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-selectin, 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

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

When to Suspect Hidden Hypercortisolism in Type 2 Diabetes: A Meta-Analysis

Objective: To investigate whether the available literature helps to identify the characteristics of patients with type 2 diabetes (T2D) more frequently associated with hidden hypercortisolism (HidHyCo). Methods: A meta-analysis was performed using studies that assessed both the prevalence of HidHyCo in patients with T2D and the characteristics of these patients with and without HidHyCo. The DerSimonian and Laird (DSL) and Hartung-Knapp-Sidik-Jonkman (HKSJ) methods were utilized. Results: Among the 18 available studies, 6 provided the necessary data. The association between HidHyCo and advanced T2D (based on the patients’ description given in each study in the presence of microvascular/macrovascular complications or insulin treatment plus hypertension or hypertension treated with 2 or more drugs), hypertension, insulin treatment, and dyslipidemia was reported in 5 (2184 patients), 6 (2283 patients), 3 (1440 patients), and 3 (987 patients) studies, respectively. HidHyCo was associated with advanced T2D as assessed by both the DSL (odds ratio [OR], 3.4; 95% confidence interval [95% CI], 2.12-5.67) and HKSJ (OR, 3.60; 95% CI, 2.03-6.41) methods and with the prevalence of hypertension or insulin treatment as assessed by the DSL method (OR, 1.92; 95% CI, 1.05-3.50 and OR, 2.29; 95% CI, 1.07-4.91, respectively) but not as assessed by the HKSJ method. Conclusion: Patients with advanced T2D have a higher prevalence of HidHyCo. These data inform about the selection of patients with T2D for HidHyCo screening

Italian consensus statement (2020) on return to play after lower limb muscle injury in football (soccer)

Return to play (RTP) decisions in football are currently based on expert opinion. No consensus guideline has been published to demonstrate an evidence-based decision-making process in football (soccer). Our aim was to provide a framework for evidence-based decision-making in RTP following lower limb muscle injuries sustained in football. A 1-day consensus meeting was held in Milan, on 31 August 2018, involving 66 national and international experts from various academic backgrounds. A narrative review of the current evidence for RTP decision-making in football was provided to delegates. Assembled experts came to a consensus on the best practice for managing RTP following lower limb muscle injuries via the Delphi process. Consensus was reached on (1) the definitions of return to training' and return to play' in football. We agreed on return to training' and RTP in football, the appropriate use of clinical and imaging assessments, and laboratory and field tests for return to training following lower limb muscle injury, and identified objective criteria for RTP based on global positioning system technology. Level of evidence IV, grade of recommendation D

Italian consensus conference on guidelines for conservative treatment on lower limb muscle injuries in athlete.

Provide the state of the art concerning (1) biology and aetiology, (2) classification, (3) clinical assessment and (4) conservative treatment of lower limb muscle injuries (MI) in athletes. Seventy international experts with different medical backgrounds participated in the consensus conference. They discussed and approved a consensus composed of four sections which are presented in these documents. This paper represents a synthesis of the consensus conference, the following four sections are discussed: (i) The biology and aetiology of MIs. A definition of MI was formulated and some key points concerning physiology and pathogenesis of MIs were discussed. (ii) The MI classification. A classification of MIs was proposed. (iii) The MI clinical assessment, in which were discussed anamnesis, inspection and clinical examination and are provided the relative guidelines. (iv) The MI conservative treatment, in which are provided the guidelines for conservative treatment based on the severity of the lesion. Furthermore, instrumental therapy and pharmacological treatment were discussed. Knowledge of the aetiology and biology of MIs is an essential prerequisite in order to plan and conduct a rehabilitation plan. Another important aspect is the use of a rational MI classification on prognostic values. We propose a classification based on radiological investigations performed by ultrasonography and MRI strongly linked to prognostic factors. Furthermore, the consensus conference results will able to provide fundamental guidelines for diagnostic and rehabilitation practice, also considering instrumental therapy and pharmacological treatment of MI. Expert opinion, level IV

Limitations of the DiaRem Score in Predicting Remission of Diabetes Following Roux-En-Y Gastric Bypass (RYGB) in an ethnically Diverse Population from a Single Institution in the UK

Purpose This study aimed to determine the predictive power of the DiaRem score following Roux-en-Y gastric bypass to identify patients who would have diabetes remission at 1 year in an ethnically diverse population. Methods We performed a retrospective review of 262 patients with type 2 diabetes mellitus who underwent RYGB at the Imperial Weight Centre, UK, from 2007 to 2014. Data was collected on the parameters required to calculate the DiaRem score as well as pre- and post-surgical weight and the ethnicity of the subjects. Results The studied cohort was ethnically diverse (61.3 % Caucasian, 10.3 % Asian, 5.3 % black, 2.6 % mixed and 20.6 % other). At 1-year post-surgery, there were significant reductions in mean weight (133.4 to 94.3 kg) and BMI (46.7 to 33.3 kg/m2). The mean HbA1c decreased from 8.2 to 6.1 %, and 32.5 % of the cohort underwent either partial or complete remission. 67.8 % of the patients that were classified in group 1 of the DiaRem score (most likely to have remission) had complete remission. However, 22.9 % of the patients predicted to have the least chance of remission had either partial or complete remission. Conclusions In this ethnically diverse cohort, the DiaRem score remains a useful tool to predict diabetes remission in those that have a low DiaRem score (high chance for remission) but was more limited in its predictive power in those with a high DiaRem score (least likely to have remission). Caution must be used in the application of this model in populations other than the US white Caucasian population used to derive the score