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Findings from previous small studies have been reassuring regarding the safety of treatment with hydroxychloroquine (HCQ) during pregnancy. In one recent study, it was demonstrated that the frequency of major birth defects was increased in women who had received HCQ at a dose of ≥400 mg/day during pregnancy. This study was undertaken to examine pregnancy outcomes among women following the use of HCQ.The study cohort comprised pregnant women who were prospectively enrolled in the MotherToBaby/Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Study and were receiving treatment with HCQ. For the control groups, disease-matched women without HCQ exposure and healthy women were randomly selected from the same source, with subject matching using a 1:1 ratio. Data were collected through interviews, medical records, and dysmorphology examinations. Pregnancy outcome measures included the presence or absence of major and minor birth defects, rates of spontaneous abortion, rates of preterm delivery, and infant growth measures.Between 2004 and 2018, 837 pregnant women met the criteria for study inclusion, including 279 women exposed to HCQ during pregnancy and 279 women in each unexposed control group. Sixty pregnant women (7.2%) were lost to follow-up. Among the women with live births, major birth defects occurred as a pregnancy outcome in 20 (8.6%) of 232 women with HCQ exposure in the first trimester, compared to 19 (7.4%) of 256 disease-matched unexposed controls (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 0.61-2.26) and 13 (5.4%) of 239 healthy controls (adjusted OR 0.76, 95% CI 0.28-2.05). Risks did not differ in women who were receiving an HCQ dose of ≥400 mg/day. No pattern of birth defects was identified. There were no differences in the rates of spontaneous abortion or preterm delivery between groups. Occurrence of infant growth deficiencies did not differ in the HCQ-exposed group compared to the disease-matched unexposed control group, except in the infant's head circumference at birth (adjusted OR 1.85, 95% CI 1.07-3.20).In this study, there was no evidence of an increased risk of structural birth defects or other adverse outcomes among women receiving HCQ during pregnancy, with the exception of infant head circumference at birth. For pregnant women being treated with HCQ, these findings are reassuring.

The concern about the offspring’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.

Objective Thyroid disorders including hyperthyroidism are common during pregnancy. Untreated hyperthyroidism can result in adverse outcomes for pregnancy. Methods Iodine, propylthiouracil (PTU), carbimazole (CMZ), and methimazole (MMI) are common medications for hyperthyroidism treatment. The literature regarding antithyroid medication use in pregnancy and breastfeeding is reviewed. Results Animal studies for PTU have suggested congenital anomalies while animal studies for MMI have only indicated adverse outcomes at higher doses than used in humans. Epidemiological studies have noted an increased risk of congenital anomalies for PTU less often than CMZ or MMI but the epidemiological evidence remains mixed. A pattern of anomalies has been described for CMZ and MMI, from both case and epidemiological studies, including choanal atresia, aplasia cutis congenita, and other facial, heart, gastrointestinal, and skin anomalies. Closer examination of cases indicates that a few cases of the anomalies have occurred without exposure to CMZ or MMI and outside of the proposed critical period. PTU has a small risk of hepatotoxicity which rarely results in liver transplantation and death. Some authors have suggested that PTU be prescribed in early pregnancy and switched to MMI in late pregnancy. Untreated hyperthyroidism, from either a lack of medications or switching medications during the first trimester, may also increase the chance of congenital anomalies. Multiple case studies and larger epidemiological studies have failed to provide clear, consistent outcomes for the use of PTU, CMZ, and MMI in pregnancy. MMI and PTU both enter the breastmilk in small amounts. Conclusion Additional research is needed to assist in the medical management and exposure counseling of pregnant and breastfeeding women with hyperthyroidism.

