Ex vivo physiological compression of human osteoarthritis cartilage modulates cellular and matrix components

Mechanical stimulation appears to play a key role in cartilage homeostasis maintenance, but it can also contribute to osteoarthritis (OA) pathogenesis. Accumulating evidence suggests that cartilage loading in the physiological range contributes to tissue integrity maintenance, whereas excessive or reduced loading have catabolic effects. However, how mechanical stimuli can regulate joint homeostasis is still not completely elucidated and few data are available on human cartilage. We aimed at investigating human OA cartilage response to ex vivo loading at physiological intensity. Cartilage explants from ten OA patients were subjected to ex vivo controlled compression, then recovered and used for gene and protein expression analysis of cartilage homeostasis markers. Compressed samples were compared to uncompressed ones in presence or without interleukin 1ß (IL-1ß) or interleukin 4 (IL-4). Cartilage explants compressed in combination with IL-4 treatment showed the best histological scores. Mechanical stimulation was able to significantly modify the expression of collagen type II (collagen 2), aggrecan, SOX9 transcription factor, cartilage oligomeric matrix protein (COMP), collagen degradation marker C2C and vascular endothelial growth factor (VEGF). Conversely, ADAMTS4 metallopeptidase, interleukin 4 receptor alpha (IL4Ra), chondroitin sulfate 846 epitope (CS846), procollagen type 2 C-propeptide (CPII) and glycosaminoglycans (GAG) appeared not modulated. Our data suggest that physiological compression of OA human cartilage modulates the inflammatory milieu by differently affecting the expression of components and homeostasis regulators of the cartilage extracellular matrix

Nightmare disorder and REM sleep behavior disorder in inflammatory arthritis: Possibility beyond neurodegeneration.

OBJECTIVES:To investigate the prevalence of REM sleep behavior disorder (RBD) in patients with inflammatory arthritis (IA) to ascertain if RBD could be an internal red flag signaling a fluctuating state of inflammation based on the theory of "protoconsciousness". MATERIALS & METHODS:One hundred and three patients with a confirmed diagnosis of IA were consecutively recruited. The patients underwent general (IA activity, functional status, laboratory tests) and neurological evaluations. A neurologist investigated RBD and REM sleep parasomnias in a semi-structured interview. Sleep quality was assessed with the Pittsburgh Sleep Quality Index, while the risk of obstructive sleep apnea syndrome (OSAS) was evaluated with the Berlin questionnaire. Beck Depression Inventory II and State-Trait Anxiety Inventory investigated depression and anxiety. RESULTS:Patients had a mean age of 53.7 ± 14.6 years, 65% were women; 57.3% were in a clinically active phase of IA. Two women fulfilled ICSD-3 criteria for RBD appearing 11 years after and 20 years before IA onset respectively. 31 patients scored positive for nightmare disorder (ND), 8 for recurrent isolated sleep paralysis. 65 (63.1%) patients reported poor sleep quality and 25 (24.3%) resulted at high risk for OSAS. 32 (31.0%) patients scored positively for depression or anxiety. CONCLUSIONS:The prevalence of RBD in patients with IA did not differ from that in the general population, whereas ND presented a 2-fold increased prevalence. Whether RBD can be considered a red flag signaling an internal danger remains an open question, while ND may be a new player in this intriguing relation

Mesenchymal stromal cells from a progressive pseudorheumatoid dysplasia patient show altered osteogenic differentiation

Background: Progressive pseudorheumatoid dysplasia (PPRD) is a rare autosomal recessive non-inflammatory skeletal disease with childhood onset and is characterized by a progressive chondropathy in multiple joints, and skeletal abnormalities. To date, the etiopathological relationship between biological modification occurring in PPRD and genetic mutation remains an open issue, partially due to the limited availability of biological samples obtained from PPRD patients for experimental studies. Case presentation: We describe the clinical features of a PPRD patient and experimental results obtained from the biological characterization of PPRD mesenchymal stromal cells (MSCs) and osteoblasts (OBs) compared to normal cell populations. Phenotypic profile modifications were found in PPRD compared to normal subjects, essentially ascribed to decreased expression of CD146, osteocalcin (OC) and bone sialoprotein in PPRD MSCs and enhanced CD146, OC and collagen type I expression in PPRD OBs. Gene expression of Dickkopf-1, a master inhibitor of WNT signaling, was remarkably increased in PPRD MSCs compared to normal expression range, whereas PPRD OBs essentially exhibited higher OC gene expression levels. PPRD MSCs failed to efficiently differentiate into mature OBs, so showing a greatly impaired osteogenic potential. Conclusions: Since all regenerative processes require stem cell reservoirs, compromised functionality of MSCs may lead to an imbalance in bone homeostasis, suggesting a potential role of MSCs in the pathological mechanisms of PPRD caused by WNT1-inducible signaling pathway protein-3 (WISP3) mutations. In consideration of the lack of compounds with proven efficacy in such a rare disease, these data might contribute to better identify new specific and effective therapeutic approaches

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 vaccine hesitancy in systemic sclerosis

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Insulin signaling in arthritis

Inflammatory arthritis is burdened by an increased risk of metabolic disorders. Cytokines and other mediators in inflammatory diseases lead to insulin resistance, diabetes and hyperlipidemia. Accumulating evidence in the field of immunometabolism suggests that the cause-effect relationship between arthritis and metabolic abnormalities might be bidirectional. Indeed, the immune response can be modulated by various factors such as environmental agents, bacterial products and hormones. Insulin is produced by pancreatic cells and regulates glucose, fat metabolism and cell growth. The action of insulin is mediated through the insulin receptor (IR), localized on the cellular membrane of hepatocytes, myocytes and adipocytes but also on the surface of T cells, macrophages, and dendritic cells. In murine models, the absence of IR in T-cells coincided with reduced cytokine production, proliferation, and migration. In macrophages, defective insulin signaling resulted in enhanced glycolysis affecting the responses to pathogens. In this review, we focalize on the bidirectional cause-effect relationship between impaired insulin signaling and arthritis analyzing how insulin signaling may be involved in the aberrant immune response implicated in arthritis and how inflammatory mediators affect insulin signaling. Finally, the effect of glucose-lowering agents on arthritis was summarized.Pathophysiology and treatment of rheumatic disease

Diagnostic accuracy of a velcro sound detector (VECTOR) for interstitial lung disease in rheumatoid arthritis patients: The InSPIRAtE validation study (INterStitial pneumonia in rheumatoid ArThritis with an electronic device)

Background: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. Methods: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. Results: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. Conclusions: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease

[Disease activity assessment in large vessel vasculitis]

Disease activity assessment in large vessel vasculitis (LVV) is often challenging for physicians. In this study, we compared the assessment of disease activity based on inflammatory markers, clinical indices (Indian Takayasu Activity Score [ITAS] and the Kerr/National Institute of Health indices [Kerr/NIH]), and 18F-Fluorodesossiglucose (FGD) vascular uptake at positron emission tomography (Pet). We found that Pet results did not statistically correlate with the clinical indices ITAS and Kerr/NIH, because FDG uptake was increased (grade>2 on a 0-3 scale in at least one evaluated vascular segment) in many patients with inactive disease according to clinical and laboratory parameters (i.e., negative ITAS and Kerr/NIH indices as well as normal erythrocyte sedimentation rate (ESR) and C-reactive protein (PCR)). Similarly, interleukin- 6 and its soluble receptor did not statistically correlate with disease activity. In contrast, clinical indices showed a significant correlation between each other and with inflammatory markers (VES and PCR). These data suggest that while clinical indices and inflammatory markers may be useful to assess disease activity, Pet may be more sensitive