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BackgroundLow medication adherence is a well known issue in the management of patients with systemic autoimmune diseases (SAD), little however is known on adherence to medication during pregnancy, especially in these patients with high risk pregnancies.ObjectivesThis study is aimed at evaluating the level of adherence to medication in pregnant patients with SAD in comparison with non-pregnant patients with SAD, and at identifying determinants of low adherence.MethodsPregnant and non-pregnant patients with an established diagnosis of SAD were consecutively enrolled. Pregnant patients were included in a tight monitoring protocol for high risk pregnancies, and treatments were checked every month. The following data were collected at enrolment: epidemiological and demographic characteristics, disease duration and type of medications. Each patient completed the following anonymous questionnaires: the 8-item Morisky Medication Adherence Scale (MMAS-8) and Hospital Anxiety and Depression Scale (HADS) to assess the presence of anxiety and depression. With regard to MMAS-8, we assessed adherence to hydroxychloroquine (HCQ) and to other disease modifying antirheumatic drugs (DMARDs) separately. We considered a score ≥ 6 as indicator of good adherence. Vitamins and dietary supplements were not considered.ResultsA total of 80 pregnant women and 72 non-pregnant women were enrolled. Clinical data and results of the questionnaires are summarized in Table 1.Table 1.Characteristics of the cohortPregnant patients N=80Non-pregnant patients N=72P valueAge at study entry (years, mean ±SD)35.8±4.340.1±12.20.001Disease duration (years, mean ±SD)8.5±6.68.6±9.1n.sNumber of tablets/day (mean ±SD)4.3±1.64.1±1.8n.sNumber of assumption/day (mean ±SD)1.4±0.61.6±0.8n.sScore MMAS for HCQ (mean ±SD)6.99±0.26.38±0.20.039Score MMAS for other DMARDs (mean ±SD)6.99±0.36.39±0.20.018Patients with good adherence to HCQ (%)38/50 (76.0%)34/59 (57.6%)0.044Patients with good adherence to medications (%)53/71 (74.6%)37/60 (61.7%)n.sPatients with low adherence to HCQ (%)12/50 (24%)25/59 (42.4%)0.044Patients with low adherence to medications (%)18/71 (25.4%)23/60 (38.3%)n.sAnxiety (%)20 (25%)30 (41.7%)0.029Depression (%)11 (13.7%)19 (26.4%)0.051MMAS-8 score was significantly higher in pregnant women both for HCQ (p=0.039) and other DMARDs (p=0.018), as well as the rate of patients with good medication adherence for HCQ (76.0% vs 57.6%, p=0.044). The rate of patients with good medication adherence for other DMARDs was higher in pregnant patients (74.6% vs 61.7%) but this different was not statistically different.Demographic and clinical characteristics and the number of therapies received didn’t seem to influence treatment adherence. Fifty patients (32.8%) suffered from anxiety, and this disorder was a significant determinant of low medication adherence in all groups. Conversely, depression didn’t seem to have an impact on adherence on neither group.ConclusionOverall, pregnant patients with SAD had a good adherence to prescribed medication; nevertheless, 25% of patients didn’t take therapies adequately despite being closely monitored in a dedicated clinic for high risk pregnancies and an adequate pregnancy counselling; anxiety seems to be one determinant of low medications adherence both in pregnant and non-pregnant women.Disclosure of InterestsNone declared

BackgroundGlucocorticoids (GC) are a cornerstone for the treatment of Systemic Lupus Erythematosus (SLE) manifestations but there is still open debate concerning their optimal therapeutic employment.ObjectivesTo describe and compare the GC therapeutic strategies used in a real-life setting for the initial treatment of SLE flares.MethodsThis study is a retrospective analysis of data from a monocentric cohort of SLE patients who registered a disease flare between 2015 and 2020. Flares were first categorized in “pulse-treated” (PT) and “non pulse-treated” (NPT). PT flares were then divided into “low-dose regimen” (250 mg iv 6MP for 3 consecutive days or less) and “high-dose regimen” (more than 250 mg iv 6MP for 3 days). GC daily and cumulative 6MP doses, rate of remission and relapse were evaluated at 3, 6 and 12 months.Results101 flares were analyzed (30 PT and 71 NPT). PT flares were more severe in terms of median SLEDAI (PT 16(12-22) vs NPT 8(5-10) p=0,00) and BILAG score index (BILAG A PT 71% vs NPT 30% p=0,001). PT patients received significantly higher GC doses at 1 month (PT median cumulative dose 1372 IQR 1028 – 3076 mg of 6MP vs NPT median 160 IQR 120-288 mg of 6MP, p=0,000), 6 months (PT median cumulative dose 2964 IQR 2294 – 4305 mg of 6MP vs NPT 880 IQR 720 – 1284 mg of 6MP, p=0,000) and 12 months (PT median cumulative dose 3510 IQR 3014-5025 vs NPT median cumulative dose 1571 IQR 1098 – 2122 mg of 6MP, p=0,000). Characteristics of flares that were treated with low-dose (N=19) or high-dose (N=11) pulse regimen are summarized in Table 1. As expected, the “low-dose regimen” subgroup received lower cumulative GC dosage over time. However, no statistically significant differences were found neither in term of disease severity at baseline nor in term of disease activity, remission rates or new flares over time.Table 1.Comparison between low-dose pulse regimen and high-dose pulse regimen in terms of cumulative GC dose and outcome in the first year after a SLE flareMedian GC doses (6MP)Low-dose regimenN=19 (63,33%)High-dose regimenN=11 (36,67%)P value Median SLEDAI16 (12 -20)18 (8-24)0,6186BILAG score (A, B, C)A=14, B=4, C=1A=10, B=1, C=00,488Cum. dose 1 mo1350 (1028 – 1534)1752 (960 – 2356)0,126Cum. dose 3 mos1858 (1604 – 2463)2784 (2184 – 3240)0,040Cum. dose 6 mos2450 (2218 – 3586)3456 (2906 – 4380)0,029Cumulative doses 12 mos3150 (2851 - 4448)4246 (3591 – 5772)0,011Remission 3 mos no – (%)2 (10%)0 (0%)0,265Remission 6 mos no – (%)8 (42%)1 (9%)0,057Remission 12 mos no – (%)12 (63%)5 (45%)0,346Median SLEDAI 3 mos4 (2 – 9)9 (4 – 12)0,138Median SLEDAI 6 mos3 (0 - 4)4 (0 – 9)0,154Median SLEDAI 12 mos2 (0 – 5)2 (0 – 12)0,363New flares 6 mos no – (%)2 (10%)1 (9%)0,900New flares 12 mos no – (%)2 (10%)2 (18%)0,552GC=glucocorticoids, 6MP=6-methylprednisolone, no=number, Cum.=cumulative, mos=monthsConclusionThese data suggest that in a real-life setting, pulse GC therapy is preferred over oral administration for severe SLE flares and entails administration of high cumulative doses of GC. However, the experience outlined suggests that the low-dose pulse regimen is as effective in remission induction of severe flares as the high-dose regimen, allowing significant GC sparing. Since the cumulative GC dose is a known strong predictor of organ damage, strategies aimed to minimize the GC dosage should be encouraged.Disclosure of InterestsNone declared

