277 research outputs found
Predictive factors of remission in juvenile idiopathic arthritis patients treated with biological therapies 13-year experience of a single center
No full textPREDICTIVE FACTORS OF REMISSION IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS TREATED WITH BIOLOGICAL THERAPIES. 13-YEAR EXPERIENCE OF A SINGLE CENTER M. Romano1, I. Pontikaki1, I. Ardoino2, M. Gattinara1, E. del giudice3, P. Boracchi2, S. Lodi-Rizzini1, P.L. Meroni1, V. Gerloni1 1Division of Rheumatology, Istituto Ortopedico G.Pini 2Unit of Medical Statistic and Biometry “G.A. Maccacaro”, University of Milan, Italy., Milan 3Dep. of Pediatrics, Sapienza, University of Rome, Italy, Rome, Italy Background: Juvenile Idiopathic Arthritis (JIA) is the most prevalent chronic rheumatic disease in childhood. The term JIA means a group of clinically heterogeneous arthritides, beginning before the age of 16 years, of unknown cause, and persistent for more then 6 weeks. The prognosis is often severe and many children are still suffering from active disease in adulthood. Objectives: Juvenile Idiopathic Arthritis (JIA) is the most prevalent chronic rheumatic disease in childhood. The term JIA means a group of clinically heterogeneous arthritides, beginning before the age of 16 years, of unknown cause, and persistent for more then 6 weeks. The prognosis is often severe and many children are still suffering from active disease in adulthood. Methods: All JIA patients (pts) treated in our Center with BTs, are prospective followed every 2 months for the evaluation of safety and efficacy (according to ACR-Pedi core set criteria). Charts of all 363 pts enrolled between November 1999 and November 2012, have been reviewed. In total 750 BTs were administered to our 363 pts. The outcome measures needed to define the achievement of the status of ID, CRM and CR, at several follow-up moments, were analysed. Results: Two hundred ninety-four JIA pts (who received in total 535 BT) were statistically evaluated for predicting factors of CRM during the 1st course of BT. Median age at disease onset was 5.4 yrs (mean 6.7, range 0.5-16). At starting of the 1st BT median disease duration was 7.9 yrs (mean 9.6, range 0.2 - 41.4), median age was 15.2 yrs (mean 16.3, range 1.9 - 49.8). Median treatment duration of the 1st BT was 2.06 yrs (mean 1.96, range 0.03-10.35). CRM was achieved with 172 out of all 535 BTs (32.1%) and with 136 out of 294 1st courses of BTs (46.2%). 136 out of 172 successful treatments (79.1%) were 1st BTs. During the 1st BT, 136 out of 294 pts (46.3%) obtained one or more periods of CRM of variable duration. Only 4 pts reached CR. The statistical multivariate analysis showed that the probability of CRM with the 1st BT is positively correlated with male gender (p=0.005), non-soJIA (p<0.05) and shorter disease duration before starting the 1st BT (p<0.05). Conclusions: Upon treatment with the 1st BT, nearly half of children and young people affected by JIA, although they had suffered from long-standing, refractory disease non responder to DMARDs, reached at least one sustained period of CRM. Nevertheless a persistent CR off medication remains a rare event. References: 1. Wallace CA, Ruperto N, Giannini EH. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol 2004;31:2290-4. 2. Lurati A, Salmaso A, Gerloni V, Gattinara M, Fantini F. Accuracy of Wallace criteria for clinical remission in juvenile idiopathic arthritis: a cohort study of 761 consecutive cases. J Rheumatol. 2009 Jul;36(7):1532-5. 3. Fantini F, Gerloni V, Gattinara M, Cimaz R, Arnoldi C, Lupi E. Remission in juvenile chronic arthritis: a cohort study of 683 consecutive cases with a mean 10 year followup. J Rheumatol. 2003 Mar;30(3):579-84
Fostering collaboration between start-ups and students for mutually beneficial inspiring learning
No full textThis two-voiced paper is the result of a student-teacher interaction in which the teacher simply paves the floor for a student’s narrative and commentary, from their perspective, of an innovative projectbased studio experience. By partnering with an incubation and start-up program for social innovators in Milan, university faculty considered how to design a studio to stimulate both students and innovators in their different educational and personal trajectories by organising "pairs of teams" with the same design goal(s), conscientious of social innovation, environmental sustainability within a circular economy, and striving for radical solutions. The team for which this student-author is sharing their experience in this paper has been paired with the start-up team “NoLo Ricicla - ilVespaio”, whose innovation idea was based on the question “How could a system of plastic packaging recovery, production and distribution of recycled artefacts be organised on a neighbourhood scale in the neighbourhood of NoLo?
