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Background Levodopa-carbidopa intestinal gel infusion (LCIG) is a therapeutic option for advanced Parkinson disease (PD) patients with troublesome motor complications, unresponsive to conventional oral treatment. There is some evidence to suggest that the genetic background may influence the clinical presentation and rate of progression of PD. Whether the genetic background influences the outcome of device-assisted therapies is currently debated. Some studies have investigated the effectiveness of deep brain stimulation (DBS) in PD patients with different genetic background, while evidence is lacking regarding LCIG. Methods A cohort of LCIG patients underwent genetic testing. The motor and neuropsychological outcomes of LCIG were retrospectively analyzed. Results Fifty-six patients were analyzed, nine of them (15%) had at least one mutation/variant in a PD-associated gene: five GBA1, two SNCA, one LRRK2, one PRKN; 13 (23%) carried the BDNF Val66Met polymorphism. The mean duration of follow-up was 4.9 ± 2.6 years. There were no significant differences in motor or neuropsychological outcomes between patients with and without these gene mutations/variants. No cognitive worsening was observed at follow-up among GBA-PD patients, and they responded well to LCIG in terms of motor symptoms. Conclusions Overall, we observed a significant benefit in terms of motor complications in our cohort, including patients carrying genetic mutations/variants. Due to the small sample and limited number of patients carrying genetic mutations/variants, no definitive conclusions can be drawn yet on the genotype impact on LCIG outcome. A careful selection of patients, regardless of the genetic background, is pivotal for an optimal outcome of LCIG.

Patients with Systemic lupus erythematosus (SLE) experience musculoskeletal involvement in up to 90% of cases. Clinical presentation includes arthralgia, non-erosive arthritis, erosive arthritis and Jaccoud's arthropathy [1]. Recently, thanks to the use of ultrasound (US), several studies have demonstrated the presence of a subclinical joint and peri-articular inflammatory state, especially in patients with non-specific symptoms [2]. However, studies involved a small number of patients and there is a lack of predictive factors of disease progression to more aggressive forms as well of specific and validated clinimetric indices in patients with SLE. To evaluate joint and peri-articular involvement in SLE patients with different patter of musculoskeletal involvement by US. To evaluate the strength of the clinimetric indices already validated in other rheumatologic diseases (DAS28, CDAI, SDAI) in patients with SLE. To analyse the predictive value of laboratory data (autoantibody profile, complement levels, acute phase reactants) in joint involvement. Consecutive SLE patients (18-65 years old), who fulfilled the EULAR/ACR 2019 criteria, were enrolled: 20 without symptomatic musculoskeletal involvement (Group 1) 19 with arthralgias without structural joint alterations (Group 2), 11 patients with estabilshed musculoskeletal involvement (Group 3). All patients undergo ultrasound evaluation with Esaote MyLab70 device with a 6-18 mmHz linear probe; wrists, metacarpophalangeal and proximal interphalangea joints, all finger flexors, wrist extensors and flexors at the hands, elbows, long head of the biceps and Achilles tendon were evaluated. All abnormalities were defined according to OMERACT EULAR Score System. [9]. DAS28 CDAI and SDAI and the most recent blood tests (ANA ENA FR anti CCP anti DNA ESR CRP C3 C4) were recorded; hands and wrists X-ray were performed according to good clinical practice. Fifty females were enrolled. Clinical characteristics during the disease course and serological and clinimeric scores at the time of enrollement are reported in Table 1. Group 1: US detected synovitis (grade 1–3) in 7 (35%) patients, mainly wrists and hands, Group 2: US detected synovitis (grade 1–3) in 5 (26.3%) patients mainly hands, elbows and wrists. Group 3: US detected synovitis (grade 1–3) in 7 (63.7%) patients, mainly knees elbows Achilles tendon, hands. Our study confirmed that the musculoskeletal involvement in SLE is underestimated. Although not statistically significant, the groups showed differences in synovitis involvement. The percentage of asymptomatic patients with ultrasound signs of synovitis, especially of the hands and wrists, is higher than expected and almost comparable with symptomatic arthralgia patients. No association with clinimetric and laboratory tests were highlighted. As expected, the group of patients with known arthritis more frequently had ultrasonographic changes and signs of systemic disease activity.Our study suggests how necessary and interesting it is to prospectively evaluate in the future how the joint disease will progress in asymptomatic patients, and who will develop, for example, bone erosions or Jaccoud's arthropathy. [1]Ball EM, Bell AL. Rheumatology (Oxford) 2012; 51: 771–779 [2]Piga M et al. Semin Arthritis Rheum 2016; 46: 217–224. NIL. None Declared. Table 1clinical characteristics of patients and disease activity at the time of observationGROUP 1GROUP 2GROUP 3AGE (yr, median)42,240,4847,2AGE AT DIAGNOSIS (yr, median)29,622,329,4DISEASE DURATION (months, mean)150,3217,5218,2MUCOCUTANEOUS involvement % (EVER)605055NEPHRITIS % (EVER)403545NPSLE involvement % (EVER)251020SEROSITIS% (EVER)201510HAEMATOLOGICAL involvement % (EVER)506055CONSTITUTIONAL involvement % (EVER)507065Disease activity at at the time of USpositive anti dsDNA %404070LOW C3/C4 %45/5550/4565/70SLEDAI median2.631.534.86DAS28 mean1.531.572.24SDAI mean1.213.7411.37CDAI mean13.476.55CPR (mg/dl) mean0.322.054.75