BackgroundAntiphospholipid Syndrome (APS) is a rare autoimmune disease characterized by thrombotic events and/or pregnancy morbidities in the presence of confirmed positivity for antiphospholipid antibodies (aPL). Complement was demonstrated to be involved in aPL-related pregnancy loss in animal models and several groups investigated the significance of complement levels in human disease. C3 and C4 serum levels were assessed in several cohorts of pregnant patients with APS and/or aPL positivity in order to relate complement consumption with adverse pregnancy outcome (APO).According to some authors, hydroxychloroquine (HCQ) can control the activation of the complement system, improve pregnancy outcome and reduce aPL title.ObjectivesThis study was designed to verify the effect of HCQ in addition to low dose aspirin (LDA) + low molecular weight heparin (LMWH) treatment in a multicenter cohort of primary APS (PAPS) and aPL carriers pregnant women and the possible correlation with preconception serum C3/C4 levels.MethodsMedical records of pregnant women with confirmed positivity for aPL antibodies attending twelve referral centers from January 2010 to December 2020 were retrospectively evaluated. We considered as aPL-related APO: spontaneous abortions (ResultsWe have analyzed 164 singleton PAPS/aPL carrier pregnancies (22 aPL carriers - 13%) in 128 patients: all were treated with combination therapy (LDA+LMWH), and in 30 HCQ was added. 58 pregnancies (43%) had low levels of preconception C3/C4. A triple aPL positivity was observed in 54 pregnancies, 14 of them were treated with combination therapy + HCQ. When considering the whole cohort, the addition of HCQ had not significantly improved the gestational outcome. Further stratification was performed on the basis of complement consumption. In the group of patients with preconception low C3/C4 levels the addition of HCQ had not significantly improved pregnancy outcome. We have lastly evaluated 40 pregnancies with a high-risk profile (triple aPL positivity and complement consumption), in which we have found that HCQ significantly improved gestational outcome (p=0.018, Table 1).Table 1.Relationship between APO, therapy during pregnancy and risk profile.All pregnancies (n=164)Reduced C3/C4 (n=58)Triple aPL+ and reduced C3/C4 (n=40)LDA+LMWH (n, %)LDA+LMWH+HCQ (n, %)pLDA+LMWH (n, %)LDA+LMWH+HCQpLDA+LMWHLDA+LMWH+HCQp(n, %)(n, %)(n, %)APO62 (46%)16 (53%)ns32 (68%)4 (36%)ns23 (77%)3 (30%)0.018No APO72 (54%)14 (47%)15 (32%)7 (64%)7 (23%)7 (70%)Total1343047113010This observation could not be confirmed in patients with single or double aPL positivity.ConclusionThe study shows that administering HCQ in addition to combination therapy can improve gestational outcome in aPL/PAPS high-risk patients. This observation confirms that HCQ exerts a beneficial effect on aPL pregnancies by complement inhibition as it was shown in animal models. In addition, our results provide the clinicians a useful tool to implement conventional treatment in patients at high risk of pregnancy complication or loss.References[1]De Carolis S, et al. Is there any role for the hydroxychloroquine (HCQ) in refractory obstetrical antiphospholipid syndrome (APS) treatment? Autoimmun Rev 2015;14:760-2.[2]Mekinian A, et al. The efficacy of hydroxychloroquine for obstetrical outcome in antiphospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev 2015;40:498-502.[3]Mekinian A et al. Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome? Autoimmun Rev 2015;14:23-9.Disclosure of InterestsNone declared

