GISEA: an Italian biological agents registry in rheumatology

The GISEA registry is an independent database that was established by the Italian Group for the Study of Early Arthritis (GISEA) in 2008, funded by the Italian Association of Rheumatic Patients (ANMAR - ONLUS). In line with the network's epidemiological strategy, the initial protocol was designed to collect long-term follow-up data concerning patients with rheumatic diseases treated with biological agents in order to investigate the realworld characteristics in terms of disease activity, comorbidities and survival on treatment. We here describe the design and methodology used to collect patient data. Information concerning demographics, disease activity, treatment changes (including the reasons for changing and the duration of each therapy), concomitant therapies and adverse events is available to all the members of the study groups by means of a web-based interface that allows queries and the presentation of numerical data, as well as graphics to illustrate trends. Fourteen Italian rheumatology centres have contributed patients to the database which, at the time writing, includes 5145 patients (72% women) with a mean age of 53 years (range 16-88). The initial diagnoses were rheumatoid arthritis (3494 patients, 67.9%), psoriatic arthritis (833, 16.2%), ankylosing spondylitis (493, 9.6%), undifferentiated spondylo-arthritides (307, 5.9%), enteropathic arthritis (14, 0.3%) and spondylitis following reactive arthritis (4, 0.1%). These patients have been followed for up to 10 years, and 1927 (35.8%) have been treated for at least three years. The biological treatments received include etanercept, infliximab, anakinra, adalimumab, abatacept, rituximab and tocilizumab. A total of 2926 adverse events have been observed, with 1171 patients (22%) reporting at least one. Analysis of the accumulated data will provide insights into the critical early phase of the studied arthritides, and enable us to identify the clinical and laboratory profiles that may predict responsiveness to a specific therapy

On Observing Dynamic Prioritised Actions in SOC

We study the impact on observational semantics for SOC of priority mechanisms which combine dynamic priority with local pre-emption. We define manageable notions of strong and weak labelled bisimilarities for COWS, a process calculus for SOC, and provide alternative characterisations in terms of open barbed bisimilarities. These semantics show that COWS’s priority mechanisms partially recover the capability to observe receive actions (that could not be observed in a purely asynchronous setting) and that high priority primitives for termination impose specific conditions on the bisimilarities

On Secure Implementation of an IHE XUA-Based Protocol for Authenticating Healthcare Professionals

The importance of the Electronic Health Record (EHR) has been addressed in recent years by governments and institutions.Many large scale projects have been funded with the aim to allow healthcare professionals to consult patients data. Properties such as confidentiality, authentication and authorization are the key for the success for these projects. The Integrating the Healthcare Enterprise (IHE) initiative promotes the coordinated use of established standards for authenticated and secure EHR exchanges among clinics and hospitals. In particular, the IHE integration profile named XUA permits to attest user identities by relying on SAML assertions, i.e. XML documents containing authentication statements. In this paper, we provide a formal model for the secure issuance of such an assertion. We first specify the scenario using the process calculus COWS and then analyse it using the model checker CMC. Our analysis reveals a potential flaw in the XUA profile when using a SAML assertion in an unprotected network. We then suggest a solution for this flaw, and model check and implement this solution to show that it is secure and feasible

A Case of Osteonecrosis of the Jaw in a Patient with Crohn's Disease Treated with Infliximab

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse drug reaction, occurring in patients undergoing treatments with antiresorptive or antiangiogenic agents, such as bisphosphonates, denosumab, or bevacizumab, for different oncologic and non-oncologic diseases. The aim of this study was to report a case of MRONJ in a patient taking infliximab, an anti-TNF-alpha antibody used to treat Crohn's disease, rheumatoid arthritis, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. Case Report: A 49-year-old female patient affected by Crohn's disease, who had been undergoing 250 mg intravenous infliximab every six weeks for 12 years, with no history of antiresorptive or antiangiogenic agent administration, came to our attention for post-surgical MRONJ, associated with a wide cutaneous necrotic area of her anterior mandible. Following antibiotic cycles, the patient underwent surgical treatment with wide bone resection and debridement of necrotic tissues; after prolonged follow-up (16 months), the patient completely healed without signs of recurrence. Conclusions: Prevention of MRONJ by dental check-up before and during treatments with antiresorptive treatments (bisphosphonates or denosumab) is a well-established procedure. Although further studies are required to confirm the role of infliximab in MRONJ, based on the results of this study, we propose that patients who are going to be treated with infliximab should also undergo dental check-up before starting therapy, to possibly avoid MRONJ onset

Safety of anti-tumor necrosis factor-α therapy in patients with rheumatoid arthritis and chronic hepatitis C virus infection

