POS1344 EVALUATING THE MULTIVISCERAL INVOLVEMENT ON ADULT-ONSET STILL'S DISEASE TO RETRIEVE IMAGING-BASED DIFFERENCES IN PATIENTS WITH AND WITHOUT MACROPHAGE ACTIVATION SYNDROME; RESULTS FROM A SINGLE-CENTRE OBSERVATIONAL STUDY

Background:Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder usually affecting young adults, burdened by life-threatening complications, mainly macrophage activation syndrome (MAS), a secondary form of hemophagocytic lymphohistiocytosis [1]. In this context, the importance of an accurate assessment of AOSD is suggested to promptly recognise the multivisceral involvement of the disease which is associated with life-threatening complications. The assessment of the most aggressive subsets of the disease could guide the clinicians when to apply additional resources but avoiding unnecessary expenditures in patients with a less severe clinical picture.Objectives:In this study, we aimed at describing the multivisceral involvement of the disease to retrieve imaging-based differences in AOSD patients with and without MAS.Methods:The present evaluation has been designed as a cross-sectional study to descriptively compare the multivisceral involvement in AOSD patients with and without MAS. Patients admitted to our Institution, who underwent a total body CT scan, were selected from our historical cohort and assessed. Clinical and CT scan characteristics of AOSD patients with and without MAS were compared. Clinical and CT scan characteristics of AOSD patients with and without MAS were analysed by parametric or non-parametric t tests for all continuous variables, and chi squared test was used for categorical ones, as appropriate. Furthermore, possible correlations among radiological outcomes with laboratory markers and systemic score were estimated by using a point-biserial coefficient correlation.Results:This study evaluated 39 AOSD patients (men 64.1%), mean age of 48.8±16.6 years). Out of those, 14 patients (35.9%) were complicated by MAS. These patients showed higher values of ferritin [AOSD: 770.0 (1306.5) ng/mL vs MAS: 2926.3 (4918.5) ng/mL p=0.003] and systemic score (AOSD: 4.6±1.4 vs MAS: 6.9±1.7, p<0.0001). AOSD patients with MAS presented a higher prevalence of lung disease than others (AOSD: 56.0% vs MAS 85.7% p=0.048). Lung disease correlated with the systemic score (coefficient 0.491, p=0.003). AOSD patients with MAS were more frequently characterised by hepatomegaly (AOSD: 12.0% vs MAS: 50.0% p=0.019) and splenomegaly (AOSD: 16.0% vs MAS 50.0% p=0.033), respectively, than others. Hepatomegaly correlated with CRP (coefficient 0.421, p=0.016), ferritin (coefficient 0.397, p=0.020), and systemic score (coefficient 0.391, p=0.022). Furthermore, the presence of splenomegaly correlated with the systemic score (coefficient 0.439, p=0.009). CT scan features of abdominal effusions were more frequently observed in AOSD patients with MAS than those without this complication (AOSD: 12.0% vs 57.1% p=0.007). Finally, a higher percentage of AOSD patients with MAS showed a significant lymph node enlargement, either mediastinal or abdominal, than others on CT scan (AOSD: 36.0% vs MAS 71.4% p=0.048). The presence of lymphadenomegaly correlated with the systemic score (coefficient 0.368, p=0.032).Conclusion:Our findings showed a higher prevalence of multiorgan involvement in AOSD patients with MAS, suggesting imaging-based differences, although other studies are needed to fully assess this issue. Pulmonary disease, hepatomegaly, splenomegaly, lymph nodes enlargement, and abdominal effusions were associated with these more aggressive patients.References:[1]Giacomelli R, Ruscitti P, Shoenfeld Y. A comprehensive review on adult onset Still's disease. J Autoimmun. 2018 Sep;93:24-36.Disclosure of Interests:None declare

The joint involvement in adult onset Still's disease is characterised by a peculiar magnetic resonance imaging and a specific transcriptomic profile