BackgroundSystemic lupus erythematosus (SLE) is a heterogeneous disease which can affect various organs and is characterized by different clinical phenotypes. While the treatment of renal involvement is quite standardized, the therapeutic approach to extra-renal manifestations is subjected to a degree of variability.Objectives1. To describe extra-renal disease flares in terms of clinical phenotype and outcomes in SLE patients 2. To compare data from a real-life setting with a machine learning (ML) approach.MethodsThis study is a retrospective analysis of data from a monocentric cohort of SLE patients who experienced a disease flare between 2015 and 2020. Each flare was followed for one year and was classified according to the organ involvement and categorized according to the BILAG definition of flare. At baseline and at 3,6,12 months the following variables were collected: disease activity (SELENA-SLEDAI score), ongoing therapy and disease state (DORIA definition of remission). Demographic data and previous organ involvement were retrieved from clinical charts. Flares’ features at baseline and during follow up were analyzed in terms of explained variance across the dataset’s Principal Components and clustered with a hierarchical unsupervised learning approach. A ML model based on neural networks was built to early detect flares’ therapeutic difficulty: it was validated after data augmentation to satisfy statistical requirements during the training phase.Results66 extra-renal flares were investigated (Table 1); 5 flares (7.5%) were treated with glucocorticoid (GC) pulses and 61 (92.5%) with oral GC therapy, while an immunosuppressive (IS) treatment was prescribed in 44 flares (66.7%). The remission rate at 12 months for the whole group was 50%, with musculo-skeletal (MS) flares, mucocutaneous (MC) flares and others (neuropsychiatric, cardiopulmonary, constitutional, haematologic) that was respectively 63.6%, 31.3% and 41.2%, showing lower rate of remission for MC flares. In 12 months, 17 flares (25.8%) did not respond to treatment (non-responders), requiring an increase in the dose of GC or the introduction of a new IS therapy. Using a machine learning approach, we were able to identify 4 flare clusters, grouping flares in relation to phenotypic characteristics (Figure 1), and recognized statistically relevant features for patients’ stratification (cluster 1“flare in systemic disease with high activity”, cluster 2 “outcast flares”, cluster 3 “flare in polymorphic disease with mild activity” and cluster 4 “recurrent skin flares”). Interestingly, cluster 4 (recurrent skin flares) was associated with the lowest rate of remission at 12 months with respect to clusters 1, 2, and 3 (33% vs 40%, 76.5% and 56% respectively). Moreover the neural network model correctly predicts difficult to treat flares in up to 80% of the casesTable 1.WHOLE GROUPMUSKELMUCOCUTCONSTITUTIONALCARDIOPULMHAEMATOLNEUROpNUMBER (%)6633 (50)16 (24.2)7 (10.6)4 (6.1)5 (7.6)1 (1.5)SLEDAI at baseline median (IQR)7 (4-29)8 (6-10)5.5 (4-10)5 (4-9)9 (4.5-12)5 (5-6)29 (29-29)SLEDAI 12 mos median (IQR)2 (0-20)0.5 (0-4)3 (0-4)3 (2 – 4)0 (0-0)2 (0-3)14 (14 – 14)REMISSION 12 mos number (%)33 (50)21 (63.6)5 (31.3)4 (57.1)2 (40)2 (40%)1 (100)0.217NON RESPONSE 12 mos number (%)17 (25.8)8 (25)5 (31.3)2 (28.6)1 (20)1 (20%)1 (100)0.467Figure 1.Flare clusters.ConclusionThese data suggest that, in a real-life setting, the clinical response rate to therapy of patients with an extra-renal flare is not satisfactory, thus identifying an unmet need in the treatment of SLE and highlighting the absence of a standard treatment. Both the real-life data and the machine learning approach identify flares with MC manifestations as the most difficult to treat with the lower rate of remission after one year. Further prospective studies are necessary to improve the neural network model; ML techniques could help in the early identification of difficult to treat flares to be candidates for new and more aggressive therapeutic strategies for extra-renal manifestations.Disclosure of InterestsNone declared

BackgroundFatigue in SLE has a multifactorial origin and disease activity seems to contribute only minimally to its genesis. Therefore, non-pharmacological therapeutic strategies should also be considered in the management of fatigue. There is some evidence on the effectiveness of aerobic exercise programs in improving fatigue, without a negative impact on disease manifestations.Objectivesthe aim of this study was to analyze fatigue and Health Related Quality of Life (HRQoL) in a monocentric cohort of patients with SLE, in a condition of stable remission or low disease activity, before and after a program of physical exercise, through the administration of validated Patient Reported Outcomes (PROs).Methodsthis is a cross-sectional interventional study which included patients with SLE, aged between 18 and 55 years, in a condition of stable (≥12 months) remission (DORIS)1 or low disease activity (LLDAS)2. Patients enrolled had a FACIT score ≤40 in the previous 6 months. Patients with other possible causes of fatigue (e.g.: anemia, hypothyroidism, severe vitamin D deficiency), active arthritis or physical disabilities were excluded. For each patient, demographics, comorbidities, treatment, clinical and laboratory data were collected. Disease activity was evaluated with the SELENA-SLEDAI and organ damage with the SLICC/DI. Each patient completed the following PROs before and after the interventional program: SF-36, FACIT-Fatigue, LIT, HADS. Due to the limitations related to the COVID-19 pandemic, the physical exercise sessions were carried out using the Google Meet digital platform. Patients were asked to participate to at least 70% of the lessons. The physical exercise program included moderate intensity aerobic exercises (muscle strengthening, joint mobility, breathing, static and dynamic stretching, balance and neuro-dynamics); workouts were performed 3 times a week, consisting of 60 minutes each. The program lasted for 12 weeks.Resultswe enrolled 12 female patients, regularly followed at the Rheumatology Unit of Pisa; only 9 of them completed the study (mean age 38.56 ± 9.1 years; median disease duration 7 years (IQR 5,25-9,75)). 8/9 were in stable remission, while 1/9 was in LLDAS for the presence of leukopenia.2/9 patients presented organ damage, one for cataract and one for renal insufficiency, while none presented damage in the musculoskeletal system. 33.3% of patients had fibromyalgia. 88.8% was on treatment with Hydroxychloroquine, 55.5% was on low dose steroids (2±1.9 mg/daily), 33.3% was on Mycophenolate Mofetil; only 1 patient was on Belimumab. All PROs showed a trend to improvement at the end of the 12-week program of physical activity (Table 1). We demonstrated a statistically significant improvement of: FACIT, LIT, depression score of the HADS and MCS of the SF-36. The items of role physical (RP), vitality (VT) and mental health (MH) of the SF-36 also showed a significant improvement.Table 1.Scores of PROs before and after the physical exercise program.PROsMean scores at baselineMean scores after the 12-week exercise programpFACIT30.2 ± 4.939.3 ± 7.20.01PF73.18 ± 10.978.9 ± 10.50.18RP50 ± 13.267.4 ± 18.60.03BP52 ± 12.154.1 ± 11.10.73GH41.7 ± 11.148.4 ± 11.10.07VT34.7 ± 12.559.0 ± 14.20.002SF58.3 ± 15.666.7 ± 16.70.3RE55.5 ± 21.569.4 ± 18.00.13MH58.3 ± 15.867.2 ± 16.20.03PCS43.8 ± 4.046.1 ± 4.80.19MCS38.6 ± 8.845.6 ± 8.70.03LIT36.9 ± 14.227.5 ± 14.10.05HADS (A)9 ± 4.47.7 ± 3.20.4HADS (D)7.9 ± 4.45.1 ± 2.960.05ConclusionIn a small cohort of SLE patients in remission but with severe fatigue, in the difficult context of COVID-19 pandemic, we demonstrated that an online program of physical exercise may determine a significant improvement of fatigue, perception of disease burden and mental health. In the context of a multidisciplinary management, finding effective intervention programs to improve fatigue and HRQoL in SLE patients appears of utmost importance, with the final aim of improving patients’ health status.References[1]PMID 27884822; 2PMID 26458737Disclosure of InterestsNone declared