The prevalence of concurrent rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection is probably underestimated because of the increasing spread of this virus worldwide, especially in developing countries. In these patients, anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy may aggravate hepatitis and increase viremia. We evaluated the safety of these treatments, which remain controversial. Thirty-one HCV-positive patients (23 women, 8 men, mean age 59+/-13 yrs, mean disease duration 13+/-11.5 SD yrs) with active RA [Disease Activity Score 28 (DAS28)>3.2] unresponsive to conventional therapies were treated with TNF-alpha blockers (infliximab 11, etanercept 17, adalimumab 3) at standard dosages. Safety and efficacy were evaluated at the third month of treatment and at the patient's last observation. A significant clinical-serological improvement was recorded at the 3-month reevaluation. Mean values of patients assessment of general health on visual analog scale (range 0.100) decreased from 69+/-29 (SD) to 35+/-27 (por=2 log10) in 4 cases. Previous observations had suggested the safety of TNF-alpha blockers for treatment of RA in patients with concurrent HCV infection. Given the clinical-therapeutic implications, our results support the safety of TNF-alpha blockers in patients with HCV, provided there is close monitoring of clinical and virological data (mainly ALT and HCV viremia)

Extracorporeal shock waves down-regulate the expression of interleukin-10 and tumor necrosis factor-alpha in osteoarthritic chondrocytes

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to investigate the effects of extra corporeal shock waves (ESW) therapy on the metabolism of healthy and osteoarthritic human chondrocytes, and particularly on the expression of IL-10, TNF-alpha and beta1 integrin.</p> <p>Methods</p> <p>Human adult articular cartilage was obtained from 9 patients (6 male and 3 females), with primary knee osteoarthritis (OA), undergoing total joint replacement and from 3 young healthy donors (HD) (2 males, 1 female) with joint traumatic fracture. After isolation, chondrocytes underwent ESW treatment (electromagnetic generator system, MINILITH SL1, STORZ MEDICAL) at different parameters of impulses, energy levels and energy flux density. After that, chondrocytes were cultured in 24-well plate in DMEM supplemented with 10% FCS for 48 hours and then beta₁integrin surface expression and intracellular IL-10 and TNF-alpha levels were evaluated by flow-cytometry.</p> <p>Results</p> <p>At baseline, osteoarthritic chondrocytes expressed significantly lower levels of beta1 integrin and higher levels and IL-10 and TNF-alpha levels. Following ESW application, while beta1 integrin expression remain unchanged, a significant decrease of IL-10 and TNF-alpha intracellular levels was observed both in osteoarthritic and healthy chondrocytes. IL-10 levels decreased at any impulses and energy levels, while a significant reduction of TNF-alpha was mainly found at middle energies.</p> <p>Conclusion</p> <p>Our study confirmed that osteoarthritic chondrocytes express low beta₁integrin and high TNF-alpha and IL-10 levels. Nonetheless, ESW treatment application down-regulate the intracellular levels of TNF-alpha and IL-10 by chondrocytes, suggesting that ESW might restore TNF-alpha and IL-10 production by osteoarthritic chondrocytes at normal levels. However, further in vivo and in vitro studies are necessary to establish if ESW can represent a viable option in the treatment of OA.</p

Study on the differences of BMI between olms found in cave and the ones sampled in spring

The olm (Proteus anguinus) is a blind amphibian, depigmented and with an extremely reduced metabolism. These are adaptations to cave life that allow the animals to exploit this hostile (from a human perspective) habitat. Adaptations to cave life, should prevent successful exploitation of the external environment. However, although the Proteus is a cave animal, it has been reported by some authors in the spring environment, Our previous results showed that this presence, would seem not to be random, in but linked to very specific factors such as hydroperiod the absence of potential predators. In the light of these results, we have conducted a study with the aim of verifying whether the Proteus benefits from exploiting the trophic resources occurring in springs. Since June 2020 we have sampled 64 springs and 12 caves in the Monfalcone province, each olm found during the sampling was photographed, measured and weighed. A total of 73 different olms were analyzed and the Body Mass Index (BMI) was calculated for each individual. Olms found in springs had a significantly higher BMI than those found in caves. The BMI of springs’ olms was significantly related to amount of the trophic available, evidencing that they took advantages from exploiting the external environment. These results contribute to support the hypothesis of the non-random presence of the Proteus in the spring environment, the olm, in fact, seem to benefit from this type of habitat taking advantage of the greater number of resources present in it

Orchestrating Tuple-based Languages

The World Wide Web can be thought of as a global computing architecture supporting the deployment of distributed networked applications. Currently, such applications can be programmed by resorting mainly to two distinct paradigms: one devised for orchestrating distributed services, and the other designed for coordinating distributed (possibly mobile) agents. In this paper, the issue of designing a pro- gramming language aiming at reconciling orchestration and coordination is investigated. Taking as starting point the orchestration calculus Orc and the tuple-based coordination language Klaim, a new formalism is introduced combining concepts and primitives of the original calculi. To demonstrate feasibility and effectiveness of the proposed approach, a prototype implementation of the new formalism is described and it is then used to tackle a case study dealing with a simplified but realistic electronic marketplace, where a number of on-line stores allow client applications to access information about their goods and to place orders