Adult onset Still's disease (AOSD) is a rare systemic autoinflammatory disease, characterised by fever, arthritis, and skin rash, and joint involvement is one of its clinical manifestations. The aims of this work were to assess joint involvement, to describe main patterns of involvement, and associated clinical characteristics. In this work, we aimed at assessing the joint involvement in AOSD by using MRI, to describe main patterns and associated clinical characteristics. In addition, we aimed at assessing the global transcriptomic profile of synovial tissues in AOSD to elucidate possible pathogenic pathways involved. We also evaluated the global transcriptomic profile of synovial tissues to elucidate possible pathogenic pathways involved in the disease. Thus, AOSD patients, who underwent to MRI exam on joints, were assessed to describe patterns of joint involvement and associated clinical characteristics. Some synovial tissues were collected for RNA-sequencing purposes. The most common MRI finding was the presence of synovitis on 60.5%, mainly in peripheral affected joints, with low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. Bone oedema and MRI-bone erosions were reported on 34.9% and 25.6% MRI exams, respectively. Patients with MRI-bone erosions showed a higher prevalence of splenomegaly, a more frequent chronic disease course, lower levels of erythrocyte sedimentation rate, and ferritin. In AOSD synovial tissues, a hyper-expression of interleukin (IL)-1, IL-6, and TNF pathways was shown together with ferritin genes. In conclusion, in AOSD patients, the most common MRI-finding was the presence of synovitis, characterised by intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. MRI-bone erosions and bone oedema were also observed. In AOSD synovial tissues, IL-1, IL-6, and TNF pathways together with ferritin genes resulted to be hyper-expressed

Tendon Fascicle-Inspired Nanofibrous Scaffold of Polylactic acid/Collagen with Enhanced 3D-Structure and Biomechanical Properties

Surgical treatment of tendon lesions still yields unsatisfactory clinical outcomes. The use of bioresorbable scaffolds represents a way forward to improve tissue repair. Scaffolds for tendon reconstruction should have a structure mimicking that of the natural tendon, while providing adequate mechanical strength and stiffness. In this paper, electrospun nanofibers of two crosslinked PLLA/Collagen blends (PLLA/Coll-75/25, PLLA/Coll-50/50) were developed and then wrapped in bundles, where the nanofibers are predominantly aligned along the bundles. Bundle morphology was assessed via SEM and high-resolution x-ray computed tomography (XCT). The 0.4-micron resolution in XCT demonstrated a biomimetic morphology of the bundles for all compositions, with a predominant nanofiber alignment and some scatter (50-60% were within 12° from the axis of the bundle), similar to the tendon microstructure. Human fibroblasts seeded on the bundles had increased metabolic activity from day 7 to day 21 of culture. The stiffness, strength and toughness of the bundles are comparable to tendon fascicles, both in the as-spun condition and after crosslinking, with moderate loss of mechanical properties after ageing in PBS (7 and 14 days). PLLA/Coll-75/25 has more desirable mechanical properties such as stiffness and ductility, compared to the PLLA/Coll-50/50. This study confirms the potential to bioengineer tendon fascicles with enhanced 3D structure and biomechanical properties

The impact of handling technique and handling frequency on laboratory mouse welfare is sex-specific

Handling is a well-known source of stress to laboratory animals and can affect variability of results and even compromise animal welfare. The conventional tail handling in mice has been shown to induce aversion and anxiety-like behaviour. Recent findings demonstrate that the use of alternative handling techniques, e.g. tunnel handling, can mitigate negative handling-induced effects. Here, we show that technique and frequency of handling influence affective behaviour and stress hormone release of subjects in a sex-dependent manner. While frequent tail handling led to a reduction of wellbeing-associated burrowing and increased despair-like behaviour in male mice, females seemed unaffected. Instead, they displayed a stress response to a low handling frequency, which was not detectable in males. This could suggest that in terms of refinement, the impact in handling could differ between the sexes. Independently from this observation, both sexes preferred to interact with the tunnel. Mice generally explored the tunnel more often than the tail-handling hands of the experimenter and showed more positively rated approaches, e.g. touching or climbing, and at the same time, less defensive burrowing, indicating a strong preference for the tunnel