BackgroundA growing interest has been addressed to the study of lung involvement in systemic autoimmune diseases. Non-serositic pulmonary manifestations have also been described in SLE. However, little is known about their exact prevalence, clinical features and outcomes.ObjectivesTo describe the prevalence, clinical and immunological characteristics of symptomatic non-serositic lung involvement in a monocentric cohort of SLE patients.MethodsThis observational, retrospective study included patients with SLE, regularly followed at the Rheumatology Unit of Pisa, that presented a clinically relevant non-serositic pulmonary involvement during their disease history. Patients with lung manifestations related to other causes (e.g. infections, emphysema, Chronic Obstructive Lung Disease, bronchial asthma etc.) were excluded. The following data were collected from clinical charts: demographics, smoke exposure, comorbidities, respiratory symptoms, disease duration and disease activity (SELENA-SLEDAI) at the onset of lung involvement, immunological profile, treatment, CT and spirometry parameters.ResultsOver 450 SLE patients in regular follow-up, we found 11 female patients with a history of clinically relevant non-serositic lung involvement: 7 interstitial lung disease (ILD), 2 acute lupic pneumonitis (ALP), 1 diffuse alveolar hemorrhage (DAH) and 1 shrinking lung syndrome. 45.4% of patients had a history of smoke exposure and had stopped smoking on average 9 years before the onset of lung manifestations. For the 2 patients with ALP, this was the first manifestation of SLE. Among the other 9 patients, lung involvement was diagnosed after a mean disease duration of 14 ± 15 years. At the diagnosis of pulmonary involvement, 10/11 patients presented respiratory symptoms and an overall active disease, with a median SLEDAI of 9 (IQR 6-13). Clinical characteristics are summarized in Table 1. All patients were hospitalized and 2 of them (1 ALP and 1 DAH) were admitted in intensive care unit.Table 1.Clinical characteristics at the diagnosis of lung involvementSystemicActive skin manifestations36%Arthritis36%Fever36%Leukopenia36%Hypocomplementemia91%Anti-dsDNA positivity36%RespiratoryDyspnea54%Exertional dyspnea18%Cough45%Acute respiratory failure27%As for the immunologic profile, SSA/Ro60 were positive in 72% of patients and SSA/Ro52, SSB, U1-RNP in 36%; 36% had Sjogren Syndrome (SS) in overlap.Spirometry was available for 6/11 patients: a restrictive pattern and a moderate/severe reduction of diffusing capacity of the lung for carbon monoxide was found in 5 patients.In the ILD subgroup, the most prevalent CT pattern was the Non-specific interstitial pneumonia (NSIP) (5/7). 2 patients presented a Bronchiolitis obliterans/organizing pneumonia (BOOP) pattern.Lung involvement was the driving manifestation in the treatment choice for 6/11 patients: 1 DAH, 2 ALP, 1 Shrinking lung and 2 ILD. All received pulse steroids and in 3 cases (2 ILD and 1 DAH) cyclophosphamide was added for the induction treatment; the patient with Shrinking lung had an overlap SS and was treated with Rituximab.At last visit (mean follow-up of 8 ± 8.7 years since lung disease onset), 7/11 patients presented no respiratory symptoms and a complete resolution of CT alterations. 3/11 presented a residual exertional dyspnea and mild spirometry alterations. No patients developed respiratory insufficiency; only 1 patient died for cardiovascular complications.ConclusionIn our large cohort of SLE patients, non-serositic lung involvement seems to be overall rare; the most frequent type of lung manifestation is ILD which appears to be associated with anti-SSA/SSB and anti-U1RNP positivity. The low prevalence of lung involvement (2.4%) in our cohort could be due to the presence of patients with a subclinical involvement. Further studies are needed to assess the real prevalence of subclinical lung manifestations in SLE and to identify the clinical phenotype of patients more prone to develop pulmonary disease.Disclosure of InterestsDavide Schilirò: None declared, Elena Elefante: None declared, Chiara Stagnaro: None declared, Viola Signorini: None declared, Dina Zucchi: None declared, Francesca Trentin: None declared, Gaetano La Rocca: None declared, Linda Carli: None declared, Francesco Ferro: None declared, Chiara Tani: None declared, Marta Mosca Speakers bureau: advisor LILLY, ASTRA ZENECA, GSK, Consultant of: advisor LILLY, ASTRA ZENECA, GSK