BackgroundSome factors associated with severe COVID-19 outcomes have been identified in patients with psoriasis (PsO) and inflammatory/autoimmune rheumatic diseases, namely older age, male sex, comorbidity burden, higher disease activity, and certain medications such as rituximab. However, information about specificities of patients with PsO, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), including disease modifying anti-rheumatic drugs (DMARDs) specifically licensed for these conditions, such as IL-17 inhibitors (IL-17i), IL-23/IL-12 + 23 inhibitors (IL-23/IL-12 + 23i), and apremilast, is lacking.ObjectivesTo determine characteristics associated with severe COVID-19 outcomes in people with PsO, PsA and axSpA.MethodsThis study was a pooled analysis of data from two physician-reported registries: the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), comprising patients with PsO/PsA, and the COVID-19 Global Rheumatology Alliance (GRA) registry, comprising patients with PsA/axSpA. Data from the beginning of the pandemic up to 25 October, 2021 were included. An ordinal severity outcome was defined as: 1) not hospitalised, 2) hospitalised without death, and 3) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics (age, sex, time period of infection), comorbidities (hypertension, other cardiovascular disease [CVD], chronic obstructive lung disease [COPD], asthma, other chronic lung disease, chronic kidney disease, cancer, smoking, obesity, diabetes mellitus [DM]), rheumatic/skin disease (PsO, PsA, axSpA), physician-reported disease activity, and medication exposure (methotrexate, leflunomide, sulfasalazine, TNFi, IL17i, IL-23/IL-12 + 23i, Janus kinase inhibitors (JAKi), apremilast, glucocorticoids [GC] and NSAIDs). Age-adjustment was performed employing four-knot restricted cubic splines. Country-adjustment was performed using random effects.ResultsA total of 5008 individuals with PsO (n=921), PsA (n=2263) and axSpA (n=1824) were included. Mean age was 50 years (SD 13.5) and 51.8% were male. Hospitalisation (without death) was observed in 14.6% of cases and 1.8% died. In the multivariable model, the following variables were associated with severe COVID-19 outcomes: older age (Figure 1), male sex (OR 1.53, 95%CI 1.29-1.82), CVD (hypertension alone: 1.26, 1.02-1.56; other CVD alone: 1.89, 1.22-2.94; vs no hypertension and no other CVD), COPD or asthma (1.75, 1.32-2.32), other lung disease (2.56, 1.66-3.97), chronic kidney disease (2.32, 1.50-3.59), obesity and DM (obesity alone: 1.36, 1.07-1.71; DM alone: 1.85, 1.39-2.47; obesity and DM: 1.89, 1.34-2.67; vs no obesity and no DM), higher disease activity and GC intake (remission/low disease activity and GC intake: 1.96, 1.36-2.82; moderate/severe disease activity and no GC intake: 1.35, 1.05-1.72; moderate/severe disease activity and GC intake 2.30, 1.41-3.74; vs remission/low disease activity and no GC intake). Conversely, the following variables were associated with less severe COVID-19 outcomes: time period after 15 June 2020 (16 June 2020-31 December 2020: 0.42, 0.34-0.51; 1 January 2021 onwards: 0.52, 0.41-0.67; vs time period until 15 June 2020), a diagnosis of PsO (without arthritis) (0.49, 0.37-0.65; vs PsA), and exposure to TNFi (0.58, 0.45-0.75; vs no DMARDs), IL17i (0.63, 0.45-0.88; vs no DMARDs), IL-23/IL-12 + 23i (0.68, 0.46-0.997; vs no DMARDs) and NSAIDs (0.77, 0.60-0.98; vs no NSAIDs).ConclusionMore severe COVID-19 outcomes in PsO, PsA and axSpA are largely driven by demographic factors (age, sex), comorbidities, and active disease. None of the DMARDs typically used in PsO, PsA and axSpA, were associated with severe COVID-19 outcomes, including IL-17i, IL-23/IL-12 + 23i, JAKi and apremilast.AcknowledgementsWe thank all the contributors to the COVID-19 PsoProtect, GRA and EULAR Registries.Disclosure of InterestsNone declared

BackgroundPatients with autoimmune systemic diseases (ASDs) can be counted among frail populations as regards the predisposition to COVID-19 due to the frequent visceral organ involvement and comorbidities, as well as the ongoing immunomodulating treatments.ObjectivesOur long-term multicenter telephone survey prospectively investigated the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients during the first 3 pandemic waves.MethodsA large series of 3,918 ASD patients (815 M, 3103 F; mean age 59±12SD years) was consecutively recruited at the 36 referral centers of COVID-19 & ASD Italian Study Group. In particular, ASD series encompassed the following conditions: rheumatoid arthritis (n: 981), psoriatic arthritis (n: 471), ankylosing spondylitis (n: 159), systemic sclerosis (n: 1,738), systemic lupus (172), systemic vasculitis (n: 219), and a miscellany of other ASDs (n: 178). The development of COVID-19 was recorded by means of telephone survey using standardized symptom-assessment questionnaire (1).ResultsA significantly increased prevalence of COVID-19 (8.37% vs 6.49%; pInterestingly, a significantly higher COVID-19-related death rate was observed in systemic sclerosis patients compared to the Italian general population (6.29% vs 2.95%; p=0.018). Other adverse prognostic factors to develop COVID-19 were the patients’ older age, male gender, pre-existing ASD-related interstitial lung involvement, and chronic steroid treatment. Conversely, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs 46.99%; p=0.000), as well as the chronic administration of low dose aspirin in a subgroup of SSc patients (with 5.57% vs without 27.84%; p=0.000).ConclusionThe cumulative impact of COVID-19 on ASD patients after the first 3 pandemic waves revealed less severe than that observed during the first phase of pandemic (1), especially with regards to the death rate that was comparable to the Italian general population in spite of the increased prevalence of complicating COVID-19 in the same ASD series.Ongoing long-term treatments, mainly csDMARDs, might usefully contribute to generally positive outcomes of in this frail patients’ population.Of note, a significantly increased COVID-19-related mortality was recorded in only SSc patients’ subgroup, possibly favored by pre-existing lung fibrosis. Among different ASD, SSc deserves special attention, since it shares the main pathological alterations with COVID-19, namely the interstitial lung involvement and the endothelial injury responsible for diffuse microangiopathy.Besides SSc, the patients’ subgroups characterized by older age, chronic steroid treatment, pre-existing interstitial lung disease, and/or impaired COVID-19 vaccine response (1-3), may deserve well-designed prevention and management strategies.References[1]Ferri C, et al. Ann Rheum Dis. 2020 Oct 14 doi: 10.1136/annrheumdis-2020-219113.[2]Ferri C et al. J Autoimmun. 2021 Dec;125:102744. doi: 10.1016/j.jaut.2021.102744.[3]Visentini M et al. Ann Rheum Dis. 2021 Nov 24. doi: 10.1136/annrheumdis-2021-221248Disclosure of InterestsNone declared