Predictive factors of tmj involvement in 230 consecutive jia patients regularly screened from 2000 to 2014 in a single pediatric rheumatology centre
No full textBackground: Juvenile Idiopathic Arthritis (JIA) has been shown to involve frequently the temporo-mandibular joint (TMJ). An important prognostic aspect is to diagnose and treat it promptly.
Objectives: To evaluate in a consecutive JIA patients (pts) cohort, regularly screened from year 2000 to 2014, the predictive factors of the TMJ involvement.
Methods: 230 consecutive pts (152 females, 78 males) affected by JIA according to ILAR classification, 164 oligoarthritis, 4 polyarthritis rheumatoid factor (RF) +, 34 polyarthritis RF-, 22 systemic onset JIA (soJIA), 4 enthesitis-related arthritis (ERA) HLA B27+, and 2 psoriatic arthritis were included in a retrospective evaluation. Mean disease onset age was 6.5 yrs (range 1-16), mean disease duration 12.7 yrs (range 0.2-46.2).
We analyzed the correlation between TMJ involvement with the following items: ILAR categories, age at onset, gender, pattern of articular involvement (large joints, small ones, hips, cervical spine).
Results: 88/230 patients (38.3%), 36.8% of females and 41% of males showed a clinical TMJ involvement. Mean age at onset (or diagnosis) of TMJ involvement was 8.3 yrs. 62/88 pts (70.5%) had a bilateral clinical signs of condylar alteration.
The involvement of TMJ was observed in 38.3% of the whole population (54.5% of oligoarthritis, 27.3% polyarthritis RF negative, 2.3% polyarthritis RF positive, 9.1% soJIA, 4.5% ERA and 2.3% juvenile psoriatic arthritis)
3 cases (2 females and 1 male) presented with an involvement of TMJ at the diagnosis of JIA.
The rate of TMJ involvement was higher in the pts with an early onset of the disease (52.3% in the 0-6 yrs group, vs 36.4% in 7-12 yrs group and 11.3% in 13-16 yrs group).
In 56/88 pts (63.3%) TMJ disease was associated with an involvement of large joints, in 4/88 (4.54%) with small joints, in 24/88 (27.7%) with hips and in 18/88 (20.45%) with cervical spine.
Conclusions: An early onset of JIA, the oligoarticular ILAR category and a pattern of large joints involvement seem correlated with a higher rate of TMJ disease. Predictive factors of TMJ involvement should be confirmed in a larger JIA population and may be useful for clinicians to adopt appropriate prevention strategies of TMJ disease
Drug survival and reasons for discontinuation of the first course of biological therapy in 363 juvenile idiopathic arthritis patients
No full textBackground: The introduction of TNF-blocking agents since 2000 has tremendously changed the treatment of JIA. From randomized controlled trials (RCTs) there is evidence that TNF-blocking agents are efficacious and safe, but data on their long-term expected and unexpected effects remain relatively scarce.
Objectives: To determine long-term effectiveness and safety of 1st biological treatment (BT) in a cohort of 363 Juvenile Idiopathic Arthritis (JIA) pts, non-responders to DMARDs, in terms of drug survival (continuation rate on therapy) and to identify the baseline predictors of treatment discontinuation.
Methods: Each JIA pt enrolled in BT is prospectively assessed at the start of treatment and then every 2 months for the evaluation of safety and efficacy according to ACR-Pedi core set criteria. All clinical charts of pts who started a BT between Nov'99 and Jul'10 have been reviewed. Survival analysis methods suitable for competing risks were used to study time to drug discontinuation due to disease control (defined according to Wallace criteria) or failure (adverse event [AE], lack of efficacy [LaE] or loss of efficacy [LoE].