BackgroundPregnancy is a topic of fundamental importance for women living with autoimmune rheumatic diseases (ARD). Efforts at national and international levels have been put in the collection and harmonization of data in order to implement an evidence-based management of pregnant patients.ObjectivesThe P-RHEUM.it study was designed as a nationwide, web-based longitudinal observational cohort study to collect data about pregnancy in ARD in 26 centers in Italy. The study started in May 2018 and has been supported by the Italian Society for Rheumatology.MethodsPregnant patients with a definite rheumatic disease according international criteria were enrolled up to gestational week (GW) 20. The course of maternal disease activity, the use of medications, fetal and maternal complications, and the quality of life (EuroQoL questionnaire) were collected for each trimester, as well as pregnancy outcome, mode of delivery, neonatal complications, and maternal and children’s follow-up to 6 months after delivery, including the screening for post-partum depression by means of EPDS (Edinburgh Postnatal Depression Scale).ResultsAs of December 2021, 758 pregnancies had been enrolled, 205 (27%) ongoing and 553 (73%) with outcome. Pregnancy loss occurred in 54 (9.8%) cases (40 spontaneous miscarriages; 6 voluntary terminations). Live births were 495 (89.5%), perinatal death occurred in 4 (0.7%) cases. Table 1 reports on the group of 495 live births, along with subgroups of Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE), the two most represented diseases. Regarding treatments, 166 (30%) pregnancies were exposed to corticosteroids, 239 (43%) to hydroxychloroquine, 59 (10.7%) to csDMARDs, 84 (15.2%) to TNF inhibitors, 1 (0.2%) to non-TNFi bDMARDs, 299 (54%) to low dose acetylsalicylic acid, and 126 (22.8%) to heparin.Table 1.PREGNANCIES WITH LIVE BIRTHS, EXCLUDING PERINATAL DEATHSTotal pregnancies (n=495)RA pregnancies (n=69)SLE pregnancies (n=93)Age at conception (years)34 (31 - 37)34.5 (32 - 38)34 (31 - 36)Disease duration (years)6.1 (2.2 - 11.1)7.1 (4.3 - 11.6)9.3 (5.9 - 15.9)Caucasian431 (87.8%)53 (79.1%)75 (80.6%)Never smokers358 (73.8%)53 (80.3%)66 (71.7%)Body Mass Index >3045 (9.5%)7 (10.3%)5 (5.6%)Arterial Hypertension6 (1.2%)0 (0%)2 (2.2%)Time to pregnancy (months)3 (1 - 6)3 (1 - 6)3 (0 - 10)Physician-reported flares in the 12 months prior to conception107 (23%)22 (34.4%)13 (14.8%)Physician global assessment at enrolment (VAS 0-100)5 (0 - 17)5 (0 - 20)4 (0 - 10)Patient global health at enrolment (VAS 0-100)18 (7 - 30)10 (5 - 29)10 (5 - 25)EuroQoL at enrolment (-1.6 – 1)1 (0.8 - 1)1 (0.8 - 1)1 (0.8 - 1)Flares during pregnancy35 (7.1%)6 (8.7%)7 (7.5%)Hypertensive disturbances*8 (1.7%)1 (1.6%)6 (6.6%)Delivery at term (≥37 GW)410 (85.1%)53 (77.9%)74 (80.4%)Spontaneous vaginal delivery173 (35.9%)23 (33.8%)23 (25.3%)Congenital malformations11 (2.4%)2 (3.1%)1 (1.1%)Small for gestational age (SGA) neonate24 (4.9%)1 (1.4%)9 (9.9%)Breastfeeding in the first 4 weeks after delivery341 (79.7%)45 (77.6%)59 (76.6%)EPDS score at risk for post-partum depression22 (14.1%)0 (0%)3 (10.3%)Continuous variables are expressed as median (interquartile range); *gestational hypertension/preeclampsia/HELLP syndrome/eclampsia.ConclusionMultiple factors may have contributed to the high rate of live births, including good disease control before and during pregnancy thanks to the use of anti-rheumatic drugs and low frequency of general risk factors. SLE pregnancy was affected by a higher frequency of complications (hypertensive disturbances, SGA babies) as compared to RA pregnancy. Nearly 80% of patients breastfed in the first month after delivery. For the first time, data about the screening questionnaire for post-partum depression were collected, showing at least 1 out 10 patients can be at risk.References[1]Meissner Y et al. Arthritis Res Ther;21(1):241; Ann Rheum Dis. 2021;80(1):49-56.AcknowledgementsP-RHEUM.it study is supported by the Italian Society for Rheumatology (SIR). All the Investigators are acknowledged for their contribution.Disclosure of InterestsNone declared

BackgroundThe optimization of HRQoL in SLE patients is defined as one of the treatment goals in the 2019 EULAR recommendations1 for the management of SLE. Most studies have examined HRQoL at one point in time, while the few longitudinal studies do not report a clear variation in Patient Reported Outcomes (PROs) with respect to changes in disease activity. It would be important to understand if, even in a real-life setting, the improvement of patients’ HRQoL may represent an achievable target.Objectivesthe aim of this study was to analyze HRQoL over time in a monocentric cohort of patients with SLE and investigate which disease-related factors determine short-term variation of HRQoL in a real-life setting.Methodsthis is a longitudinal, prospective monocentric study which included consecutive adult outpatients with SLE (1997 ACR classification criteria), regularly followed at the Rheumatology Unit of Pisa. Patients were enrolled over a period of 2 years, before the pandemic outbreak, and had at least 2 assessments per year. For each patient, demographics, comorbidities, treatment, clinical and laboratory data were collected. Disease activity was evaluated with the SELENA-SLEDAI and organ damage with the SLICC/DI. We defined as a significant variation of disease activity, a difference of clinical SELENA-SLEDAI ≥ 4 points between 2 subsequent evaluations. At each visit, patients completed the following PROs: SF-36, FACIT-Fatigue and LIT.Resultswe enrolled 210 consecutive SLE patients, mainly female (93.8%) and of Caucasian ethnicity (97.1%), with a mean age at enrollment of 45.1±12.7 years and a median disease duration of 13 years (IQR 5-21). At baseline, the median SLEDAI of the cohort was 2 (IQR 0-4). The most frequent active disease manifestations were: articular (17.1%) and hematological (15.2%); 6.7% of patients had active renal disease. 47.14% had a SLICC-DI > 0 with a median SLICC-DI among them of 2 (IQR 1-3). 11.43% of patients had a concomitant fibromyalgia. Most patients were on Hydroxychloroquine (78.1%) and low dose glucocorticoid (55.2%), with a median daily dose of 2 mg (IQR 0-4) of prednisone equivalent; 41.4% were on conventional immunosuppressants and 11.9% on biologics, mainly belimumab. The median scores of PROs at enrollment are reported in Table 1. At baseline, fibromyalgia confirmed to have a significant negative impact on all PROs after adjustment for confounding factors (pppTable 1.PROs scores at baseline.PROsMedian scores at baselineSF-36 PCS58 (IQR 49.09- 68)SF-36 MCS57 (IQR 46.42-67)FACIT42 (IQR 32-46)LIT20 (IQR 7.5-40)Conclusionour findings seem to suggest that HRQoL over time in outpatients with longstanding SLE tends to be stable (maybe because patients are able to adapt to their illness) or varies unpredictably, maybe influenced by not disease-related factors. Further studies are needed to better understand which factors influence HRQoL over time and which questionnaires are more sensitive to catch its variation.References[1]PMID: 30926722Disclosure of InterestsNone declared