Background:SARS-CoV-2 infection poses a serious challenge for patients with rheumatic autoimmune systemic diseases (ASD), characterized by marked immune-system dysregulation and frequent visceral organ involvement.Objectives:To evaluate the impact of Covid-19 pandemic in a large series of Italian patients with ASD.Methods:Our multicenter telephone survey (8-week period, March-April 2020) included a large series of 2,994 patients (584 M, 2,410 F, mean age 58.9±13.4SD years) with ASD followed at 34 tertiary referral centers of 14 regions of northern, central, and southern Italian macro areas, characterized by different prevalence of SARS-CoV-2 infection. According to currently used criteria, Covid-19 was classified as definite Covid-19 (signs or symptoms of Covid-19 confirmed by positive oral/nasopharyngeal swabs at PCR testing) or highly suspected Covid-19 (signs or symptoms highly suggestive of Covid-19, but not confirmed by PCR testing due to limited availability of virological tests in that period). The results were analyzed performing the Odds Ratio by Java-Stat 2-way Contingency Table Analysis.Results:The main findings of the survey study revealed a significantly increased prevalence of Covid-19 in:a.the whole series of ASD patients (definite Covid-19: 22/2994, 0.73%; p=0.0007;definite Covid-19 plus highly suspected Covid-19: 74/2,994, 2.47%; phttps://www.epicentro.iss.it/en/coronavirus/sars-cov-2-national-surveillance-system).b.the subgroup of patients with connective tissue diseases or systemic vasculitis (n = 1,901) compared to the subgroup of inflammatory arthritis (n = 1,093), namely rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (definite Covid-19: 19/1,901, 0.99%, vs 3/1,093, 0.27%; p=0.036; definite Covid-19 plus highly suspected Covid-19: 69/1,901, 3.6%, vs 5/1,093, 0.45%; pc.the subgroup of patients with pre-existing interstitial lung involvement (n = 526) compared to those without (n = 2,468) (definite Covid-19: 10/526, 1.90%, vs 12/2,468, 0.48%; p=0.0015; definite Covid-19 plus highly suspected Covid-19: 33/526, 6.27%, vs 41/2,468, 1.66%; pOf interest, the prevalence of Covid-19 did not correlate with presence/absence of different comorbidities, mainly diabetes, cardio-vascular and/or renal disorders, as well as of ongoing treatments with biological DMARDs; while patients treated with conventional DMARDs showed a significantly lower prevalence of Covid-19 compared to those without. Covid-19 was more frequently observed in the patients’ populations from northern and central compared to southern Italian macro area with lower diffusion of pandemic. Clinical manifestations of Covid-19, observed in 74 patients, were generally mild or moderate; 4/9 individuals requiring hospital admission died for severe pneumonia.Conclusion:The prevalence of Covid-19 observed in ASD patients during the first wave of pandemic was significantly higher than that observed in Italian general population; moreover, the actual prevalence of Covid-19 might be underestimated due to the high number of mild variants as well as the possible clinical overlapping between these two conditions. Patients with ASD should be invariably regarded as ‘frail patients’ during the pandemic course, considering the risk of worse outcome in the acute phase of Covid-19, as well as the potential long-term effects of viral infection.The statistically significant association of Covid-19 with connective tissue diseases/systemic vasculitis, as well as with pre-existing interstitial lung involvement, suggests the presence of distinct clinico-pathological ASD subsets, characterized by markedly different patients’ vulnerability to SARS-CoV-2 infection.Disclosure of Interests:None declared

Maternal pregestational diabetes mellitus is associated with an increased risk for congenital malformations of about 2-4 times the background risk. Notably, the types and patterns of congenital malformations associated with maternal diabetes are nonrandom, with a well-established increased risk for specific classes of malformations, especially of the heart, central nervous system, and skeleton. While the increased risk in clinical and epidemiological studies is well documented in the literature, a precise estimate of overall birth prevalence of these specific congenital malformations among women with maternal pregestational diabetes, is lacking. The purpose of this study was to determine total prevalence of structural malformations associated with maternal pregestational diabetes mellitus in a population-based study. We identified infants with specific birth defects whose mother had pregestational diabetes mellitus in the Utah Birth Defect Network (UBDN), an active birth defects surveillance program that registers the occurrence of selected structural defects in the state of Utah. We defined specific maternal diabetes-related malformations based on epidemiologic and clinical studies in the literature. Of the 825,138 recorded Utah births between 2001 and 2016, a total of 91 cases were identified as likely having diabetic embryopathy within UBDN data. The prevalence of diabetes-related congenital malformation cases was calculated per year; the overall prevalence of diabetes-related malformations 2001-2016 was 1.1 per 10,000 births in Utah (95% CI, 0.9-1.3). Knowledge of the overall prevalence of diabetes-related malformations is important in predicting the number of cases that are potentially prevented with the implementation of programs to foster preconceptional management of maternal pregestational diabetes.