Results: In total 750 different courses of BTs were administered to our 363 pts. In 287/363 pts a BT treatment is still ongoing, 147 pts maintain the 1st BT, 140 pts switched one or more times. 298 pts were included in the analysis for drug discontinuation. A median follow-up on treatment, before discontinuation due to every causes, was 53.7 months (range 0.45-124.45). One hundred and sixty-five pts discontinued BT: 27 due to disease control, 135 because of failure (78 AEs, 12 LaE and 45 LoE), 3 pts temporarily stopped for pregnancy. Among 135 pts who discontinued for failure, 117 switched to a 2nd BT. Among 27 pts who discontinued due to disease control, 13 pts restarted on BT for relapse of disease activity (10 pts restarted with the same BT, 3 switched to a different one). Predictors of discontinuation due to AE were female gender (p=0.1) and longer disease duration (p=0.02). Predictors of discontinuation due to LaE or LoE were systemic onset and polyarthritis FR positive (vs other JIA subtypes) (p<0.05) and use of mAb-anti-TNF (vs sTNFR) (p=0.02). Predictors of discontinuation due to inactive disease were male gender and shorter disease duration (p<0.05).
Conclusions: Although only few pts discontinued BT due to a complete and persistent disease control, the majority of them remained on BT for a long time, suggesting that in our cohort of JIA pts, affected by a severe long lasting refractory disease, BT was globally well tolerate and efficacious in controlling the disease.
References:
1. Gerloni V, Pontikaki I, Gattinara M, Fantini F. Focus on adverse events of tumour necrosis factor α blockade in juvenile idiopathic arthritis in an open monocentric long-term prospective study of 163 patients. Ann Rheum Dis 2008; 67: 1145-52.
2. Tynjälä P, Vähäsalo P, Honkanen V, Lahdenne P. Drug survival of the first and second course of anti-TNF agents in juvenile idiopathic arthritis. Ann Rheum Dis 2009; 68: 552-7
La expansión de la tutela resarcitoria en el Derecho italiano
No full textThe author shows us the expansion of the compensatory protection in Italian law, narrating some
very important events in the jurisprudence of his country. Thus, for example, he comments on the Meroni
case, in which it was assessed whether damages to credit rights, in other words, relative rights, could be compensated. Finally, he shows us the risks that arise in the event of an overflow of the compensatory protection,
as occurred with the birth of the so-called “existential damage”, a category that later had to be corrected by
the jurisprudence
Accelerated Atherosclerosis in Autoimmune Diseases
No full textAtherosclerosis (AS) is a chronic inflammatory disease of arterial vessels, leading to chronic and acute ischemic damage or hemorrhages in virtually any organ. Atherosclerotic plaque formation is the result of inflammatory processes that mediate lymphocyte and macrophage infiltration, lipid intra- and inter-cellular deposition, and eventually smooth muscle cell migration/proliferation and fibrosis. Adaptive and innate immune responses against exogenous as well as self-antigens cooperate in triggering such processes. The atherogenic processes may be magnified and accelerated in patients with autoimmune rheumatic diseases (AIRDs) because of the underlying immune abnormalities, the consequent systemic inflammation and the effects of some concomitant chronic therapies. As a matter of fact, accelerated AS is responsible for increased mortality and morbidity in almost all AIRDs, nowadays. Diagnostic strategies to detect early atherosclerotic lesions and to apply preventive therapeutical approaches have been proposed in order to avoid complications related to accelerated AS in AIRDs. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2008, 2024
Can ultrasound be useful in detection of inactive disease in patients affected by jia? An observational case-control study of 128 subjects
No full textBackground: Musculoskeletal Ultrasound (MSUS) is commonly used to detect synovial inflammation in adults affected by inflammatory rheumatisms. MSUS in children is nowadays still a challenge. For this reason MSUS in JIA is still seldom known and used by pediatric rheumatologists.
Objectives: To study if grey scale (GSUS) and Power Doppler Ultrasound (PDUS) can better identify subclinical synovitis than physical examination and could be added to Wallace criteria of inactive disease (ID) to better identify JIA patients (pts) on Clinical Remission (CR).