BackgroundAlthough several studies report a high incidence of pulmonary manifestations in SLE, lung involvement is often underestimated in SLE clinical assessment [1]. This is also mirrored by the absence of pulmonary manifestations other than pleurisy in the old and new classification criteria for SLE [2]. Moreover, limited evidence on the management of SLE-related pulmonary manifestations is available.ObjectivesTo assess prevalence and clinical impact of the spectrum of SLE-related pulmonary manifestations and their association with patient autoantibody profiles in a large SLE cohort and to describe the effectiveness of different therapeutic approaches in distinct clinical settings.MethodsPatients followed at the Lupus Clinics of ASST G. Pini-CTO and San Raffaele Hospital (Milan, Italy) were enrolled. Data regarding demographics, disease characteristics, autoantibody profile, pulmonary manifestations, damage accrual and treatment were collected. The following types of lung involvement were recorded: pleurisy, acute lupus pneumonitis, interstitial lung disease (ILD), alveolar haemorrhage, pulmonary embolism, arterial pulmonary hypertension and shrinking lung syndrome.ResultsOf the 471 SLE patients enrolled, we identified 78 patients (16.5%) displaying at least one pulmonary manifestation. Epidemiological data on each manifestation are reported in Table 1. Pleurisy was the most common pulmonary manifestations and manifested at disease onset in most cases (56%).Patient home environment (urban vs countryside) did not seem to impact the risk of developing lung disease. Damage accrual was relevant, as 2/3 of patients displayed at least 1 point increase in SLICC Damage Index (SDI) after the onset of lung involvement in comparison to baseline. All patients received at least one steroid course. Immunosuppressive treatment choices and efficacy differed among distinct manifestations: only half of the patients with pleurisy received immunosuppression, mainly azathioprine, with 100% of improvement, while 80% of cases of ILD received immunosuppression, predominantly mycophenolate, with a 50% risk of non-response.By comparing demographics and clinical characteristics among cases and controls, we found a significantly lower median age at disease onset (p=0.002) and a higher frequency of male sex (18% vs 9%; p=0.07), joint involvement (p=0.02) and constitutional symptoms (p=0.02) in patients with lung involvement, while no differences were observed in the autoantibody profile, including anti-dsDNA and anti-ENA autoantibodies.ConclusionOur study confirms that, in addition to the known epidemiological burden of pleurisy, other types of pulmonary involvement can complicate the disease course and contribute to damage accrual. In particular, ILD can frequently occur and respond to immunosuppressants in only half cases. Consistent with the association of lung involvement with increased morbidity, higher-risk categories for severe disease such as males and subjects with early-onset SLE were more represented among patients with pulmonary manifestations.References[1] Amarnani R, et al. Front. Med. 2021; 7:610257.[2] Aringer M, et al. Ann Rheum Dis. 2019; 78:1151-1159.[3] Smith EMD, Clin Immunol. 2019; 209:108274.[4] Ryu S, et al. Lupus Sci Med. 2017;):e000221.Table 1.Demographic and disease characteristics of SLE patients with lung involvementDemographics and clinical characteristicsFemales, n (%)65 (83)Age at diagnosis (years): median (IQR)29 (22 – 39)Disease duration (years): mean ±DS19 ± 12Subjects with >0 and >1 point SDI increase from baseline: n (%)48 (61.5); 26 (33)Lung involvementN (%)immunosuppressive therapy, %Pleurisy61 (78)49Acute pneumonitis4 (5)100ILD15 (19)80PAH6 (8)50Pulmonary embolism4 (5)50Shrinking lung1 (1)100Alveolar hemorrage4 (5)100Acknowledgements:NIL.Disclosure of InterestsMaria Gerosa: None declared, Giuseppe Alvise Ramirez: None declared, Lorenza Maria Argolini: None declared, Isabella Scotti: None declared, Carolina Artusi: None declared, Luca Moroni: None declared, Enrica Bozzolo: None declared, Maria Rosa Pellico: None declared, Ludovica Cavallo: None declared, Lorenzo Dagna: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, and UCB,

