Human osteoarthritic cartilage shows reduced in vivo expression of IL-4, a chondroprotective cytokine that differentially modulates IL-1β-stimulated production of chemokines and matrix-degrading enzymes in vitro

open10noThis work was supported by grants from Rizzoli Orthopaedic Institute (Ricerca Corrente); University of Bologna (RFO); MIUR (FIRB-RBAP10KCNS); “Cinque per mille” Funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.BACKGROUND: In osteoarthritis (OA), an inflammatory environment is responsible for the imbalance between the anabolic and catabolic activity of chondrocytes and, thus, for articular cartilage derangement. This study was aimed at providing further insight into the impairment of the anabolic cytokine IL-4 and its receptors in human OA cartilage, as well as the potential ability of IL-4 to antagonize the catabolic phenotype induced by IL-1β. METHODOLOGY/PRINCIPAL FINDINGS: The in vivo expression of IL-4 and IL-4 receptor subunits (IL-4R, IL-2Rγ, IL-13Rα1) was investigated on full thickness OA or normal knee cartilage. IL-4 expression was found to be significantly lower in OA, both in terms of the percentage of positive cells and the amount of signal per cell. IL-4 receptor type I and II were mostly expressed in mid-deep cartilage layers. No significant difference for each IL-4 receptor subunit was noted. IL-4 anti-inflammatory and anti-catabolic activity was assessed in vitro in the presence of IL-1β and/or IL-4 for 24 hours using differentiated high density primary OA chondrocyte also exhibiting the three IL-4 R subunits found in vivo. Chemokines, extracellular matrix degrading enzymes and their inhibitors were evaluated at mRNA (real time PCR) and protein (ELISA or western blot) levels. IL-4 did not affect IL-1β-induced mRNA expression of GRO-α/CXCL1, IL-8/CXCL8, ADAMTS-5, TIMP-1 or TIMP-3. Conversely, IL-4 significantly inhibited RANTES/CCL5, MIP-1α/CCL3, MIP-1β/CCL4, MMP-13 and ADAMTS-4. These results were confirmed at protein level for RANTES/CCL5 and MMP-13. CONCLUSIONS/SIGNIFICANCE: Our results indicate for the first time that OA cartilage has a significantly lower expression of IL-4. Furthermore, we found differences in the spectrum of biological effects of IL-4. The findings that IL-4 has the ability to hamper the IL-1β-induced release of both MMP-13 and CCL5/RANTES, both markers of OA chondrocytes, strongly indicates IL-4 as a pivotal anabolic cytokine in cartilage whose impairment impacts on OA pathogenesis.openAssirelli E.; Pulsatelli L.; Dolzani P.; Platano D.; Olivotto Eleonora .; Filardo G.; Trisolino G.; Facchini A.; Borzì R.M.; Meliconi R.Assirelli E.; Pulsatelli L.; Dolzani P.; Platano D.; Olivotto Eleonora .; Filardo G.; Trisolino G.; Facchini A.; Borzì R.M.; Meliconi R

Higher 90-Day Mortality after Surgery for Hip Fractures in Patients with COVID-19: A Case-Control Study from a Single Center in Italy

The mortality of hip fracture (HF) patients is increased by concomitant COVID-19; however, evidence is limited to only short follow-up. A retrospective matched case-control study was designed with the aim to report the 90-day mortality and determine the hazard ratio (HR) of concomitant HF and COVID-19 infection. Cases were patients hospitalized for HF and diagnosed with COVID-19. Controls were patients hospitalized for HF not meeting the criteria for COVID-19 diagnosis and were individually matched with each case through a case-control (1:3) matching algorithm. A total of 89 HF patients were treated during the study period, and 14 of them were diagnosed as COVID-19 positive (overall 15.7%). Patients' demographic, clinical, and surgical characteristics were similar between case and control groups. At 90 days after surgery, 5 deaths were registered among the 14 COVID-19 cases (35.7%) and 4 among the 42 HF controls (9.5%). COVID-19-positive cases had a higher risk of mortality at 30 days (HR = 4.51; p = 0.0490) and 90 days (HR = 4.50; p = 0.025) with respect to controls. Patients with concomitant HF and COVID-19 exhibit high perioperative mortality, which reaches a plateau of nearly 30-35% after 30 to 45 days and is stable up to 90 days. The mortality risk is more than four-fold higher in patients with COVID-19

Covid-19 And Rheumatic Autoimmune Systemic Diseases: Role of Pre-Existing Lung Involvement and Ongoing Treatments

The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations

Capitolo 11.3 "Malattia da deposizione di cristalli di calcio pirofosfato"

In questo capitolo la malattia da deposizione di cristalli di calcio pirofosfato viene affrontata descrivendo l'epidemiologia, il quadro clinico, le indagini di laboratorio e strumentali, l'etiologia e la patogenesi, la diagnosi e la terapia

Synovial inflammation drives structural damage in hand osteoarthritis: A narrative literature review