A new polycyclic antibiotic, pradimicin-IRD, was isolated from actinobacteria

Some herbicides are suspected of promoting teratogenic, carcinogenic and mutagenic events. Detection of induced mitotic crossing-over has proven to be an indirect way of testing the carcinogenic properties of suspicious substances, because mitotic crossing-over is involved in the multistep process of carcinogenesis. We examined mitotic crossing-over induced by two commercial herbicides (diuron and trifluralin) in diploid strains of Aspergillus nidulans based on the homozygotization index. Low doses (2.5 microg/mL) of diuron were sufficient to increase the mean homozygotization index in 2.1 and 11.3 times for UT448//UT196 and Dp II-I//UT196, respectively, whereas the same dose of trifluralin increased this mean only 1.2 (UT448//UT196) and 3.5 (Dp II-I//UT196) times, respectively. The lower homozygotization index value found for trifluralin could be due to its interference with mitotic crossing-over in eukaryotic cells. We concluded that the diploid Dp II-I//UT196 of A. nidulans is more sensitive to organic compounds than UT448//UT196; these compounds cause recombinational events at a greater frequency in the latter diploid. This system holds promise as an initial test for carcinogenicity of organic compounds, including herbicides.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:23:37Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:39:04Z : No. of bitstreams: 1 2-s2.0-47949095090.pdf: 631051 bytes, checksum: 02bef8fe066a3dd6178e430b04842b01 (MD5) Made available in DSpace on 2014-05-27T11:23:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-07-30 As a contribution towards detecting the genetic effects of low doses of genotoxic physical agents, this paper deals with the consequences of low-dose X-rays in the Aspergillus nidulans genome. The irradiation doses studied were those commonly used in dental clinics (1-5 cGy). Even very low doses promoted increased mitotic crossing-over frequencies in diploid strains heterozygous for several genetic markers including the ones involved in DNA repair and recombination mechanisms. Genetic markers of several heterozygous strains were individually analyzed disclosing that some markers were especially sensitive to the treatments. These markers should be chosen as bio-indicators in the homozygotization index assay to better detect the recombinogenic/ carcinogenic genomic effects of low-dose X-rays. ©FUNPEC-RP. Faculdade de Odontologia Universidade de Franca, Franca, SP Faculdade de Odontologia Universidade de São Paulo, Ribeirão Preto, SP Centro Universitário Moura Lacerda, Ribeirão Preto, SP Departamento de Parasitologia Instituto de Ciências Biomédicas Universidade de São Paulo, São Paulo, SP Departamento de Ciências Biológicas and Biotecnologia Universidade do Estado de São Paulo, Assis, SP

A compositional study of twenty-two marble artefacts from the medieval Benedictine Abbey of San Caprasio at Aulla (North-western Tuscany, Central Italy) has been carried out. The mineralogical and petrographic analyses, the estimation of the maximum grain size of the calcite crystals, and the determination of carbon and oxygen stable isotopes support a provenance of most marbles from the Apuan Alps quarries (Italy). Only some marbles indicate a probable provenance from the islands of Paros and Thasos in the eastern Mediterranean area.

Koinobiont parasitoids use several strategies to regulate the host's physiological processes during parasitism. Although many aspects of host–parasitoid interactions have been explored, studies that attempted to assess the effects of parasitism on the availability of inorganic elements in the host are virtually nonexistent. Therefore, we aimed to evaluate the effects of parasitism on the concentrations of inorganic elements in the fat bodies of larvae of Diatraea saccharalis (Lepidoptera: Crambidae) during the development of the parasitoid Cotesia flavipes (Hymenoptera: Braconidae), by using total reflection X-ray fluorescence (TXRF). TXRF analysis allowed comparisons of the changes in the availability of the elements P, S, K, Ca, Cr, Fe, Ni, Cu, and Zn in the fat body tissues of D. saccharalis larvae parasitized by C. flavipes. Overall, the concentration of inorganic elements was higher early in parasitoid development (1 and 3 days after parasitism) compared to non-parasitized larvae, but much lower towards the end of parasitoid development (7 and 9 days after parasitism). Ca, K, and S were reduced after the fifth day of parasitism, which affected the total abundance of inorganic elements observed in the fat bodies of the parasitized hosts. The regulatory mechanisms or pathological effects related to the observed variation of the host inorganic elements induced by the parasitoid remain unknown, but there might be a strategy to make these elements available to the parasitoid larvae at the end of their development, when higher metabolic activity of the host fat body is required to sustain parasitoid growth. The observed variation of the host's inorganic elements could also be related to the known effects of parasitism on the host's immune response.

Total RNA from lipopolysaccharide (LPS)-stimulated rat macrophages used to treat protoplasts from an Aspergillus nidulans strain originated the RT2 regenerated strain, whose culture supernatant showed anti-inflammatory activity in Wistar rats. The protein fraction presenting such anti-inflammatory activity was purified and biochemically identified. The screening of the fraction responsible for such anti-inflammatory property was performed by evaluating the inhibition of carrageenan-induced paw edema in male Swiss mice. Biochemical analyses of the anti-inflammatory protein used chromatography, carbohydrates quantification of the protein sample, amino acids content analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Total sugar quantification revealed 32% glycosylation of the protein fraction. Amino acid analysis of such fraction showed a peculiar pattern presenting 29% valine. SDS-PAGE revealed that the protein sample is pure and its molecular weight is about 40kDa. Intravenous injection of the isolated substance into mice significantly inhibited carrageenan-induced paw edema. The isolated glycoprotein decreased carrageenan-induced paw edema in a prostaglandin-dependent phase, suggesting an inhibitory effect of the isolated glycoprotein on prostaglandin synthesis.