Objectives Few clinical trials reported the comparative short-term efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) versus medical therapy in advanced Parkinson's disease (PD). However, the comparative efficacy, safety and the potential disease-modifying effect of these treatments have not been investigated over a longer follow-up period. Methods In this study, we organised a ‘retrospective control group’ to compare medical and surgical therapies over a long-term period. We assessed a group of PD patients suitable for STN-DBS but successively treated with medical therapies for reasons not related to PD, and a group of similar consecutive STN-DBS patients. We thus obtained two groups comparable at baseline, which were re-evaluated after an average follow-up of 6 years (range 4–11). Results Patients treated with STN-DBS showed a long-lasting superior clinical efficacy on motor fluctuations, with a significant reduction in the average percentage of the waking day spent in ‘OFF’ and in the duration and disability of dyskinesia. Moreover, operated patients showed a better outcome in the activities of daily living in ‘Medication-OFF’ condition. On the other hand, a similar progression of motor score and cognitive/behavioural alterations was observed between the two groups, apart from phonemic verbal fluency, which significantly worsened in STN-DBS patients. Conclusions To our knowledge, this is the first long-term comparison between medical and surgical therapies; a superior efficacy of STN-DBS was observed on motor disability, while no significant differences were observed in the progression of motor symptoms and, apart from phonemic verbal fluency, of neuropsychological alterations.

BackgroundThrombosis of arteries in the central nervous system (CNS) represents the most frequent CNS manifestation and the most frequent arterial event in antiphospholipid syndrome (APS). Previous in vivo studies demonstrated that beta2 glycoprotein I (β2GPI) - the main antigenic target for anti-phospholipid antibodies (aPL) - does not localize in brain in resting conditions. However, β2GPI is detectable on the brain vascular endothelium in association with IgG and complement elements in immunized mice treated with lipopolysaccharide. These data suggest that after an appropriate second hit, β2GPI can play a critical role of in APS CNS damage, likely interacting with the complement system. To date, the pathophysiological functions of β2GPI in brain ischemic injury have not been investigated.ObjectivesTo investigate the presence and the distribution of the activated form of β2GPI in the ischemic brain at different time points.MethodsEleven-week old male mice underwent focal cerebral ischemia induced by 60' transient middlecerebral artery occlusion (tMCAo), or sham-operation. Mice were sacrified at 90', 6h, 24h, 48h, 4d or 7d after tMCAo to obtain brains and plasma. The presence and time course of β2GPI deposition within the ischemic territory and its spatial distribution relative to blood vessels and brain cells were defined the by post mortem immunofluorescence and confocal microscopy. The activated β2GPI was detected by anti-beta2 glycoprotein I minibody (MBB2) – a human monoclonal IgG antibody targeting β2GPI domain I.Resultsβ2GPI was present in the ischemic brain tissue starting from 90' after ischemic onset and was still detectable at 7d. β2GPI localized within blood vessels and in brain parenchyma at all times. Notably, at 24h β2GPI was mainly extravascular and colocalized with neurons (NeuN positive cells). Sham-operated mice showed only a faint signal for β2GPI.Conclusionsβ2GPI is present in its activated conformation in the brain vessels and tissue after experimental cerebral ischemia. It localizes on neurons in brain ischemic areas. These data suggest that an ischemic/inflammatory hit may up-regulate β2GPI tissue presence and may expose the N-terminal domain I of the molecule which is thougth to be the main target for pathogenic aPL.Disclosure of InterestNone declared

