Orbiting Frog Otolith experiment (OFO-A): Data reduction and control experimentation

The OFO-A mission was prepared as a part of a special program of vestibular physiology with the purpose of studying in which way the lack of the gravity pull will affect the functioning of that part of the labyrinth which controls balance. The gravitational components corresponded to the different head positions, namely, the gravity sensitive or positioning receptors. It is evident that in weightlessness the gravity sensitive receptors are deprived of their primary input

ACTIVITY OF MONOMERIC SECOND MITOCHONDRIAL ACTIVATOR OF CASPASES (SMAC) MIMETIC COMPOUNDS ON HUMAN FIBROBLAST-LIKE SYNOVIOCYTES FROM RHEUMATOID ARTHRITIS PATIENTS

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by systemic and intrarticular inflammation. Fibroblast-like synoviocytes (FLSs) in RA have an activated phenotype with increased expression of pro-inflammatory cytokines and matrix metalloproteiases, which sustain chronic inflammation and damage bone and cartilage. RA-FLSs also display resistance to apoptosis, which accounts for the synovial membrane hyperplasia. SMAC-mimetic compounds antagonise the activity of inhibitors of apoptosis proteins (IAPs), which regulate apoptotic and inflammatory pathways. We investigated whether SMAC127 had pro-apoptotic and anti-inflammatory effects on RA-FLSs. To better recreate an optimal in vitro model of the intrrticular environment, we also studied the effects of the addition of synovial fluid (SF) to cultures. We found that SMAC 127 could down-regulate IAPs levels and could effectively induce apoptosis - as demonstrated by apoptosis assays with Annexin V in different culture conditions and caspase-3 cleavage. Furthermore, SMAC 127 could down-regulate pro-inflammatory cytokines (TNF-alpha, IL-15 and IL-6) and induce an up-regulation of the anti-inflammatory cytokine IL-10. The levels of marix metalloproteinase-1 (MMP-1) where also reduced, whereas we did not observe any significant effects on RANKL/OPG axis. Based on these results, SMAC mimetic compounds could be a very useful treatment in patients with RA since the very early stage of the disease

Fibromyalgia and Shoulder Surgery : a Systematic Review and a Critical Appraisal of the Literature

Fibromyalgia is a common musculoskeletal syndrome characterized by chronic widespread pain and other systemic manifestations, which has demonstrated a contribution to higher postoperative analgesic consumption to other surgeries such as hysterectomies and knee and hip replacements. The aim of this review is to search current literature for studies considering the impact of fibromyalgia on clinical outcomes of patients undergoing shoulder surgery. A systematic literature review was conducted in PubMed/Medline, Embase, and ClinicalTrials.gov in February 2019. Studies were selected based on the following participants, interventions, comparisons, outcomes, and study design criteria: adult patients undergoing surgery for shoulder pain (P); diagnosis of fibromyalgia (I); patients without fibromyalgia (C); outcome of surgery in terms of pain or analgesic or non-steroidal anti-inflammatory drugs consumption (O); case series, retrospective studies, observational studies, open-label studies, randomized clinical trials, systematic reviews and meta-analyses were included (S). Authors found 678 articles, of which four were found eligible. One retrospective study showed that patients with fibromyalgia had worse clinical postoperative outcomes; two retrospective studies reported a higher opioid prescription in patients with fibromyalgia and one prospective observational study found that a higher fibromyalgia survey score correlated with lower quality of recovery scores two days after surgery. The scarce and low-quality evidence available does not allow confirming that fibromyalgia has an impact on postoperative outcomes in shoulder surgery. Future studies specifically focusing on shoulder surgery outcomes may help improvement and personalization of the management of patients with fibromyalgia syndrome (PROSPERO 2019, CRD42019121180)

Rheumatoid Nodules Predating Seroconversion and Rheumatoid Arthritis: An Uncommon Case Report