Objective. Systemic sclerosis (SSc) is a severe multiple-organ disease charac- terised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society of Rheumatology pro- moted the registry SPRING (Systemic sclerosis Progression INvestiGation). Methods. The SPRING is a multi- centre rheumatological cohort study encompassing the wide scleroder- ma spectrum, namely the primary Raynaud’s phenomenon (pRP), sus- pected secondary RP, Very Early Diag- nosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteris- tics of 2,028 Italian patients’ popula- tion at the initial phase of enrollment, mainly focusing on the cohort of 1,538 patients with definite SSc. Results. Definite SSc showed signifi- cantly higher prevalence of digital ul- cers, capillaroscopic ‘late’ pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cu- taneous subset, and anti-Scl70 sero- positivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased preva- lence of unfavorable clinico-serologi- cal features. Conclusion. Nationwide registries with suitable patients’ subsetting and follow-up studies since the prodromal phase of the disease may give us valu- able insights on the SSc natural history and main prognostic factors.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting millions of people. Genome-wide association studies (GWAS) have found >25 genetic risk factors and at least 15 loci directly associated with PD. Recent advances in Next Generation DNA Sequencing technologies, such as the semiconductor-based Ion Torrent platform, make multigene sequencing cheaper, faster, and more reliable. Objectives: Our objective was to test the power of the Next Generation Sequencing technology to analyze a large cohort samples of PD patients from Southern Italy by screening the majority of the most relevant PD-related genes known for single and compound mutations. Methods: To achive a rapid,robust, and cost-effective genetic analysis of a PD cohort, we designed a multiplex, amplicon based gene panel made by 42 genes. We conducted parallel sequencing using the Ion Torrent Personal Genome Machine (PGM)(®) system to detect mutations in 42 blood DNA samples from PD patients. To process data from PGM Ion Torrent runs, Ion Torrent Suite (TS) software v. 5.10 was used. Annotation was made using ANNOVAR and the variants where priorized using a standard filtering pipeline. Results: After bioinformatics analysis and filtering, 98% coverage of the targeted regions was obtained with at least >200-fold mean depth. We detected 50 coding nonsynonymous variants (indels, single-nucleotide variations (SNVs) and frameshift variants with a MAF

Duodeno-pancreatic and extrahepatic biliary tree injuries are rare in both adult and pediatric trauma patients, and due to their anatomical location, associated injuries are very common. Mortality is primarily related to associated injuries, but morbidity remains high even in isolated injuries. Optimal management of duodeno-bilio-pancreatic injuries is dictated primarily by hemodynamic stability, clinical presentation, and grade of injury. Endoscopic and percutaneous interventions have increased the ability to non-operatively manage these injuries. Late diagnosis and treatment are both associated to increased morbidity and mortality. Sequelae of late presentations of pancreatic injury and complications of severe pancreatic trauma are also increasingly addressed endoscopically and with interventional radiology procedures. However, for moderate and severe extrahepatic biliary and severe duodeno-pancreatic injuries, immediate operative intervention is preferred as associated injuries are frequent and commonly present with hemodynamic instability or peritonitis. The aim of this paper is to present the World Society of Emergency Surgery (WSES) and American Association for the Surgery of Trauma (AAST) duodenal, pancreatic, and extrahepatic biliary tree trauma management guidelines. © 2019 The Author(s).

Introduction: Vanishing white matter disease (VWM) is an autosomal recessive leukodystrophy caused by mutations genes encoding the translational initiation factor 2B: EIF2B1-EIFB5. It is a heterogeneous neurological disorder with prominent cerebellar ataxia and spasticity in childhood-onset form and behavioural changes, dementia and seizures in adult-onset form (#15% of cases). The course of the disease is chronic progressive with episodes of stress-provoked rapid neurological deterioration. Purpose of the study: We present the case of a 60 years old patient, MTHFR homozygous, presenting white matter lesions and a subcortical vascular encephalopathy being diagnosed. To investigate a possible genetic cause, suspecting CADASIL, genetic and genomic analysis were performed. Materials and Methods: For genetic and genomic investigations, Sanger sequencing of NOTCH3 gene, linked to CADASIL disease, and Next Generation Sequencing (NGS) analysis were performed on the patient. NOTCH3 sequencing was performed using primer pairs for all 22 exons, while for NGS analysis, we used a genes panel including 753 genes involved in neurological diseases. Libraries were prepared using Ion Ampliseq Library preparation kit 2.0 (Thermo Fisher Scientific) and they were run on Ion Torrent PGM (Thermo Fisher Scientific). We performed the alignment using Torrent Suite v. 5.10 and we used ANNOVAR for annotation step. Results: Sanger sequencing did not reveal any mutation in NOTCH3 gene, excluding CADASIL disease as the genetic cause responsible for the clinical history of our patient. NGS detected a novel heterozygous non- synonimous variant in exon 5 of EIF2B3 gene (c. C554G; p. S185C), whose mutations have been strongly related to leukoencephalopathy and VWM disease. Furthermore, all in silico analysis conducted on this variant predicts its deleterious impact that could affect protein function. Conclusion: S185C variant in EIF2B3 gene was discovered in an atypical condition of adult onset Leukodistrophy, a disease that usually occurs in childhood. It is uncertain if S185C could be responsible for the clinical history of our patient or if the peculiarity of his symptoms could be related to the potential contribution of this new detected variant on the phenotypical spectrum observed in the disease.