Methods: 100 consecutive pts with JIA (age 18mo-25yrs) according to ILAR classification, with ID according to Wallace criteria, and 28 healthy controls were submitted to the MSUS of 42 joints (MCPs, PIPs, wrists, elbows, shoulders, hips, knees, ankles and MTPs). MSUS was performed immediately after clinical evaluation, by 3 trained sonographers (ODL, VR, AS), blinded to clinical findings, who recorded synovial hyperplasia, joint effusion and PDUS. Apparatus used: GE Logiq P5 with an 8-12MHz linear probe and Esaote MyLab 70 with a 6-18MHz linear probe. Intraobserver and interobserver reproducibility of US was assessed. In each joint, synovial hyperplasia/joint effusion were graded as follows: 0=absent, 1=mild, 2=moderate and 3=marked. PDUS was graded as follows: 0=absent, 1=presence of single vessel dot, 2=presence of confluent vessel dots in less than half of the synovial area and 3=presence of confluent vessel dots in more than half of the synovial area. A joint with US synovitis was defined as a joint in which any of the 3 US abnormalities was detectable. PDUS was considered positive in the presence of vessel dots on PDUS images only out of growing cartilage and if it was not a bone nutrition vessel. The US examination technique as well as the definitions and scoring of US features were based on published guidelines provided by the OMERACT in adults.
Results: MSUS revealed the presence of 1 or more alterations of the synovial structures (effusion, hyperplasia or positive PDUS) in 23 out of 100 pts who satisfied the clinical criteria of ID according to Wallace definition (23%). 9 pts (39% out of 23 active pts & 9% out of all 100 pts) have only one joint involved. The other 14 pts (61% out of 23 active pts & 14% out of all 100 pts) presented US activity in more than one joint. 43 of the 4200 examined joints were active at US (1,02%). In 17 of these 43 joints (39%) US revealed joint effusion, hyperplasia and PDUS. In 29 joints (67%) there were only two of these US features. No abnormalities were found in healthy controls.
Conclusions: Our data confirm the usefulness of US in pediatric joint examination to identify active joints in JIA pts, to set up an appropriate treatment and to define inactive disease in a more accurate way than referring only to Wallace criteria. Further studies are needed to understand if these findings are related to a greater frequency of relapses
Trim17, novel E3 ubiquitin-ligase, initiates neuronal apoptosis
No full textAccumulating data indicate that the ubiquitin-proteasome system controls apoptosis by regulating the level and the function of key regulatory proteins. In this study, we identified Trim17, a member of the TRIM/RBCC protein family, as one of the critical E3 ubiquitin ligases involved in the control of neuronal apoptosis upstream of mitochondria. We show that expression of Trim17 is increased both at the mRNA and protein level in several in vitro models of transcription-dependent neuronal apoptosis. Expression of Trim17 is controlled by the PI3K/Akt/GSK3 pathway in cerebellar granule neurons (CGN). Moreover, the Trim17 protein is expressed in vivo, in apoptotic neurons that naturally die during post-natal cerebellar development. Overexpression of active Trim17 in primary CGN was sufficient to induce the intrinsic pathway of apoptosis in survival conditions. This pro-apoptotic effect was abolished in Bax(-/-) neurons and depended on the E3 activity of Trim17 conferred by its RING domain. Furthermore, knock-down of endogenous Trim17 and overexpression of dominant-negative mutants of Trim17 blocked trophic factor withdrawal-induced apoptosis both in CGN and in sympathetic neurons. Collectively, our data are the first to assign a cellular function to Trim17 by showing that its E3 activity is both necessary and sufficient for the initiation of neuronal apoptosis. Cell Death and Differentiation (2010) 17, 1928-1941; doi: 10.1038/cdd.2010.73; published online 18 June 201
THE BOREXINO IMPACT IN THE GLOBAL ANALYSIS OF NEUTRINO DATA
No full textThis thesis reports on work I carried out within the Borexino collaboration in the past three years. The main purpose of my work was to collect, analyze and understand the implications of the Borexino results in neutrino oscillation physics and in solar physics. We first studied the impact of each single piece of information coming from the
Borexino experiment in determining the allowed regions of the (tan(theta_12), D m2_21) space of parameters. Concerning the neutrino oscillations field, we combined the Borexino results with those obtained by the other solar experiment (Gallex/GNO, SAGE, Homestake, Super
Kamiokande, SNO) and we showed that, thanks to the Borexino inclusion, the LOW region of MSW regime is, for the first time, strongly disfavored by solar neutrino data alone.
For what concerns solar Physics, in order to study the Standard Solar Model parameters and to look deeper into the low/high metallicity controversy, we left Phi(7Be) and Phi(8B) as free parameters of the fit. Under the luminosity constraint, we showed how, at present, solar neutrino data cannot discriminate between the low/high metallicity hypothesis in the standard solar model
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