Rheumatoid nodulosis is a benign condition associated with mild or no arthritis. Differently from classical rheumatoid nodules, which are relatively common in patients with long-standing rheumatoid arthritis, particularly in rheumatoid factor (RF)-positive patients, rheumatoid nodulosis may rarely precede arthritis onset and even seroconversion. We describe the clinical course of a patient with isolated painful rheumatoid nodules, who subsequently experienced RF and anti-citrullinated protein antibodies (ACPA) seroconversion and finally developed overt rheumatoid arthritis. This case should raise clinical awareness to consider rheumatoid nodulosis as a possible diagnosis even in the absence of arthritis and of RF positivity, whenever facing with isolated subcutaneous nodules

Tocilizumab Effects on Coagulation Factor XIII in Patients with Rheumatoid Arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic systemic auto-immune disease associated with a prothrombotic state. Tocilizumab, an interleukin-6 receptor inhibitor, is highly effective in controlling disease activity and thrombotic risk. Factor XIII (FXIII), involved in thrombotic complications, has been reported to be reduced in RA patients during maintenance treatment with tocilizumab, but no data are available before and after the drug administration. Thus, we investigated the effects of tocilizumab on FXIII, thrombin generation and inflammation in patients with RA na\uefve for the drug. Methods: We studied 15 consecutive adult patients with RA at baseline and 4 weeks after the onset of parenteral administration of tocilizumab, measuring disease activity and plasma levels of C-reactive protein (CRP), FXIII, and prothrombin fragments F1+2 by immunoenzymatic methods. Fifteen healthy subjects, sex-and age-matched with patients, served as normal controls for laboratory measurements. Results: At baseline, patients with established RA had a median DAS28 of 4.8 (3.2\u20138.3) and, compared to healthy controls, had higher plasma levels of CRP (p < 0.0001), FXIII (p = 0.017) and F1+2 (p < 0.0001). Four weeks after starting treatment with tocilizumab, based on the EULAR response criteria, eight patients were classifiable as responders and seven as non-responders. In responders, we observed a statistically significant reduction not only of the values of DAS28 and CRP (p = 0.012 for both), ut also of plasma levels of FXIII (p = 0.05) and F1+2 (p = 0.025). In non-responders, all the studied parameters were unchanged. Conclusion: The decrease of FXIII and F1+2 levels after tocilizumab treatment observed only in those patients who responded to the drug indicates that the effect of tocilizumab on the prothrombotic state is linked to the control of inflammation and disease activity and not to a direct effect of the drug, thus contributing to the reduction of the cardiovascular risk

Management of Painful Shoulder Arthroplasty: A Narrative Review

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Ultrasound Detection of Subquadricipital Recess Distension

Joint bleeding is a common condition for people with hemophilia and, if untreated, can result in hemophilic arthropathy. Ultrasound imaging has recently emerged as an effective tool to diagnose joint recess distension caused by joint bleeding. However, no computer-aided diagnosis tool exists to support the practitioner in the diagnosis process. This paper addresses the problem of automatically detecting the recess and assessing whether it is distended in knee ultrasound images collected in patients with hemophilia. After framing the problem, we propose two different approaches: the first one adopts a one-stage object detection algorithm, while the second one is a multi-task approach with a classification and a detection branch. The experimental evaluation, conducted with $483$ annotated images, shows that the solution based on object detection alone has a balanced accuracy score of $0.74$ with a mean IoU value of $0.66$, while the multi-task approach has a higher balanced accuracy value ($0.78$) at the cost of a slightly lower mean IoU value

The Role of Ultrasonography in the Assessment of Skeletal Hand Involvement in Systemic Sclerosis

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Total Joint Arthroplasty in Patients with Inflammatory Rheumatic Diseases

Since its introduction, total joint arthroplasty (TJA) has improved the quality of life of patients with degenerative joint disorders. In the last decades, a number of conventional and biological disease-modifying antirheumatic drugs have become available for the treatment of patients with inflammatory rheumatic diseases (IRD), leading to a reduction in the need to undergo TJA. However, TJA is still frequently performed in IRD patients. Both rheumatologists and orthopedics should be aware that patients with IRD have a peculiar perioperative risk profile due to disease-related, patient-related, and surgery-related risk factors. On the basis of current evidence, TJA is a safe procedure for IRD patients as long as an accurate risk stratification and a multidisciplinary approach are applied. We here describe the current strategies for an appropriate surgical management of osteoarthritis in IRD patients and the fascinating opening perspectives that surgeons and clinicians may expect in the future