Abstract: Background: Ultrasound is one of the most promising candidates for the detection of inflammation and structural damage in hand osteoarthritis. Objective: To evaluate new advances of US as a diagnostic and prognostic tool in hand osteoarthritis assessment. Methods: We conducted a Medline on PubMed search for articles about \u201cultrasonography\u201d and \u201chand OA\u201d published between January 2012 and 15th April 2016, limiting our search to articles on human adults in English, excluding those involving systemic inflammatory diseases, visualization of joints other than hands, ultrasound guided injections and surgical procedures. Reviews, case reports, letters, position statements and ex vivo studies were excluded. Concordance between ultrasound and conventional radiography and magnetic resonance imaging was evaluated. Results: Total 46 records were identified, and 16 articles were selected: four showed only ultrasound structural damage (osteophytes, cartilage pathology), six only ultrasound inflammatory variables (synovial thickness, effusion and power Doppler signal), six should considered both ultrasound structural and inflammatory features as well as erosions and two were epidemiological studies. Ultrasound synovitis and power Doppler signal were more frequent in erosive hand osteoarthritis. Followup studies found that ultrasound inflammatory features at baseline are independently associated with radiographic progression; power Doppler signal was the strongest predictor of structural damage. Ultrasound is a reliable tool for cartilage and osteophyte assessment (when performed with static images) and shows a good concordance with magnetic resonance imaging for osteophytes, erosions and synovitis. Conclusions: Ultrasound detected inflammation may predict radiographic progression and may be used in prospective clinical trials of hand osteoarthritis and in everyday clinical practice

Sclerodermic patients: an interdisciplinary approach

We experience our life through the skin: from the first loving contact to the last painful separation. Therefore the skin \u201creminds\u201d all the conflicts between the individual and the external environment. Nowadays there is a great agreement in identifying these conflicts as responsible for the majority of the psychopathologies. The present work aimed at investigating the psychosomatic features of scleroderma (i.e. the thickening and tightening of the skin) using the Analytic Psychodrama method. This method, through scenes, allows to make conscious different unconscious conflicts, as well as to interpret them. Method. We studied a group of five women (age: 35-70 years old) for one year. We collected the individual experiences reported by the patients, focusing on the ones that are crucial in the formation of psychosomatic symptoms: the specific relationship with the mother and with the father, the possible arrival of one or more younger siblings, the specific affection/dynamics of the primary and following milieu. We measured the relational structures between the participants - closeness vs. distance - before and after the group work. Results and conclusions. Collected data suggest that during the formation of their early personality patients experienced a mother affectively cold, needy or lacking of contact signals. As a result their skin was not trained to soften up, delighting in maternalwarmth and protection. Conversely the skin adapted to defense itself autonomously. The used method, the Analytic Psychodrama, allowed us to investigate different aspects of the psychic life of each participant. We identified important changes in participants\u2019 body perception as well as in physical contact with the others. We observed these changes also in the family context. Resting on these results, we predict further long-term effects of our approach. According to the principles of psychosomatic medicine, it should affect also the specific clinical aspects of scleroderma

Analysis of cartilage biomarkers in erosive and non-erosive osteoarthritis of the hands

none5noneSILVESTRI T.; PULSATELLI L.; DOLZANI P.; PUNZI L.; MELICONI R.SILVESTRI T.; PULSATELLI L.; DOLZANI P.; PUNZI L.; MELICONI R

Prognostic value of a combined panel of soluble and genetic biomarkers in patients with early arthritis

At present, to help clinical decision-making, a model that full successfully predicts UA outcome, easily assessable in clinical practice, is lacking. However, in order to address the goal of early identification of UA patients with high risk to develop RA, prediction model has been proposed. All these models estimate the frequency of progression to RA related to the calculated score attributed to defined clinical and laboratory parameter. Up to now, in all proposed models, the assessment of soluble biomarkes included are limited to RF and anti-CCP antibody evaluation. Model proposed by Van der Helm appears to be the main algorithm that has been extensively applied in different cohort of UA patients in order to evaluated the accuracy in outcome prediction (Van der Helm-Van Mil AHN et al, Arthritis Rheum, 2007: Van der Helm-Van Mil AHN et al, Arthritis Rheum, 2008). This algorithm appear to have a good accuracy for predicting outcome of UA patients presenting respectively low (=/<6.0) (91% did not develop RA) and high (=/>8) score (84% develop RA). Unfortunately, this model appear to be inadequate in estimating the risk in 25% of UA with an intermediate score. More recently, in 2010, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) developed new criteria for facilitating the early identification of UA patient with highest probability to develop persistent or erosive RA. Recent studies, aiming to evaluate the diagnostic performance of ACR/EULAR 2010 criteria, showed good predictive value for UA patient scored =/>6, overlapping accuracy of Van der Helm algorithm (Alves C et al., Ann Rheum Dis, 2011; Cader MZ, Ann Rheum Dis, 2011). On the other hand, in these cohorts of patient a relevant rate of patients who needed to be treated during follow-up, did not fulfill the ACR/EULAR 2010 criteria at baseline. Thus, misclassification may be a relevant issue when treatment decision are taken according to this algorithm. These evidence underline that predicting power improvement of clinical useful model, easily assessable in clinical practice, is greatly needed. ACR/EULAR working group for defining 2010 classification criteria stated that genetic, proteomic, serological or imaging biomarkers that provide a more robust basis for risk stratification will be considered for a modification or amendment of the 2010 criteria. To reach this goal, data concerning multiple evaluation of a large set of molecules in UA patients are needed. Therefore, evaluation of a composite (genetic and soluble) biomarker profile in a cohort of recent onset UA patients (prospectively assessed), utilizing multiplex-detection technology approach, appear to be original and innovative because: - allow to analyze a vast number of candidate biomarkers - may identify a reliable soluble biomarker profile in recent onset UA patients in relationship to clinical outcome - may define the genetic network of epistatic interaction that underlie the susceptibility to develop RA in early UA patients. - may add power in predicting early UA outcome comparing to prognostic model currently followed in clinical practice Combined detection of multiple indicators may define a molecular signature that allows the simultaneously identification of diagnostic/prognostic features of individuals patients, thus leading forward to the practice of personalized medicine