Objective The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. Methods We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18–55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). Results At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A “Disease Knowledge Index” (DKI) was created to investigate the degree of patients’ information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. Conclusion Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.

Background Rheumatic Diseases (RD) frequently affect women during reproductive age, therefore counselling on family planning is crucial for their quality of life. Children’s outcome is a major topic, but no large studies are available. Objectives To assess the long-term health conditions of children born to women with RD in a large multicentre cohort. Methods 24 Rheumatology Centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to consecutive patients (18–55 years) in September 2015. Data were analysed dividing children upon maternal diagnosis: Chronic Arthritides (CA) and Connective Tissue Diseases (CTD). Results Data were collected for 320 children (166 males, 52%) born to 184 mothers (63 CA and 121 CTD). At the time of interview, children had a mean age of 17.1±9.6 years. Preterm delivery ( Conclusions In this long-term follow-up of children born to mothers with RD in this large, multicenter study of randomly interviewed women each AIID did not display a significantly increased frequency as compared to the literature; only coeliac showed a mild increased frequency. Children with LD had a tendency to cluster in the group of mothers with CTD, especially after maternal diagnosis (4/63, 6.3%), with a higher frequency as compared to general paediatric population. No significant relationships between ND/LD and prematurity, intrauterine drug exposure or maternal autoantibodies were identified. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma. The authors wish to thank Patients Associations and Participants to the survey. Disclosure of Interest None declared

Background Rheumatic Diseases (RD) frequently affect women during reproductive age, therefore counselling on family planning is crucial for their quality of life. Children’s outcome is a major topic, but no large studies are available. This study aimed at assessing the long-term health conditions of children born to women with RD. Methods 24 Italian Rheumatology Centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to consecutive patients (aged 18–55) during September 2015. Data were analysed dividing children upon maternal diagnosis: Chronic Arthritides (CA) and Connective Tissue Diseases (CTD). Results Data were collected for 320 children born to 184 mothers (63 CA and 121 CTD). At the time of interview, children had a mean age of 17.1±9.6 years. Pre-term delivery ( The occurrence of an autoimmune/inflammatory disease (AIID) and/or neurodevelopmental disorders (ND)/learning disabilities (LD) is reported in table 1. Twelve children (3.7%) were diagnosed with an AIID, mostly coeliac disease (8/12, 67%). Eleven children (3.4%) were diagnosed as having a ND and/or LD by a Paediatric Neuropsychiatrist. Data of in utero exposure to maternal autoantibodies and/or anti-rheumatic drugs were retrieved for 280 children (87.5%) and a comparison was performed between affected (n=11) and not-affected children (n=258). No association was found with ND/LD and in utero exposure to autoantibodies (ANA, anti-Ro, anti-dsDNA, aPL) or drugs (HCQ,AZA or steroids), neither with sex, preterm birth, birth weight or maternal diagnosis. Conclusions The long-term follow-up of children born to mothers with RD did not raise particular concerns in terms of relevant health problems. In particular, each AIID did not display a significantly increased frequency as compared to the literature. Children with ND/LD had a tendency to cluster in the group of mothers with CTD, especially after maternal diagnosis, with a higher frequency as compared to GPP (7.9% vs 3%). Our data suggest that the development of ND/LD in children of patients with RD cannot be linked exclusively to maternal disease. The results of this study can be reassuring for patients with RD about problems in the offspring possibly related to their disease.

Purpose Cone Beam Computed Tomography (CBCT) is a growing modality of complementary radiodiagnostic. It is applied in a wide range of clinical applications like dentistry, interventional radiology in an operating room and radiotherapy. When a new CBCT is to be installed, a preventive structural shielding design is needed in order to evaluate and limit the dose in the adjacent rooms under the national regulation thresholds. Scatter dose at a specific point is an essential input for a radiation protection project. Unfortunately we did not find in literature any systematic data set for scatter dose from a CBCT; values ranging from 2 to 40 μSv/scan at 1 m distance from the centre of the scattering media are reported in the European Commission Document “Radiation Protection N. 172” [1] and relative to dentistry applications. In the report ICRP 129 [2] the dose to the eye of an operator was reported ranging from 28 to 79 μSv for CBCT hepatic arterial embolisation and biliary tube placement procedures. The purpose of this work was to systematic measure the scatter ambient dose equivalent from a CBCT installed on a linac. Methods Primary kilovoltage beam was generated by a CBCT mounted on a VARIAN TRUEBEAM linear accelerator. The target is composed by tungsten (95%) and rhodium (5%); the permanent source filtration was 2.7 mm Alluminium with an additional filtration made of 0.89 mm Titanium. The primary beam irradiated an anthropomorphic CIRS Atom 701-D phantom (adult male phantom at thorax level) during a single complete gantry rotation. Scatter ambient equivalent dose was measured for 4 energy levels (80 K V p , 100 K V p , 125 K V p and 140 K V p ) and for 3 collimations (approximately 7 cm, 16 cm and 23 cm corresponding to a small, medium and large collimation) along the longitudinal axis (axis around which the X-ray source was rotating). Measurements were performed at a height from the floor equal to the isocentric level and repeated for different angles between the longitudinal axis and the line formed by the center of the irradiated region in the phantom and the measurement point. The used survey meter was the ATOMTEX AT1121. Results The scatter radiation (H*(10) in μSv/mA*min at 1 m distance from the center of the irradiated region in the phantom to the measurement point) was not isotropic at different angles for the same irradiation conditions. For radiation protection purpose only the maximum measured values are reported in the following table. Conclusions The reported H*(10) values give an idea of the scattered radiation from a kilovoltage CBCT installed on a VARIAN TRUEBEAM linac. A new CBCT installation with similar spectral features (e.g. same target and filtration) and outside a radiotherapy environment may benefit from these measurements for radiation protection purposes.

