NVC in non-rheumatic disease

Nailfold video-capillaroscopy (NVC) is a useful diagnostic tool, used to early detect abnormalities in micro-circulation, providing a qualitative description of microvascular anomalies in Raynaud’s phenomenon. NVC role in the diagnosis of Systemic Sclerosis is well known. In other rheumatic conditions such as connective tissue diseases, vasculitis, and arthritis, the NVC anomalies are often included in a scleroderma like pattern. The use of NVC in non-rheumatic diseases (NRD), with remarkable microvascular damage, as diabetes, is not standardized yet, although several research studies are carrying on. The aim of this article is to provide a resume of published results in order to lay the groundwork for the employment of NVC both in the diagnosis and follow up of microvascular complication in NRD. Furthermore, we mention NVC findings in pathologies without well recognize microvascular damages in their pathogenesis : micro-vessels abnormalities may suggest a different point of view

Adipokines and Chronic Rheumatic Diseases: from Inflammation to Bone Involvement

AbstractBesides its well-known role as energy storage tissue, adipose tissue is a biologically active tissue that can also be considered as an endocrine organ, as it is able to secrete adipokines. These bioactive factors, similar in structure to cytokines, are involved in several physiological and pathological conditions, such as glucose homeostasis, angiogenesis, blood pressure regulation, control of food intake, and also inflammation and bone homeostasis via endocrine, paracrine, and autocrine mechanisms. Given their pleiotropic functions, the role of adipokines has been evaluated in chronic rheumatic osteoarticular inflammatory diseases, particularly focusing on their effects on inflammatory and immune response and on bone alterations. Indeed, these diseases are characterized by different bone complications, such as local and systemic bone loss and new bone formation. The aim of this review is to summarize the role of adipokines in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, osteoarthritis, and osteoporosis, especially considering their role in the pathogenesis of bone complications typical of these conditions

Lipid peroxidation and apoptotic response in rat brain areas induced by long-term administration of nandrolone: the mutual crosstalk between ROS and NF-kB

The aim of this study was to evaluate the played by oxidative stress in the apoptotic response in different brain areas of rats chronically treated with supra-physiological doses of nandrolone decanoate (ND). Immunohistochemical study and Western blot analysis were performed to evaluate cells' apoptosis and to measure the effects of expression of specific mediators, such as NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), Bcl-2 (B-cell lymphoma 2), SMAC/DIABLO (second mitochondria-derived activator of caspases/direct IAP-binding protein with low PI) and VMAT2 (vesicular monoamine transporter 2) on apoptosis. The results of the present study indicate that a long-term administration of ND promotes oxidative injury in rat brain specific areas. A link between oxidative stress and NF-κB signalling pathways is supported by our results. In addition to high levels of oxidative stress, we consistently observed a strong immunopositivity to NF-κB. It has been argued that one of the pathways leading to the activation of NF-κB could be under reactive oxygen species (ROS)-mediated control. In fact, growing evidence suggests that although in limited doses, endogenous ROS may play an activating role in NF-κB signalling, while above a certain threshold, they may negatively impact upon this signalling. However, a mutual crosstalk between ROS and NF-κB exists and recent studies have shown that ROS activity is subject to negative feedback regulation by NF-κB, and that this negative regulation of ROS is the means through which NF-κB counters programmed cells

Immunohistochemical evaluation of aquaporin-4 and its correlation with CD68, IBA-1, HIF-1α, GFAP, and CD15 expressions in fatal traumatic brain injury