Total reflection X-ray fluorescence (TXRF) was used to evaluate the availability and contamination of inorganic elements in sediment samples from Atibaia River, located at Piracicaba Basin, near the Campinas region, Sao Paulo State, Brazil. The total contents (geological matrix) and the concentration of elements weakly linked to the sediment (available fraction) were determined. The availability of these elements was evaluated through the ratios between available fractions and total contents. The results showed that the elements Mn, Ni, Cu and Zn are easily available in the aquatic environment.

This study uses fishes as indicators of metal contamination in the Piracicaba Basin and also for evaluation of the risks to human health by the ingestion of fish contaminated by metals and other potentially toxic elements. Based on total reflection X-ray fluorescence analysis, Al, Si, P, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn and Ba were detected and evaluated in the muscle and viscus (liver, intestine and stomach) of fish collected in the Piracicaba River.

The objective of this study was to use synchrotron radiation total reflection X-ray fluorescence analysis (SR-TXRF) for the determination of metals and other elements in food available to the population in commercial establishments, in order to evaluate the risks of contamination by these products. The analyzed species were vegetables, leafy vegetables, fruits, cereal and grain. The results indicated that some species were contaminated by Cr, Cu, Zn and Pb with concentrations much higher than the reference values.

In this study the concentrations of P, S, Cl, K, Ca, Mn, Fe, Zn and Br in twenty-nine brands of national and international beers were determined by synchrotron radiation total reflection X-ray fluorescence analysis (SR-TXRF). The results were compared with the limits established by the Brazilian legislation and the nutritional values established by National Agricultural Library (NAL, USA). The measurements were performed at the X-Ray Fluorescence Beamline at Brazilian National Synchrotron Light Laboratory, in Campinas, Sao Paulo, Brazil, using a polychromatic beam for excitation. A small volume of 5 ml of beers containing an internal standard used to correct geometry effects was analyzed without pretreatment. The measuring time was 100 seconds and the detection limits obtained varied from 1 mg . l-1 for Mn and Fe to 15 mg . l-1 for P.

With the aid of the analytical energy dispersive X-ray fluorescence technique with radioisotope excitation, the concentrations of metals in commercial tablets containing 0.25 mg of digoxin were estimated. Concentrations ranging from 2.99 to 10.70 µg of Fe; 1.59 to 2.30 µg of Ni; 0.94 to 5.48 µg of Cu and 0.11 to 5.72 µg of Zn were found per tablet analyzed. The experimental detection limits for these elements varied from 13.03 to 22.57 µg l−1, while the relative errors made in the quantification of these metals were lower than 15%.

Actinomycetes, especially those belonging to the genus Streptomyces, are economically important from a biotechnological standpoint: they produce antibiotics, anticancer compounds and a variety of bioactive substances that are potentially applicable in the agrochemical and pharmaceutical industries. This paper combined accurate-mass electrospray tandem mass spectrometry in the full scan and product ion scan modes with compounds library data to identify the major compounds in the crude extract produced by Streptomyces sp. AMC 23; it also investigated how sodiated nonactin ([M + Na](+)) fragmented. Most product ions resulted from elimination of 184 mass units due to consecutive McLafferty-type rearrangements. The data allowed identification of four macrotetrolides homologous to nonactin (monactin, isodinactin, isotrinactin/trinactin and tetranactin) as well as three related linear dimer compounds (nonactyl nonactoate, nonactyl homononactoate and homononactyl homononactoate). The major product ions of the sodiated molecules of these compounds also originated from elimination of 184 and 198 mass units. UPLC-MS/MS in the neutral loss scan mode helped to identify these compounds on the basis of the elimination of 184 and 198 mass units. This method aided monitoring of the relative production of these compounds for 32 days and revealed that the biosynthetic process began with increased production of linear dimers as compared with macrotetrolides. These data could facilitate dereplication and identification of these compounds in other microbial crude extracts.

p. 920-924 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-01-22T15:20:14Z No. of bitstreams: 1 0100-40422007000400030.pdf: 107046 bytes, checksum: b218c9a46ce9f8e49563bade04b991f5 (MD5) Made available in DSpace on 2014-01-22T15:20:14Z (GMT). No. of bitstreams: 1 0100-40422007000400030.pdf: 107046 bytes, checksum: b218c9a46ce9f8e49563bade04b991f5 (MD5) Previous issue date: 2007 Honey is a food used since the most remote times, appreciated for its characteristic flavor, considerable nutritional value and medicinal properties; however, little information exists about the presence of chemical elements in it. The objectives of this work were to determine the chemical elements present in 38 honey samples, collected directly from beekeepers from the State of Piauí, Brazil and to verify whether they presented any contamination. The chemical elements were determined by means of Total Reflection X-ray Fluorescence. The means of three replicates were: K (109.671 ± 17.487), Ca (14.471 ± 3.8797), Ti (0.112 ± 0.07), Cr (0.196 ± 0.11), Mn (0.493 ± 0.103), Fe (1.722 ± 0.446), Co (0.038), Ni (0.728 ± 0.706), Cu (0.179 ± 0.0471), Zn (0.967 ± 0.653), Se (not detected), Br (not detected), Rb (0.371 ± 0.097), Sr (0.145 ± 0.45), Ba (11.681), Hg (not detected), and Pb (0.863) µg g-1.

Mercury (Hg) pollution is one of the most serious environmental problems. Due to public concern prompted by the symptoms displayed by people who consumed contaminated fish in Minamata, Japan in 1956, Hg pollution has since been kept under constant surveillance. However, despite considerable accumulation of knowledge on the noxious effects of ingested or inhaled Hg, especially for humans, there is virtually nothing known about the genotoxic effects of Hg. Because increased mitotic crossing over is assumed to be the first step leading to carcinogenesis, we used a sensitive short-term test (homozygotization index) to look for DNA alterations induced by Hg fumes. In one Aspergillus nidulans diploid strain (UT448//UT184), the effects of the Hg fumes appeared scattered all over the DNA, causing 3.05 times more recombination frequencies than the mean for other strains. Another diploid (Dp II-I//UT184) was little affected by Hg. This led us to hypothesize that a genetic factor present in the UT184 master strain genome, close to the nicB8 genetic marker, is responsible for this behavior. These findings corroborate our previous findings that the homozygotization index can be used as a bioassay for rapid and efficient assessment of ecotoxicological hazards.