Background Systemic sclerosis (SSc) is an autoimmune condition characterized by polymorphic clinical presentations, high morbidity and mortality. It would be therefore valuable to identify biomarkers for diagnosis, prediction of organ involvement and disease subset. Objectives Aim of this study was to retrospectively assess the role of serum anti-IFI16 antibodies and NT-proBNP levels as candidate biomarkers in a cohort of scleroderma patients. Methods 100 SSc patients (49 with diffuse disease) were enrolled in this study; patients with PAH and renal insufficiency were excluded from NT-proBNP analysis. We investigated the relationship between the two candidate biomarkers and several scleroderma clinical manifestations (severe interstitial lung disease, cardiac involvement, digital ulcers, calcinosis, arthritis) and variables (age, disease duration, BP, Hb, mRSS, ESR, DLCO). Serum anti-IFI16 antibodies were detected by a home-made semi-quantitative ELISA, NT-proBNP levels were measured by the Roche immunoassay. Statistical analysis was performed using STATA 11. Results NT-proBNP was significantly increased in patients with heart involvement compared to those without (p=0.0003, 95%CI 57-232). A cut-off value of 130pg/mL gave a specificity of 70% and a sensibility of 74% to predict cardiac involvement (area under ROC curve 0.746; 95%CI 0.63-0.86), with a predictive negative value of 85%. Moreover, NT-proBNP levels>130pg/mL were strong predictors of heart involvement (OR 7). Not surprisingly, NT-proBNP levels were negatively correlated with LVEF (r=-0.266; p=0.002). Conversely, there was no association between anti-IFI16 antibodies and cardiac involvement (p=0.505). No other association was reported between the two candidate biomarkers and clinical manifestations of SSc. There was no significant difference between disease subsets in NT-proBNP levels (p=0.12) and anti-IFI16 antibodies titers (p=0.71). We report a significant association between NT-proBNP and age (r=0.315; p=0.003), disease duration (r=0.287; p=0.008), ESR (p=0.0086) and DLCO (r=-0.356; p=0.001) while anti-IFI16 antibodies were not significantly associated with any of the clinical variables. Conclusions Given the high negative predictive value, NT-proBNP may be a useful tool to identify scleroderma heart disease. SSc related cardiac involvement still heralds a poor prognosis, with 1% of annual mortality attributable to cardiac disease. Future studies are warranted to establish its role as surrogate biomarker. Disclosure of Interest None Declared

Dysbiosis has been described in systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), Sjögren’s syndrome (SjS), and primary anti-phosholipid syndrome (PAPS), however the biological implications of these associations are often elusive. Stool and plasma samples from 114 subjects, including in SLE (n = 27), SjS (n = 23), PAPs (n = 11) and undifferentiated connective tissue (UCTD, n = 26) patients, and geographically-matched healthy controls (HCs, n = 27), were collected for microbiome (16s rRNA gene sequencing) and metabolome (high-performance liquid chromatography coupled to mass spectrometry) analysis to identify shared characteristics across diseases. Out of 130 identified microbial genera, a subset of 29 bacteria was able to differentiate study groups (area under receiver operating characteristics (AUROC) = 0.730 ± 0.025). A fair classification was obtained with a subset of 41 metabolic peaks out of 254 (AUROC = 0.748 ± 0.021). In both models, HCs were well separated from SADs, while UCTD largely overlapped with the other diseases. In all of the SADs pro-tolerogenic bacteria were reduced, while pathobiont genera were increased. Metabolic alterations included two clusters comprised of: (a) members of the acylcarnitine family, positively correlating with a Prevotella-enriched cluster and negatively correlating with a butyrate-producing bacteria-enriched cluster; and (b) phospholipids, negatively correlating with butyrate-producing bacteria. These findings demonstrate a strong interaction between intestinal microbiota and metabolic function in patients with SADs.

We present FoG-STAR, a dataset collected using wearable sensors, designed to support the development and evaluation of algorithms for detecting and characterizing freezing of gait (FoG) in people with Parkinson’s disease (PD). The dataset includes recordings from 22 participants who performed a series of standardized motor tasks while wearing four inertial measurement units (IMUs) on the ankles, wrist, and lower back. Each IMU recorded tri-axial accelerometer and gyroscope data. Participants completed seven structured tasks, including walking with/without cognitive/motor dual-tasks, 360-degree turning, and the timed-up-and-go test, which comprises six types of activities (sitting, standing, sit-to-stand, stand-to-sit, walking, and turning). The dataset features detailed annotations from two expert clinical raters, who marked the onset and offset of 101 FoG episodes, and labelled specific FoG manifestations. In addition, the duration of each activity and task segment was annotated. This multi-level annotation framework allows for studying FoG in the context of dynamic motor behavior and provides a valuable resource for the development of machine learning models aimed at FoG detection, severity assessment, and activity recognition in PD.