granulocytic and monocytic lineages. It is predominantly produced by activated T cells, natural killer (NK) cells and mast cells and supports the growth-promoting effects of SCF on mast cell precursors. IL-3 causes severe hypersensivity reactions and plays a pivotal role in exacerbating the inflammatory response in vivo. Here we report the interrelationship between IL-3 and mast cells.

Nerve growth factor interactions with mast cells.

Neuropeptides are involved in neurogenic inflammation where there is vasodilation and plasma protein extravasion in response to this stimulus. Nerve growth factor (NGF), identified by Rita Levi Montalcini, is a neurotrophin family compound which is important for survival of nociceptive neurons during their development. Therefore, NGF is an important neuropeptide which mediates the development and functions of the central and peripheral nervous system. It also exerts its proinflammatory action, not only on mast cells but also in B and T cells, neutrophils and eosinophils. Human mast cells can be activated by neuropeptides to release potent mediators of inflammation, and they are found throughout the body, especially near blood vessels, epithelial tissue and nerves. Mast cells generate and release NGF after degranulation and they are involved in iperalgesia, neuroimmune interactions and tissue inflammation. NGF is also a potent degranulation factor for mast cells in vitro and in vivo, promoting differentiation and maturation of these cells and their precursor, acting as a co-factor with interleukin-3. In conclusion, these studies are focused on cross-talk between neuropeptide NGF and inflammatory mast cells.

Role of mast cells in atherosclerosis: a classical inflammatory disease.

Atherosclerosis is an inflammatory disease and hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Variance in plasma LDL cholesterol concentration may be associated with differences in cardiovascular disease risk and high levels of lipids are associated with increased risk of developing atherosclerosis. Macrophages, which generate pro-inflammatory cytokines, mainly interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-alpha), are deeply involved in atherosclerosis, as well as mast cells which generate several cytokines, including IL-6 and IFN-gamma, and chemokines such as eotaxin, MCP-1 and RANTES involved in monocyte recruitment and differentiation in the arterial wall. In addition, mast cells participate in lipid retention and vascular cell remodeling, and are mediators of innate and adaptive immunity during atherosclerosis. Mast cells which accumulate in the human arterial intima and adventitia during atherosclerotic plaque progression, release vasoactive and angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid metabolites, histamine, cytokines/chemokines, platelet activating factor (PAF) and proteolytic enzymes. Mast cells can be activated by pro-inflammatory stimuli, including cytokines, hypercholesterolemia, and hyperglycemia, and trigger the endothelial expression of adhesion molecules such as P-selection, vascular cell adhesion molecule-1 (VCAM-1) and chemokines which mediate the recruitment and adhesion of leukocytes. The participation of mast cells in atherosclerosis is still an enigma and it may be of therapeutic interest to clarify this process.