Fenarimol, a systemic pyrimidine carbinol fungicide, is considered to be not genotoxic or weakly genotoxic, although the available toxicological data are controversial and incomplete. Our results obtained in vitro with leukocytes of two different rodent species (rat and mouse) show that fenarimol affects DNA, as detected by the single-cell gel electrophoresis (SCGE, Comet) assay. This fungicide is able to induce DNA damage in a dose-related manner, with significant effectiveness at 36 nM, but without significant interspecies differences. Simultaneous exposure of rat leukocytes to fenarimol (36-290nM) and a model genotoxic compound (50 ?g/ml bleomycin) produced a supra-additive cytotoxic and genotoxic effect. This supports previous findings suggesting possible co-toxic, co-mutagenic, cancer-promoting and co-carcinogenic potential of fenarimol, and modification of the effects of other xenobiotics found to be influenced by this agrotoxic chemical, with consequent different toxicological events. The potential for DNA strand breaks to act as a biomarker of genetic toxicity in plants in vivo was also considered, in view of the fact that higher plants represent reliable sensors in an ecosystem. Significant DNA breakage was observed in the nuclei of Impatiens balsamina leaves after in vivo treatment with fenarimol (145 nM, 1 h). More than 50% of the cells showed such DNA damage. Made available in DSpace on 2017-09-19T00:13:03Z (GMT). No. of bitstreams: 1 PoliEvaluation6441.pdf: 120825 bytes, checksum: 9fa0f3513b3287a905f174888b7d4c96 (MD5) Previous issue date: 2006-10-04

Recentes melhoramentos tecnológicos permitem que um método de XRF in vivo forneça sensibilidade para diagnósticos ou monitorando em aplicações biomédicas. Em casos de desordens sanguíneas hereditárias como a ß -Thalassaemia ou uma desordem genética como a Haemochromatosis, há uma alta concentração de elementos como Fe, Zn e Cu na pele e órgãos internos, devido ao tratamento dessas anormalidades ou devido à própria deficiência orgânica causada pela doença. Os níveis de Fe relacionados com os pacientes portadores da ß -Thalassaemia são determinados, no momento, medindo-se uma proteína da corrente sanguínea, chamada ferritina. O monitoramento da proteína é ineficaz em várias situações, como quando o paciente sofre qualquer alteração no seu quadro clínico. Atualmente, as principais formas de medir os níveis desses metais é através da biópsia do fígado, que é invasiva e potencialmente perigosa, apresentando uma taxa de mortalidade de 0,1 %, e por suscetibilidade magnética que emprega um supercondutor quântico, esta é altamente cara e há apenas três principais centros médicos no mundo que dispõe desse equipamento. Este trabalho investiga o uso de um detector SiPin-diodo e uma fonte de 238Pu (13 e 17 keV; 13 %; 95,2 mCi; 86 anos) para a medida de níveis de Fe na pele compatível com os níveis associados à doença ß -Thalassaemia. Foram analisados espectros de XRF usando um grupo de programas do AXIL - WinQXAS elaborados e disseminados pela IAEA. O coeficiente de determinação do modelo de calibração (curva de sensibilidade) foi de 0,97. Medidas em simulados de pele que contém concentrações de Fe de 15 a 150 partes por milhões (ppm), indicam que se pode medir Fe em níveis da ordem de 13 ppm, usando-se períodos de medida de 50 segundos e dose na superfície da pele de menos de 10 mSv. A literatura informa níveis de Fe na pele de 15,0 a 60,0 ppm em pessoas normais e de 70 a 150 ppm em pacientes portadores da ß -Thalassaemia. Não há registro na literatura sobre níveis de Fe na pele de portadores de Trypanosoma cruzi. Assim, a metodologia empregada permite a medida in vivo, na pele, da concentração de Fe nos níveis desejados. Recent technological improvements allow the method of in vivo XRF to supply useful sensibility for diagnostics or monitoring in biomedical applications. In cases of hereditary sanguine disorders as the â -Thalassaemia or a genetic disorder like Haemochromatosis, there is a high concentration of elements as Fe, Zn and Cu in the skin and internal organs, due to the treatment of those abnormalities or due to the own dysfunction caused by the disease. The levels of Fe related to the patient bearers of the â -Thalassaemia are determined, at the moment, measuring a protein in the sanguine current, called ferritin. The monitoring of the protein is ineffective in several situations, such as when the patient suffers any disturbance of health. Nowadays, the main forms of measuring the levels of those metals through hepatic storage are the biopsy of the liver, that is invasive and potentially dangerous, presenting a rate of mortality of 0,1%, and through magnetic susceptibilities that employs a quantum superconductor, which is highly expensive and there are only three main world medical centers with this equipment. This work investigates the use of a Si PIN-diode detector and a 238Pu source (13 and 17keV; 13%; 95.2mCi; 86y) for the measurement of Fe skin levels compatible with those associated to the disease â -Thalassaemia. XRF spectra were analyzed using a set of AXIL-WinQXAS programs elaborated and disseminated by the IAEA. The determination coefficient of the calibration model (sensitivity curve) was 0.97. Measurements on skin phantoms containing concentrations of Fe in the range from 15 to 150 parts per million (ppm), indicate that we are able to detect Fe at levels of the order of 13 ppm, using monitoring periods of 50 seconds and skin entrance dose less than 10 mSv. The literature reports skin Fe levels from 15.0 to 60.0 ppm in normal persons and from 70 to 150 ppm in thalassaemics patients. So, the employed methodology allows the in vivo measurement of the skin Fe concentration in wanted levels.