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Our understanding of its pathobiology has substantially increased. Following TBI, the following occur, edema formation, brain swelling, increased intracranial pressure, changes in cerebral blood flow, hypoxia, neuroinflammation, oxidative stress, excitotoxicity, and apoptosis. Experimental animal models have been developed. However, the difficulty in mimicking human TBI explains why few neuroprotective strategies, drawn up on the basis of experimental studies, have translated into improved therapeutic strategies for TBI patients. In this study, we retrospectively examined brain samples in 145 cases of death after different survival times following TBI, to investigate aquaporin-4 (AQP4) expression and correlation with hypoxia, and neuroinflammation in human TBI. Antibodies anti-glial fibrillary acid protein (GFAP), aquaporin-4 (AQP4), hypoxia induced factor-1α (HIF-1α), macrophage/phagocytic activation (CD68), ionized calcium-binding adapter molecule-1 (IBA-1), and neutrophils (CD15) were used. AQP4 showed a significant, progressive increase between the control group and groups 2 (one-day survival) and 3 (three-day survival). There were further increases in AQP4 immunopositivity in groups 4 (seven-day survival), 5 (14-dayssurvival), and 6 (30-day survival), suggesting an upregulation of AQP4 at 7 to 30 days compared to group 1. GFAP showed its highest expression in non-acute cases at the astrocytic level compared with the acute TBI group. Data emerging from the HIF-1α reaction showed a progressive, significant increase. Immunohistochemistry with IBA-1 revealed activated microglia starting three days after trauma and progressively increasing in the next 15 to 20 days after the initial trauma. CD68 expression demonstrated basal macrophage and phagocytic activation mostly around blood vessels. Starting from one to three days of survival after TBI, an increase in the number of CD68 cells was progressively observed; at 15 and 30 days of survival, CD68 showed the most abundant immunopositivity inside or around the areas of necrosis. These findings need to be developed further to gain insight into the mechanisms through which brain AQP4 is upregulated. This could be of the utmost clinicopathological importance

Phenotyping of chondrocytes from human osteoarthritic cartilage: chondrocyte expression of beta integrins and correlation with anatomic injury

Chondrocyte-ECM (extracellular matrix) interactions are believed to play a pivotal role in the development and metabolic homeostasis of articular cartilage. Cell surface adhesion molecules have been reported to modulate chondrocyte binding to ECM (collagen, fibronectin, laminin) and they also act as transducers of critical signals in many biological processes such as growth, differentiation, migration and matrix synthesis. Recently, it has been shown that normal human articular chondrocytes strongly express beta1 integrins, which are constituted by a common chain (beta1) and a variable alphachain, but the behaviour of these molecules in human osteoarthritic cartilage has not been extensively investigated. We studied the expression of beta integrins (beta1-5, alpha1-6, av chains), LFA-1, ICAM-1 and CD44, on freshly isolated chondrocytes obtained from 10 osteoarthritic patients undergoing surgical knee replacement. Chondrocytes were isolated by enzymatic digestion from three zones of each articular cartilage with a differing degree of macroscopic and microscopic damage. Integrin expression and cell cycle analysis were carried out by flowcytometry. Chondrocytes from costal cartilages of 5 human foetuses were also studied. Chondrocytes from osteoarthritic cartilage expressed high levels of beta1 integrin and, at different percentages, all the alphachains. The alphachain most frequently expressed was alpha1, foilowed by alpha3, alpha5, alpha2, alphav. Integrin expression decreased from the least to the most damaged zone of articular cartilage and cell cycle analysis showed that proliferating chondrocytes (S phase) were prevalent on the latter zone. beta2, beta3, beta2, beta5, CD44, LFA-1/ICAM-1 complex were very low expressed. Fetal chondrocytes strongly expressed beta1 and beta5 chains. These data provide evidence to show that integrin expression on human chondrocytes changes in osteoarthritis and suggest that perturbations of chondrocyte-ECM signalling occur in the development of the disease. The different pattern of expression of beta1 and beta5 chains on adult and fetal chondrocytes leads to speculate that integrins play a key role in control of cartilage morphogenesis and differentiation

Arthritis in Systemic Lupus Erythematosus: From 2022 International GISEA/OEG Symposium