Background Rheumatic diseases (RD) predominantly affect young women during reproductive age. Pregnancy, contraception and family planning (FP) are crucial for the quality of life of these patients. Objectives We aimed to investigate 9women9s health9 through a self-reported questionnaire. Answers from patients with connective tissue diseases (CTD) vs chronic arthritis (CA) were compared. Methods 24 centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to women with RD (18–45years) regularly attending their outpatient clinics. Results Answers were collected from 249 CTD vs 149 CA patients. Their desire to have children was influenced by RD in 40% of cases: half of them reduced the number of children they wanted (Table 1). 39% CA vs 29% CTD were afraid of being mother because of disability. 24% CTD vs. 18% CA had at least one miscarriage; 21% CTD vs. 2% CA had more than one. 31% CTD and 34% CA were never asked about their desire to have children. 61% CTD vs 70% CA received counselling about contraception, given by a gynaecologist (G) (58% vs 64%), rheumatologist (R) (22% vs 14%) or both (7% vs 9%). 60% in both groups received a counselling before pregnancy: 34% vs 39% from R and G, 14% vs 22% by R. This positively changed family planning in 64% vs 59%. We created a Knowledge Index (based on the average of the normalized performed scores on 6 key questions for different sections): 55% CTD patients vs 44% CA had a medium-high score. A higher score directly correlated with the desire to became pregnant and with a multidisciplinary counselling. Conclusions This survey suggested that CTD have a major impact on FP and family size, possibly mediated by the increased rate of miscarriages as compared to CA. Concerns about reproductive issues could be positively overcome by adequate counselling. Rheumatologists should implement the discussion about FP and the compatibility of drugs with pregnancy in the management of young women with RD, especially those with CTD for whom contraception and pregnancy have particular implications. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma Thanks to Patients9 Associations and Participants Disclosure of Interest None declared

Background Methotrexate (MTX) is the DMARD of first choice in the treatment of rheumatoid arthritis (RA). Objectives To investigate the clinical characteristics and describe therapeutic approaches in RA patients ongoing MTX not achieving a DAS28 “low disease activity” score. Methods This is a case-control analysis including 186 patients (mean age±SD, 61±12 years, 16% males) who did not achieve a DAS28 “low disease activity” score (defined by a value ≤3.2) and 558 age- and gender-frequency-matched (1:3), randomly selected controls (mean age age±SD, 61±13 years) who achieved a DAS28 “low disease activity” from the original cohort investigated in the MARI study. The MARI study enrolled RA patients on treatment for at least 12-month with MTX. Demographic, clinical, laboratory and pharmacological characteristics of patients recorded at baseline visit were considered for the current analysis. We first compared the characteristics of patients who reached the endpoint with those of subjects who did not by univariate analyses, thereafter, we performed a multivariate model to identify predictors of not achieving the endpoint. We further investigated the therapeutic approaches in patients not achieving the endpoint. Results Compared to patients with a DAS28 ≤3.2, subjects not achieving the endpoint presented with a significant higher (mean±SD) weight and BMI (DAS28 ≤3.2: 25±4 versus DAS28 >3.2: 26±5, P=.022), and longer duration of symptoms (months±SD) before the RA diagnosis (11±15 versus 15±20, P=.009). A higher proportion of subjects within the group not achieving the endpoint presented with polyarticular disease (DAS28 ≤3.2: 57% versus DAS28 >3.2: 96%, P 3.2 (P=.004). In the logistic regression analysis, the variables predictive of a DAS28 >3.2 were polyarticular disease (OR 4.0, 95% CI 2.4–6.7, P 3.2: 13% versus DAS28 ≤3.2: 4%, P Conclusions Our results identified a number of variables potentially associated the risk of not achieving a DAS28 “low disease activity” score in RA patients ongoing MTX treatment. Longitudinal studies are warranted. Disclosure of Interest None declared

Background Rheumatic diseases (RD) affect women during reproductive age. Children9s outcome is a major topic for counselling on family planning, but no large studies are available. Objectives We aimed at assessing the long-term health conditions of children born to mothers with RD through a self-reported questionnaire. Methods 24 Rheumatology Centers distributed the questionnaire (65 multiple choice and 12 open-answer questions) to consecutive women with RD attending their outpatient clinic during September 2015. Data were compared according to maternal diagnosis (MD) -chronic arthritis (CA) or connective tissue disease (CTD)- and to the timing of pregnancy (before or after MD of RD). Results The survey yielded data about 269 children born to 184 mothers (63 CA, 121 CTD). According to MD, children had a mean age of 17.1 (±9.6 SD) and 14.4 (±9.0 SD) years at the time of interview, and male children were 52/93 (56%) and 91/176 (52%), respectively. Twenty-nine children in the CA group (31.2%) and 64 in the CTDs group (36.4%) were born after MD of RD. Pre-term delivery (before 37 weeks) was observed in 48 cases (17.8%), mostly children born to mothers with CTD (37/48, 77%). Regarding school performance, 12 children (4.5%) repeated one year of school, in 7 cases for indolence, in 3 for learning disabilities (LD)/health problems (HP), in 2 for family problems. Eleven of these children were born before MD. Overall, 9 children (3.3%) were diagnosed with a LD and 53 children were affected by HP requiring either hospitalization or evaluation by a Specialist (Table). Three children (1%) were affected by autoimmune disease. Conclusions The long-term follow-up of children born to women with RD is reassuring of an outcome similar to that of the general pediatric population (GPP). Autoimmune diseases are not frequent. Problems seem to cluster in children born to CTD, especially after MD, with a higher frequency of LD (6.3% vs 2.5–3.5% of GPP), but no particular pattern of exposure to maternal autoantibodies nor drugs was observed. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma Thanks to Patients Associations and Participants to the survey Disclosure of Interest None declared

We present the results from the spectroscopic monitoring of WR 140 (WC7pd + O5.5fc) during its latest periastron passage in January 2009. The observational campaign consisted of a constructive collaboration between amateur and professional astronomers and took place at half a dozen locations, including Teide Observatory, Observatoire de Haute Provence, Dominion Astrophysical Observatory and Observatoire

We present an autoradiography tool to be used mainly for genetic studies. It performs a quantitative analysis of radioactivity and can follow a dynamic process. We designed several applications, in particular one aimed at detecting hybridization of radio-labeled DNA fragments with known DNA-probes deposited on a micro-array. The technique is based on GaAs pixel array detector and low threshold, large dynamic range and good sensitivity integrated electronics developed for medical applications, suitable to detect markers (gamma or beta) such as 14C, 35S, 33P, 32P, 125I, even at very low activities. A Monte Carlo simulation of β− detection in GaAs is presented here in order to study the spatial resolution characteristics of such a system. For several biological applications, the electronics is required to perform at high temperatures (from 37° to 68°): we present here studies of noise and minimum threshold as a function of the temperature.

The Oe stars HD45314 and HD60848 have recently been found to exhibit very different X-ray properties: whilst HD60848 has an X-ray spectrum and emission level typical of most OB stars, HD45314 features a much harder and brighter X-ray emission, making it a so-called gamma Cas analogue. Monitoring the optical spectra could provide hints towards the origin of these very different behaviours. We analyse a large set of spectroscopic observations of HD45314 and HD60848, extending over 20 years. We further attempt to fit the H-alpha line profiles of both stars with a simple model of emission line formation in a Keplerian disk. Strong variations in the strengths of the H-alpha, H-beta, and He I 5876 emission lines are observed for both stars. In the case of HD60848, we find a time lag between the variations in the equivalent widths of these lines. The emission lines are double peaked with nearly identical strengths of the violet and red peaks. The H-alpha profile of this star can be successfully reproduced by our model of a disk seen under an inclination of 30 degrees. In the case of HD45314, the emission lines are highly asymmetric and display strong line profile variations. We find a major change in behaviour between the 2002 outburst and the one observed in 2013. This concerns both the relationship between the equivalent widths of the various lines and their morphologies at maximum strength (double-peaked in 2002 versus single-peaked in 2013). Our simple disk model fails to reproduce the observed H-alpha line profiles of HD45314. Our results further support the interpretation that Oe stars do have decretion disks similar to those of Be stars. Whilst the emission lines of HD60848 are explained by a disk with a Keplerian velocity field, the disk of HD45314 seems to have a significantly more complex velocity field that could be related to the phenomenon that produces its peculiar X-ray emission., Accepted for Publication in A&A

This article, “Associations between the birth of an infant with major congenital anomalies and subsequent risk of mortality in their mothers” (1), adds to the growing literature revealing the adverse health condition of caretakers of children with severe chronic disease (2,3). Using population-based registries in Denmark, the authors have extended the literature to now include mothers of children with major congenital anomalies and have used as the definitive metric of health, the subsequent death of the mother and her cause of death. Their findings demonstrate an increased risk of death of the mother both within the first 10 years and over the first 35 years after the child’s birth, particularly from cardiovascular and respiratory diseases. The authors suggest that the adverse impact on the child’s mother over the long-term may be a response related to the stress of caring for a child with a birth defect/birth defects.

We have investigated the detection performance of GaAs detectors made with different thickness and contact geometries. A comparison is made between these detection capabilities and the imaging requirements for the following medical applications: digital mammography, digital chest radiography and nuclear medicine. Experimental results and preliminary images are presented and discussed.