Musculoskeletal involvement is one of the most common manifestations of systemic lupus erythematosus (SLE), with a negative impact on both quality of life and overall prognosis. SLE arthritis can be classified into three different subtypes, with different prevalence and characteristic biomarkers and MRI findings. Identifying the pathogenetic mechanisms underlying musculoskeletal manifestations' development is crucial to develop therapeutic strategies to suppress synovial inflammation, prevent erosions and deformities, and improve SLE patients' quality of life. Hence, here we discuss the main pathogenetic mechanisms and therapeutic approaches of musculoskeletal manifestations of SLE from the 2022 International GISEA/OEG Symposium

Cardiovascular Risk Prediction in Ankylosing Spondylitis: From Traditional Scores to Machine Learning Assessment

Abstract Introduction The performance of seven cardiovascular (CV) risk algorithms is evaluated in a multicentric cohort of ankylosing spondylitis (AS) patients. Performance and calibration of traditional CV predictors have been compared with the novel paradigm of machine learning (ML). Methods A retrospective analysis of prospectively collected data from an AS cohort has been performed. The primary outcome was the first CV event. The discriminatory ability of the algorithms was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), which is like the concordance-statistic (c-statistic). Three ML techniques were considered to calculate the CV risk: support vector machine (SVM), random forest (RF), and k-nearest neighbor (KNN). Results Of 133 AS patients enrolled, 18 had a CV event. c-statistic scores of 0.71, 0.61, 0.66, 0.68, 0.66, 0.72, and 0.67 were found, respectively, for SCORE, CUORE, FRS, QRISK2, QRISK3, RRS, and ASSIGN. AUC values for the ML algorithms were: 0.70 for SVM, 0.73 for RF, and 0.64 for KNN. Feature analysis showed that C-reactive protein (CRP) has the highest importance, while SBP and hypertension treatment have lower importance. Conclusions All of the evaluated CV risk algorithms exhibit a poor discriminative ability, except for RRS and SCORE, which showed a fair performance. For the first time, we demonstrated that AS patients do not show the traditional ones used by CV scores and that the most important variable is CRP. The present study contributes to a deeper understanding of CV risk in AS, allowing the development of innovative CV risk patient-specific models

Multiprofessional and Intrahospital Experience for Diagnosis and Treatment of Pulmonary Arterial Hypertension

Background. Referral centres for pulmonary hypertension will provide care by a multiprofessional team, which should as a minimum comprise: consultant physicians with a special interest in PH, clinical nurse specialist, radiologist, cardiologist with expertise in echocardiography. Aims. this study sought to determine whether the experience of the establishment of a clinic for pulmonary arterial hypertension, initially created only for the treatment and diagnosis of heart failure, may be considered positive. Methods. From 1 July 2008 to January 1, 2012 we evaluated 80 patients in our ambulatory dedicated to the diagnosis and treatment of PAH. All patients were performed to clinical evaluation, ECG, and echocardiography with estimation of the sPAP. Then we evaluated the functional capacity through cardiopulmonary exercise testing or six minute walking test (6MWT). RHC was required to confirm the diagnosis of pulmonary arterial hypertension. Results. 80 patients (mean age: 50.9 ± 18.68 years, 31 males) were evaluated in our center; the largest groups subjected to screening were thalassemia (21 subjects), rheumatologic patients (18 patients), respirators, suspected of “outof Proportion” (12 patients) and 4 patients with OSAS. 8 adult congenital heart patients. A diagnosis of PAH after right heart catheterization was possible in 25 cases. In particular, among patients with pulmonary arterial hypertension, 8 had a rheumatic etiology (systemic sclerosis), 2 postthromboembolic disease, 5 patients had congenital heart disease, 1 patient with HIV infection, 1 patient with thalassemia major, 1 chronic lymphocytic leukemia and 1 with myelodysplasia. Conclusions. The initial experience of our center and network within our hospital may be considered positive, because it permitted to patients easy access to hospital services, to undertake a comprehensive prognostic stratification and to recognize the early signs of worsening in subsequent tests