A GaAs pixel detector designed for digital mammography, equipped with a 36-channel single photon counting discrete read-out electronics, was tested using a test object developed for quality control purposes in mammography. Each pixel was 200×200 μm2 large, and 200 μm deep. The choice of GaAs with respect to silicon (largely used in other applications and with a more established technique) has been made because of the much better detection efficiency at mammographic energies, combined with a very good charge collection efficiency achieved thanks to new ohmic contacts. This GaAs detector is able to perform a measurement of low-contrast details, with minimum contrast lower (nearly a factor two) than that typically achievable with standard mammographic film+screen systems in the same conditions of clinical routine. This should allow for an earlier diagnosis of breast tumour masses. Due to these encouraging results, the next step in the evolution of our imaging system based on GaAs detectors has been the development of a VLSI front-end prototype chip (MEDIPIX ) in order to cover a much larger diagnostic area. The chip reads 64×64 channels in single photon counting mode, each one 170 μm wide. Each channel contains also a test input where a signal can be simulated, injecting a known charge through a 16 f F capacitor. Fake signals have been injected via the test input measuring and equalizing minimum thresholds for all the channels. On an average, in most of the performing chips available up to now, we have found that it is possible to set a threshold as low as 1800 electrons with an RMS of 150 electrons (10 standard deviations lower than the 20 keV photon signal roughly equivalent to 4500 electrons). The detector, bump-bonded to the chip, will be tested and a ladder of detectors will be prepared to be able to scan large surface objects.

The realization of low resistivity and stable contacts on p-type CdTe is still challenging, especially if high annealing temperatures must be avoided. In this paper, the electrical characteristics of Sb/sub 2/Te/sub 3/ contacts on p-type CdTe single crystals are studied. It is found that the resistivity of the contacts is low and constant with time.

We present preliminary results of a 3-month campaign carried out in the framework of the Mons project, where time-resolved Halpha observations are used to study the wind and circumstellar properties of a number of OB stars., 2 pages, 1 figure. To appear in proceedings of IAUS272 'Active OB Stars: Structure, Evolution, Mass Loss and Critical Limits'

To evaluate the psychometric properties of an index based on 3 patient reported outcomes measures, termed PRO-CLinical ARthritis Activity (PRO-CLARA), in order to facilitate rapid and easy rheumatoid arthritis (RA) activity assessment in daily routine.196 patients partially or not responding to disease modifying anti-rheumatic drugs (DMARDs), consented to participate in a multicentre cross-sectional study. For the evaluation of the psychometric properties of the PRO-CLARA, this population has been compared to another cohort of 247 outpatients with RA who were participating in a long-term observational study and who satisfying minimal disease activity and remission definitions. All patients completed the PRO-CLARA, combining patient's physical function, self-administered tender joint count and perception of global health status into a single measure of disease activity. Additional comparator composite indices were analysed. Internal consistency was assessed with Cronbach's alpha coefficient. A confirmatory factor analysis was carried out to test factor structure. Concurrent validity was analyzed using Spearman's correlations and cross-tabulations. Discriminant validity to distinguish patients with active and non-active disease was assessed with receiver operating characteristic (ROC) curve analysis. For agreement analysis, kappa statistics were calculated.In testing for internal consistency, we found that Cronbach's alpha for the PRO-CLARA was 0.893, indicating high reliability. PRO-CLARA proved to be significantly correlated to established RA activity assessment tools. The area under ROC curve of the PRO-CLARA gives identical results to those provided by other comparator indices.The study showed satisfactory psychometric properties of the PRO-CLARA.

In this paper we present the results of an experimental study concerning different contact deposition processes on Semi-Insulating (S.I.) GaAs detectors aiming to study and optimize their performance in terms of leakage current, break-down voltage, charge collection efficiency and energy resolution when irradiated with 60 KeV photons; in particular the effect of the mesa etching treatment on the Schottky barrier side of the detectors has been studied. Such treatment certainly improves the detector performances related to the very important issue of the electric field uniformity. Detectors with satisfactory features in view of their possible application to Digital Radiography have been obtained.

Solid state detectors made of Si (4.8/spl times/8 mm/sup 2/) and GaAs (6.4/spl times/8 mm/sup 2/) pixel matrices bump-bonded to the Omega2 and Omega3 electronic read-out systems, developed at CERN for H.E.P. experiments, have been used to obtain autoradiographic images of clusters of human epithelial cells and DNA fragments separated via electrophoresis, both labeled with /sup 32/P. The system has shown a good minimum detectable activity per unit area of 2.10/sup -4/ cps mm/sup -2/, and has proved linear for a count rate in the range 0.2-20 cpa, typical of autoradiography. The pixel dimensions are 75/spl times/500 /spl mu/m/sup 2/ (Si-Omega2) and 50/spl times/500 /spl mu/m/sup 2/ (GaAs-Omega3), respectively. We are able to clearly localize clusters of cells which have incorporated the radioactive tracer and DNA fragments on an electrophoretic gel on paper (blots).

We describe a coordinated effort to identify the core features of a parent-controlled personal health record for children with special health care needs, involving parents, care givers, and healthcare providers. A summary of the core features is presented, emphasizing needs that are not commonly recognized as functions of a generic personal health record. Our goal was to identify requirements for personal records that empower parents to effectively obtain, organize, understand, and communicate the information necessary to help their children receive the best possible care.